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Sample records for auc

  1. Adaptive Subgradient Methods for Online AUC Maximization

    OpenAIRE

    Ding, Yi; Zhao, Peilin; Hoi, Steven C. H.; Ong, Yew-Soon

    2016-01-01

    Learning for maximizing AUC performance is an important research problem in Machine Learning and Artificial Intelligence. Unlike traditional batch learning methods for maximizing AUC which often suffer from poor scalability, recent years have witnessed some emerging studies that attempt to maximize AUC by single-pass online learning approaches. Despite their encouraging results reported, the existing online AUC maximization algorithms often adopt simple online gradient descent approaches that...

  2. Direct AUC optimization of regulatory motifs.

    Science.gov (United States)

    Zhu, Lin; Zhang, Hong-Bo; Huang, De-Shuang

    2017-07-15

    The discovery of transcription factor binding site (TFBS) motifs is essential for untangling the complex mechanism of genetic variation under different developmental and environmental conditions. Among the huge amount of computational approaches for de novo identification of TFBS motifs, discriminative motif learning (DML) methods have been proven to be promising for harnessing the discovery power of accumulated huge amount of high-throughput binding data. However, they have to sacrifice accuracy for speed and could fail to fully utilize the information of the input sequences. We propose a novel algorithm called CDAUC for optimizing DML-learned motifs based on the area under the receiver-operating characteristic curve (AUC) criterion, which has been widely used in the literature to evaluate the significance of extracted motifs. We show that when the considered AUC loss function is optimized in a coordinate-wise manner, the cost function of each resultant sub-problem is a piece-wise constant function, whose optimal value can be found exactly and efficiently. Further, a key step of each iteration of CDAUC can be efficiently solved as a computational geometry problem. Experimental results on real world high-throughput datasets illustrate that CDAUC outperforms competing methods for refining DML motifs, while being one order of magnitude faster. Meanwhile, preliminary results also show that CDAUC may also be useful for improving the interpretability of convolutional kernels generated by the emerging deep learning approaches for predicting TF sequences specificities. CDAUC is available at: https://drive.google.com/drive/folders/0BxOW5MtIZbJjNFpCeHlBVWJHeW8 . dshuang@tongji.edu.cn. Supplementary data are available at Bioinformatics online.

  3. Hydrodynamic Modeling and Its Application in AUC.

    Science.gov (United States)

    Rocco, Mattia; Byron, Olwyn

    2015-01-01

    The hydrodynamic parameters measured in an AUC experiment, s(20,w) and D(t)(20,w)(0), can be used to gain information on the solution structure of (bio)macromolecules and their assemblies. This entails comparing the measured parameters with those that can be computed from usually "dry" structures by "hydrodynamic modeling." In this chapter, we will first briefly put hydrodynamic modeling in perspective and present the basic physics behind it as implemented in the most commonly used methods. The important "hydration" issue is also touched upon, and the distinction between rigid bodies versus those for which flexibility must be considered in the modeling process is then made. The available hydrodynamic modeling/computation programs, HYDROPRO, BEST, SoMo, AtoB, and Zeno, the latter four all implemented within the US-SOMO suite, are described and their performance evaluated. Finally, some literature examples are presented to illustrate the potential applications of hydrodynamics in the expanding field of multiresolution modeling. © 2015 Elsevier Inc. All rights reserved.

  4. Evaluation of a Novel Glucose Area Under the Curve (AUC) Monitoring System: Comparison with the AUC by Continuous Glucose Monitoring.

    Science.gov (United States)

    Ugi, Satoshi; Maegawa, Hiroshi; Morino, Katsutaro; Nishio, Yoshihiko; Sato, Toshiyuki; Okada, Seiki; Kikkawa, Yasuo; Watanabe, Toshihiro; Nakajima, Hiromu; Kashiwagi, Atsunori

    2016-08-01

    Management of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET) for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM) by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration. Twenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels. AUC predicted by MIET correlated well with that measured by CGM (r=0.93). Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours), indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours. Our system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration.

  5. Evaluation of a Novel Glucose Area Under the Curve (AUC Monitoring System: Comparison with the AUC by Continuous Glucose Monitoring

    Directory of Open Access Journals (Sweden)

    Satoshi Ugi

    2016-07-01

    Full Text Available BackgroundManagement of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC using minimally invasive interstitial fluid extraction technology (MIET for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration.MethodsTwenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels.ResultsAUC predicted by MIET correlated well with that measured by CGM (r=0.93. Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours, indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours.ConclusionOur system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration.

  6. Partial AUC maximization for essential gene prediction using genetic algorithms.

    Science.gov (United States)

    Hwang, Kyu-Baek; Ha, Beom-Yong; Ju, Sanghun; Kim, Sangsoo

    2013-01-01

    Identifying genes indispensable for an organism's life and their characteristics is one of the central questions in current biological research, and hence it would be helpful to develop computational approaches towards the prediction of essential genes. The performance of a predictor is usually measured by the area under the receiver operating characteristic curve (AUC). We propose a novel method by implementing genetic algorithms to maximize the partial AUC that is restricted to a specific interval of lower false positive rate (FPR), the region relevant to follow-up experimental validation. Our predictor uses various features based on sequence information, protein-protein interaction network topology, and gene expression profiles. A feature selection wrapper was developed to alleviate the over-fitting problem and to weigh each feature's relevance to prediction. We evaluated our method using the proteome of budding yeast. Our implementation of genetic algorithms maximizing the partial AUC below 0.05 or 0.10 of FPR outperformed other popular classification methods.

  7. Online Nonlinear AUC Maximization for Imbalanced Data Sets.

    Science.gov (United States)

    Hu, Junjie; Yang, Haiqin; Lyu, Michael R; King, Irwin; So, Anthony Man-Cho

    2017-01-27

    Classifying binary imbalanced streaming data is a significant task in both machine learning and data mining. Previously, online area under the receiver operating characteristic (ROC) curve (AUC) maximization has been proposed to seek a linear classifier. However, it is not well suited for handling nonlinearity and heterogeneity of the data. In this paper, we propose the kernelized online imbalanced learning (KOIL) algorithm, which produces a nonlinear classifier for the data by maximizing the AUC score while minimizing a functional regularizer. We address four major challenges that arise from our approach. First, to control the number of support vectors without sacrificing the model performance, we introduce two buffers with fixed budgets to capture the global information on the decision boundary by storing the corresponding learned support vectors. Second, to restrict the fluctuation of the learned decision function and achieve smooth updating, we confine the influence on a new support vector to its k-nearest opposite support vectors. Third, to avoid information loss, we propose an effective compensation scheme after the replacement is conducted when either buffer is full. With such a compensation scheme, the performance of the learned model is comparable to the one learned with infinite budgets. Fourth, to determine good kernels for data similarity representation, we exploit the multiple kernel learning framework to automatically learn a set of kernels. Extensive experiments on both synthetic and real-world benchmark data sets demonstrate the efficacy of our proposed approach.

  8. Vancomycin AUC24 /MIC Ratio in Patients with Methicillin-Resistant Staphylococcus aureus Pneumonia.

    Science.gov (United States)

    Ji, Misuk; Kim, Hyun-Ki; Kim, Soo-Kyung; Lee, Woochang; Sung, Heungsup; Chun, Sail; Kim, Mi-Na; Min, Won-Ki

    2016-09-01

    Vancomycin is the treatment of choice for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. The area under the concentration-time curve from 0 to 24 hr (AUC24 )/minimum inhibitory concentration (MIC) ratio was recently introduced as a parameter for assessing clinical outcome by S. aureus. This study was purposed to apply the vancomycin AUC24 /MIC in patients with MRSA pneumonia. Forty-seven patients with confirmed lower respiratory infection caused by MRSA during 2011 were enrolled. All patients were treated with vancomycin. Clinical characteristics and laboratory data were collected. AUC24 /MIC values were calculated as previously reported and patients were divided into two groups based on the bacteriologic response, which was eradicated or not, and an AUC24 /MIC value (above or below 400). MRSA infections were eradicated in 39 patients but 8 patients had persistent MSRA infection in the following cultures. The mean AUC24 /MIC values and vancomycin concentrations were not statistically different between patients with and without MRSA eradication. All 13 patients with a vancomycin MIC of 2 mg/L had an AUC24 /MIC below 400. AUC24 /MIC might not be a reliable indicator for assessing treatment response of vancomycin in MRSA pneumonia. Relationship between vancomycin AUC24 /MIC and therapeutic outcome needs to undergo further studies, including sufficiently large sample size. © 2015 Wiley Periodicals, Inc.

  9. Preparation and characterization of antibacterial Au/C core-shell composite

    Energy Technology Data Exchange (ETDEWEB)

    Gao Yanhong [Department of Chemistry and Institute of Nanochemistry, Jinan University, 601 Huangpudadaoxi Road, Guangzhou 510632, Guangdong (China); Centers for Disease Control and Prevention of Guangdong Province, Guangzhou 510300, Guangdong (China); Zhang Nianchun [Department of Chemistry and Institute of Nanochemistry, Jinan University, 601 Huangpudadaoxi Road, Guangzhou 510632, Guangdong (China); Zhong Yuwen [Centers for Disease Control and Prevention of Guangdong Province, Guangzhou 510300, Guangdong (China); Cai Huaihong [Department of Chemistry and Institute of Nanochemistry, Jinan University, 601 Huangpudadaoxi Road, Guangzhou 510632, Guangdong (China); Liu Yingliang, E-mail: tliuyl@jnu.edu.cn [Department of Chemistry and Institute of Nanochemistry, Jinan University, 601 Huangpudadaoxi Road, Guangzhou 510632, Guangdong (China)

    2010-09-01

    An environment-friendly oxidation-reduction method was used to prepare Au/C core-shell composite using carbon as core and gold as shell. The chemical structures and morphologies of Au/C core-shell composite and carbon sphere were characterized by X-ray diffraction, transmission electron microscope, energy dispersion X-ray spectrometry (EDS) and X-ray photoelectron spectroscopy (XPS). The antibacterial properties of the Au/C core-shell composite against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Candida albicans (C. albicans) were examined by the disk diffusion assay and minimal inhibition concentration (MIC) methods. In addition, antibacterial ability of Au/C core-shell composite was observed by atomic force microscope. Results demonstrated that gold homogeneously supported on the surface of carbon spheres without aggregation and showed efficient antibacterial abilities.

  10. An extension of the receiver operating characteristic curve and AUC-optimal classification.

    Science.gov (United States)

    Takenouchi, Takashi; Komori, Osamu; Eguchi, Shinto

    2012-10-01

    While most proposed methods for solving classification problems focus on minimization of the classification error rate, we are interested in the receiver operating characteristic (ROC) curve, which provides more information about classification performance than the error rate does. The area under the ROC curve (AUC) is a natural measure for overall assessment of a classifier based on the ROC curve. We discuss a class of concave functions for AUC maximization in which a boosting-type algorithm including RankBoost is considered, and the Bayesian risk consistency and the lower bound of the optimum function are discussed. A procedure derived by maximizing a specific optimum function has high robustness, based on gross error sensitivity. Additionally, we focus on the partial AUC, which is the partial area under the ROC curve. For example, in medical screening, a high true-positive rate to the fixed lower false-positive rate is preferable and thus the partial AUC corresponding to lower false-positive rates is much more important than the remaining AUC. We extend the class of concave optimum functions for partial AUC optimality with the boosting algorithm. We investigated the validity of the proposed method through several experiments with data sets in the UCI repository.

  11. Suitability of the AUC Ratio as an Indicator of the Pharmacokinetic Advantage in HIPEC.

    Science.gov (United States)

    Mas-Fuster, Maria Isabel; Ramon-Lopez, Amelia; Lacueva, Javier; Más-Serrano, Patricio; Nalda-Molina, Ricardo

    2018-02-01

    The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. Asymptotic distribution of ∆AUC, NRIs, and IDI based on theory of U-statistics.

    Science.gov (United States)

    Demler, Olga V; Pencina, Michael J; Cook, Nancy R; D'Agostino, Ralph B

    2017-09-20

    The change in area under the curve (∆AUC), the integrated discrimination improvement (IDI), and net reclassification index (NRI) are commonly used measures of risk prediction model performance. Some authors have reported good validity of associated methods of estimating their standard errors (SE) and construction of confidence intervals, whereas others have questioned their performance. To address these issues, we unite the ∆AUC, IDI, and three versions of the NRI under the umbrella of the U-statistics family. We rigorously show that the asymptotic behavior of ∆AUC, NRIs, and IDI fits the asymptotic distribution theory developed for U-statistics. We prove that the ∆AUC, NRIs, and IDI are asymptotically normal, unless they compare nested models under the null hypothesis. In the latter case, asymptotic normality and existing SE estimates cannot be applied to ∆AUC, NRIs, or IDI. In the former case, SE formulas proposed in the literature are equivalent to SE formulas obtained from U-statistics theory if we ignore adjustment for estimated parameters. We use Sukhatme-Randles-deWet condition to determine when adjustment for estimated parameters is necessary. We show that adjustment is not necessary for SEs of the ∆AUC and two versions of the NRI when added predictor variables are significant and normally distributed. The SEs of the IDI and three-category NRI should always be adjusted for estimated parameters. These results allow us to define when existing formulas for SE estimates can be used and when resampling methods such as the bootstrap should be used instead when comparing nested models. We also use the U-statistic theory to develop a new SE estimate of ∆AUC. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Stable Au-C bonds to the substrate for fullerene-based nanostructures

    Czech Academy of Sciences Publication Activity Database

    Chutora, Taras; Redondo, Jesús R.L.R.; de la Torre Cerdeño, Bruno; Švec, Martin; Jelínek, Pavel; Vázquez, Héctor

    2017-01-01

    Roč. 8, č. 1 (2017), s. 1073-1079 ISSN 2190-4286 R&D Projects: GA ČR GA15-19672S Institutional support: RVO:68378271 Keywords : Au-C bonds * density functional theory (DFT) * fullerenes * scanning tunneling microscopy (STM) * sputtering Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.127, year: 2016

  14. [The Academy of Trauma Surgery (AUC). Service provider and management organization of the DGU].

    Science.gov (United States)

    Sturm, J A; Hoffmann, R

    2016-02-01

    At the beginning of this century the German Trauma Society (DGU) became extensively active with an initiative on quality promotion, development of quality assurance and transparency regarding treatment of the severely injured. A white book on "Medical care of the severely injured" was published, focusing on the requirements on structural quality and especially procedural quality. The impact of the white book was immense and a trauma network with approved trauma centers, structured and graded for their individual trauma care performance, was developed. In order to monitor and document the required quality of care, a registry was needed. Furthermore, for cooperation within the trauma networks innovative methods for digital transfer of radiological images and patient documents became necessary. Finally, the auditing criteria for trauma centers had and still have to be completed with advanced medical education and training programs. In order to realize the implementation of such a broad spectrum of economically relevant and increasingly complex activities the Academy of Trauma Surgery (AUC) was established as a subsidiary of the DGU in 2004. The AUC currently has four divisions: 1) networks and health care structures, 2) registries and research management, 3) telemedicine, 4) medical education and training, all of which serve the goal of the initiative. The AUC is a full service provider and management organization in compliance with the statutes of the DGU. According to these statutes the business operations of the AUC also cover projects for numerous groups of patients, projects for the joint society the German Society for Orthopedics and Trauma (DGOU) as well as other medical institutions. This article describes the success stories of the trauma network (TraumaNetzwerk DGU®), the TraumaRegister DGU®, the telecooperation platform TKmed®, the new and fast-growing orthogeriatric center initiative (AltersTraumaZentrum DGU®) and the division of medical education and

  15. Characterization of Au3+ species in Au/C catalysts for the hydrochlorination reaction of acetylene

    OpenAIRE

    Conte, M.; Davies, C.J.; Morgan, D.J.; Carley, A.F.; Johnston, P.; Hutchings, G.J.

    2014-01-01

    A set of Au/C catalysts for the gas phase hydrochlorination of acetylene to vinyl chloride monomer were prepared using a range of strong acids as impregnating solvents and varying the preparation drying temperature. The most active catalyst is the material prepared using aqua regia as solvent with an intermediate drying temperature of 140 °C. The effects of the catalyst preparation parameters on the catalytic activity are examined using XPS and TPR as analytical tools. In particular, the use ...

  16. Survival associated pathway identification with group Lp penalized global AUC maximization

    Directory of Open Access Journals (Sweden)

    Liu Zhenqiu

    2010-08-01

    Full Text Available Abstract It has been demonstrated that genes in a cell do not act independently. They interact with one another to complete certain biological processes or to implement certain molecular functions. How to incorporate biological pathways or functional groups into the model and identify survival associated gene pathways is still a challenging problem. In this paper, we propose a novel iterative gradient based method for survival analysis with group Lp penalized global AUC summary maximization. Unlike LASSO, Lp (p 1. We first extend Lp for individual gene identification to group Lp penalty for pathway selection, and then develop a novel iterative gradient algorithm for penalized global AUC summary maximization (IGGAUCS. This method incorporates the genetic pathways into global AUC summary maximization and identifies survival associated pathways instead of individual genes. The tuning parameters are determined using 10-fold cross validation with training data only. The prediction performance is evaluated using test data. We apply the proposed method to survival outcome analysis with gene expression profile and identify multiple pathways simultaneously. Experimental results with simulation and gene expression data demonstrate that the proposed procedures can be used for identifying important biological pathways that are related to survival phenotype and for building a parsimonious model for predicting the survival times.

  17. Thermal Analysis of the Decomposition of Ammonium Uranyl Carbonate (AUC) in Different Atmospheres

    DEFF Research Database (Denmark)

    Hälldahl, L.; Sørensen, Ole Toft

    1979-01-01

    The intermediate products formed during thermal decomposition of ammonium uranyl carbonate (AUC) in different atmospheres, (air, helium and hydrogen) have been determined by thermal analysis, (TG, and DTA) and X-ray analysis. The endproducts observed are U3O8 and UO2 in air/He and hydrogen......, respectively. The following intermediate products were observed in all atmospheres: http://www.sciencedirect.com.globalproxy.cvt.dk/cache/MiamiImageURL/B6THV-44K80TV-FB-1/0?wchp=dGLzVlz-zSkWW X-ray diffraction analysis showed that these phases were amorphous....

  18. Aqua regia activated Au/C catalysts for the hydrochlorination of acetylene

    OpenAIRE

    Conte, Marco; Davies, Catherine; Morgan, David John; Davies, Thomas E.; Elias, David J.; Carley, Albert Frederick; Johnston, Peter; Hutchings, Graham John

    2013-01-01

    Au/C catalysts are effective materials for the gas phase hydrochlorination of acetylene to vinyl chloride\\ud monomer, and to date, the most effective catalyst preparation protocol makes use of impregnation using\\ud aqua regia. In the present study, the effect of this solvent is evaluated and discussed in detail by modifying\\ud the ratio of HCl and HNO3 and the temperature of the impregnation step. These factors are observed to\\ud affect the Au3+/Au0\\ud ratio of the final catalyst, in addition ...

  19. Innovative preparation of Au/C by replication of gold-containing mesoporous silica catalysts

    KAUST Repository

    Kerdi, Fatmé

    2010-01-01

    A new strategy, based on the nanocasting concept, has been used to prepare gold nanoparticles (NPs) highly dispersed in meso-structured carbons. Gold is first introduced in various functionalized mesostructured silicas (MCM-48 and SBA-15) and particles are formed inside the porosity upon reduction of Au 3+ cations. Silica pores are then impregnated with a carbon precursor and the composite material is heated at 900°C under vacuum. Silica is then removed by acid leaching, leading to partially encapsulated gold particles in mesoporous carbon. Carbon prevents aggregation of gold particles at high temperature, both the mean size and distribution being similar to those observed in silica. However, while Au@SiO2 exhibit significant catalytic activity in the aerobic oxidation of trans-stilbene in the liquid phase, its Au@C mesostructured replica is quite inactive. © 2010 Elsevier B.V. All rights reserved.

  20. Evaluating the predictive abilities of community occupancy models using AUC while accounting for imperfect detection

    Science.gov (United States)

    Zipkin, Elise F.; Grant, Evan H. Campbell; Fagan, William F.

    2012-01-01

    The ability to accurately predict patterns of species' occurrences is fundamental to the successful management of animal communities. To determine optimal management strategies, it is essential to understand species-habitat relationships and how species habitat use is related to natural or human-induced environmental changes. Using five years of monitoring data in the Chesapeake and Ohio Canal National Historical Park, Maryland, USA, we developed four multi-species hierarchical models for estimating amphibian wetland use that account for imperfect detection during sampling. The models were designed to determine which factors (wetland habitat characteristics, annual trend effects, spring/summer precipitation, and previous wetland occupancy) were most important for predicting future habitat use. We used the models to make predictions of species occurrences in sampled and unsampled wetlands and evaluated model projections using additional data. Using a Bayesian approach, we calculated a posterior distribution of receiver operating characteristic area under the curve (ROC AUC) values, which allowed us to explicitly quantify the uncertainty in the quality of our predictions and to account for false negatives in the evaluation dataset. We found that wetland hydroperiod (the length of time that a wetland holds water) as well as the occurrence state in the prior year were generally the most important factors in determining occupancy. The model with only habitat covariates predicted species occurrences well; however, knowledge of wetland use in the previous year significantly improved predictive ability at the community level and for two of 12 species/species complexes. Our results demonstrate the utility of multi-species models for understanding which factors affect species habitat use of an entire community (of species) and provide an improved methodology using AUC that is helpful for quantifying the uncertainty in model predictions while explicitly accounting for

  1. Effect of Truncating AUC at 12, 24 and 48 hr When Evaluating the Bioequivalence of Drugs with a Long Half-Life.

    Science.gov (United States)

    Moreno, Isabel; Ochoa, Dolores; Román, Manuel; Cabaleiro, Teresa; Abad-Santos, Francisco

    2016-01-01

    Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalent. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  2. Exploration of analysis methods for diagnostic imaging tests: problems with ROC AUC and confidence scores in CT colonography.

