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Sample records for modelling treatment effects

  1. 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.

  2. 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.

  3. Integrating Multiscale Modeling with Drug Effects for Cancer Treatment.

    Science.gov (United States)

    Li, Xiangfang L; Oduola, Wasiu O; Qian, Lijun; Dougherty, Edward R

    2015-01-01

    In this paper, we review multiscale modeling for cancer treatment with the incorporation of drug effects from an applied system's pharmacology perspective. Both the classical pharmacology and systems biology are inherently quantitative; however, systems biology focuses more on networks and multi factorial controls over biological processes rather than on drugs and targets in isolation, whereas systems pharmacology has a strong focus on studying drugs with regard to the pharmacokinetic (PK) and pharmacodynamic (PD) relations accompanying drug interactions with multiscale physiology as well as the prediction of dosage-exposure responses and economic potentials of drugs. Thus, it requires multiscale methods to address the need for integrating models from the molecular levels to the cellular, tissue, and organism levels. It is a common belief that tumorigenesis and tumor growth can be best understood and tackled by employing and integrating a multifaceted approach that includes in vivo and in vitro experiments, in silico models, multiscale tumor modeling, continuous/discrete modeling, agent-based modeling, and multiscale modeling with PK/PD drug effect inputs. We provide an example application of multiscale modeling employing stochastic hybrid system for a colon cancer cell line HCT-116 with the application of Lapatinib drug. It is observed that the simulation results are similar to those observed from the setup of the wet-lab experiments at the Translational Genomics Research Institute.

  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...... to observe the same person in both the treated and untreated states, but it also turns out to be straightforward to implement. Formulae are provided to compute mean treatment effects as well as their distributional versions. A Monte Carlo simulation study is carried out to illustrate how the methodology can...

  5. 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...... to observe the same person in both the treated and untreated states, but it also turns out to be straightforward to implement. Formulae are provided to compute mean treatment effects as well as their distributional versions. A Monte Carlo simulation study is carried out to illustrate how the methodology can...

  6. Assessing Model Treatment of Drought Legacy Effects in the Amazon

    Science.gov (United States)

    Kolus, H. R.; Huntzinger, D. N.; Schwalm, C.; Fisher, J. B.; Cook, R. B.; Fang, Y.; Jacobson, A. R.; Michalak, A.; Schaefer, K. M.; Wei, Y.

    2015-12-01

    Extreme climate events play an important and potentially lasting role in terrestrial carbon cycling and storage. In particular, satellite and in-situ measurements have shown that forest recovery time following severe drought can extend several years beyond the return to normal climate conditions. However, terrestrial ecosystem models generally do not account for the physiological mechanisms that cause these legacy effects and, instead, assume complete and rapid vegetation recovery from drought. Using a suite of fifteen land surface models from the Multi-scale Synthesis and Terrestrial Model Intercomparison Project (MsTMIP), we assess models' ability to capture legacy effects by analyzing the spatial and temporal extent of modeled vegetation response to the 2005 Amazon drought. We compare the simulated primary production and ecosystem exchange (GPP, NPP, NEE) to previous recovery-focused analysis of satellite microwave observations of canopy backscatter. Further, we evaluate the specific model characteristics that control the timescale and magnitude of simulated vegetation recovery from drought. Since climate change is expected to increase the frequency and severity of extreme climate events, improving models' ability to simulate the legacy effects of these events will likely refine estimates of the land carbon sink and its interannual variability.

  7. The Impact of Five Missing Data Treatments on a Cross-Classified Random Effects Model

    Science.gov (United States)

    Hoelzle, Braden R.

    2012-01-01

    The present study compared the performance of five missing data treatment methods within a Cross-Classified Random Effects Model environment under various levels and patterns of missing data given a specified sample size. Prior research has shown the varying effect of missing data treatment options within the context of numerous statistical…

  8. Quality of data computational models and telemedicine treatment effects

    NARCIS (Netherlands)

    Larburu, Nekane; Bults, Richard G.A.; Widya, Ing; Hermens, Hermie 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 d

  9. A review on numerous modeling approaches for effective, economical and ecological treatment wetlands.

    Science.gov (United States)

    Kumar, J L G; Zhao, Y Q

    2011-03-01

    Constructed wetlands (CWs) for wastewater treatment have evolved substantially over the last decades and have been recognized as an effective means of "green technology" for wastewater treatment. This paper reviews the numerous modeling approaches ranging from simple first-order models to more complex dynamic models of treatment behaviour in CWs. The main objective of the modeling work is to better understand the process in CWs and optimize design criteria. A brief study in this review discusses the efforts taken to describe the process-based model for the efficient removal of pollutants in CWs. Obtaining better insights is essential to understand the hydraulic and biochemical processes in CWs. Currently, employed modeling approaches can be seen in two categories, i.e. "black-box models" and "process-based models". It is evident that future development in wetland technology will depend on improved scientific knowledge of internal treatment mechanisms.

  10. Variable selection for propensity score models when estimating treatment effects on multiple outcomes: a simulation study.

    Science.gov (United States)

    Wyss, Richard; Girman, Cynthia J; LoCasale, Robert J; Brookhart, Alan M; Stürmer, Til

    2013-01-01

    It is often preferable to simplify the estimation of treatment effects on multiple outcomes by using a single propensity score (PS) model. Variable selection in PS models impacts the efficiency and validity of treatment effects. However, the impact of different variable selection strategies on the estimated treatment effects in settings involving multiple outcomes is not well understood. The authors use simulations to evaluate the impact of different variable selection strategies on the bias and precision of effect estimates to provide insight into the performance of various PS models in settings with multiple outcomes. Simulated studies consisted of dichotomous treatment, two Poisson outcomes, and eight standard-normal covariates. Covariates were selected for the PS models based on their effects on treatment, a specific outcome, or both outcomes. The PSs were implemented using stratification, matching, and weighting (inverse probability treatment weighting). PS models including only covariates affecting a specific outcome (outcome-specific models) resulted in the most efficient effect estimates. The PS model that only included covariates affecting either outcome (generic-outcome model) performed best among the models that simultaneously controlled measured confounding for both outcomes. Similar patterns were observed over the range of parameter values assessed and all PS implementation methods. A single, generic-outcome model performed well compared with separate outcome-specific models in most scenarios considered. The results emphasize the benefit of using prior knowledge to identify covariates that affect the outcome when constructing PS models and support the potential to use a single, generic-outcome PS model when multiple outcomes are being examined. Copyright © 2012 John Wiley & Sons, Ltd.

  11. 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

    2017-01-01

    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. PMID:28856046

  12. Quasi-likelihood estimation of average treatment effects based on model information

    Institute of Scientific and Technical Information of China (English)

    Zhi-hua SUN

    2007-01-01

    In this paper, the estimation of average treatment effects is considered when we have the model information of the conditional mean and conditional variance for the responses given the covariates. The quasi-likelihood method adapted to treatment effects data is developed to estimate the parameters in the conditional mean and conditional variance models. Based on the model information, we define three estimators by imputation, regression and inverse probability weighted methods.All the estimators are shown asymptotically normal. Our simulation results show that by using the model information, the substantial efficiency gains are obtained which are comparable with the existing estimators.

  13. Quasi-likelihood estimation of average treatment effects based on model information

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this paper, the estimation of average treatment effects is considered when we have the model information of the conditional mean and conditional variance for the responses given the covariates. The quasi-likelihood method adapted to treatment effects data is developed to estimate the parameters in the conditional mean and conditional variance models. Based on the model information, we define three estimators by imputation, regression and inverse probability weighted methods. All the estimators are shown asymptotically normal. Our simulation results show that by using the model information, the substantial efficiency gains are obtained which are comparable with the existing estimators.

  14. Effects of historically portrayed modeling and group treatment on self-observation: A comparison with agoraphobics

    NARCIS (Netherlands)

    Emmelkamp, Paul M.G.; Emmelkamp-Benner, Ank

    1975-01-01

    The effects of historically portrayed modeling and group treatment on self-observation were determined in a factorial design with agoraphobic patients. Group 1 saw a videofilm and was treated individually; group 2 saw the film and received group treatment; group 3 did not see the film and received i

  15. 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

    2014-01-01

    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 inte

  16. A design-by-treatment interaction model for network meta-analysis with random inconsistency effects.

    Science.gov (United States)

    Jackson, Dan; Barrett, Jessica K; Rice, Stephen; White, Ian R; Higgins, Julian P T

    2014-09-20

    Network meta-analysis is becoming more popular as a way to analyse multiple treatments simultaneously and, in the right circumstances, rank treatments. A difficulty in practice is the possibility of 'inconsistency' or 'incoherence', where direct evidence and indirect evidence are not in agreement. Here, we develop a random-effects implementation of the recently proposed design-by-treatment interaction model, using these random effects to model inconsistency and estimate the parameters of primary interest. Our proposal is a generalisation of the model proposed by Lumley and allows trials with three or more arms to be included in the analysis. Our methods also facilitate the ranking of treatments under inconsistency. We derive R and I(2) statistics to quantify the impact of the between-study heterogeneity and the inconsistency. We apply our model to two examples.

  17. Meta-analysis methods for synthesizing treatment effects in multisite studies: hierarchical linear modeling (HLM perspective

    Directory of Open Access Journals (Sweden)

    Sema A. Kalaian

    2003-06-01

    Full Text Available The objectives of the present mixed-effects meta-analytic application are to provide practical guidelines to: (a Calculate..treatment effect sizes from multiple sites; (b Calculate the overall mean of the site effect sizes and their variances; (c..Model the heterogeneity in these site treatment effects as a function of site and program characteristics plus..unexplained random error using Hierarchical Linear Modeling (HLM; (d Improve the ability of multisite evaluators..and policy makers to reach sound conclusions about the effectiveness of educational and social interventions based on..multisite evaluations; and (e Illustrate the proposed methodology by applying these methods to real multi-site research..data.

  18. A model to describe potential effects of chemotherapy on critical radiobiological treatments

    Science.gov (United States)

    Rodríguez-Pérez, D.; Desco, M. M.; Antoranz, J. C.

    2016-08-01

    Although chemo- and radiotherapy can annihilate tumors on their own. they are also used in coadjuvancy: improving local effects of radiotherapy using chemotherapy as a radiosensit.izer. The effects of radiotherapy are well described by current radiobiological models. The goal of this work is to describe a discrete radiotherapy model, that has been previously used describe high radiation dose response as well as unusual radio-responses of some types of tumors (e.g. prostate cancer), to obtain a model of chemo+radiotherapy that can describe how the outcome of their combination is a more efficient removal of the tumor. Our hypothesis is that, although both treatments haven different mechanisms, both affect similar key points of cell metabolism and regulation, that lead to cellular death. Hence, we will consider a discrete model where chemotherapy may affect a fraction of the same targets destroyed by radiotherapy. Although radiotherapy reaches all cells equally, chemotherapy diffuses through a tumor attaining lower concentration in its center and higher in its surface. With our simulations we study the enhanced effect of combined therapy treatment and how it depends on the tissue critical parameters (the parameters of the lion-extensive radiobiological model), the number of “targets” aimed at by chemotherapy, and the concentration and diffusion rate of the drug inside the tumor. The results show that an equivalent, cliemo-radio-dose can be computed that allows the prediction of the lower radiation dose that causes the same effect than a radio-only treatment.

  19. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-01

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

  1. Anticonvulsant effects of acute treatment with cyane-carvone at repeated oral doses in epilepsy models.

    Science.gov (United States)

    Marques, Thiago Henrique Costa; Marques, Maria Leonildes Boavista Gomes Castelo Branco; Medeiros, Jand-Venes Rolim; Lima, Tamires Cardoso; de Sousa, Damião Pergentino; de Freitas, Rivelilson Mendes

    2014-09-01

    Epilepsy affects about 40 million people worldwide. Many drugs block seizures, but have little effect in preventing or curing this disease. So the search for new drugs for epilepsy treatment using animal models prior to testing in humans is important. Increasingly pharmaceutical industries invest in the Re​search & Drug Development area to seek safe and effective new therapeutic alternatives to the currently available epilepsy treatment. In this perspective, natural compounds have been investigated in epilepsy models, particularly the monoterpenes obtained from medicinal plants. In our study we investigated the effects of cyane-carvone (CC), a synthetic substance prepared from natural a monoterpene, carvone, against pilocarpine- (PILO), pentylenetetrazole- (PTZ) and picrotoxine (PTX)-induced seizures in mice after acute treatment with repeated oral doses (CC 25, 50 and 75 mg/kg) for 14 days. CC in all doses tested showed increase in latency to first seizure, decrease in percentages of seizuring animals as well as reduction percentages of dead animals (pepilepsy models. In addition, our data suggest that CC could act in an allosteric site of GABAA, which would be different from the site in which BDZ acts, since flumazenil was not able to reverse any of CC effects on the modulation of seizure parameters related with epilepsy models investigated. New studies should be conducted to investigate CC effects in other neurotransmitter systems. Nevertheless, our study reinforces the hypothesis that CC could be used, after further research, as a new pharmaceutical formulation and a promising alternative for epilepsy treatment, since it showed anticonvulsant effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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. ...... treatment. A higher number of bed-days in Hospital-based Rehabilitation did not influence the effect on the outcomes measured........ Hospital-based Rehabilitation, an intensified inpatient treatment model, Integrated Treatment, an intensified model of Assertive Community Treatment, and standard treatment were compared for patients with first-episode schizophrenia-spectrum disorders. Ninety-four patients with first-episode schizophrenia......-spectrum disorders estimated to benefit from long-term hospitalization were included consecutively from the Copenhagen OPUS-trial and randomized to the three treatment models. At 1-year follow-up, Hospital-based Rehabilitation and Integrated Treatment had better scores on symptoms in the negative dimension...

  3. 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.

  4. Cardioprotective and anti-inflammatory effects of treatment with Adenocaine/Mg2+ in a porcine model of endotoxemia

    DEFF Research Database (Denmark)

    Granfeldt, Asger

    Cardioprotective and anti-inflammatory effects of treatment with Adenocaine/Mg2+ in a porcine model of endotoxemia American Heart Scientific sessions Resuscitation Science symposium 16-20 November......Cardioprotective and anti-inflammatory effects of treatment with Adenocaine/Mg2+ in a porcine model of endotoxemia American Heart Scientific sessions Resuscitation Science symposium 16-20 November...

  5. 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.

  6. 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.

  7. Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis.

    Science.gov (United States)

    Gomez, G B; Dowdy, D W; Bastos, M L; Zwerling, A; Sweeney, S; Foster, N; Trajman, A; Islam, M A; Kapiga, S; Sinanovic, E; Knight, G M; White, R G; Wells, W A; Cobelens, F G; Vassall, A

    2016-12-01

    Despite improvements in treatment success rates for tuberculosis (TB), current six-month regimen duration remains a challenge for many National TB Programmes, health systems, and patients. There is increasing investment in the development of shortened regimens with a number of candidates in phase 3 trials. We developed an individual-based decision analytic model to assess the cost-effectiveness of a hypothetical four-month regimen for first-line treatment of TB, assuming non-inferiority to current regimens of six-month duration. The model was populated using extensive, empirically-collected data to estimate the economic impact on both health systems and patients of regimen shortening for first-line TB treatment in South Africa, Brazil, Bangladesh, and Tanzania. We explicitly considered 'real world' constraints such as sub-optimal guideline adherence. From a societal perspective, a shortened regimen, priced at USD1 per day, could be a cost-saving option in South Africa, Brazil, and Tanzania, but would not be cost-effective in Bangladesh when compared to one gross domestic product (GDP) per capita. Incorporating 'real world' constraints reduces cost-effectiveness. Patient-incurred costs could be reduced in all settings. From a health service perspective, increased drug costs need to be balanced against decreased delivery costs. The new regimen would remain a cost-effective option, when compared to each countries' GDP per capita, even if new drugs cost up to USD7.5 and USD53.8 per day in South Africa and Brazil; this threshold was above USD1 in Tanzania and under USD1 in Bangladesh. Reducing the duration of first-line TB treatment has the potential for substantial economic gains from a patient perspective. The potential economic gains for health services may also be important, but will be context-specific and dependent on the appropriate pricing of any new regimen.

  8. 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

  9. Dynamic Treatment Effects.

    Science.gov (United States)

    Heckman, James J; Humphries, John Eric; Veramendi, Gregory

    2016-02-01

    This paper develops robust models for estimating and interpreting treatment effects arising from both ordered and unordered multistage decision problems. Identification is secured through instrumental variables and/or conditional independence (matching) assumptions. We decompose treatment effects into direct effects and continuation values associated with moving to the next stage of a decision problem. Using our framework, we decompose the IV estimator, showing that IV generally does not estimate economically interpretable or policy relevant parameters in prototypical dynamic discrete choice models, unless policy variables are instruments. Continuation values are an empirically important component of estimated total treatment effects of education. We use our analysis to estimate the components of what LATE estimates in a dynamic discrete choice model.

  10. Bayesian inference of baseline fertility and treatment effects via a crop yield-fertility model.

    Directory of Open Access Journals (Sweden)

    Hungyen Chen

    Full Text Available To effectively manage soil fertility, knowledge is needed of how a crop uses nutrients from fertilizer applied to the soil. Soil quality is a combination of biological, chemical and physical properties and is hard to assess directly because of collective and multiple functional effects. In this paper, we focus on the application of these concepts to agriculture. We define the baseline fertility of soil as the level of fertility that a crop can acquire for growth from the soil. With this strict definition, we propose a new crop yield-fertility model that enables quantification of the process of improving baseline fertility and the effects of treatments solely from the time series of crop yields. The model was modified from Michaelis-Menten kinetics and measured the additional effects of the treatments given the baseline fertility. Using more than 30 years of experimental data, we used the Bayesian framework to estimate the improvements in baseline fertility and the effects of fertilizer and farmyard manure (FYM on maize (Zea mays, barley (Hordeum vulgare, and soybean (Glycine max yields. Fertilizer contributed the most to the barley yield and FYM contributed the most to the soybean yield among the three crops. The baseline fertility of the subsurface soil was very low for maize and barley prior to fertilization. In contrast, the baseline fertility in this soil approximated half-saturated fertility for the soybean crop. The long-term soil fertility was increased by adding FYM, but the effect of FYM addition was reduced by the addition of fertilizer. Our results provide evidence that long-term soil fertility under continuous farming was maintained, or increased, by the application of natural nutrients compared with the application of synthetic fertilizer.

  11. 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.

  12. Treatment of Fluctuation Effects in Mean-field Models of Chain Stretching

    Science.gov (United States)

    Douglas, Jack; Mansfield, Marc

    1997-03-01

    Many recent studies of chain stretching in block copolymer materials, polymer brushes, and many-arm stars have been formulated in terms of mean- field models, leading generally to power-law potentials describing the chain stretching arising from interchain and intrachain excluded volume interactions. This type of model has been highly successful, but fluctuation effects associated with finite chain length are often neglected in model calculations. We investigate whether fluctuation effects can be accounted for by reintroducing these effective pseudo-potentials into a path-integral description to calculate the chain streching. Numerical treatment of chain swelling with repulsive power-law potentials leads to universal scaling curves which are similar to those found for chain swelling due to excluded volume in polymer solutions. Density profiles are also calculated and the parabolic potential led to a density profile having a "foot" for finite chain lengths, as in measurements on polymer "brushes". Analytic calculations indicate a general relation between the polymer size exponent nu and the power of the potential which also holds for Hamiltonian dynamical systems and thus the 2/3 power law describing the strong segregation scaling of block copolymer lamellae with chain mass corresponds to Kepler's third law of planetary motion relating the orbital scale to its period.

  13. 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...

  14. 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...

  15. 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...

  16. Statistical Models of Treatment Effects in Chronic Hepatitis B and C

    NARCIS (Netherlands)

    B.E. Hansen (Bettina)

    2010-01-01

    textabstractThis thesis regards treatment effects in patients with chronic hepatitis B and C, and focuses on the tools that are used to analyse these effects. In this introduction the clinical background of hepatitis B and C along with the current treatment options are described. Clinical questions

  17. 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....... Efficient and good modeling practice therefore requires the use of a proper set of guidelines, thus grounding the modeling studies on a general and systematic framework. Last but not least, general limitations of WWTP models – more specifically activated sludge models – are introduced since these define...

  18. 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....... Efficient and good modeling practice therefore requires the use of a proper set of guidelines, thus grounding the modeling studies on a general and systematic framework. Last but not least, general limitations of WWTP models – more specifically, activated sludge models – are introduced since these define...

  19. 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

    2016-01-01

    Purpose 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. Methods 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. Results 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

  20. Effect of antioxidant treatment on spinal GABA neurons in a neuropathic pain model in the mouse.

    Science.gov (United States)

    Yowtak, June; Wang, Jigong; Kim, Hee Young; Lu, Ying; Chung, Kyungsoon; Chung, Jin Mo

    2013-11-01

    One feature of neuropathic pain is a reduced spinal gamma-aminobutyric acid (GABA)-ergic inhibitory function. However, the mechanisms behind this attenuation remain to be elucidated. This study investigated the involvement of reactive oxygen species in the spinal GABA neuron loss and reduced GABA neuron excitability in spinal nerve ligation (SNL) model of neuropathic pain in mice. The importance of spinal GABAergic inhibition in neuropathic pain was tested by examining the effects of intrathecally administered GABA receptor agonists and antagonists in SNL and naïve mice, respectively. The effects of SNL and antioxidant treatment on GABA neuron loss and functional changes were examined in transgenic GAD67-enhanced green fluorescent protein positive (EGFP+) mice. GABA receptor agonists transiently reversed mechanical hypersensitivity of the hind paw in SNL mice. On the other hand, GABA receptor antagonists made naïve mice mechanically hypersensitive. Stereological analysis showed that the numbers of enhanced green fluorescent protein positive (EGFP+) GABA neurons were significantly decreased in the lateral superficial laminae (I-II) on the ipsilateral L5 spinal cord after SNL. Repeated antioxidant treatments significantly reduced the pain behaviors and prevented the reduction in EGFP+ GABA neurons. The response rate of the tonic firing GABA neurons recorded from SNL mice increased with antioxidant treatment, whereas no change was seen in those recorded from naïve mice, which suggested that oxidative stress impaired some spinal GABA neuron activity in the neuropathic pain condition. Together the data suggest that neuropathic pain, at least partially, is attributed to oxidative stress, which induces both a GABA neuron loss and dysfunction of surviving GABA neurons. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. Long-term effects of methadone maintenance treatment with different psychosocial intervention models.

    Directory of Open Access Journals (Sweden)

    Lirong Wang

    Full Text Available This study evaluated the long-term effects of different psychosocial intervention models in methadone maintenance treatment (MMT in Xi'an China. Patients from five MMT clinics were divided into three groups receiving MMT only, MMT with counseling psychology (CP or MMT with contingency management (CM. A five-year follow-up was carried out with daily records of medication, monthly random urine morphine tests, and tests for anti-HIV and anti-HCV every six months. Drug use behavior was recorded six months after initial recruitment using a survey. Adjusted RRs and their 95% confidence intervals (CIs were estimated using an unconditional logistic regression model or a Cox proportional hazard model. A total of 2662 patients were recruited with 797 in MMT, 985 in MMT with CP, and 880 in MMT with CM. Following six months of treatment, the injection rates of MMT with CP and MMT with CM groups were significantly lower than that of MMT (5.1% and 6.9% vs. 16.3%, x²  =  47.093 and 29.908, respectively; P<0.05. HIV incidences for MMT, MMT with CP and MMT with CM at the five year follow-up were 20.09, 0.00 and 10.02 per ten thousand person-years, respectively. HCV incidences were 18.35, 4.42 and 6.61 per hundred person-years, respectively, demonstrating that CP and CM were protective factors for HCV incidence (RR  =  0.209 and 0.414, with range of 0.146-0.300 and 0.298-0.574, respectively. MMT supplemented with CP or CM can reduce heroin use and related risk behaviors, thereby reducing the incidence of HIV and HCV.

  2. Effects of Electroacupuncture Treatment on Bone Cancer Pain Model with Morphine Tolerance

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    Lei Sima

    2016-01-01

    Full Text Available Objective. To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP rat model with morphine tolerance and explore changes of calcitonin-gene related peptide (CGRP expression in dorsal root ganglion (DRG. Methods. Forty SD rats were divided into five groups: sham, CIBP (B, CIBP + morphine (BM, CIBP + electroacupuncture (BE, and CIBP + morphine + electroacupuncture (BME. B, BM, BE, and BME groups were prepared CIBP model. The latter three groups then accepted morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days consecutively (M1 to M9. Mechanical withdraw threshold (MWT was evaluated. Results. BE group only had differences in M1, M2, and M3 compared to B group (P<0.01. From M5, BM group showed significantly decreased MWT. Electroacupuncture could obtain analgesic effects only at early stage (M1 to M5. From M5 to M9, BME had the differences with BM group (P<0.01. IOD value of CGRP in BM and BME was substantially less than in B group. CGRP in BME was significantly lower than that in BM group (P<0.01. Conclusion. When used in combination with electroacupuncture, morphine could result in improving analgesic effects and reducing tolerance. CGRP may be associated with pain behaviors.

  3. Behavioural and EEG effects of chronic rapamycin treatment in a mouse model of tuberous sclerosis complex.

    Science.gov (United States)

    Cambiaghi, Marco; Cursi, Marco; Magri, Laura; Castoldi, Valerio; Comi, Giancarlo; Minicucci, Fabio; Galli, Rossella; Leocani, Letizia

    2013-04-01

    Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. TSC is characterized by benign tumors arising in different organs and severe neuropsychiatric symptoms, such as epilepsy, intellectual disability, autism, anxiety and depressive behaviour. Rapamycin is a potent inhibitor of mTOR and its efficacy in treating epilepsy and neurological symptoms remains elusive. In a mouse model in which Tsc1 has been deleted in embryonic telencephalic neural stem cells, we analyzed anxiety- and depression-like behaviour by elevated-plus maze (EPM), open-field test (OFT), forced-swim test (FST) and tail-suspension test (TST), after chronic administration of rapamycin. In addition, spectral analysis of background EEG was performed. Rapamycin-treated mutant mice displayed a reduction in anxiety- and depression-like phenotype, as shown by the EPM/OFT and FST, respectively. These results were inline with EEG power spectra outcomes. The same effects of rapamycin were observed in wild-type mice. Notably, in heterozygous animals we did not observe any EEG and/or behavioural variation after rapamycin treatment. Together these results suggest that both TSC1 deletion and chronic rapamycin treatment might have a role in modulating behaviour and brain activity, and point out to the potential usefulness of background EEG analysis in tracking brain dysfunction in parallel with behavioural testing.

  4. Modeled Osteopathic Manipulative Treatments: A Review of Their in Vitro Effects on Fibroblast Tissue Preparations.

    Science.gov (United States)

    Zein-Hammoud, Manal; Standley, Paul R

    2015-08-01

    A key osteopathic tenet involves the body's ability to self-heal. Osteopathic manipulative treatment (OMT) has been evolved to improve this healing capacity. The authors' in vitro work has focused on modeling 2 common OMT modalities: myofascial release (MFR) and counterstrain. Their studies have evaluated the effects of these modalities on wound healing, cytokine secretion, and muscle repair. The key components of the host response to mechanical forces are fibroblasts, which are the main fascial cells that respond to different types of strain by secreting anti-inflammatory chemicals and growth factors, thus improving wound healing and muscle repair processes. The purpose of this review is to discuss the cellular and molecular mechanisms by which MFR and other OMT modalities work, in particular, the role of strained fibroblasts in inflammation, wound healing, and muscle repair and regeneration. Changing MFR parameters, such as magnitude, duration, direction, and frequency of strain, might uniquely affect the physiologic response of fibroblasts, muscle contraction, and wound healing. If such results are clinically translatable, the mechanisms underlying the clinical outcomes of OMT modalities will be better understood, and these treatments will be more widely accepted as evidence-based, first-line therapies.

  5. 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…

  6. 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.

  7. Which one is more effective for the treatment of rat sepsis model: thalidomide or etanercept?

    Science.gov (United States)

    Ilhan, N; Susam, S; Gul, H F; Bardas, R; Ilhan, N

    2017-01-01

    We aimed to investigate the protective effect of selected treatment agents on liver injury in lipopolysaccharide (LPS)-induced rat sepsis model. The sepsis includes complex inflammatory responses between a microbial pathogen and the host immune system, and leads to organ failure and also death. This study was performed with 29 male Wistar Albino rats. Rats were divided randomly into five groups: Sham group, LPS-treated sepsis group, LPS+thalidomide treated group, LPS+etanercept treated group and LPS+thalidomide+etanercept treated group, respectively. Liver tissue tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) levels were determined by enzyme-linked immuno-sorbent assay (ELISA) method. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was performed using western blot analysis. The levels of tissue TNF-α, IL-1β and IL-6 were found statistically significantly higher in sepsis group than in the sham group. TNF-α levels were found statistically significantly decreased in LPS+etanercept and LPS+thalidomide+etanercept treated groups when compared with LPS group (p sepsis. So, the present study may have significant clinical relevance, but clinical trials are needed to confirm these results (Tab. 1, Fig. 1, Ref. 36).

  8. 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.

  9. Effect of hydrothermal treatment model on stability and bioactivity of microarc oxidized titania coatings

    Science.gov (United States)

    Zhou, Jianhong; Shao, Jianmin; Han, Yong

    2014-06-01

    Different types of Sr-doped hydroxyapatite (Sr-HA) nanorod arrays were prepared on microarc oxidized (MAOed) TiO2 coatings after hydrothermal treatment (HT) for 24 h in the case of different HT models, namely the MAOed TiO2 coatings to be hanged up in the autoclave without touching the HT solution (termed as H-HT) and immersed in the HT solution (termed as I-HT). The MAO+H-HT (HT in the case of H-HT model) and MAO+I-HT (HT in the case of I-HT model) coatings are multilayered by nanorod-shaped Sr-HA as outer layer, Ca0.5Sr0.5TiO3 as middle layer and TiO2 as inner layer adjacent to Ti substrate. The Sr-HA nanorods on the coatings are randomly oriented, homogeneous and a similar mean diameter of 70 nm. However, the lateral spacing between the Sr-HA nanorods on MAO+H-HT coating is much smaller compared with those on MAO+I-HT coating. The effects of the HT models on the roughness, in vitro structure and bond strength stability and apatite inducing ability of the coatings were examined. AFM evaluation reveals that the coatings have a similar microscale roughness. The as-MAOed, MAO+H-HT and MAO+I-HT coatings exhibit long-term structure and adhesive strength stability as indicated by immersion tests in physiological saline solutions for 0-48 weeks, although their adhesive strengths decrease a little after immersion in physiological saline solutions, for example, to about 10.2%, 7.8% and 6.9% at 48 weeks, respectively. Furthermore, the MAO+H-HT coating can induce apatite formation after 12 h of SBF immersion due to the compacted Sr-HA nanorods layer, and the induced apatite prefers to nucleate on the basal-faceted surfaces of Sr-HA nanorods.

  10. 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.

  11. TREATMENT EFFECTS 101

    Directory of Open Access Journals (Sweden)

    Thelma J. Mielenz

    2015-10-01

    Full Text Available Physical therapy researchers are interested in how beneficial an intervention is or the “treatment effect.” There are many measures of treatment effect that are applicable for understanding the efficacy and effectiveness of health interventions. Given that each treatment effect has its own set of advantages and disadvantages, understanding these characteristics can help guide which measure is most appropriate for a specific study. This article presents the more common treatment effects for both dichotomous and continues outcomes. The overall aim is to serve as a guide to newer physical therapy researchers on using and interpreting treatment effects.

  12. 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

  13. Siblings’ Perceptions of Differential Treatment, Fairness, and Jealousy and Adolescent Adjustment: A Moderated Indirect Effects Model

    Science.gov (United States)

    Loeser, Meghan K.; Whiteman, Shawn D.; McHale, Susan M.

    2016-01-01

    Youth's perception of parents’ differential treatment (PDT) are associated with maladjustment during adolescence. Although the direct relations between PDT and youth's maladjustment have been well established, the mechanisms underlying these associations remain unclear. We addressed this gap by examining whether sibling jealousy accounted for the links between PDT and youth's depressive symptoms, self-worth, and risky behaviors. Additionally, we examined whether youth's perceptions of fairness regarding their treatment as well as the gender constellation of the dyad moderated these indirect relations (i.e., moderated-indirect effects). Participants were first- and second-born adolescent siblings (M = 15.96, SD = .72 years for older siblings, M = 13.48, SD = 1.02 years for younger siblings) and their parents from 197 working and middle class European American families. Data were collected via home interviews. A series of Conditional Process Analyses revealed significant indirect effects of PDT through sibling jealousy to all three adjustment outcomes. Furthermore, perceptions of fairness moderated the relations between PDT and jealousy, such that the indirect effects were only significant at low (−1 SD) and average levels of fairness. At high levels of fairness (+1 SD) there was no association between PDT, jealousy, and youth adjustment. Taken together, results indicate that youth and parents would benefit from engaging in clear communication regarding the reasoning for the occurrence of differential treatment, likely maximizing youth and parent perceptions of that treatment as being fair, and in turn mitigating sibling jealousy and maladjustment. PMID:27867295

  14. Siblings' Perceptions of Differential Treatment, Fairness, and Jealousy and Adolescent Adjustment: A Moderated Indirect Effects Model.

    Science.gov (United States)

    Loeser, Meghan K; Whiteman, Shawn D; McHale, Susan M

    2016-08-01

    Youth's perception of parents' differential treatment (PDT) are associated with maladjustment during adolescence. Although the direct relations between PDT and youth's maladjustment have been well established, the mechanisms underlying these associations remain unclear. We addressed this gap by examining whether sibling jealousy accounted for the links between PDT and youth's depressive symptoms, self-worth, and risky behaviors. Additionally, we examined whether youth's perceptions of fairness regarding their treatment as well as the gender constellation of the dyad moderated these indirect relations (i.e., moderated-indirect effects). Participants were first- and second-born adolescent siblings (M = 15.96, SD = .72 years for older siblings, M = 13.48, SD = 1.02 years for younger siblings) and their parents from 197 working and middle class European American families. Data were collected via home interviews. A series of Conditional Process Analyses revealed significant indirect effects of PDT through sibling jealousy to all three adjustment outcomes. Furthermore, perceptions of fairness moderated the relations between PDT and jealousy, such that the indirect effects were only significant at low (-1 SD) and average levels of fairness. At high levels of fairness (+1 SD) there was no association between PDT, jealousy, and youth adjustment. Taken together, results indicate that youth and parents would benefit from engaging in clear communication regarding the reasoning for the occurrence of differential treatment, likely maximizing youth and parent perceptions of that treatment as being fair, and in turn mitigating sibling jealousy and maladjustment.

  15. Evaluation of the effect of thymoquinone treatment on wound healing in a rat burn model.

    Science.gov (United States)

    Selçuk, Caferi Tayyar; Durgun, Mustafa; Tekin, Recep; Yolbas, Lyas; Bozkurt, Mehmet; Akçay, Cemal; Alabalk, Ulas; Basarali, Mustafa Kemal

    2013-01-01

    Thymoquinone (TQ) is a plant extract that has been shown to have antimicrobial, anti-inflammatory, and antioxidant effects. Because of these activities, the authors hypothesized that TQ would reduce inflammation and oxidative stress and accelerate wound closure in a rat model of deep second-degree burns. For the purposes of this study, 40 Sprague-Dawley rats were divided into five groups of eight rats each. Group 1 was the control group, group 2 was the silver sulfadiazine group, group 3 was treated with systemic TQ, group 4 received topical TQ, and group 5 was administered topical and systemic TQ. After the deep second-degree burn damage was created, daily dressing changes and TQ administration were continued in the study groups for a period of 21 days. Systemic TQ was administered intraperitoneally at a dose of 2 mg/kg/day, whereas the topical treatment was applied using a 0.5% solution. The changes in the wound site were observed macroscopically, histopathologically, microbiologically, and biochemically in all groups. The smallest necrotic areas were observed at the end of the study in the groups that were administered a combination of systemic and topical TQ, or solely topical TQ (6.1 ± 1.6 cm and 6.7 ± 0.4 cm, respectively), whereas the largest necrotic areas were observed in the control group (11.2 ± 1.2cm). The total antioxidant state levels in the control group were significantly lower than in the other groups (P oxidative stress levels were lower in the TQ groups compared with the control group (P oxidative stress and accelerated the rate of wound closure or reepithelialization.

  16. Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease

    Science.gov (United States)

    Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Álvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

    2012-01-01

    BACKGROUND AND PURPOSE MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. EXPERIMENTAL APPROACH We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. KEY RESULTS According to our results, supplementation with riboflavin or coenzyme Q10 effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. CONCLUSIONS AND IMPLICATIONS Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. PMID:22747838

  17. 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

    in a pig model. METHODS: Gottingen minipigs were randomized to oral CsA treatment or as controls. At 0, 5, 10, 15, 20 and 25 weeks body weight, blood pressure, serum creatinine, and whole blood CsA levels were measured. Magnetic resonance imaging was used to estimate relative glomerular filtration rate (r......A treatment with 20 mg/kg/day for 6 months causes increased serum creatinine, blood pressure, RVR, and renal volume along with a decrease in RBF in accordance with data obtained in humans. The initial temporal changes in renal volume and function during CsA administration have similarities to the functional......GFR), renal blood flow (RBF), kidney length and volume. Renal vascular resistance (RVR) was calculated. Kidney tissue biopsies were taken and volume fraction of cortical interstitial tissue estimated by a stereology-based method. RESULTS: CsA induced significant increases in serum creatinine, blood pressure...

  18. [Effect of aspirin administration for the treatment of osteoporosis in ovariectomized rat model].

    Science.gov (United States)

    Chen, Zhi-wen; Wu, Zi-xiang; Sang, Hong-xun; Qin, Guo-liang; Wang, Li-song; Feng, Jing; Wang, Jun; Li, Xiao-juan; Wang, Jian-chao; Zhang, Da

    2011-04-05

    To explore the therapeutic effects of aspirin on postmenopausal osteoporosis and understand its action mechanism. Forty three-month-old female SD rats were randomly divided into 5 groups (n = 8 each): sham group, OVX group and aspirin groups (A1, A2 & A3). The OVX and aspirin groups were ovariectomized (OVX). All rats underwent BMD (bone mineral density) scan at the time of OVX and 3 months after OVX. After the animal model of osteoporosis was established, aspirin groups were intragastrically administered at a dose of 8.93 mg×kg(-1)×d(-1) (A1), 26.79 mg×kg(-1)×d(-1) (A2) and 80.36 mg×kg(-1)×d(-1) (A3) daily in OVX rats. Three months later, the BMD and micro-architecture of vertebrae were measured by dual-energy X-ray absorptiometry and microtomography. Alkaline phosphatase and osteocalcin were measured in peripheral blood. The trabecular architecture changes were observed by histomorphology. Axial compression tests were used to evaluate the mechanical properties of vertebral specimens and three-point bending tests used for femur shaft. Three months after ovariectomy, BMD was significantly lower than preoperative. BMD in aspirin treated groups was significantly higher than that in OVX group. Alkaline phosphatase in peripheral blood decreased significantly in aspirin groups than those in OVX, but osteocalcin had no significant difference between aspirin and OVX groups. The microtomography reconstruction analysis also showed that the trabecular thickness, trabecular number and BMD increased significantly in aspirin groups than those in OVX. And there was no significant difference between A3 and sham groups. The results of biomechanical test showed that the maximum compression load of lumbar spine and three-point bending load of femur shaft were significantly higher in aspirin groups than those in OVX group. Aspirin can promote trabecular bone remodeling, improve three-dimensional structure of trabecular bone and increase bone density of cancellous in

  19. 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

  20. 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

  1. Fuel treatment effects on modeled landscape level fire behavior in the northern Sierra Nevada

    Science.gov (United States)

    J.J. Moghaddas; B.M. Collins; K. Menning; E.E.Y. Moghaddas; S.L. Stephens

    2010-01-01

    Across the western United States, decades of fire exclusion combined with past management history have contributed to the current condition of extensive areas of high-density, shade-tolerant coniferous stands that are increasingly prone to high-severity fires. Here, we report the modeled effects of constructed defensible fuel profile zones and group selection...

  2. Optimizing human hepatocyte models for metabolic phenotype and function: effects of treatment with dimethyl sulfoxide (DMSO).

    Science.gov (United States)

    Nikolaou, Nikolaos; Green, Charlotte J; Gunn, Pippa J; Hodson, Leanne; Tomlinson, Jeremy W

    2016-11-01

    Primary human hepatocytes are considered to be the "gold standard" cellular model for studying hepatic fatty acid and glucose metabolism; however, they come with limitations. Although the HepG2 cell line retains many of the primary hepatocyte metabolic functions they have a malignant origin and low rates of triglyceride secretion. The aim of this study was to investigate whether dimethyl sulfoxide supplementation in the media of HepG2 cells would enhance metabolic functionality leading to the development of an improved in vitro cell model that closely recapitulates primary human hepatocyte metabolism. HepG2 cells were cultured in media containing 1% dimethyl sulfoxide for 2, 4, 7, 14, and 21 days. Gene expression, protein levels, intracellular triglyceride, and media concentrations of triglyceride, urea, and 3-hydroxybutyrate concentrations were measured. Dimethyl sulfoxide treatment altered the expression of genes involved in lipid (FAS, ACC1, ACC2, DGAT1, DGAT2, SCD) and glucose (PEPCK, G6Pase) metabolism as well as liver functionality (albumin, alpha-1-antitrypsin, AFP). mRNA changes were paralleled by alterations at the protein level. DMSO treatment decreased intracellular triglyceride content and lactate production and increased triglyceride and 3-hydroxybutyrate concentrations in the media in a time-dependent manner. We have demonstrated that the addition of 1% dimethyl sulfoxide to culture media changes the metabolic phenotype of HepG2 cells toward a more primary human hepatocyte phenotype. This will enhance the currently available in vitro model systems for the study of hepatocyte biology related to pathological processes that contribute to disease and their response to specific therapeutic interventions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  3. Consistent treatment of viscoelastic effects at junctions in one-dimensional blood flow models

    Science.gov (United States)

    Müller, Lucas O.; Leugering, Günter; Blanco, Pablo J.