    Science.gov (United States)

    Mallett, Susan; Halligan, Steve; Collins, Gary S; Altman, Doug G

    2014-01-01

    Different methods of evaluating diagnostic performance when comparing diagnostic tests may lead to different results. We compared two such approaches, sensitivity and specificity with area under the Receiver Operating Characteristic Curve (ROC AUC) for the evaluation of CT colonography for the detection of polyps, either with or without computer assisted detection. In a multireader multicase study of 10 readers and 107 cases we compared sensitivity and specificity, using radiological reporting of the presence or absence of polyps, to ROC AUC calculated from confidence scores concerning the presence of polyps. Both methods were assessed against a reference standard. Here we focus on five readers, selected to illustrate issues in design and analysis. We compared diagnostic measures within readers, showing that differences in results are due to statistical methods. Reader performance varied widely depending on whether sensitivity and specificity or ROC AUC was used. There were problems using confidence scores; in assigning scores to all cases; in use of zero scores when no polyps were identified; the bimodal non-normal distribution of scores; fitting ROC curves due to extrapolation beyond the study data; and the undue influence of a few false positive results. Variation due to use of different ROC methods exceeded differences between test results for ROC AUC. The confidence scores recorded in our study violated many assumptions of ROC AUC methods, rendering these methods inappropriate. The problems we identified will apply to other detection studies using confidence scores. We found sensitivity and specificity were a more reliable and clinically appropriate method to compare diagnostic tests.

  3. Discrepancy in Vancomycin AUC/MIC Ratio Targeted Attainment Based upon the Susceptibility Testing in Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Seenae Eum

    2016-09-01

    Full Text Available This study demonstrated a statistically significant difference in vancomycin minimum inhibitory concentration (MIC for Staphylococcus aureus between a common automated system (Vitek 2 and the E-test method in patients with S. aureus bloodstream infections. At an area under the serum concentration time curve (AUC threshold of 400 mg∙h/L, we would have reached the current Infectious Diseases Society of America (IDSA/American Society of Health System Pharmacists (ASHP/Society of Infectious Diseases Pharmacists (SIDP guideline suggested AUC/MIC target in almost 100% of patients while using the Vitek 2 MIC data; however, we could only generate 40% target attainment while using E-test MIC data (p < 0.0001. An AUC of 450 mg∙h/L or greater was required to achieve 100% target attainment using either Vitek 2 or E-test MIC results.

  4. Intranasal Pharmacokinetic Data for Triptans Such as Sumatriptan and Zolmitriptan Can Render Area Under the Curve (AUC) Predictions for the Oral Route: Strategy Development and Application

    DEFF Research Database (Denmark)

    Srinivas, Nuggehally R.; Syed, Muzeeb

    2016-01-01

    ), mean negative error (MNE), root mean square error (RMSE), correlation coefficient (r), and the goodness of the AUC fold prediction were used to evaluate the two triptans. Also, data from the mean concentration profiles at time points of 1 hour (sumatriptan) and 3 hours (zolmitriptan) were used...... for the AUC prediction. The Cmax vs. AUC models displayed excellent correlation for both sumatriptan (r = .9997; P r = .9999; P ... of the AUC values was established by a rigorous statistical approach....

  5. Exploration of analysis methods for diagnostic imaging tests: problems with ROC AUC and confidence scores in CT colonography.

    Directory of Open Access Journals (Sweden)

    Susan Mallett

    Full Text Available BACKGROUND: Different methods of evaluating diagnostic performance when comparing diagnostic tests may lead to different results. We compared two such approaches, sensitivity and specificity with area under the Receiver Operating Characteristic Curve (ROC AUC for the evaluation of CT colonography for the detection of polyps, either with or without computer assisted detection. METHODS: In a multireader multicase study of 10 readers and 107 cases we compared sensitivity and specificity, using radiological reporting of the presence or absence of polyps, to ROC AUC calculated from confidence scores concerning the presence of polyps. Both methods were assessed against a reference standard. Here we focus on five readers, selected to illustrate issues in design and analysis. We compared diagnostic measures within readers, showing that differences in results are due to statistical methods. RESULTS: Reader performance varied widely depending on whether sensitivity and specificity or ROC AUC was used. There were problems using confidence scores; in assigning scores to all cases; in use of zero scores when no polyps were identified; the bimodal non-normal distribution of scores; fitting ROC curves due to extrapolation beyond the study data; and the undue influence of a few false positive results. Variation due to use of different ROC methods exceeded differences between test results for ROC AUC. CONCLUSIONS: The confidence scores recorded in our study violated many assumptions of ROC AUC methods, rendering these methods inappropriate. The problems we identified will apply to other detection studies using confidence scores. We found sensitivity and specificity were a more reliable and clinically appropriate method to compare diagnostic tests.

  6. Synthesis of Au/C and Au/Pani for anode electrodes in glucose microfluidic fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Guerra-Balcazar, M.; Morales-Acosta, D.; Castaneda, F.; Arriaga, L.G. [Centro de Investigacion y Desarrollo Tecnologico en Electroquimica, 76703 Queretaro (Mexico); Ledesma-Garcia, J. [Division de Investigacion y Posgrado, Facultad de Ingenieria, Universidad Autonoma de Queretaro, 76010 Queretaro (Mexico)

    2010-06-15

    Gold nanoparticles have been prepared by two methods: chemical (ex-situ, Au/C) by two phase protocol, and electrochemical (in-situ, Au/Pani) by electroreduction of gold ions on a polyaniline film and compared as anode catalysts in a glucose microfluidic fuel cell. In this paper the structural characteristics and electrocatalytic properties were investigated by X-ray diffraction and electrochemical measurements. The catalytic behavior of both anodes was tested in a microfluidic fuel cell with a reference electrode incorporated, by means of linear sweep voltammetry (LSV), showing a cathodic shift in the glucose oxidation peak for Au/Pani. Results show a higher power density (0.5 mW cm{sup -} {sup 2}) for Au/C anode compared with an already reported value, where a glucose microfluidic fuel cell was used in similar conditions. (author)

  7. Colombia’s Attempt at Peace: An Analysis of the Demobilization of the Auto-Defensas Unidas de Colombia (AUC)

    Science.gov (United States)

    2007-03-01

    19th Movement Paras – Former or current members of the AUC or other paramilitary style organizations found throughout Colombia SENA – Servicio ...of Colombia’s Servicio National de Aprendizaje or National Training Service (SEDA – Spanish acronym) is explained. The SEDA has existed since the...is divided into the Academic and Occupational Module.47 Individuals are tested at the beginning of the phase in order to determine their baseline

  8. Exploration of Analysis Methods for Diagnostic Imaging Tests: Problems with ROC AUC and Confidence Scores in CT Colonography

    OpenAIRE

    Susan Mallett; Steve Halligan; Collins, Gary S.; Altman, Doug G

    2014-01-01

    BACKGROUND: Different methods of evaluating diagnostic performance when comparing diagnostic tests may lead to different results. We compared two such approaches, sensitivity and specificity with area under the Receiver Operating Characteristic Curve (ROC AUC) for the evaluation of CT colonography for the detection of polyps, either with or without computer assisted detection. METHODS: In a multireader multicase study of 10 readers and 107 cases we compared sensitivity and specificity, using ...

  9. Reconstrucción de las redes sociales: el caso de las FARC, el ELN y las ACCU-AUC

    Directory of Open Access Journals (Sweden)

    Plata Caviedes, Juan Camilo

    2006-06-01

    Full Text Available It is explored a strategy to analyze the press releases made by the FARC, the ELN, and the ACCU-AUC. It is based on the minimal grammatical structure: Subject- Action - Object. Using this grammatical triplet, the network of connections are built up; and then, some of the Social Network Analysis tools are applied to it. Some mechanisms related with these structural properties are identified: a To define for each actor a distinctive set of relationships; b the part is different from the whole; c the emphasized topics do the work of putting near a set of nodes.

  10. Innovative Route to Prepare of Au/C Catalysts by Replication of Gold-containing Mesoporous Silicas

    KAUST Repository

    Kerdi, Fatmé

    2011-12-23

    Gold-catalyzed aerobic epoxidations in the liquid phase are generally performed in low-polarity solvents, in which conventional oxide-supported catalysts are poorly dispersed. To improve the wettability of the catalytic powder and, thus, the efficiency of the catalyst, gold nanoparticles (NPs) have been dispersed on meso-structured carbons. Gold is first introduced in functionalized mesostructured silica and particles are formed inside the porosity. Silica pores are then impregnated with a carbon precursor and the composite material is heated at 900 °C under vacuum or nitrogen. Silica is then removed by acid leaching, leading to partially encapsulated gold particles in mesoporous carbon. Carbon prevents aggregation of gold particles at high temperature, both the mean size and distribution being similar to those observed in silica. However, while Au@SiO2 exhibit significant catalytic activity in the aerobic oxidation of trans-stilbene in the liquid phase, its Au@C mesostructured replica is quite inactive.

  11. Association between the AUC0-24/MIC Ratio of Vancomycin and Its Clinical Effectiveness: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Peng Men

    Full Text Available A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research.This current systematic review aimed to evaluate the available evidence for the association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400.PubMed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM were systematically searched. Manual searching was also applied. Both RCTs and observational studies comparing the clinical outcomes of high AUC0-24/MIC groups versus low AUC0-24/MIC groups were eligible. Two reviewers independently extracted the data. The primary outcomes were mortality and infection treatment failure. Risk ratios (RRs with 95% confidence intervals (95%CIs were calculated.No RCTs were retrieved. Nine cohort studies were included in the meta-analysis. Mortality rates were significantly lower in high AUC0-24/MIC groups (RR = 0.47, 95%CI = 0.31-0.70, p<0.001. The rates of infection treatment failure were also significantly lower in high AUC/MIC groups and were consistent after correcting for heterogeneity (RR = 0.39, 95%CI = 0.28-0.55, p = 0.001. Subgroup analyses showed that results were consistent whether MIC values were determined by broth microdilution (BMD method or Etest method. In studies using the BMD method, breakpoints of AUC0-24/MIC all fell within 85% to 115% of 400.This meta-analysis demonstrated that achieving a high AUC0-24/MIC of vancomycin could significantly decrease mortality rates by 53% and rates of infection treatment failure by 61%, with 400 being a reasonable target.

  12. Truncated AUC in the evaluation of fluconazole bioequivalence. A cross-over, randomised, open-label study in healthy volunteers.

    Science.gov (United States)

    Portolés, Antonio; Almeida, Susana; Terleira, Ana; de Pablo, Itziar; Filipe, Augusto; Cruz Caturla, Maria; Moreno, Alfonso

    2004-01-01

    The bioequivalence of two capsule formulations (test and reference) containing 200 mg fluconazole (CAS 86386-73-4) was assessed in 24 healthy volunteers in an open, randomised, crossover, 2 periods x 2 sequences single dose study with a minimum washout period of 14 days. Plasma samples were obtained over 168 h (at baseline, 1 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 120 h and 168 h after administration) and fluconazole concentrations were determined by means of an HPLC-WV method (limit of quantification: 0.2 microg/mL). Pharmacokinetic parameters used for bioequivalence assessment (AUClast, AUCinf and Cmax) were determined from the fluconazole concentration data using non-compartmental analysis. The results showed that all 90% confidence intervals (obtained by ANOVA) were 100.89-110.24 for Cmax, 99.07-107.35 for AUClast and 95.42-105.17 for AUCinf, that is, all within the predefined ranges. Furthermore AUCs truncated at 24, 48, 72 and 120 h were also within the 80-125% range. It may be therefore concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption.

  13. Carbonated water (CW) process waste reuse for ammonium-uranyl-carbonate (AUC) production and its gains on the environmental, economic and social aspects

    Energy Technology Data Exchange (ETDEWEB)

    Carnaval, Joao Paulo R.; Santos, Rafael D. dos; Barbosa, Rodrigo A.; Lauer, Sergio, E-mail: joaocarnaval@inb.gov.br, E-mail: rafaelsantos@inb.gov.br, E-mail: rodrigobarbosa@inb.gov.br, E-mail: lauer@inb.gov.br [Industias Nucleares do Brasil S.A. (INB), Resende, RJ (Brazil)

    2013-07-01

    In the INB nuclear fuel cycle, the pellets production is based on UO{sub 2} powder made by AUC (Ammonium-Uranyl-Carbonate) route. AUC formation occurs by fluidising of UF{sub 6}, NH{sub 3} and CO{sub 2} in a vase containing usually pure water, and this exothermal reaction has AUC as direct product. The mass formed is filtered, washed with CW, washed again with methano solution, dried with air and conducted to the fluidized bed furnace, to be converted to UO{sub 2} powder. At this point, the dried AUC decompounds to UO{sub 3}, NH{sub 3} and C0{sub 2}, these 2 gases are absorbed at the gases washer, formin go the carbonated water (CW), whit is basically a (NH{sub 4}){sub 2}CO{sub 3} solution. The UO{sub 2+x} is reduced and stabilized to UO{sub 2} powder, which is conducted to pellets production. During the process, a considerable amount of this aqueous waste is generated and goes for effluent treatment. After that, the solution is sent for spray-dryer for power formation, and stock. This treatment demands equipment, energy and time, representing considerable costs of the company beyond the human risks involved on the drying step. The purpose of this work is to present a study of the carbonated water use as substitute of pure water in the AUC formation step. At this point, tests were made varying the CW loads for the AUC precipitation, and the control was made by the UO{sub 2} powder properties. The carbonated water used for AUC precipitation has been tested at several levels and the results has demonstrated full viability to become a definitive process step (INB, Resende site). It has been demonstrated the great resources economy caused by the waste reuse and the guarantee product quality. This represents such an environmental gain and also economic and social aspects got improved. (author)

  14. Proposal for a Revised Programme of Studies at the Faculty of Engineering, Ondo State University Using the Pedagogical Model at AUC as Reference

    DEFF Research Database (Denmark)

    Jørgensen, Mogens B.; Borch, Ole; Esan, A. A.

    by AUC Staff. It will, of course, remain a requirement that minimum requirements laid down by the National Universities Commission are met. This was taken into account when preparing the proposal. The report is seen as a first important step towards the introduction of the AUC pedagogical model at OSUA......The present report suggests a revised Programme of Studies at the Faculty of Engineering at Ondo State University. The proposal is based on the present undergraduate teaching programme at the Faculty but at the same time it introduces the pedagogical approach in use at Aalborg University...... as a method of training engineers. The content of the proposed undergraduate teaching programme will to a great extent remain the same as at present and it therefore reflects the objectives of OSUA and the Faculty. At the same time it reflects the ideas regarding the pedagogical approach brought forward...

  15. A perspective for biowaivers of human bioequivalence studies on the basis of the combination of the ratio of AUC to the dose and the biopharmaceutics classification system.

    Science.gov (United States)

    Sakuma, Shinji; Tachiki, Hidehisa; Uchiyama, Hitoshi; Fukui, Yasunobu; Takeuchi, Naohiro; Kumamoto, Kazuo; Satoh, Tomonori; Yamamoto, Yoshinobu; Ishii, Emi; Sakai, Yoshiyuki; Takeuchi, Susumu; Sugita, Masaru; Yamashita, Shinji

    2011-08-01

    The ratio of AUC to the dose (AUC/dose) was previously found as a parameter that predicts a risk of bioinequivalence of oral drug products. On the basis of the combination of this parameter and the biopharmaceutics classification system (BCS), a perspective for biowaivers of human bioequivalence studies is discussed. Databases of bioequivalence studies using immediate-release solid oral dosage forms were disclosed by 6 Japanese generic pharmaceutical companies, and the number of subjects required for demonstrating bioequivalence between generic and reference products was plotted as a function of AUC/dose for each BCS category. A small variation in the number of subjects was constantly observed in bioequivalence studies using dosage forms containing an identical BCS class 1 or class 3 drug, even though formulations of the generic product differ between companies. The variation was extremely enlarged when the drugs were substituted with BCS class 2 drugs. Rate-determining steps in oral absorption of highly water-soluble BCS class 1 and class 3 drugs are independent of formulations when there is no significant difference in the in vitro dissolution profiles between formulations. The small variation observed for both BCS categories indicates that the number of subjects converges into one value for each drug. Our analysis indicates the appropriateness of biowaiver of bioequivalence studies for immediate-release solid oral dosage forms containing not only BCS class 1 drugs but also class 3 drugs.

  16. Application of multi-SNP approaches Bayesian LASSO and AUC-RF to detect main effects of inflammatory-gene variants associated with bladder cancer risk.

    Science.gov (United States)

    de Maturana, Evangelina López; Ye, Yuanqing; Calle, M Luz; Rothman, Nathaniel; Urrea, Víctor; Kogevinas, Manolis; Petrus, Sandra; Chanock, Stephen J; Tardón, Adonina; García-Closas, Montserrat; González-Neira, Anna; Vellalta, Gemma; Carrato, Alfredo; Navarro, Arcadi; Lorente-Galdós, Belén; Silverman, Debra T; Real, Francisco X; Wu, Xifeng; Malats, Núria

    2013-01-01

    The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL), a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk.

  17. Application of multi-SNP approaches Bayesian LASSO and AUC-RF to detect main effects of inflammatory-gene variants associated with bladder cancer risk.

    Directory of Open Access Journals (Sweden)

    Evangelina López de Maturana

    Full Text Available The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL, a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk.

  18. Dynamical coupling of PBPK/PD and AUC-based toxicity models for arsenic in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Liao, C.-M. [Ecotoxicological Modeling Center, Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan 10617 (China)]. E-mail: cmliao@ntu.edu.tw; Liang, H.-M. [Ecotoxicological Modeling Center, Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan 10617 (China); Chen, B.-C. [Department of Post-Modern Agriculture, Mingdao University, Changhua, Taiwan 52345 (China); Singh Sher [Center of Genomics Medicine, School of Medicine, National Taiwan University, Taipei, Taiwan 10617 (China); Tsai, J.-W. [Ecotoxicological Modeling Center, Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan 10617 (China); Chou, Y.-H. [Ecotoxicological Modeling Center, Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan 10617 (China); Lin, W.-T. [Environment Change Research Center, Academia Sinica, Nankang, Taipei, Taiwan 11517 (China)

    2005-05-01

    A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models were developed for arsenic (As) in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan. The PBPK/PD model structure consisted of muscle, gill, gut wall, alimentary canal, and liver, which were interconnected by blood circulation. We integrate the target organ concentrations and dynamic response describing uptake, metabolism, and disposition of As and the associated area-under-curve (AUC)-based toxicological dynamics following an acute exposure. The model validations were compared against the field observations from real tilapia farms and previously published uptake/depuration experimental data, indicating that predicted and measured As concentrations in major organs of tilapia were in good agreement. The model was utilized to reasonably simulate and construct a dose-dependent dynamic response between mortality effect and equilibrium target organ concentrations. Model simulations suggest that tilapia gills may serve as a surrogate sensitive biomarker of short-term exposure to As. This integrated As PBPK/PD/AUC model quantitatively estimates target organ concentration and dynamic response in tilapia and is a strong framework for future waterborne metal model development and for refining a biologically-based risk assessment for exposure of aquatic species to waterborne metals under a variety of scenarios. - Integrated toxicity models can identify dynamic responses of fish to arsenic.

  19. Preparation of Pt Au/C and Pt Au Bi/C electrocatalysts using electron beam irradiation for ethanol electro-oxidation in alkaline medium

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Dionisio F.; Geraldes, Adriana N.; Cardoso, Elisangela S.Z.; Gomes, Thiago B.; Linardi, Marcelo; Oliveira Neto, Almir; Spinace, Estevam V., E-mail: dfsilva@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Pt Au/C (50:50) and PtAuBi/C electrocatalysts with Pt:Au:Bi atomic ratios of 50:40:10, 50:30:20 and 50:10:40 were prepared in water/2-propanol using electron beam irradiation. The materials were characterized by X-ray diffraction (XRD) and the electro-oxidation of ethanol was studied by chronoamperometry at room temperature. The X-ray diffraction measurements for all electrocatalysts prepared showed four peaks, which are associated with the planes of the face-centered cubic (fcc) structure characteristic of Pt and Pt alloys. For PtAuBi/C it was also observed the presence of a mixture of BiPt alloys and bismuth phases. The average crystallite sizes for Pt/C, PtAu/C, PtAuBi/C (50:40:10), PtAuBi/C (50:30:20) and PtAuBi/C (50:10:40) were in the range of 2.0 - 4.0 nm. The activity of the electrocatalysts for ethanol oxidation in alkaline medium showed that PtAuBi/C (50:40:10) had a higher performance for ethanol oxidation compared to others electrocatalysts prepared. (author)

  20. Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios.

    Science.gov (United States)

    Williams, J Andrew; Hyland, Ruth; Jones, Barry C; Smith, Dennis A; Hurst, Susan; Goosen, Theunis C; Peterkin, Vincent; Koup, Jeffrey R; Ball, Simon E

    2004-11-01

    Glucuronidation is a listed clearance mechanism for 1 in 10 of the top 200 prescribed drugs. The objective of this article is to encourage those studying ligand interactions with UDP-glucuronosyltransferases (UGTs) to adequately consider the potential consequences of in vitro UGT inhibition in humans. Spurred on by interest in developing potent and selective inhibitors for improved confidence around UGT reaction phenotyping, and the increased availability of recombinant forms of human UGTs, several recent studies have reported in vitro inhibition of UGT enzymes. In some cases, the observed potency of UGT inhibitors in vitro has been interpreted as having potential relevance in humans via pharmacokinetic drug-drug interactions. Although there are reported examples of clinically relevant drug-drug interactions for UGT substrates, exposure increases of the aglycone are rarely greater than 100% in the presence of an inhibitor relative to its absence (i.e., AUCi/AUC clinical relevance of potent in vitro inhibition of UGT enzymes will be assessed, taking the following into account: in vitro data on the enzymology of glucuronide formation from aglycone, pharmacokinetic principles based on empirical data for inhibition of metabolism, and clinical data on the pharmacokinetic drug-drug interactions of drugs primarily cleared by glucuronidation. Copyright 2004 The American Society for Pharmacology and Experimental Therapeutics

  1. The effect of the nonhuman external regulator’s answer-until-correct (AUC) versus knowledge-of-result (KR) task feedback on children’s behavioral regulation during learning tasks

    NARCIS (Netherlands)

    Agina, Adel Masaud; Agina, Adel M.; Kommers, Petrus A.M.; Steehouder, M.F.

    2011-01-01

    The present study was conducted to shed a new light on the nonhuman’s external regulation effect on children’s behavioral regulation through investigating the effect of the computer’s task feedback answer-until-correct (AUC) versus knowledge-of-result (KR) with 40 preschool children (boys/girls)

  2. Biología reproductiva de Convolvulus chilensis (Convolvulaceae en una población de Aucó (centro-norte de Chile Reproductive biology of Convolvulus chilensis (Convolvulaceae in a population of Aucó (north-central Chile

    Directory of Open Access Journals (Sweden)

    Lorena H. Suárez

    2004-12-01

    Full Text Available Convolvulus chilensis es una hierba perenne, única representante endémica de la familia Convolvulaceae en Chile. Se estudió el sistema de reproducción, fenología, morfología y longevidad floral de C. chilensis en una población natural ubicada en la localidad de Aucó, dentro de la Reserva Nacional Las Chinchillas, IV Región, Chile. Se montó un experimento de polinización controlada considerando los tratamientos de polinización natural, polinización cruzada, autopolinización manual, autopolinización automática y apomixis, evaluándose su efecto sobre la formación de frutos y el número de semillas producidas por fruto. Adicionalmente, se compararon los siguientes atributos de la progenie según tipo de polinización (autopolinización o polinización cruzada: peso de semilla, germinación, altura y número de hojas de plántulas de ocho semanas en condiciones de invernadero. Se encontró que C. chilensis es una especie autocompatible, parcialmente autógama (capaz de autopolinizarse sin mediador y parcialmente apomíctica (capaz de producir semillas sin participación de gameto masculino. La longevidad floral fue estimada en 5,25 h. Durante este período, aproximadamente en 1,5 h hay disponibilidad de polen en los estambres. El período de floración se extiende por 22 semanas (agosto a enero. El tratamiento de apomixis presentó el menor porcentaje de formación de frutos y la menor cantidad de semillas por flor en comparación a los tratamientos de polinización natural, cruzada manual, autopolinización automática y autopolinización manual, los cuales no mostraron diferencias entre sí en ambos atributos. El tipo de polinización (autopolinización o polinización cruzada no afecta el desempeño de la progenie en los atributos de semilla y plántula evaluadosThe perennial herb Convolvulus chilensis is the only endemic species of the Convolvulaceae in Chile. The breeding system, phenology, morphology and floral longevity of C

  3. Factores psicosociales que inciden en la reintegración social de tres reclusos con vínculos a los grupos armados ilegales (FARC-EP, UC-ELN y AUC) del Centro Penitenciario y Carcelario de Villahermosa

    OpenAIRE

    Tatiana A. Romero Rodríguez; Natalia Restrepo Acuña; Ivonne L. Díaz

    2009-01-01

    Esta investigación exploró los factores psicosociales que facilitan o dificultan la Reintegración Social en tres sujetos con vínculos a los grupos armados ilegales (FARC-EP, UC-ELN y AUC) que se encuentran en el Centro Penitenciario y Carcelario de Villahermosa. Estos factores fueron: percepción del conflicto armado en Colombia y de la dinámica del grupo armado ilegal y del patio. Se utilizó metodología cualitativa con diseño descriptivo-exploratorio, la recolección de información se realizó ...

  4. Factores psicosociales que inciden en la Reintegración Social de tres reclusos con vínculos a los grupos armados ilegales (FARC-EP, UC-ELN y AUC) del Centro Penitenciario y Carcelario de Villahermosa

    OpenAIRE

    Romero Rodríguez, Tatiana A.; Restrepo Acuña, Natalia; L. Díaz., Ivonne

    2010-01-01

    Esta investigación exploró los factores psicosociales que facilitan o dificultan la Reintegración Social en tres sujetos con vínculos a los grupos armados ilegales (FARC-EP, UC-ELN y AUC) que se encuentran en el Centro Penitenciario y Carcelario de Villahermosa. Estos factores fueron: percepción del conflicto armado en Colombia y de la dinámica del grupo armado ilegal y del patio. Se utilizó metodología cualitativa con diseño descriptivo-exploratorio, la recolección de información se realizó ...

  5. Incidencia de la desmovilización de las AUC en la política de seguridad ciudadana y convivencia de Bogotá D.C durante el periodo 2004 -2013

    OpenAIRE

    Molano Rojas, Juan Pablo

    2015-01-01

    El interés de este Estudio de Caso, tiene como objetivo analizar la incidencia de la desmovilización de las Autodefensas Unidas de Colombia (AUC) en la Política de Seguridad Ciudadana y Convivencia de Bogotá (PSCCB) durante el periodo 2004 – 2013. Se identifica y analiza, cómo se incluyó un programa para desmovilizados en la Política de Seguridad Ciudadana y Convivencia; además de la reconfiguración de las estructuras del crimen organizado tras dicha desmovilización. Lo anterior, para explica...

  6. Factores psicosociales que inciden en la reintegración social de tres reclusos con vínculos a los grupos armados ilegales (FARC-EP, UC-ELN y AUC del Centro Penitenciario y Carcelario de Villahermosa

    Directory of Open Access Journals (Sweden)

    Tatiana A. Romero Rodríguez

    2009-01-01

    Full Text Available Esta investigación exploró los factores psicosociales que facilitan o dificultan la Reintegración Social en tres sujetos con vínculos a los grupos armados ilegales (FARC-EP, UC-ELN y AUC que se encuentran en el Centro Penitenciario y Carcelario de Villahermosa. Estos factores fueron: percepción del conflicto armado en Colombia y de la dinámica del grupo armado ilegal y del patio. Se utilizó metodología cualitativa con diseño descriptivo-exploratorio, la recolección de información se realizó por medio de entrevistas a profundidad y los participantes fueron tres hombres ubicados en los patios: 2, 4 y 9. La información recolectada se sistematizó por medio del software Ethnograph versión 5.0. Los principales hallazgos fueron: 1 la percepción sobre el conflicto armado contiene elementos estructurales, económicos, culturales que legitiman el mantenimiento del mismo, y 2 se replica la dinámica del grupo armado ilegal en la dinámica grupal al interior de la prisión, teniendo en cuenta esto, se concluye que estos factores dificultan el proceso de reintegración social.

  7. Dramatic effect of redox pre-treatments on the CO oxidation activity of Au/Ce(0.50)Tb(0.12)Zr(0.38)O(2-x) catalysts prepared by deposition-precipitation with urea: a nano-analytical and nano-structural study.

    Science.gov (United States)

    del Río, Eloy; López-Haro, Miguel; Cíes, José M; Delgado, Juan J; Calvino, José J; Trasobares, Susana; Blanco, Ginesa; Cauqui, Miguel A; Bernal, Serafín

    2013-08-04

    Nano-structural and nano-analytical studies show that the dramatic difference in CO oxidation activity observed between two Au/Ce0.50Tb0.12Zr0.38O2-x samples prepared by deposition-precipitation with urea and further activated under oxidising or reducing conditions is due to the poisoning effect of a very thin layer of carbon grown on the pre-reduced catalyst.

  8. 78 FR 47427 - AUC, LLC Reno Creek, In Situ

    Science.gov (United States)

    2013-08-05

    ... discretion of the presiding officer, be permitted to make a limited appearance under 10 CFR 2.315(a), by... and resolve requests for access to SUNSI, and motions for protective orders, in a timely fashion in...

  9. 78 FR 51753 - AUC, LLC Reno Creek, In Situ Project, New Source Material License Application

    Science.gov (United States)

    2013-08-21

    ... at the NRC's PDR, Room O1-F21, One White Flint North, 11555 Rockville Pike, Rockville, Maryland 20852... plant for uranium concentration using ion exchange columns. Final processing is conducted in the central..., ambient background, pollutant sources, and the potential for degradation; Noise: Ambient, sources, and...

  10. Optimal sparse sampling for estimating ganciclovir/valganciclovir AUC in solid organ transplant patients using NONMEN.

    Science.gov (United States)

    Padullés Caldés, Ariadna; Colom, Helena; Caldes, Anna; Cerezo, Gema; Torras, Joan; Grinyó, Josep M; Lloberas, Núria

    2014-06-01

    Ganciclovir and valganciclovir (GCV/VGCV) are used for the treatment and prophylaxis of cytomegalovirus in solid organ transplant (SOT) patients. An area under the time-concentration curve of 40-50 μg × h/mL is related to efficacy. Therapeutic drug monitoring could prevent suboptimal drug exposure and adverse events, but obtaining full concentration profiles is not feasible. Sampling optimization by developing a reliable and clinically applicable limited sampling strategy (LSS) may simplify dose adjustment. An LSS was developed using an original pharmacokinetic (PK) data set of 40 full profiles from 20 adult SOT patients. The LSS was developed based on population and Bayesian prediction approaches. Population PK parameters from a previous model were used for simulation or as priors (NONMEM version 7.2). Median percentage of prediction error and median of absolute percentage prediction error were calculated for plasma clearance (CL) and central compartment distribution volume (V(2)). Bias and precisions were compared using 1-way analysis of variance (SPSSv19.0). Sampling windows were designed according to the PK profile previously observed with the entire set of data. The 4 windows selected were distributed from 0.5 to 1.5 hours, 2 to 3 hours, 4 to 5 hours, and 6 to 8 hours. Predose and concentrations beyond 8 hours were not considered in any case because simulated negative concentrations occurred in both cases. Predicted exposure using 3 sampling times (0.5-1.5, 4-5, and 6-8 hours) showed the best predictive performance, by either the population or Bayesian approaches. Bias and imprecision for CL and V(2) were 0 and 0.60%, and -0.78% and 0.78%, respectively. GCV/VCG area under the time-concentration curve in SOT patients could be predicted with acceptable accuracy for clinical management and dose individualization using LSS. The estimator of GCV/VGC, using 3 concentrations measured at 0.5-1.5, 4-5, and 6-8 hours after drug intake, could be used for dose adjustment.

  11. Influence of crystal/particle size and gold content of a structured Au/C based sorbent on mercury capture

    Science.gov (United States)

    Gómez-Giménez, C.; Ballestero, D.; Ferrer, N.; Rubio, B.; Izquierdo, M. T.

    2017-11-01

    A sorbent based on gold nanoparticles deposited by direct reduction of a gold salt on a structured carbon surface has been prepared to be used in the mercury capture at low concentrations. A total of 13 samples have been obtained varying preparation conditions (stirring rate, gold salt concentration and contact time). A kinetic study of the gold reduction on the carbon surface has been carried out, indicating that the calculated reaction rate constant corresponds to the diffusion rate equation. The study of the influence of gold salt concentration on the reduction potential of the gold showed that the use of a high concentration gold salt solution shifts the reduction reaction to gold reduction. Mercury capture capacity cannot be directly related with either gold content or average particle size or average crystal size, but the study of the grain size distribution can explain the mercury capture performance of the samples.

  12. Mesostructured Au/C materials obtained by replication of functionalized SBA-15 silica containing highly dispersed gold nanoparticles

    KAUST Repository

    Kerdi, Fatmé

    2011-04-01

    The preparation and characterization of highly dispersed gold nanoparticles in ordered mesoporous carbons CMK-3 are reported. These carbons were obtained using gold-containing functionalized SBA-15 silicas as hard templates. Two series of Au/SiO2 templates were prepared, depending on the nature of the functionalization molecule. While ammonium-functionalized silicas gave gold particles with a size determined by the pores of the silica support, the use of mercaptopropyltrimethoxysilane as grafting molecule afforded the possibility to control the particle size inside the mesopores. Both series gave highly ordered mesoporous carbons with gold particles incorporated in the carbon nanorods. However, the gold particle size in mesoporous carbons was the same for both series and apparently did not depend on the nature of the silica template. Both Au/SiO2 templates and their corresponding Au/CMK-3 materials have been characterized by X-ray diffraction, nitrogen adsorption/desorption, chemical analysis, solid-state nuclear magnetic resonance and transmission electron microscopy. They were also used as catalysts in the aerobic oxidation of cyclohexene and trans-stilbene in the liquid phase. © 2010 Elsevier Inc. All rights reserved.

  13. Captura de mercurio en oxicombustión de carbón con un sorbente regenerable basado en Au/C

    OpenAIRE

    Gómez Giménez, Carmen

    2017-01-01

    El mercurio es un elemento extremadamente tóxico que se encuentra de manera omnipresente en la naturaleza. La exposición a este contaminante, a través de la inhalación o/y la ingestión, puede suponer un riesgo para la salud y el medioambiente. La principal fuente antropogénica de emisión de mercurio a la atmósfera es la combustión de combustibles fósiles, en especial la de carbón. Durante la combustión de carbón el mercurio se volatiliza como mercurio elemental, Hg(0). Posteriormente, a me...

  14. Virtual Clinical Studies to Examine the Probability Distribution of the AUC at Target Tissues Using Physiologically-Based Pharmacokinetic Modeling: Application to Analyses of the Effect of Genetic Polymorphism of Enzymes and Transporters on Irinotecan Induced Side Effects.

    Science.gov (United States)

    Toshimoto, Kota; Tomaru, Atsuko; Hosokawa, Masakiyo; Sugiyama, Yuichi

    2017-08-01

    To establish a physiologically-based pharmacokinetic (PBPK) model for analyzing the factors associated with side effects of irinotecan by using a computer-based virtual clinical study (VCS) because many controversial associations between various genetic polymorphisms and side effects of irinotecan have been reported. To optimize biochemical parameters of irinotecan and its metabolites in the PBPK modeling, a Cluster Newton method was introduced. In the VCS, virtual patients were generated considering the inter-individual variability and genetic polymorphisms of enzymes and transporters. Approximately 30 sets of parameters of the PBPK model gave good reproduction of the pharmacokinetics of irinotecan and its metabolites. Of these, 19 sets gave relatively good description of the effect of UGT1A1 *28 and SLCO1B1 c.521T>C polymorphism on the SN-38 plasma concentration, neutropenia, and diarrhea observed in clinical studies reported mainly by Teft et al. (Br J Cancer. 112(5):857-65, 20). VCS also indicated that the frequency of significant association of biliary index with diarrhea was higher than that of UGT1A1 *28 polymorphism. The VCS confirmed the importance of genetic polymorphisms of UGT1A1 *28 and SLCO1B1 c.521T>C in the irinotecan induced side effects. The VCS also indicated that biliary index is a better biomarker of diarrhea than UGT1A1 *28 polymorphism.

  15. Small improvement in the area under the receiver operating characteristic curve indicated small changes in predicted risks.

    Science.gov (United States)

    Martens, Forike K; Tonk, Elisa C M; Kers, Jannigje G; Janssens, A Cecile J W

    2016-11-01

    Adding risk factors to a prediction model often increases the area under the receiver operating characteristic curve (AUC) only slightly, particularly when the AUC of the model was already high. We investigated whether a risk factor that minimally improves the AUC may nevertheless improve the predictive ability of the model, assessed by integrated discrimination improvement (IDI). We simulated data sets with risk factors and event status for 100,000 hypothetical individuals and created prediction models with AUCs between 0.50 and 0.95. We added a single risk factor for which the effect was modeled as a certain odds ratio (OR 2, 4, 8) or AUC increment (ΔAUC 0.01, 0.02, 0.03). Across all AUC values of the baseline model, for a risk factor with the same OR, both ΔAUC and IDI were lower when the AUC of the baseline model was higher. When the increment in AUC was small (ΔAUC 0.01), the IDI was also small, except when the AUC of the baseline model was >0.90. When the addition of a risk factor shows minimal improvement in AUC, predicted risks generally show minimal changes too. Updating risk models with strong risk factors may be informative for a subgroup of individuals, but not at the population level. The AUC may not be as insensitive as is frequently argued. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Evaluation of Postprandial Glucose Excursion Using a Novel Minimally Invasive Glucose Area-Under-the-Curve Monitoring System

    Directory of Open Access Journals (Sweden)

    Sachi Kuranuki

    2013-01-01

    Full Text Available Objective: To develop a minimally invasive interstitial fluid extraction technology (MIET to monitor postprandial glucose area under the curve (AUC without blood sampling, we evaluated the accuracy of glucose AUC measured by MIET and compared with that by blood sampling after food intake. Methods: Interstitial fluid glucose AUC (IG-AUC following consumption of 6 different types of foods was measured by MIET. MIET consisted of stamping microneedle arrays, placing hydrogel patches on the areas, and calculating IG-AUC based on glucose levels in the hydrogels. Glycemic index (GI was determined using IG-AUC and reference AUC measured by blood sampling. Results: IG-AUC strongly correlated with reference AUC (R = 0.91, and GI determined using IG-AUC showed good correlation with that determined by reference AUC (R = 0.88. Conclusions: IG-AUC obtained by MIET can accurately predict the postprandial glucose excursion without blood sampling. In addition, feasibility of GI measurement by MIET was confirmed.

  17. Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36

    DEFF Research Database (Denmark)

    Iepsen, Eva W; Lundgren, Julie; Holst, Jens J

    2016-01-01

    OBJECTIVE: The hormones glucagon-like peptide 1 (GLP-1), peptide YY3-36 (PYY3-36), ghrelin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon have all been implicated in the pathogenesis of obesity. However, it is unknown whether they exhibit adaptive changes with respect......-week very low-calorie diet (800kcal/day). After weight loss, participants entered a 52-week weight maintenance protocol. Plasma levels of GLP-1, PYY3-36, ghrelin, GIP and glucagon during a 600-kcal meal were measured before weight loss, after weight loss and after 1 year of weight maintenance. Area...... under the curve (AUC) was calculated as total AUC (tAUC) and incremental AUC (iAUC). RESULTS: Weight loss was successfully maintained for 52 weeks. iAUC for GLP-1 increased by 44% after weight loss (P3-36 increased by 74% after weight loss...

  18. "Assessment of different bioequivalent metrics in Rifampin bioequivalence study "

    Directory of Open Access Journals (Sweden)

    "Rouini MR

    2002-08-01

    Full Text Available The use of secondary metrics has become special interest in bioequivalency studies. The applicability of partial area method, truncated AUC and Cmax/AUC has been argued by many authors. This study aims to evaluate the possible superiority of these metrics to primary metrics (i.e. AUCinf, Cmax and Tmax. The suitability of truncated AUC for assessment of absorption extent as well as Cmax/AUC and partial AUC for the evaluation of absorption rate in bioequivalency determination was investigated following administration of same product as test and reference to 7 healthy volunteers. Among the pharmacokinetic parameters obtained, Cmax/AUCinf was a better indicator or absorption rate and the AUCinf was more sensitive than truncated AUC in evaluation of absorption extent.

  19. Differential islet and incretin hormone responses in morning versus afternoon after standardized meal in healthy men

    DEFF Research Database (Denmark)

    Lindgren, Ola; Mari, Andrea; Deacon, Carolyn F

    2009-01-01

    .3 mmol/liter, P = 0.001). AUC30(insulin) (4.9 +/- 0.6 vs. 2.8 +/- 0.4 nmol/liter . 30 min; P = 0.012), AUC30(tGLP-1) (300 +/- 40 vs. 160 +/- 30 pmol/liter . 30 min, P = 0.002), AUC30(iGIP) (0.7 +/- 0.1 vs. 0.3 +/- 0.1 nmol/liter . 30 min, P = 0.002), and AUC30(tGIP) (1.1 +/- 0.1 vs. 0.6 +/- 0.1 nmol/liter...

  20. Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Tommy Kyaw Tun

    2016-01-01

    Full Text Available Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48 containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR, hyperandrogenaemia, or PCOS status. 26 women with PCOS (age 30.4±1.2 years (mean ± SEM, body mass index (BMI 36.8±1.5 kg/m2 and 26 non-PCOS subjects (age 34.1±0.9 years, BMI 31.5±1.0 kg/m2 were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG was higher and AUC-high-density lipoprotein (AUC-HDL lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI, AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden.

  1. Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer.

    Science.gov (United States)

    Dowling, Paul; Clarke, Colin; Hennessy, Kim; Torralbo-Lopez, Beatriz; Ballot, Jo; Crown, John; Kiernan, Ingrid; O'Byrne, Kenneth J; Kennedy, M John; Lynch, Vincent; Clynes, Martin

    2012-08-15

    Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models were fitted to the resulting data, and the classification ability of the proteins was evaluated using receiver-operating characteristic curve and leave-one-out cross-validation (LOOCV). The most accurate individual candidate biomarkers were C3 for breast cancer [area under the curve (AUC) = 0.89, LOOCV = 73%], CLI for CRC (AUC = 0.98, LOOCV = 90%), HP for small cell lung carcinoma (AUC = 0.97, LOOCV = 88%), C3 for lung adenocarcinoma (AUC = 0.94, LOOCV = 89%) and HP for squamous cell carcinoma of the lung (AUC = 0.94, LOOCV = 87%). The best dual combination of biomarkers using LR analysis were found to be AHSG + C3 (AUC = 0.91, LOOCV = 83%) for breast cancer, CLI + HP (AUC = 0.98, LOOCV = 92%) for CRC, C3 + SAA (AUC = 0.97, LOOCV = 91%) for small cell lung carcinoma and HP + SAA for both adenocarcinoma (AUC = 0.98, LOOCV = 96%) and squamous cell carcinoma of the lung (AUC = 0.98, LOOCV = 84%). The high AUC values reported here indicated that these candidate biomarkers have the potential to discriminate accurately between control and cancer groups both individually and in combination with other proteins. Copyright © 2011 UICC.