    2016-06-01

    While the numerical discretization of one-dimensional blood flow models for vessels with viscoelastic wall properties is widely established, there is still no clear approach on how to couple one-dimensional segments that compose a network of viscoelastic vessels. In particular for Voigt-type viscoelastic models, assumptions with regard to boundary conditions have to be made, which normally result in neglecting the viscoelastic effect at the edge of vessels. Here we propose a coupling strategy that takes advantage of a hyperbolic reformulation of the original model and the inherent information of the resulting system. We show that applying proper coupling conditions is fundamental for preserving the physical coherence and numerical accuracy of the solution in both academic and physiologically relevant cases.

  4. The effect of vegetation on pesticide dissipation from ponded treatment wetlands: quantification using a simple model.

    Science.gov (United States)

    Rose, Michael T; Crossan, Angus N; Kennedy, Ivan R

    2008-07-01

    Field data shows that plants accelerate pesticide dissipation from aquatic systems by increasing sedimentation, biofilm contact and photolysis. In this study, a graphical model was constructed and calibrated with site-specific and supplementary data to describe the loss of two pesticides, endosulfan and fluometuron, from a vegetated and a non-vegetated pond. In the model, the major processes responsible for endosulfan dissipation were alkaline hydrolysis and sedimentation, with the former process being reduced by vegetation and the latter enhanced. Fluometuron dissipation resulted primarily from biofilm reaction and photolysis, both of which were increased by vegetation. Here, greater photolysis under vegetation arose from faster sedimentation and increased light penetration, despite shading. Management options for employing constructed wetlands to polish pesticide-contaminated agricultural runoff are discussed. The lack of easily fulfilled sub-models and data describing the effect of aquatic vegetation on water chemistry and sedimentation is also highlighted.

  5. Effect on epileptogenesis of carbamazepine treatment during the silent period of the pilocarpine model of epilepsy.

    Science.gov (United States)

    Capella, H M; Lemos, T

    2002-01-01

    This study addresses the question of epileptogenesis by investigating the effects of carbamazepine (CBZ) on the silent period of the pilocarpine model of epilepsy. Adult Wistar rats were subjected to status epilepticus (SE) induced by pilocarpine and treated with CBZ or saline, i.p, during 56 days. Latency for the first spontaneous seizure, incidence, frequency, and duration of seizures were monitored for seizures and the hippocampal damage. CBZ did not abort the epileptogenesis but minimized the expression of seizures and hippocampal damage.

  6. 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 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......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...... 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....

  7. 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.

  8. Bayesian Treatment Effects Models with Variable Selection for Panel Outcomes with an Application to Earnings Effects of Maternity Leave

    OpenAIRE

    Jacobi, Liana; Wagner, Helga; Frühwirth-Schnatter, Sylvia

    2014-01-01

    Child birth leads to a break in a woman's employment history and is considered one reason for the relatively poor labor market outcomes observed for women compared to men. However, the time spent at home after child birth varies significantly across mothers and is likely driven by observed and, more importantly, unobserved factors that also affect labor market outcomes directly. In this paper we propose two alternative Bayesian treatment modeling and inferential frameworks for panel outcomes ...

  9. 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.

  10. Modelling beam transport and biological effectiveness to develop treatment planning for ion beam radiotherapy

    CERN Document Server

    Grzanka, Leszek

    2014-01-01

    Radiation therapy with carbon ions is a novel technique of cancer radiotherapy, applicable in particular to treating radioresistant tumours at difficult localisations. Therapy planning, where the medical physicist, following the medical prescription, finds the optimum distribution of cancer cells to be inactivated by their irradiation over the tumour volume, is a basic procedure of cancer radiotherapy. The main difficulty encountered in therapy planning for ion radiotherapy is to correctly account for the enhanced radiobiological effectiveness of ions in the Spread Out Bragg Peak (SOBP) region over the tumour volume. In this case, unlike in conventional radiotherapy with photon beams, achieving a uniform dose distribution over the tumour volume does not imply achieving uniform cancer cell inactivation. In this thesis, an algorithm of the basic element (kernel) of a treatment planning system (TPS) for carbon ion therapy is developed. The algorithm consists of a radiobiological part which suitably corrects for ...

  11. 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.

  12. 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.

  13. Estimating treatment effect in a proportional hazards model in randomized clinical trials with all-or-nothing compliance.

    Science.gov (United States)

    Li, Shuli; Gray, Robert J

    2016-09-01

    We consider methods for estimating the treatment effect and/or the covariate by treatment interaction effect in a randomized clinical trial under noncompliance with time-to-event outcome. As in Cuzick et al. (2007), assuming that the patient population consists of three (possibly latent) subgroups based on treatment preference: the ambivalent group, the insisters, and the refusers, we estimate the effects among the ambivalent group. The parameters have causal interpretations under standard assumptions. The article contains two main contributions. First, we propose a weighted per-protocol (Wtd PP) estimator through incorporating time-varying weights in a proportional hazards model. In the second part of the article, under the model considered in Cuzick et al. (2007), we propose an EM algorithm to maximize a full likelihood (FL) as well as the pseudo likelihood (PL) considered in Cuzick et al. (2007). The E step of the algorithm involves computing the conditional expectation of a linear function of the latent membership, and the main advantage of the EM algorithm is that the risk parameters can be updated by fitting a weighted Cox model using standard software and the baseline hazard can be updated using closed-form solutions. Simulations show that the EM algorithm is computationally much more efficient than directly maximizing the observed likelihood. The main advantage of the Wtd PP approach is that it is more robust to model misspecifications among the insisters and refusers since the outcome model does not impose distributional assumptions among these two groups. © 2016, The International Biometric Society.

  14. The effect of tendon surface treatment on cell attachment for potential enhancement of tendon graft healing: an ex vivo model.

    Science.gov (United States)

    Hashimoto, Takahiro; Sun, Yu-Long; An, Kai-Nan; Amadio, Peter C; Zhao, Chunfeng

    2012-12-01

    For both tendon allografts and autografts, the surface, initially optimized for gliding, may not be ideal to facilitate tissue integration for graft healing to host tendon or bone. As a prelude to studying tendon-bone integration, we investigated the effect of surface treatments with trypsin or mechanical abrasion on cell attachment to the tendon surface in a canine ex vivo intrasynovial tendon tissue culture model. Intrasynovial tendon allograft surfaces were seeded with cells after the following treatments: (1) no treatment, (2) mechanical abrasion, (3) trypsin, and (4) abrasion and trypsin. The area covered by cells was determined using confocal laser microscopy at one and two weeks. Results were compared to untreated extrasynovial tendon. Additional tendons were characterized with scanning electron microscopy. Tendons with trypsin treatment had significantly more surface coverage with cells than the other groups, after both one and two weeks of culture. In terms of the cellular shape and size, cells on tendons with trypsin treatment spread more and were more polygonal in shape, whereas tendons with mechanical abrasion with/without trypsin treatment contained smaller, more spindle-like cells. Surface roughening can affect cell behavior with topographical stimulation. Trypsin surface digestion exposes a mesh-like structure on the tendon surface, which could enhance cell adherence and, possibly, tendon/bone healing.

  15. 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

  16. Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Liu, Weilin; Struik, Dicky; Nies, Vera J M; Jurdzinski, Angelika; Harkema, Liesbeth; de Bruin, Alain; Verkade, Henkjan J; Downes, Michael; Evans, Ronald M; van Zutphen, Tim; Jonker, Johan W

    2016-02-23

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with obesity and type 2 diabetes. Currently, there is no approved pharmacological treatment for this disease, but improvement of insulin resistance using peroxisome proliferator-activated receptor-γ (PPARγ) agonists, such as thiazolidinediones (TZDs), has been shown to reduce steatosis and steatohepatitis effectively and to improve liver function in patients with obesity-related NAFLD. However, this approach is limited by adverse effects of TZDs. Recently, we have identified fibroblast growth factor 1 (FGF1) as a target of nuclear receptor PPARγ in visceral adipose tissue and as a critical factor in adipose remodeling. Because FGF1 is situated downstream of PPARγ, it is likely that therapeutic targeting of the FGF1 pathway will eliminate some of the serious adverse effects associated with TZDs. Here we show that pharmacological administration of recombinant FGF1 (rFGF1) effectively improves hepatic inflammation and damage in leptin-deficient ob/ob mice and in choline-deficient mice, two etiologically different models of NAFLD. Hepatic steatosis was effectively reduced only in ob/ob mice, suggesting that rFGF1 stimulates hepatic lipid catabolism. Potentially adverse effects such as fibrosis or proliferation were not observed in these models. Because the anti-inflammatory effects were observed in both the presence and absence of the antisteatotic effects, our findings further suggest that the anti-inflammatory property of rFGF1 is independent of its effect on lipid catabolism. Our current findings indicate that, in addition to its potent glucose-lowering and insulin-sensitizing effects, rFGF1 could be therapeutically effective in the treatment of NAFLD.

  17. 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.

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:25253417

  18. Temperature, plant species and residence time effects on nitrogen removal in model treatment wetlands.

    Science.gov (United States)

    Allen, C R; Stein, O R; Hook, P B; Burr, M D; Parker, A E; Hafla, E C

    2013-01-01

    Total nitrogen (TN) removal in treatment wetlands (TWs) is challenging due to nitrogen cycle complexity and the variation of influent nitrogen species. Plant species, season, temperature and hydraulic loading most likely influence root zone oxygenation and appurtenant nitrogen removal, especially for ammonium-rich wastewater. Nitrogen data were collected from two experiments utilizing batch-loaded (3-, 6-, 9- and 20-day residence times), sub-surface TWs monitored for at least one year during which temperature was varied between 4 and 24 °C. Synthetic wastewater containing 17 mg/l N as NH4 and 27 mg/l amino-N, 450 mg/l chemical oxygen demand (COD), and 13 mg/l SO4-S was applied to four replicates of Carex utriculata, Schoenoplectus acutus and Typha latifolia and unplanted controls. Plant presence and species had a greater effect on TN removal than temperature or residence time. Planted columns achieved approximately twice the nitrogen removal of unplanted controls (40-95% versus 20-50% removal) regardless of season and temperature. TWs planted with Carex outperformed both Typha and Schoenoplectus and demonstrated less temperature dependency. TN removal with Carex was excellent at all temperatures and residence times; Schoenoplectus and Typha TN removal improved at longer residence times. Reductions in TN were not accompanied by increases in NO3, which was consistently below 1 mg/l N.

  19. 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.

  20. Effects of timely insulin treatment on protection of β cells in a rat model of type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    周迎生; 高妍; 郭晓蕙; 李斌; 王抒; 迟家敏

    2004-01-01

    Background Insulin treatment plays a key role in management of diabetes mellitus. Clinical researches showed that extra improvements in restoration of insulin secretion of pancreatic β cells were found in patients with newly diagnosed type 2 diabetes. The purpose of this study was to investigate the effects of early insulin treatment on insulin mRNA expression and morphological alterations of β cells in a Sprague Dawley (SD) rat model of type 2 diabetes. Methods A rat model of type 2 diabetes mellitus (T2DM) was induced by a high fat diet (high energy, HE) and low doses of streptozotoxin (STZ, 40 mg/kg). A group of diabetic rats was then injected with protamine zinc insulin (PZI, 1-2 U·kg-1·d-1) for one week. Insulin mRNA expression, morphological features of pancreatic islets, and metabolic parameters were examined in rats using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and other techniques. Results In insulin-treated diabetic rats, insulin mRNA levels prominently increased by 81.3% (P<0.05), as compared with untreated diabetic rats. Moreover, timely insulin treatment noticeably improved the insulin content of β cells, with an increase of 10.2% (P<0.05), despite a slight reduction in fasting blood glucose (FBG), triglyceride (TG), and free fatty acid (FFA) levels, as compared to an untreated diabetic group. Conclusion Insulin treatment at the onset of T2DM effectively improves insulin synthesis, as confirmed by morphological changes to β cells in a rat model of type 2 diabetes.

  1. Cardiological aging in SAM model: effect of chronic treatment with growth hormone.

    Science.gov (United States)

    Forman, K; Vara, E; García, C; Ariznavarreta, C; Escames, G; Tresguerres, J A F

    2010-06-01

    The purpose of this study was to investigate the effect of aging on different parameters related to inflammation, oxidative stress and apoptosis in hearts from two types of male mice models: senescence-accelerated mice (SAM-P8) and senescence-accelerated-resistant (SAM-R1), and the influence of chronic administration of Growth Hormone (GH) on old SAM-P8 mice. Forty male mice were used. Animals were divided into five experimental groups: two 10 month old untreated groups (SAM-P8/SAM-R1), two 2 month old young groups (SAM-P8/SAM-R1) and one 10 month old group (SAM-P8) treated with GH for 30 days. The expression of tumor necrosis factor-alpha, interleukin 1, interleukin 10, heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases, NFkB, Bad, Bax and Bcl-2 were determined by real-time reverse transcription polymerase chain reaction (RT-PCR). Results were submitted to a two way ANOVA statistical evaluation using the Statgraphics program. Inflammation, as well as, oxidative stress and apoptosis markers were increased in the heart of old SAM-P8 males, as compared to young controls and this situation was not observed in the old SAM-R1 mice. Exogenous GH administration reverted the effect of aging in the described parameters of old SAM-P8 mice. Our results suggest that inflammation, apoptosis and oxidative stress could play an important role in the observed cardiovascular alterations related to aging of SAM-P8 mice and that GH may play a potential protective effect on the cardiovascular system of these animals.

  2. Symptom Effects on Employment in a Structural Model of Mental Illness and Treatment: Analysis of Patients with Schizophrenia.

    Science.gov (United States)

    Slade, Eric; Salkever, David

    2001-03-01

    BACKGROUND: There is a long tradition in the health and mental health economics literatures of estimating the impacts of disorders on employment and earnings. Several analyses have associated mental illness with poorer labor market outcomes, often using indicators of disorders to measure mental illness, but it is unclear to what extent unobserved medical treatment biases the estimated impacts of disorders on labor market outcomes. In this study we argue that in order to judge the true employment costs of mental illness and the potential benefits of treatment it is necessary to account for the structural relationship between treatment, symptoms, and employment outcomes. AIMS OF THE STUDY: The study proposes a structural model for understanding mental illness impacts on employment and empirically estimates one element of this structural model that links symptoms of schizophrenia to patients' employment status. In addition, we use our empirical estimates to simulate employment consequences of more effective treatment and reductions in symptom levels. EMPIRICAL METHODS: Our empirical analyses use a sample of 1,643 adults with a schizophrenia diagnosis. We predict the likelihood of three outcomes - not employed, employed in a sheltered or supported job, and employed in a non-supported job. Analyses include measures of demographic characteristics, illness history, location differences, and detailed symptom measures. RESULTS: We find that negative symptoms have a substantial adverse impact on participation in both non-supported jobs and in sheltered or supported jobs. The impacts on employment of other symptoms of schizophrenia are not as large, but significant effects are also found for symptoms of depression. Simulations suggest, however, that only one-third of consumers would be employed in any type of job even given a large reduction in symptom levels. DISCUSSION: Negative symptoms are particularly important for role functioning and employment. The marginal effect on

  3. Cost effectiveness of intermittent screening followed by treatment versus intermittent preventive treatment during pregnancy in West Africa: analysis and modelling of results from a non-inferiority trial.

    Science.gov (United States)

    Fernandes, Silke; Sicuri, Elisa; Halimatou, Diawara; Akazili, James; Boiang, Kalifa; Chandramohan, Daniel; Coulibaly, Sheikh; Diawara, Sory Ibrahim; Kayentao, Kassoum; Ter Kuile, Feiko; Magnussen, Pascal; Tagbor, Harry; Williams, John; Woukeu, Arouna; Cairns, Matthew; Greenwood, Brian; Hanson, Kara

    2016-09-23

    Emergence of high-grade sulfadoxine-pyrimethamine (SP) resistance in parts of Africa has led to growing concerns about the efficacy of intermittent preventive treatment of malaria during pregnancy (IPTp) with SP. The incremental cost-effectiveness of intermittent screening and treatment (ISTp) with artemether-lumefantrine (AL) as an alternative strategy to IPTp-SP was estimated followed by a simulation of the effects on cost-effectiveness of decreasing efficacy of IPTp-SP due to SP resistance. The analysis was based on results from a multi-centre, non-inferiority trial conducted in West Africa. A decision tree model was analysed from a health provider perspective. Model parameters for all trial countries with appropriate ranges and distributions were used in a probabilistic sensitivity analysis. Simulations were performed in hypothetical cohorts of 1000 pregnant women who received either ISTp-AL or IPTp-SP. In addition a cost-consequences analysis was conducted. Trial estimates were used to calculate disability-adjusted-life-years (DALYs) for low birth weight and severe/moderate anaemia (both shown to be non-inferior for ISTp-AL) and clinical malaria (inferior for ISTp-AL). Cost estimates were obtained from observational studies, health facility costings and public procurement databases. Results were calculated as incremental cost per DALY averted. Finally, the cost-effectiveness changes with decreasing SP efficacy were explored by simulation. Relative to IPTp-SP, delivering ISTp-AL to 1000 pregnant women cost US$ 4966.25 more (95 % CI US$ 3703.53; 6376.83) and led to a small excess of 28.36 DALYs (95 % CI -75.78; 134.18), with LBW contributing 81.3 % of this difference. The incremental cost-effectiveness ratio was -175.12 (95 % CI -1166.29; 1267.71) US$/DALY averted. Simulations show that cost-effectiveness of ISTp-AL increases as the efficacy of IPTp-SP decreases, though the specific threshold at which ISTp-AL becomes cost-effective depends on assumptions

  4. Systematic review and economic modelling of the effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence.

    Science.gov (United States)

    Imamura, M; Abrams, P; Bain, C; Buckley, B; Cardozo, L; Cody, J; Cook, J; Eustice, S; Glazener, C; Grant, A; Hay-Smith, J; Hislop, J; Jenkinson, D; Kilonzo, M; Nabi, G; N'Dow, J; Pickard, R; Ternent, L; Wallace, S; Wardle, J; Zhu, S; Vale, L

    2010-08-01

    To assess the clinical effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence (SUI) through systematic review and economic modelling. The Cochrane Incontinence Group Specialised Register, electronic databases and the websites of relevant professional organisations and manufacturers, and the following databases: CINAHL, EMBASE, BIOSIS, Science Citation Index and Social Science Citation Index, Current Controlled Trials, ClinicalTrials.gov and the UKCRN Portfolio Database. The study comprised three distinct elements. (1) A survey of 188 women with SUI to identify outcomes of importance to them (activities of daily living; sex, hygiene and lifestyle issues; emotional health; and the availability of services). (2) A systematic review and meta-analysis of non-surgical treatments for SUI to find out which are most effective by comparing results of trials (direct pairwise comparisons) and by modelling results (mixed-treatment comparisons - MTCs). A total of 88 randomised controlled trials (RCTs) and quasi-RCTs reporting data from 9721 women were identified, considering five generic interventions [pelvic floor muscle training (PFMT), electrical stimulation (ES), vaginal cones (VCs), bladder training (BT) and serotonin-noradrenaline reuptake inhibitor (SNRI) medications], in many variations and combinations. Data were available for 37 interventions and 68 treatment comparisons by direct pairwise assessment. Mixed-treatment comparison models compared 14 interventions, using data from 55 trials (6608 women). (3) Economic modelling, using a Markov model, to find out which combinations of treatments (treatment pathways) are most cost-effective for SUI. Titles and abstracts identified were assessed by one reviewer and full-text copies of all potentially relevant reports independently assessed by two reviewers. Any disagreements were resolved by consensus or arbitration by a third person. Direct pairwise comparison and MTC

  5. Bioluminescence-Based Tumor Quantification Method for Monitoring Tumor Progression and Treatment Effects in Mouse Lymphoma Models.

    Science.gov (United States)

    Cosette, Jeremie; Ben Abdelwahed, Rym; Donnou-Triffault, Sabrina; Sautès-Fridman, Catherine; Flaud, Patrice; Fisson, Sylvain

    2016-07-07

    Although bioluminescence imaging (BLI) shows promise for monitoring tumor burden in animal models of cancer, these analyses remain mostly qualitative. Here we describe a method for bioluminescence imaging to obtain a semi-quantitative analysis of tumor burden and treatment response. This method is based on the calculation of a luminoscore, a value that allows comparisons of two animals from the same or different experiments. Current BLI instruments enable the calculation of this luminoscore, which relies mainly on the acquisition conditions (back and front acquisitions) and the drawing of the region of interest (manual markup around the mouse). Using two previously described mouse lymphoma models based on cell engraftment, we show that the luminoscore method can serve as a noninvasive way to verify successful tumor cell inoculation, monitor tumor burden, and evaluate the effects of in situ cancer treatment (CpG-DNA). Finally, we show that this method suits different experimental designs. We suggest that this method be used for early estimates of treatment response in preclinical small-animal studies.

  6. Modelling Cost-Effectiveness of Biologic Treatments Based on Disease Activity Scores for the Management of Rheumatoid Arthritis in Spain

    Directory of Open Access Journals (Sweden)

    Ariel Beresniak

    2011-01-01

    Full Text Available Background. The objective of this simulation model was to assess the cost-effectiveness of different biological treatment strategies based on levels of disease activity in Spain, in patients with moderate to severe active RA and an insufficient response to at least one anti-TNF agent. Methods. Clinically meaningful effectiveness criteria were defined using DAS28 scores: remission and Low Disease Activity State (LDAS thresholds. Monte-Carlo simulations were conducted to assess cost-effectiveness over 2 years of four biological sequential strategies composed of anti-TNF agents (adalimumab, infliximab, abatacept or rituximab, in patients with moderate to severe active RA and an insufficient response to etanercept as first biological agent. Results. The sequential strategy including etanercept, abatacept and adalimumab appeared more efficacious over 2 years (102 days in LDAS compared to the same sequence including rituximab as second biological option (82 days in LDAS. Cost-effectiveness ratios showed lower costs per day in LDAS with abatacept (427 € compared to rituximab as second biological option (508 €. All comparisons were confirmed when using remission criteria. Conclusion. Model results suggest that in patients with an insufficient response to anti-TNF agents, the biological sequences including abatacept appear more efficacious and cost-effective than similar sequences including rituximab or cycled anti-TNF agents.

  7. Effect of treatment with simvastatin on bone microarchitecture of the femoral head in an osteoporosis animal model.

    Science.gov (United States)

    Monteiro, Lucas Oliveira; Macedo, Ana Paula; Shimano, Roberta Carminati; Shimano, Antônio Carlos; Yanagihara, Gabriela Rezende; Ramos, Junia; Paulini, Marina Ribeiro; Tocchini de Figueiredo, Fellipe Augusto; Gonzaga, Miliane Gonçalves; Issa, João Paulo Mardegan

    2016-08-01

    The objective of this study was to evaluate the microarchitecture and trabecular bone strength at the distal region of the femur, and its biomechanical properties with simvastatin administration with two different doses in ovariectomized (OVX) rats. Ninety rats were divided into six groups to evaluate treatment with the simvastatin drug (n = 15): SH (Sham surgery), SH-5 (5 mg simvastatin), SH-20 (20 mg simvastatin), OVX, OVX-5, and OVX-20. Euthanasia was performed at three different times, five animals per period: 7, 14, and 28 days. The effectiveness of the treatments was evaluated by mechanical testing and histomorphometric analysis of the femurs. The results of analysis by the linear model of mixed effects showed 20 mg of simvastatin results in increased trabecular bone after 14 days (P = 0.039) of ingestion in ovariectomized animals. However, ingestion of 5 mg of simvastatin is able to sensitize the trabecular bone only at 28 days (P = 0.005) of ingestion. In the mechanical tests stiffness improves within 28 days (P = 0.003). Regarding maximum strength, no statistical differences were observed. According to these results, it can be concluded that for a decrease in oral intake, longer treatment times are required. Microsc. Res. Tech. 79:684-690, 2016. © 2016 Wiley Periodicals, Inc.

  8. 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. Pre-cl

  9. Thalidomide Effects in Patients with Hereditary Hemorrhagic Telangiectasia During Therapeutic Treatment and in Fli-EGFP Transgenic Zebrafish Model

    Institute of Scientific and Technical Information of China (English)

    Hong-Ling Peng; Yi-Fang Yi; Shun-Ke Zhou; Si-Si Xie; Guang-Sen Zhang

    2015-01-01

    Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis,mucocutaneous telangiectasia, and arteriovenous malformations.The efficacy of traditional treatments for HHT is very limited.The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model.Methods: HHT was diagnosed according to Shovlin criteria.Five HHT patients were treated with thalidomide (100 mg/d).The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide.The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis.Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-β3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment.Results: The average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P =0.009).The "telangiectatic spot" on the tongue almost vanished;CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation.The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-β3 mRNA expression of five patients was lower after thalidomide therapy.The plasma VEGF protein expression was down-regulated in HHT patients.Conclusions: Thalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-β3 and VEGF in HHT patients.It also leads to vascular remodeling in the zebrafish model.

  10. 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.

  11. Anticonvulsant Effects of Combined Treatment with Citicoline and Valproate on the Model of Acute Generalized Convulsions Induced by Pentylenetetrazole in Wistar Rats.

    Science.gov (United States)

    Karpova, M N; Kuznetsova, L V; Zin'kovskii, K A; Klishina, N V

    2016-02-01

    We studied anticonvulsant effects of combined treatment with citicoline, a nootropic substance with neuroregenerative and neuroprotective activities, and valproate, an antiepileptic agent widely used in the treatment of epilepsy, on the model of pentylenetetrazole-induced (75 mg/kg, intraperitoneally) acute generalized convulsions in male Wistar rats. Combined treatment with citicoline and valproate in minimum effective doses (70 and 300 mg/kg, respectively) potentiated the anticonvulsant properties of both agents.

  12. Treatment scale-up to achieve global HCV incidence and mortality elimination targets: a cost-effectiveness model.

    Science.gov (United States)

    Scott, Nick; McBryde, Emma S; Thompson, Alexander; Doyle, Joseph S; Hellard, Margaret E

    2017-08-01

    The WHO's draft HCV elimination targets propose an 80% reduction in incidence and a 65% reduction in HCV-related deaths by 2030. We estimate the treatment scale-up required and cost-effectiveness of reaching these targets among injecting drug use (IDU)-acquired infections using Australian disease estimates. A mathematical model of HCV transmission, liver disease progression and treatment among current and former people who inject drugs (PWID). Treatment scale-up and the most efficient allocation to priority groups (PWID or patients with advanced liver disease) were determined; total healthcare and treatment costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) compared with inaction were calculated. 5662 (95% CI 5202 to 6901) courses per year (30/1000 IDU-acquired infections) were required, prioritised to patients with advanced liver disease, to reach the mortality target. 4725 (3278-8420) courses per year (59/1000 PWID) were required, prioritised to PWID, to reach the incidence target; this also achieved the mortality target, but to avoid clinically unacceptable HCV-related deaths an additional 5564 (1959-6917) treatments per year (30/1000 IDU-acquired infections) were required for 5 years for patients with advanced liver disease. Achieving both targets in this way cost $A4.6 ($A4.2-$A4.9) billion more than inaction, but gained 184 000 (119 000-417 000) QALYs, giving an ICER of $A25 121 ($A11 062-$A39 036) per QALY gained. Achieving WHO elimination targets with treatment scale-up is likely to be cost-effective, based on Australian HCV burden and demographics. Reducing incidence should be a priority to achieve both WHO elimination goals in the long-term. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. SmEdA vibro-acoustic modelling in the mid-frequency range including the effect of dissipative treatments

    Science.gov (United States)

    Hwang, H. D.; Maxit, L.; Ege, K.; Gerges, Y.; Guyader, J.-L.

    2017-04-01

    Vibro-acoustic simulation in the mid-frequency range is of interest for automotive and truck constructors. The dissipative treatments used for noise and vibration control such as viscoelastic patches and acoustic absorbing materials must be taken into account in the problem. The Statistical modal Energy distribution Analysis (SmEdA) model consists in extending Statistical Energy Analysis (SEA) to the mid-frequency range by establishing power balance equations between the modes of the different subsystems. The modal basis of uncoupled-subsystems that can be estimated by the finite element method in the mid-frequency range is used as input data. SmEdA was originally developed by considering constant modal damping factors for each subsystem. However, this means that it cannot describe the local distribution of dissipative materials. To overcome this issue, a methodology is proposed here to take into account the effect of these materials. This methodology is based on the finite element models of the subsystems that include well-known homogenized material models of dissipative treatments. The Galerkin method with subsystem normal modes is used to estimate the modal damping loss factors. Cross-modal coupling terms which appear in the formulation due to the dissipative materials are assumed to be negligible. An approximation of the energy sharing between the subsystems damped by dissipative materials is then described by SmEdA. The different steps of the method are validated experimentally by applying it to a laboratory test case composed of a plate-cavity system with different configurations of dissipative treatments. The comparison between the experimental and the simulation results shows good agreement in the mid-frequency range.

  14. PCP-based mice models of schizophrenia: differential behavioral, neurochemical and cellular effects of acute and subchronic treatments.

    Science.gov (United States)

    Castañé, Anna; Santana, Noemí; Artigas, Francesc

    2015-11-01

    N-methyl-D-aspartate receptor (NMDA-R) hypofunction has been proposed to account for the pathophysiology of schizophrenia. Thus, NMDA-R blockade has been used to model schizophrenia in experimental animals. Acute and repeated treatments have been successfully tested; however, long-term exposure to NMDA-R antagonists more likely resembles the core symptoms of the illness. To explore whether schizophrenia-related behaviors are differentially induced by acute and subchronic phencyclidine (PCP) treatment in mice and to examine the neurobiological bases of these differences. Subchronic PCP induced a sensitization of acute locomotor effects. Spontaneous alternation in a T-maze and novel object recognition performance were impaired after subchronic but not acute PCP, suggesting a deficit in working memory. On the contrary, reversal learning and immobility in the tail suspension test were unaffected. Subchronic PCP significantly reduced basal dopamine but not serotonin output in medial prefrontal cortex (mPFC) and markedly decreased the expression of tyrosine hydroxylase in the ventral tegmental area. Finally, acute and subchronic PCP treatments evoked a different pattern of c-fos expression. At 1 h post-treatment, acute PCP increased c-fos expression in many cortical regions, striatum, thalamus, hippocampus, and dorsal raphe. However, the increased c-fos expression produced by subchronic PCP was restricted to the retrosplenial cortex, thalamus, hippocampus, and supramammillary nucleus. Four days after the last PCP injection, c-fos expression was still increased in the hippocampus of subchronic PCP-treated mice. Acute and subchronic PCP administration differently affects neuronal activity in brain regions relevant to schizophrenia, which could account for their different behavioral effects.

  15. Tract shape modeling detects changes associated with preterm birth and neuroprotective treatment effects

    Directory of Open Access Journals (Sweden)

    Devasuda Anblagan

    2015-01-01

    Tract topology is a biomarker of preterm brain injury. The data provide proof of concept that tract-averaged dMRI parameters have utility for evaluating tissue effects of perinatal neuroprotective strategies.

  16. Progressive effect of beta amyloid peptides accumulation on CA1 pyramidal neurons: a model study suggesting possible treatments

    Directory of Open Access Journals (Sweden)

    Viviana eCulmone

    2012-07-01

    Full Text Available Several independent studies show that accumulation of β-amyloid (Aβ peptides , one of the characteristic hallmark of Alzheimer’s Disease (AD, can affect normal neuronal activity in different ways. However, in spite of intense experimental work to explain the possible underlying mechanisms of action, a comprehensive and congruent understanding is still lacking. Part of the problem might be the opposite ways in which Aβ have been experimentally found to affect the normal activity of a neuron; for example, making a neuron more excitable (by reducing the A- or DR-type K+ currents or less excitable (by reducing synaptic transmission and Na+ current. The overall picture is therefore confusing, since the interplay of many mechanisms makes it difficult to link individual experimental findings with the more general problem of understanding the progression of the disease. This is an important issue, especially for the development of new drugs trying to ameliorate the effects of the disease. We addressed these paradoxes through computational models. We first modeled the different stages of AD by progressively modifying the intrinsic membrane and synaptic properties of a realistic model neuron, while accounting for multiple and different experimental findings and by evaluating the contribution of each mechanism to the overall modulation of the cell’s excitability. We then tested a number of manipulations of channel and synaptic activation properties that could compensate for the effects of Aβ. The model predicts possible therapeutic treatments in terms of pharmacological manipulations of channels’ kinetic and activation properties. The results also suggest how and which mechanisms can be targeted by a drug to restore the original firing conditions.

  17. Outcomes and Cost-Effectiveness of Two Nicotine Replacement Treatment Delivery Models for a Tobacco Quitline

    Directory of Open Access Journals (Sweden)

    Lija Greenseid

    2011-05-01

    Full Text Available Many tobacco cessation quitlines provide nicotine replacement therapy (NRT in the U.S. but consensus is lacking regarding the best shipping protocol or NRT amounts. We evaluated the impact of the Minnesota QUITPLAN® Helpline’s shift from distributing NRT using a single eight-week shipment to a two-shipment protocol. For this observational study, the eight week single-shipment cohort (n = 247 received eight weeks of NRT (patches or gum at once, while the split-shipment cohort (n = 160 received five weeks of NRT (n = 94, followed by an additional three weeks of NRT if callers continued with counseling (n = 66. Patient satisfaction, retention, quit rates, and cost associated with the three groups were compared. A higher proportion of those receiving eight weeks of NRT, whether in one or two shipments, reported that the helpline was “very helpful” (77.2% of the single-shipment group; 81.1% of the two-shipment group than those receiving five weeks of NRT (57.8% of the one-shipment group (p = 0.004. Callers in the eight week two-shipment group completed significantly more calls (3.0 than callers in the five week one-shipment group (2.4 or eight week single-shipment group (1.7 (p < 0.001. Using both responder and intent-to-treat calculations, there were no significant differences in 30-day point prevalence abstinence at seven months among the three protocol groups even when controlling for demographic and tobacco use characteristics, and treatment group protocol. The mean cost per caller was greater for the single-shipment phase than the split-shipment phase ($350 vs. $326 due to the savings associated with not sending a second shipment to some participants. Assuming no difference in abstinence rates resulting from the protocol change, cost-per-quit was lowest for the five week one-shipment group ($1,155, and lower for the combined split-shipment cohort ($1,242 than for the single-shipment cohort ($1,350. Results of this evaluation indicate that

  18. 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.

  19. 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.

  20. Therapeutic effect of topical application of curcumin during treatment of radiation burns in a mini-pig model.

    Science.gov (United States)

    Kim, Joongsun; Park, Sunhoo; Jeon, Byung-Suk; Jang, Won-Seok; Lee, Sun-Joo; Son, Yeonghoon; Rhim, Kyung-Jin; Lee, Soong In; Lee, Seung-Sook

    2016-12-30

    Curcumin protects the skin against radiation-induced epidermal damage and prevents morphological changes induced by irradiation skin, thereby maintaining the epidermal thickness and cell density of basal layers. In this study, the effects of topical curcumin treatment on radiation burns were evaluated in a mini-pig model. Histological and clinical changes were observed five weeks after radiation exposure to the back (⁶⁰Co gamma-radiation, 50 Gy). Curcumin was applied topically to irradiated skin (200 mg/cm²) twice a day for 35 days. Curcumin application decreased the epithelial desquamation after irradiation. Additionally, when compared to the vehicle-treated group, the curcumin-treated group showed reduced expression of cyclooxygenase-2 and nuclear factor-kappaB. Furthermore, irradiation prolonged healing of biopsy wounds in the exposed area, whereas curcumin treatment stimulated wound healing. These results suggest that curcumin can improve epithelial cell survival and recovery in the skin and therefore be used to treat radiation burns.

  1. Protective effect of treatment with thiamine or benfotiamine on liver oxidative damage in rat model of acute ethanol intoxication.

    Science.gov (United States)

    Portari, Guilherme Vannucchi; Ovidio, Paula Payão; Deminice, Rafael; Jordão, Alceu Afonso

    2016-10-01

    The aim of this study was to evaluate possible beneficial effects of treatment with thiamine or benfotiamine in an animal model of acute ethanol intoxication. Thirty male Wistar rats were separated at random into three groups of 10 animals each: Ethanol (E), Ethanol treated with thiamine (T) and Ethanol treated with benfotiamine (BE). Rats were gavaged with single dose of ethanol (5g/kg, 40% v:v). After 30min of ethanol gavage the animals were treated with thiamine or benfotiamine. Six hours after first gavage, the animals were euthanized and blood and liver samples were collected for ethanol and oxidative stress biomarkers quantification. Serum ethanol levels were higher in animals treated with thiamine or benfotiamine while hepatic alcohol levels were higher in animals of the group treated with benfotiamine comparing to controls or thiamine treated groups. The lipid peroxidation biomarkers were diminished for the groups treated with thiamine or benfotiamine comparing to E animals. Concerning protein oxidative damage parameters, they were enhanced for animals treated with benfotiamine in relation to other groups. In conclusion, the treatment with thiamine or benfotiamine even 30min after the massive dose of ethanol has proven to be beneficial against liver damage. Improved results were obtained with benfotiamine in relation to oxidative damage from aqueous compartments. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Gaussian process modeling in conjunction with individual patient simulation modeling: a case study describing the calculation of cost-effectiveness ratios for the treatment of established osteoporosis.

    Science.gov (United States)

    Stevenson, M D; Oakley, J; Chilcott, J B

    2004-01-01

    Individual patient-level models can simulate more complex disease processes than cohort-based approaches. However, large numbers of patients need to be simulated to reduce 1st-order uncertainty, increasing the computational time required and often resulting in the inability to perform extensive sensitivity analyses. A solution, employing Gaussian process techniques, is presented using a case study, evaluating the cost-effectiveness of a sample of treatments for established osteoporosis. The Gaussian process model accurately formulated a statistical relationship between the inputs to the individual patient model and its outputs. This model reduced the time required for future runs from 150 min to virtually-instantaneous, allowing probabilistic sensitivity analyses-to be undertaken. This reduction in computational time was achieved with minimal loss in accuracy. The authors believe that this case study demonstrates the value of this technique in handling 1st- and 2nd-order uncertainty in the context of health economic modeling, particularly when more widely used techniques are computationally expensive or are unable to accurately model patient histories.

  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. Cost-effectiveness of early-initiated treatment for advanced-stage epithelial ovarian cancer patients: a modeling study

    NARCIS (Netherlands)

    Hoyer, T.; Bekkers, R.L.; Gooszen, H.G.; Massuger, L.F.A.G.; Rovers, M.M.; Grutters, J.P.C.

    2014-01-01

    OBJECTIVE: Between diagnosis and primary treatment of patients with epithelial ovarian cancer (EOC), gaps of several weeks exist. Reducing these time intervals may benefit the patient and may lead to a reduction of costs. We explored the cost-effectiveness of early-initiated treatment of patients wi

  5. Ceftobiprole medocaril is an effective treatment against methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis in a rat model.

    Science.gov (United States)

    Barnea, Y; Navon-Venezia, S; Kuzmenko, B; Artzi, N; Carmeli, Y

    2014-03-01

    Methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis after median sternotomy is a major complication of cardiac surgery with significant morbidity and mortality rates. We evaluated the efficacy of ceftobiprole medocaril in a new rat model of mediastinitis and compared it to vancomycin. The model was induced in 92 rats. Infection was induced immediately after median sternotomy by the injection of MRSA (strain 3020, 1 × 10(7) cfu/rat) into the sternal bone. After 24 h, rats (groups of 6-8) were treated intraperitoneally for 5 days or 14 days by either: (i) saline (control, q8h), (ii) ceftobiprole medocaril (70 or 100 mg/kg, q8h), or (iii) vancomycin (50 mg/kg, q12h). Efficacy was determined by a reduction in bacterial cfu in the sternum and spleen tissues. Comparisons were performed using the Mann-Whitney test. A 5-day treatment course of ceftobiprole at both doses tested lead to a significant reduction in MRSA load in the sternum (p ceftobiprole lead to a complete clearance of MRSA from the sternum, similarly to vancomycin. Ceftobiprole also showed a significant effect on eliminating MRSA dissemination to the spleen compared to saline-treated rats. Ceftobiprole was effective in treating MRSA mediastinitis in the rat model. In the 5-day course, ceftobiprole showed a significant reduction in sternal MRSA counts and was superior to vancomycin. After 14 days, both ceftobiprole and vancomycin showed clearance of MRSA from the sternum in more than 50 % of rats and almost complete clearance in the remainder.

  6. A model-based cost-effectiveness analysis of osteoporosis screening and treatment strategy for postmenopausal Japanese women.

    Science.gov (United States)

    Yoshimura, M; Moriwaki, K; Noto, S; Takiguchi, T

    2017-02-01

    Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years.

  7. Cost-effectiveness of olanzapine long-acting injection in the treatment of patients with schizophrenia in the United States: a micro-simulation economic decision model.

    Science.gov (United States)

    Furiak, Nicolas M; Ascher-Svanum, Haya; Klein, Robert W; Smolen, Lee J; Lawson, Anthony H; Montgomery, William; Conley, Robert R

    2011-04-01

    To compare, from the perspective of third-party payers in the United States health care system, the cost-effectiveness of olanzapine long-acting injection (LAI, depot) with alternative antipsychotic agents including risperidone-LAI, paliperidone-LAI, haloperidol-LAI, and oral olanzapine, in the treatment of patients with schizophrenia who have been non-adherent or partially adherent with oral antipsychotics. A 1-year micro-simulation economic decision model was developed to simulate the dynamics of usual care of patients with schizophrenia who continue, discontinue, switch, or restart their medication. The model uses a range of clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation rates by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct health care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outputs include annual total direct cost (US$) per treatment and incremental cost-effectiveness values per additional QALY gained. Model results found that the olanzapine-LAI treatment strategy was more effective (greater QALYs) and less costly than risperidone-LAI, paliperidone-LAI, and haloperidol-LAI. In addition, olanzapine-LAI was both more effective and more costly, with an estimated incremental cost/QALY of $26,824 compared to oral olanzapine. The base-case and multiple sensitivity analyses found olanzapine-LAI to remain within acceptable cost-effective ranges (micro-simulation model finds the olanzapine-LAI treatment strategy to result in better effectiveness and to be a cost-effective alternative compared to oral olanzapine and the LAI formulations of risperidone, paliperidone, and haloperidol in the treatment of non-adherent and partially adherent patients with schizophrenia in the United States. A key limitation is the assumption how

  8. 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

    in several studies. METHOD: Thirty-nine Sprague-Dawley rats with AR were randomized to ten weeks of medical treatment with carvedilol or no treatment. Treatment was initiated either early or late after AR induction. The effect of carvedilol was assessed by serial echocardiography and invasive hemodynamic...... 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....... CONCLUSION: Carvedilol did not improve left ventricular remodeling or function in rats with surgically induced AR. Despite relative bradycardia, we did not find carvedilol to negatively impact the heart, either when treatment was initiated early or late in the course of disease....