  2. Protein–Protein interaction site prediction in Homo sapiens and E ...

    Indian Academy of Sciences (India)

    The average AUC scores in the 10-fold cross-validation experiments are measured as 79.94% and 80.48% for the Homo sapiens and E. coli organisms respectively. On the independent test datasets, AUC scores are obtained as 76.59% and 80.17% respectively for the two organisms. In almost all cases, the developed ...

  3. Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2015-01-01

    Full Text Available Purpose. To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD using contrast-enhanced ultrasound (CEUS method. Materials and Methods. 79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA group and a high SUA group. Contrast-enhanced ultrasound (CEUS was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis. Results. Normal controls (NCs had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P<0.05. DKD patients with low urinary uric acid (UUA excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P<0.05. Conclusion. Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.

  4. Novel Inhibitors of Protein-Protein Interaction for Prostate Cancer Therapy

    Science.gov (United States)

    2012-04-01

    sophisticated technology - a Nuance™ fluorescence microscope (Caliper/PerkinElmer) equipped with spectral deconvolution and AUC integration software - available...fluorescence was quantitated using the Nuance™ fluorescence microscope equipped with spectral deconvolution and AUC integration software. Amount of JunD co

  5. An excellence initiative in liberal arts and science education: the case of Amsterdam University College

    NARCIS (Netherlands)

    van der Wende, Marijk; Wang, Q; Cheng, Y.

    2013-01-01

    Amsterdam University College (AUC) was established in 2009 as an excellence initiative jointly undertaken by the University of Amsterdam (UvA) and VU University Amsterdam (VU). AUC is a selective and residential honours college that offers an international liberal arts and sciences bachelor

  6. Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease.

    Science.gov (United States)

    Wang, Ling; Cheng, Jia-Fen; Sun, Li-Ping; Song, Ya-Xiang; Guo, Le-Hang; Xu, Jun-Mei; Wu, Tian-Fu; Mohan, Chandra; Peng, Ai; Xu, Hui-Xiong; Liu, Xin-Ying

    2015-01-01

    To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method. 79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis. Normal controls (NCs) had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P < 0.05). DKD patients with low urinary uric acid (UUA) excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P < 0.05). Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.

  7. Six Different Fat Tolerance Tests in Young, Healthy Subjects

    DEFF Research Database (Denmark)

    Rasmussen, Ole Winther; Lauszus, Finn Friis

    2016-01-01

    ) was dtermined for the postprandial values. Results: The meals with six types of butters had similar postprandial response even if the saturated fat content varied with 50%.Gender significantly affected the TG responses, as time to pesk was 90 minutes in women and 180 min in men. Postprandial AUC was higherwith...... respect to TG (pcholesterol (pcholesterol (pcholesterol was lowest in men (AUC, p

  8. Predicting the potential distribution of invasive silver carp ...

    African Journals Online (AJOL)

    The area under the receiver operating characteristics curve (AUC) was used to evaluate model performance. Both the native and introduced range model accurately predicted species occurrences (AUC 0.98 and 0.94, respectively). Most of the north-eastern part of South Africa, including the Limpopo River Basin, where the ...

  9. Improvement of risk prediction by genomic profiling: reclassification measures versus the area under the receiver operating characteristic curve.

    Science.gov (United States)

    Mihaescu, Raluca; van Zitteren, Moniek; van Hoek, Mandy; Sijbrands, Eric J G; Uitterlinden, André G; Witteman, Jacqueline C M; Hofman, Albert; Hunink, M G Myriam; van Duijn, Cornelia M; Janssens, A Cecile J W

    2010-08-01

    Reclassification is observed even when there is no or minimal improvement in the area under the receiver operating characteristic curve (AUC), and it is unclear whether it indicates improved clinical utility. The authors investigated total reclassification, net reclassification improvement, and integrated discrimination improvement for different DeltaAUC using empirical and simulated data. Empirical analyses compared prediction of type 2 diabetes risk based on age, sex, and body mass index with prediction updated with 18 established genetic risk factors. Simulated data were used to investigate measures of reclassification against DeltaAUCs of 0.005, 0.05, and 0.10. Total reclassification and net reclassification improvement were calculated for all possible cutoff values. The AUC of type 2 diabetes risk prediction improved from 0.63 to 0.66 when 18 polymorphisms were added, whereas total reclassification ranged from 0% to 22.5% depending on the cutoff value chosen. In the simulation study, total reclassification, net reclassification improvement, and integrated discrimination improvement increased with higher DeltaAUC. When DeltaAUC was low (0.005), net reclassification improvement values were close to zero, integrated discrimination improvement was 0.08% (P > 0.05), but total reclassification ranged from 0 to 6.7%. Reclassification increases with increasing AUC but predominantly varies with the cutoff values chosen. Reclassification observed in the absence of AUC increase is unlikely to improve clinical utility.

  10. Acute ischemic stroke prognostication, comparison between ...

    African Journals Online (AJOL)

    The areas under receiver operating characteristic curve (AUC) were compared between the three scores. Results: Twenty-five (19.7%) patients died, and seventy-two (56.7%) had unfavourable outcome. The NIHSS, the GCS, and the FOUR score were not different in predicting in-hospital mortality (AUC: 0.783, 0.779, 0.796 ...

  11. Effect of Probenecid on Pharmacokinetics and Tolerability of Olmesartan in Healthy Chinese Volunteers

    Directory of Open Access Journals (Sweden)

    Kun-Yan Li, PhD

    2014-12-01

    Conclusions: Probenecid increases the exposure speed of olmesartan by increasing the AUC0–48, AUC0→∞, and Css-av. The combined treatment of olmesartan medoxomil with probenecid may increase the occurrence of genitourinary side effects. ClinicalTrials.gov identifier: NCT01907373.

  12. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources 2018 AAD election Call for nominations Call ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding ...

  13. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources 2018 AAD election Call for nominations Call ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding ...

  14. Validation of a multimarker model for assessing risk of type 2 diabetes from a five-year prospective study of 6784 Danish people (Inter99)

    DEFF Research Database (Denmark)

    Urdea, Mickey; Kolberg, Janice; Wilber, Judith

    2009-01-01

    to the sequestered validation set, the PreDx DRS showed the same performance (AUC = 0.838), thus validating the model. This model had a better AUC than any other single measure from a fasting sample. Moreover, the model provided further risk stratification among high-risk subpopulations with impaired fasting glucose...

  15. Alpha-1 antitrypsin and granulocyte colony-stimulating factor as serum biomarkers of disease severity in ulcerative colitis

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Nielsen, Ole Haagen; Seidelin, Jakob Benedict

    2015-01-01

    disease severity. RESULTS: Alpha-1 antitrypsin (AAT) differentiated between mild and moderate UC (area under the curve [AUC] = 0.79) with a sensitivity of 0.90 and a specificity of 0.70, thereby exceeding the predictive ability of CRP (AUC = 0.52). Combining alpha-1 antitrypsin and granulocyte colony...

  16. Correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion

    Directory of Open Access Journals (Sweden)

    Jing Wan

    2017-04-01

    Full Text Available Objective: To study the correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion. Methods: A total of 128 patients with thyroid papillary carcinoma who received surgical treatment in the hospital between May 2013 and May 2016 were collected, CEUS was used to make clear the peak intensity (PI and area under the curve (AUC of tumor tissue and surrounding normal tissue, and the median of PI and AUC was referred to further divide the patients into high PI group and low PI group as well as high AUC group and low AUC group, 64 cases in each group. Fluorescent quantitative PCR was used to determine proliferation and invasion gene mRNA expression in tumor tissues. Results: PI and AUC levels in tumor tissue were lower than those in surrounding normal tissue; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low PI group were higher than those of high PI group, and invasion gene Ki-67 mRNA expression was higher than that of high PI group while P53 and MRP-1 mRNA expression were lower than those of high PI group; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low AUC group were higher than those of high AUC group, and invasion gene Ki-67 mRNA expression was higher than that of high AUC group while P53 and MRP-1 mRNA expression were lower than those of high AUC group. Conclusion: Thyroid papillary carcinoma CEUS parameters PI and AUC levels can quantifiably reflect the cancer cell proliferation and invasion activity.

  17. A global goodness-of-fit test for receiver operating characteristic curve analysis via the bootstrap method.

    Science.gov (United States)

    Zou, Kelly H; Resnic, Frederic S; Talos, Ion-Florin; Goldberg-Zimring, Daniel; Bhagwat, Jui G; Haker, Steven J; Kikinis, Ron; Jolesz, Ferenc A; Ohno-Machado, Lucila

    2005-10-01

    Medical classification accuracy studies often yield continuous data based on predictive models for treatment outcomes. A popular method for evaluating the performance of diagnostic tests is the receiver operating characteristic (ROC) curve analysis. The main objective was to develop a global statistical hypothesis test for assessing the goodness-of-fit (GOF) for parametric ROC curves via the bootstrap. A simple log (or logit) and a more flexible Box-Cox normality transformations were applied to untransformed or transformed data from two clinical studies to predict complications following percutaneous coronary interventions (PCIs) and for image-guided neurosurgical resection results predicted by tumor volume, respectively. We compared a non-parametric with a parametric binormal estimate of the underlying ROC curve. To construct such a GOF test, we used the non-parametric and parametric areas under the curve (AUCs) as the metrics, with a resulting p value reported. In the interventional cardiology example, logit and Box-Cox transformations of the predictive probabilities led to satisfactory AUCs (AUC=0.888; p=0.78, and AUC=0.888; p=0.73, respectively), while in the brain tumor resection example, log and Box-Cox transformations of the tumor size also led to satisfactory AUCs (AUC=0.898; p=0.61, and AUC=0.899; p=0.42, respectively). In contrast, significant departures from GOF were observed without applying any transformation prior to assuming a binormal model (AUC=0.766; p=0.004, and AUC=0.831; p=0.03), respectively. In both studies the p values suggested that transformations were important to consider before applying any binormal model to estimate the AUC. Our analyses also demonstrated and confirmed the predictive values of different classifiers for determining the interventional complications following PCIs and resection outcomes in image-guided neurosurgery.

  18. Assessment of early thromboelastometric variables from extrinsically activated assays with and without aprotinin for rapid detection of fibrinolysis.

    Science.gov (United States)

    Dirkmann, Daniel; Görlinger, Klaus; Peters, Jürgen

    2014-09-01

    Although thromboelastometry (ROTEM®) and thrombelastography can be used for bedside diagnosis of fibrinolysis, the time needed for detection is often prolonged. Since untreated fibrinolysis can result in consumption of coagulation factors and bleeding, early diagnosis and decision making are desirable. Accordingly, we assessed ROTEM variables from extrinsically activated assays with (APTEM) and without (EXTEM) addition of aprotinin for their ability to rapidly identify fibrinolysis. Specifically, we tested the hypotheses that prolonged clotting time, clot formation time, low clot firmness (at 5, 10, 15, and 20 minutes, designated A5, A10, A15, and A20, respectively), low maximum clot firmness (MCF) in EXTEM assays, and differences in these variables from parallel APTEM and EXTEM assays (designated as Δvariables) predict fibrinolysis. Data from 411 thromboelastometric measurements (obtained from 352 patients) with fibrinolysis and from 2537 measurements without fibrinolysis (obtained from 1605 patients) were assessed and analyzed using receiver operating characteristics. Data were analyzed as a pooled fibrinolysis cohort, and subanalyses were performed from sets assigned to categories of fibrinolysis related to the timing of thrombus lysis (i.e., a decrease of clot firmness to fibrinolysis. AUCs were compared to identify the variable providing the best predictive association with fibrinolysis. As a secondary end point, optimum cutoff values at the point estimate corresponding to the greatest Youden index were calculated along with the respective sensitivities and specificities. In the pooled cohort, clot formation time (AUC: 0.652 [0.016]), α-angle (AUC: 0.675 [0.015]), A5 (AUC: 0.718 [0.013]), A10 (AUC: 0.734 [0.0.13]), A15 (AUC: 0.752 [0.013]), A20 (AUC: 0.771 [0.013]), and MCF (AUC: 0.799 [0.012]) predicted fibrinolysis. Fibrinolysis was also predicted by ΔA15 (AUC: 0.675 [0.016]), ΔA20 (AUC: 0.719 [0.015]), and ΔMCF (AUC: 0.812 [0.013]). AUCs increased in

  19. Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.

    Directory of Open Access Journals (Sweden)

    Silke A Herzberg-Schäfer

    Full Text Available BACKGROUND: To date, fasting state- and different oral glucose tolerance test (OGTT-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced fasting state-/OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms (SNPs known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures (p≤0.05. The indices were ranked according to their associations' statistical power, and the ranks an index obtained for its associations with all the tested SNPs (or a subset were summed up resulting in a final ranking. This approach revealed area under the curve (AUC(Insulin(0-30/AUC(Glucose(0-30 as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUC(Insulin(0-30/AUC(Glucose(0-30, corrected insulin response (CIR, AUC(C-Peptide(0-30/AUC(Glucose(0-30, AUC(C-Peptide(0-120/AUC(Glucose(0-120, two different formulas for the incremental insulin response from 0-30 min, i.e., the insulinogenic indices (IGI(2 and IGI(1, and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function (HOMA-B; p<0.05. AUC(C-Peptide(0-120/AUC(Glucose(0-120 was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last. CONCLUSIONS/SIGNIFICANCE: With AUC(Insulin(0

  20. Prediction of area under the curve for a p-glycoprotein, a CYP3A4 and a CYP2C9 substrate using a single time point strategy: assessment using fexofenadine, itraconazole and losartan and metabolites.

    Science.gov (United States)

    Srinivas, Nuggehally R

    2016-01-01

    In the present age of polypharmacy, limited sampling strategy becomes important to verify if drug levels are within the prescribed threshold limits from efficacy and safety considerations. The need to establish reliable single time concentration dependent models to predict exposure becomes important from cost and time perspectives. A simple unweighted linear regression model was developed to describe the relationship between Cmax versus AUC for fexofenadine, losartan, EXP3174, itraconazole and hydroxyitraconazole. The fold difference, defined as the quotient of the observed and predicted AUC values, were evaluated along with statistical comparison of the predicted versus observed values. The correlation between Cmax versus AUC was well established for all the five drugs with a correlation coefficient (r) ranging from 0.9130 to 0.9997. Majority of the predicted values for all the five drugs (77%) were contained within a narrow boundary of 0.75- to 1.5-fold difference. The r values for observed versus predicted AUC were 0.9653 (n = 145), 0.8342 (n = 76), 0.9524 (n = 88), 0.9339 (n = 89) and 0.9452 (n = 66) for fexofenadine, losartan, EXP3174, itraconazole and hydroxyitraconazole, respectively. Cmax versus AUC relationships were established for all drugs and were amenable for limited sampling strategy for AUC prediction. However, fexofenadine, EXP3174 and hydroxyitraconazole may be most relevant for AUC prediction by a single time concentration as judged by the various criteria applied in this study.

  1. Joint confidence region estimation for area under ROC curve and Youden index.

    Science.gov (United States)

    Yin, Jingjing; Tian, Lili

    2014-03-15

    In the field of diagnostic studies, the area under the ROC curve (AUC) serves as an overall measure of a biomarker/diagnostic test's accuracy. Youden index, defined as the overall correct classification rate minus one at the optimal cut-off point, is another popular index. For continuous biomarkers of binary disease status, although researchers mainly evaluate the diagnostic accuracy using AUC, for the purpose of making diagnosis, Youden index provides an important and direct measure of the diagnostic accuracy at the optimal threshold and hence should be taken into consideration in addition to AUC. Furthermore, AUC and Youden index are generally correlated. In this paper, we initiate the idea of evaluating diagnostic accuracy based on AUC and Youden index simultaneously. As the first step toward this direction, this paper only focuses on the confidence region estimation of AUC and Youden index for a single marker. We present both parametric and non-parametric approaches for estimating joint confidence region of AUC and Youden index. We carry out extensive simulation study to evaluate the performance of the proposed methods. In the end, we apply the proposed methods to a real data set. Copyright © 2013 John Wiley & Sons, Ltd.

  2. A pilot pharmacologic biomarker study in HLA-haploidentical hematopoietic cell transplant recipients.

    Science.gov (United States)

    Bemer, Meagan J; Sorror, Mohamed; Sandmaier, Brenda M; O'Donnell, Paul V; McCune, Jeannine S

    2013-09-01

    Eleven patients diagnosed with various hematologic malignancies receiving an HLA-haploidentical hematopoietic cell transplant (HCT) participated in an ancillary biomarker trial. The goal of the trial was to evaluate potential pharmacologic biomarkers pertinent to the conditioning regimen [fludarabine monophosphate (fludarabine) and cyclophosphamide (CY)] or postgrafting immunosuppression [CY and mycophenolate mofetil (MMF)] in these patients. We characterized the interpatient variability of nine pharmacologic biomarkers. The biomarkers evaluated were relevant to fludarabine (i.e., area under the curve (AUC) of 2-fluoro-ara-A or F-ara-A), CY (i.e., AUCs of CY and four of its metabolites), and MMF (i.e., total mycophenolic acid (MPA) AUC, unbound MPA AUC, and inosine monophosphate dehydrogenase (IMPDH) activity). Interpatient variability in the pharmacologic biomarkers was high. Among those related to HCT conditioning, the interpatient variability ranged from 1.5-fold (CY AUC) to 4.0-fold (AUC of carboxyethylphosphoramide mustard, a metabolite of CY). Among biomarkers evaluated as part of postgrafting immunosuppression, the interpatient variability ranged from 1.7-fold (CY AUC) to 4.9-fold (IMPDH area under the effect curve). There was a moderate correlation (R (2) = 0.441) of within-patient 4-hydroxycyclophosphamide formation clearance. Considerable interpatient variability exists in the pharmacokinetic and drug-specific biomarkers potentially relevant to clinical outcomes in HLA-haploidentical HCT recipients. Pharmacodynamic studies are warranted to optimize the conditioning regimen and postgrafting immunosuppression administered to HLA-haploidentical HCT recipients.

  3. Valganciclovir dosing using area under the curve calculations in pediatric solid organ transplant recipients.

    Science.gov (United States)

    Villeneuve, David; Brothers, Adam; Harvey, Eric; Kemna, Mariska; Law, Yuk; Nemeth, Thomas; Gantt, Soren

    2013-02-01

    Pediatric valganciclovir dosing recommendations have not been extensively validated for prevention or treatment for CMV infection. As such, we performed a pharmacokinetic study to compare different valganciclovir dosing regimens and the potential benefits of individualized dose adjustments in children following organ transplantation. Ganciclovir AUCs were calculated from four plasma drug levels in pediatric SOT recipients aged six months through three yr receiving valganciclovir suspension by mouth. Of the 28 ganciclovir AUC calculations performed, 11 (39%) were outside the therapeutic target range of 40-60 mcg h/L leading to a valganciclovir dose adjustment. Current manufacturer-recommended dosing based on BSA and CrCl was estimated to result in therapeutic AUCs in fewer patients than the simple weight-based formula used in our institution (4 vs. 13; p = 0.017). An AUC calculation using only the two- and five-h measurements was strongly correlated with the AUC using all four time measurements (R(2) = 0.846; p < 0.001). A simple weight-based dosing approach gives a higher probability for therapeutic AUCs compared to the manufacturer-recommended dosing in pediatric transplant patients aged six months through three yr with normal renal function. An AUC calculated using two sample times might allow for fewer blood draws in the future. © 2012 John Wiley & Sons A/S.

  4. Disadvantages of using the area under the receiver operating characteristic curve to assess imaging tests: A discussion and proposal for an alternative approach

    Energy Technology Data Exchange (ETDEWEB)

    Halligan, Steve [University College London, Centre for Medical Imaging, University College Hospital, London (United Kingdom); Altman, Douglas G. [University of Oxford, Centre for Statistics in Medicine, Oxford (United Kingdom); Mallett, Susan [University of Oxford, Department of Primary Care Health Sciences, Oxford (United Kingdom)

    2015-04-01

    The objectives are to describe the disadvantages of the area under the receiver operating characteristic curve (ROC AUC) to measure diagnostic test performance and to propose an alternative based on net benefit. We use a narrative review supplemented by data from a study of computer-assisted detection for CT colonography. We identified problems with ROC AUC. Confidence scoring by readers was highly non-normal, and score distribution was bimodal. Consequently, ROC curves were highly extrapolated with AUC mostly dependent on areas without patient data. AUC depended on the method used for curve fitting. ROC AUC does not account for prevalence or different misclassification costs arising from false-negative and false-positive diagnoses. Change in ROC AUC has little direct clinical meaning for clinicians. An alternative analysis based on net benefit is proposed, based on the change in sensitivity and specificity at clinically relevant thresholds. Net benefit incorporates estimates of prevalence and misclassification costs, and it is clinically interpretable since it reflects changes in correct and incorrect diagnoses when a new diagnostic test is introduced. ROC AUC is most useful in the early stages of test assessment whereas methods based on net benefit are more useful to assess radiological tests where the clinical context is known. Net benefit is more useful for assessing clinical impact. (orig.)

  5. Association between interdental plaque acidogenicity and caries risk at surface level: a cross sectional study in primary dentition.

    Science.gov (United States)

    Cagetti, Maria Grazia; Campus, Guglielmo; Sale, Silvana; Cocco, Fabio; Strohmenger, Laura; Lingström, Peter

    2011-03-01

    In schoolchildren the most commonly decayed primary teeth are molars affecting proximal adjacent surfaces especially. To determine whether a more acidic plaque in response to sucrose challenge is detected in children with more carious lesions. Plaque pH measurements, using the microtouch technique, were carried out in interproximal spaces between primary molars, in 157 high caries risk children (314 sites and caries status of the 628 proximal surfaces recorded). The area under the curve (AUC(5.7) and AUC(6.2) ) was analyzed. The AUC(5.7) and the AUC(6.2) showed a statistically significant difference between plaque adjacent to proximal surfaces with or without caries. Differences for AUC(5.7) and AUC(6.2) were recorded between one decayed surface compared to two decayed surfaces (P<0.01) whereas a statistical significant difference was only observed for AUC(5.7) , when the areas under the curve were obtained near one decayed surface compared to two sound surfaces (P=0.04). The higher acidogenicity of the dental plaque found in presence of a proximal carious lesion in primary maxillary molars represents an additional risk factor for the adjacent surface. This finding may help clinicians in treatment decisions. © 2010 The Authors. International Journal of Paediatric Dentistry © 2010 BSPD, IAPD and Blackwell Publishing Ltd.

  6. Evaluation of a minimally invasive system for measuring glucose area under the curve during oral glucose tolerance tests: usefulness of sweat monitoring for precise measurement.

    Science.gov (United States)

    Sakaguchi, Kazuhiko; Hirota, Yushi; Hashimoto, Naoko; Ogawa, Wataru; Hamaguchi, Tomoya; Matsuo, Toshihiro; Miyagawa, Jun-ichiro; Namba, Mitsuyoshi; Sato, Toshiyuki; Okada, Seiki; Tomita, Koji; Matsuhisa, Munehide; Kaneto, Hideaki; Kosugi, Keisuke; Maegawa, Hiroshi; Nakajima, Hiromu; Kashiwagi, Atsunori

    2013-05-01

    We developed a system for measuring glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET). Sweat contamination during interstitial fluid glucose (IG) extraction affects the accuracy of glucose AUC measurement, because this technology uses extracted sodium ion levels as an internal standard. Therefore, we developed a sweat monitoring patch to reduce this effect and investigated its efficacy in volunteers undergoing oral glucose tolerance tests (OGTTs). Fifty diabetes mellitus inpatients and 10 healthy subjects undergoing the 75 g OGTT were included. Two sites on the forearm were pretreated with microneedle arrays, then hydrogels for interstitial fluid extraction were placed on the treated sites. Simultaneously, hydrogels for sweat monitoring were placed on untreated sites near the treated sites. Plasma glucose (PG) levels were measured every 30 min for 2 h to calculate reference AUC values. Using MIET, IG AUC was calculated from extracted glucose and sodium ion levels after attachment of the hydrogel for 2 h. Good correlation between IG AUC measurements using MIET and reference AUCs measured using PG levels was confirmed over a wide AUC range (202-610 mg/h/dl) after correction for the sweat-induced error detected by the hydrogel patches on the nonpretreated skin. Strong correlation between IG AUC and peak glucose levels indicates that glucose spikes can be easily detected by this system. We confirmed the effectiveness of a sweat monitoring patch for precise AUC measurement using MIET. This novel, easy-to-use system has potential for glucose excursion evaluation in daily clinical practice. © 2013 Diabetes Technology Society.

  7. Effect of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease.

    Science.gov (United States)

    Nakamura, Akihiro; Monma, Yuto; Kajitani, Shoko; Noda, Kazuki; Nakajima, Sota; Endo, Hideaki; Takahashi, Tohru; Nozaki, Eiji

    2016-09-01

    Both postprandial hyperlipidemia and hyperinsulinemia have been thought to play an important role in the development of atherosclerosis, and to be a potent risk factor for cardiovascular event. To examine effects of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease (CAD), a total of 112 consecutive male pati ents with angiographically confirmed CAD were loaded with a high-fat and high-glucose test meal. CAD patients were divided into three groups as "non-diabetic", "prediabetic", and "diabetic" CAD groups. The serum triglyceride (TG) and remnant-like particle cholesterol (RLP-C) levels at the 6th hour in diabetic CAD group showed significantly higher than non-diabetic CAD group, and the incremental area under the curves (iAUCs) of these levels in diabetic CAD group were significantly greater than non-diabetic CAD group (TG, P = 0.0194; RLP-C, P = 0.0219). There were no significant differences in the iAUCs of TG or RLP-C between prediabetic and non-diabetic CAD group. The AUCs of plasma insulin levels or insulin resistance index (IRI): (AUCs of insulin) × (AUCs of glucose) as the insulin resistance marker were greater in diabetic CAD group than non-diabetic CAD group (insulin, P = 0.0373; IRI, P = 0.0228). The AUCs of serum TG or RLP-C levels showed a correlation with the AUCs of plasma insulin (AUC-TG, r = 0.5437, P index (AUC-TG, r = 0.7724, P lipid metabolism in CAD patients.

  8. Disadvantages of using the area under the receiver operating characteristic curve to assess imaging tests: a discussion and proposal for an alternative approach.

    Science.gov (United States)

    Halligan, Steve; Altman, Douglas G; Mallett, Susan

    2015-04-01

    The objectives are to describe the disadvantages of the area under the receiver operating characteristic curve (ROC AUC) to measure diagnostic test performance and to propose an alternative based on net benefit. We use a narrative review supplemented by data from a study of computer-assisted detection for CT colonography. We identified problems with ROC AUC. Confidence scoring by readers was highly non-normal, and score distribution was bimodal. Consequently, ROC curves were highly extrapolated with AUC mostly dependent on areas without patient data. AUC depended on the method used for curve fitting. ROC AUC does not account for prevalence or different misclassification costs arising from false-negative and false-positive diagnoses. Change in ROC AUC has little direct clinical meaning for clinicians. An alternative analysis based on net benefit is proposed, based on the change in sensitivity and specificity at clinically relevant thresholds. Net benefit incorporates estimates of prevalence and misclassification costs, and it is clinically interpretable since it reflects changes in correct and incorrect diagnoses when a new diagnostic test is introduced. ROC AUC is most useful in the early stages of test assessment whereas methods based on net benefit are more useful to assess radiological tests where the clinical context is known. Net benefit is more useful for assessing clinical impact. • The area under the receiver operating characteristic curve (ROC AUC) measures diagnostic accuracy. • Confidence scores used to build ROC curves may be difficult to assign. • False-positive and false-negative diagnoses have different misclassification costs. • Excessive ROC curve extrapolation is undesirable. • Net benefit methods may provide more meaningful and clinically interpretable results than ROC AUC.

  9. Pitfalls in Prediction Modeling for Normal Tissue Toxicity in Radiation Therapy: An Illustration With the Individual Radiation Sensitivity and Mammary Carcinoma Risk Factor Investigation Cohorts

    Energy Technology Data Exchange (ETDEWEB)

    Mbah, Chamberlain, E-mail: chamberlain.mbah@ugent.be [Department of Basic Medical Sciences, Faculty of Health Sciences, Ghent University, Ghent (Belgium); Department of Mathematical Modeling, Statistics, and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Ghent (Belgium); Thierens, Hubert [Department of Basic Medical Sciences, Faculty of Health Sciences, Ghent University, Ghent (Belgium); Thas, Olivier [Department of Mathematical Modeling, Statistics, and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Ghent (Belgium); National Institute for Applied Statistics Research Australia, University of Wollongong, Wollongong, New South Wales (Australia); De Neve, Jan [Department of Data Analysis, Faculty of Psychology and Educational Sciences, Ghent University, Ghent (Belgium); Chang-Claude, Jenny; Seibold, Petra; Botma, Akke [Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg (Germany); West, Catharine [Translational Radiobiology Group, Institute of Cancer Sciences, Radiotherapy Related Research, Christie Hospital NHS Trust, University of Manchester, Manchester (United Kingdom); De Ruyck, Kim [Department of Basic Medical Sciences, Faculty of Health Sciences, Ghent University, Ghent (Belgium)

    2016-08-01

    Purpose: To identify the main causes underlying the failure of prediction models for radiation therapy toxicity to replicate. Methods and Materials: Data were used from two German cohorts, Individual Radiation Sensitivity (ISE) (n=418) and Mammary Carcinoma Risk Factor Investigation (MARIE) (n=409), of breast cancer patients with similar characteristics and radiation therapy treatments. The toxicity endpoint chosen was telangiectasia. The LASSO (least absolute shrinkage and selection operator) logistic regression method was used to build a predictive model for a dichotomized endpoint (Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer score 0, 1, or ≥2). Internal areas under the receiver operating characteristic curve (inAUCs) were calculated by a naïve approach whereby the training data (ISE) were also used for calculating the AUC. Cross-validation was also applied to calculate the AUC within the same cohort, a second type of inAUC. Internal AUCs from cross-validation were calculated within ISE and MARIE separately. Models trained on one dataset (ISE) were applied to a test dataset (MARIE) and AUCs calculated (exAUCs). Results: Internal AUCs from the naïve approach were generally larger than inAUCs from cross-validation owing to overfitting the training data. Internal AUCs from cross-validation were also generally larger than the exAUCs, reflecting heterogeneity in the predictors between cohorts. The best models with largest inAUCs from cross-validation within both cohorts had a number of common predictors: hypertension, normalized total boost, and presence of estrogen receptors. Surprisingly, the effect (coefficient in the prediction model) of hypertension on telangiectasia incidence was positive in ISE and negative in MARIE. Other predictors were also not common between the 2 cohorts, illustrating that overcoming overfitting does not solve the problem of replication failure of prediction models completely

  10. Linearity of levodropropizine, a new antitussive drug, in the healthy volunteer.

    Science.gov (United States)

    Borsa, M; Glavenna, G; Ferrari, M P; Canali, S; Giachetti, C; Zanolo, G

    1991-01-01

    The object of this study was to determine whether the pharmacokinetics of levodropropizine were linear. Twelve healthy adult male volunteers received oral doses use of 30, 60 and 90 mg of levodropropizine. A cross-over design was used. With the exception of Cmax, and AUC the pharmacokinetics of levodropropizine in the dose range studied are similar. The relationship between the doses and AUCs and the statistical comparison of AUCs (Anova test and Westlake test) confirm that in the range 30-90 mg the plasma pharmacokinetics of levodropropizine are linear.

  11. Pharmacokinetics of mycophenolic acid and estimation of exposure using multiple linear regression equations in Chinese renal allograft recipients.

    Science.gov (United States)

    Zhou, Pei-Jun; Xu, Da; Yu, Zi-Cheng; Wang, Xiang-Hui; Shao, Kun; Zhao, Ju-Ping

    2007-01-01

    To investigate the pharmacokinetics of mycophenolic acid (MPA) in Chinese adult renal allograft recipients, and to generate the validated model equations for estimation of the MPA area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) with a limited sampling strategy. The pharmacokinetics in 75 Chinese renal allograft recipients treated with mycophenolate mofetil 2 g/day in combination with cyclosporin and corticosteroids were determined. The MPA concentration was assayed by high-performance liquid chromatography at pre-dose (C(0)) and at 0.5 (C(0.5)), 1 (C(1)), 1.5 (C(1.5)), 2 (C(2)), 4 (C(4)), 6 (C(6)), 8 (C(8)), 10 (C(10)) and 12 (C(12)) hours after dosing on day 14 post-transplant. Patients were randomly divided into: (i) a model group (n = 50) to generate the model equations by multiple stepwise regression analysis for estimation of the MPA AUC by a limited sampling strategy; and (ii) a validation group (n = 25) to evaluate the predictive performance of the model equations. The mean MPA AUC(12) was 52.97 +/- 15.09 mg . h/L, ranging from 24.0 to 102.3 mg . h/L. The patient's age and serum albumin level had a significant impact on the MPA AUC(12). The correlation between the pre-dose MPA trough level (C(0)) and the MPA AUC(12) was poor (r(2) = 0.02, p = 0.33). Model equations 7 (MPA AUC(12) = 14.81 + 0.80 . C(0.5) + 1.56 . C(2) + 4.80 . C(4), r(2) = 0.70) and 11 (MPA AUC(12) = 11.29 + 0.51 . C(0.5) + 2.13 . C(2) + 8.15 . C(8), r(2) = 0.88) were selected for MPA AUC calculation in Chinese patients, resulting in good agreements between the estimated MPA AUC and the full MPA AUC(12), with a mean prediction error of +/-10.1 and +/-6.9 mg . h/L, respectively. In Chinese renal allograft recipients, MPA pharmacokinetics manifest substantial interindividual variability, and the MPA AUC(12) tends to be higher than that in Caucasian patients receiving the same dose of mycophenolate mofetil. Two validated model equations with three sampling timepoints

  12. Bug bites and stings: When to see a dermatologist

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  18. Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and type 2-diabetic patients using exendin [9-39] as a GLP-1 receptor antagonist

    DEFF Research Database (Denmark)

    Nauck, Michael A; Kind, J; Köthe, Lars D

    2016-01-01

    We quantified the contribution of GLP-1 as a mediator of the therapeutic effects of dipeptidyl peptidase 4 (DPP-4) inhibition (vildagliptin) by using the GLP-1 receptor antagonist exendin [9-39] in patients with type 2 diabetes and in healthy subjects. Thirty-two patients with type 2 diabetes...... and 29 age-and weight-matched healthy control subjects were treated in randomized order with 100 mg once daily vildagliptin or placebo for 10 days. Meal tests were performed (days 9 and 10) without and with a high-dose intravenous infusion of exendin [9-39]. The main end point was the ratio of the areas...... under the curve (AUCs) of integrated insulin secretion rates (total AUC(ISR)) and glucose (total AUC(glucose)) over 4 h after the meal. Vildagliptin treatment more than doubled responses of intact GLP-1 and glucose-dependent insulinotropic polypeptide and lowered glucose responses without changing AUC...

  19. Dandruff: How to Treat

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  18. How to Stop Biting Your Nails

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    Full Text Available ... in Medical Dermatology™ Excellence in Dermatopathology™ Excellence in Pediatric Dermatology™ Donate Search Menu Donate Member resources and ... Dialogues in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement ...

  19. Bug bites and stings: When to see a dermatologist

    Medline Plus

    Full Text Available ... in Medical Dermatology™ Excellence in Dermatopathology™ Excellence in Pediatric Dermatology™ Donate Search Menu Donate Member resources and ... Dialogues in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement ...

  20. MEA 86 Compound data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data file contains the full raw parameter data for the 86 compounds tested in the developmental MEA assay, as well as Area Under the Curve (AUC) calculations...

  1. Bug bites and stings: When to see a dermatologist

    Medline Plus

    Full Text Available ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding ... measures Clinical guidelines Appropriate use criteria Choosing Wisely Education Online Learning Center MOC Component parts FAQs Recognized ...

  2. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding ... measures Clinical guidelines Appropriate use criteria Choosing Wisely Education Online Learning Center MOC Component parts FAQs Recognized ...

  3. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding ... measures Clinical guidelines Appropriate use criteria Choosing Wisely Education Online Learning Center MOC Component parts FAQs Recognized ...

  4. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ... complex. The most effective way to treat and control dandruff is to use dandruff shampoo and scalp ...

  5. Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Lund, Søren S; Tarnow, Lise; Frandsen, Merete

    2008-01-01

    the curve (AUC) for plasma glucose, triglycerides and free fatty acids (FFA) changed equally between treatments. In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during...... daily or vice versa each during 4 months with 1-month washout between interventions. METHODS: Postprandial metabolism was evaluated by a standard test meal (3515 kJ; 54% fat, 13% protein and 33% carbohydrate) with blood sampling 0-6 h postprandially. RESULTS: Fasting levels and total area under...... metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)). AUC differences remained significant after adjusting for fasting levels. CONCLUSIONS: In non-obese T2DM patients, metformin reduced postprandial levels...

  6. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Dialogues in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement ... Scope of practice Truth in advertising Public and patients SPOT Skin Cancer™ Community programs & events Learn about ...

  7. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ... for the best product recommendation for your hair type. Be careful when using a dandruff shampoo that ...

  8. Bug bites and stings: When to see a dermatologist

    Medline Plus

    Full Text Available ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ... Meetings and events 2018 Annual Meeting Registration General information Housing & travel Education Exhibit hall Mobile app Derm ...

  9. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ... Meetings and events 2018 Annual Meeting Registration General information Housing & travel Education Exhibit hall Mobile app Derm ...

  10. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ... Meetings and events 2018 Annual Meeting Registration General information Housing & travel Education Exhibit hall Mobile app Derm ...

  11. Searching for prostate cancer by fully automated magnetic resonance imaging classification: deep learning versus non-deep learning

    National Research Council Canada - National Science Library

    Xinggang Wang; Wei Yang; Jeffrey Weinreb; Juan Han; Qiubai Li; Xiangchuang Kong; Yongluan Yan; Zan Ke; Bo Luo; Tao Liu; Liang Wang

    2017-01-01

    ...) patients with prostatitis or prostate benign hyperplasia (BPH). In fully automated detection of PCa patients, deep learning had a statistically higher area under the receiver operating characteristics curve (AUC...

  12. Bug bites and stings: When to see a dermatologist

    Medline Plus

    Full Text Available ... and events Make a difference Career planning Media Relations Toolkit AAD apps Academy meeting Chronic urticaria—for members Chronic urticaria—for public Dermatology World Dialogues in Dermatology JAAD Mohs AUC ...

  13. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... and events Make a difference Career planning Media Relations Toolkit AAD apps Academy meeting Chronic urticaria—for members Chronic urticaria—for public Dermatology World Dialogues in Dermatology JAAD Mohs AUC ...

  14. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... and events Make a difference Career planning Media Relations Toolkit AAD apps Academy meeting Chronic urticaria—for members Chronic urticaria—for public Dermatology World Dialogues in Dermatology JAAD Mohs AUC ...

  15. Cyclosporine C2 levels have impact on incidence of rejection in de novo lung but not heart transplant recipients: the NOCTURNE study

    DEFF Research Database (Denmark)

    Iversen, Martin; Nilsson, Folke; Sipponen, Jorma

    2009-01-01

    BACKGROUND: Cyclosporine (CsA) absorption varies early after transplantation and can be accurately assessed by the area under the absorption curve (AUC). The 2-hour post-dose (C2) level of CsA in whole blood is reported to be a useful surrogate marker of CsA AUC in kidney and liver transplant...... monitoring, but should be further explored in thoracic organ recipients. METHODS: In a 12-month study we included de novo lung (n = 95) and heart (n = 96) recipients. All participants received cyclosporine (Sandimmun Neoral) monitored by C0 and blood was collected for analysis of C2 retrospectively....... Abbreviated AUC (AUC(0-4)) was measured at 7 days and 3 months. Primary outcome was C2 relation to the frequency of acute cellular rejection (ACR) needing treatment and possible decline in measured glomerular filtration rate (mGFR). Recipients were divided into lower, middle and upper third C2 groups based...

  16. Strategy for the Prediction of Steady-State Exposure of Digoxin to Determine Drug-Drug Interaction Potential of Digoxin With Other Drugs in Digitalization Therapy.

    Science.gov (United States)

    Srinivas, Nuggehally R

    2016-01-20

    Digoxin, a narrow therapeutic index drug, is widely used in congestive heart failure. However, the digitalization therapy involves dose titration and can exhibit drug-drug interaction. Ctrough versus area under the plasma concentration versus time curve in a dosing interval of 24 hours (AUC0-24h) and Cmax versus AUC0-24h for digoxin were established by linear regression. The predictions of digoxin AUC0-24h values were performed using published Ctrough or Cmax with appropriate regression lines. The fold difference, defined as the quotient of the observed/predicted AUC0-24h values, was evaluated. The mean square error and root mean square error, correlation coefficient (r), and goodness of the fold prediction were used to evaluate the models. Both Ctrough versus AUC0-24h (r = 0.9215) and Cmax versus AUC0-24h models for digoxin (r = 0.7781) showed strong correlations. Approximately 93.8% of the predicted digoxin AUC0-24h values were within 0.76-fold to 1.25-fold difference for Ctrough model. In sharp contrast, the Cmax model showed larger variability with only 51.6% of AUC0-24h predictions within 0.76-1.25-fold difference. The r value for observed versus predicted AUC0-24h for Ctrough (r = 0.9551; n = 177; P < 0.001) was superior to the Cmax (r = 0.6134; n = 275; P < 0.001) model. The mean square error and root mean square error (%) for the Ctrough model were 11.95% and 16.2% as compared to 67.17% and 42.3% obtained for the Cmax model. Simple linear regression models for Ctrough/Cmax versus AUC0-24h were derived for digoxin. On the basis of statistical evaluation, Ctrough was superior to Cmax model for the prediction of digoxin AUC0-24h and can be potentially used in a prospective setting for predicting drug-drug interaction or lack of it.