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

    Science.gov (United States)

    Zhong, Shan-Shan; Xiang, Ya-Juan; Liu, Pen-Ju; He, Yang; Yang, Ting-Ting; Wang, Yang-Yang; Rong, A; Zhang, Jun; Liu, Guang-Zhi

    2017-10-05

    As a traditional Chinese medicine, Cordyceps sinensis (CS) possesses a variety of immunoregulatory properties. This study aimed to explore the therapeutic potential of CS in a mice model of multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein35-55to induce EAE, followed by an instant intragastric feeding with a low dosage of CS (low-CS group, n = 5), high dosage of CS (high-CS group, n = 5), or the same volume of normal saline (control group, n = 5). All the mice were observed for clinical assessment. Over the 30 days of CS treatment, flow cytometry was used to detect the frequency of helper T-cell (Th) subsets, Th1 and Th17, and CD4+ CD25+ regulatory T cells in the spleen and lymph nodes. Meanwhile, pathological changes in brain were determined using both hematoxylin-eosin and luxol fast blue staining. Data were analyzed using the one-way analysis of variance (ANOVA). Over the 15 and 30 days of CS treatment, the clinical assessment for EAE demonstrated that both high-CS group (2.51 ± 0.31 and 2.26 ± 0.39 scores, respectively) and low-CS group (2.99 ± 0.40 and 2.69 ± 0.46, respectively) had lower disease severity scores than those of control group (3.57 ± 0.53 and 3.29 ± 0.53, all P < 0.01, respectively). Meanwhile, after 15 and 30 days, the high-CS group (19.18 ± 1.34 g and 20.41 ± 1.56 g, respectively) and low-CS group (18.07 ± 1.18 g and 19.48 ± 1.69 g, respectively) had a lower body weight, as compared with control group (16.85 ± 1.15 g and 18.22 ± 1.63 g, all P < 0.01, respectively). At 30 days post-CS treatment, there was a lower Th1 frequency in the lymph nodes (2.85 ± 1.54% and 2.77 ± 1.07% vs. 5.35 ± 1.34%, respectively; P < 0.05) and spleens (3.96 ± 1.09% and 3.09 ± 0.84% vs. 5.07 ± 1.50%, respectively; P < 0.05) and less inflammatory infiltration and demyelination in the brain of CS-treated mice than that of control group. Our preliminary

  10. On the effects of malaria treatment on parasite drug resistance--probability modelling of genotyped malaria infections.

    Science.gov (United States)

    Kum, Cletus Kwa; Thorburn, Daniel; Ghilagaber, Gebrenegus; Gil, Pedro; Björkman, Anders

    2013-10-12

    We compare the frequency of resistant genes of malaria parasites before treatment and at first malaria incidence after treatment. The data come from a clinical trial at two health facilities in Tanzania and concerns single nucleotide polymorphisms (SNPs) at three positions believed to be related to resistance to malaria treatment. A problem is that mixed infections are common, which both obscures the underlying frequency of alleles at each locus as well as the associations between loci in samples where alleles are mixed. We use combinatorics and quite involved probability methods to handle multiple infections and multiple haplotypes. The infection with the different haplotypes seemed to be independent of each other. We showed that at two of the three studied SNPs, the proportion of resistant genes had increased after treatment with sulfadoxine-pyrimethamine alone but when treated in combination with artesunate, no effect was noticed. First recurrences of malaria associated more with sulfadoxine-pyrimethamine alone as treatment than when in combination with artesunate. We also found that the recruited children had two different ongoing malaria infections where the parasites had different gene types.

  11. A combined treatment of hydration and dynamical effects for the modeling of host-guest binding thermodynamics: the SAMPL5 blinded challenge

    Science.gov (United States)

    Pal, Rajat Kumar; Haider, Kamran; Kaur, Divya; Flynn, William; Xia, Junchao; Levy, Ronald M.; Taran, Tetiana; Wickstrom, Lauren; Kurtzman, Tom; Gallicchio, Emilio

    2017-01-01

    As part of the SAMPL5 blinded experiment, we computed the absolute binding free energies of 22 host-guest complexes employing a novel approach based on the BEDAM single-decoupling alchemical free energy protocol with parallel replica exchange conformational sampling and the AGBNP2 implicit solvation model specifically customized to treat the effect of water displacement as modeled by the Hydration Site Analysis method with explicit solvation. Initial predictions were affected by the lack of treatment of ionic charge screening, which is very significant for these highly charged hosts, and resulted in poor relative ranking of negatively versus positively charged guests. Binding free energies obtained with Debye-Hückel treatment of salt effects were in good agreement with experimental measurements. Water displacement effects contributed favorably and very significantly to the observed binding affinities; without it, the modeling predictions would have grossly underestimated binding. The work validates the implicit/explicit solvation approach employed here and it shows that comprehensive physical models can be effective at predicting binding affinities of molecular complexes requiring accurate treatment of conformational dynamics and hydration.

  12. 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.

    Science.gov (United States)

    Yu, Wenhua; Li, Changping; Fu, Xiaomeng; Cui, Zhuang; Liu, Xiaoqian; Fan, Linlin; Zhang, Guan; Ma, Jun

    2014-01-01

    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. 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. 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. 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 breastfeeding can not be ignored, we still suggest

  13. 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

  14. 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

    2015-10-01

    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.

  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. Evidence for pyronaridine as a highly effective partner drug for treatment of artemisinin-resistant malaria in a rodent model.

    Science.gov (United States)

    Henrich, Philipp P; O'Brien, Connor; Sáenz, Fabián E; Cremers, Serge; Kyle, Dennis E; Fidock, David A

    2014-01-01

    The increasing prevalence in Southeast Asia of Plasmodium falciparum infections with delayed parasite clearance rates, following treatment of malaria patients with the artemisinin derivative artesunate, highlights an urgent need to identify which of the currently available artemisinin-based combination therapies (ACTs) are most suitable to treat populations with emerging artemisinin resistance. Here, we demonstrate that the rodent Plasmodium berghei SANA strain has acquired artemisinin resistance following drug pressure, as defined by reduced parasite clearance and early recrudescence following daily exposure to high doses of artesunate or the active metabolite dihydroartemisinin. Using the SANA strain and the parental drug-sensitive N strain, we have interrogated the antimalarial activity of five ACTs, namely, artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine, and the newest combination artesunate-pyronaridine. By monitoring parasitemia and outcome for 30 days following initiation of treatment, we found that infections with artemisinin-resistant P. berghei SANA parasites can be successfully treated with artesunate-pyronaridine used at doses that are curative for the parental drug-sensitive N strain. No other partner drug combination was as effective in resolving SANA infections. Of the five partner drugs tested, pyronaridine was also the most effective at suppressing the recrudescence of SANA parasites. These data support the potential benefit of implementing ACTs with pyronaridine in regions affected by artemisinin-resistant malaria.

  17. Degenerative effects of cobalt-chloride treatment on neurons and microglia in a porcine retina organ culture model.

    Science.gov (United States)

    Kuehn, S; Hurst, J; Rensinghoff, F; Tsai, T; Grauthoff, S; Satgunarajah, Y; Dick, H B; Schnichels, S; Joachim, S C

    2017-02-01

    In order to understand the pathological processes of retinal diseases, experimental models are necessary. Cobalt, as part of the vitamin B12 complex, is important for neuronal integrity. However, it is known that high quantities of cobalt induce cytotoxic mechanisms via hypoxia mimicry. Therefore, we tested the degenerative effect of cobalt chloride (CoCl2) on neurons and microglia in a porcine retina organ culture model. Organotypic cultures of porcine retinas were cultured and treated with different concentrations of CoCl2 (0, 100, 300 and 500 μM) for 48 h. After four and eight days, CoCl2 induced a strong degeneration of the porcine retina, starting at 300 μM. A loss of retinal ganglion cells (RGCs, Brn-3a), amacrine cells (calretinin) and bipolar cells (PKCα) was observed. Additionally, a high expression of hypoxia induced factor-1a (HIF-1a) and heat shock protein 70 (HSP70) was noted at both points in time. Also, the Caspase 3 protein was activated and P21 expression was induced. However, only at day four, the Bax/Bcl-2 ratio was increased. The effect of CoCl2 was not restricted to neurons. CoCl2 concentrations reduced the microglia amount (Iba1) and activity (Iba1 + Fcγ-Receptor) at both points in time. These damaging effects on microglia were surprising, since CoCl2 causes hypoxia and a pro-inflammatory environment. However, high concentrations of CoCl2 also seem to be toxic to these cells. Similar degenerative mechanisms as in comparison to retinal ischemia animal models were observed. In summary, an effective and reproducible hypoxia-mimicking organotypic model for retinal degeneration was established, which is easy to handle and ready for drug studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Characterization of wastewater treatment plant microbial communities and the effects of carbon sources on diversity in laboratory models.

    Directory of Open Access Journals (Sweden)

    Sangwon Lee

    Full Text Available We are developing a laboratory-scale model to improve our understanding and capacity to assess the biological risks of genetically engineered bacteria and their genetic elements in the natural environment. Our hypothetical scenario concerns an industrial bioreactor failure resulting in the introduction of genetically engineered bacteria to a downstream municipal wastewater treatment plant (MWWTP. As the first step towards developing a model for this scenario, we sampled microbial communities from the aeration basin of a MWWTP at three seasonal time points. Having established a baseline for community composition, we investigated how the community changed when propagated in the laboratory, including cell culture media conditions that could provide selective pressure in future studies. Specifically, using PhyloChip 16S-rRNA-gene targeting microarrays, we compared the compositions of sampled communities to those of inocula propagated in the laboratory in simulated wastewater conditionally amended with various carbon sources (glucose, chloroacetate, D-threonine or the ionic liquid 1-ethyl-3-methylimidazolium chloride ([C2mim]Cl. Proteobacteria, Bacteroidetes, and Actinobacteria were predominant in both aeration basin and laboratory-cultured communities. Laboratory-cultured communities were enriched in γ-Proteobacteria. Enterobacteriaceae, and Aeromonadaceae were enriched by glucose, Pseudomonadaceae by chloroacetate and D-threonine, and Burkholderiacea by high (50 mM concentrations of chloroacetate. Microbial communities cultured with chloroacetate and D-threonine were more similar to sampled field communities than those cultured with glucose or [C2mim]Cl. Although observed relative richness in operational taxonomic units (OTUs was lower for laboratory cultures than for field communities, both flask and reactor systems supported phylogenetically diverse communities. These results importantly provide a foundation for laboratory models of industrial

  19. 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.

  20. Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche

    Science.gov (United States)

    Jørgensen, A; Young, J; Nielsen, J E; Joensen, U N; Toft, B G; Rajpert-De Meyts, E; Loveland, K L

    2014-01-01

    Background: Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. Methods: Human testis and testis cancer specimens from orchidectomies were cultured in ‘hanging drops' and effects of activin A and follistatin treatment were investigated in seminoma cultures. Results: Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. Conclusions: Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche. PMID:24781282

  1. The effect of Filmed modeling on the anxious and cooperative behavior of 4-6 years old children during dental treatment: A randomized clinical trial study.

    Science.gov (United States)

    Paryab, Mehrsa; Arab, Zeinab

    2014-07-01

    The aim of this study was to evaluate the effect of Filmed modeling in comparison with commonly used Tell-Show-Do technique (T.S.D) on the anxious and cooperative behavior of 4-6 years old children during dental practice. Forty six children aged 4-6 years were enrolled in this study and randomly allocated into two groups. Group I: At the first visit, the procedure of Tell-Show-Do, and at the second visit, the treatment procedures were performed by the dentist for the children. Group II: At the first visit, children watched a film consisting of the procedure of Tell-Show-Do performed on a child model. At the second visit, treatment procedures were performed. In both groups, during the treatment procedure, index of heart rate was measured and behaviors of children were recorded. The children's anxious and cooperative behaviors on the recordings were quantified according to Venham and Frankl rating scales, respectively. The data were compared between two groups using T-test method. All statistical references were made at 0.05. There were no statistically significant differences in heart rate measures, clinical anxiety and cooperative behavior scores of children between the two groups (P = 0.6). Filmed modeling can be an efficient alternative method to Tell-Show-Do technique in pre-appointment preparation of the 4-6 years old children during dental treatment.

  2. Cost-Effective Fuel Treatment Planning

    Science.gov (United States)

    Kreitler, J.; Thompson, M.; Vaillant, N.

    2014-12-01

    The cost of fighting large wildland fires in the western United States has grown dramatically over the past decade. This trend will likely continue with growth of the WUI into fire prone ecosystems, dangerous fuel conditions from decades of fire suppression, and a potentially increasing effect from prolonged drought and climate change. Fuel treatments are often considered the primary pre-fire mechanism to reduce the exposure of values at risk to wildland fire, and a growing suite of fire models and tools are employed to prioritize where treatments could mitigate wildland fire damages. Assessments using the likelihood and consequence of fire are critical because funds are insufficient to reduce risk on all lands needing treatment, therefore prioritization is required to maximize the effectiveness of fuel treatment budgets. Cost-effectiveness, doing the most good per dollar, would seem to be an important fuel treatment metric, yet studies or plans that prioritize fuel treatments using costs or cost-effectiveness measures are absent from the literature. Therefore, to explore the effect of using costs in fuel treatment planning we test four prioritization algorithms designed to reduce risk in a case study examining fuel treatments on the Sisters Ranger District of central Oregon. For benefits we model sediment retention and standing biomass, and measure the effectiveness of each algorithm by comparing the differences among treatment and no treat alternative scenarios. Our objective is to maximize the averted loss of net benefits subject to a representative fuel treatment budget. We model costs across the study landscape using the My Fuel Treatment Planner software, tree list data, local mill prices, and GIS-measured site characteristics. We use fire simulations to generate burn probabilities, and estimate fire intensity as conditional flame length at each pixel. Two prioritization algorithms target treatments based on cost-effectiveness and show improvements over those

  3. Differential behavioural and neurochemical outcomes from chronic paroxetine treatment in adolescent and adult rats: a model of adverse antidepressant effects in human adolescents?

    Science.gov (United States)

    Karanges, Emily; Li, Kong M; Motbey, Craig; Callaghan, Paul D; Katsifis, Andrew; McGregor, Iain S

    2011-05-01

    Selective serotonin reuptake inhibitor use is associated with increased risk of suicidal ideation in adolescent humans, yet the neuropharmacological basis of this phenomenon is unknown. Consequently, we examined the behavioural and neurochemical effects of chronic paroxetine (PRX) treatment in adult and adolescent rats. Rats received PRX in their drinking water (target dose 10 mg/kg) for 22 d, during which time they were assessed for depression- and anxiety-like behaviours. Subsequent ex-vivo analyses examined serum PRX concentrations, striatal neurotransmitter content, and regional serotonin and dopamine transporter (SERT, DAT) binding density. After 11-12 d treatment, PRX-treated adolescent rats showed a significant inhibition of social interaction while adults were unaffected. After 19-20 d treatment, adolescents failed to show an antidepressant-like effect of PRX treatment on the forced swim test (FST), while PRX-treated adults showed a typical decrease in immobility and increase in swimming. Two PRX-treated adolescents died unexpectedly after the FST suggesting a compromised response to physical stress. Despite their greater apparent adverse reaction to the drug, adolescents had significantly lower plasma PRX than adults at day 22 of treatment. Chronic PRX treatment had similar effects in adults and adolescents on striatal 5-HT (unchanged relative to controls) and 5-HIAA levels (decreased), while markers of dopaminergic function (DOPAC, HVA, DA turnover) were increased in adults only. SERT density was up-regulated in the amygdala in PRX-treated adolescents only while DAT density in the nucleus accumbens was down-regulated only in PRX-treated adults. These data suggest that the immature rat brain responds differently to PRX and that this might be of use in modelling the atypical response of human adolescents to antidepressants. The age-specific PRX-induced changes in dopaminergic markers and SERT and DAT binding provide clues as to the neural mechanisms

  4. [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.

  5. SU-E-T-146: Effects of Uncertainties of Radiation Sensitivity of Biological Modelling for Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Oita, M [Department of Radiological Technology, Graduate School of Health Sciences, Okayama University (Japan); Department of Life System, Institute of Technology and Science, Graduate School, The Tokushima University (Japan); Uto, Y; Hori, H [Department of Life System, Institute of Technology and Science, Graduate School, The Tokushima University (Japan); Tominaga, M [Department of Radiological Technology, Institute of Health Biosciences, Graduate School, The Tokushima University (Japan); Sasaki, M [Department of Radiology, Tokushima University Hospital (Japan)

    2014-06-01

    Purpose: The aim of this study was to evaluate the distribution of uncertainty of cell survival by radiation, and assesses the usefulness of stochastic biological model applying for gaussian distribution. Methods: For single cell experiments, exponentially growing cells were harvested from the standard cell culture dishes by trypsinization, and suspended in test tubes containing 1 ml of MEM(2x10{sup 6} cells/ml). The hypoxic cultures were treated with 95% N{sub 2}−5% CO{sub 2} gas for 30 minutes. In vitro radiosensitization was also measured in EMT6/KU single cells to add radiosensitizer under hypoxic conditions. X-ray irradiation was carried out by using an Xray unit (Hitachi X-ray unit, model MBR-1505R3) with 0.5 mm Al/1.0 mm Cu filter, 150 kV, 4 Gy/min). In vitro assay, cells on the dish were irradiated with 1 Gy to 24 Gy, respectively. After irradiation, colony formation assays were performed. Variations of biological parameters were investigated at standard cell culture(n=16), hypoxic cell culture(n=45) and hypoxic cell culture(n=21) with radiosensitizers, respectively. The data were obtained by separate schedule to take account for the variation of radiation sensitivity of cell cycle. Results: At standard cell culture, hypoxic cell culture and hypoxic cell culture with radiosensitizers, median and standard deviation of alpha/beta ratio were 37.1±73.4 Gy, 9.8±23.7 Gy, 20.7±21.9 Gy, respectively. Average and standard deviation of D{sub 50} were 2.5±2.5 Gy, 6.1±2.2 Gy, 3.6±1.3 Gy, respectively. Conclusion: In this study, we have challenged to apply these uncertainties of parameters for the biological model. The variation of alpha values, beta values, D{sub 50} as well as cell culture might have highly affected by probability of cell death. Further research is in progress for precise prediction of the cell death as well as tumor control probability for treatment planning.

  6. Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Somkuwar, Sucharita S; Kantak, Kathleen M; Dwoskin, Linda P

    2015-08-30

    Attention deficit hyperactivity disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in spontaneously hypertensive rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax)× first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Antitumor effects of electrochemical treatment

    Institute of Scientific and Technical Information of China (English)

    Héctor Manuel Camué Ciria; Maraelys Morales González; Lisset Ortíz Zamora; Luis Enrique Bergues Cabrales; Gustavo Victoriano Sierra González; Luciana Oliveira de Oliveira; Rodrigo Zanella

    2013-01-01

    Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas.This treatment is noted for its great effectiveness,minimal invasiveness and local effect.Several studies have been conducted worldwide to evaluate the antitumoral effect of this therapy.In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained.By this reason,researchers have suggested various mechanisms to explain how direct electric current destroys tumor cells.Although,it is generally accepted this treatment induces electrolysis,electroosmosis and electroporation in tumoral tissues.However,action mechanism of this alternative modality on the tumor tissue is not well understood.Although the principle of Electrochemical treatment is simple,a standardized method is not yet available.The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process.The present work analyzes the latest and most important research done on the electrochemical treatment of tumors.We conclude with our point of view about the destruction mechanism features of this alternative therapy.Also,we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy.In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done.Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.

  8. 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.

  9. Seeing the invisible: how mathematical models uncover tumor dormancy, reconstruct the natural history of cancer, and assess the effects of treatment.

    Science.gov (United States)

    Hanin, Leonid

    2013-01-01

    The hypothesis of early metastasis was debated for several decades. Dormant cancer cells and surgery-induced acceleration of metastatic growth were first observed in clinical studies and animal experiments conducted more than a century ago; later, these findings were confirmed in numerous modern studies.In this primarily methodological work, we discuss critically important, yet largely unobservable, aspects of the natural history of cancer, such as (1) early metastatic dissemination; (2) dormancy of secondary tumors; (3) treatment-related interruption of metastatic dormancy, induction of angiogenesis, and acceleration of the growth of vascular metastases; and (4) the existence of cancer stem cells. The hypothesis of early metastasis was debated for several decades. Dormant cancer cells and surgery-induced acceleration of metastatic growth were first observed in clinical studies and animal experiments conducted more than a century ago; later, these findings were confirmed in numerous modern studies.We focus on the unique role played by very general mathematical models of the individual natural history of cancer that are entirely mechanistic yet, somewhat paradoxically, essentially free of assumptions about specific nature of the underlying biological processes. These models make it possible to reconstruct in considerable detail the individual natural history of cancer and retrospectively assess the effects of treatment. Thus, the models can be used as a tool for generation and validation of biomedical hypotheses related to carcinogenesis, primary tumor growth, its metastatic dissemination, growth of metastases, and the effects of various treatment modalities. We discuss in detail one such general model and review the conclusions relevant to the aforementioned aspects of cancer progression that were drawn from fitting a parametric version of the model to data on the volumes of bone metastases in one breast cancer patient and 12 prostate cancer patients.

  10. Incorporation of advanced aerosol activation treatments into CESM/CAM5: model evaluation and impacts on aerosol indirect effects

    Science.gov (United States)

    Gantt, B.; He, J.; Zhang, X.; Zhang, Y.; Nenes, A.

    2014-07-01

    One of the greatest sources of uncertainty in the science of anthropogenic climate change is from aerosol-cloud interactions. The activation of aerosols into cloud droplets is a direct microphysical linkage between aerosols and clouds; parameterizations of this process link aerosol with cloud condensation nuclei (CCN) and the resulting indirect effects. Small differences between parameterizations can have a large impact on the spatiotemporal distributions of activated aerosols and the resulting cloud properties. In this work, we incorporate a series of aerosol activation schemes into the Community Atmosphere Model version 5.1.1 within the Community Earth System Model version 1.0.5 (CESM/CAM5) which include factors such as insoluble aerosol adsorption and giant cloud condensation nuclei (CCN) activation kinetics to understand their individual impacts on global-scale cloud droplet number concentration (CDNC). Compared to the existing activation scheme in CESM/CAM5, this series of activation schemes increase the computation time by ~10% but leads to predicted CDNC in better agreement with satellite-derived/in situ values in many regions with high CDNC but in worse agreement for some regions with low CDNC. Large percentage changes in predicted CDNC occur over desert and oceanic regions, owing to the enhanced activation of dust from insoluble aerosol adsorption and reduced activation of sea spray aerosol after accounting for giant CCN activation kinetics. Comparison of CESM/CAM5 predictions against satellite-derived cloud optical thickness and liquid water path shows that the updated activation schemes generally improve the low biases. Globally, the incorporation of all updated schemes leads to an average increase in column CDNC of 150% and an increase (more negative) in shortwave cloud forcing of 12%. With the improvement of model-predicted CDNCs and better agreement with most satellite-derived cloud properties in many regions, the inclusion of these aerosol activation

  11. 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

  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. Rectus femoris transfer and musculo-skeletal modeling: effect of surgical treatment on gait and on rectus femoris kinematics.

    Science.gov (United States)

    Desailly, Eric; Khouri, Nejib; Sardain, Philippe; Yepremian, Daniel; Lacouture, Patrick

    2011-10-01

    Spasticity of the rectus femoris (RF) is one of the possible causes of stiff knee gait (SKG) in cerebral palsy. Musculoskeletal studies have shown that in SKG, length and speed of the RF are affected. No evaluation had been made to quantify the modifications of those parameters after surgery. The effect of this operation on gait quality and on RF kinematics was assessed in this study in order to identify kinematic patterns that may aid its diagnosis. For 26 transfers, clinical gait analysis pre- and post-surgery was used to compute the Gait Deviation Index (GDI) and Goldberg's index. The kinematics of the Original RF path (ORFp) was studied before and after surgery. The expression ORFp was chosen to avoid any confusion between this modeling parameter, whose computation was unchanged, and the actual anatomical path that was modified by surgery. The gait quality was improved (+18±12GDI) and there was an inverse relation between the pre-operative GDI and its improvement. The Golberg's index was improved (88% of the cases). The operation had a significant effect on the normalization of the timings of maximum length and speed of the ORFp. The improvement of SKG was correlated with the normalization of the timing of the ORFp's maximum length. The global improvement of the gait quality and of the SKG was demonstrated. Some parameters of muscular kinematics (RF length and velocity) have been standardized, showing an effect of the transfer not only during the swing, but also during stance. The premature timing of the ORFp peak length has been identified as a prognostic factor of a successful surgical outcome.

  14. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment.

    Science.gov (United States)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders; Sandi, Carmen

    2010-10-01

    Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core symptom of depression, was assessed by measuring consumption of a palatable solution. Exposure to CUS reduced intake of a palatable solution and this effect was prevented by chronic antidepressant treatment. Moreover, chronic antidepressant treatment decreased depressive-like behavior in a modified forced swim test in stressed rats. Present evidence suggests a role for brain-derived neurotrophic factor (BDNF) in depression. BDNF mRNA levels in the ventral and dorsal hippocampus were assessed by in situ hybridization. Exposure to CUS was not correlated with a decrease but rather with an increase in BDNF mRNA expression in both the dentate gyrus of the dorsal hippocampus and the CA3 region of the ventral hippocampus indicating that there is no simple link between depression-like behaviors per se and brain BDNF levels in rats. However, a significant increase in BDNF mRNA levels in the dentate gyrus of the dorsal hippocampus correlated with chronic antidepressant treatment emphasizing a role for BDNF in the mechanisms underlying antidepressant activity.

  15. Molecular effects of fractional ablative erbium:YAG laser treatment with multiple stacked pulses on standardized human three-dimensional organotypic skin models.

    Science.gov (United States)

    Schmitt, Laurenz; Amann, P M; Marquardt, Y; Heise, R; Czaja, K; Gerber, P A; Steiner, T; Hölzle, F; Baron, Jens Malte

    2017-05-01

    The molecular changes in gene expression following ablative laser treatment of skin lesions, such as atrophic scars and UV-damaged skin, are not completely understood. A standardized in vitro model of human skin, to study the effects of laser treatment on human skin, has been recently developed. Therefore, the aim of the investigation was to examine morphological and molecular changes caused by fractional ablative erbium:YAG laser treatment on an in vitro full-thickness 3D standardized organotypic model of human skin. A fractional ablative erbium:YAG laser was used to irradiate organotypic human 3D models. Laser treatments were performed at four different settings using a variety of stacked pulses with similar cumulative total energy fluence (60 J/cm(2)). Specimens were harvested at specified time points and real-time PCR (qRT-PCR) and microarray studies were performed. Frozen sections were examined histologically. Three days after erbium:YAG laser treatment, a significantly increased mRNA expression of matrix metalloproteinases and their inhibitors (MMP1, MMP2, MMP3, TIMP1, and TIMP2), chemokines (CXCL1, CXCL2, CXCL5, and CXCL6), and cytokines such as IL6, IL8, and IL24 could be detected. qRT-PCR studies confirmed the enhanced mRNA expression of IL6, IL8, IL24, CXCLs, and MMPs. In contrast, the mRNA expression of epidermal differentiation markers, such as keratin-associated protein 4, filaggrin, filaggrin 2, and loricrin, and antimicrobial peptides (S100A7A, S100A9, and S100A12) as well as CASP14, DSG2, IL18, and IL36β was reduced. Four different settings with similar cumulative doses have been tested (N10%, C10%, E10%, and W25%). These laser treatments resulted in different morphological changes and effects on gene regulations. Longer pulse durations (1000 μs) especially had the strongest impact on gene expression and resulted in an upregulation of genes, such as collagen-1A2, collagen-5A2, and collagen-6A2, as well as FGF2. Histologically, all treatment

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

    Science.gov (United States)

    2011-01-01

    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, respectively. Therefore

  17. 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

  18. 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-path dec......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...... in 2004 DDK. The expected overall 6-month remission rate was higher for 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...

  19. Beneficial effect of melatonin treatment on inflammation, apoptosis and oxidative stress on pancreas of a senescence accelerated mice model.

    Science.gov (United States)

    Cuesta, Sara; Kireev, Roman; García, Cruz; Forman, Katherine; Escames, Germaine; Vara, Elena; Tresguerres, Jesús A F

    2011-01-01

    This study has investigated the effect of aging on parameters of inflammation, oxidative stress and apoptosis in pancreas obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and resistant mice (SAMR1). Animals of 2 (young) and 10 months of age (old) were used (n = 64). The influence of the administration of melatonin in the drinking water for one month at two different dosages (1 and 10mg/(kg day) on old SAMP8 mice on these parameters was also studied. SAMP8 mice showed with age a significant increase in the relative expression of pancreatic genes involved in inflammation, oxidative stress and apoptosis. Furthermore the protein expression of several NFκB subunits was also enhanced. On the contrary aged SAMR1 mice did not show significant increases in these parameters. Melatonin administration to SAMP8 mice was able to reduce these age related alterations at the two used dosages. Copyright © 2011. Published by Elsevier Ireland Ltd.

  20. 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.

  1. 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.

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

    OpenAIRE

    Azouni, Khalid G; 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 arri...

  3. Estimation of the effect of the degree of sewage treatment on the status of pollution along the coastline of the Mediterranean Sea using broad scale modelling.

    Science.gov (United States)

    Stamou, Anastasios I; Kamizoulis, George

    2009-02-01

    A preliminary investigation was performed to estimate the effect of the degree of treatment in Sewage Treatment Plants (STPs) on the status of pollution along the coastlines of the Mediterranean Sea. Data from questionnaires and the literature were collected and processed (a) to identify 18 approximate 1D surface coastal currents, (b) to estimate their prevailing direction and average flow velocity and (c) to estimate the water pollution loads and identify their locations of discharge. Then, a simplified 1D water quality model was formulated and applied for the existing conditions and two hypothetical scenarios: (1) all coastal cities have STPs with secondary treatment and (2) all coastal cities have STPs with tertiary treatment to determine BOD(5), TN and TP concentrations in the 18 surface coastal currents. Calculated concentrations were compared and discussed. A main conclusion is that, to reduce pollution in the Mediterranean Sea measures should be adopted for upgrading the water quality of the rivers discharging into the Mediterranean Sea, along with the construction of STPs for all the coastal cities.

  4. 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.

  5. Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease

    NARCIS (Netherlands)

    Liu, Weilin; Struik, Dicky; Nies, Vera J. M.; Jurdzinski, Angelika; Harkema, Liesbeth; de Bruin, Alain; Verkade, Henkjan J.; Downes, Michael; Evans, Ronald M.; van Zutphen, Tim; Jonker, Johan W.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with obesity and type 2 diabetes. Currently, there is no approved pharmacological treatment for this disease, but improvement of insulin resistance using peroxisome proliferator-activated

  6. 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

    The main objective of this paper is to demonstrate how including the occurrence of filamentous bulking sludge in a secondary clarifier model will affect the predicted process performance during the simulation of WWTPs. The IWA Benchmark Simulation Model No. 2 (BSM2) is hereby used as a simulation...

  7. A hyaluronic acid-salmon calcitonin conjugate for the local treatment of osteoarthritis: chondro-protective effect in a rabbit model of early OA.

    Science.gov (United States)

    Mero, Anna; Campisi, Monica; Favero, Marta; Barbera, Carlo; Secchieri, Cynthia; Dayer, Jean M; Goldring, Mary B; Goldring, Steven R; Pasut, Gianfranco

    2014-08-10

    Osteoarthritis (OA) is characterized by chronic degeneration of joints, involving mainly the articular cartilage and the underlying bone, and severely impairing the quality of life of the patient. Although with limited efficacy, currently available pharmacological treatments for OA aim to control pain and to retard disease progression. Salmon calcitonin (sCT) is a drug which has been shown to have therapeutic effects in experimental arthritis by inhibiting both bone turnover and cartilage degradation and reducing the activities of matrix metalloproteinases (MMP). High molecular weight hyaluronic acid (HA) is used as a lubricant in OA therapy, and, interestingly, HA polymers may normalize the levels of MMP-1, -3 and -13. We demonstrated that sCT rapidly clears from the knee joint of rat animal model, after intra-articular (i.a.) administration, and it induces systemic effects. Here, sCT was conjugated to HA (200kDa) with the aim of prolonging the residence time of the polypeptide in the joint space by reducing its clearance. An aldehyde derivative of HA was used for N-terminal site-selective coupling of sCT. The activity of sCT was preserved, both in vitro and in vivo, after its conjugation and the i.a. injection of HA-sCT did not trigger any systemic effects in rats. The efficacy of HA-sCT treatment was tested in a rabbit OA model and clear chondro-protective effect was proven by macro- and microscopic assessments and histological findings. Our results indicate that HAylation of sCT increases the size of the polypeptide in a stable covalent manner and delays its passage into the blood stream. We conclude that HA conjugation prolongs the anti-catabolic effects of sCT in joint tissues, including the synovial membrane and cartilage.

  8. Cost effectiveness of a lidocaine 5% medicated plaster compared with pregabalin for the treatment of postherpetic neuralgia in the UK: a Markov model analysis.

    Science.gov (United States)

    Ritchie, Mark; Liedgens, Hiltrud; Nuijten, Mark

    2010-01-01

    Published analyses have demonstrated that the lidocaine (lignocaine) plaster is a cost-effective treatment for postherpetic neuralgia (PHN) relative to gabapentin or pregabalin. However, these analyses have been based on indirect comparisons from placebo-controlled trials, and there is evidence of a discrepancy between the outcomes of direct and indirect analyses. Fortunately, recent publication of the results of a head-to-head trial comparing the lidocaine plaster and pregabalin in patients with PHN or diabetic polyneuropathy allows customization of the existing model to more accurately reflect the relative cost effectiveness of these two products. To assess the cost-effectiveness of the lidocaine 5% medicated plaster compared with pregabalin for the treatment of PHN in the UK primary-care setting. A Markov model has been developed to assess the costs and benefits of the lidocaine plaster and pregabalin over a 6-month time horizon for the treatment of patients with PHN who are intolerant to tricyclic antidepressants and in whom analgesics are ineffective or contraindicated. The model structure allows for differences in costs, utilities (derived from published data and from the head-to-head trial) and transition probabilities between the initial 30-day run-in period and maintenance therapy, and also takes account of add-in medication and drugs received by patients discontinuing therapy. The calculation was based on data from the recent head-to-head trial described above. Additional data sources included published literature, discussions with a Delphi panel, official price/tariff lists and national population statistics. The study was conducted from the perspective of the UK National Health Service (NHS). The base-case analysis (1.71 lidocaine plasters per day used in the head-to-head trial for the PHN population) indicated that the total cost of treating PHN patients for 6 months with the lidocaine plaster was pound 980 per patient treated, compared with pound 784

  9. 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.

  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. [Rehabilitative treatment of cerebral apoplectic insults in advanced age and evaluating its effectiveness--results of a model project].

    Science.gov (United States)

    Schütte, T; Summa, J D; Platt, D

    1984-01-01

    This report is of a two year study of stroke rehabilitation. Given certain conditions with specialized personnel and equipment the rehabilitation of elderly stroke patients can be managed co-operatively in hospitals and old age care centres. The rehabilitation of stroke affected is based on the support of multidisciplinary diagnosis and interdisciplinary teamwork between physicians, physiotherapists, occupational therapists, speech therapists, psychologists and social workers. Each patient requires an individual treatment program. In this study were 72 patients ranging in age from 42-87 years, average age 73 years. They had been judged as progressively degenerative and helpless following their stroke and consequently regarded as patients for a nursing home. Following special rehabilitation treatment 75% (54 patients) had improved enough that it was possible for them to return to their homes. Only 12.5% (9 patients) had to remain in a nursing home. 6.6% (4 patients) transferred to an old people's home. 6.9% (9 patients) were readmitted to hospital because of additional serious complications. The average duration of rehabilitative treatment was 72.3 days. The degree of hemiplegia and the patients ability to lead their own active daily independent life was reviewed before and after rehabilitation and used as control. 76.6% showed an improvement in their motor function. 61.1% returned to their own independent daily life as measured by ADL-Indices. (a. Barthel Index, b. ADL-Index-Katz-, c. Patient Classification for Long Term Care-Jones-, d. Crichton Royal Behavioural Rating Scale-Robinson-.).(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Neuroinflammatory and oxidative stress phenomena in MPS IIIA mouse model: the positive effect of long-term aspirin treatment.

    Science.gov (United States)

    Arfi, Audrey; Richard, Magali; Gandolphe, Christelle; Bonnefont-Rousselot, Dominique; Thérond, Patrice; Scherman, Daniel

    2011-05-01

    Sanfilippo disease (MPS IIIA) is an autosomal recessive lysosomal storage disorder resulting from sulfamidase deficiency, which is characterized by severe neurological impairment. Various tissues of MPS IIIA mice accumulate undegraded glycosaminoglycans and mimic the human neurodegenerative disorder, and are an excellent tool to both delineate disease pathogenesis and test potential therapies. The relationship between abnormal glycosaminoglycan storage and neurodysfunction remains ill defined. Pathways such as inflammation or oxidative stress have been highlighted in many neurodegenerative disorders, including lysosomal storage diseases, as major components of the neuropathology. By using quantitative polymerase chain reaction, we have compared the expression of selected genes in normal and MPS IIIA mouse cerebral tissues, focusing on inflammation, apoptosis and oxidative stress-related genes. We have identified several genes strongly over-expressed in the central nervous system of a MPS IIIA mouse, reflecting a neurological deterioration state. We have used these genes as markers to follow-up a long-term aspirin treatment. Aspirin treatment led to the normalization of inflammation- and oxidative stress-related mRNA levels in treated MPS IIIA mouse brains. A biochemical correction of an oxidative stress phenomenon both in the brain and peripheral organs of treated MPS IIIA mice was also obtained. These results suggest that anti-inflammatory intervention may be of potential benefit in MPS IIIA disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Antioxidant Pre-Treatment Reduces the Toxic Effects of Oxalate on Renal Epithelial Cells in a Cell Culture Model of Urolithiasis

    Directory of Open Access Journals (Sweden)

    Tomislav Kizivat

    2017-01-01

    Full Text Available Urolithiasis is characterized by the formation and retention of solid crystals within the urinary tract. Kidney stones are mostly composed of calcium oxalate, which predominantly generates free radicals that are toxic to renal tubular cells. The aim of the study is to explore possible effects of antioxidant pre-treatment on inhibition of oxidative stress. Three cell lines were used as in vitro model of urolithiasis: MDCK I, MDCK II and LLC-PK1. Oxidative stress was induced by exposure of cells to sodium oxalate in concentration of 8 mM. In order to prevent oxidative stress, cells were pre-treated with three different concentrations of l-arginine and vitamin E. Oxidative stress was evaluated by determining the expression of superoxide dismutase (SOD, osteopontin (OPN, and by the concentration of glutathione (GSH. In all three cell lines, pre-treatment of antioxidants increased cell survival. Positive correlation of SOD and OPN expression as well as GSH concentration was observed in all groups of cells. Our results indicate that an antioxidant pre-treatment with l-arginine and vitamin E is able to hamper oxalate-induced oxidative stress in kidney epithelial cells and as such could play a role in prevention of urolithiasis.

  14. Beneficial effects of treatment with transglutaminase inhibitor cystamine on the severity of inflammation in a rat model of inflammatory bowel disease.

    Science.gov (United States)

    Elli, Luca; Ciulla, Michele M; Busca, Giuseppe; Roncoroni, Leda; Maioli, Claudio; Ferrero, Stefano; Bardella, Maria Teresa; Bonura, Antonella; Paliotti, Roberta; Terrani, Claudia; Braidotti, Paola

    2011-03-01

    Inflammatory bowel disease (IBD) represents a socially and clinically relevant disorder, characterized by intestinal chronic inflammation. Cystamine (CysN) is a multipotent molecule with healthy effects and, moreover, it is an inhibitor of transglutaminases (TGs), including the TG type 2 (TG2), an enzyme with pleiotropic functions, involved in different pathways of inflammation and central in the pathogenesis of some human disorders as the IBD. Our aim was to evaluate the effect of CysN in an IBD rat model. A total of 30 rats were divided into 4 groups: controls without treatment (CTR; n=7); receiving the 2,4,6-trinitrobenzene sulfonic acid enema (TNBS group; n=8); treated with TNBS enema plus oral CysN (TNBS-CysN group; n=8); treated with CysN (CysN group; n=7). After killing, bowel inflammation was evaluated applying specific scores. TG activity, TG2 and isopeptide bond immunohistochemical expression, and tumor necrosis factor-α (TNF-α) were evaluated in the colonic tissue, such as interleukin-6 (IL-6) serological levels (ELISA). TG2 was also evaluated on the luminal side of the colon by immunoautoradiography. Colonic samples from IBD patients were compared with animal results. TNBS-CysN group developed a less severe colitis compared with the TNBS group (macroscopic score 0.43±0.78 vs 3.28±0.95, microscopic score 6.62±12.01 vs 19.25±6.04, P<0.05, respectively) associated with a decrease of TG activity, TG2 and isopeptide bond immunohistochemical expression, TNF-α and IL-6 levels. No statistically significant differences were found between CysN and CTR groups. The colonic immunolocalization of TG2 was comparable in humans affected by IBD and TNBS-administered animals. This is the first demonstration that treatment with a CysN has an anti-inflammatory effect, reducing severity of colitis in a rat model. CysN could be tested as a possible treatment or co-treatment in IBD therapeutic trials.

  15. Effects of a non thermal plasma treatment alone or in combination with gemcitabine in a MIA PaCa2-luc orthotopic pancreatic carcinoma model.

    Science.gov (United States)

    Brullé, Laura; Vandamme, Marc; Riès, Delphine; Martel, Eric; Robert, Eric; Lerondel, Stéphanie; Trichet, Valérie; Richard, Serge; Pouvesle, Jean-Michel; Le Pape, Alain

    2012-01-01

    Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.

  16. Effects of a non thermal plasma treatment alone or in combination with gemcitabine in a MIA PaCa2-luc orthotopic pancreatic carcinoma model.

    Directory of Open Access Journals (Sweden)

    Laura Brullé

    Full Text Available Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.

  17. Effect of Antifungal Treatment in a Diet-Based Murine Model of Disseminated Candidiasis Acquired via the Gastrointestinal Tract.

    Science.gov (United States)

    Kadosh, David; Najvar, Laura K; Bocanegra, Rosie; Olivo, Marcos; Kirkpatrick, William R; Wiederhold, Nathan P; Patterson, Thomas F

    2016-11-01

    Candida albicans, normally found as a commensal in the gut, is a major human fungal pathogen responsible for both mucosal and systemic infections in a wide variety of immunocompromised individuals, including cancer patients and organ transplant recipients. The gastrointestinal tract represents a major portal of entry for the establishment of disseminated candidiasis in many of these individuals. Here we report the development of a diet-based mouse model for disseminated candidiasis acquired via the gastrointestinal tract. Using this model, as well as an appropriate immunosuppression regimen, we demonstrate that dissemination of C. albicans from the gastrointestinal tract can result in mortality within 30 days postinfection. We also show a significant increase in fungal burden in systemic organs, but not gastrointestinal tract organs, upon immunosuppression. Importantly, we demonstrate that the administration of two widely used antifungals, fluconazole and caspofungin, either pre- or postimmunosuppression, significantly reduces fungal burdens. This model should prove to be of significant value for testing the ability of both established and experimental therapeutics to inhibit C. albicans dissemination from the gastrointestinal tract in an immunocompromised host as well as the subsequent mortality that can result from disseminated candidiasis.

  18. 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.

  19. 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.

    Science.gov (United States)

    Shafaroodi, Hamed; Hassanipour, Mahsa; Mousavi, Zahra; Rahimi, Nastaran; Dehpour, Ahmad Reza

    2015-10-01

    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.

  20. Hybrid Sludge Modeling in Water Treatment Processes

    OpenAIRE

    Brenda, Marian

    2015-01-01

    Sludge occurs in many waste water and drinking water treatment processes. The numeric modeling of sludge is therefore crucial for developing and optimizing water treatment processes. Numeric single-phase sludge models mainly include settling and viscoplastic behavior. Even though many investigators emphasize the importance of modeling the rheology of sludge for good simulation results, it is difficult to measure, because of settling and the viscoplastic behavior. In this thesis, a new method ...

  1. Cryopreservation of Bone Marrow Mononuclear Cells Alters Their Viability and Subpopulation Composition but Not Their Treatment Effects in a Rodent Stroke Model

    Directory of Open Access Journals (Sweden)

    Bing Yang

    2016-01-01

    Full Text Available The systemic administration of autologous bone marrow (BM derived mononuclear cells (MNCs is under investigation as a novel therapeutic modality for the treatment of ischemic stroke. Autologous applications raise the possibility that MNCs could potentially be stored as a banked source. There have been no studies that investigate the effects of cryopreservation of BM-MNCs on their functional abilities in stroke models. In the present study, C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAo for 60 minutes and then divided into two treatment groups: fresh MNCs versus cryopreserved MNCs. BM-MNCs were collected at 22 hours after MCAo and were stored in liquid nitrogen for 12 months in cryopreserved MNCs group. BM-MNCs cellular viability, composition, and phenotype of the various subpopulations of mice BM-MNCs were evaluated by flow cytometry, and the behavioral recovery of stroke animals was tested with freshly harvested MNCs versus cryopreserved MNCs by corner test and ladder rung test. We found that long-term cryopreservation negatively impacts the cellular viability of bone marrow MNCs. Cryopreservation also alters the cellular composition of various subpopulations within the MNCs. However, despite the changes observed in cryopreserved cells, both fresh and frozen MNCs have similar beneficial effect on behavioral and histological outcomes.

  2. [Home treatment--a treatment model of integrated care in Hamburg].

    Science.gov (United States)

    Schöttle, Daniel; Ruppelt, Friederike; Karow, Anne; Lambert, Martin

    2015-03-01

    Treatment models like "Crisis Resolution and Hometreatment (CRHT)" or "Assertive Community Treatment" (ACT), were found to be effective, enhancing the qualitative level of treatment for patients with severe mental disorders. In Germany, these are implemented only sporadically until today, often as part of a cross-sectoral Integrated Care (IC) treatment system. We will present the implementation of an "Assertive Community Treatment" embedded into an IC-treatment model in Hamburg and discuss the 3-year-outcomes. The IC-treatment model has been designed for severe mentally ill patients with psychotic disorders. Since May 2007 the model is financed by different health insurances as a managed-care "capitation-model" and its effectiveness gets continuously evaluated. The model proved to be effective in earlier studies were compared with standard care low rates of service disengagement were found as well as significantly improved psychopathology, psychosocial functioning, quality of life, satisfaction with care and adherence, while being cost effective. The rates of involuntary admissions declined to 10% in comparison to the years before. In 2011 the model was specified to the indication "first-episode adolescents and young adults in the age of 12-29" in a government-funded study "Integrated Care in Early Psychosis, ICEP Study". In this study an interdisciplinary team of child, adolescent and adult psychiatrists was implemented and since 2012 it is financed by the involved health insurances throughout an expansion of the §140 SGB V agreement.

  3. Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment.

    Science.gov (United States)

    Ledeganck, Kristien J; Boulet, Gaëlle A; Horvath, Caroline A; Vinckx, Marleen; Bogers, Johannes J; Van Den Bossche, Rita; Verpooten, Gert A; De Winter, Benedicte Y

    2011-09-01

    Renal magnesium (Mg(2+)) and sodium (Na(+)) loss are well-known side effects of cyclosporine (CsA) treatment in humans, but the underlying mechanisms still remain unclear. Recently, it was shown that epidermal growth factor (EGF) stimulates Mg(2+) reabsorption in the distal convoluted tubule (DCT) via TRPM6 (Thébault S, Alexander RT, Tiel Groenestege WM, Hoenderop JG, Bindels RJ. J Am Soc Nephrol 20: 78-85, 2009). In the DCT, the final adjustment of renal sodium excretion is regulated by the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which is activated by the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to gain more insight into the molecular mechanisms of CsA-induced hypomagnesemia and hyponatremia. Therefore, the renal expression of TRPM6, TRPM7, EGF, EGF receptor, claudin-16, claudin-19, and the NCC, and the effect of the RAAS on NCC expression, were analyzed in vivo in a rat model of CsA nephrotoxicity. Also, the effect of EGF administration on these parameters was studied. CsA significantly decreased the renal expression of TRPM6, TRPM7, NCC, and EGF, but not that of claudin-16 and claudin-19. Serum aldosterone was significantly lower in CsA-treated rats. In control rats treated with EGF, an increased renal expression of TRPM6 together with a decreased fractional excretion of Mg(2+) (FE Mg(2+)) was demonstrated. EGF did not show this beneficial effect on TRPM6 and FE Mg(2+) in CsA-treated rats. These data suggest that CsA treatment affects Mg(2+) homeostasis via the downregulation of TRPM6 in the DCT. Furthermore, CsA downregulates the NCC in the DCT, associated with an inactivation of the RAAS, resulting in renal sodium loss.

  4. The effect of unpaid caregiving intensity on labour force participation: results from a multinomial endogenous treatment model.

    Science.gov (United States)

    Nguyen, Ha Trong; Connelly, Luke Brian

    2014-01-01

    It is well acknowledged that the intensity of caregiving affects the labour force participation of caregivers. The literature so far has not, however, been able to control effectively for the endogeneity of caregiving intensity. This paper contributes by dealing with the endogeneity of unpaid caregiving intensity when examining its impact on the labour force participation of caregivers. We distinguish between care provided to people who cohabit with the care recipient and care provided to recipients who reside elsewhere, as well as between primary and secondary caring roles. We address the endogeneity of selection in various care intensity roles via an instrumental variables approach, using the health status of potential care recipients as instruments. Data from wave 8 of the Household Income and Labour Dynamics in Australia survey which was undertaken in 2008 are used. We focus on a sample of 7845 working age males and females. Ruling out the endogeneity of any caregiving intensity role, we find that caregiving has a significant deterrent effect on caregivers' employment. This deterrent effect however is concentrated among those who identify as the main caregiver and the result appears to be the same irrespective of gender. Providing care as the main caregiver reduces the probability of employment by approximately 12 percentage points for both males and females, regardless of whether or not the caregivers cohabit with the care recipients. By contrast, we find no statistically significant impact of providing care as a secondary caregiver on the employment probabilities of either males or females. These results are germane to the development of policies that may affect informal caregiving and, thereby, the labour force decisions of carers.

  5. 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.

  6. Analysis of laser transmission and thermal effects on the inner root surface during periodontal treatment with a 940-nm diode laser in an in vitro pocket model.

    Science.gov (United States)

    Falkenstein, Fabian; Gutknecht, Norbert; Franzen, René

    2014-12-01

    The purpose of this study was to analyze thermal effects during laser-assisted periodontal treatment. An in vitro model for temperature measurements was developed to investigate different laser settings regarding pulp safety. Additionally, the influence of transmission on pulp temperature elevation was evaluated. Longitudinal root sections were irradiated with a 940-nm diode laser with 1.0 and 1.5 W in continuous wave mode. According to wall thicknesses, irradiation times were adjusted to 20 s for upper and 10 s for lower incisors, respectively. Transmission was relatively low in both upper (4.8% to 8.3% of incident power) and lower incisors (10.2% to 15.0%). Samples were embedded in a polyurethane model and six thermocouples were affixed. Regardless of dentine thickness, the middle third of the root was identified to be the area with the most heat load, where a temperature rise of 7.5°C (1.0 W) and 10.5°C (1.5 W) was registered in upper incisors. A difference of 1.5°C to 3°C was detected in lower incisors compared with uppers. All settings were safe except for 1.5 W, 20 s. Transmission affected heat generation remarkably. The proposed model provides advantages regarding heat transfer and enables for spatially resolved temperature measurements.

  7. Development of a new model for the induction of chronic kidney disease via intraperitoneal adenine administration, and the effect of treatment with gum acacia thereon.

    Science.gov (United States)

    Al Za'abi, Mohammed; Al Busaidi, Mahfouda; Yasin, Javid; Schupp, Nicole; Nemmar, Abderrahim; Ali, Badreldin H

    2015-01-01

    Oral adenine (0.75% w/w in feed), is an established model for human chronic kidney disease (CKD). Gum acacia (GA) has been shown to be a nephroprotective agent in this model. Here we aimed at developing a new adenine-induced CKD model in rats via a systemic route (intraperitoneal, i.p.) and to test it with GA to obviate the possibility of a physical interaction between GA and adenine in the gut. Adenine was injected i.p. (50 or 100 mg/Kg for four weeks), and GA was given concomitantly in drinking water at a concentration of 15%, w/v. Several plasma and urinary biomarkers of oxidative stress were measured and the renal damage was assessed histopathologically. Adenine, at the two given i.p. doses, significantly reduced body weight, and increased relative kidney weight, water intake and urine output. It dose-dependently increased plasma and urinary inflammatory and oxidative stress biomarkers, and caused morphological and histological damage resembling that which has been reported with oral adenine. Concomitant treatment with GA significantly mitigated almost all the above measured indices. Administration of adenine i.p. induced CKD signs very similar to those induced by oral adenine. Therefore, this new model is quicker, more practical and accurate than the original (oral) model. GA ameliorates the CKD effects caused by adenine given i.p. suggesting that the antioxidant and anti-inflammatory properties possessed by oral GA are the main mechanism for its salutary action in adenine-induced CKD, an action that is independent of its possible interaction with adenine in the gut.

  8. 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

    OpenAIRE

    2012-01-01

    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 ta...

  9. Assessment of the Effect of Artesunate on the Developing Bones of Wistar Rat Animal Model of Malaria Treatment

    Directory of Open Access Journals (Sweden)

    Sunday Samuel Adebisi

    2010-02-01

    Full Text Available AIM: Among its contemporaries, artesunate, a semisynthetic artemisinin antimalarial is presently being esteemed above others as a ready combatant against the malaria menace plaguing most parts of the tropics; one, for being less or non-resisted by the parasite and two, less allergy-provoking to the users. However, recent clinical observations and experimental studies had implicated this drug to be embryo-fetal toxic and this had since generated research interests such as this, to ascertain the extent of the effects of artesunate on the morphology, weights and dimensions of the developing Wistar rat bones METHOD: Oral doses of 2mg/kg and 4mg/kg body weight were administered to each experimental pregnant Wistar rat from the 9th to the 11th day of gestation–being the active osteogenic period in this animal. Two rats were sacrificed each day from days 12 to 21 and foetuses retrieved and the following assessed on the skeleton: wet weights, dry weights, ash weights, fat free weights and total body weights, plus dimensions of long bones and pelvic bones. RESULTS: Compared to the control, all the parameters assessed were negatively affected in the treated groups, being more severe in the 4mg/kg rats. CONCLUSION: Artesunate, even at relatively low dosages appears to be hazardous to the structural integrity of bones particularly when administered at critical period of development, a point to note in the global quest to combat malaria cum polio, the presently well acknowledged ravaging twin menace in the tropics. [TAF Prev Med Bull 2010; 9(1.000: 23-28

  10. Hydraulic modelling of drinking water treatment plant operations

    Directory of Open Access Journals (Sweden)

    K. J. Borger

    2008-10-01

    Full Text Available For a drinking water treatment plant simulation, water quality models, a hydraulic model, a process-control model, an object model, data management, training and decision-support features and a graphic user interface have been integrated. The integration of a hydraulic model in the simulator is necessary to correctly determine the division of flows over the plant's lanes and, thus, the flow through the individual treatment units, based on valve positions and pump speeds. The flow through a unit 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. Using this library, a hydraulic model was set up and validated for the drinking water treatment plant Harderbroek.

  11. Treatment of Sexual Offenders: Research, Best Practices, and Emerging Models

    Science.gov (United States)

    Yates, Pamela M.

    2013-01-01

    Treatment of sexual offenders has evolved substantially over the years; various theoretical and practice models of treatment been developed, modified, refined, and proposed over time. The predominant current recommended approach, supported by research, adheres to specific principles of effective correctional intervention, follows a…

  12. 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...

  13. Heroin epidemics, treatment and ODE modelling.

    Science.gov (United States)

    White, Emma; Comiskey, Catherine

    2007-07-01

    The UN [United Nations Office on Drugs and Crime (UNODC): World Drug Report, 2005, vol. 1: Analysis. UNODC, 2005.], EU [European Monitoring Centre for Drugs and Drug Addiction (EMCDDA): Annual Report, 2005.http://annualreport.emcdda.eu.int/en/home-en.html.] and WHO [World Health Organisation (WHO): Biregional Strategy for Harm Reduction, 2005-2009. HIV and Injecting Drug Use. WHO, 2005.] have consistently highlighted in recent years the ongoing and persistent nature of opiate and particularly heroin use on a global scale. While this is a global phenomenon, authors have emphasised the significant impact such an epidemic has on individual lives and on society. National prevalence studies have indicated the scale of the problem, but the drug-using career, typically consisting of initiation, habitual use, a treatment-relapse cycle and eventual recovery, is not well understood. This paper presents one of the first ODE models of opiate addiction, based on the principles of mathematical epidemiology. The aim of this model is to identify parameters of interest for further study, with a view to informing and assisting policy-makers in targeting prevention and treatment resources for maximum effectiveness. An epidemic threshold value, R(0), is proposed for the drug-using career. Sensitivity analysis is performed on R(0) and it is then used to examine the stability of the system. A condition under which a backward bifurcation may exist is found, as are conditions that permit the existence of one or more endemic equilibria. A key result arising from this model is that prevention is indeed better than cure.

  14. 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 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.

  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. 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.

  17. 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

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

    Science.gov (United States)

    Sahraoui, Afaf; Winzell, Maria Sörhede; Gorman, Tracy; Smith, Dave M; Skrtic, Stanko; Hoeyem, Merete; Abadpour, Shadab; Johansson, Lars; Korsgren, Olle; Foss, Aksel; Scholz, Hanne

    2015-01-01

    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, maintaining beta

  19. Self-administered treatment in stepped-care models of depression treatment.

    Science.gov (United States)

    Scogin, Forrest R; Hanson, Ashley; Welsh, Douglas

    2003-03-01

    Stepped behavioral health care models have begun to receive increased attention. Self-administered treatments deserve consideration as an element in these models for some disorders and for some consumers. Features suggesting inclusion include low cost, wide availability, and evidence-based status. We present a stepped-care model for depression inclusive of a self-administered treatment component. We also discuss cautions such as depression severity and consumer preference. Evaluation of the efficacy and cost effectiveness of this approach to depression treatment is necessary. Copyright 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 341-349, 2003.

  20. 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......) 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....

  1. Mathematical modeling of endovenous laser treatment (ELT

    Directory of Open Access Journals (Sweden)

    Wassmer Benjamin

    2006-04-01

    Full Text Available Abstract Background and objectives Endovenous laser treatment (ELT has been recently proposed as an alternative in the treatment of reflux of the Great Saphenous Vein (GSV and Small Saphenous Vein (SSV. Successful ELT depends on the selection of optimal parameters required to achieve an optimal vein damage while avoiding side effects. Mathematical modeling of ELT could provide a better understanding of the ELT process and could determine the optimal dosage as a function of vein diameter. Study design/materials and methods The model is based on calculations describing the light distribution using the diffusion approximation of the transport theory, the temperature rise using the bioheat equation and the laser-induced injury using the Arrhenius damage model. The geometry to simulate ELT was based on a 2D model consisting of a cylindrically symmetric blood vessel including a vessel wall and surrounded by an infinite homogenous tissue. The mathematical model was implemented using the Macsyma-Pdease2D software (Macsyma Inc., Arlington, MA, USA. Damage to the vein wall for CW and single shot energy was calculated for 3 and 5 mm vein diameters. In pulsed mode, the pullback distance (3, 5 and 7 mm was considered. For CW mode simulation, the pullback speed (1, 2, 3 mm/s was the variable. The total dose was expressed as joules per centimeter in order to perform comparison to results already reported in clinical studies. Results In pulsed mode, for a 3 mm vein diameter, irrespective of the pullback distance (2, 5 or 7 mm, a minimum fluence of 15 J/cm is required to obtain a permanent damage of the intima. For a 5 mm vein diameter, 50 J/cm (15W-2s is required. In continuous mode, for a 3 mm and 5 mm vein diameter, respectively 65 J/cm and 100 J/cm are required to obtain a permanent damage of the vessel wall. Finally, the use of different wavelengths (810 nm or 980 nm played only a minor influence on these results. Discussion and conclusion The parameters

  2. 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. 

  3. Preliminary investigation of the effects of topical mixture of Lawsonia inermis L. and Ricinus communis L. leaves extract in treatment of osteoarthritis using MIA model in rats.

    Science.gov (United States)

    Ziaei, Atousa; Sahranavard, Shamim; Gharagozlou, Mohammad Javad; Faizi, Mehrdad

    2016-05-03

    Many plants have been introduced in Iranian traditional medicine for treatment of different joint problems including knee pain. Topical application of the mixture of Lawsonia inermis L. leaves (Henna) with aqueous extract of Ricinus communis L. leaves have been mentioned to have significant effects on reducing knee pain. The present study was designed to evaluate the analgesic and anti-inflammatory effects of the mixture of these two herbs in male rats. We induced knee osteoarthritis as a model of chronic pain by intra-articular injection of mono sodium iodoacetate (MIA). Mechanical allodynia, hotplate latency test, spontaneous movements and gait analysis were used for the evaluation of analgesic activity. Anti-inflammatory activity was evaluated by measuring the diameter and the volume of the injected paw compared to contralateral paw. These tests were monitored at days 1, 3, 7, 14 and 21 of MIA administration. Histopathological evaluations were also used to assess the efficacy of the treatment on inflammation and lesions in knee tissue. In all tests, diclofenac topical gel was used as a positive control. The herbal extracts, their mixture, and vehicle or diclofenac gel were administered daily for 14 days by topical route. The mixture of these two extracts significantly reduced the knee joint width and volume of the injected paws and also improved foot prints in gait analysis after 3 days of MIA injection. Analysis of mechanical allodynia (after 21 days), hotplate latency test (after 10 days), spontaneous movements (after 7 days) and in positive control group (after 3 days in all tests and in mechanical allodynia after 14 days) compared to the vehicle group, showed significant effects. Topical usage of the selected formulation made significant histopathological changes on the knee of the rats. Compared to the vehicle group, the tests and diclofenac groups showed less reactions characterized by negligible edema and a few scattered inflammatory lymphoid

  4. Modeling Severe Fever with Thrombocytopenia Syndrome Virus Infection in Golden Syrian Hamsters: Importance of STAT2 in Preventing Disease and Effective Treatment with Favipiravir.

    Science.gov (United States)

    Gowen, Brian B; Westover, Jonna B; Miao, Jinxin; Van Wettere, Arnaud J; Rigas, Johanna D; Hickerson, Brady T; Jung, Kie-Hoon; Li, Rong; Conrad, Bettina L; Nielson, Skot; Furuta, Yousuke; Wang, Zhongde

    2017-02-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease endemic in parts of Asia. The etiologic agent, SFTS virus (SFTSV; family Bunyaviridae, genus Phlebovirus) has caused significant morbidity and mortality in China, South Korea, and Japan, with key features of disease being intense fever, thrombocytopenia, and leukopenia. Case fatality rates are estimated to be in the 30% range, and no antivirals or vaccines are approved for use for treatment and prevention of SFTS. There is evidence that in human cells, SFTSV sequesters STAT proteins in replication complexes, thereby inhibiting type I interferon signaling. Here, we demonstrate that hamsters devoid of functional STAT2 are highly susceptible to as few as 10 PFU of SFTSV, with animals generally succumbing within 5 to 6 days after subcutaneous challenge. The disease included marked thrombocytopenia and inflammatory disease characteristic of the condition in humans. Infectious virus titers were present in the blood and most tissues 3 days after virus challenge, and severe inflammatory lesions were found in the spleen and liver samples of SFTSV-infected hamsters. We also show that SFTSV infection in STAT2 knockout (KO) hamsters is responsive to favipiravir treatment, which protected all animals from lethal disease and reduced serum and tissue viral loads by 3 to 6 orders of magnitude. Taken together, our results provide additional insights into the pathogenesis of SFTSV infection and support the use of the newly described STAT2 KO hamster model for evaluation of promising antiviral therapies. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease for which there are currently no therapeutic options or available vaccines. The causative agent, SFTS virus (SFTSV), is present in China, South Korea, and Japan, and infections requiring medical attention result in death in as many as 30% of the cases. Here, we describe a novel model of SFTS in hamsters genetically

  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

    . Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (microCT) demonstrated that these effects were not due to changes in cancer progression. The difference...

  6. Modeling and Hemofiltration Treatment of Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Robert S. Parker

    2016-10-01

    Full Text Available The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL-6, tumor necrosis factor (TNF, and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC algorithm was synthesized to control a hemoadsorption (HA device, a blood purification treatment for acute inflammation. A particle filter (PF algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i the apparent primary mechanism of HA efficacy is white blood cell (WBC capture, with cytokine capture a secondary benefit; and (ii differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

  7. 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

  8. 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...

  9. Metabolic syndrome-associated sperm alterations in an experimental rabbit model: relation with metabolic profile, testis and epididymis gene expression and effect of tamoxifen treatment.

    Science.gov (United States)

    Marchiani, Sara; Vignozzi, Linda; Filippi, Sandra; Gurrieri, Bruna; Comeglio, Paolo; Morelli, Annamaria; Danza, Giovanna; Bartolucci, Gianluca; Maggi, Mario; Baldi, Elisabetta

    2015-02-05

    The influence of metabolic syndrome (MetS) on sperm quality and function is debated. Using a well-established high fat diet (HFD) rabbit model resembling human MetS, including development of hypogonadism, we demonstrate that HFD decreased sperm motility, morphology and acrosome reaction in response to progesterone and increased sperm cholesterol content. All the above parameters were associated with most MetS features, its severity and plasma testosterone (T) at univariate analysis. After T adjustment, sperm morphology and motility retained a significant association, respectively, with mean arterial pressure and circulating cholesterol levels. MetS modified the expression of inflammatory and tissue remodelling genes in the testis and of aquaporins in the epididymis. In a multivariate analysis, sperm morphology resulted associated with testis expression of fibronectin and collagen type 1 genes, whereas motility with epididymis aquaporin 1 gene. Administration of tamoxifen, used in the treatment of idiopathic male infertility, to HFD rabbits partially restored motility, but further decreased morphology and increased spontaneous acrosome reaction, without restoring responsiveness to progesterone. Overall our results indicate that development of MetS produces detrimental effects on sperm quality and functionality by inducing metabolic disorders leading to alterations in testis and epididymis functions and evidence a role of hypertension as a new determinant of abnormal sperm morphology, in line with a previous human study from our group.

  10. 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.

  11. Sequential treatment with cytarabine and decitabine has an increased anti-leukemia effect compared to cytarabine alone in xenograft models of childhood acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Sarah M Leonard

    Full Text Available The current interest in epigenetic priming is underpinned by the belief that remodelling of the epigenetic landscape will sensitise tumours to subsequent therapy. In this pre-clinical study, paediatric AML cells expanded in culture and primary AML xenografts were treated with decitabine, a DNA demethylating agent, and cytarabine, a frontline cytotoxic agent used in the treatment of AML, either alone or in combination. Sequential treatment with decitabine and cytarabine was found to be more effective in reducing tumour burden than treatment with cytarabine alone suggesting that the sequential delivery of these agents may a have real clinical advantage in the treatment of paediatric AML. However we found no evidence to suggest that this outcome was dependent on priming with a hypomethylating agent, as the benefits observed were independent of the order in which these drugs were administered.

  12. Modelling AIDS epidemic and treatment with difference equations

    Directory of Open Access Journals (Sweden)

    Ramani A

    2004-01-01

    Full Text Available We propose two models for the description of the dynamics of an AIDS epidemic and of the effect of a combined-drugs AIDS treatment based on difference equations. We show that our interacting population model, despite its extreme simplicity, describes adequately the evolution of an AIDS epidemic. A cellular-automaton analogue of the discrete system of equations is presented as well. In the case of drug treatment, we identify two different regimes corresponding to efficient and inefficient medication. The effect of the discreteness of the equations is also studied.

  13. Modelling AIDS epidemic and treatment with difference equations

    Directory of Open Access Journals (Sweden)

    A. S. Carstea

    2004-07-01

    Full Text Available We propose two models for the description of the dynamics of an AIDS epidemic and of the effect of a combined-drugs AIDS treatment based on difference equations. We show that our interacting population model, despite its extreme simplicity, describes adequately the evolution of an AIDS epidemic. A cellular-automaton analogue of the discrete system of equations is presented as well. In the case of drug treatment, we identify two different regimes corresponding to efficient and inefficient medication. The effect of the discreteness of the equations is also studied.

  14. 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.

  15. 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.

  16. 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.

  17. Enhancement of Antitumor Effect of Tegafur/Uracil (UFT) plus Leucovorin by Combined Treatment with Protein-Bound Polysaccharide, PSK, in Mouse Models

    Institute of Scientific and Technical Information of China (English)

    Ryoji Katoh; Mitsuru Ooshiro

    2007-01-01

    We evaluated the antitumor effect of combined therapy with tegafur/uracil (UFT) plus leucovorin (LV) (UFT/LV)and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly.UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.

  18. A cost-effectiveness analysis of celecoxib compared with diclofenac in the treatment of pain in osteoarthritis (OA) within the Swedish health system using an adaptation of the NICE OA model.

    Science.gov (United States)

    Brereton, Nicholas; Pennington, Becky; Ekelund, Mats; Akehurst, Ronald

    2014-09-01

    Celecoxib for the treatment of pain resulting from osteoarthritis (OA) was reviewed by the Tandvårds- och läkemedelsförmånsverket-Dental and Pharmaceutical Benefits Board (TLV) in Sweden in late 2010. This study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus a PPI in a Swedish setting. The National Institute for Health and Care Excellence (NICE) in the UK developed a health economic model as part of their 2008 assessment of treatments for OA. In this analysis, the model was reconstructed and adapted to a Swedish perspective. Drug costs were updated using the TLV database. Adverse event costs were calculated using the regional price list of Southern Sweden and the standard treatment guidelines from the county council of Stockholm. Costs for treating cardiovascular (CV) events were taken from the Swedish DRG codes and the literature. Over a patient's lifetime treatment with celecoxib plus a PPI was associated with a quality-adjusted life year (QALY) gain of 0.006 per patient when compared to diclofenac plus a PPI. There was an increase in discounted costs of 529 kr per patient, which resulted in an incremental cost-effectiveness ratio (ICER) of 82,313 kr ($12,141). Sensitivity analysis showed that treatment was more cost effective in patients with an increased risk of bleeding or gastrointestinal (GI) complications. The results suggest that celecoxib plus a PPI is a cost effective treatment for OA when compared to diclofenac plus a PPI. Treatment is shown to be more cost effective in Sweden for patients with a high risk of bleeding or GI complications. It was in this population that the TLV gave a positive recommendation. There are known limitations on efficacy in the original NICE model.

  19. 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

    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...... 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...... 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....

  20. Post-treatment Effects of Topiramate Treatment for Heavy Drinking

    Science.gov (United States)

    Kranzler, Henry R.; Wetherill, Reagan; Feinn, Richard; Pond, Timothy; Gelernter, Joel; Covault, Jonathan

    2014-01-01

    Background We examined whether the effects of topiramate and a single nucleotide polymorphism (SNP; rs2832407) in GRIK1, which encodes a kainate receptor subunit, persisted following a 12-week, placebo-controlled trial in 138 heavy drinkers with a treatment goal of reduced drinking. During treatment, topiramate 200 mg/day significantly reduced heavy drinking days and increased the frequency of abstinent days (Kranzler et al. 2014a). In the European-American (EA) subsample (n=122), rs2832407 moderated the treatment effect on heavy drinking. Methods Patients were re-interviewed 3 and 6 months after the end of treatment. During treatment, we obtained 92.4% of drinking data, with 89.1% and 85.5% complete data at the 3- and 6-month follow-up visits, respectively. We examined four outcomes over time in the overall sample and the EA subsample: percent heavy drinking days (PHDD), percent days abstinent (PDA), serum γ-glutamyl transpeptidase (GGTP) concentration, and a measure of alcohol-related problems. Results In the full sample, the lower PHDD and higher PDA seen with topiramate treatment were no longer significant during follow-up. Nonetheless, the topiramate-treated patients had lower alcohol-related problem scores during treatment and both follow-up periods. Further, in the EA subsample, the greater reduction in PHDD seen during treatment in rs2832407*C-allele homozygotes persisted throughout follow-up, with no significant effects in A-allele carriers. A reduction in GGTP concentration was consistent with the reduction in heavy drinking, but did not reach statistical significance. Conclusion There are persistent therapeutic effects of topiramate in heavy drinkers, principally in rs2832407*C-allele homozygotes. PMID:25581656

  1. 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.

  2. Cost-effectiveness of early treatment for retinopathy of prematurity.

    Science.gov (United States)

    Kamholz, Karen L; Cole, Cynthia H; Gray, James E; Zupancic, John A F

    2009-01-01

    The Early Treatment for Retinopathy of Prematurity trial demonstrated that peripheral retinal ablation of eyes with high-risk prethreshold retinopathy of prematurity (early treatment) is associated with improved visual outcomes at 9 months' corrected gestational age compared with treatment at threshold disease (conventional management). However, early treatment increased the frequency of laser therapy, anesthesia with intubation, treatment-related systemic complications, and the need for repeat treatments. To determine the cost-effectiveness of an early treatment strategy for retinopathy of prematurity compared with conventional management. We developed a stochastic decision analytic model to assess the incremental cost of early treatment per eye with severe visual impairment prevented. We derived resource-use and efficacy estimates from the Early Treatment for Retinopathy of Prematurity trial's published outcome data. We used a third-party payer perspective. Our primary analysis focused on outcomes from birth through 9 months' corrected gestational age. A secondary analysis used a lifetime horizon. Parameter uncertainty was quantified by using probabilistic and deterministic sensitivity analyses. The incremental cost-effectiveness of early treatment was $14,200 per eye with severe visual impairment prevented. There was a 90% probability that the cost-effectiveness of early treatment would be less than $40,000 per eye with severe visual impairment prevented and a 0.5% probability that early treatment would be cost-saving (less costly and more effective). Limiting early treatment to more severely affected eyes (eyes with "type 1 retinopathy of prematurity" as defined by the Early Treatment for Retinopathy of Prematurity trial) had a cost-effectiveness of $6,200 per eye with severe visual impairment prevented. Analyses that considered long-term costs and outcomes found that early treatment was cost-saving. Early treatment of retinopathy of prematurity is both

  3. 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.

  4. 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

  5. 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

    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...... the sensitive fraction of the commensal flora.Growth parameters for competing bacterial strains were estimated from the combined in vitro pharmacodynamic effect of two antimicrobials using the relationship between concentration and net bacterial growth rate. Predictions of in vivo bacterial growth were...

  6. Modeling treatment couches in the Pinnacle treatment planning system: Especially important for arc therapy

    Energy Technology Data Exchange (ETDEWEB)

    Duggar, William Neil, E-mail: wduggar@umc.edu [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Nguyen, Alex [Ironwood Cancer and Research Center, Chandler, AZ (United States); Stanford, Jason; Morris, Bart; Yang, Claus C. [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States)

    2016-04-01

    This study is to demonstrate the importance and a method of properly modeling the treatment couch for dose calculation in patient treatment using arc therapy. The 2 treatment couch tops—Aktina AK550 and Elekta iBEAM evo—of Elekta LINACs were scanned using Philips Brilliance Big Bore CT Simulator. Various parts of the couch tops were contoured, and their densities were measured and recorded on the Pinnacle treatment planning system (TPS) using the established computed tomography density table. These contours were saved as organ models to be placed beneath the patient during planning. Relative attenuation measurements were performed following procedures outlined by TG-176 as well as absolute dose comparison of static fields of 10 × 10 cm{sup 2} that were delivered through the couch tops with that calculated in the TPS with the couch models. A total of 10 random arc therapy treatment plans (5 volumetric-modulated arc therapy [VMAT] and 5 stereotactic body radiation therapy [SBRT]), using 24 beams, were selected for this study. All selected plans were calculated with and without couch modeling. Each beam was evaluated using the Delta{sup 4} dosimetry system (Delta{sup 4}). The Student t-test was used to determine statistical significance. Independent reviews were exploited as per the Imaging and Radiation Oncology Core head and neck credentialing phantom. The selected plans were calculated on the actual patient anatomies with and without couch modeling to determine potential clinical effects. Large relative beam attenuations were noted dependent on which part of the couch top beams were passing through. Substantial improvements were also noted for static fields both calculated with the TPS and delivered physically when the couch models were included in the calculation. A statistically significant increase in agreement was noted for dose difference, distance to agreement, and γ-analysis with the Delta{sup 4} on VMAT and SBRT plans. A credentialing review showed

  7. 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...

  8. Longitudinal Evaluation of a Scale-up Model for Teaching Mathematics with Trajectories and Technologies: Persistence of Effects Three Years after the Treatment

    Science.gov (United States)

    Clements, Douglas H.; Sarama, Julie; Layzer, Carolyn; Unlu, Fatih; Wolfe, Christopher B.; Spitler, Mary Elaine

    2013-01-01

    Education needs generalizable models to scale up evidence-based practices and programs and longitudinal research evaluating the persistence of the effect of their implementation. This is particularly important given the "deep, systemic incapacity of U.S. schools, and the practitioners who work in them, to develop, incorporate, and extend new…

  9. [Cost-effectiveness Analysis of Panitumumab Plus mFOLFOX6 Compared to Bevacizumab Plus mFOLFOX6 for First-line Treatment of Patients with Wild-type RAS Metastatic Colorectal Cancer--Czech Republic Model Adaptation].

    Science.gov (United States)

    Fínek, J; Skoupá, J; Jandová, P

    2015-01-01

    Pharmacoeconomic assessments are a part of the decision process not only during reimbursement setting, but in clinical practice as well. The presented cost-effectiveness analysis assesses panitumumab+mFOLFOX6 vs. bevacizumab+mFOLFOX6 in 1st line treatment of patients with wildtype RAS metastatic colorectal cancer (mCRC) in the Czech environment. The adaptation of a Markov model considers the healthcare perspective; clinical data (efficacy, healthcare utilization and adverse events) are derived from a head-to-head comparison (PEAK study). Health states included in the model: progression free on treatment, progression (with/ without active treatment), resection of metastases, disease-free after successful resection and death. Actual reimbursement levels were used to estimate costs, published literature to estimate duration of 2nd line treatment. The analysis assumes a lifetime horizon; uncertainty was limited by performing one-way and probabilistic sensitivity analyses. Analysis outcomes are life-years gained (LYG) and quality-adjusted life-years (QALYs). Panitumumab+mFOLFOX6 is more effective and more costly in 1st line patients with wildtype RAS mCRC. Incremental costs per QALY are 837,270 CZK, per LYG 615,022 CZK; however, below the willingness-to-pay threshold applied in the Czech Republic. Panitumumab+mFOLFOX6 is cost-effective in 1st line treatment of patients with wildtype RAS mCRC compared to bevacizumab+mFOLFOX6 in the Czech setting.

  10. 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

  11. Treatment Effects on Neonatal EEG.

    Science.gov (United States)

    Obeid, Rawad; Tsuchida, Tammy N

    2016-10-01

    Conventional EEG and amplitude-integrated electroencephalography are used in neonates to assess prognosis and significant changes in brain activity. Neuroactive medications and hypothermia can influence brain activity and therefore alter EEG interpretation. There are limited studies on the effect of these therapies on neonatal EEG background activity. Medication effects on the EEG or amplitude-integrated electroencephalography include increased interburst interval duration, voltage suppression, and sleep disruption. The effect is transient in term newborns but can be persistent in premature newborns. Although therapeutic hypothermia does not produce significant changes in EEG activity, it does change the time point at which EEG can accurately predict neurodevelopmental outcome. It is important to account for these effects on the EEG to avoid inaccurate interpretation that may affect prognostication.

  12. 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.

  13. Dissimilar effect of perming and bleaching treatments on cuticles: advanced hair damage model based on elution and oxidation of S100A3 protein.

    Science.gov (United States)

    Kizawa, Kenji; Inoue, Takafumi; Yamaguchi, Masahito; Kleinert, Peter; Troxler, Heinz; Heizmann, Claus W; Iwamoto, Yoshimichi

    2005-01-01

    Hair treatment chemicals induce sudden and severe hair damage. In this study, we examined cuticles from untreated, permed, and bleached hair that were mechanically discriminated by shaking in water. Both perming and bleaching treatments are prone to easily delaminate cuticles. Confocal microscopy revealed that the cuticles of permed hair were delaminated with larger pieces than untreated ones. On the other hand, the cuticles of bleached hair tend to fragment into small peptides. At the minimum concentration of thioglycolate required to elute S100A3 protein from the endocuticle into the reductive permanent waving lotion, enlarged delaminated cuticle fragments were observed. Although S100A3 is retained in bleached hair, S100A3 is irreversibly oxidized upon bleaching treatment. It is likely that the oxidative cleavage of disulfide bonds between cuticle-constituting proteins, including S100A3, results in the fragile property of cuticles. Here we present a more comprehensive model of hair damage based on a diverse mechanism of cuticle delamination.

  14. Shungite carbon catalytic effect on coal treatment

    Energy Technology Data Exchange (ETDEWEB)

    Grigorieva, E.N.; Rozhkova, N.N. [Russian Academy of Sciences, Moscow (Russian Federation). Institute for High Temperature

    1999-07-01

    The catalytic ability of shungite carbon in reactions of coal organic matter models appeared to be due to its fullerene structure only. Transition metal sulphides present in shungite carbon are not active in the conditions of coal treatment. Shungite carbon was shown to exhibit an acceleration of thermolysis of coal and organic matter models, mainly dehydrogenation. 5 refs., 1 tabs.

  15. 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

  16. Net-Zero-Energy Model for Sustainable Wastewater Treatment.

    Science.gov (United States)

    Yan, Peng; Qin, Rong-Cong; Guo, Jin-Song; Yu, Qiang; Li, Zhe; Chen, You-Peng; Shen, Yu; Fang, Fang

    2017-01-17

    A large external energy input prevents wastewater treatment from being environmentally sustainable. A net-zero-energy (NZE) wastewater treatment concept based on biomass energy recycling was proposed to avoid wasting resources and to promote energy recycling in wastewater treatment plants (WWTPs). Simultaneously, a theoretical model and boundary condition based on energy balance were established to evaluate the feasibility of achieving NZE in WWTPs; the model and condition were employed to analyze data from 20 conventional WWTPs in China. A total of six WWTPs can currently export excess energy, eight WWTPs can achieve 100% energy self-sufficiency by adjusting the metabolic material allocation, and six municipal WWTPs cannot achieve net-zero energy consumption based on the evaluation of the theoretical model. The NZE model offset 79.5% of the electricity and sludge disposal cost compared with conventional wastewater treatment. The NZE model provides a theoretical basis for the optimization of material regulation for the effective utilization of organic energy from wastewater and promotes engineering applications of the NZE concept in WWTPs.

  17. Comparison the treatment effects between simultaneous dual frequency and single frequency irradiation of ultrasound in a murine model of breast adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Mahboobeh Alamolhoda

    2010-12-01

    Full Text Available Introduction: Transient cavitations induced by low frequency irradiation of ultrasound can be used to treat tumors. Previous studies in in-vitro experiments have shown that induced cavitation by dual or multiple frequencies of ultrasound is greater than induced cavitation by single frequency irradiation. In this study, we compared and evaluated the treatment effects of dual frequency irradiation of ultrasound (1 MHz and 150 kHz and single frequency irradiation in in-vivo experiments on breast adenocarcinoma tumors. Material and Method: In this study, the tumor-bearing mice were divided into 5 groups: control, sham, treated group for 30 min with 150 kHz frequency in continuous mode, another group with 1 MHz frequency in pulse mode, and treated group with combined dual frequency ultrasound (150 kHz in continuous mode and 1 MHz in 80% pulse mode. To evaluate the effects of ultrasound irradiation on tumor growth delay, the volumes of the tumors were investigated for 30 days. Tumor growth delay parameters including relative volume, inhibition ratio percentage and the required times for the tumor volume to reach to two (T2 and five (T5 times its initial volume were calculated. Results: The results showed that the treated groups with single frequency irradiation of 150 kHz continuous mode and 1 MHz pulse mode and combined dual frequency had statistically significant differences in tumor relative volume percentage during the period of 3 to 24 days after treatment (p

  18. Lymphedema as a Cancer Treatment Side Effect

    Science.gov (United States)

    ... Navigating Cancer Care > Side Effects > Lymphedema Request Permissions Lymphedema Approved by the Cancer.Net Editorial Board , 05/ ... years after cancer treatment has ended. Symptoms of lymphedema People with lymphedema in their arm or leg ...