  17. A boosting method for maximizing the partial area under the ROC curve

    Directory of Open Access Journals (Sweden)

    Eguchi Shinto

    2010-06-01

    Full Text Available Abstract Background The receiver operating characteristic (ROC curve is a fundamental tool to assess the discriminant performance for not only a single marker but also a score function combining multiple markers. The area under the ROC curve (AUC for a score function measures the intrinsic ability for the score function to discriminate between the controls and cases. Recently, the partial AUC (pAUC has been paid more attention than the AUC, because a suitable range of the false positive rate can be focused according to various clinical situations. However, existing pAUC-based methods only handle a few markers and do not take nonlinear combination of markers into consideration. Results We have developed a new statistical method that focuses on the pAUC based on a boosting technique. The markers are combined componentially for maximizing the pAUC in the boosting algorithm using natural cubic splines or decision stumps (single-level decision trees, according to the values of markers (continuous or discrete. We show that the resulting score plots are useful for understanding how each marker is associated with the outcome variable. We compare the performance of the proposed boosting method with those of other existing methods, and demonstrate the utility using real data sets. As a result, we have much better discrimination performances in the sense of the pAUC in both simulation studies and real data analysis. Conclusions The proposed method addresses how to combine the markers after a pAUC-based filtering procedure in high dimensional setting. Hence, it provides a consistent way of analyzing data based on the pAUC from maker selection to marker combination for discrimination problems. The method can capture not only linear but also nonlinear association between the outcome variable and the markers, about which the nonlinearity is known to be necessary in general for the maximization of the pAUC. The method also puts importance on the accuracy of

  18. Der Weg der paramilitärischen Autodefensas Unidas de Colombia zur politischen Anerkennung

    OpenAIRE

    Oldenburg, Silke; Lengert, Kristofer

    2006-01-01

    Im Rahmen der Friedensverhandlungen zwischen kolumbianischer Regierung und den paramilitärischen Autodefensas Unidas de Colombia (AUC) wurde erstmals öffentlichkeitswirksam über deren Demobilisierung verhandelt. Die AUC beabsichtigen damit, ihre Transformation vom militärischen hin zum politi- schen Akteur in der Öffentlichkeit zu vollziehen, wobei sich jedoch eine reale Auflösung der militärischen, wirtschaftlichen und sozialen Strukturen der paramilitärischen Netzwerke nicht abzeichnet. Anh...

  19. Sensitivity and specificity of neuropsychological tests for dementia

    African Journals Online (AJOL)

    (AUC) values for dementia v. non-dementia participants ranged from 0.519 for the digit span (forward) to 0.828 for the digit symbol (90 s), with 14 of the 29 test scores achieving significance (p<0.05). AUC values for MCI participants ranged from 0.754 for controlled oral word association test (COWAT) Animal to 0.507 for the ...

  20. Fully automated structural MRI of the brain in clinical dementia workup.

    Science.gov (United States)

    Persson, Karin; Selbæk, Geir; Brækhus, Anne; Beyer, Mona; Barca, Maria; Engedal, Knut

    2017-06-01

    Background The dementia syndrome has been regarded a clinical diagnosis but the focus on supplemental biomarkers is increasing. An automatic magnetic resonance imaging (MRI) volumetry method, NeuroQuant® (NQ), has been developed for use in clinical settings. Purpose To evaluate the clinical usefulness of NQ in distinguishing Alzheimer's disease dementia (AD) from non-dementia and non-AD dementia. Material and Methods NQ was performed in 275 patients diagnosed according to the criteria of ICD-10 for AD, vascular dementia and Parkinson's disease dementia (PDD); the Winblad criteria for mild cognitive impairment; the Lund-Manchester criteria for frontotemporal dementia; and the revised consensus criteria for Lewy body dementia (LBD). Receiver operating curve (ROC) analyses with calculation of area under the curve (AUC) and regression analyses were carried out. Results Forebrain parenchyma (AUC 0.82), hippocampus (AUC 0.80), and inferior lateral ventricles (AUC 0.78) yielded the highest AUCs for AD/non-dementia discrimination. Only hippocampus (AUC 0.62) and cerebellum (AUC 0.67) separated AD from non-AD dementia. Cerebellum separated AD from PDD-LBD (AUC 0.83). Separate multiple regression analyses adjusted for age and gender, showed that memory (CERAD 10-word delayed recall) (beta 0.502, P dementia (beta -0.392, P dementia fairly well but generally poorer from non-AD dementia. Degree of memory impairment, age, and gender, but not diagnostic distinction, were associated to the hippocampus volume in adjusted analyses. Surprisingly, cerebellum was found relevant in separating AD from PDD-LBD.

  1. Analytical Ultracentrifugation: Sedimentation Velocity and Sedimentation Equilibrium

    OpenAIRE

    Cole, James L.; Lary, Jeffrey W.; Moody, Thomas; Thomas M Laue

    2008-01-01

    Analytical ultracentrifugation (AUC) is a versatile and powerful method for the quantitative analysis of macromolecules in solution. AUC has broad applications for the study of biomacromolecules in a wide range of solvents and over a wide range of solute concentrations. Three optical systems are available for the analytical ultracentrifuge (absorbance, interference and fluorescence) that permit precise and selective observation of sedimentation in real time. In particular, the fluorescence sy...

  2. Is procalcitonin to C-reactive protein ratio useful for the detection of late onset neonatal sepsis?

    Science.gov (United States)

    Hahn, Won-Ho; Song, Joon-Hwan; Kim, Ho; Park, Suyeon

    2017-03-09

    Procalcitonin (PCT) has been reported as a sensitive marker for neonatal bacterial infections. Recently, small numbers of studies reported usefulness of PCT/C-reactive protein (CRP) ratio in detection of infectious conditions in adults. Thus, we conducted this study to evaluate PCT/CRP ratio in late onset neonatal sepsis. Serum PCT and CRP was measured in blood samples from 7 to 60 days after birth in 106 of neonates with late onset sepsis and 212 of controls who were matched with gestational age, postnatal age, birth weight, and gender. Areas under ROC curve (AUC) were calculated, and pairwise comparisons between ROC curves were performed. As a result, CRP (AUC 0.96) showed best performance in detection of sepsis from healthy controls compared with PCT (AUC 0.87) and PCT/CRP ratio (AUC 0.62); CRP > PCT > PCT/CRP ratio in pairwise comparison (p sepsis from healthy controls compared with PCT/CRP ratio (AUC 0.54); CRP = PCT > PCT/CRP ratio in pairwise comparison (p detection of blood culture proven sepsis from suspected sepsis, PCT (AUC 0.70), and PCT/CRP ratio (AUC 0.73) showed better performance compared with CRP (AUC 0.51); PCT = PCT/CRP ratio > CRP in pairwise comparison (p sepsis and healthy controls. However, PCT/CRP ratio seems to be helpful in distinguishing proven sepsis from suspected sepsis together with PCT. Further studies are warranted to elucidate the efficacy of PCT/CRP ratio with enrollment of enough numbers of infants.

  3. Risk of impaired glucose tolerance in normal weight hirsute women during four years observation

    DEFF Research Database (Denmark)

    Andries, Magdalene; Glintborg, Dorte; Andersen, Marianne

    2010-01-01

    unchanged BMI compared to baseline but increased fasting and 2 hour glucose levels. Impaired OGTT outcome during follow-up was seen in 14/66 (21.2%) women, 5/66 (7.6%) developed diabetes. Women who took oral contraceptives had a significantly decreased area under the curve (AUC) for insulin during follow......-up, whereas AUC glucose levels increased. The present data supported a high risk of diabetes in only moderately overweight hirsute women....

  4. Association of Anthropometric Measurement Methods with Cardiovascular Disease Risk in Turkey

    Directory of Open Access Journals (Sweden)

    Kaan Sözmen

    2016-03-01

    Full Text Available Objective: The aim of this study is to compare the predic­tive power of anthropometric indices for risk of developing Coronary Heart Disease (CHD or CHD death. Methods: We used cross-sectional data from nationally representative Chronic Diseases and Risk Factors Sur­vey conducted by the Ministry of Health in 2011. Body mass index (BMI, waist circumference (WC, waist-to-hip ratio (WHR, waist to height ratio (WHtR, body adiposity index (BAI and A Body Shape Index (ABSI formed the anthropometric measures. For each participant risk of de­veloping CHD or dying from CVDs were calculated based on Framingham and SCORE risk equations. Predictive ability of anthropometric measurements was assessed by receiver operating characteristic (ROC curves. Results: Anthropometric measurements of central obe­sity recorded higher area under the ROC curve (AUC values than BMI in both men and women. While ABSI had the highest AUC values for Framingham 10-year pre­dicted risk (FRS for CHD death (AUC = 0.613, SCORE 10-year risk for CVD death (AUC = 0.633, in women AUC for ABSI was the highest for only SCORE risk threshold (AUC = 0.705. Among women, WHtR was found to be the best indicator for estimating CHD incidence (AUC = 0.706 and death from CVD (AUC = 0.696. Conclusion: Compared to traditional anthropometric measurements such as BMI, ABSI was a better indicator for given thresholds for estimating the risk of developing CHD and CVD death in men. Among women WHtR made better predictions for FRS thresholds, however, ABSI was better for predicting 10-year risk of CVD death calculated by SCORE risk equation.

  5. Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease.

    Science.gov (United States)

    Deja, Stanislaw; Porebska, Irena; Kowal, Aneta; Zabek, Adam; Barg, Wojciech; Pawelczyk, Konrad; Stanimirova, Ivana; Daszykowski, Michal; Korzeniewska, Anna; Jankowska, Renata; Mlynarz, Piotr

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) and lung cancer are widespread lung diseases. Cigarette smoking is a high risk factor for both the diseases. COPD may increase the risk of developing lung cancer. Thus, it is crucial to be able to distinguish between these two pathological states, especially considering the early stages of lung cancer. Novel diagnostic and monitoring tools are required to properly determine lung cancer progression because this information directly impacts the type of the treatment prescribed. In this study, serum samples collected from 22 COPD and 77 lung cancer (TNM stages I, II, III, and IV) patients were analyzed. Then, a collection of NMR metabolic fingerprints was modeled using discriminant orthogonal partial least squares regression (OPLS-DA) and further interpreted by univariate statistics. The constructed discriminant models helped to successfully distinguish between the metabolic fingerprints of COPD and lung cancer patients (AUC training=0.972, AUC test=0.993), COPD and early lung cancer patients (AUC training=1.000, AUC test=1.000), and COPD and advanced lung cancer patients (AUC training=0.983, AUC test=1.000). Decreased acetate, citrate, and methanol levels together with the increased N-acetylated glycoproteins, leucine, lysine, mannose, choline, and lipid (CH3-(CH2)n-) levels were observed in all lung cancer patients compared with the COPD group. The evaluation of lung cancer progression was also successful using OPLS-DA (AUC training=0.811, AUC test=0.904). Based on the results, the following metabolite biomarkers may prove useful in distinguishing lung cancer states: isoleucine, acetoacetate, and creatine as well as the two NMR signals of N-acetylated glycoproteins and glycerol. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease.

    Science.gov (United States)

    Lindeberg, S; Jönsson, T; Granfeldt, Y; Borgstrand, E; Soffman, J; Sjöström, K; Ahrén, B

    2007-09-01

    Most studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat, carbohydrate, fibre, fruits and vegetables. Instead, we aimed to compare diets that were available during human evolution with more recently introduced ones. Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were randomised to receive (1) a Palaeolithic ('Old Stone Age') diet (n = 14), based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; or (2) a Consensus (Mediterranean-like) diet (n = 15), based on whole grains, low-fat dairy products, vegetables, fruits, fish, oils and margarines. Primary outcome variables were changes in weight, waist circumference and plasma glucose AUC (AUC Glucose(0-120)) and plasma insulin AUC (AUC Insulin(0-120)) in OGTTs. Over 12 weeks, there was a 26% decrease of AUC Glucose(0-120) (p = 0.0001) in the Palaeolithic group and a 7% decrease (p = 0.08) in the Consensus group. The larger (p = 0.001) improvement in the Palaeolithic group was independent (p = 0.0008) of change in waist circumference (-5.6 cm in the Palaeolithic group, -2.9 cm in the Consensus group; p = 0.03). In the study population as a whole, there was no relationship between change in AUC Glucose(0-120) and changes in weight (r = -0.06, p = 0.9) or waist circumference (r = 0.01, p = 1.0). There was a tendency for a larger decrease of AUC Insulin(0-120) in the Palaeolithic group, but because of the strong association between change in AUC Insulin(0-120) and change in waist circumference (r = 0.64, p = 0.0003), this did not remain after multivariate analysis. A Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference.

  7. Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome.

    Science.gov (United States)

    Jakimov, Tamara; Mrdović, Igor; Filipović, Branka; Zdravković, Marija; Djoković, Aleksandra; Hinić, Saša; Milić, Nataša; Filipović, Branislav

    2017-12-31

    To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC=0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC=0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC=0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC=0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC=0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC=0.88; 95% CI 1.018-1.072) and on discharge (AUC=0.78; 95% CI 1.000-1.058). In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR.

  8. Identification of single-site gold catalysis in acetylene hydrochlorination

    OpenAIRE

    Malta, Grazia; Kondrat, Simon A.; Freakley, Simon J.; Davies, Catherine; Lu, Li; Dawson, Simon; Thetford, Adam; Gibson, Emma K.; Morgan, David John; Jones, Wilm; Wells, Peter Bernard; Johnston, Peter; Catlow, Charles Ricahrd A.; Kiely, Christopher John; Hutchings, Graham John

    2017-01-01

    There remains considerable debate over the active form of gold under operating conditions of a recently validated gold catalyst for acetylene hydrochlorination. We have performed an in situ x-ray absorption fine structure study of gold/carbon (Au/C) catalysts under acetylene hydrochlorination reaction conditions and show that highly active catalysts comprise single-site cationic Au entities whose activity correlates with the ratio of Au(I):Au(III) present. We demonstrate that these Au/C catal...

  9. A comparison of two diagnostic performance measures: signal-to-noise ratio versus partial area under receiver operating characteristic curve.

    Science.gov (United States)

    Taner, Mehmet Tolga; Sezen, Bulent; Atwat, Kamal

    2013-01-01

    This paper aims to compare two diagnostic performance measures, i.e. signal-to-noise ratio (S/N ratio) and partial area under receiver operating characteristic curves (pAUC). It proposes the use of S/N ratio rather than pAUC for establishing optimal cut-off point for diagnostic biomarkers. This paper discusses the properties, uses, advantages and shortcomings of the two performance measures, namely the partial area under receiver operating characteristic curve (pAUC) and Taguchi's signal-to-noise (S/N) ratio. The benefits of S/N ratio have been illustrated in a sample of four biomarkers, each having five cut-off points. The S/N ratio is compared to the pAUC index. The SAS software is employed to calculate pAUC and AUC. This paper shows that S/N ratio can be used as a measure of diagnostic accuracy. The cut-off point with the highest S/N ratio is the optimal cut-off point for the biomarker. The proposed method has the advantages of being easier, more practical and less costly than that of pAUC. This paper includes implications for the development of a more practical, equally powerful and less costly means of measuring clinical accuracy thereby reducing the costs and risks resulting from wrong selection of cut-off point can be decreased. This paper supports suggestions in the recent literature to replace pAUC with a new, more meaningful index.

  10. Receiver Operating Characteristic (ROC) Curve Analysis for Medical Diagnostic Test Evaluation.

    Science.gov (United States)

    Hajian-Tilaki, Karimollah

    2013-01-01

    This review provides the basic principle and rational for ROC analysis of rating and continuous diagnostic test results versus a gold standard. Derived indexes of accuracy, in particular area under the curve (AUC) has a meaningful interpretation for disease classification from healthy subjects. The methods of estimate of AUC and its testing in single diagnostic test and also comparative studies, the advantage of ROC curve to determine the optimal cut off values and the issues of bias and confounding have been discussed.

  11. Randomized two-way cross-over bioequivalence study of two amoxicillin formulations and inter-ethnicity pharmacokinetic variation in healthy Malay volunteers.

    Science.gov (United States)

    Liew, Kai Bin; Loh, Gabriel Onn Kit; Tan, Yvonne Tze Fung; Peh, Kok Khiang

    2014-09-01

    The objectives of this study were to develop a new deproteinization method to extract amoxicillin from human plasma and evaluate the inter-ethnic variation of amoxicillin pharmacokinetics in healthy Malay volunteers. A single-dose, randomized, fasting, two-period, two-treatment, two-sequence crossover, open-label bioequivalence study was conducted in 18 healthy Malay adult male volunteers, with one week washout period. The drug concentration in the sample was analyzed using high-performance liquid chromatography (UV-vis HPLC). The mean (standard deviation) pharmacokinetic parameter results of Moxilen® were: peak concentration (Cmax ), 6.72 (1.56) µg/mL; area under the concentration-time graph (AUC0-8 ), 17.79 (4.29) µg/mL h; AUC0-∞ , 18.84 (4.62) µg/mL h. Those of YSP Amoxicillin® capsule were: Cmax , 6.69 (1.44) µg/mL; AUC0-8 , 18.69 (3.78) µg/mL h; AUC00-∞ , 19.95 (3.81) µg/mL h. The 90% confidence intervals for the logarithmic transformed Cmax , AUC0-8 and AUC0-∞ of Moxilen® vs YSP Amoxicillin® capsule was between 0.80 and 1.25. Both Cmax and AUC met the predetermined criteria for assuming bioequivalence. Both formulations were well tolerated. The results showed significant inter-ethnicity variation in pharmacokinetics of amoxicillin. The Cmax and AUC of amoxicillin in Malay population were slightly lower compared with other populations. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Pharmacokinetics of Rolapitant in Patients With Mild to Moderate Hepatic Impairment.

    Science.gov (United States)

    Wang, Jing; Wang, Xiaodong; Zhang, Zhi-Yi; Arora, Sujata; Lu, Sharon; Kansra, Vikram

    2018-01-12

    Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. This was a phase 1 open-label, parallel-group pharmacokinetic and safety study of a single oral dose of 180 mg of rolapitant and its major active metabolite, M19, in subjects with mild and moderate hepatic impairment compared with healthy matched controls. Pharmacokinetics were assessed by a mixed-model analysis of variance of log-transformed values for maximum observed plasma concentration (C max ), observed time at C max (t max ), area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC 0-t ), and AUC from time 0 to 120 hours (AUC 0-120 ), with hepatic group as a fixed effect. Mean rolapitant C max , AUC 0-t , and AUC 0-120 were similar in the mild hepatic impairment and healthy control groups. In subjects with moderate hepatic impairment, AUC 0-t was similar and C max was 25% lower than in healthy controls. Mean M19 C max and AUC 0-t were similar in the mild hepatic impairment group and healthy controls, but impairment versus healthy controls. Fraction of unbound rolapitant was comparable in all groups for rolapitant and M19. Rolapitant was well tolerated in all groups, without serious adverse events. Pharmacokinetic differences between healthy subjects and those with mild or moderate hepatic impairment are unlikely to pose a safety risk and do not warrant predefined dosage adjustment in the presence of hepatic impairment. © 2018, The American College of Clinical Pharmacology.

  13. Bioequivalence of Alendronate and Vitamin D3 in a Combination Tablet Versus Corresponding-Dose Individual Tablets in Healthy Taiwanese Volunteers, Determined Using a Novel Plasma Alendronate Assay

    Directory of Open Access Journals (Sweden)

    D. Hamish Wright, PhD

    2015-12-01

    Conclusions: The combination tablet was considered bioequivalent to coadministration based on ALN AUC0–∞ and unadjusted vitamin D3 parameters. Slight differences for ALN AUC0–last and Cmax (upper 90% CIs outside the bounds were not considered clinically significant. The combination tablet was well tolerated. No serious adverse experiences were reported. © 2015. The Authors. Published by Elsevier Inc. All rights reserved.

  14. Prediction of Ischemic Stroke-Associated Pneumonia: A Comparison between 3 Scores.

    Science.gov (United States)

    Helmy, Tamer Abdallah; Abd-Elhady, Mohamed Abd-Elalim; Abdou, Mohammed

    2016-11-01

    Stroke is a leading cause of death and disability worldwide. Among all poststroke complications, pneumonia constitutes a major complication with a strong impact on morbidity and mortality. To identify patients at high risk of stroke-associated pneumonia (SAP) and to tailor a prophylactic approach, a reliable scoring model for prediction may be useful in daily stroke care. This study aimed to compare the performance of the Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity (A(2)DS(2)) score, the acute ischemic stroke-associated pneumonia score (AIS-APS), and the Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) score in predicting SAP. Seventy consecutive patients with ischemic stroke admitted to the Critical Care Medicine Department of Alexandria Main University Hospital were included. Patients were prospectively followed up for primary outcome of pneumonia within the first 7 days after admission diagnosed by the Centers for Disease Control and Prevention criteria. Accuracy in predicting outcome measures was assessed by calculating the area under receiver operating characteristic curve (AUC). Twenty-six (37.1%) patients developed pneumonia by the seventh day; the A(2)DS(2) score AUC was .847 (95% CI: .741-.922), and the AIS-APS AUC was .798 (95% CI: .685-.884). The PANTHERIS score AUC was .715 (95% CI: .595-.817). The A(2)DS(2) score AUC was significantly higher than the AIS-APS and the PANTHERIS score AUCs (P = .048 and P = .009 respectively), and the AIS-APS AUC was significantly higher than the PANTHERIS score AUC (P = .044). The A(2)DS(2) score is a valid tool for the prediction of SAP based on routinely collected data, and among the 3 studied scores, it shows the best performance in predicting SAP. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Limited sampling strategy for the estimation of mycophenolic acid area under the curve in Tunisian renal transplant patients.