  19. Natural Acne Treatment: What's Most Effective?

    Science.gov (United States)

    ... and young adults with mild to moderate acne. Aloe vera. A 50 percent aloe vera gel was combined with a conventional acne ... Elsevier; 2014. Hajheydari Z, et al. Effect of Aloe vera topical gel combined with tretinoin in treatment ...

  20. Cost-effectiveness of Voriconasole in treatment of invasive aspregillosis

    Directory of Open Access Journals (Sweden)

    N. N. Climko

    2009-01-01

    Full Text Available Invasive aspergillosis (IA is widespread infectious implication in immunodeficient patients, characterized by severe clinical manifestations and high mortality. This article presents the first case of pharmacoeconomical analysis of Voriconasole in treatment of IA compared with alternative therapies in Russia. Using mathematic modeling methods, we evalued total costs (including costs of IA treatment, clinical effectiveness and IA-related mortality in each therapy group. Obtained results showed the dominating of Voriconasole because of its high effectiveness and lower costs compared with caspofungine or amphotericine B. Total costs of therapy with Voricinasole were up to 30% lower compared with caspofungine and up to 70% lower compared with amphotericine B. Performed univariate sensitivity analysis showed that cost-effectiveness of anti-IA treatment depends mostly on clinical effectiveness of antimycotics rather than drug costs. Thus, treatment with Voriconasole is cost-effective in IA patients.

  1. Modelling of Water Turbidity Parameters in a Water Treatment Plant

    Directory of Open Access Journals (Sweden)

    A. S. KOVO

    2005-01-01

    Full Text Available The high cost of chemical analysis of water has necessitated various researches into finding alternative method of determining portable water quality. This paper is aimed at modelling the turbidity value as a water quality parameter. Mathematical models for turbidity removal were developed based on the relationships between water turbidity and other water criteria. Results showed that the turbidity of water is the cumulative effect of the individual parameters/factors affecting the system. A model equation for the evaluation and prediction of a clarifier’s performance was developed:Model: T = T0(-1.36729 + 0.037101∙10λpH + 0.048928t + 0.00741387∙alkThe developed model will aid the predictive assessment of water treatment plant performance. The limitations of the models are as a result of insufficient variable considered during the conceptualization.

  2. Cost Effectiveness of Imiquimod 5% Cream Compared with Methyl Aminolevulinate-Based Photodynamic Therapy in the Treatment of Non-Hyperkeratotic, Non-Hypertrophic Actinic (Solar) Keratoses: A Decision Tree Model

    OpenAIRE

    Wilson, Edward C F

    2010-01-01

    Background: Actinic keratosis (AK) is caused by chronic exposure to UV radiation (sunlight). First-line treatments are cryosurgery, topical 5-fluorouracil (5-FU) and topical diclofenac. Where these are contraindicated or less appropriate, alternatives are imiquimod and photodynamic therapy (PDT). Objective: To compare the cost effectiveness of imiquimod and methyl aminolevulinate-based PDT (MAL-PDT) from the perspective of the UK NHS. Methods: A decision tree model was populated with data fro...

  3. Treatment of model solutions and wastewater containing selected hazardous metal ions using a chitin/lignin hybrid material as an effective sorbent.

    Science.gov (United States)

    Bartczak, Przemysław; Klapiszewski, Łukasz; Wysokowski, Marcin; Majchrzak, Izabela; Czernicka, Weronika; Piasecki, Adam; Ehrlich, Hermann; Jesionowski, Teofil

    2017-12-15

    A chitin/lignin material with defined physicochemical and morphological properties was used as an effective adsorbent of environmentally toxic metals from model systems. Particularly significant is its use in the neutralization of real industrial wastes. The ions Ni(2+), Cu(2+), Zn(2+) and Pb(2+) were adsorbed on the functional sorbent, confirming the high sorption capacity of the newly obtained product, primarily due to the presence on its surface of numerous active functional groups from the component biopolymers. The kinetics of the process of ion adsorption from model solution were investigated, and the experimental data were found to fit significantly better to a type 1 pseudo-second-order kinetic model, as confirmed by the high correlation coefficient of 0.999 for adsorption of both nickel(II) copper(II) zinc(II) and lead(II) ions. The experimental data obtained on the basis of adsorption isotherms corresponded to the Langmuir model. The sorption capacity of the chitin/lignin material was measured at 70.41 mg(Ni(2+))/g, 75.70 mg(Cu(2+))/g, 82.41 mg(Zn(2+))/g and 91.74 mg(Pb(2+))/g. Analysis of thermodynamic parameters confirmed the endothermic nature of the process. It was also shown that nitric acid is a very effective desorbing (regenerating) agent, enabling the chitin/lignin material to be reused as an effective sorbent of metal ions. The sorption abilities of the chitin/lignin system with respect to particular metal ions can be ordered in the sequence Ni(2+)

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

    NARCIS (Netherlands)

    van der Helm, A.W.C.

    2007-01-01

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

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

    African Journals Online (AJOL)

    Among these activities, wastewater treatment plays a crucial role. In this work, a Streeter-Phelps dissolved oxygen model (DO) is implemented in a ... The Olifants River catchment modelled in this study features 9 wastewater treatment plants.

  6. 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.

  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. 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; Tiranti, Valeria

    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.

  9. Dose effect evaluation and therapeutic window of the neuro-EPO nasal application for the treatment of the focal ischemia model in the Mongolian gerbil.

    Science.gov (United States)

    Teste, Iliana Sosa; Tamos, Yuneidys Mengana; Cruz, Yamila Rodríguez; Cernada, Adriana Muñoz; Rodríguez, Janette Cruz; Martínez, Nelvis Subirós; Antich, Rosa Maria Coro; González-Quevedo, Alina; Rodríguez, Julio Cesar García

    2012-01-01

    Cerebrovascular disease is the third leading cause of death and the leading cause of disability in Cuba and in several developed countries. A possible neuroprotective agent is the rHu-EPO, whose effects have been demonstrated in models of brain ischemia. The Neuro-EPO is a derivative of the rHu-EPO that avoids the stimulation of erythropoiesis. The aim of this study was to determine the Neuro-EPO delivery into the central nervous system (CNS) to exert a neuroprotective effect in cerebral ischemia model of the Mongolian gerbil. The Neuro-EPO in a rate of 249.4 UI every 8 hours for 4 days showed 25% higher viability efficacy (P > 0.01), improving neurological score and behavior of the spontaneous exploratory activity, the preservation of CA3 areas of the hippocampus, the cortex, and thalamic nuclei in the focal ischemia model of the Mongolian gerbil. In summary, this study, the average dose-used Neuro-EPO (249.4 UI/10 μL/every 8 hours for 4 days), proved to be valid indicators of viability, neurological status, and spontaneous exploratory activity, being significantly lower than that reported for the systemically use of the rHu-EPO as a neuroprotectant. Indeed, up to 12 h after brain ischemia is very positive Neuro-EPO administration by the nasal route as a candidate for neuroprotection.

  10. In silico models of alcohol dependence and treatment

    Directory of Open Access Journals (Sweden)

    Boris eKovatchev

    2012-02-01

    Full Text Available In this paper we view alcohol dependence and the response to treatment as a recurrent bio-behavioral process developing in time and propose formal models of this process combining behavior and biology in silico. The behavioral components of alcohol dependence and treatment are formally described by a stochastic process of human behavior, which serves as an event generator challenging the metabolic system. The biological component is driven by the biochemistry of alcohol intoxication described by deterministic models of ethanol pharmacodynamics and pharmacokintetics to enable simulation of drinking addiction in humans. Derived from the known physiology of ethanol and the literature of both ethanol intoxication and ethanol absorption, the different models are distilled into a minimal model (as simple as the complexity of the data allows that can represent any specific patient. We use these modeling and simulation techniques to explain responses to placebo and ondansetron treatment observed in clinical studies. Specifically, the response to placebo was explained by a reduction of the probability of environmental reinforcement, while the effect of ondansetron was explained by a gradual decline in the degree of ethanol-induced neuromodulation. Further, we use in silico experiments to study critical transitions in blood alcohol levels after specific average number of drinks per day, and propose the existence of two critical thresholds in the human - one at 5 and another at 11 drinks/day - at which the system shifts from stable to critical and to super critical state indicating a state of alcohol addiction. The advantages of such a model-based investigation are that 1 the process of instigation of alcohol dependence and its treatment can be deconstructed into meaningful steps, which allow for individualized treatment tailoring, and 2 physiology and behavior can be quantified in different (animal or human studies and then the results can be integrated

  11. 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.

  12. 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.

  13. Effective Treatment of Staphylococcal Scalded Skin Syndrome with Platelet Microbicidal Protein in CBRB-Rb(8.17)1Iem Mice Model.

    Science.gov (United States)

    Miroshnikov, Sergey A; Gritsenko, Viktor A; Ivanov, Iuri B

    2015-09-01

    Skin and soft-tissue infections are among the most common infections. Staphylococcus aureus may cause a number of toxin-mediated diseases, including staphylococcal scalded skin syndrome (SSSS). The therapeutic efficacy of some antimicrobial peptides was recently evaluated in a mouse model of SSSS. This study is the first in vivo demonstration of the use of PMP to improve outcome of SSSS. Twenty-four CBRB-Rb(8.17)1Iem female mice naturally infected by endogenous S. aureus with SSSS symptoms were used in this work and divided into two equal groups. From neck of each mouse was isolated and identified endogenous exfoliative producing strain of S. aureus. PMP was obtained from human platelets and tested against Bacillus subtilis ATCC 6633. PMP had bactericidal activity against B. subtilis ATTC 6633 and endogenous strain of S. aureus at 2.0 ± 0.5 and 14.5 ± 0.5 µg/ml, respectively. At 4 weeks, the mice of experimental group were treated subcutaneous near exfoliative zone with 0.2 ml of PMP in final concentration 10 µg/ml every day. Control mice was injected with 0.2 ml 0.9% NaCl. At 1 day of experiment maximal zone of alopecia was at PMP-treating group (380 ± 20 mm(2)) in comparison with control group (167 ± 10 mm(2), p < 0.01). At 50 day of observation (22nd day after the end of treatment), the square of alopecia in control group was 1220 ± 40 mm(2) in comparison with 870 ± 17 mm(2) in experimental group (p < 0.01). The antistaphylococcal in vivo activity of PMP demonstrated in present study makes these molecules potentially useful for treatment of SSSS.

  14. A 4D treatment planning tool for the evaluation of motion effects on lung cancer treatments

    Energy Technology Data Exchange (ETDEWEB)

    Ding, M; Newman, F; Kavanagh, B; Stuhr, K; Raben, D [Radiation Oncology Department, University of Colorado at Denver and Health Science Center, Aurora, CO 80010 (United States); Li, J S; Ma, C-M [Radiation Oncology Department, Fox Chase Cancer Center, Philadelphia, PA 19111 (United States); Gaspar, L, E-mail: meisong.ding@uchsc.edu

    2008-02-01

    In this study, a 4D treatment planning tool using an analytical model accounting for breathing motion is investigated to evaluate the motion effect on delivered dose for lung cancer treatments with three-dimensional conformal radiotherapy (3DCRT). The Monte Carlo EGS4/MCDOSE user code is used in the treatment planning dose calculation, and the patient CT data are converted into respective patient geometry files for Monte Carlo dose calculation. The model interpolates CT images at different phases of the breathing cycle from patient CT scans taken at end inspiration and end expiration phases and the chest wall position. Correlation between the voxels in a reference CT dataset and the voxels in the interpolated CT datasets at any breathing phases is established so that the dose to a voxel can be accumulated through the entire breathing cycle. Simulated lung tumors at different locations are used to demonstrate our model in 3DCRT for lung cancer treatments. We demonstrated the use of a 4D treatment planning tool in evaluating the breathing motion effect on delivered dose for different planning margins. Further studies are being conducted to use this tool to study the lung motion effect through large-scale analysis and to implement this useful tool for treatment planning dose calculation and plan evaluation for 4D radiotherapy.

  15. Pharmacological Treatment Effects on Eye Movement Control

    Science.gov (United States)

    Reilly, James L.; Lencer, Rebekka; Bishop, Jeffrey R.; Keedy, Sarah; Sweeney, John A.

    2008-01-01

    The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to…

  16. Neuroprotective Effect of Non-viral Gene Therapy Treatment Based on Tetanus Toxin C-fragment in a Severe Mouse Model of Spinal Muscular Atrophy

    Science.gov (United States)

    Oliván, Sara; Calvo, Ana C.; Rando, Amaya; Herrando-Grabulosa, Mireia; Manzano, Raquel; Zaragoza, Pilar; Tizzano, Eduardo F.; Aquilera, Jose; Osta, Rosario

    2016-01-01

    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. PMID:27605908

  17. Neuroprotective Effect of Non-viral Gene Therapy Treatment Based on Tetanus Toxin C-fragment in a Severe Mouse Model of Spinal Muscular Atrophy.

    Science.gov (United States)

    Oliván, Sara; Calvo, Ana C; Rando, Amaya; Herrando-Grabulosa, Mireia; Manzano, Raquel; Zaragoza, Pilar; Tizzano, Eduardo F; Aquilera, Jose; Osta, Rosario

    2016-01-01

    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. 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.

  19. 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...... lymph node is also reduced following a single dose of anti-C5aR, suggesting that modulation of the C5a/C5aR axis results in effects on the T cell compartment in inflammatory arthritis. In summary, these data demonstrate that blockade of C5aR leads to rapid and significant effects on arthritic disease......-type hypersensitivity arthritis (DTHA) model to study the very early effects of a blocking, non-depleting anti-C5aR mAb on joint inflammation with treatment synchronised with disease onset, an approach not previously described. The DTHA model is a single-paw inflammatory arthritis model characterised by synchronised...

  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. Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model

    National Research Council Canada - National Science Library

    Littleton, Robert M; Miller, Matthew; Hove, Jay R

    2012-01-01

    .... Here we develop the larval zebrafish (4-30 days post fertilization) as a vertebrate model of dietary plant-based treatment of hypercholesterolemia and test the effects of Crataegus laevigata in this model...

  2. Adjunctive treatment of brexpiprazole with fluoxetine shows a rapid antidepressant effect in social defeat stress model: Role of BDNF-TrkB signaling

    Science.gov (United States)

    Ma, Min; Ren, Qian; Yang, Chun; Zhang, Ji-chun; Yao, Wei; Dong, Chao; Ohgi, Yuta; Futamura, Takashi; Hashimoto, Kenji

    2016-01-01

    Addition of low doses of the atypical antipsychotic drug brexpiprazole with selective serotonin reuptake inhibitors (SSRIs) could promote antidepressant effect in patients with major depressive disorder although the precise mechanisms underlying the action of the combination are unknown. Combination of low dose of brexpiprazole (0.1 mg/kg) and SSRI fluoxetine (10 mg/kg) could promote a rapid antidepressant effect in social defeat stress model although brexpiprazole or fluoxetine alone did not show antidepressant effect. Furthermore, the combination significantly improved alterations in the brain-derived neurotrophic factor (BDNF) - TrkB signaling and dendritic spine density in the prefrontal cortex, hippocampus, and nucleus accumbens in the susceptible mice after social defeat stress. Interestingly, TrkB antagonist ANA-12 significantly blocked beneficial effects of combination of brexpiprazole and fluoxetine on depression-like phenotype. These results suggest that BDNF-TrkB signaling plays a role in the rapid antidepressant action of the combination of brexpiprazole and fluoxetine. PMID:27991542

  3. [Intensified insulin treatment is cost-effective].

    Science.gov (United States)

    Reichard, P; Alm, C; Andersson, E; Wärn, I; Rosenqvist, U

    1999-01-20

    Both the Diabetes Control and Complications Trial (DCCT) in USA/Canada, and Stockholm Diabetes Intervention Study (SDIS) showed intensified insulin treatment and reduced glycaemia to prevent complications in patients with insulin-dependent (type I) diabetes mellitus. In the DCCT, the intensified treatment was considered cost-effective. In the SDIS, investigation of the direct increase in costs due to the intensified insulin treatment showed the saving in direct costs due to the reduction in photocoagulation requirements, and in the prevalence of renal insufficiency and of amputation, to correspond to 10 years' intensive insulin treatment. Thus, as intensified insulin treatment in type I diabetes reduces direct suffering at a low cost, it may be regarded as 'evidence-based' and mandatory.

  4. Effect of Linezolid on the 50% Lethal Dose and 50% Protective Dose in Treatment of Infections by Gram-Negative Pathogens in Naive and Immunosuppressed Mice and on the Efficacy of Ciprofloxacin in an Acute Murine Model of Septicemia

    Science.gov (United States)

    Marra, Andrea; Lamb, Lucinda; Medina, Ivette; George, David; Gibson, Glenn; Hardink, Joel; Rugg, Jady; Van Deusen, Jeffrey

    2012-01-01

    Murine models of infection were used to study the effect of linezolid on the virulence of Gram-negative bacteria and to assess potential pharmacodynamic interactions with ciprofloxacin in the treatment of these infections, prompted by observations from a recent clinical trial. Naive and immunosuppressed mice were challenged with Klebsiella pneumoniae 53A1109, K. pneumoniae GC6658, and Pseudomonas aeruginosa UC12120 in acute sepsis and pulmonary infection models, using different serial dilutions of these pathogens (groups of 8 animals each). Linezolid (100 mg/kg/dose) was administered orally at 0.5 and 4.0 h postchallenge in the sepsis model and at 4 h postchallenge followed by 2 days of twice-daily treatment in the pulmonary model. Further, ciprofloxacin alone and in combination with oral linezolid was investigated in the sepsis model. Survival was assessed for 4 and 10 days postchallenge in the systemic and respiratory models, respectively. The data were fitted to a nonlinear regression analysis to determine 50% lethal doses (LD50s) and 50% protective doses (PD50s). A clinically relevant, high-dose regimen of linezolid had no significant effect on LD50 in these models. This lack of effect was independent of immune status. A combination of oral ciprofloxacin with linezolid yielded lower PD50s than oral ciprofloxacin alone (ciprofloxacin in combination, 8.4 to 32.7 mg/kg; oral ciprofloxacin, 39.4 to 88.3 mg/kg). Linezolid did not improve the efficacy of subcutaneous ciprofloxacin (ciprofloxacin in combination, 2.0 to 2.4 mg/kg; subcutaneous ciprofloxacin, 2.0 to 2.8 mg/kg). In conclusion, linezolid does not seem to potentiate infections caused by Gram-negative pathogens or to interact antagonistically with ciprofloxacin. PMID:22710118

  5. Modelling the effect of sub(lethal) heat treatment of Bacillus subtilis spores on germination rate and outgrowth to exponentially growing vegetative cells

    NARCIS (Netherlands)

    Smelt, J.P.P.M.; Bos, A.P.; Kort, R.; Brul, S.

    2008-01-01

    Spores of Bacillus subtilis were subjected to relatively mild heat treatments in distilled water and properties of these spores were studied. These spores had lost all or part of their dipicolinic acid (DPA) depending on the severity of the heat treatment. Even after relatively mild heat treatments

  6. Metabolic effects of discontinuing growth hormone treatment

    OpenAIRE

    Cowan, F; Evans, W.; Gregory, J

    1999-01-01

    AIMS—To evaluate the effects of discontinuing growth hormone (GH) treatment on energy expenditure and body composition, which might help predict those most likely to benefit from early reintroduction of GH treatment in young adult life.
METHODS—Body composition was calculated from skinfold thicknesses and dual energy x ray absorptometry (DXA). Resting metabolic rate (RMR) and whole body bone mineral content (BMC) were also measured. Measurements were made before stoppi...

  7. The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (review of Technology Appraisal No. 111): a systematic review and economic model.

    Science.gov (United States)

    Bond, M; Rogers, G; Peters, J; Anderson, R; Hoyle, M; Miners, A; Moxham, T; Davis, S; Thokala, P; Wailoo, A; Jeffreys, M; Hyde, C

    2012-01-01

    Alzheimer’s disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK. Review and update guidance to the NHS in England and Wales on the clinical effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine [acetylcholinesterase inhibitors (AChEIs)] and memantine within their licensed indications for the treatment of AD, which was issued in November 2006 (amended September 2007 and August 2009). Electronic databases were searched for systematic reviews and/or metaanalyses, randomised controlled trials (RCTs) and ongoing research in November 2009 and updated in March 2010; this updated search revealed no new includable studies. The databases searched included The Cochrane Library (2009 Issue 4, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, EconLit, ISI Web of Science Databases--Science Citation Index, Conference Proceedings Citation Index, and BIOSIS; the Centre for Reviews and Dissemination (CRD) databases--NHS Economic Evaluation Database, Health Technology Assessment, and Database of Abstracts of Reviews of Effects. The clinical effectiveness systematic review was undertaken following the principles published by the NHS CRD. We included RCTs whose population was people with AD. The intervention and comparators depended on disease severity, measured by the Mini Mental State Examination (MMSE). mild AD (MMSE 21-26)--donepezil, galantamine and rivastigmine; moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine and memantine; severe AD (MMSE costs and cost-effectiveness. Where appropriate, data were pooled using pair-wise meta-analysis, multiple outcome measures, metaregression and mixedtreatment comparisons. The decision model was based broadly on the structure of the three-state Markov model described in the previous technology

  8. 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.

  9. 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.

  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. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

  12. Musical hallucinations: review of treatment effects.

    Science.gov (United States)

    Coebergh, Jan A F; Lauw, R F; Bots, R; Sommer, I E C; Blom, J D

    2015-01-01

    Despite an increased scientific interest in musical hallucinations over the past 25 years, treatment protocols are still lacking. This may well be due to the fact that musical hallucinations have multiple causes, and that published cases are relatively rare. To review the effects of published treatment methods for musical hallucinations. A literature search yielded 175 articles discussing a total number of 516 cases, of which 147 articles discussed treatment in 276 individuals. We analyzed the treatment results in relation to the etiological factor considered responsible for the mediation of the musical hallucinations, i.e., idiopathic/hypoacusis, psychiatric disorder, brain lesion, and other pathology, epilepsy or intoxication/pharmacology. Musical hallucinations can disappear without intervention. When hallucinations are bearable, patients can be reassured without any other treatment. However, in other patients musical hallucinations are so disturbing that treatment is indicated. Distinct etiological groups appear to respond differently to treatment. In the hypoacusis group, treating the hearing impairment can yield significant improvement and coping strategies (e.g., more acoustic stimulation) are frequently helpful. Pharmacological treatment methods can also be successful, with antidepressants being possibly more helpful than antiepileptics (which are still better than antipsychotics). The limited use of acetylcholinesterase inhibitors has looked promising. Musical hallucinations occurring as part of a psychiatric disorder tend to respond well to psychopharmacological treatments targeting the underlying disorder. Musical hallucinations experienced in the context of brain injuries and epilepsy tend to respond well to antiepileptics, but their natural course is often benign, irrespective of any pharmacological treatment. When intoxication/pharmacology is the main etiological factor, it is important to stop or switch the causative substance or medication

  13. Etiology and treatment of hematological neoplasms: stochastic mathematical models.

    Science.gov (United States)

    Radivoyevitch, Tomas; Li, Huamin; Sachs, Rainer K

    2014-01-01

    Leukemias are driven by stemlike cancer cells (SLCC), whose initiation, growth, response to treatment, and posttreatment behavior are often "stochastic", i.e., differ substantially even among very similar patients for reasons not observable with present techniques. We review the probabilistic mathematical methods used to analyze stochastics and give two specific examples. The first example concerns a treatment protocol, e.g., for acute myeloid leukemia (AML), where intermittent cytotoxic drug dosing (e.g., once each weekday) is used with intent to cure. We argue mathematically that, if independent SLCC are growing stochastically during prolonged treatment, then, other things being equal, front-loading doses are more effective for tumor eradication than back loading. We also argue that the interacting SLCC dynamics during treatment is often best modeled by considering SLCC in microenvironmental niches, with SLCC-SLCC interactions occurring only among SLCC within the same niche, and we present a stochastic dynamics formalism, involving "Poissonization," applicable in such situations. Interactions at a distance due to partial control of total cell numbers are also considered. The second half of this chapter concerns chromosomal aberrations, lesions known to cause some leukemias. A specific example is the induction of a Philadelphia chromosome by ionizing radiation, subsequent development of chronic myeloid leukemia (CML), CML treatment, and treatment outcome. This time evolution involves a coordinated sequence of > 10 steps, each stochastic in its own way, at the subatomic, molecular, macromolecular, cellular, tissue, and population scales, with corresponding time scales ranging from picoseconds to decades. We discuss models of these steps and progress in integrating models across scales.

  14. Adsorption of HSA, IgG and laminin-1 on model titania surfaces--effects of glow discharge treatment on competitively adsorbed film composition.

    Science.gov (United States)

    Santos, Olga; Svendsen, Ida E; Lindh, Liselott; Arnebrant, Thomas

    2011-10-01

    This study investigated the effect of glow discharge treatment of titania surfaces on plasma protein adsorption, by means of ellipsometry and mechanically assisted SDS elution. The adsorption and film elution of three plasma proteins, viz. human serum albumin (HSA), human immunoglobulin G (IgG) and laminin-1, as well as competitive adsorption from a mixture of the three proteins, showed that the adsorbed amount of the individual proteins after 1 h increased in the order HSA

  15. Musical hallucinations: review of treatment effects

    Directory of Open Access Journals (Sweden)

    Jan eCoebergh

    2015-06-01

    Full Text Available AbstractBackground: Despite an increased scientific interest in musical hallucinations throughout the past 25 years, treatment protocols are still lacking. This may well be due to the fact that musical hallucinations have multiple causes, and that published cases are relatively rare.Objective: To review the effects of published treatment methods for musical hallucinations.Methods: A literature search yielded 175 articles discussing a total number of 516 cases, of which 147 articles discussed treatment in 276 individuals. We analysed the treatment results in relation to the aetiological factor considered responsible for the mediation of the musical hallucinations, i.e., idiopathic/hypoacusis, psychiatric disorder, brain lesion and other pathology, epilepsy or intoxication.Results: Musical hallucinations can disappear without intervention. When hallucinations are bearable, patients can be reassured without any other treatment. However, in other patients musical hallucinations are so disturbing that treatment is indicated. Distinct aetiological groups appear to respond differently to treatment. In the hypoacusis group, treating the hearing impairment can yield significant improvement and coping strategies (e.g. more acoustic stimulation are frequently helpful. Pharmacological treatment methods can also be successful, with antidepressants being more helpful than antiepileptics (which are still better than antipsychotics. The limited use of acetylcholinesterase inhibitors has looked promising. Musical hallucinations occurring as part of a psychiatric disorder tend to respond well to psychopharmacological treatments targeting the underlying disorder. Musical hallucinations experienced in the context of brain injuries and epilepsy tend to respond well to antiepileptics, but their natural course is often benign, irrespective of any pharmacological treatment. When intoxication is the main aetiological factor, it is important to stop or switch the

  16. Dissimilar effect of perming and bleaching treatments on cuticles: advanced hair damage model based on elution and oxidation of S100A3 protein

    National Research Council Canada - National Science Library

    Kizawa, Kenji; Inoue, Takafumi; Yamaguchi, Masahito; Kleinert, Peter; Troxler, Heinz; Heizmann, Claus W; Iwamoto, Yoshimichi

    2005-01-01

    .... Both perming and bleaching treatments are prone to easily delaminate cuticles. Confocal microscopy revealed that the cuticles of permed hair were delaminated with larger pieces than untreated ones...

  17. Effectiveness of Psychological and Pharmacological Treatments for Nocturnal Enuresis.

    Science.gov (United States)

    Houts, Arthur C.; And Others

    1994-01-01

    Assesses overall effectiveness of psychological and pharmacological treatments, relative effectiveness of specific treatments, and moderators of treatment effectiveness for nocturnal enuretic children via quantitative integration of research. Findings confirm that more children benefit from psychological than from pharmacological interventions and…

  18. Neuronopathic Gaucher disease: dysregulated mRNAs and miRNAs in brain pathogenesis and effects of pharmacologic chaperone treatment in a mouse model.

    Science.gov (United States)

    Dasgupta, Nupur; Xu, You-Hai; Li, Ronghua; Peng, Yanyan; Pandey, Manoj K; Tinch, Stuart L; Liou, Benjamin; Inskeep, Venette; Zhang, Wujuan; Setchell, Kenneth D R; Keddache, Mehdi; Grabowski, Gregory A; Sun, Ying

    2015-12-15

    Defective lysosomal acid β-glucosidase (GCase) in Gaucher disease causes accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) that distress cellular functions. To study novel pathological mechanisms in neuronopathic Gaucher disease (nGD), a mouse model (4L;C*), an analogue to subacute human nGD, was investigated for global profiles of differentially expressed brain mRNAs (DEGs) and miRNAs (DEmiRs). 4L;C* mice displayed accumulation of GC and GS, activated microglial cells, reduced number of neurons and aberrant mitochondrial function in the brain followed by deterioration in motor function. DEGs and DEmiRs were characterized from sequencing of mRNA and miRNA from cerebral cortex, brain stem, midbrain and cerebellum of 4L;C* mice. Gene ontology enrichment and pathway analysis showed preferential mitochondrial dysfunction in midbrain and uniform inflammatory response and identified novel pathways, axonal guidance signaling, synaptic transmission, eIF2 and mammalian target of rapamycin (mTOR) signaling potentially involved in nGD. Similar analyses were performed with mice treated with isofagomine (IFG), a pharmacologic chaperone for GCase. IFG treatment did not alter the GS and GC accumulation significantly but attenuated the progression of the disease and altered numerous DEmiRs and target DEGs to their respective normal levels in inflammation, mitochondrial function and axonal guidance pathways, suggesting its regulation on miRNA and the associated mRNA that underlie the neurodegeneration in nGD. These analyses demonstrate that the neurodegenerative phenotype in 4L;C* mice was associated with dysregulation of brain mRNAs and miRNAs in axonal guidance, synaptic plasticity, mitochondria function, eIF2 and mTOR signaling and inflammation and provides new insights for the nGD pathological mechanism.

  19. Lack of behavioral and cognitive effects of chronic ethosuximide and gabapentin treatment in the Ts65Dn mouse model of Down syndrome.

    Science.gov (United States)

    Vidal, V; García, S; Martínez, P; Corrales, A; Flórez, J; Rueda, N; Sharma, A; Martínez-Cué, C

    2012-09-18

    The Ts65Dn (TS) mouse model of Down syndrome (DS) displays a number of behavioral, neuromorphological and neurochemical phenotypes of the syndrome. Altered GABAergic transmission appears to contribute to the mechanisms responsible for the cognitive impairments in TS mice. Increased functional expression of the trisomic gene encoding an inwardly rectifying potassium channel, subfamily J, member 6 (KCNJ6) has been reported in DS and TS mice, along with the consequent impairment in GAB Aergic function. Partial display of DS phenotypes in mice harboring a single trisomy of Kcnj6 provides compelling evidence for a functional role of increased channel expression in some of the abnormal neurological phenotypes found in DS. Notably, the antiepileptic drug (AED) ethosuximide (ETH), but not other AEDs such as gabapentin (GAB), is known to inhibit KCNJ6 channels in mice. Here, we report the effect of chronic ETH and GAB on the behavioral and cognitive phenotypes of TS and disomic control (CO) mice. Neither drug significantly affected sensorimotor abilities, motor coordination or spontaneous activity in TS and CO mice. Also, ETH and GAB did not induce anxiety in the open field or plus maze tests, did not alter performance in the Morris water maze, and did not affect cued - or context - fear conditioning. Our results thus suggest that KCNJ6 may not be a promising drug target candidate in DS. As a corollary, they also show that long-term use of ETH and GAB is devoid of adverse behavioral and cognitive effects.

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

    Science.gov (United States)

    2011-03-24

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

  1. 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)

    Gonzalez, Sara Josefina; Pozzi, Emiliano C C; Monti Hughes, Andrea; Provenzano, Lucas; Koivunoro, Hanna; Carando, Daniel Germán; Thorp, Silvia Inés; Casal, Mariana Rosalía; Bortolussi, Silva; Trivillin, Verónica A; Garabalino, Marcela A; Curotto, Paula; Heber, Elisa M; Santa Cruz, Gustavo A; Kankaanranta, Leena; Joensuu, Heikki; Schwint, Amanda E

    2017-08-31

    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 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 model are

  2. Applicability of [(11)C]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.

  3. 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…

  4. 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.

  5. A model of isoniazid treatment of tuberculosis.

    Science.gov (United States)

    Lemmer, Yolandy; Grobler, Anne; Moody, Clint; Viljoen, Hendrik

    2014-12-21

    A mathematical model is presented of the growth and death of bacilli in a granuloma. The granuloma is treated with isoniazid (INH), a drug that inhibits the synthesis of mycolic acids (MA). Since MA is an essential component of cell walls, the organisms fail to reach maturity if deficient in MA. Cell wall turnover is a well-known feature of bacteria, at the exterior surface material sloughs off to foil attacks by hosts or other organisms, simultaneously synthesizing products for new cell wall assembly. Thus cell wall thickness is maintained in a dynamic equilibrium (Doyle et al., 1988). Presumably cell death is a result of loss in cell wall due to autolysis in combination with stinted replenishing. The mathematical model presented here uses differential equations to predict the effects of intracellular INH on cell wall thickness and cell viability. This analysis purposely distinguishes intracellular INH concentration from the concentration in the plasma. The concentration in the plasma depends only on the dosing. The intracellular INH concentration, however, depends on diffusion through the cell walls of the bacteria. This paper addresses the complex interactions between intracellular INH, cell wall thickness, and the rate of cell wall synthesis.

  6. Side effects of endobronchial laser treatment

    Energy Technology Data Exchange (ETDEWEB)

    Dierkesmann, R.; Huzly, A.

    1985-03-01

    Side effects that have occurred in over 250 endobronchial laser treatments are reported. The laser has been used in severe tracheal and in bronchial obstructions. In two cases significant bleeding had to be treated with tamponade. In one patient an emphysema of the mediastinum developed, in 2 further patients a small pneumothorax. Perforation of the airway was not detected and no special treatment was necessary. Three patients with life-threatening tracheal stenoses and one patient with severe stenosis of both the mainstem bronchi due to metastasis in the bifurcation lymph node had a large defect in the tracheal or bronchial wall with a deep necrosis five to twelve weeks after laser treatment; all these patients had extensive radiotherapy in addition. One patient died due to severe respiratory insufficiency, probably caused by smoke intoxication. After the laser treatment, rubber-like fibrin-rich plaques may develop, which can lead to life-threatening obstructions of the airway. It is recommended that laser bronchoscopy should be performed with the rigid bronchoscope. After treatment of tracheal lesion an endoscopic check must be performed within 24 hours. The combination of laser treatment and radiotherapy seems to involve a certain risk of large defects in the bronchial wall due to necrosis of the tumor.

  7. Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD).

    Science.gov (United States)

    dela Peña, Ike; Kim, Hee Jin; Sohn, Aeree; Kim, Bung-Nyun; Han, Doug Hyun; Ryu, Jong Hoon; Shin, Chan Young; Noh, Minsoo; Cheong, Jae Hoon

    2014-05-06

    Methylphenidate is the most commonly used stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). Research has found that methylphenidate is a "reinforcer" and that individuals with ADHD also abuse this medication. Nevertheless, the molecular consequences of long-term recreational methylphenidate use or abuse in individuals with ADHD are not yet fully known. Spontaneously hypertensive rats (SHR), the most validated and widely used ADHD animal model, were pretreated with methylphenidate (5 mg/kg, i.p.) during their adolescence (post-natal day [PND] 42-48) and tested for subsequent methylphenidate-induced conditioned place preference (CPP) and self-administration. Thereafter, the differentially expressed genes in the prefrontal cortex (PFC) and striatum of representative methylphenidate-treated SHRs, which showed CPP to and self-administration of methylphenidate, were analyzed. Genome-wide transcriptome profiling analyses revealed 30 differentially expressed genes in the PFC, which include transcripts involved in apoptosis (e.g. S100a9, Angptl4, Nfkbia), transcription (Cebpb, Per3), and neuronal plasticity (Homer1, Jam2, Asap1). In contrast, 306 genes were differentially expressed in the striatum and among them, 252 were downregulated. The main functional categories overrepresented among the downregulated genes include those involved in cell adhesion (e.g. Pcdh10, Ctbbd1, Itgb6), positive regulation of apoptosis (Perp, Taf1, Api5), (Notch3, Nsbp1, Sik1), mitochondrion organization (Prps18c, Letm1, Uqcrc2), and ubiquitin-mediated proteolysis (Nedd4, Usp27x, Ube2d2). Together, these changes indicate methylphenidate-induced neurotoxicity, altered synaptic and neuronal plasticity, energy metabolism and ubiquitin-dependent protein degradation in the brains of methylphenidate-treated SHRs, which showed methylphenidate CPP and self-administration. In addition, these findings may also reflect cognitive impairment associated with chronic

  8. Global dynamics of a colorectal cancer treatment model with cancer stem cells.

    Science.gov (United States)

    Abernathy, Kristen; Abernathy, Zachary; Brown, Kelsey; Burgess, Claire; Hoehne, Rebecca

    2017-02-01

    We present and analyze a mathematical model of the treatment of colorectal cancer using a system of nonlinear ordinary differential equations. The model describes the effectiveness of immunotherapy and chemotherapy for treatment of tumor cells and cancer stem cells (CSCs). The effects of CD8(+)T cells, natural killer cells, and interleukin proteins on tumor cells and CSCs under the influence of treatment are also illustrated. Using the method of localization of compact invariant sets, we present conditions on treatment parameters to guarantee a globally attracting tumor clearance state. Numerical simulations using estimated parameters from the literature are included to showcase various global dynamics of the model.

  9. Hydraulic modelling of drinking water treatment plant operations

    OpenAIRE

    L. C. Rietveld; Borger, K.J.; Van Schagen, K.M.; Mesman, G.A.M.; G. I. M. Worm

    2008-01-01

    For a drinking water treatment plant simulation, water quality models, a hydraulic model, a process-control model, an object model, data management, training and decision-support features and a graphic user interface have been integrated. The integration of a hydraulic model in the simulator is necessary to correctly determine the division of flows over the plant's lanes and, thus, the flow through the individual treatment units, based on valve positions and pump speeds. The flow through a un...

  10. 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 chron

  11. 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

  12. 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

    Science.gov (United States)

    Ramos, Eliézer L. P.; Santana, Silas S.; Silva, Murilo V.; Santiago, Fernanda M.; Mineo, Tiago W. P.; Mineo, José R.

    2016-01-01

    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. PMID:27933277

  13. Frozen shoulder - an effective method of treatment.

    Science.gov (United States)

    Warmington, L E

    1970-09-01

    Although there has been a considerable amount of material published on the pathology and the probable aetiology of the frozen shoulder, the same cannot be said of suggestions for an effective method of physical treatment for all stages of the condition. Some authors claim that exercises mar the recovery process (Cyriax, 1957). Others have found that the condition runs a self-limiting course of anything up to three years, and any physical treatment is "notoriously unsuccessful" in altering this pattern (Crisp and Hume Kendall, 1955). However, all agree that the recovery of frozen shoulders, treated or untreated, is prolonged, and in the acute phase of the condition, physiotherapy plays no part in the treatment of pain (Cyriax, Ibid., Crisp and Hume Kendall, Ibid., Stening, 1961).

  14. 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

  15. Effectiveness of antiretroviral treatment in Colombia.

    Science.gov (United States)

    Machado-Alba, Jorge Enrique; Vidal, Xavier

    2012-11-01

    To evaluate the effectiveness of antiretroviral therapies and factors associated with HIV/AIDS control in a population of patients treated by the Colombian Social Security Health System (SGSSS). This was a descriptive study of 510 HIV/AIDS patients treated with antiretroviral therapies in 19 cities in Colombia from June 1992-April 2011. Factors assessed from each patient's clinical history were: viral load, CD4 count, antiretroviral treatment regimens, prescribed daily doses of medications, length of disease evolution, duration of therapy, history of opportunistic diseases, and drug costs. Patients were predominantly male (75.1% males versus 24.9% women), with a mean age of 41.0 ± 11.4 years and an average length of disease progression of 72 months. All recommended treatment regimens were prescribed at the defined daily dose. Treatment was effective in 65.3% of patients (viral load Barranquilla were associated with an increased risk of uncontrolled HIV infection. The mean annual cost of drugs per patient was US$ 2,736. Factors associated with uncontrolled HIV infection, especially regarding treatment adherence, must be identified to promote solutions for health care programs treating patients with HIV/AIDS.

  16. 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.

  17. 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...

  18. 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...

  19. 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...

  20. Tool Steel Heat Treatment Optimization Using Neural Network Modeling

    Science.gov (United States)

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

    2016-11-01

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

  1. Modeling and Simulating Environmental Effects

    OpenAIRE

    Guest, Peter S.; Murphree, Tom; Frederickson, Paul A.; Guest, Arlene A.

    2012-01-01

    MOVES Research & Education Systems Seminar: Presentation; Session 4: Collaborative NWDC/NPS M&S Research; Moderator: Curtis Blais; Modeling and Simulating Environmental Effects; speakers: Peter Guest, Paul Frederickson & Tom Murphree Environmental Effects Group

  2. 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.

  3. Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD)

    OpenAIRE

    dela Peña, Ike; Kim, Hee Jin; Sohn, Aeree; Kim, Bung-Nyun; Han, Doug Hyun; Ryu, Jong Hoon; Shin, Chan Young; Noh, Minsoo; Cheong, Jae Hoon

    2014-01-01

    Background Methylphenidate is the most commonly used stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). Research has found that methylphenidate is a “reinforcer” and that individuals with ADHD also abuse this medication. Nevertheless, the molecular consequences of long-term recreational methylphenidate use or abuse in individuals with ADHD are not yet fully known. Methods Spontaneously hypertensive rats (SHR), the most validated and widely used ADHD animal mo...

  4. 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

    . 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...... by 'meta-epidemiological' re-analysis of data collected as part of systematic reviews. As inadequate quality components often co-occur, we maintain that the suspected biases must be evaluated simultaneously. Furthermore, the biases cannot safely be assumed to be homogeneous across systematic reviews...... the design of the trials as such to give estimates; a weighted regression model incorporates between-trial variation and thus gives wider confidence intervals, but is computationally lighter and can be used with trials of more general design. In both models, heterogeneity in the bias coefficients can...

  5. 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.)

  6. Investigating the long-term effect of subchronic phencyclidine-treatment on novel object recognition and the association between the gut microbiota and behavior in the animal model of schizophrenia.

    Science.gov (United States)

    Pyndt Jørgensen, B; Krych, L; Pedersen, T B; Plath, N; Redrobe, J P; Hansen, A K; Nielsen, D S; Pedersen, C S; Larsen, C; Sørensen, D B

    2015-03-15

    Subchronic phencyclidine (subPCP) treatment induces schizophrenic-like behavior in rodents, including cognitive deficits and increased locomotor sensitivity towards acute administration of PCP. Evidence is accumulating that the gut microbiota (GM) influences behavior through modulation of the microbiota-gut-brain axis, and hence, part of the variation within this animal model may derive from variation in the GM. The aims of this study was to investigate first, the duration of subPCP-induced cognitive impairment in the novel object recognition test, and second, the possible effect of subchronic PCP-treatment on the GM, and the association between the GM and the behavioral parameters. The association was further investigated by antibiotic reduction of the GM. Male Lister Hooded rats were dosed twice daily i.p. with either 5mg/kg PCP or sterile isotonic saline for seven days followed by a seven-day washout period. Rats were tested in the novel object recognition and the locomotor activity assays immediately after, three weeks after, or six weeks after washout, and the fecal GM was analyzed by high throughput sequencing. Antibiotic- and control-treated rats were tested in the same manner following washout. In conclusion, subPCP-treatment impaired novel object recognition up to three weeks after washout, whereas locomotor sensitivity was increased for at least six weeks after washout. Differences in the core gut microbiome immediately after washout suggested subPCP treatment to alter the GM. GM profiles correlated to memory performance. Administration of ampicillin abolished the subPCP-induced memory deficit. It thus seems reasonable to speculate that the GM influences memory performance, contributing to variation within the model.

  7. 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.

  8. Model application for acid mine drainage treatment processes

    Directory of Open Access Journals (Sweden)

    Nantaporn Noosai, Vineeth Vijayan, Khokiat Kengskool

    2014-01-01

    Full Text Available This paper presents the utilization of the geochemical model, PHREEQC, to investigate the chemical treatment system for Acid Mine Drainage (AMD prior to the discharge. The selected treatment system consists of treatment processes commonly used for AMD including settling pond, vertical flow pond (VFP and caustic soda pond were considered in this study. The use of geochemical model for the treatment process analysis enhances the understanding of the changes in AMD’s chemistry (precipitation, reduction of metals, etc. in each process, thus, the chemical requirements (i.e., CaCO3 and NaOH for the system and the system’s treatment efficiency can be determined. The selected treatment system showed that the final effluent meet the discharge standard. The utilization of geochemical model to investigate AMD treatment processes can assist in the process design.

  9. A practitioner's perspective on the uses and future developments for wastewater treatment modelling.

    Science.gov (United States)

    Daigger, G T

    2011-01-01

    The modern age of wastewater treatment modelling began with publication of the International Water Association (IWA) Activated Sludge Model (ASM) No.1 and has advanced significantly since. Models are schematic representations of systems that are useful for analysis to support decision-making. The most appropriate model for a particular application often incorporates only those components essential for the particular analyses to be performed (i.e. the simplest model possible). Characteristics of effective models are presented, along with how wastewater modelling is integrated into the wastewater project life cycle. The desirable characteristics of wastewater treatment modelling platforms are then reviewed. Current developments of note in wastewater treatment modelling practice include estimates of greenhouse gas emissions, incorporating uncertainty into wastewater modelling and design practice, more fundamental modelling of process chemistry, and improved understanding of the degradability of wastewater constituents in different environments. Areas requiring greater emphasis include increased use of metabolic modelling, characterisation of the hydrodynamics of suspended and biofilm biological treatment processes, and the integration of biofilm and suspended growth process modelling. Wastewater treatment models must also interface with water and wastewater management software packages. While wastewater treatment modelling will continue to advance and make important contributions to practice, it must be remembered that these are complex systems which exhibit counter-intuitive behaviour (results differ from initial expectations) and multiple dynamic steady-states which can abruptly transition from one to another.

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

    NARCIS (Netherlands)

    van der Helm, A.W.C.

    2007-01-01

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

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

    NARCIS (Netherlands)

    van der Helm, A.W.C.

    2007-01-01

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

  12. 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.

  13. Modelling and control of laser surface treatment

    NARCIS (Netherlands)

    Römer, Gerardus Richardus Benardus Engelina

    1999-01-01

    The results of laser surface treatment may vary significantly during laser surface processing. These variations arise from the sensitivity of the process to disturbances, such as varying absorptivity and the small dimensions of the work piece. To increase the reproducibility of the process, a real-t

  14. Modelling and control of laser surface treatment

    NARCIS (Netherlands)

    Römer, Gerardus Richardus, Bernardus, Engelina

    1999-01-01

    The results of laser surface treatment may vary significantly during laser surface processing. These variations arise from the sensitivity of the process to disturbances, such as varying absorptivity and the small dimensions of the work piece. To increase the reproducibility of the process, a

  15. Treatments of Precipitation Inputs to Hydrologic Models

    Science.gov (United States)

    Hydrological models are used to assess many water resources problems from agricultural use and water quality to engineering issues. The success of these models are dependent on correct parameterization; the most sensitive being the rainfall input time series. These records can come from land-based ...

  16. Modelling of environmental impacts from biological treatment of organic municipal waste in EASEWASTE.

    Science.gov (United States)

    Boldrin, Alessio; Neidel, Trine Lund; Damgaard, Anders; Bhander, Gurbakhash S; Møller, Jacob; Christensen, Thomas H

    2011-04-01

    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, anaerobic digestion and combinations hereof are available in the model, but the user can change all key parameters in the biological treatment module so that specific local plants and processes can be modelled. EASEWASTE is one of the newest waste LCA models and the biological treatment module was built partly on features of earlier waste-LCA models, but offers additional facilities, more flexibility, transparency and user-friendliness. The paper presents the main features of the module and provides some examples illustrating the capability of the model in environmentally assessing and discriminating the environmental performance of alternative biological treatment technologies in relation to their mass flows, energy consumption, gaseous emissions, biogas recovery and compost/digestate utilization.

  17. FASN Inhibition and Taxane Treatment Combine to Enhance Anti-tumor Efficacy in Diverse Xenograft Tumor Models through Disruption of Tubulin Palmitoylation and Microtubule Organization and FASN Inhibition-Mediated Effects on Oncogenic Signaling and Gene Expression.

    Science.gov (United States)

    Heuer, Timothy S; Ventura, Richard; Mordec, Kasia; Lai, Julie; Fridlib, Marina; Buckley, Douglas; Kemble, George

    2017-02-01

    Palmitate, the enzymatic product of FASN, and palmitate-derived lipids support cell metabolism, membrane architecture, protein localization, and intracellular signaling. Tubulins are among many proteins that are modified post-translationally by acylation with palmitate. We show that FASN inhibition with TVB-3166 or TVB-3664 significantly reduces tubulin palmitoylation and mRNA expression. Disrupted microtubule organization in tumor cells is an additional consequence of FASN inhibition. FASN inhibition combined with taxane treatment enhances inhibition of in vitro tumor cell growth compared to treatment with either agent alone. In lung, ovarian, prostate, and pancreatic tumor xenograft studies, FASN inhibition and paclitaxel or docetaxel combine to inhibit xenograft tumor growth with significantly enhanced anti-tumor activity. Tumor regression was observed in 3 of 6 tumor xenograft models. FASN inhibition does not affect cellular taxane concentration in vitro. Our data suggest a mechanism of enhanced anti-tumor activity of the FASN and taxane drug combination that includes inhibition of tubulin palmitoylation and disruption of microtubule organization in tumor cells, as well as a sensitization of tumor cells to FASN inhibition-mediated effects that include gene expression changes and inhibition of β-catenin. Together, the results strongly support investigation of combined FASN inhibition and taxane treatment as a therapy for a variety of human cancers. Copyright © 2016 3-V Biosciences. Published by Elsevier B.V. All rights reserved.

  18. FASN Inhibition and Taxane Treatment Combine to Enhance Anti-tumor Efficacy in Diverse Xenograft Tumor Models through Disruption of Tubulin Palmitoylation and Microtubule Organization and FASN Inhibition-Mediated Effects on Oncogenic Signaling and Gene Expression

    Directory of Open Access Journals (Sweden)

    Timothy S. Heuer

    2017-02-01

    Full Text Available Palmitate, the enzymatic product of FASN, and palmitate-derived lipids support cell metabolism, membrane architecture, protein localization, and intracellular signaling. Tubulins are among many proteins that are modified post-translationally by acylation with palmitate. We show that FASN inhibition with TVB-3166 or TVB-3664 significantly reduces tubulin palmitoylation and mRNA expression. Disrupted microtubule organization in tumor cells is an additional consequence of FASN inhibition. FASN inhibition combined with taxane treatment enhances inhibition of in vitro tumor cell growth compared to treatment with either agent alone. In lung, ovarian, prostate, and pancreatic tumor xenograft studies, FASN inhibition and paclitaxel or docetaxel combine to inhibit xenograft tumor growth with significantly enhanced anti-tumor activity. Tumor regression was observed in 3 of 6 tumor xenograft models. FASN inhibition does not affect cellular taxane concentration in vitro. Our data suggest a mechanism of enhanced anti-tumor activity of the FASN and taxane drug combination that includes inhibition of tubulin palmitoylation and disruption of microtubule organization in tumor cells, as well as a sensitization of tumor cells to FASN inhibition-mediated effects that include gene expression changes and inhibition of β-catenin. Together, the results strongly support investigation of combined FASN inhibition and taxane treatment as a therapy for a variety of human cancers.

  19. The Effects of Acupuncture in Treatment of Coronary Heart Diseases

    Institute of Scientific and Technical Information of China (English)

    孟竞壁

    2004-01-01

    A clinical study on acupuncture at point Neiguan (PC 6) was conducted on the basis of successful treatment of patients with angina pectoris and acute myocardial infarct. The effective rate (91.3%) was found to be far superior to isosorbide dinitrate and nifedipine (P<0.01). The experimental studies in animal models demonstrated that electro-acupuncture could decrease the elevated ST segments in ECGs and reduce the infarct areas induced by coronary ligation.

  20. Hybrid modelling of anaerobic wastewater treatment processes.

    Science.gov (United States)

    Karama, A; Bernard, O; Genovesi, A; Dochain, D; Benhammou, A; Steyer, J P

    2001-01-01

    This paper presents a hybrid approach for the modelling of an anaerobic digestion process. The hybrid model combines a feed-forward network, describing the bacterial kinetics, and the a priori knowledge based on the mass balances of the process components. We have considered an architecture which incorporates the neural network as a static model of unmeasured process parameters (kinetic growth rate) and an integrator for the dynamic representation of the process using a set of dynamic differential equations. The paper contains a description of the neural network component training procedure. The performance of this approach is illustrated with experimental data.

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

    CERN Document Server

    Burke, Edmund K; 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 the Nottingham University Hospitals NHS Trust, UK, are presented and show how the proposed model can be used with different policies in order to achieve good quality schedules.

  2. Modelling of Activated Sludge Wastewater Treatment

    OpenAIRE

    Kurtanjeka, Ž.; Deverić Meštrović, B.; Ležajić, Z.; Bevetek, A.; Čurlin; M.

    2008-01-01

    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 b...

  3. Rat Models of Diet-Induced Obesity and High Fat/Low Dose Streptozotocin Type 2 Diabetes: Effect of Reversal of High Fat Diet Compared to Treatment with Enalapril or Menhaden Oil on Glucose Utilization and Neuropathic Endpoints

    Directory of Open Access Journals (Sweden)

    Amey Holmes

    2015-01-01

    Full Text Available We examined whether reversal of high fat diet, stimulating weight loss, compared to two treatments previously shown to have beneficial effects, could improve glucose utilization and peripheral neuropathy in animal models of obesity and type 2 diabetes. Rats were fed a high fat diet and treated with a low dose of streptozotocin to create models of diet induced obesity or type 2 diabetes, respectively. Afterwards, rats were transferred to a normal diet or treated with enalapril or dietary enrichment with menhaden oil for 12 weeks. Obesity and to a greater extent type 2 diabetes were associated with impaired glucose utilization and peripheral neuropathy. Placing obese rats on a normal diet improved glucose utilization. Steatosis but not peripheral neuropathy was improved after placing obese or diabetic rats on a normal diet. Treating obese and diabetic rats with enalapril or a menhaden oil enriched diet generally improved peripheral neuropathy endpoints. In summary, dietary improvement with weight loss in obese or type 2 diabetic rats was not sufficient to correct peripheral neuropathy. These results further stress the need for discovery of a comprehensive treatment for peripheral neuropathy.

  4. Rat Models of Diet-Induced Obesity and High Fat/Low Dose Streptozotocin Type 2 Diabetes: Effect of Reversal of High Fat Diet Compared to Treatment with Enalapril or Menhaden Oil on Glucose Utilization and Neuropathic Endpoints.

    Science.gov (United States)

    Holmes, Amey; Coppey, Lawrence J; Davidson, Eric P; Yorek, Mark A

    2015-01-01

    We examined whether reversal of high fat diet, stimulating weight loss, compared to two treatments previously shown to have beneficial effects, could improve glucose utilization and peripheral neuropathy in animal models of obesity and type 2 diabetes. Rats were fed a high fat diet and treated with a low dose of streptozotocin to create models of diet induced obesity or type 2 diabetes, respectively. Afterwards, rats were transferred to a normal diet or treated with enalapril or dietary enrichment with menhaden oil for 12 weeks. Obesity and to a greater extent type 2 diabetes were associated with impaired glucose utilization and peripheral neuropathy. Placing obese rats on a normal diet improved glucose utilization. Steatosis but not peripheral neuropathy was improved after placing obese or diabetic rats on a normal diet. Treating obese and diabetic rats with enalapril or a menhaden oil enriched diet generally improved peripheral neuropathy endpoints. In summary, dietary improvement with weight loss in obese or type 2 diabetic rats was not sufficient to correct peripheral neuropathy. These results further stress the need for discovery of a comprehensive treatment for peripheral neuropathy.

  5. 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....

  6. 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 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 nitronaphthalenes, 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.

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

    OpenAIRE

    2013-01-01

    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 azo...

  8. Rebound effect of drugs: fatal risk of conventional treatment and pharmacological basis of homeopathic treatment

    Directory of Open Access Journals (Sweden)

    Marcus Zulian Teixeira

    2012-06-01

    Full Text Available The homeopathic model applies the secondary action or vital reaction of the organism as a therapeutic method and thus prescribes treatment by similitude, which consists in administering to ill individuals substances that cause similar symptoms in healthy individuals. The vital, homeostatic or paradoxical reaction of the organism might be explained scientifically by means of the rebound effect of modern drugs, which might cause fatal iatrogenic events after discontinuation of antipathic (a term used in alternative medicine for palliative treatment, also known as enantiopathic treatment. Although the rebound effect is studied by modern pharmacology, it is poorly communicated to and discussed among healthcare professionals, who are thus deprived of information needed for the safe management of modern drugs. This article presents an up-to-date review on the rebound effect of modern drugs that grounds the homeopathic principle of healing and calls the attention of doctors to this type of adverse effect that is usually unnoticed. The rebound effect of modern palliative drugs, which was pointed out by Hahnemann more than two centuries ago, might cause fatal adverse events and is illustrated by the examples of acetylsalicylic acid, anti-inflammatory agents, bronchodilators, antidepressants, statins, proton-pump inhibitors, etc. Although the rebound effect is expressed by a small fraction of (susceptible individuals and might be avoided by gradual tapering of antipathic drugs, it exhibits epidemiologic importance as a function of the massive use of such palliative drugs and the lack of knowledge in its regard.

  9. Desensitization and Modeling Treatments of Spider Fear Using Two Types of Scenes

    Science.gov (United States)

    Denney, Douglas R.; Sullivan, Bernard J.

    1976-01-01

    Three types of therapy were combined with two types of scenes. Spider-phobic subjects were assigned to one of the six treatment conditions or to an untreated control group. In general, (a) Desensitization and modeling therapies were equally effective; (b) modeling alone was more effective than mere exposure to the phobic object. (Author)

  10. 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

  11. 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 inhibitor

  12. 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.

  13. The impact of treatment couch modelling on RapidArc

    Energy Technology Data Exchange (ETDEWEB)

    Vanetti, Eugenio; Nicolini, Giorgia; Clivio, Alessandro; Fogliata, Antonella; Cozzi, Luca [Medical Physics Unit, Oncology Institute of Southern Switzerland, Bellinzona (Switzerland)], E-mail: lucozzi@iosi.ch

    2009-05-07

    A planning and dosimetric study was carried out on a cohort of six CT datasets from patients treated for prostate cancer to assess the impact of couch modelling on the accuracy of dose calculation for the volumetric modulated arc technique RapidArc. For each patient, RapidArc plans were optimized using the couch while final dose calculation was performed with different conditions (thin, medium, thick and no couch). Analysis was performed in terms of dose volume histograms, dose difference histograms and 3D-{gamma} tests. Pre-treatment verification measurements were performed using the PTW-729 array in conjunction with the Octavius phantom (PTW, Freiburg); similarly, HU characterization of couch was performed with the same phantom and ion chamber measurements comparing calculations and experimental data. A set of Hounsfield Units (HU) valid for low and high energy and the entire couch length was found as internal structure HU = -960, surface shell HU = -700. Analysis of dose plans showed that differences larger than 1.5 Gy for a 70 Gy prescription might be observed on significant fractions of PTVs. Smaller differences are visible in the medium low-dose regions. Pre-treatment verification on composite delivery confirmed these observations and, at the same time, showed good accuracy of dose calculations in the presence of couch modelling compared to delivery in the same conditions (GAI ranging from 95% to 100%). Results confirmed the reliability of the geometrical model build in the planning system Eclipse, and (i) there is no measurable effect if the wrong segment of the couch is used in the calculations; (ii) there are significant discrepancies of potential clinical impact at the level of the target volumes if calculations are performed without couch and delivery is performed with couch, and (iii) the effect is particularly relevant at low energy (6 MV in this case) that is the configuration clinically used by most of the centres adopting technologies based on

  14. The impact of treatment couch modelling on RapidArc.

    Science.gov (United States)

    Vanetti, Eugenio; Nicolini, Giorgia; Clivio, Alessandro; Fogliata, Antonella; Cozzi, Luca

    2009-05-07

    A planning and dosimetric study was carried out on a cohort of six CT datasets from patients treated for prostate cancer to assess the impact of couch modelling on the accuracy of dose calculation for the volumetric modulated arc technique RapidArc. For each patient, RapidArc plans were optimized using the couch while final dose calculation was performed with different conditions (thin, medium, thick and no couch). Analysis was performed in terms of dose volume histograms, dose difference histograms and 3D-gamma tests. Pre-treatment verification measurements were performed using the PTW-729 array in conjunction with the Octavius phantom (PTW, Freiburg); similarly, HU characterization of couch was performed with the same phantom and ion chamber measurements comparing calculations and experimental data. A set of Hounsfield Units (HU) valid for low and high energy and the entire couch length was found as internal structure HU = -960, surface shell HU = -700. Analysis of dose plans showed that differences larger than 1.5 Gy for a 70 Gy prescription might be observed on significant fractions of PTVs. Smaller differences are visible in the medium low-dose regions. Pre-treatment verification on composite delivery confirmed these observations and, at the same time, showed good accuracy of dose calculations in the presence of couch modelling compared to delivery in the same conditions (GAI ranging from 95% to 100%). Results confirmed the reliability of the geometrical model build in the planning system Eclipse, and (i) there is no measurable effect if the wrong segment of the couch is used in the calculations; (ii) there are significant discrepancies of potential clinical impact at the level of the target volumes if calculations are performed without couch and delivery is performed with couch, and (iii) the effect is particularly relevant at low energy (6 MV in this case) that is the configuration clinically used by most of the centres adopting technologies based on

  15. Determinants of orthodontic treatment need and demand: a cross-sectional path model study.

    Science.gov (United States)

    Taghavi Bayat, Jari; Huggare, Jan; Mohlin, Bengt; Akrami, Nazar

    2017-02-01

    To put forward a model predicting orthodontic treatment need and demand. Furthermore, to explore how much of the variance in treatment demand could be explained by a set of self-assessed measures, and how these measures relate to professionally assessed treatment need. One hundred and fifty adolescents, aged 13 years, completed a questionnaire which included a set of self-assessed measures dealing with self-esteem, such as dental and global self-esteem, various aspects of malocclusion, such as perceived malocclusion and perceived functional limitation, and treatment demand. Treatment need was assessed by Dental Health Component of the Index of Orthodontic Treatment Need grading. Path analysis was used to examine the relations between the measures and if they could predict treatment need and demand. The measures proved to be reliable and inter-correlated. Path analysis revealed that the proposed model had good fit to the data, providing a test of the unique effect of all included measures on treatment need and demand. The model explained 33% of the variance in treatment demand and 22% of the variance in treatment need. The specific age group could affect the generalizability of the findings. Moreover, although showing good fit to data, the final model is based on a combination of theoretical reasoning and semi-explorative approach. The proposed model displays the unique effect of each included measure on treatment need and demand, explaining a large proportion of the variance in perceived treatment demand and professionally assessed treatment need. The model would hopefully lead to improved and more cost-efficient predictions of treatment need and demand. © The Author 2016. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. A Novel Bio-Psychosocial-Behavioral Treatment Model in Schizophrenia.

    Science.gov (United States)

    Kim, Yong-Ku; Choi, Joonho; Park, Seon-Cheol

    2017-03-30

    Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and γ-aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well. The balance of excitation and inhibition has been associated with epigenetic modifications and thus can be analyzed in terms of a neurodevelopmental and neural circuitry perspective. Hence, a novel bio-psychosocial-behavioral model for the treatment of schizophrenia is needed to account for the non-dopaminergic systems involved in schizophrenia, rather than dopaminergic mechanisms. This model can be understood from the viewpoint of neurodevelopment and neural circuitry and should include the staging care, personalized care, preventive care, reducing the cognitive deficits, and reducing stigma. Thomas R. Insel proposed this as a goal for schizophrenia treatment to be achieved by 2030.

  17. Fast Parameters Estimation in Medication Efficacy Assessment Model for Heart Failure Treatment

    Directory of Open Access Journals (Sweden)

    Yinzi Ren

    2012-01-01

    Full Text Available Introduction. Heart failure (HF is a common and potentially fatal condition. Cardiovascular research has focused on medical therapy for HF. Theoretical modelling could enable simulation and evaluation of the effectiveness of medications. Furthermore, the models could also help predict patients’ cardiac response to the treatment which will be valuable for clinical decision-making. Methods. This study presents a fast parameters estimation algorithm for constructing a cardiovascular model for medicine evaluation. The outcome of HF treatment is assessed by hemodynamic parameters and a comprehensive index furnished by the model. Angiotensin-converting enzyme inhibitors (ACEIs were used as a model drug in this study. Results. Our simulation results showed different treatment responses to enalapril and lisinopril, which are both ACEI drugs. A dose-effect was also observed in the model simulation. Conclusions. Our results agreed well with the findings from clinical trials and previous literature, suggesting the validity of the model.

  18. 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.

  19. Measuring safety treatment effects using full Bayes non-linear safety performance intervention functions.

    Science.gov (United States)

    El-Basyouny, Karim; Sayed, Tarek

    2012-03-01

    Full Bayes linear intervention models have been recently proposed to conduct before-after safety studies. These models assume linear slopes to represent the time and treatment effects across the treated and comparison sites. However, the linear slope assumption can only furnish some restricted treatment profiles. To overcome this problem, a first-order autoregressive (AR1) safety performance function (SPF) that has a dynamic regression equation (known as the Koyck model) is proposed. The non-linear 'Koyck' model is compared to the linear intervention model in terms of inference, goodness-of-fit, and application. Both models were used in association with the Poisson-lognormal (PLN) hierarchy to evaluate the safety performance of a sample of intersections that have been improved in the Greater Vancouver area. The two models were extended by incorporating random parameters to account for the correlation between sites within comparison-treatment pairs. Another objective of the paper is to compute basic components related to the novelty effects, direct treatment effects, and indirect treatment effects and to provide simple expressions for the computation of these components in terms of the model parameters. The Koyck model is shown to furnish a wider variety of treatment profiles than those of the linear intervention model. The analysis revealed that incorporating random parameters among matched comparison-treatment pairs in the specification of SPFs can significantly improve the fit, while reducing the estimates of the extra-Poisson variation. Also, the proposed PLN Koyck model fitted the data much better than the Poisson-lognormal linear intervention (PLNI) model. The novelty effects were short lived, the indirect (through traffic volumes) treatment effects were approximately within ±10%, whereas the direct treatment effects indicated a non-significant 6.5% reduction during the after period under PLNI compared to a significant 12.3% reduction in predicted collision

  20. Cryopreservation of oocytes and embryos: use of a mouse model to investigate effects upon zona hardness and formulate treatment strategies in an in-vitro fertilization programme.

    Science.gov (United States)

    Matson, P L; Graefling, J; Junk, S M; Yovich, J L; Edirisinghe, W R

    1997-07-01

    Mouse oocytes and embryos were obtained following ovulation induction of (C57B16 x CBA) F1 animals. Zonae pellucidae were exposed to alpha-chymotrypsin in phosphate-buffered medium (PB1) supplemented with 3 mg/ml bovine serum albumin upon a heated stage (37 degrees C) and were observed constantly through an inverted microscope. The endpoint of the bioassay was the limits of the zona no longer being seen clearly at x 200 magnification, and the time taken for each zona to dissolve was recorded. A dose-dependent response in dissolution time was clearly seen, with 1% alpha-chymotrypsin being chosen as the routine working solution. Cryopreservation of 2-cell mouse embryos using propanediol did not cause zona hardening but induced a small and significant softening, as gauged by the time taken for zona dissolution (2181 +/- 167 versus 1864 +/- 82 s). Zona hardening was not suspected to occur after the freezing of human embryos as there was no difference in implantation rates per embryo for in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment cycles between fresh [IVF: 63/644 (9.7%); ICSI: 51/330 (15.5%)] and frozen embryos [IVF: 36/458 (7.9%); ICSI: 18/112 (16.1%)]. Conversely, significant hardening of the zonae of mature oocytes was seen following cryopreservation (747 +/- 393 s) compared with freshly ovulated oocytes (151 +/- 68 s). It is concluded that (i) the freezing of murine oocytes with propanediol results in zona hardening, implying a possible benefit of ICSI after the cryopreservation of human oocytes, and (ii) the cryopreservation of embryos is not associated with zona hardening or reduced implantation, making microdissection of the zona in such cases generally unwarranted.

  1. Effects of Light-Emitting Diode Photobiomodulation Therapy and BioOss as Single and Combined Treatment in an Experimental Model of Bone Defect Healing in Rats.

    Science.gov (United States)

    Havlucu, Uğur; Bölükbaşı, Nilüfer; Yeniyol, Sinem; Çetin, Şule; Özdemir, Tayfun

    2015-08-01

    The present study assesses histopathologically and histomorphometrically the effects of light-emitting diode (LED) photobiomodulation therapy (LPT) on bone healing in BioOss-filled femoral defects of rats. It has been reported that LPT modulates cellular metabolic processes, leading to an enhanced regenerative potential for biological tissues. Thirty-six male Wistar rats with femoral bone defects were divided into 4 groups: defect group (empty bone defect, without application of LPT), graft group (bone defect filled with BioOss, without application of LPT), (defect+LPT) group (empty bone defect, with application of LPT), and (graft+LPT) group (bone defect filled with BioOss, with application of LPT). An OsseoPulse LED device (wavelength: 618 nm; output power: 20 mW/cm(2)) was initiated 24 hours postsurgery and performed every 24 hours for 7, 14, and 21 days. The LPT-applied and BioOss-filled defects presented a higher amount of new bone formation with trabeculae formation. These defects showed statistically significant lower values of inflammation severity, and fewer remnants of biomaterial were present. Within the limitations of this study, LPT has positive effects on bone healing histopathologically and histomorphometrically for the defects filled with BioOss 3 weeks after the rats' femora injury.

  2. Heat treatment modelling using strongly continuous semigroups.

    Science.gov (United States)

    Malek, Alaeddin; Abbasi, Ghasem

    2015-07-01

    In this paper, mathematical simulation of bioheat transfer phenomenon within the living tissue is studied using the thermal wave model. Three different sources that have therapeutic applications in laser surgery, cornea laser heating and cancer hyperthermia are used. Spatial and transient heating source, on the skin surface and inside biological body, are considered by using step heating, sinusoidal and constant heating. Mathematical simulations describe a non-Fourier process. Exact solution for the corresponding non-Fourier bioheat transfer model that has time lag in its heat flux is proposed using strongly continuous semigroup theory in conjunction with variational methods. The abstract differential equation, infinitesimal generator and corresponding strongly continuous semigroup are proposed. It is proved that related semigroup is a contraction semigroup and is exponentially stable. Mathematical simulations are done for skin burning and thermal therapy in 10 different models and the related solutions are depicted. Unlike numerical solutions, which suffer from uncertain physical results, proposed analytical solutions do not have unwanted numerical oscillations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Applying Process-Based Models for Subsurface Flow Treatment Wetlands: Recent Developments and Challenges

    Directory of Open Access Journals (Sweden)

    Guenter Langergraber

    2016-12-01

    Full Text Available To date, only few process-based models for subsurface flow treatment wetlands have been developed. For modelling a treatment wetland, these models have to comprise a number of sub-models to describe water flow, pollutant transport, pollutant transformation and degradation, effects of wetland plants, and transport and deposition of suspended particulate matter. The two most advanced models are the HYDRUS Wetland Module and BIO-PORE. These two models are briefly described. This paper shows typical simulation results for vertical flow wetlands and discusses experiences and challenges using process-based wetland models in relation to the sub-models describing the most important wetland processes. It can be demonstrated that existing simulation tools can be applied for simulating processes in treatment wetlands. Most important for achieving a good match between measured and simulated pollutant concentrations is a good calibration of the water flow and transport models. Only after these calibrations have been made and the effect of the influent fractionation on simulation results has been considered, should changing the parameters of the biokinetic models be taken into account. Modelling the effects of wetland plants is possible and has to be considered when important. Up to now, models describing clogging are the least established models among the sub-models required for a complete wetland model and thus further development and research is required.

  4. 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.

  5. Synergistic effects of host B7-H4 deficiency and gemcitabine treatment on tumor regression and anti-tumor T cell immunity in a mouse model.

    Science.gov (United States)

    Leung, Joanne; St-Onge, Philippe; Stagg, John; Suh, Woong-Kyung

    2017-04-01

    B7-H4 (B7x/B7S1), a B7 family inhibitor of T cell activity, is expressed in multiple human cancers and correlates with decreased infiltrating lymphocytes and poor prognosis. In murine models, tumor-expressed B7-H4 enhances tumor growth and reduces T cell immunity, and blockade of tumor-B7-H4 rescues T cell activity and lowers tumor burden. This implicates B7-H4 as a target for cancer immunotherapy, yet limits the efficacy of B7-H4 blockade exclusively to patients with B7-H4+ tumors. Given the expression of B7-H4 on host immune cells, we have previously shown that BALB/c mice lacking host B7-H4 have enhanced anti-tumor profiles, yet similar 4T1 tumor growth relative to control. Given that T cell-mediated immunotherapies work best for tumors presenting tumor-associated neoantigens, we further investigated the function of host B7-H4 in the growth of a more immunogenic derivative, 4T1-12B, which is known to elicit strong anti-tumor CD8 T cell responses due to expression of a surrogate tumor-specific antigen, firefly luciferase. Notably, B7-H4 knockout hosts not only mounted greater tumor-associated anti-tumor T cell responses, but also displayed reduced tumors. Additionally, B7-H4-deficiency synergized with gemcitabine to further inhibit tumor growth, often leading to tumor eradication and the generation of protective T cell immunity. These findings imply that inhibition of host B7-H4 can enhance anti-tumor T cell immunity in immunogenic cancers, and can be combined with other anti-cancer therapies to further reduce tumor burden regardless of tumor-B7-H4 positivity.

  6. 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.

  7. Modeling precision treatment of breast cancer.

    Science.gov (United States)

    Daemen, Anneleen; Griffith, Obi L; Heiser, Laura M; Wang, Nicholas J; Enache, Oana M; Sanborn, Zachary; Pepin, Francois; Durinck, Steffen; Korkola, James E; Griffith, Malachi; Hur, Joe S; Huh, Nam; Chung, Jongsuk; Cope, Leslie; Fackler, Mary Jo; Umbricht, Christopher; Sukumar, Saraswati; Seth, Pankaj; Sukhatme, Vikas P; Jakkula, Lakshmi R; Lu, Yiling; Mills, Gordon B; Cho, Raymond J; Collisson, Eric A; van't Veer, Laura J; Spellman, Paul T; Gray, Joe W

    2013-01-01

    First-generation molecular profiles for human breast cancers have enabled the identification of features that can predict therapeutic response; however, little is known about how the various data types can best be combined to yield optimal predictors. Collections of breast cancer cell lines mirror many aspects of breast cancer molecular pathobiology, and measurements of their omic and biological therapeutic responses are well-suited for development of strategies to identify the most predictive molecular feature sets. We used least squares-support vector machines and random forest algorithms to identify molecular features associated with responses of a collection of 70 breast cancer cell lines to 90 experimental or approved therapeutic agents. The datasets analyzed included measurements of copy number aberrations, mutations, gene and isoform expression, promoter methylation and protein expression. Transcriptional subtype contributed strongly to response predictors for 25% of compounds, and adding other molecular data types improved prediction for 65%. No single molecular dataset consistently out-performed the others, suggesting that therapeutic response is mediated at multiple levels in the genome. Response predictors were developed and applied to TCGA data, and were found to be present in subsets of those patient samples. These results suggest that matching patients to treatments based on transcriptional subtype will improve response rates, and inclusion of additional features from other profiling data types may provide additional benefit. Further, we suggest a systems biology strategy for guiding clinical trials so that patient cohorts most likely to respond to new therapies may be more efficiently identified.

  8. 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…

  9. Adsorption modeling for off-gas treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ladshaw, A.; Sharma, K.; Yiacoumi, S.; Tsouris, C. [Georgia Institute of Technology, Atlanta, GA 30332-0459 (United States); De Paoli, D.W. [Oak Ridge National Laboratory: Oak Ridge, TN 37831-6181 (United States)

    2013-07-01

    Off-gas generated from the reprocessing of used nuclear fuel contains a mixture of several radioactive gases including {sup 129}I{sub 2}, {sup 85}Kr, HTO, and {sup 14}CO{sub 2}. Over the past few decades, various separation and recovery processes have been studied for capturing these gases. Adsorption data for gaseous mixtures of species can be difficult to determine experimentally. Therefore, procedures capable of predicting the adsorption behavior of mixtures need to be developed from the individual isotherms of each of the pure species. A particular isotherm model of interest for the pure species is the Generalized Statistical Thermodynamic Adsorption isotherm. This model contains an adjustable number of parameters and will therefore describe a wide range of adsorption isotherms for a variety of components. A code has been developed in C++ to perform the non-linear regression analysis necessary for the determination of the isotherm parameters, as well as the least number of parameters needed to describe an entire set of data. (authors)

  10. COST ESTIMATION MODELS FOR DRINKING WATER TREATMENT UNIT PROCESSES

    Science.gov (United States)

    Cost models for unit processes typically utilized in a conventional water treatment plant and in package treatment plant technology are compiled in this paper. The cost curves are represented as a function of specified design parameters and are categorized into four major catego...

  11. 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.

  12. Advanced modeling techniques in application to plasma pulse treatment

    Science.gov (United States)

    Pashchenko, A. F.; Pashchenko, F. F.

    2016-06-01

    Different approaches considered for simulation of plasma pulse treatment process. The assumption of a significant non-linearity of processes in the treatment of oil wells has been confirmed. Method of functional transformations and fuzzy logic methods suggested for construction of a mathematical model. It is shown, that models, based on fuzzy logic are able to provide a satisfactory accuracy of simulation and prediction of non-linear processes observed.

  13. 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......, anaerobic digestion and combinations hereof are available in the model, but the user can change all key parameters in the biological treatment module so that specific local plants and processes can be modelled. EASEWASTE is one of the newest waste LCA models and the biological treatment module was built...... partly on features of earlier waste-LCA models, but offers additional facilities, more flexibility, transparency and user-friendliness. The paper presents the main features of the module and provides some examples illustrating the capability of the model in environmentally assessing and discriminating...

  14. 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.

  15. Kriging with mixed effects models

    Directory of Open Access Journals (Sweden)

    Alessio Pollice

    2007-10-01

    Full Text Available In this paper the effectiveness of the use of mixed effects models for estimation and prediction purposes in spatial statistics for continuous data is reviewed in the classical and Bayesian frameworks. A case study on agricultural data is also provided.

  16. Evaluation of probiotic treatment in a neonatal animal model.

    Science.gov (United States)

    Lee, D J; Drongowski, R A; Coran, A G; Harmon, C M

    2000-01-01

    The clinical use of probiotic agents such as enteral Lactobacillus to enhance intestinal defense against potential luminal pathogens has been tested in vivo; however, an understanding of the mechanisms responsible for the observed protection is lacking. The purpose of this study was to evaluate the effects of Lactobacillus on bacterial translocation (BT) in a neonatal animal model. Newborn New Zealand white rabbit pups were enterally fed a 10% Formulac solution inoculated with or without a 10(8) suspension of ampicillin-resistant Escherichia coli K1 (E. coli K1A) and/or Lactobacillus casei GG (Lacto GG). Pups received either no bacteria (n = 10), Lacto GG (n = 8), E. coli K1A (n = 26), or a combination of Lacto GG and E. coli K1A (n = 33). On day 3, representative tissue specimens from the mesenteric lymph nodes (MLN), spleen (SPL), and liver (LIV) were aseptically harvested in addition to a small-bowel (SB) sample that was rinsed to remove luminal contents. The specimens were then cultured in organism-specific media. Statistical analysis was by one-way ANOVA with P values less than 0.05 considered significant. Neonatal rabbits receiving Lacto GG-supplemented formula exhibited a 25% decrease (P rabbit model. These results may have significant implications for the treatment of BT and sepsis in the human neonate and provide a model for further studies.

  17. 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.

  18. 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.

  19. New framework for standardized notation in wastewater treatment modelling

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...... notational framework which allows unique and systematic naming of state variables and parameters of biokinetic models in the wastewater treatment field. The symbols are based on one main letter that gives a general description of the state variable or parameter and several subscript levels that provide......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...

  20. Gompertz model with delays and treatment: mathematical analysis.

    Science.gov (United States)

    Bodnar, Marek; Piotrowska, Monika Joanna; Foryś, Urszula

    2013-06-01

    In this paper we study the delayed Gompertz model, as a typical model of tumor growth, with a term describing external interference that can reflect a treatment, e.g. chemotherapy. We mainly consider two types of delayed models, the one with the delay introduced in the per capita growth rate (we call it the single delayed model) and the other with the delay introduced in the net growth rate (the double delayed model). We focus on stability and possible stability switches with increasing delay for the positive steady state. Moreover, we study a Hopf bifurcation, including stability of arising periodic solutions for a constant treatment. The analytical results are extended by numerical simulations for a pharmacokinetic treatment function.

  1. Size Effect in Continuum Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Wei-Yang [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Mechanics of Materials; Foulk, James W. [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Mechanics of Materials; Huestis, Edwin M. [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Mechanics of Materials; Connelly, Kevin [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Mechanics of Materials; Song, Bo [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Mechanics of Materials; Yang, Nancy Y. C. [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Engineered Materials

    2008-09-01

    The mechanical properties of some materials (Cu, Ni, Ag, etc.) have been shown to develop strong dependence on the geometric dimensions, resulting in a size effect. Several theories have been proposed to model size effects, but have been based on very few experiments conducted at appropriate scales. Some experimental results implied that size effects are caused by increasing strain gradients and have been used to confirm many strain gradient theories. On the other hand, some recent experiments show that a size effect exists in the absence of strain gradients. This report describes a brief analytical and experimental study trying to clarify the material and experimental issues surrounding the most influential size-effect experiments by Fleck et al (1994). This effort is to understand size effects intended to further develop predictive models.

  2. Integrated modeling and heat treatment simulation of austempered ductile iron

    Science.gov (United States)

    Hepp, E.; Hurevich, V.; Schäfer, W.

    2012-07-01

    The integrated modeling and simulation of the casting and heat treatment processes for producing austempered ductile iron (ADI) castings is presented. The focus is on describing different models to simulate the austenitization, quenching and austempering steps during ADI heat treatment. The starting point for the heat treatment simulation is the simulated microstructure after solidification and cooling. The austenitization model considers the transformation of the initial ferrite-pearlite matrix into austenite as well as the dissolution of graphite in austenite to attain a uniform carbon distribution. The quenching model is based on measured CCT diagrams. Measurements have been carried out to obtain these diagrams for different alloys with varying Cu, Ni and Mo contents. The austempering model includes nucleation and growth kinetics of the ADI matrix. The model of ADI nucleation is based on experimental measurements made for varied Cu, Ni, Mo contents and austempering temperatures. The ADI kinetic model uses a diffusion controlled approach to model the growth. The models have been integrated in a tool for casting process simulation. Results are shown for the optimization of the heat treatment process of a planetary carrier casting.