    Science.gov (United States)

    Gaies, Emna; Ben Sassi, Mouna; El Jebari, Hanene; Jebabli, Nadia; Charfi, Rim; Chokri, Ichraf; Salouage, Issam; Klouz, Anis; Trabelsi, Sameh

    2017-11-01

    Mycophenolate mofetil is a prodrug widely used in renal transplantation to prevent organ rejection. It is hydrolyzed to its active compound mycophenolic acid (MPA). MPA area under the curve (AUC 0-12h ) is considered the best pharmacokinetic parameter for the estimation of MPA exposition and for prediction of rejection. MPA-AUC requires several blood samples, making it impractical for clinical practice. Therefore, development of a limited sampling strategy (LSS) to estimate MPA AUC 0-12h using three blood samples is very helpful for MPA individual dose adjustment. Results of LSS differ according to the patient background and to the drug formulation. Therefore, the purpose of this study was to develop a LSS for the estimation of MPA AUC 0-12h in Tunisian renal transplant patients treated with the generic formulation of mycophenolate mofetil (MMF ® , MEDIS). The best correlation was achieved by a profile based on three time points C 0.5h , C 1.5h , and C 4h after drug intake: AUC 0-12h  = 0.414 + 1.210 × C 0.5  + 2.256 × C 1.5  + 4.134 × C 4 (mei = 1.65% and rmse = 5.81%). The correlation between full AUC 0-12h and abbreviated AUC 0-12h was 0.917. In conclusion, this model provides a reliable and simple equation to estimate MPA AUC 0-12h for the generic formulation of mycophenolate mofetil (MMF ® ). Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

  16. Validation of the Finnish Diabetes Risk Score (FINDRISC) questionnaire for undiagnosed type 2 diabetes screening in the Slovenian working population.

    Science.gov (United States)

    Štiglic, Gregor; Fijačko, Nino; Stožer, Andraž; Sheikh, Aziz; Pajnkihar, Majda

    2016-10-01

    We performed a cross-sectional population-based study on 632 participants, aged 20-65, who were screened using the Finnish Diabetes Risk Score (FINDRISC) questionnaire. Optimal results for men were achieved at FINDRISC⩾7 (100.0% sensitivity and 0.78 AUC) and for women at FINDRISC⩾13 (60.0% sensitivity and 0.78 AUC). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Detection of Salivary Insulin Following Low versus High Carbohydrate Meals in Humans

    Directory of Open Access Journals (Sweden)

    Étienne Myette-Côté

    2017-11-01

    Full Text Available Developing non-invasive alternatives to monitor insulin levels in humans holds potential practical value for identifying individuals with, or at risk of developing, insulin resistance. The aims of this study were: (1 to determine if saliva insulin can be used to delineate between low and high postprandial insulin levels following the ingestion of mixed breakfast meals; and (2 to determine if expected differences in postprandial hyperinsulinemia between young lean and young overweight/obese participants could be detected in saliva. Sixteen individuals (n = 8 classified as normal weight (NW; BMI 20.0–24.9 kg/m2, and n = 8 classified as overweight/obese (OO; BMI ≥ 28.0 kg/m2 completed two isocaloric mixed-meal tolerance tests following an overnight fast, consisting of a low-carbohydrate (LC breakfast or a high-carbohydrate (HC breakfast. Blood and saliva samples were collected at regular intervals for two hours postprandially. In both groups, plasma and saliva insulin total area under the curve (AUC and incremental AUC (iAUC were significantly higher after the HC as compared to the LC meal (all p ≤ 0.005. Insulin AUC and iAUC in both plasma and saliva were higher in OO than in NW after the HC meal (all p ≤ 0.02 but only plasma and saliva total AUC were higher in OO after the LC meal (both p ≤ 0.01. Plasma insulin AUC was significantly correlated with salivary insulin AUC in LC (r = 0.821; p < 0.001 and HC (r = 0.882; p < 0.001. These findings indicate that saliva could potentially be used to delineate between low and high insulin levels following mixed breakfast meals.

  18. Bioequivalence study of two fluconazole capsule formulations in healthy volunteers.

    Science.gov (United States)

    Pereira, R; Fidelis, S; Vanunci, M L P; Oliveira, C H; Mendes, G D; Abib, E; Moreno, R A

    2004-01-01

    To compare the bioavailability of a fluconazole 150 mg capsule formulation from Laboratório Teuto Brasileiro Ltd., Brazil (test formulation), and Zoltec 150 mg capsule from Laboratórios Pfizer Ltd., Brazil (reference formulation), in 24 volunteers of both sexes. The study was conducted open with randomized 2-period crossover design and a 2-week washout period. Plasma samples were obtained over a 168-hour interval. Fluconazole concentrations were analyzed by combined reversed-phase liquid chromatography and tandem mass spectrometry (LC/MS/MS) with positive ion electrospray ionization using selected ion monitoring method. From the fluconazole plasma concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-inf) and C(max). Geometric mean of fluconazole/Zoltec 150 mg individual percent ratio was 102.6% for AUC(last), 102.2% for AUC(0-inf) and 109.4% for C(max). The 90% confidence intervals were 97.3-108.2%, 97.0-107.8%, and 103.1-116.0%, respectively. Since the 90% CI for both Cmax, AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that fluconazole 150 mg capsule was bioequivalent to Zoltec 150 mg, according to both the rate and extent of absorption.

  19. 2017 multimodality appropriate use criteria for noninvasive cardiac imaging: Export consensus of the Asian society of cardiovascular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Beck, Kyong Min Sarah [Dept. of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Kim, Jeong A [Dept. of Radiology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang (Korea, Republic of); Choe, Yeon Hyeon [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); and others

    2017-11-15

    In 2010, the Asian Society of Cardiovascular Imaging (ASCI) provided recommendations for cardiac CT and MRI, and this document reflects an update of the 2010 ASCI appropriate use criteria (AUC). In 2016, the ASCI formed a new working group for revision of AUC for noninvasive cardiac imaging. A major change that we made in this document is the rating of various noninvasive tests (exercise electrocardiogram, echocardiography, positron emission tomography, single-photon emission computed tomography, radionuclide imaging, cardiac magnetic resonance, and cardiac computed tomography/angiography), compared side by side for their applications in various clinical scenarios. Ninety-five clinical scenarios were developed from eight selected pre-existing guidelines and classified into four sections as follows: 1) detection of coronary artery disease, symptomatic or asymptomatic; 2) cardiac evaluation in various clinical scenarios; 3) use of imaging modality according to prior testing; and 4) evaluation of cardiac structure and function. The clinical scenarios were scored by a separate rating committee on a scale of 1–9 to designate appropriate use, uncertain use, or inappropriate use according to a modified Delphi method. Overall, the AUC ratings for CT were higher than those of previous guidelines. These new AUC provide guidance for clinicians choosing among available testing modalities for various cardiac diseases and are also unique, given that most previous AUC for noninvasive imaging include only one imaging technique. As cardiac imaging is multimodal in nature, we believe that these AUC will be more useful for clinical decision making.

  20. RELATIVE BIOAVAILABILITY OF OMEPRAZOLE CAPSULES AFTER ORAL DOSING

    Directory of Open Access Journals (Sweden)

    SAYED ABOLFAZL MOSTAFAVI

    2004-09-01

    Full Text Available Omeprazole, a proton pump inhibitor, effectively suppresses the gastric acid secretion in the parietal cells of stomach. Pharmacokinetics and relative bioavailability of generic products of omeprazole were compared with innovator product, Losec. Twelve healthy adult volunteers participated in the study which was conducted according to a randomized, open-label single dose Latin square cross over design. The preparations were compared using area under the plasma concentration – time curve (AUC, peak plasma concentration (Cmax, and time to reach peak plasma concentration (tmax. The two generic capsules proved to be bioequivalent with brand-name omeprazole with regard to the pharmacokinetic parameters Cmax, AUC0-t, AUC0-inf and tmax. Moreover the parametric confidence intervals (90% for the ratio of the Cmax, AUC0-8 and AUC0-∞ values lie between 0.8-1.2. The test formulations were found bioequivalent to the reference formulation by the one-way ANOVA test procedure. On the basis of these results, the 3 formulations were considered to be bioequivalent. Two subjects demonstrated increase in AUCs and high Cmax after administration of either product which may attribute to the ethnic disposition of omeprazole in these subjects.

  1. Beef cattle body temperature during climatic stress: a genome-wide association study

    Science.gov (United States)

    Howard, Jeremy T.; Kachman, Stephen D.; Snelling, Warren M.; Pollak, E. John; Ciobanu, Daniel C.; Kuehn, Larry A.; Spangler, Matthew L.

    2014-09-01

    Cattle are reared in diverse environments and collecting phenotypic body temperature (BT) measurements to characterize BT variation across diverse environments is difficult and expensive. To better understand the genetic basis of BT regulation, a genome-wide association study was conducted utilizing crossbred steers and heifers totaling 239 animals of unknown pedigree and breed fraction. During predicted extreme heat and cold stress events, hourly tympanic and vaginal BT devices were placed in steers and heifers, respectively. Individuals were genotyped with the BovineSNP50K_v2 assay and data analyzed using Bayesian models for area under the curve (AUC), a measure of BT over time, using hourly BT observations summed across 5-days (AUC summer 5-day (AUCS5D) and AUC winter 5-day (AUCW5D)). Posterior heritability estimates were moderate to high and were estimated to be 0.68 and 0.21 for AUCS5D and AUCW5D, respectively. Moderately positive correlations between direct genomic values for AUCS5D and AUCW5D (0.40) were found, although a small percentage of the top 5 % 1-Mb windows were in common. Different sets of genes were associated with BT during winter and summer, thus simultaneous selection for animals tolerant to both heat and cold appears possible.

  2. Sustained effects of a protein and lipid preload on glucose tolerance in type 2 diabetes patients.

    Science.gov (United States)

    Tricò, D; Filice, E; Baldi, S; Frascerra, S; Mari, A; Natali, A

    2016-09-01

    Small amounts of nutrients given as a 'preload' can reduce post-meal hyperglycaemic peaks in type 2 diabetes (T2D) patients by activating a number of mechanisms involved in glucose homoeostasis. This study was undertaken to ascertain whether this positive effect extends to the late absorptive phase and to identify the main mechanisms involved. Eight well-controlled T2D patients, aged 40-70 years, were randomized to consume a 'preload' of either water or non-glucidic nutrients (50g of Parmesan cheese, one boiled egg) 30min before a 300-min oral glucose tolerance test. After the nutrient preload, significant reductions were observed in peak glucose (-49%; P<0.02), total plasma glucose (iAUC: -28%; P<0.03), exogenous glucose (iAUC: -30%; P<0.03) and insulin clearance (-28%; P<0.04), with enhancement of insulin secretion (iAUC: +22%; P<0.003). These effects were associated with higher plasma levels of GLP-1 (iAUC: +463%; P<0.002), GIP (iAUC: +152%; P<0.0003) and glucagon (iAUC: +144%; P<0.0002). In T2D patients, a protein and lipid preload improves glucose tolerance throughout the whole post-absorptive phase mainly by reducing the appearance of oral glucose, and improving both beta-cell function and insulin bioavailability. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Effect of ketoconazole on the pharmacokinetics of oral bosutinib in healthy subjects.

    Science.gov (United States)

    Abbas, Richat; Hug, Bruce A; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

    2011-12-01

    Bosutinib (SKI-606), a dual inhibitor of Src and Abl tyrosine kinases, is being developed for the treatment of chronic myelogenous leukemia. The effect of coadministration of ketoconazole on the pharmacokinetic (PK) profile of bosutinib was evaluated in an open-label, randomized, 2-period, crossover study. Healthy subjects (fasting) received a single dose of oral bosutinib 100 mg alone and with multiple once-daily doses of oral ketoconazole 400 mg. PK sampling occurred through 96 hours. The least square geometric mean treatment ratios (90% confidence interval [CI]) of C(max(bosutinib+ketoconazole))/C(max(bosutinib alone)), AUC(T(bosutinib+ketoconazole))/AUC(T(bosutinib alone)), and AUC((bosutinib+ketoconazole))/AUC((bosutinib alone)) were assessed. Compared with bosutinib administered alone, coadministration with ketoconazole increased bosutinib C(max) 5.2-fold, AUC(T) 7.6-fold, and AUC 8.6-fold. Ketoconazole coadministration decreased the mean apparent clearance of bosutinib approximately 9-fold and increased the mean (SD) terminal half-life from 46.2 (16.4) hours to 69.0 (29.1) hours. The incidence of adverse events (AEs) was comparable between the 2 treatments. The most common AEs were headache, nausea, and increased blood creatinine. No safety-related discontinuations or serious AEs occurred. These PK results indicate that bosutinib is susceptible to interaction with potent CYP3A4 inhibitors.

  4. Omeprazole hydroxylation is inhibited by a single dose of moclobemide in homozygotic EM genotype for CYP2C19

    Science.gov (United States)

    Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin; Yang, Byung-Hwan; Shin, Sang-Goo; Yim, Dong-Seok

    2002-01-01

    Aims The pharmacokinetics of omeprazole and its metabolites in healthy subjects were evaluated to determine if a single dose of moclobemide inhibited CYP2C19 activity. Methods Sixteen volunteers, of whom eight were extensive metabolizers (EM) and eight were poor metabolizers for CYP2C19, participated in two studies. Venous blood samples were collected for 24 h after oral ingestion of 40 mg omeprazole with or without 300 mg moclobemide coadministration. The pharmacokinetic change of omeprazole, omeprazole sulphone and 5-hydroxyomeprazole concentrations were assessed to test for an interaction between omeprazole and moclobemide. Results The coadministration of moclobemide in EMs approximately doubled the mean AUC (from 1834 to 3760 ng ml−1 h) and Cmax (from 987 to 1649 ng ml−1) of omeprazole, and increased the AUC of omeprazole sulphone without changing AUC ratio of omeprazole to omeprazole sulphone. Moclobemide coadministration more than doubled the AUC ratio of omeprazole to 5-hydroxyomeprazole (from 2.5 to 5.3) in EMs, too. There was a significant decrease in Cmax and AUC of 5-hydroxyomeprazole in PMs but no significant changes were seen in the results for omeprazole and omeprazole sulphone AUCs. Conclusions A single dose of moclobemide resulted in significant suppression of CYP2C19 activity in EMs. We conclude that physicians prescribing moclobemide should pay attention to its pharmacokinetic interactions even on the first day of coadministration with CYP2C19 substrates. PMID:11966672

  5. Lung ultrasonography as a direct measure of evolving respiratory dysfunction and disease severity in patients with acute pancreatitis.

    Science.gov (United States)

    Skouras, Christos; Davis, Zoe A; Sharkey, Joanne; Parks, Rowan W; Garden, O James; Murchison, John T; Mole, Damian J

    2016-02-01

    The value of lung ultrasonography in the diagnosis of respiratory dysfunction and severity stratification in patients with acute pancreatitis (AP) was investigated. Over a 3-month period, 41 patients (median age: 59.1 years; 21 males) presenting with a diagnosis of potential AP were prospectively recruited. Each participant underwent lung ultrasonography and the number of comet tails was linked with contemporaneous clinical data. Group comparisons, areas under the curve (AUC) and respective measures of diagnostic accuracy were investigated. A greater number of comet tails were evident in patients with respiratory dysfunction (P = 0.021), those with severe disease (P respiratory dysfunction and AP severity as variables of interest (AUC = 0.783, 95% C.I.: 0.544-0.962, and AUC = 0.996, 95% C.I.: 0.982-1.000, respectively). Examining all lung quadrants except for the lower lateral resulted in greater AUCs for contemporaneous and maximum CRP (AUC = 0.708, 95% C.I.: 0.510-0.883, and AUC = 0.800, 95% C.I.: 0.640-0.929). Ultrasonography of non-dependent lung parenchyma can reliably detect evolving respiratory dysfunction in AP. This simple bedside technique shows promise as an adjunct to severity stratification. Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  6. Screening for panic-related anxiety in emergency department patients with cardiopulmonary complaints: A comparison of two self-report instruments.

    Science.gov (United States)

    Sung, Sharon C; Ma, Jackie; Earnest, Arul; Rush, A John; Lim, Leslie E C; Ong, Marcus E H

    2018-02-16

    The present study examined 1) the accuracy of two self-report measures for detecting panic-related anxiety in emergency department (ED) patients with cardiopulmonary complaints; and 2) whether modified scoring resulted in improved performance. English-speaking adults presenting to the ED of a large public hospital with palpitations, chest pain, dizziness, or difficulty breathing were evaluated for the presence of panic-related anxiety with the Structured Clinical Interview for DSM-IV (SCID) over a one-year period. Patients completed the panic disorder modules of the Patient Health Questionnaire (PHQ-PD) and Psychiatric Diagnostic Screening Questionnaire (PDSQ-PD). Sensitivity, specificity, area under the curve (AUC), and predictive values were compared for various cut-offs and scoring algorithms using SCID diagnosis of panic attacks (in the absence of panic disorder) or panic disorder as the reference standard. In this sample of 200 participants, the majority had a chief complaint of chest pain and 46.5% met SCID criteria for panic-related anxiety. The PDSQ-PD demonstrated only fair operating characteristics for panic attacks (AUC = 0.57) and good operating characteristics for panic disorder (AUC = 0.79). The PHQ-PD achieved adequate operating characteristics (AUC = 0.66) for panic attacks and good operating characteristics for panic disorder (AUC = 0.76) using a modified scoring algorithm or a single screening question (AUC = 0.72). Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Direct estimation of the area under the receiver operating characteristic curve in the presence of verification bias.

    Science.gov (United States)

    He, Hua; Lyness, Jeffrey M; McDermott, Michael P

    2009-02-01

    The area under a receiver operating characteristic (ROC) curve (AUC) is a commonly used index for summarizing the ability of a continuous diagnostic test to discriminate between healthy and diseased subjects. If all subjects have their true disease status verified, one can directly estimate the AUC nonparametrically using the Wilcoxon statistic. In some studies, verification of the true disease status is performed only for a subset of subjects, possibly depending on the result of the diagnostic test and other characteristics of the subjects. Because estimators of the AUC based only on verified subjects are typically biased, it is common to estimate the AUC from a bias-corrected ROC curve. The variance of the estimator, however, does not have a closed-form expression and thus resampling techniques are used to obtain an estimate. In this paper, we develop a new method for directly estimating the AUC in the setting of verification bias based on U-statistics and inverse probability weighting (IPW). Closed-form expressions for the estimator and its variance are derived. We also show that the new estimator is equivalent to the empirical AUC derived from the bias-corrected ROC curve arising from the IPW approach. Copyright (c) 2008 John Wiley & Sons, Ltd.

  8. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Eunice Kazue Kano

    2015-03-01

    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  9. Impact of correlation of predictors on discrimination of risk models in development and external populations.

    Science.gov (United States)

    Kundu, Suman; Mazumdar, Madhu; Ferket, Bart

    2017-04-19

    The area under the ROC curve (AUC) of risk models is known to be influenced by differences in case-mix and effect size of predictors. The impact of heterogeneity in correlation among predictors has however been under investigated. We sought to evaluate how correlation among predictors affects the AUC in development and external populations. We simulated hypothetical populations using two different methods based on means, standard deviations, and correlation of two continuous predictors. In the first approach, the distribution and correlation of predictors were assumed for the total population. In the second approach, these parameters were modeled conditional on disease status. In both approaches, multivariable logistic regression models were fitted to predict disease risk in individuals. Each risk model developed in a population was validated in the remaining populations to investigate external validity. For both approaches, we observed that the magnitude of the AUC in the development and external populations depends on the correlation among predictors. Lower AUCs were estimated in scenarios of both strong positive and negative correlation, depending on the direction of predictor effects and the simulation method. However, when adjusted effect sizes of predictors were specified in the opposite directions, increasingly negative correlation consistently improved the AUC. AUCs in external validation populations were higher or lower than in the derivation cohort, even in the presence of similar predictor effects. Discrimination of risk prediction models should be assessed in various external populations with different correlation structures to make better inferences about model generalizability.

  10. Role of CYP24A1, VDR and GC gene polymorphisms on deferasirox pharmacokinetics and clinical outcomes.

    Science.gov (United States)

    Allegra, S; Cusato, J; De Francia, S; Arduino, A; Longo, F; Pirro, E; Massano, D; De Nicolò, A; Piga, A; D'Avolio, A

    2017-11-21

    β-Thalassemia patients develop deficiency in vitamin D absorption and liver hydroxylation, resulting in extremely low calcitriol levels. We explored the role of single-nucleotide polymorphisms (SNPs) involved in vitamin D metabolism, transport and activity on deferasirox pharmacokinetics and outcomes (effectiveness trough levels (Ctrough) and the area under the curve (AUC) cutoffs of 20 μg ml-1 and 360 μg ml-1 h-1, respectively; nonresponse AUC limit of 250 μg ml-1 h-1). Ninety-nine β-thalassemic patients were enrolled. Drug plasma Ctrough and AUC were measured by the high-performance liquid chromatography system coupled with an ultraviolet determination method. Allelic discrimination for VDR, CYP24A1, CYP27B1 and GC gene SNPs was performed by real-time PCR. CYP24A1 22776 TT significantly influenced Cmin and negatively predicted it in regression analysis. CYP24A1 3999 CC was associated with Ctrough and Cmin and was a negative predictor of Tmax, whereas CYP24A1 8620 GG seemed to have a role in Ctrough, AUC, t1/2 and Cmin, and was an AUC negative predictor factor. Considering treatment outcome, Cdx2 and GC 1296 were retained in regression analysis as AUC efficacy cutoff negative predictors.The Pharmacogenomics Journal advance online publication, 21 November 2017; doi:10.1038/tpj.2017.43.