  3. Effects of Acupotomy Treatment on Cervical X-rays in a Rabbit Model of Cervical Spondylosis%针刀干预对颈椎病兔颈椎X线影像学的影响

    Institute of Scientific and Technical Information of China (English)

    郭长青; 刘福水; 钟鼎文; 张义

    2013-01-01

    Objective:This study was expected to observe the effects of acupotomy treatment on cervical X -rays in a rabbit model of cer-vical spondylosis ( CS) .Methods:Six months old New Zealand rabbits were divided into 4 groups randomly:normal control group ,model group,acupotomy group,electro-acupuncture group.CS models were made by the method of flexed neck posture for long-term.After modeling ,acupotomy and electro-acupuncture were applied to treat acupotomy group and electro-acupuncture group respectively .Changes of cervical X-rays taken before and after modeling ,and after treatment.Results:After modeling,cervical X-rays showed that there were changes in cervical lordosis ,narrowed lordotic curve with posterior convexity ,a decrease in discs height ,narrowed intervertebrale foramen and overgrowth of osteophytes in anterior and posterior vertebral bodies in some rabbits .There was obvious improvement in X-rays after acupotomy treatment;cervical lordosis straightened ,intervertebral foramen widened in some rabbits ,and there was no obvious change of osteophytes before and after treatment .After modeling,the cervical X-ray scores of the model group ,acupotomy group and electro-acu-puncture group increased significantly in comparison with that of normal control group (P0.05). The reduction of X-ray scores before and after treatment in acupotomy group had a significant difference compared with the electro -acu-puncture group (P<0.05).Conclusion:Acupotomy in the treatment of cervical spondylosis can effectively restore cervical lordosis ,im-prove cervical X-ray image,reestablish cervical biomechanical balance .%目的:观察针刀干预对颈椎病兔颈椎X线影像学的的影响。方法:6月龄新西兰兔随机分为空白组、模型组、针刀组、电针组,采用长期低头位方法制备颈椎病模型。造模后对针刀组、电针组进行治疗干预。各组动物于造模前后、干预后3个时间节点拍摄颈椎X线片。结果:颈椎X线

  4. Effects of sonochemical treatment on meteoritic nanodiamonds

    Science.gov (United States)

    Fisenko, Anatolii V.; Verchovsky, Sasha B.; Shiryaev, Andrei A.; Semjonova, Luba F.

    2017-01-01

    A nanodiamond-rich fraction (NDF) separated from the Orgueil meteorite was subjected to a high-intensity ultrasonic treatment in a weakly acidic aqueous solution. After sedimentation by centrifugation, two fractions of grains (suspension, designated as OD7C and sediment, designated as OD7D) with different properties have been obtained. The following effects of the sonication were revealed from comparison of the contents and isotope compositions of C, N, and Xe released during stepped pyrolysis and combustion of the fractions OD7C and OD7D, the initial NDF and two grain-size fractions (OD10 and OD15) produced without sonication (a) surface layer of the sonicated diamond grains is modified to different extent in comparison with nontreated ones, (b) in some grains concentrations of the bulk N and Xe a reduced significantly, and (c) nondiamond nitrogen containing phases (e.g., Si3N4) have been destroyed. It is suggested that combined effects of the sonication and centrifugation observed for the fractions OD7C and OD7D are due to differences in surface chemistry of the nanodiamond grains, which statistically influences behavior of nanoparticles during the sonication resulting in their preferential modification in the different reaction zones of the cavitating fluid.

  5. 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.

  6. 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.

  7. Modelling of enhanced CSO treatment in secondary clarifiers with a modified Activated Sludge Model no. 3.

    Science.gov (United States)

    Ahnert, M; Günther, N; Kuehn, V; Krebs, P; Svardal, K; Spatzierer, G

    2008-01-01

    An alternative approach for combined water treatment as opposed to its CSO discharge into receiving water is its bypass to the inlet of secondary clarifiers (SC). To analyse the processes and to evaluate the performance of this approach, experiments and numerical modelling were carried out. In batch and pilot scale experiments major effects were identified and quantified. The Activated Sludge Model No. 3 (ASM3) was modified to simulate the batch and pilot scale experiments for implementation of the bypass-specific processes and thus to set up an overall balance of the relevant compounds. With some modifications of ASM3, good agreement of the modelling results with measurements of COD, nitrogen and phosphorus were achieved. (c) IWA Publishing 2008.

  8. 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

  9. New framework for standardized notation in wastewater treatment modelling.

    Science.gov (United States)

    Corominas, L L; Rieger, L; Takács, I; Ekama, G; Hauduc, H; Vanrolleghem, P A; Oehmen, A; Gernaey, K V; van Loosdrecht, M C M; Comeau, Y

    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 notational framework which allows unique and systematic naming of state variables and parameters of biokinetic models in the wastewater treatment field. The symbols are based on one main letter that gives a general description of the state variable or parameter and several subscript levels that provide greater specification. Only those levels that make the name unique within the model context are needed in creating the symbol. The paper describes specific problems encountered with the currently used notation, presents the proposed framework and provides additional practical examples. The overall result 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. 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

  11. Elimination of African onchocerciasis: modeling the impact of increasing the frequency of ivermectin mass treatment.

    Directory of Open Access Journals (Sweden)

    Luc E Coffeng

    Full Text Available The African Programme for Onchocerciasis Control (APOC is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently.

  12. Effect of Xanthone Derivatives on Animal Models of Depression

    Directory of Open Access Journals (Sweden)

    Xu Zhao, MD

    2014-12-01

    Conclusions: Within certain dose ranges, xanthone derivatives 1101 and 1105 have similar effects to venlafaxine hydrochloride in the treatment of depression as suggested by behavioral despair animal models using rats and mice.

  13. Selecting Effective Treatments: A Comprehensive, Systematic Guide to Treating Mental Disorders. Revised Edition.

    Science.gov (United States)

    Seligman, Linda

    This book presents an overview of the major types of mental disorders, accompanied by treatment models that are structured, comprehensive, grounded in research, and likely to be effective. Chapter topics are: (1) "Introduction to Effective Treatment Planning"; (2) "Mental Disorders in Infants, Children, and Adolescents"; (3) "Situationally…

  14. 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 filt

  15. Feedback from Outcome Measures and Treatment Effectiveness, Treatment Efficiency, and Collaborative Practice: A Systematic Review.

    Science.gov (United States)

    Gondek, Dawid; Edbrooke-Childs, Julian; Fink, Elian; Deighton, Jessica; Wolpert, Miranda

    2016-05-01

    Due to recent increases in the use of feedback from outcome measures in mental health settings, we systematically reviewed evidence regarding the impact of feedback from outcome measures on treatment effectiveness, treatment efficiency, and collaborative practice. In over half of 32 studies reviewed, the feedback condition had significantly higher levels of treatment effectiveness on at least one treatment outcome variable. Feedback was particularly effective for not-on-track patients or when it was provided to both clinicians and patients. The findings for treatment efficiency and collaborative practice were less consistent. Given the heterogeneity of studies, more research is needed to determine when and for whom feedback is most effective.

  16. An Integrated Model for Identifying Linkages Between the Management of Fuel Treatments, Fire and Ecosystem Services

    Science.gov (United States)

    Bart, R. R.; Anderson, S.; Moritz, M.; Plantinga, A.; Tague, C.

    2015-12-01

    Vegetation fuel treatments (e.g. thinning, prescribed burning) are a frequent tool for managing fire-prone landscapes. However, predicting how fuel treatments may affect future wildfire risk and associated ecosystem services, such as forest water availability and streamflow, remains a challenge. This challenge is in part due to the large range of conditions under which fuel treatments may be implemented, as response is likely to vary with species type, rates of vegetation regrowth, meteorological conditions and physiographic properties of the treated site. It is also due to insufficient understanding of how social factors such as political pressure, public demands and economic constraints affect fuel management decisions. To examine the feedbacks between ecological and social dimensions of fuel treatments, we present an integrated model that links a biophysical model that simulates vegetation and hydrology (RHESSys), a fire spread model (WMFire) and an empirical fuel treatment model that accounts for agency decision-making. We use this model to investigate how management decisions affect landscape fuel loads, which in turn affect fire severity and ecosystem services, which feedback to management decisions on fuel treatments. We hypothesize that this latter effect will be driven by salience theory, which predicts that fuel treatments are more likely to occur following major wildfire events. The integrated model provides a flexible framework for answering novel questions about fuel treatments that span social and ecological domains, areas that have previously been treated separately.

  17. An epidemic model for cholera with optimal control treatment

    OpenAIRE

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

    2016-01-01

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

  18. Benchmarking biological nutrient removal in wastewater treatment plants: influence of mathematical model assumptions

    DEFF Research Database (Denmark)

    Flores-Alsina, Xavier; Gernaey, Krist V.; Jeppsson, Ulf

    2012-01-01

    This paper examines the effect of different model assumptions when describing biological nutrient removal (BNR) by the activated sludge models (ASM) 1, 2d & 3. The performance of a nitrogen removal (WWTP1) and a combined nitrogen and phosphorus removal (WWTP2) benchmark wastewater treatment plant...

  19. 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…

  20. The Character-Disordered Family: A Community Treatment Model for Family Sexual Abuse.

    Science.gov (United States)

    Anderson, Lorna M.; Shafer, Gretchen

    1979-01-01

    A collaborative approach to treating sexually abusive families is described, in which such families are viewed as analogous to "character-disordered" individuals. This model, unlike traditional voluntary treatment models, is explained to assume that effective intervention requires authoritative control and careful coordination of all…

  1. 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…

  2. 3D finite element model for treatment of cleft lip

    Science.gov (United States)

    Jiao, Chun; Hong, Dongming; Lu, Hongbing; Wang, Jianqi; Lin, Qin; Liang, Zhengrong

    2009-02-01

    Cleft lip is a congenital facial deformity with high occurrence rate in China. Surgical procedure involving Millard or Tennison methods is usually employed for treatment of cleft lip. However, due to the elasticity of the soft tissues and the mechanical interaction between skin and maxillary, the occurrence rate of facial abnormality or dehisce is still high after the surgery, leading to multiple operations of the patient. In this study, a framework of constructing a realistic 3D finite element model (FEM) for the treatment of cleft lip has been established. It consists of two major steps. The first one is the reconstruction of a 3D geometrical model of the cleft lip from scanning CT data. The second step is the build-up of a FEM for cleft lip using the geometric model, where the material property of all the tetrahedrons was calculated from the CT densities directly using an empirical curve. The simulation results demonstrated (1) the deformation procedure of the model step-by-step when forces were applied, (2) the stress distribution inside the model, and (3) the displacement of all elements in the model. With the computer simulation, the minimal force of having the cleft be repaired is predicted, as well as whether a given force sufficient for the treatment of a specific individual. It indicates that the proposed framework could integrate the treatment planning with stress analysis based on a realistic patient model.

  3. Understanding Treatment Effect Terminology in Pain and Symptom Management Research.

    Science.gov (United States)

    Garrido, Melissa M; Dowd, Bryan; Hebert, Paul L; Maciejewski, Matthew L

    2016-09-01

    Within health services and medical research, there is a wide variety of terminology related to treatment effects. Understanding differences in types of treatment effects is especially important in pain and symptom management research where nonexperimental and quasiexperimental observational data analysis is common. We use the example of a palliative care consultation team leader considering implementation of a medication reconciliation program and a care-coordination intervention reported in the literature to illustrate population-level and conditional treatment effects and to highlight the sensitivity of values of treatment effects to sample selection and treatment assignment. Our goal is to facilitate appropriate reporting and interpretation of study results and to help investigators understand what information a decision maker needs when deciding whether to implement a treatment. Greater awareness of the reasons why treatment effects may differ across studies of the same patients in the same treatment settings can help policy makers and clinicians understand to whom a study's results may be generalized.

  4. Modeling AIDS survival after initiation of antiretroviral treatment by Weibull models with changepoints

    Directory of Open Access Journals (Sweden)

    Yiannoutsos Constantin T

    2009-06-01

    Full Text Available Abstract Background Mortality of HIV-infected patients initiating antiretroviral therapy in the developing world is very high immediately after the start of ART therapy and drops sharply thereafter. It is necessary to use models of survival time that reflect this change. Methods In this endeavor, parametric models with changepoints such as Weibull models can be useful in order to explicitly model the underlying failure process, even in the case where abrupt changes in the mortality rate are present. Estimation of the temporal location of possible mortality changepoints has important implications on the effective management of these patients. We briefly describe these models and apply them to the case of estimating survival among HIV-infected patients who are initiating antiretroviral therapy in a care and treatment programme in sub-Saharan Africa. Results As a first reported data-driven estimate of the existence and location of early mortality changepoints after antiretroviral therapy initiation, we show that there is an early change in risk of death at three months, followed by an intermediate risk period lasting up to 10 months after therapy. Conclusion By explicitly modelling the underlying abrupt changes in mortality risk after initiation of antiretroviral therapy we are able to estimate their number and location in a rigorous, data-driven manner. The existence of a high early risk of death after initiation of antiretroviral therapy and the determination of its duration has direct implications for the optimal management of patients initiating therapy in this setting.

  5. Effect of timing of count events on estimates of sea lice abundance and interpretation of effectiveness following bath treatments.

    Science.gov (United States)

    Gautam, R; Vanderstichel, R; Boerlage, A S; Revie, C W; Hammell, K L

    2017-03-01

    Effectiveness of sea lice bath treatment is often assessed by comparing pre- and post-treatment counts. However, in practice, the post-treatment counting window varies from the day of treatment to several days after treatment. In this study, we assess the effect of post-treatment lag time on sea lice abundance estimates after chemical bath treatment using data from the sea lice data management program (Fish-iTrends) between 2010 and 2014. Data on two life stages, (i) adult female (AF) and (ii) pre-adult and adult male (PAAM), were aggregated at the cage level and log-transformed. Average sea lice counts by post-treatment lag time were computed for AF and PAAM and compared relative to treatment day, using linear mixed models. There were 720 observations (treatment events) that uniquely matched pre- and post-treatment counts from 53 farms. Lag time had a significant effect on the estimated sea lice abundance, which was influenced by season and pre-treatment sea lice levels. During summer, sea lice were at a minimum when counted 1 day post-treatment irrespective of pre-treatment sea lice levels, whereas in the spring and autumn, low levels were observed for PAAM over a longer interval of time, provided the pre-treatment sea lice levels were >5-10.

  6. Ni/γ-Al2O3 Catalyst for CO2 Reforming of Benzene as a Model Compound of Biomass Gasification Tar: Promotional Effect of Ultrasonic Treatment on Catalytic Performance

    Science.gov (United States)

    Li, B.; Chen, H. P.; Yang, H. P.; Yang, G. L.; Wang, X. H.; Zhang, S. H.

    This paper aims to understand the promotional effect of ultrasonic treatment on catalytic performance of Ni/γ-Al2O3 catalyst for CO2 reforming of benzene as a model compound of tar derived from biomass gasification, and the catalytic cracking mechanism was also discussed. Firstly, three Ni/γ-Al2O3catalysts were prepared by ultrasonic impregnation as the ultrasonic power variantat0, 120 and 500W, andthephysicochemical property of catalysts were characterized using N2-adsorption, SEM and XRD, etc. Then the catalytic performance of three catalysts for CO2 reforming of benzene wastestedin amicro-reactor.Theoutlet gaswas measured using a Micro-GC. Finally, the coking amount on the catalyst surface was measured by thermogravimetry (TG). The results showed that ultrasonic treatment significanüy modified the pore size distribution of the catalysts especiallyin theporesize range of 10-50nm andalso improved the capability of the coke resistance. It's beneficial to increase the lifetime of the catalyst. Meanwhile, lower ultrasonic power(120W) was more favorableto improve the coke resistance of the catalyst in the power range tested (120 and 500W). The main surface reactions over Ni/γ-Al2O3 catalysts included two steps: Firstly, benzeneadsorbed on the catalyst surface, the metal active sites dehydrogenation took place, and the residual molecule fragments (coke precursor) wouldcondense further which led to coke formation.Then, CO2 reacted with coke precursor and coke for coke elimination. The first step carriedout very quickly, and the second step was the rate-determining step.To reduce the cokedeposition on the catalyst surface, the performance of CO2 adsorption and activation and surface oxygen transmission capacity should be improved further.

  7. Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale.

    Science.gov (United States)

    Girerd, Nicolas; Rabilloud, Muriel; Pibarot, Philippe; Mathieu, Patrick; Roy, Pascal

    2016-01-01

    In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events. The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery. The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged 70. The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification.

  8. Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale.

    Directory of Open Access Journals (Sweden)

    Nicolas Girerd

    Full Text Available In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events.The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery.The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05 whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61. The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged 70.The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification.

  9. Optimal vaccination and treatment of an epidemic network model

    Science.gov (United States)

    Chen, Lijuan; Sun, Jitao

    2014-08-01

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

  10. Modeling Patient Treatment With Medical Records: An Abstraction Hierarchy to Understand User Competencies and Needs.

    Science.gov (United States)

    St-Maurice, Justin D; Burns, Catherine M

    2017-07-28

    Health care is a complex sociotechnical system. Patient treatment is evolving and needs to incorporate the use of technology and new patient-centered treatment paradigms. Cognitive work analysis (CWA) is an effective framework for understanding complex systems, and work domain analysis (WDA) is useful for understanding complex ecologies. Although previous applications of CWA have described patient treatment, due to their scope of work patients were previously characterized as biomedical machines, rather than patient actors involved in their own care. An abstraction hierarchy that characterizes patients as beings with complex social values and priorities is needed. This can help better understand treatment in a modern approach to care. The purpose of this study was to perform a WDA to represent the treatment of patients with medical records. The methods to develop this model included the analysis of written texts and collaboration with subject matter experts. Our WDA represents the ecology through its functional purposes, abstract functions, generalized functions, physical functions, and physical forms. Compared with other work domain models, this model is able to articulate the nuanced balance between medical treatment, patient education, and limited health care resources. Concepts in the analysis were similar to the modeling choices of other WDAs but combined them in as a comprehensive, systematic, and contextual overview. The model is helpful to understand user competencies and needs. Future models could be developed to model the patient's domain and enable the exploration of the shared decision-making (SDM) paradigm. Our work domain model links treatment goals, decision-making constraints, and task workflows. This model can be used by system developers who would like to use ecological interface design (EID) to improve systems. Our hierarchy is the first in a future set that could explore new treatment paradigms. Future hierarchies could model the patient as a

  11. [Effectiveness of N-acetylcysteine in the treatment of schizophrenia].

    Science.gov (United States)

    Miyake, Nobumi; Miyamoto, Seiya

    2016-04-01

    Oxidative stress and neuroinflammation have recently been focused on the pathological hypotheses of schizophrenia. N-acetylcysteine (NAC) is a precursor of endogenous antioxidant glutathione and has antioxidant, anti-inflammatory, and neuroprotective properties. NAC is widely available as an over-the-counter nutritional supplement. Increasing lines of evidence suggest that NAC is effective for various mental disorders. In randomized controlled trials, treatment with NAC as an add-on to antipsychotics showed beneficial effects and safety profiles in patients with chronic schizophrenia. The results of a recent preclinical study using a neurodevelopmental model of schizophrenia suggest that NAC may have promising effects in an early stage of schizophrenia and an at-risk mental state. However, there is little clinical evidence for the efficacy and safety of NAC at these stages of schizophrenia. In this review, we summarize the evidence regarding the effectiveness of NAC for the treatment of schizophrenia and its prodromal stage. We also introduce the preliminary results of our research on NAC.

  12. Lasso adjustments of treatment effect estimates in randomized experiments.

    Science.gov (United States)

    Bloniarz, Adam; Liu, Hanzhong; Zhang, Cun-Hui; Sekhon, Jasjeet S; Yu, Bin

    2016-07-05

    We provide a principled way for investigators to analyze randomized experiments when the number of covariates is large. Investigators often use linear multivariate regression to analyze randomized experiments instead of simply reporting the difference of means between treatment and control groups. Their aim is to reduce the variance of the estimated treatment effect by adjusting for covariates. If there are a large number of covariates relative to the number of observations, regression may perform poorly because of overfitting. In such cases, the least absolute shrinkage and selection operator (Lasso) may be helpful. We study the resulting Lasso-based treatment effect estimator under the Neyman-Rubin model of randomized experiments. We present theoretical conditions that guarantee that the estimator is more efficient than the simple difference-of-means estimator, and we provide a conservative estimator of the asymptotic variance, which can yield tighter confidence intervals than the difference-of-means estimator. Simulation and data examples show that Lasso-based adjustment can be advantageous even when the number of covariates is less than the number of observations. Specifically, a variant using Lasso for selection and ordinary least squares (OLS) for estimation performs particularly well, and it chooses a smoothing parameter based on combined performance of Lasso and OLS.

  13. Deterministic treatment of model error in geophysical data assimilation

    CERN Document Server

    Carrassi, Alberto

    2015-01-01

    This chapter describes a novel approach for the treatment of model error in geophysical data assimilation. In this method, model error is treated as a deterministic process fully correlated in time. This allows for the derivation of the evolution equations for the relevant moments of the model error statistics required in data assimilation procedures, along with an approximation suitable for application to large numerical models typical of environmental science. In this contribution we first derive the equations for the model error dynamics in the general case, and then for the particular situation of parametric error. We show how this deterministic description of the model error can be incorporated in sequential and variational data assimilation procedures. A numerical comparison with standard methods is given using low-order dynamical systems, prototypes of atmospheric circulation, and a realistic soil model. The deterministic approach proves to be very competitive with only minor additional computational c...

  14. 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.

  15. 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.

  16. On the Treatment of Airline Travelers in Mathematical Models

    Science.gov (United States)

    Johansson, Michael A.; Arana-Vizcarrondo, Neysarí; Biggerstaff, Brad J.; Staples, J. Erin; Gallagher, Nancy; Marano, Nina

    2011-01-01

    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. PMID:21799782

  17. 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.

  18. Mixed Effects Models for Complex Data

    CERN Document Server

    Wu, Lang

    2009-01-01

    Presenting effective approaches to address missing data, measurement errors, censoring, and outliers in longitudinal data, this book covers linear, nonlinear, generalized linear, nonparametric, and semiparametric mixed effects models. It links each mixed effects model with the corresponding class of regression model for cross-sectional data and discusses computational strategies for likelihood estimations of mixed effects models. The author briefly describes generalized estimating equations methods and Bayesian mixed effects models and explains how to implement standard models using R and S-Pl

  19. Effect of treatment pressure on treatment quality and bending properties of red pine lumber

    Science.gov (United States)

    Patricia K. Lebow; Stan T. Lebow; William J. Nelson

    2010-01-01

    Although higher treatment pressures have the potential to improve preservative penetration, higher pressures may possibly result in greater reduction in mechanical properties. The present study evaluated the effect of treatment pressure on the treatment quality and mechanical properties of red pine (Pinus resinosa Ait.) lumber. End-matched sections of red pine lumber...

  20. Effects of Ultrasonic Treatment on Residue Properties

    Institute of Scientific and Technical Information of China (English)

    Sun Yudong; Zhang Qiang; Shi Honghong; Wang Xue; Liu Bo

    2013-01-01

    The changes in properties and structural parameters of four vacuum residue samples before and after ultrasonic treatment were analyzed. Ultrasonic treatment could increase the carbon residue value, decrease the average molecular weight and viscosity, which can barely inlfuence the density of vacuum residue. Meanwhile the constitution of residue can be varied including the decrease in the content of saturates, aromatics and asphaltenes, while the increase in the content of resins can lead to an increase in the total content of asphaltenes and resins. Among the four kinds of residue samples, there is a common trend that the more the content of asphaltenes in feedstock is, the more the increase in the content of resins, the more signiifcant decrease in the aromatic content and the less decrease in the saturates content after ultrasonic treatment of residue would be. Changes in the structure and content of asphaltenes caused by ultrasonic treatment have a signiifcant impact on the changes in residue properties. Ultrasonic treatment has changed the structural parameters of residue such as decrease in the total carbon number of average molecule (CTotal), the total number of rings (RT), the aromatic carbon number (CA),the aromatic rings number (RA) and the naphthenic rings number (RN) , and increase of characterization factor (KH). The study has indicated that ultrasonic treatment of vacuum residue can change the average structure of residue, and the changes in the content and structure of asphaltenes are the main cause leading to property changes. The results of residue hydrotreat-ing revealed that coke yield decreased, whereas the gas and light oil yield and conversion increased after ultrasonic treat-ment of vacuum residue.

  1. 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.

  2. Explanatory models of mental disorders and treatment practices ...

    African Journals Online (AJOL)

    Western medical services.11 This claim assumes that African ... healers' explanatory models (EMs) and treatment practices for psychotic and ... Traditional healers' views on the nature of the problem, cause, .... “The ancestors are trying to tell that person that ... that mentally ill people may lose their jobs, making them.

  3. A model for in utero endoscopic treatment of myelomeningocele.

    Science.gov (United States)

    Copeland, M L; Bruner, J P; Richards, W O; Sundell, H W; Tulipan, N B

    1993-09-01

    An animal model for intrauterine surgical treatment of myelomeningocele is described using sheep. We report the technical feasibility of endoscopic intrauterine skin graft placement over surgically induced defects, including over exposed spinal cord. These grafts exclude amniotic fluid from the underlying lesion and provide a matrix for fetal skin growth below the graft. The potential for human application is discussed.

  4. 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

    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...... 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....... the sensitive fraction of the commensal flora.Growth parameters for competing bacterial strains were estimated from the combined in vitro pharmacodynamic effect of two antimicrobials using the relationship between concentration and net bacterial growth rate. Predictions of in vivo bacterial growth were...

  5. Toy models for wrapping effects

    Science.gov (United States)

    Penedones, João; Vieira, Pedro

    2008-08-01

    The anomalous dimensions of local single trace gauge invariant operators in Script N = 4 supersymmetric Yang-Mills theory can be computed by diagonalizing a long range integrable Hamiltonian by means of a perturbative asymptotic Bethe ansatz. This formalism breaks down when the number of fields of the composite operator is smaller than the range of the Hamiltonian which coincides with the order in perturbation theory at study. We analyze two spin chain toy models which might shed some light on the physics behind these wrapping effects. One of them, the Hubbard model, is known to be closely related to Script N = 4 SYM. In this example, we find that the knowledge of the effective spin chain description is insufficient to reconstruct the finite size effects of the underlying electron theory. We compute the wrapping corrections for generic states and relate them to a Luscher like approach. The second toy models are long range integrable Hamiltonians built from the standard algebraic Bethe ansatz formalism. This construction is valid for any symmetry group. In particular, for non-compact groups it exhibits an interesting relation between wrapping interactions and transcendentality.

  6. Early onset of treatment effects with oral risperidone

    Directory of Open Access Journals (Sweden)

    Naber Dieter

    2007-01-01

    Full Text Available Abstract Background The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia. Methods In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14. Results Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore. Conclusion Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration.

  7. Explanatory models and mental health treatment: is vodou an obstacle to psychiatric treatment in rural Haiti?

    Science.gov (United States)

    Khoury, Nayla M; Kaiser, Bonnie N; Keys, Hunter M; Brewster, Aimee-Rika T; Kohrt, Brandon A

    2012-09-01

    Vodou as an explanatory framework for illness has been considered an impediment to biomedical psychiatric treatment in rural Haiti by some scholars and Haitian professionals. According to this perspective, attribution of mental illness to supernatural possession drives individuals to seek care from houngan-s (Vodou priests) and other folk practitioners, rather than physicians, psychologists, or psychiatrists. This study investigates whether explanatory models of mental illness invoking supernatural causation result in care-seeking from folk practitioners and resistance to biomedical treatment. The study comprised 31 semi-structured interviews with community leaders, traditional healers, religious leaders, and biomedical providers, 10 focus group discussions with community members, community health workers, health promoters, community leaders, and church members; and four in-depth case studies of individuals exhibiting mental illness symptoms conducted in Haiti's Central Plateau. Respondents invoked multiple explanatory models for mental illness and expressed willingness to receive treatment from both traditional and biomedical practitioners. Folk practitioners expressed a desire to collaborate with biomedical providers and often referred patients to hospitals. At the same time, respondents perceived the biomedical system as largely ineffective for treating mental health problems. Explanatory models rooted in Vodou ethnopsychology were not primary barriers to pursuing psychiatric treatment. Rather, structural factors including scarcity of treatment resources and lack of psychiatric training among health practitioners created the greatest impediments to biomedical care for mental health concerns in rural Haiti.

  8. Mathematical modeling of brain tumors: effects of radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Powathil, G [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1 (Canada); Kohandel, M [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1 (Canada); Sivaloganathan, S [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1 (Canada); Oza, A [Center for Mathematical Medicine, Fields Institute for Research in Mathematical Sciences, Toronto, Ontario M5T 3J1 (Canada); Milosevic, M [Radiation Medicine Program, Princess Margaret Hospital, and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada)

    2007-06-07

    Gliomas, the most common primary brain tumors, are diffusive and highly invasive. The standard treatment for brain tumors consists of a combination of surgery, radiation therapy and chemotherapy. Over the past few years, mathematical models have been applied to study untreated and treated brain tumors. In an effort to improve treatment strategies, we consider a simple spatio-temporal mathematical model, based on proliferation and diffusion, that incorporates the effects of radiotherapeutic and chemotherapeutic treatments. We study the effects of different schedules of radiation therapy, including fractionated and hyperfractionated external beam radiotherapy, using a generalized linear quadratic (LQ) model. The results are compared with published clinical data. We also discuss the results for combination therapy (radiotherapy plus temozolomide, a new chemotherapy agent), as proposed in recent clinical trials. We use the model to predict optimal sequencing of the postoperative (combination of radiotherapy and adjuvant, neo-adjuvant or concurrent chemotherapy) treatments for brain tumors.

  9. 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.

  10. Mathematical modeling of genesis and treatment of chronic myeloid leukemia.

    Science.gov (United States)

    Horn, Matthias; Loeffler, Markus; Roeder, Ingo

    2008-01-01

    Chronic myeloid leukemia (CML) is a clonal hematopoietic disorder induced by translocation of chromosomes 9 and 22, resulting in an overproduction of myeloid blood cells. CML-specific characteristics include a latency time of several years, a period of coexistence of malignant and normal cells and an eventual dominance of the malignant clone. Different drug therapies are available, most notably imatinib, which inhibits the oncogenic BCR-ABL1 tyrosine kinase. Although the chromosomal aberration causing CML is well known, the resulting dynamic effects on the system behavior are not sufficiently understood yet. Here, we apply an already established mathematical model of hematopoietic stem cell organization. Based on parameter estimates for normal hematopoiesis, we systematically explore the changes in these parameters necessary to reproduce CML-specific characteristics regarding emergence and course of disease as well as a variety of qualitative and quantitative clinical data on CML treatment. Our results indicate that 1 or more of the following mechanisms are compatible with the induction of a dominant clone in the proposed model: a retarded differentiation process, a reduced turnover time or a defective cell-microenvironment interaction of the neoplastic cells. However, in order to explain the massive overproduction of malignant cells, an unregulated and abnormal activation of leukemia stem cells into cycle has to be assumed additionally. Based on our simulation results we conclude that CML dynamics can most appropriately be explained by a modulation of the cell-microenvironment interactions of leukemia stem cells, including both the process of stem cell silencing and activation into cycle.

  11. Effect of presowing magnetic treatment on properties of pea

    Science.gov (United States)

    Iqbal, M.; Haq, Z. U.; Jamil, Y.; Ahmad, M. R.

    2012-02-01

    The pea seeds were exposed to full-wave rectified sinusoidal magnetic fields. The effects of electromagnetic treatment on seedling growth and chlorophyll contents and have been investigated. Seed were sown after magnetic field treatment according to ISTA under controlled laboratory conditions. The magnetic filed treatment of seeds increased the growth significantly (Pmagnetic field could be used to enhance the growth in pea plant.

  12. Hepatic late adverse effects after antineoplastic treatment for childhood cancer

    NARCIS (Netherlands)

    Mulder, Renee L.; van Dalen, Elvira C.; Van den Hof, Malon; Bresters, Dorine; Koot, Bart G. P.; Castellino, Sharon M.; Loke, Yoon; Leclercq, Edith; Post, Piet N.; Caron, Huib N.; Postma, Aleida; Kremer, Leontien C. M.

    2011-01-01

    Background Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood ca

  13. Two models of suicide treatment: evaluation and recommendations.

    Science.gov (United States)

    Pulakos, J

    1993-01-01

    Treating suicidal patients is one of the most stressful aspects of psychotherapeutic work. This paper describes and evaluates two models of therapy with suicidal patients. The crisis-intervention model, which assumes suicidal feelings are acute and suicide is preventable; and the continuing-therapy model, which emphasizes chronic suicidal feelings and posits that suicide is not preventable. Ethical and legal issues as well as treatment strategies from each model are described. Both therapy models stress the importance of assessing, understanding, and validating the patient's feelings as well as establishing a good therapeutic relationship. The crisis intervention model recommends an active, directive intervention while the continuing therapy model emphasizes ongoing therapy principles. After reviewing the different models, this article concludes that the assumptions of the crisis-intervention model are not supported while those of the continuing-therapy model are. In addition, it is concluded that there are more therapeutic advantages to employing the continuing-therapy model. These include taking short-term risks to acquire long-term gain, treating the patient as a responsible adult and seeing the suicidal behavior in the context of the total personality.

  14. Treatment of food anaphylaxis with traditional Chinese herbal remedies: from mouse model to human clinical trials.

    Science.gov (United States)

    Wang, Julie

    2013-08-01

    To describe the development of a novel treatment for food allergy, named the food allergy herbal formula-2 (FAHF-2), that is based on traditional Chinese medicine. FAHF-2 has proven to be well tolerated and effective for the treatment of food allergies in murine models of peanut and multiple food allergies. These results are accompanied by evidence of favorable immune modulation, and the effects are persistent after the discontinuation of treatment. Early clinical trials demonstrate the safety and tolerability of this formula in individuals with food allergies. An ongoing Phase II clinical trial will evaluate the efficacy of FAHF-2 in protecting individuals from allergen-induced allergic reactions during oral food challenges. FAHF-2 is an herbal formula that has a high safety profile and has shown to prevent anaphylaxis in murine models of food allergy. Similar findings in clinical trials could bring a novel treatment for food allergies.

  15. 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-typ...

  16. 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.

  17. 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...

  18. Musical hallucinations : review of treatment effects

    NARCIS (Netherlands)

    Coebergh, Jan A F; Lauw, R F; Bots, R; Sommer, I E C; Blom, J D

    2015-01-01

    BACKGROUND: Despite an increased scientific interest in musical hallucinations over the past 25 years, treatment protocols are still lacking. This may well be due to the fact that musical hallucinations have multiple causes, and that published cases are relatively rare. OBJECTIVE: To review the effe

  19. Musical hallucinations : review of treatment effects

    NARCIS (Netherlands)

    Coebergh, Jan A. F.; Lauw, R. F.; Bots, R.; Sommer, I. E. C.; Blom, J. D.

    2015-01-01

    Background: Despite an increased scientific interest in musical hallucinations over the past 25 years, treatment protocols are still lacking. This may well be due to the fact that musical hallucinations have multiple causes, and that published cases are relatively rare. Objective: To review the effe

  20. Effect of aspirin treatment on chondromalacia patellae.

    Science.gov (United States)

    Bentley, G; Leslie, I J; Fischer, D

    1981-01-01

    Twenty-nine patients (21 females and 8 males) with chondromalacia patellae diagnosed by arthroscopy were randomly allocated to receive aspirin or placebo for 3 months. Clinical and arthroscopic examination after 3 months showed no significant change in symptoms, signs, or macroscopic appearances in either group. Surgical treatment was performed in 14 patients for deteriorating symptoms. Images PMID:7008711

  1. Effect of cyanoacrylate treatment of cavity walls.

    Science.gov (United States)

    Fukushi, Y; Fusayama, T

    1980-04-01

    Cyanoacrylate treatment of the cavity wall for composite resin restoration failed to keep adhesion when set, but the marginal closure improved markedly both in vivo and vitro, even when thermal-cycled. It irritated the pulp slightly only at the beginning. Ethylcyanoacrylate was superior to methylcyanoacrylate in regard to adhesion, leakage and pulp response.

  2. 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. Interv

  3. 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

  4. Cognitive effects of olanzapine treatment in schizophrenia.

    Science.gov (United States)

    McGurk, Susan R; Lee, M A; Jayathilake, K; Meltzer, Herbert Y

    2004-05-10

    Improvement in some but not all domains of cognition during treatment with the atypical antipsychotic drugs clozapine, quetiapine, olanzapine, and risperidone has been reported in some but not all studies. It has been recently suggested that these reports are an artifact, related to lessening of the impairment due to typical neuroleptic drugs and anticholinergic agents. The purpose of this study was to further test the hypothesis that olanzapine, an atypical antipsychotic drug reported to have anticholinergic properties, improves cognition in patients with schizophrenia, including domains of cognition related closely to work and social function (ie, verbal learning and memory) and that this improvement is independent of improvement in psychopathology. Thirty-four patients with schizophrenia who were partial responders to typical antipsychotic drug treatment were evaluated with a comprehensive neurocognitive battery, including measures of executive functioning; verbal and visual learning and memory; working memory; immediate, selective, and sustained attention; perceptual/motor processing; and motor skills prior to and following treatment with olanzapine for 6 weeks. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology in patients treated with typical antipsychotic drugs. Subjects were switched to olanzapine (average dose 13.4 mg, range 5-20 mg) and reassessed following 6 weeks and 6 months of treatment. Significant improvement was noted in 9 of 19 cognitive tests, including measures of selective attention, verbal learning and memory, and verbal fluency. No cognitive test was worsened by olanzapine treatment. Improvements in the BPRS Total and Positive Symptom Subscale scores were noted. Improvements in verbal learning and memory, sustained attention, and psychomotor tracking were independent of improvement in psychopathology. These data suggest that olanzapine improved some but not all cognitive deficits in schizophrenia, including verbal

  5. 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 are obtai......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...... then propose a new heteroskedasticity consistent standard error formula that is fully automatic and robust to both (conditional) heteroskedasticity of unknown form and the inclusion of possibly many covariates. We apply our findings to three settings: (i) parametric linear models with many covariates, (ii...

  6. 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.

  7. 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.

  8. Treatment of non-ideality in the SPACCIM multiphase model - Part 1: Model development

    Science.gov (United States)

    Rusumdar, A. J.; Wolke, R.; Tilgner, A.; Herrmann, H.

    2016-01-01

    Ambient tropospheric deliquesced particles generally comprise a complex mixture of electrolytes, organic compounds, and water. Dynamic modeling of physical and chemical processes in this complex matrix is challenging. Thus, up-to-date multiphase chemistry models generally do not consider non-ideal solution effects. Therefore, the present study was aimed at presenting further development of the SPACCIM (Spectral Aerosol Cloud Chemistry Interaction Model) through treatment of solution non-ideality, which has not been considered before. The present paper firstly describes the model developments including (i) the implementation of solution non-ideality in aqueous-phase reaction kinetics in the SPACCIM framework, (ii) the advancements in the coupling scheme of microphysics and multiphase chemistry and (iii) the required adjustments of the numerical schemes, especially in the sparse linear solver and the calculation of the Jacobian. Secondly, results of sensitivity investigations are outlined, aiming at the evaluation of different activity coefficient modules and the examination of the contributions of different intermolecular forces to the overall activity coefficients. Finally, first results obtained with the new model framework are presented. The SPACCIM parcel model was developed and, so far, applied for the description of aerosol-cloud interactions. To advance SPACCIM also for modeling physical and chemical processes in deliquesced particles, the solution non-ideality has to be taken into account by utilizing activities in reaction terms instead of aqueous concentrations. The main goal of the extended approach was to provide appropriate activity coefficients for solved species. Therefore, an activity coefficient module was incorporated into the kinetic model framework of SPACCIM. Based on an intercomparison of different activity coefficient models and the comparison with experimental data, the AIOMFAC approach was implemented and extended by additional interaction

  9. Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models

    Science.gov (United States)

    van der Wijk, Lars; Proost, Johannes H.; Sinha, Bhanu; Touw, Daan J.

    2017-01-01

    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 avoid

  10. 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.

  11. Stochastic modeling to identify requirements for centralized monitoring of distributed wastewater treatment.

    Science.gov (United States)

    Hug, T; Maurer, M

    2012-01-01

    Distributed (decentralized) wastewater treatment can, in many situations, be a valuable alternative to a centralized sewer network and wastewater treatment plant. However, it is critical for its acceptance whether the same overall treatment performance can be achieved without on-site staff, and whether its performance can be measured. In this paper we argue and illustrate that the system performance depends not only on the design performance and reliability of the individual treatment units, but also significantly on the monitoring scheme, i.e. on the reliability of the process information. For this purpose, we present a simple model of a fleet of identical treatment units. Thereby, their performance depends on four stochastic variables: the reliability of the treatment unit, the respond time for the repair of failed units, the reliability of on-line sensors, and the frequency of routine inspections. The simulated scenarios show a significant difference between the true performance and the observations by the sensors and inspections. The results also illustrate the trade-off between investing in reactor and sensor technology and in human interventions in order to achieve a certain target performance. Modeling can quantify such effects and thereby support the identification of requirements for the centralized monitoring of distributed treatment units. The model approach is generic and can be extended and applied to various distributed wastewater treatment technologies and contexts.

  12. Assessment of Antimicrobial Treatment Strategies in Pig Production Using Mathematical Models

    DEFF Research Database (Denmark)

    Ahmad, Amais

    strategies. Dosing factors, along with the in vivo epidemiological parameters, govern the relation between resistance and antimicrobial use. Mathematical modeling and simulation techniques have been used over the past two decades to evaluate the effect of these factors on the development of resistance......, and are considered to be powerful tools in designing treatment strategies. The overall aim of the thesis was to develop an in vivo bacterial growth model to predict and assess the effect of dosing factor on resistance growth in order to optimize treatment strategies. Specific aims were to a) estimate pharmacodynamic...... (PD) parameters of E. coli strains representative of the Danish porcine E. coli strains, when these are exposed to tetracycline and ampicillin, b) characterize the PD effect of combined concentrations of tetracycline and ampicillin, and c) evaluate the treatment strategies that better suppress...

  13. Geometric treatment of the gravitomagnetic clock effect

    CERN Document Server

    Tartaglia, A

    2000-01-01

    We have developed a general geometric treatment of the GCE valid for any stationary axisymmetric metric. The method is based on the remark that the world lines of objects rotating along spacely circular trajectories are in any case, for those kind of metrics, helices drawn on the flat bidimensional surface of a cylinder. Applying the obtained formulas to the special cases of the Kerr and weak field metric for a spinning body, known results for time delays and synchrony defects are recovered.

  14. Invisalign: current guidelines for effective treatment.

    Science.gov (United States)

    Kuncio, Daniel A

    2014-03-01

    Invisalign is an increasingly popular technique for aligning teeth and correcting malocclusions orthodontically. This article analyzes the current professional literature published on Invisalign and the benefits and risks of using the technique for both patients and doctors. The steady increase in the number of cases treated with Invisalign and where the technique is going in the future is investigated. Ten guidelines for Invisalign treatment and patient selection are given, along with case examples.

  15. 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.

  16. 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.

  17. Mechanical effects in cookoff modeling

    Energy Technology Data Exchange (ETDEWEB)

    Gross, R.J.; Baer, M.R.; Hobbs, M.L.

    1994-07-01

    Complete cookoff modeling of energetic material in confined geometries must couple thermal, chemical and mechanical effects. In the past, modeling has focused on the prediction of the onset of combustion behavior based only on thermal-chemistry effects with little or no regard to the mechanical behavior of the energetic material. In this paper, an analysis tool is outlined which couples thermal, chemical, and mechanical behavior for one-dimensional Geometries comprised of multi-materials. A reactive heat flow code, XCHEM, and a quasistatic mechanics code, SANTOS, have been completely coupled using, a reactive, elastic-plastic constitutive model describing pressurization of the energetic material. This new Thermally Reactive Elastic-plastic explosive code, TREX, was developed to assess the coupling, of mechanics with thermal chemistry making multidimensional cookoff analysis possible. In this study, TREX is applied to confined and unconfined systems. The confined systems simulate One-Dimensional Time to explosion (ODTX) experiments in both spherical and cylindrical configurations. The spherical ODTX system is a 1.27 cm diameter sphere of TATB confined by aluminum exposed to a constant external temperature. The cylindrical ODTX system is an aluminum tube filled with HMX, NC, and inert exposed to a constant temperature bath. Finally. an unconfined system consisting of a hollow steel cylinder filled with a propellant composed of Al, RMX, and NC, representative of a rocket motor, is considered. This model system is subjected to transient internal and external radiative/convective boundary conditions representative of 5 minutes exposure to a fire. The confined systems show significant pressure prior to ignition, and the unconfined system shows extrusion of the propellent suggesting that the energetic material becomes more shock sensitive.

  18. BCG-mediated bladder cancer immunotherapy: identifying determinants of treatment response using a calibrated mathematical model.

    Science.gov (United States)

    Rentsch, Cyrill A; Biot, Claire; Gsponer, Joël R; Bachmann, Alexander; Albert, Matthew L; Breban, Romulus

    2013-01-01

    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.

  19. A Theory-Based Treatment Model for Psychopathy

    Science.gov (United States)

    Wallace, John F.; Newman, Joseph P.

    2004-01-01

    The most salient characteristic of the psychopath is the propensity to engage in maladaptive and inappropriate behavior of all sorts, including antisocial and criminal actions. Consequently, there is considerable interest--particularly in the field of criminology--in determining what sorts of treatment interventions are likely to be effective in…

  20. A Theory-Based Treatment Model for Psychopathy

    Science.gov (United States)

    Wallace, John F.; Newman, Joseph P.

    2004-01-01

    The most salient characteristic of the psychopath is the propensity to engage in maladaptive and inappropriate behavior of all sorts, including antisocial and criminal actions. Consequently, there is considerable interest--particularly in the field of criminology--in determining what sorts of treatment interventions are likely to be effective in…

  1. Effect of thermal treatments on arsenic species contents in food.

    Science.gov (United States)

    Devesa, V; Vélez, D; Montoro, R

    2008-01-01

    In arsenic-endemic and other areas, food is an important path of exposure to this contaminant. Food is generally consumed in processed form, after a preservation treatment or cooking, which may alter the concentrations and chemical forms of arsenic. This article summarizes and discusses the work so far published on the effect that thermal treatment used in the cooking or processing of food, including sterilization and preservation stages, has on total arsenic and arsenic species contents. It also reviews possible transformations in arsenic species. The studies included use model systems or food products of marine or vegetable origin. Processing may cause a considerable increase or decrease in the real arsenic intake from food. For example, traditional washing and soaking of Hizikia fusiforme seaweed, which has very high inorganic arsenic contents, may reduce the contents by up to 60%. On the other hand, all the arsenic present in cooking water may be retained during boiling of rice, increasing the contents of this metalloid to significant levels from a toxicological viewpoint. This calls for modifications in arsenic risk assessment, hitherto based on analysis of the raw product. It is necessary to consider the effect of processing on total arsenic and arsenical species in order to obtain a realistic view of the risk associated with intake in arsenic-endemic and other areas.

  2. Explanatory models of depression and treatment adherence to antidepressant medication

    DEFF Research Database (Denmark)

    Buus, Niels; Johannessen, Helle; Stage, Kurt Bjerregaard

    2012-01-01

    BACKGROUND: Adherence to antidepressant medication is a challenging clinical issue, which reduces treatment efficacy: 30-60% of all patients commencing treatment with antidepressants are estimated to stop taking the medication within the first 12 weeks. Patients' personal beliefs about depression...... analysed thematically with "explanatory models" as the starting point. RESULTS: Patients had ambiguous experiences of depression and antidepressants. Patients explained their illness and the medical treatment in experience-near terms. Explanations of the reasons for depression were psychosocial and biology...... and antidepressants are regarded as central influences on adherence. OBJECTIVES: The aim was to gain detailed insight into patients' personal accounts of depression and use of antidepressant medication and to relate these accounts to the patients' self-reported level of adherence. METHODS: In-depth, qualitative...

  3. Alcoholics Anonymous and the Minnesota Model of treatment in Iceland.

    Science.gov (United States)

    McMenamin, Daniel; Warren, Matthew; Tyrfingsson, Thornorarinn; Hansdóttir, Ingunn; Dermatis, Helen; Galanter, Marc; McMahon, Caitlin

    2011-01-01

    This study was undertaken to provide an initial characterization of the current status of patients admitted to an alcoholism treatment program in Iceland. Consistent with the Minnesota Model, 12-step facilitation has been a central component of the program since its inception. Of the 94 patients assessed in this study, 67% were male and 40% had attended over 90 AA meetings prior to admission. The mean number of drinking days during the month prior to admission was 15.51 days and the mean length of hospital stay was 12.32 days. At time of hospital discharge, 39% were referred to residential treatment. Significant predictors of referral to residential treatment included having attended less than 90 AA meetings prior to admission and length of stay.

  4. The effect of treatment history on therapeutic outcome: psychological and neurobiological underpinnings.

    Directory of Open Access Journals (Sweden)

    Simon Kessner

    Full Text Available It is increasingly recognized that the efficacy of medical treatments is determined in critical part by the therapeutic context in which it is delivered. An important characteristic of that context is treatment history. We recently reported first evidence for a carry-over of treatment experience to subsequent treatment response across different treatment approaches. Here we expand on these findings by exploring the psychological and neurobiological underpinnings of the effect of treatment experience on future treatment response in an experimental model of placebo analgesia with a conditioning procedure. In a combined behavioral and neuroimaging study we experimentally induced positive or negative experiences with an analgesic treatment in two groups of healthy human subjects. Subsequently we compared responses to a second, different analgesic treatment between both groups. We found that participants with an experimentally induced negative experience with the first treatment showed a substantially reduced response to a second analgesic treatment. Intriguingly, several psychological trait variables including anxiety, depression and locus of control modulate the susceptibility for the effects of prior treatment experiences on future treatment outcome. These behavioral effects were supported by neuroimaging data which showed significant differences in brain regions encoding pain and analgesia between groups. These differences in activation patterns were present not only during the pain phase, but also already prior to painful stimulation and scaled with the individual treatment response. Our data provide behavioral and neurobiological evidence showing that the influence of treatment history transfers over time and over therapeutic approaches. Our experimental findings emphasize the careful consideration of treatment history and a strictly systematic treatment approach to avoid negative carry-over effects.

  5. 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.

  6. 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.

  7. Skeletal metastasis: treatments, mouse models,and the Wnt signaling

    Institute of Scientific and Technical Information of China (English)

    Kenneth C.Valkenburg; Matthew R.Steensma; Bart O.Williams; Zhendong Zhong

    2013-01-01

    Skeletal metastases result in significant morbidity and mortality.This is particularly true of cancers with a strong predilection for the bone,such as breast,prostate,and lung cancers.There is currently no reliable cure for skeletal metastasis,and palliative therapy options are limited.The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target.Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments.In this review,we discuss pathologic process of bone metastasis,the roles of the Wnt signaling,and the available experimental models and treatments.

  8. Scientific and conceptual flaws of coercive treatment models in addiction.

    Science.gov (United States)

    Uusitalo, Susanne; van der Eijk, Yvette

    2016-01-01

    In conceptual debates on addiction, neurobiological research has been used to support the idea that addicted drug users lack control over their addiction-related actions. In some interpretations, this has led to coercive treatment models, in which, the purpose is to 'restore' control. However, neurobiological studies that go beyond what is typically presented in conceptual debates paint a different story. In particular, they indicate that though addiction has neurobiological manifestations that make the addictive behaviour difficult to control, it is possible for individuals to reverse these manifestations through their own efforts. Thus, addicted individuals should not be considered incapable of making choices voluntarily, simply on the basis that addiction has neurobiological manifestations, and coercive treatment models of addiction should be reconsidered in this respect.

  9. 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 sta

  10. Reverse translation of failed treatments can help improving the validity of preclinical animal models

    NARCIS (Netherlands)

    't Hart, Bert A.

    2015-01-01

    A major challenge in translational research is to reduce the currently high proportion of new candidate treatment agents for neuroinflammatory disease, which fail to reproduce promising effects observed in animal models when tested in patients. This disturbing situation has raised criticism against

  11. Pioglitazone treatment restores in vivo muscle oxidative capacity in a rat model of diabetes

    NARCIS (Netherlands)

    Wessels, B.; Ciapaite, J.; van den Broek, N. M. A.; Houten, S. M.; Nicolay, K.; Prompers, J. J.

    2015-01-01

    Aim: To determine the effect of pioglitazone treatment on in vivo and ex vivo muscle mitochondrial function in a rat model of diabetes. Methods: Both the lean, healthy rats and the obese, diabetic rats are Zucker Diabetic Fatty (ZDF) rats. The homozygous fa/fa ZDF rats are obese and diabetic. The he

  12. Development of an odorant emission model for sewage treatment works.

    Science.gov (United States)

    Gostelow, P; Parsons, S A; Cobb, J

    2001-01-01

    In the field of odour assessment, much attention has been paid to the measurement of odour concentration. Whilst the concentration of an odour at a receptor is a useful indicator of annoyance, the concentration at the source tells only half the story. The emission rate - the product of odour concentration and air flow rate - is required to appreciate the significance of odour sources. Knowledge of emission rates allows odour sources to be ranked in terms of significance and facilitates appropriate selection and design of odour control units. The emission rate is also a key input for atmospheric dispersion models. Given the increasing importance of odour to sewage treatment works operators, there is a clear need for predictive methods for odour emission rates. Theory suggests that the emission of odorants from sewage to air is controlled by mass transfer resistances in both the gas and liquid phase. These are in turn controlled by odorant and emission source characteristics. The required odorant characteristics are largely known, and mass transfer from many different types of emission sources have been studied. Sewage treatment processes can be described by one or more of six characteristic emission sources, these being quiescent surfaces, channels, weirs and drop structures, diffused aeration, surface aeration and flow over media. This paper describes the development of odorant mass transfer models for these characteristic emission types. The models have been applied in the form of spreadsheet models to the prediction of H2S emissions and the results compared with commercial VOC emission models.

  13. 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.

  14. Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer's Disease Mouse Model.

    Science.gov (United States)

    Manousopoulou, Antigoni; Saito, Satoshi; Yamamoto, Yumi; Al-Daghri, Nasser M; Ihara, Masafumi; Carare, Roxana O; Garbis, Spiros D

    2016-01-01

    The aim of this study was to examine hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer's disease mouse model using cilostazol as a chemical stimulus. Eight-month-old mice were assigned to vehicle or cilostazol treatment for three months and hemispheres were analyzed using quantitative proteomics. Bioinformatics interpretation showed that following treatment, aggregation of blood platelets significantly decreased in the right hemisphere whereas neurodegeneration significantly decreased and synaptic transmission increased in the left hemisphere only. Our study provides novel evidence on cerebral laterality of pharmacologic activity, with important implications in deciphering regional pharmacodynamic effects of existing drugs thus uncovering novel hemisphere-specific therapeutic targets.

  15. 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

  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. Regulatory odour model development: Survey of modelling tools and datasets with focus on building effects

    DEFF Research Database (Denmark)

    Olesen, H. R.; Løfstrøm, P.; Berkowicz, R.;

    dispersion models for estimating local concentration levels in general. However, the report focuses on some particular issues, which are relevant for subsequent work on odour due to animal production. An issue of primary concern is the effect that buildings (stables) have on flow and dispersion. The handling...... of building effects is a complicated problem, and a major part of the report is devoted to the treatment of building effects in dispersion models...

  18. Mathematical Model of ComputerHeat Treatment and Its Simulation

    Institute of Scientific and Technical Information of China (English)

    PanJiansheng; ZhangWeimin; TianDong; GuJianfeng; HuMingjuan

    2004-01-01

    Computer simulation on heat treatment is the foundation of intelligent heat treatment. The simulations of temperature field,phase transformation, stress/strain complicate quenching operation were realized by using the model of three dimensional non-linear finite element method and the treatment methods of abruptly changing interface conditions. The simulation results basically fit those measured in experiments. The intelligent sealed multipurpose furnace production line has been developed based on the combination of computer simulation on gaseous carburizing and computer control technology. More than 3000 batches of workpieces have been processed on this production line, and all are up to standard. The application of computer simulation technology can significantly improve the loading ability and reliability of nitriding and carburizing workpieces, reduce heat treatment distortion, and shorten carburizing duration. It is recommended that the reliable product design without redundancy should be performed with the combination of the CAD of mechanical products, the CAE of materials selection and heat treatment, and the dynamic evaluation technology of product reliability.

  19. Screening, prevention and treatment of cervical cancer -- a global and regional generalized cost-effectiveness analysis.

    Science.gov (United States)

    Ginsberg, Gary Michael; Edejer, Tessa Tan-Torres; Lauer, Jeremy A; Sepulveda, Cecilia

    2009-10-09

    The paper calculates regional generalized cost-effectiveness estimates of screening, prevention, treatment and combined interventions for cervical cancer. Using standardised WHO-CHOICE methodology, a cervical cancer model was employed to provide estimates of screening, vaccination 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. In regions characterized by high income, low mortality and high existing treatment coverage, the addition of any screening programme to the current high treatment levels is very cost-effective. However, based on projections of the future price per dose (representing the economic costs of the vaccination excluding monopolistic rents and vaccine development cost) vaccination is the most cost-effective intervention. In regions characterized by low income, low mortality and existing treatment coverage around 50%, expanding treatment with or without combining it with screening appears to be cost-effective or very cost-effective. Abandoning treatment in favour of screening in a no-treatment scenario would not be cost-effective. Vaccination is usually the most cost-effective intervention. Penta or tri-annual PAP smears appear to be cost-effective, though when combined with HPV-DNA testing they are not cost-effective. In regions characterized by low income, high mortality and low treatment levels, expanding treatment with or without adding screening would be very cost-effective. A one off vaccination plus expanding treatment was usually very cost-effective. One-off PAP or VIA screening at age 40 are more cost-effective than other interventions though less effective overall. From a cost-effectiveness perspective, consideration should be given to implementing

  20. Logging on for Better Sleep: RCT of the Effectiveness of Online Treatment for Insomnia

    Science.gov (United States)

    Vincent, Norah; Lewycky, Samantha

    2009-01-01

    Study Objectives: Despite effective cognitive behavioral treatments for chronic insomnia, such treatments are underutilized.1,2 This study evaluated the impact of a 5-week, online treatment for insomnia. Design: This was a randomized controlled trial with online treatment and waiting list control conditions. Participants: Participants were 118 adults with chronic insomnia. Setting: Participants received online treatment from their homes. Intervention: Online treatment consisted of psychoeducation, sleep hygiene, and stimulus control instruction, sleep restriction treatment, relaxation training, cognitive therapy, and help with medication tapering. Measurements and Results: From pre- to post-treatment, there was a 33% attrition rate, and attrition was related to referral status (i.e., drop-outs were more likely to have been referred for treatment rather than recruited from the community). Using a mixed model analysis of variance procedure (ANOVA), results showed that online treatment produced statistically significant improvements in the primary end points of sleep quality, insomnia severity, and daytime fatigue. Online treatment also produced significant changes in process variables of pre-sleep cognitive arousal and dysfunctional beliefs about sleep. Conclusions: Implications of these findings are that identification of who most benefits from online treatment is a worthy area of future study. Citation: Vincent N; Lewycky S. Logging on for better sleep: RCT of the effectiveness of online treatment for insomnia. SLEEP 2009;32(6):807-815. PMID:19544758

  1. 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.

  2. Infantile pyknocytosis: effectiveness of erythropoietin treatment

    Directory of Open Access Journals (Sweden)

    Eleonora Buzzi

    2013-04-01

    Full Text Available Infantile pyknocytosis is a rare form of neonatal haemolytic anaemia with unusual red cell morphology. Anaemia is mostly severe and red blood cells transfusion is often needed. In this report, we have described a male child aged 10 days, born at 37 weeks + 3 days, who presented neonatal jaundice and severe anaemia. After a careful peripheral blood smear examination, infantile pyknocytosis was diagnosed. A treatment with recombinant subcutaneous erythropoietin (1,000 UI/prokg/week in conjunction with iron supplementation (6 mg/kg/day was started. The therapy was reduced 6 weeks after the beginning and discontinued 4 weeks after the reaching of a steady state of the haemoglobin values. After 12 months of follow up, the patient showed no anaemia and pyknocytosis.

  3. Effectiveness of the Treatment Readiness and Induction Program for increasing adolescent motivation for change.

    Science.gov (United States)

    Becan, Jennifer E; Knight, Danica K; Crawley, Rachel D; Joe, George W; Flynn, Patrick M

    2015-03-01

    Success in substance abuse treatment is improved by problem recognition, desire to seek help, and readiness to engage in treatment, all of which are important aspects of motivation. Interventions that facilitate these at treatment induction for adolescents are especially needed. The purpose of this study is to assess the effectiveness of TRIP (Treatment Readiness and Induction Program) in promoting treatment motivation. Data represent 519 adolescents from 6 residential programs who completed assessments at treatment intake (time 1) and 35 days after admission (time 2). The design consisted of a comparison sample (n=281) that had enrolled in treatment prior to implementation of TRIP (standard operating practice) and a sample of clients that had entered treatment after TRIP began and received standard operating practice enhanced by TRIP (n=238). Repeated measures ANCOVAs were conducted using each time 2 motivation scale as a dependent measure. Motivation scales were conceptualized as representing sequential stages of change. LISREL was used to test a structural model involving TRIP participation, gender, drug use severity, juvenile justice involvement, age, race-ethnicity, prior treatment, and urgency as predictors of the stages of treatment motivation. Compared to standard practice, adolescents receiving TRIP demonstrated greater gains in problem recognition, even after controlling for the other variables in the model. The model fit was adequate, with TRIP directly affecting problem recognition and indirectly affecting later stages of change (desire for help and treatment readiness). Future studies should examine which specific components of TRIP affect change in motivation.

  4. Effectiveness of the Treatment Readiness and Induction Program for Increasing Adolescent Motivation for Change

    Science.gov (United States)

    Becan, Jennifer E.; Knight, Danica K.; Crawley, Rachel D.; Joe, George W.; Flynn, Patrick M.

    2014-01-01

    Success in substance abuse treatment is improved by problem recognition, desire to seek help, and readiness to engage in treatment, all of which are important aspects of motivation. Interventions that facilitate these at treatment induction for adolescents are especially needed. The purpose of this study is to assess the effectiveness of TRIP (Treatment Readiness and Induction Program) in promoting treatment motivation. Data represent 519 adolescents from 6 residential programs who completed assessments at treatment intake (Time 1) and 35 days after admission (Time 2). The design consisted of a comparison sample (n = 281) that had enrolled in treatment prior to implementation of TRIP (standard operating practice) and a sample of clients that had entered treatment after TRIP began and received standard operating practice enhanced by TRIP (n = 238). Repeated measures ANCOVAs were conducted using each Time 2 motivation scale as a dependent measure. Motivation scales were conceptualized as representing sequential stages of change. LISREL was used to test a structural model involving TRIP participation, gender, drug use severity, juvenile justice involvement, age, race-ethnicity, prior treatment, and urgency as predictors of the stages of treatment motivation. Compared to standard practice, adolescents receiving TRIP demonstrated greater gains in problem recognition, even after controlling for the other variables in the model. The model fit was adequate, with TRIP directly affecting problem recognition and indirectly affecting later stages of change (desire for help and treatment readiness). Future studies should examine which specific components of TRIP affect change in motivation. PMID:25456094

  5. HIV treatment as prevention: modelling the cost of antiretroviral treatment--state of the art and future directions.

    Directory of Open Access Journals (Sweden)

    Gesine Meyer-Rath

    Full Text Available Policy discussions about the feasibility of massively scaling up antiretroviral therapy (ART to reduce HIV transmission and incidence hinge on accurately projecting the cost of such scale-up in comparison to the benefits from reduced HIV incidence and mortality. We review the available literature on modelled estimates of the cost of providing ART to different populations around the world, and suggest alternative methods of characterising cost when modelling several decades into the future. In past economic analyses of ART provision, costs were often assumed to vary by disease stage and treatment regimen, but for treatment as prevention, in particular, most analyses assume a uniform cost per patient. This approach disregards variables that can affect unit cost, such as differences in factor prices (i.e., the prices of supplies and services and the scale and scope of operations (i.e., the sizes and types of facilities providing ART. We discuss several of these variables, and then present a worked example of a flexible cost function used to determine the effect of scale on the cost of a proposed scale-up of treatment as prevention in South Africa. Adjusting previously estimated costs of universal testing and treatment in South Africa for diseconomies of small scale, i.e., more patients being treated in smaller facilities, adds 42% to the expected future cost of the intervention.

  6. 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.

  7. Impact of Generic Alendronate Cost on the Cost-Effectiveness of Osteoporosis Screening and Treatment

    OpenAIRE

    Smita Nayak; Roberts, Mark S.; Greenspan, Susan L.

    2012-01-01

    INTRODUCTION: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. METHODS: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorp...

  8. [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.

  9. 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

  10. 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 bot

  11. Treatment of non-ideality in the multiphase model SPACCIM - Part 1: Model development

    Science.gov (United States)

    Rusumdar, A. J.; Wolke, R.; Tilgner, A.; Herrmann, H.

    2015-06-01

    Ambient tropospheric deliquesced particles generally comprise a complex mixture of electrolytes, organic compounds, and water. Dynamic modeling of physical and chemical processes in this complex matrix is challenging. Thus, up-to-date multiphase chemistry models do generally not consider non-ideal solution effects. Therefore, the present study was aimed at the further development of the SPACCIM model to treat both complex multiphase chemistry and phase transfer processes considering newly non-ideality properties of concentrated aerosol solutions. The present paper describes firstly, the performed model development including (i) the kinetic implementation of the non-ideality in the SPACCIM framework, (ii) the advancements in the coupling scheme of microphysics and multiphase chemistry and (iii) the required adjustments of the numerical schemes, especially in the sparse linear solver and the calculation of the Jacobian. Secondly, results of performed sensitivity investigations are outlined aiming at the evaluation of different activity coefficient modules and the examination of the contributions of different intermolecular forces to the overall activity coefficients. Finally, first results obtained with the new model framework are presented. The main product of the performed model development is the new kinetic model approach SPACCIM-SpactMod, which utilizes activities in reaction terms instead of aqueous concentrations. Based on an intercomparison of different activity coefficient models and the comparison with experimental data, AIOMFAC was selected as base model and extended by additional interaction parameters from literature for mixed organic-inorganic systems. Moreover, the performance and the capability of the applied activity coefficient module were evaluated by means of water activity measurements, literature data and results of other thermodynamic equilibrium models. Comprehensive comparison studies showed that the SpactMod (SPACCIM activity coefficient

  12. Treatment of non-ideality in the multiphase model SPACCIM – Part 1: Model development

    Directory of Open Access Journals (Sweden)

    A. J. Rusumdar

    2015-06-01

    Full Text Available Ambient tropospheric deliquesced particles generally comprise a complex mixture of electrolytes, organic compounds, and water. Dynamic modeling of physical and chemical processes in this complex matrix is challenging. Thus, up-to-date multiphase chemistry models do generally not consider non-ideal solution effects. Therefore, the present study was aimed at the further development of the SPACCIM model to treat both complex multiphase chemistry and phase transfer processes considering newly non-ideality properties of concentrated aerosol solutions. The present paper describes firstly, the performed model development including (i the kinetic implementation of the non-ideality in the SPACCIM framework, (ii the advancements in the coupling scheme of microphysics and multiphase chemistry and (iii the required adjustments of the numerical schemes, especially in the sparse linear solver and the calculation of the Jacobian. Secondly, results of performed sensitivity investigations are outlined aiming at the evaluation of different activity coefficient modules and the examination of the contributions of different intermolecular forces to the overall activity coefficients. Finally, first results obtained with the new model framework are presented. The main product of the performed model development is the new kinetic model approach SPACCIM-SpactMod, which utilizes activities in reaction terms instead of aqueous concentrations. Based on an intercomparison of different activity coefficient models and the comparison with experimental data, AIOMFAC was selected as base model and extended by additional interaction parameters from literature for mixed organic–inorganic systems. Moreover, the performance and the capability of the applied activity coefficient module were evaluated by means of water activity measurements, literature data and results of other thermodynamic equilibrium models. Comprehensive comparison studies showed that the SpactMod (SPACCIM

  13. Computational models as predictors of HIV treatment outcomes for the Phidisa cohort in South Africa

    Directory of Open Access Journals (Sweden)

    Andrew Revell

    2016-02-01

    Full Text Available 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, using cases from the Phidisa cohort in South Africa.Methods: Cases from Phidisa of treatment change following failure were identified that had the following data available: baseline CD4 count and viral load, details of failing and previous antiretroviral drugs, drugs in new regimen and time to follow-up. The HIV Resistance Response Database Initiative’s (RDI’s models used these data to predict the probability of a viral load < 50 copies/mL at follow-up. The models were also used to identify effective alternative combinations of three locally available drugs.Results: The models achieved accuracy (area under the receiver–operator characteristic curve of 0.72 when predicting response to therapy, which is less accurate than for an independent global test set (0.80 but at least comparable to that of genotyping with rules-based interpretation. The models were able to identify alternative locally available three-drug regimens that were predicted to be effective in 69% of all cases and 62% of those whose new treatment failed in the clinic.Conclusion: The predictive accuracy of the models for these South African patients together with the results of previous studies suggest that the RDI’s models have the potential to optimise treatment selection and reduce virological failure in different patient populations, without the use of a genotype.Keywords: HIV therapy; mathematical modelling; treatment; genotype

  14. 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.

  15. Hyperhidrosis and Its Treatment: A Safe and Effective Alternative in the Treatment of Palmoplantar Hyperhidrosis, Iontophoresis

    Directory of Open Access Journals (Sweden)

    Deren Özcan

    2011-03-01

    Full Text Available Primary hyperhidrosis is characterized by excessive sweating of unknown cause which most commonly involves the palms, soles, and axillae in a bilateral and symmetrical fashion. Since it leads to physical discomfort and psychosocial difficulties in the affected individuals, it should be treated effectively. However, treatment can be challenging as its pathophysiology is poorly understood. There are several treatment options, including topical or systemic medications and surgical or non-surgical invasive techniques. Iontophoresis is the introduction of ionized substances into the surface tissues by means of an electric current. It is a non-invasive, safe, well tolerated, and effective treatment method for primary hyperhidrosis without long-term adverse effects and compensatory hyperhidrosis. Iontophoresis is suggested as a first-line therapy in severe palmoplantar hyperhidrosis and second-line therapy in milder cases that are unresponsive to topical treatments. In axillary hyperhidrosis it is less effective and not practical to use. Being time consuming and requiring maintenance therapy are its most important disadvantages. In this article, hyperhidrosis and the principal treatment options, the indications of iontophoresis for the treatment of primary hyperhidrosis, its mechanism of action, treatment protocol and procedure, adverse effects, and contraindications are reviewed.

  16. Effects of verbenalin on prostatitis mouse model

    Science.gov (United States)

    Miao, Mingsan; Guo, Lin; Yan, Xiaoli; Wang, Tan; Li, Zuming

    2015-01-01

    The aim of this study was to observe the treatment characteristics of verbenalin on a prostatitis mouse model. Give Xiaozhiling injection in the prostate locally to make a prostatitis mouse model. High, medium and low doses of verbenalin were each given to different mouse groups. The amount of water was determined in 14th, 28th. The number of white cells and lecithin corpuscle density in prostatic fluid were determined. Morphological changes in the prostate, testis, epididymis and kidney were detected. Compared with the model control group, the mice treated with high, medium and low doses of verbenalin had significantly increased amounts of water, and prostate white blood cell count and prostate volume density (Vv) were decreased significantly, the density of lecithin corpuscle score increased, and pathologic prostatitis changes were significantly reduced. Pathological change in the testis was significantly reduced and the change in the epididymis was obviously reduced. The thymic cortex thickness and the number of lymphocytes increased significantly and could reduce the renal pathological changes in potential. Verbenalin has a good therapeutic effect on the prostatitis mouse model. PMID:26858560

  17. Effective treatment for malignant mediastinal teratoma.

    Science.gov (United States)

    Parker, D; Holford, C P; Begent, R H; Newlands, E S; Rustin, G J; Makey, A R; Bagshawe, K D

    1983-12-01

    Primary malignant mediastinal teratoma is a rare tumour previously regarded as inevitably fatal. In a series of eight male patients with a mean age of 24 years five remain alive and well. All patients showed raised serum concentrations of human chorionic gonadotrophin or alpha fetoprotein. The patients were treated with intermittent combination chemotherapy that included cisplatin. Six patients responded to chemotherapy with a fall in human chorionic gonadotrophin or alpha fetoprotein to near normal levels and they then had radical excision of the remaining tumour. Living malignant tumour was found in four of the specimens and these patients received postoperative chemotherapy. One patient died after eight months and the remaining five patients are alive and well 13-136 months after the start of treatment. The two patients who did not undergo surgery died at one month and 15 months. Intermittent combination chemotherapy and carefully timed radical excision of these tumours would appear to have produced better results than have been reported in other series.

  18. Preventive effects of sevoflurane treatment on lung inflammation in rats

    Institute of Scientific and Technical Information of China (English)

    Shu-Ye Song; Bing Zhou; Shuang-Mei Yang; Guo-Ze Liu; Jian-Min Tian; Xiu-Qin Yue

    2013-01-01

    Objective: To observe the effects of sevoflurane treatment on lung inflammation in rats with lipopoIysaccharide-induced acute lung injury (ALI). Methods: The rat model of ALI was established by intratracheal instillation of lipopolysaccharide (LPS). 45 infantile SD rats [body weight (272±15) g] were randomly divided into 3 groups (n=15): control group, LPS group, sevoflurane group. NS (1 mL/kg) was instillated in rats’airways of control group; LPS (5 mg/kg) was instillated in rats’airways of LPS group. Sevoflurane group rats received sevoflurane (2.4%) inhalation for a hour after LPS was instillated in rats’airways. Six hours after NS or LPS instillation, all rats were exsanguinated. Lung tissues were examined by HE staining. Expressions of TNF-α and ICAM1 mRNA were detected by semiquantitative RT-PCR techniques. The protein level of TNF-α and ICAM1 were assessed by western blot techniques. Results: In LPS group the permeability of lung tissues increased, organizational structure severely damaged and the alveolar wall tumed thick, with interstitial edema and Europhiles infiltrated increasingly. The LPS group had higher mRNA expressions of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05), and LPS group had higher protein level of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05). Conclusions: Sevoflurane treatment can attenuate lung inflammation in rats with lipopolysaccharide-induced acute lung injury.

  19. 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.

  20. Study on kinetic model of microwave thermocatalytic treatment of biomass tar model compound.

    Science.gov (United States)

    Anis, Samsudin; Zainal, Z A

    2014-01-01

    Kinetic model parameters for toluene conversion under microwave thermocatalytic treatment were evaluated. The kinetic rate constants were determined using integral method based on experimental data and coupled with Arrhenius equation for obtaining the activation energies and pre-exponential factors. The model provides a good agreement with the experimental data. The kinetic model was also validated with standard error of 3% on average. The extrapolation of the model showed a reasonable trend to predict toluene conversion and product yield both in thermal and catalytic treatments. Under microwave irradiation, activation energy of toluene conversion was lower in the range of 3-27 kJ mol(-1) compared to those of conventional heating reported in the literatures. The overall reaction rate was six times higher compared to conventional heating. As a whole, the kinetic model works better for tar model removal in the absence of gas reforming within a level of reliability demonstrated in this study.

  1. Improved treatment of radiation effects on the skin

    Energy Technology Data Exchange (ETDEWEB)

    Wandl, E.O.; Kaercher, K.H.; Wandl-Hainberger, I.

    1985-04-29

    The treatment concept developed by K.H. Kaercher was extended by a therapy using Elasten S cream. In the course of a highvoltage therapy using fast electrons or cobalt-60, interesting aspects in the treatment and progression of the radiation reactions of the skin were established. The dermato-therapeutic principles layed down by K.H. Kaercher with the treatment palette used hitherto, have without doubt invariably proven their value. The exclusive powder treatment, however, may be made more practical by application of the new treatment cream in accordance with the intervals in radiation treatment or as a basic treatment towards the end of therapy. Furthermore it is ideally suited for the care and after-treatment of skin, strained by radiation. It reduces considerably the remaining visible radiation reactions. The treatment with powder and emulsion has for more than 10 years proven effective. After the excellent results of the new cream during radiation treatment, additional positive effects are expected in a long-term trial which will be reported on separately.

  2. Adsorption of natural organic matter and disinfection byproduct precursors from surface water onto TiO2 nanoparticles: pH effects, isotherm modelling and implications for using TiO2 for 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 TiO2 into drinking water treatment processes. The goal of this study was to expand on the current understanding of NOM adsorption on TiO2 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 TiO2 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.

  3. The effectiveness of extended care model on treatment compliance and quality of life in patients with tu-berculosis%延续护理模式在肺结核患者康复中的应用与效果

    Institute of Scientific and Technical Information of China (English)

    罗惠倩; 徐艳芳; 杨连芳

    2015-01-01

    目的:评价延续护理模式(ECM)对改善肺结核(TB)患者的依从性及生活质量的效果。方法选择2012年3月至2013年3月在我院接诊的TB患者468例,234例接受抗结核治疗并进行ECM干预,作为试验组;另234例按常规抗结核进行治疗,作为对照组。对两组患者的依从性、生活质量和预后满意度分别进行调查。结果试验组患者依从性总分以及康复训练、生活作息、复诊随访3个单项依从性高于对照组(P<0.05)。试验组TH、RP、MH、VT、RE和SF这6项评分高于对照组(P<0.05);试验组的生活质量总分为(604.6±128.4)分,高于对照组(516.9±118.9)分(P<0.05)。试验组满意度达到89.7%。结论通过ECM能够提高TB患者疾病相关知识,使日常生活行为更加规范,提高治疗依从性、生活质量及满意度,值得在临床推广应用。%Objective To evaluate the effectiveness of extended care model(ECM) on treatment compliance and quality of life in patients with tuberculosis. Methods Totally 468 patients with tuberculosis were divided into two groups. ECM was applied in the experimental group in addition to routine anti-tuberculosis treatment. The outcomes were evaluated using patient compliance,quality of life and patient satisfaction with prognosis. Results The patient compliance score(t=5.057,P=0.002) and factor scores in rehabilitation(t=4.332,P=0.014),lifestyle(t=5.747,P=0.019) and referral follow-up(t=3.403,P=0.023) in the experimental group were significantly higher than those of the control group. The factor scores in total health(TH),role physical(RP),mental health(MH),vitality(VT),role emo-tional(RE) and social function(SF) in the experimental group were significantly higher than those of the control group(P<0.05). The total score of quality of life in the experimental group was significantly higher than that of the control group (604.6 points versus 516 points,t=2.691,P=0.041). The

  4. Random Effect and Latent Variable Model Selection

    CERN Document Server

    Dunson, David B

    2008-01-01

    Presents various methods for accommodating model uncertainty in random effects and latent variable models. This book focuses on frequentist likelihood ratio and score tests for zero variance components. It also focuses on Bayesian methods for random effects selection in linear mixed effects and generalized linear mixed models

  5. Migraine treatment: a chain of adverse effects.

    Science.gov (United States)

    Veloso, Tiago Sousa; Cambão, Mariana Seixas

    2015-01-01

    This clinical vignette presents a 14 years old female, with a past medical history relevant only for migraine with typical aura of less than monthly frequency, complaining of a severe unilateral headache with rising intensity for the previous 4 h, associated with nausea, vomiting, photophobia and phonophobia. This episode of migraine with aura in a patient with recurrent migraine was complicated by side effects of medical diagnostic and therapeutic procedures (extrapyramidal symptoms, delirium, post-lumbar puncture headache, hospital admission) all of which could have been prevented-quaternary prevention. This case illustrates several important messages in migraine management: (1) use of acetaminophen is not based in high-quality evidence and better options exist; (2) among youngsters, domperidone should be preferred over metoclopramide because it does not cross the blood-brain barrier; (3) moderate to severe migraine crisis can be managed with triptans in teenagers over 12 years old; (4) it is important to recognize adverse drug effects; (5) harmful consequences of medical interventions do occur; (6) the school community must be informed about chronic diseases of the young.

  6. A plant-wide energy model for wastewater treatment plants: application to anaerobic membrane bioreactor technology.

    Science.gov (United States)

    Pretel, R; Robles, A; Ruano, M V; Seco, A; Ferrer, J

    2016-09-01

    The aim of this study is to propose a detailed and comprehensive plant-wide model for assessing the energy demand of different wastewater treatment systems (beyond the traditional activated sludge) in both steady- and unsteady-state conditions. The proposed model makes it possible to calculate power and heat requirements (W and Q, respectively), and to recover both power and heat from methane and hydrogen capture. In order to account for the effect of biological processes on heat requirements, the model has been coupled to the extended version of the BNRM2 plant-wide mathematical model, which is implemented in DESSAS simulation software. Two case studies have been evaluated to assess the model's performance: (1) modelling the energy demand of two urban wastewater treatment plants based on conventional activated sludge and submerged anaerobic membrane bioreactor (AnMBR) technologies in steady-state conditions and (2) modelling the dynamics of reactor temperature and heat requirements in an AnMBR plant in unsteady-state conditions. The results indicate that the proposed model can be used to assess the energy performance of different wastewater treatment processes and would thus be useful, for example, WWTP design or upgrading or the development of new control strategies for energy savings.

  7. An investigation of scale effects in family substance abuse treatment programs

    Directory of Open Access Journals (Sweden)

    Lee A James

    2010-07-01

    Full Text Available Abstract This short report investigates scale effects in family substance abuse treatment programs. In Massachusetts, the family substance abuse treatment programs were much more costly than other adult residential treatment models. State officials were concerned that the "scale" or size of these programs (averaging just eight families was too small to be economical. Although the sample size (just nine programs was too small to permit reliable inference, the data clearly signalled the importance of "scale effects" in these family substance abuse treatment programs. To further investigate scale effects in family substance abuse treatment programs, data from the Center for Substance Abuse Treatment's (CSAT's Residential Women and Children and Pregnant and Postpartum Women (RWC-PPW Demonstration were re-analyzed, focusing on the relationship between cost per family-day and the estimated average family census. This analysis indicates strong economies of scale up until an average family census of about 14, and less apparent scale effects beyond that point. In consideration of these and other study findings, a multidisciplinary interagency team redesigned the Massachusetts' family treatment program model. The new programs are larger than the former family treatment programs, with each new program having capacity to treat 11 to 15 families depending on family makeup.

  8. Ischemic heart disease: effectiveness and safety of statin treatment ...

    African Journals Online (AJOL)

    Ischemic heart disease: effectiveness and safety of statin treatment in a malaysian tertiary healthcare facility. ... Tropical Journal of Pharmaceutical Research ... and safety of statins in ischemic heart disease (IHD) patients in a Malaysian tertiary ...

  9. effects of mulching, fertilizer, seeding and seedling treatments on ...

    African Journals Online (AJOL)

    Mgina

    treatment had an effect of increasing mortality of non-woody species and selectively ... soil moisture storage, thermal insulation, ... focal point of restoration activities dealing ... Comparison of environmental attributes of the two sites studied.

  10. Prolotherapy: An Effective Treatment for Low Back Pain?

    Science.gov (United States)

    ... Is prolotherapy an effective treatment for chronic low back pain? Answers from Brent A. Bauer, M.D. Prolotherapy is a ... pain. Studies of prolotherapy in people with low back pain have had mixed results. A combination of prolotherapy ...

  11. Evaluation of Therapeutic Effects of Radiotherapy during Treatment ...

    African Journals Online (AJOL)

    therapeutic effects of radiotherapy during treatment of lung adenocarcinoma. Methods: Eighteen mice with .... reconstruction of the cross-sectional images of the coronal plane .... breast tumor from mediastinal metastases to further improve the ...

  12. Cost-effectiveness analysis of Mectizan treatment Programmes for ...

    African Journals Online (AJOL)

    Cost-effectiveness analysis of Mectizan treatment Programmes for Onchocerciasis Control: Operational Experiences in two districts of Southwestern Nigeria. ... Vol 8, No 1 (2009) >. Log in or Register to get access to full text downloads.

  13. 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.

  14. A generalised model for individualising a treatment recommendation based on group-level evidence from randomised clinical trials.

    Science.gov (United States)

    Marcucci, Maura; Sinclair, John C

    2013-08-13

    Randomised controlled trials report group-level treatment effects. However, an individual patient confronting a treatment decision needs to know whether that person's expected treatment benefit will exceed the expected treatment harm. We describe a flexible model for individualising a treatment decision. It individualises group-level results from randomised trials using clinical prediction guides. We constructed models that estimate the size of individualised absolute risk reduction (ARR) for the target outcome that is required to offset individualised absolute risk increase (ARI) for the treatment harm. Inputs to the model include estimates for the individualised predicted absolute treatment benefit and harm, and the relative value assigned by the patient to harm/benefit. A decision rule recommends treatment when the predicted benefit exceeds the predicted harm, value-adjusted. We also derived expressions for the maximum treatment harm, or the maximum relative value for harm/benefit, above which treatment would not be recommended. For the simpler model, including one kind of benefit and one kind of harm, the indi