  11. Bioequivalence of generic and branded amoxicillin capsules in healthy human volunteers.

    Science.gov (United States)

    Pathak, Priyanka; Pandit, Vijaya A; Dhande, Priti P

    2017-01-01

    The Medical Council of India urges doctors to prescribe generic drugs as far as possible. The Indian Medical Association had responded earlier saying that it requires guarantees on the quality of generic forms of drugs. Although no published scientific reports are available on the issue of therapeutic inequivalence, unconfirmed clinician accounts and newspaper reports of therapeutic inequivalence exist. This study was planned to ascertain whether bioequivalence of branded and generic amoxicillin capsule is comparable. An open-label, randomized, single-dose, two-treatment, two-sequence, two-period crossover oral bioequivalence study was conducted in 12 healthy, adult human subjects under fasting condition. Serum samples, collected at 8 time points, were analyzed by a validated ultraviolet spectrophotometer method. Pharmacokinetic (PK) parameters such as area under the curve (AUC)0-t, AUC0-∞, Cmax, and Tmax were determined along with time above minimum inhibitory concentration (MIC). The log-transformed PK parameters (Cmax, AUC0-t, AUC0-∞) were analyzed using a Two One-Sided Test ANOVA in SAS for each parameter. Tmax and MIC were analyzed by Wilcoxon rank-sum test in GraphPad Prism. Geometric mean ratio of Cmax fell within bioequivalence criteria. The upper and lower confidence limits of both AUC0-t and AUC0-∞ geometric mean ratio fell below bioequivalence criteria. Time above MIC of generic preparation was significantly lower than that of branded version. The generic capsule was not bioequivalent to the branded amoxicillin capsule.

  12. Rapid and simple profiling of lipoproteins by polyacrylamide-gel disc electrophoresis to determine the heterogeneity of low-density lipoproteins (LDLs) including small, dense LDL.

    Science.gov (United States)

    Nakano, Takanari; Inoue, Ikuo; Seo, Makoto; Takahashi, Seiichiro; Awata, Takuya; Komoda, Tsugikazu; Katayama, Shigehiro

    2009-01-01

    This study aimed to explore the potential of polyacrylamide-gel disc electrophoresis (PAGE) for lipoprotein profiling in clinical practice. Blood samples were collected from 146 patients with type 2 diabetes mellitus and lipid parameters were assayed by PAGE, including small, dense low-density lipoprotein (LDL) (n = 41), and triglyceride-rich lipoprotein remnant cholesterol (n = 37). We also used a commercial kit to measure small, dense LDL (n = 41). By PAGE, we obtained the percentage of the area under the curve (AUC %) of each peaks and calculated respective AUC% x total cholesterol (AUC%xTC) values. The calculated values of LDL-AUC%xTC, small LDL-AUC%xTC, and HDL-AUC%xTC values were correlated well with values from homogeneous assay for LDL-cholesterol, small, dense LDL-cholesterol, and HDL-cholesterol assays (r = 0.94, 0.81, and 0.89, respectively). PAGE combined with measurement of total cholesterol and triglycerides provides a rapid evaluation of anti- or pro-atherogenic lipoproteins and a simple profiling system for both the "quantity" and "quality" of lipoproteins, allowing a better assessment of the risk of coronary artery diseases. This article discusses several methods for simple and rapid lipid profiling and outlines some recent patents relevant to the methods.

  13. A COMPARISON OF MAZUR'S k AND AREA UNDER THE CURVE FOR DESCRIBING STEEP DISCOUNTERS.

    Science.gov (United States)

    Yoon, Jin H; De La Garza, Richard; Newton, Thomas F; Suchting, Robert; Weaver, Matthew T; Brown, Gregory S; Omar, Yasmine; Haliwa, Ilana

    2017-09-01

    Delay discounting describes how a reward loses value as a function of increasing delay to its receipt and has been reliably associated with a variety of vulnerable populations including those with substance use disorders (SUDs). Two commonly used models to assess delay discounting in the field of SUDs include log k derived from Mazur's hyperbolic equation and area under the curve (AUC). In the current study, we compared log k with AUC on delay discounting data obtained from non-treatment seeking, cocaine- and methamphetamine-dependent volunteers. We specifically chose this population in order to obtain a distribution of relatively steep discounters. The results show that the relationship between AUC and log k is better described by a quadratic rather than a linear function. In other words, changes in discounting, as measured by AUC and log k, are reflected differently across a range of obtained responses. Additionally, the distribution of AUC values was skewed, which appears to be more likely among populations exhibiting greater discounting. Finally, closer examination of indifference points revealed that AUC was almost perfectly predicted by the area from the two longest delays, with relatively less input from shorter delays. Given these results, researchers should exercise additional caution when deciding which method to assess discounting data and how final results are to be interpreted, particularly when dealing with relatively high rates of discounting. High rates of discounting are likely in populations with impulsive disorders such as those with SUDs.

  14. Area Under the Curve as a Novel Metric of Behavioral Economic Demand for Alcohol

    Science.gov (United States)

    Amlung, Michael; Yurasek, Ali; McCarty, Kayleigh N.; MacKillop, James; Murphy, James G.

    2015-01-01

    Behavioral economic purchase tasks can be readily used to assess demand for a number of addictive substances including alcohol, tobacco and illicit drugs. However, several methodological limitations associated with the techniques used to quantify demand may reduce the utility of demand measures. In the present study, we sought to introduce area under the curve (AUC), commonly used to quantify degree of delay discounting, as a novel index of demand. A sample of 207 heavy drinking college students completed a standard alcohol purchase task and provided information about typical weekly drinking patterns and alcohol-related problems. Level of alcohol demand was quantified using AUC – which reflects the entire amount of consumption across all drink prices - as well as the standard demand indices (e.g., intensity, breakpoint, Omax, Pmax, and elasticity). Results indicated that AUC was significantly correlated with each of the other demand indices (rs = .42–.92), with particularly strong associations with Omax (r = .92). In regression models, AUC and intensity were significant predictors of weekly drinking quantity and AUC uniquely predicted alcohol-related problems, even after controlling for drinking level. In a parallel set of analyses, Omax also predicted drinking quantity and alcohol problems, although Omax was not a unique predictor of the latter. These results offer initial support for using AUC as an index of alcohol demand. Additional research is necessary to further validate this approach and to examine its utility in quantifying demand for other addictive substances such as tobacco and illicit drugs. PMID:25895013

  15. Two meals with different carbohydrate, fat and protein contents render equivalent postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin.

    Science.gov (United States)

    Ohlsson, Bodil; Darwiche, Gassan; Roth, Bodil; Höglund, Peter

    2016-11-01

    The aim was to compare postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin between a control breakfast and a moderately low-carbohydrate test breakfast, given randomly after 10-h fast. Blood samples were collected before and repeatedly after the meal. Plasma calprotectin, cortisol, triglycerides and zonulin were analyzed. The total area under the curve (tAUC) and change in AUC from baseline (dAUC) were calculated. Ratios between the test and control values were calculated to investigate equivalence. Healthy volunteers (8 men and 12 women; 46.0 ± 14.5 years) were included. tAUCs of cortisol and triglycerides did not differ between the breakfasts (p = 0.158 versus p = 0.579). Cortisol dAUCs were decreased and triglyceride dAUCs were increased after both breakfasts, with no differences between the breakfasts (p = 0.933 versus p = 0.277). Calprotectin and zonulin levels were unaffected. The meals were bioequivalent for cortisol, triglycerides and zonulin, but not for calprotectin.

  16. Bioequivalence and pharmacokinetics of two zidovudine formulations in healthy Brazilian volunteers: an open-label, randomized, single-dose, two-way crossover study.

    Science.gov (United States)

    Dos Reis Serra, Cristina Helena; Mori Koono, Eunice Emiko; Kano, Eunice Kazue; Schramm, Simone Grigoleto; Armando, Yara Popst; Porta, Valentina

    2008-05-01

    Zidovudine is a thymidine nucleoside reverse transcriptase inhibitor with activity against HIV type 1. Some (approximately 8) generic formulations of zidovudine are available in Brazil; however, based on a literature search, information concerning their bioavailability and pharmacokinetic properties in the Brazilian population has not been reported. The aim of this study was to compare the bioavailability and pharmacokinetic properties of 2 capsule formulations of zidovudine 100 mg in healthy Brazilian volunteers. This open-label, randomized, 2-way crossover study utilized a 1-week washout period between doses. Blood samples were collected for 8 hours after a single dose of zidovudine 100-mg test (Zidovudina, Fundação para o Remédio Popular, São Paulo, Brazil) or reference formulation (Retrovir, GlaxoSmithKline, Philadelphia, Pennsylvania). Plasma zidovudine concentrations were determined using a validated high-performance liquid chromatography method with ultraviolet detection at 265 nm. C(max), T(max), AUC(0-t), AUC(0-infinity), t(1/2), and the elimination constant (k(e)) were determined using noncompartmental analysis. The formulations were considered bioequivalent if the 90% CIs for C(max), AUC(0-t), and AUC(0-infinity) fell within the interval of 80% to 125%,the regulatory definition set by the US Food and Drug Administration (FDA). Twenty-four healthy volunteers (12 males, 12 females; mean age, 27 years; weight, 60 kg; height, 167 cm) were enrolled and completed the study. The 90% CIs of the treatment ratios for the logarithmic transformed values of C(max), AUC(max)0-t, and AUC(0-infinity) were 80.0% to 113.6%, 93.9% to 109.7%, and 93.6% to 110.1%, respectively. The values for the test and reference formulations were within the FDA bioequivalence definition intervals of 80% to 125%. In this small study in healthy subjects, no statistically significant differences in C(max), AUC(0-t), and AUC(0-infinity) were found between the test and reference

  17. Influence of food on the oral bioavailability of rupatadine tablets in healthy volunteers: a single-dose, randomized, open-label, two-way crossover study.

    Science.gov (United States)

    Solans, Anna; Carbó, Marcel Lí; Peña, Juana; Nadal, Teresa; Izquierdo, Iñaki; Merlos, Manuel

    2007-05-01

    Rupatadine is an oral active antihistamine for the management of diseases with allergic inflammatory conditions, such as perennial and seasonal rhinitis and chronic idiopathic urticaria. Oral rupatadine has been approved for the treatment of allergic rhinitis and chronic urticaria in adults and adolescents in several European countries. The purpose of this study was to describe the effect of the concomitant intake of food on the pharmacokinetic profile and bioavailability of a single dose of rupatadine. This was a single-dose, randomized, open-label, 2-way crossover study in which healthy male and female volunteers received a single, 20-mg oral dose of rupatadine under fed and fasting conditions. Blood samples were collected and plasma concentrations of rupatadine and its active metabolites desloratadine and 3-hydroxydesloratadine were determined by liquid chromatography tandem mass spectrometry. Tolerability was based on the recording of adverse events (AEs), physical examinations, electrocardiograms, and laboratory tolerability tests immediately before each treatment period and at the final visit of the study. Twenty-four volunteers (12 males; mean [SD] age, 25.4 [5.3] years [range, 18-34 years]; mean [SD] weight, 71.2 [4.3] kg [range, 64-77 kg]; 12 females; mean [SD] age, 26.8 [6.5] years [range, 18-38 years]; mean [SD] weight, 58.4 [6.8] kg, [range 50-69 kg]) were enrolled and randomized with equal distribution of sex. A significant increase in AUC from drug administration to the final quantifiable sample (AUC(0-t)) and AUC from drug administration to infinity (AUC(0-infinity)) values of rupatadine was seen under fed conditions without affecting C(max). The ratios (90% CI) of the mean log-transformed AUC(0-t) and AUC(0-infinity) for rupatadine revealed a significant increase in AUC(0-t) (ratio 131%; 90% CI, 111%-154%) and AUC(0-infinity) (ratio 133%; 90% CI, 113%-156%), whereas C(max) remained unaltered (ratio 97%; 90% CI, 80%-116%). Plasma concentration

  18. Pharmacokinetic/pharmacodynamic analysis of teicoplanin in patients with MRSA infections

    Directory of Open Access Journals (Sweden)

    Matsumoto K

    2016-03-01

    Full Text Available Kazuaki Matsumoto,1 Erika Watanabe,1 Naoko Kanazawa,1 Tomohide Fukamizu,1 Akari Shigemi,1 Yuta Yokoyama,1,2 Kazuro Ikawa,2 Norifumi Morikawa,2 Yasuo Takeda1 1Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 2Department of Clinical Pharmacotherapy, Hiroshima University, Hiroshima, Japan Background: Teicoplanin is a glycopeptide antibiotic that has been used to treat serious, invasive infections caused by Gram-positive bacteria. The area under the drug concentration–time curve (AUC/minimum inhibitory concentration (MIC was identified as a pharmacokinetic–pharmacodynamic (PK–PD parameter of glycopeptide antibiotics that correlated with bacteriological responses and clinical outcomes. Although optimized dosing regimens based on PK–PD are needed, a PK–PD analysis of teicoplanin against methicillin-resistant Staphylococcus aureus (MRSA infections has not yet been performed. Thus, this study examined patients with MRSA infections, who were administered with teicoplanin in order to determine the target AUC/MIC ratio. Methods: This study retrospectively assessed data obtained as part of our routine therapeutic drug monitoring (TDM of teicoplanin therapy in 46 patients with MRSA infections at Kagoshima University Hospital. Serum concentrations of teicoplanin were determined using a fluorescence polarization immunoassay system and used for a Bayesian PK estimation to estimate AUC for 24 hours (AUC24. The MIC value for teicoplanin was determined using a standardized agar dilution method. The effects of teicoplanin were evaluated in terms of bacteriological responses by a quantitative assessment. Results: The estimated AUC24/MIC ratios with and without bacteriological responses were 926.6±425.2 µg·h/mL (n=34 and 642.2±193.9 µg·h/mL, respectively (n=12; P<0.05. On the basis of a logistic regression analysis, AUC24/MIC ratios of 500 µg·h/mL, 700 µg·h/mL, and

  19. Using symptom and interference questionnaires to identify recovery among children with anxiety disorders.

    Science.gov (United States)

    Evans, Rachel; Thirlwall, Kerstin; Cooper, Peter; Creswell, Cathy

    2017-07-01

    Questionnaires are widely used in routine clinical practice to assess treatment outcomes for children with anxiety disorders. This study was conducted to determine whether 2 widely used child and parent report questionnaires of child anxiety symptoms and interference (Spence Child Anxiety Scale [SCAS-C/P] and Child Anxiety Impact Scale [CAIS-C/P]) accurately identify recovery from common child anxiety disorder diagnoses as measured by a 'gold-standard' diagnostic interview. Three hundred thirty-seven children (7-12 years, 51% female) and their parents completed the ADIS-IV-C/P diagnostic interview and questionnaire measures (SCAS-C/P and CAIS-C/P) before (Time 1) and after (Time 2) treatment or wait-list. Time 2 parent reported interference (CAIS-P) was found to be a good predictor of absence of any diagnoses (area under the curve [AUC] = .81). In terms of specific diagnoses, Time 2 SCAS-C/P separation anxiety subscale (SCAS-C/P-SA) identified recovery from separation anxiety disorder well (SCAS-C-SA, AUC = .80; SCAS-P-SA, AUC = .82) as did the CAIS-P (AUC = .79). The CAIS-P also successfully identified recovery from social phobia (AUC = .78) and generalized anxiety disorder (AUC = .76). These AUC values were supported by moderate to good sensitivity (.70-.78) and specificity (.70-.73) at the best identified cut-off scores. None of the measures successfully identified recovery from specific phobia. The results suggest that questionnaire measures, particularly the CAIS-P, can be used to identify whether children have recovered from common anxiety disorders, with the exception of specific phobias. Cut-off scores have been identified that can guide the use of routine outcome measures in clinical practice. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Relationship between body weight and the increment in serum brain-derived neurotrophic factor after oral glucose challenge in men with obesity and metabolic syndrome: A prospective study.

    Science.gov (United States)

    Lee, I-Te; Wang, Jun-Sing; Fu, Chia-Po; Lin, Shih-Yi; Sheu, Wayne Huey-Herng

    2016-10-01

    Brain-derived neurotrophic factor (BDNF) plays a role in energy homeostasis. However, the postprandial BDNF change has not been well investigated. We hypothesized that the BDNF increment after oral glucose challenge is associated with body weight.To address this possibility, man adults with obesity in conjunction with metabolic syndrome were compared with normal weight controls at baseline in the initial cross-sectional protocol. The obese subjects then underwent a 12-week program for body-weight reduction in the prospective protocol. The area under the curve (AUC) of serum BDNF was recorded during a 75 g oral glucose tolerant test and the BDNF AUC index was defined as [(AUC of BDNF) - (fasting BDNF2 hours)]/(fasting BDNF2 hours).A total of 25 controls and 36 obese subjects completed the study assessments. In the cross-sectional protocol, the BDNF AUC index was significantly higher in the obese subjects than in the controls (9.0 ± 16.5% vs. - 8.0 ± 22.5%, P = 0.001). After weight reduction (from 97.0 ± 12.5 kg to 88.6 ± 12.9 kg, P body weight was significantly associated with the BDNF AUC index after the study (95% CI between 0.21 and 1.82, P = 0.015). Using 6% weight reduction as a cut-off value, a larger weight reduction was able to reliably predict a negative BDNF AUC index.In conclusion, a high BDNF AUC index was observed for obese men in this study, whereas the index value significantly decreased after body-weight reduction. These findings suggest that postprandial BDNF increment may be associated with obesity.

  1. ''Textural analysis of multiparametric MRI detects transition zone prostate cancer''

    Energy Technology Data Exchange (ETDEWEB)

    Sidhu, Harbir S.; Johnston, Edward W.; Taylor, Stuart A.; Halligan, Steve [Centre for Medical Imaging, University College London, London (United Kingdom); University College London Hospitals NHS Foundation Trust, London (United Kingdom); Benigno, Salvatore; Dikaios, Nikos [Centre for Medical Imaging, University College London, London (United Kingdom); Ganeshan, Balaji [Institute of Nuclear Medicine, University College London, University College Hospital, London (United Kingdom); Allen, Clare; Kirkham, Alex [University College London Hospitals NHS Foundation Trust, London (United Kingdom); Groves, Ashley M. [University College London Hospitals NHS Foundation Trust, London (United Kingdom); Institute of Nuclear Medicine, University College London, University College Hospital, London (United Kingdom); Ahmed, Hashim U.; Emberton, Mark [University College London Hospitals NHS Foundation Trust, London (United Kingdom); University College London, Research Department of Urology, London (United Kingdom); Punwani, Shonit [Centre for Medical Imaging, University College London, London (United Kingdom); University College London Hospitals NHS Foundation Trust, London (United Kingdom); Centre for Medical Imaging, University College London and University College London Hospitals NIHR Biomedical Research Centre, London (United Kingdom)

    2017-06-15

    To evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour. Sixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had 'significant' TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis. ADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83). Textural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion. (orig.)

  2. Therapeutic actions of an insulin receptor activator and a novel peroxisome proliferator-activated receptor gamma agonist in the spontaneously hypertensive obese rat model of metabolic syndrome X.

    Science.gov (United States)

    Velliquette, Rodney A; Friedman, Jacob E; Shao, J; Zhang, Bei B; Ernsberger, Paul

    2005-07-01

    Insulin resistance clusters with hyperlipidemia, impaired glucose tolerance, and hypertension as metabolic syndrome X. We tested a low molecular weight insulin receptor activator, demethylasterriquinone B-1 (DMAQ-B1), and a novel indole peroxisome proliferator-activated receptor gamma agonist, 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid (PPEIA), in spontaneously hypertensive obese rats (SHROB), a genetic model of syndrome X. Agents were given orally for 19 days. SHROB showed fasting normoglycemia but impaired glucose tolerance after an oral load, as shown by increased glucose area under the curve (AUC) [20,700 mg x min/ml versus 8100 in lean spontaneously hypertensive rats (SHR)]. Insulin resistance was indicated by 20-fold excess fasting insulin and increased insulin AUC (6300 ng x min/ml versus 990 in SHR). DMAQ-B1 did not affect glucose tolerance (glucose AUC = 21,300) but reduced fasting insulin 2-fold and insulin AUC (insulin AUC = 4300). PPEIA normalized glucose tolerance (glucose AUC = 9100) and reduced insulin AUC (to 3180) without affecting fasting insulin. PPEIA also increased food intake, fat mass, and body weight gain (81 +/- 12 versus 45 +/- 8 g in untreated controls), whereas DMAQ-B1 had no effect on body weight but reduced subscapular fat mass. PPEIA but not DMAQ-B1 reduced blood pressure. In skeletal muscle, insulin-stimulated phosphorylation of the insulin receptor and insulin receptor substrate protein 1-associated phosphatidylinositol 3-kinase activity were decreased by 40 to 55% in SHROB relative to lean SHR. PPEIA, but not DMAQ-B1, enhanced both insulin actions. SHROB also showed severe hypertriglyceridemia (355 +/- 42 mg/dl versus 65 +/- 3 in SHR) attenuated by both agents (DMAQ-B1, 228 +/- 18; PPEIA, 79 +/- 3). Both these novel antidiabetic agents attenuate insulin resistance and hypertriglyceridemia associated with metabolic syndrome but via distinct mechanisms.

  3. Quantitative flow measurement after placing a flow diverter for a distal internal carotid artery aneurysm.

    Science.gov (United States)

    Chen, Chien-Wei; Wong, Ho-Fai; Ye, Yu-Ling; Chen, Yao-Liang; Chen, Wei-Liang; Ou, Chang-Hsien; Tsai, Yuan-Hsiung

    2017-12-01

    To evaluate the differences in arterial flow after flow diverter placement using quantitative flow measurements based on digital subtraction angiography (DSA). Between November 2013 and November 2015, all patients who had flow diverters placed for distal internal carotid artery (ICA) aneurysms were reviewed. Patients in whom the stent was placed across the ostia of the ophthalmic artery (OphA) and anterior choroidal artery (AChA) were enrolled. Five regions of interest were selected: the proximal ICA (as a reference), terminal ICA, middle cerebral artery (MCA), anterior cerebral artery (ACA), OphA, and AChA. The values of the peak, time-to-peak (TTP), and area under the curve (AUC) were analyzed using a quantitative DSA technique. The study enrolled 13 patients. The quantitative flow analysis showed improved flow in the terminal ICA (peak and AUC, p=0.036 and p=0.04, respectively), MCA (AUC, p=0.023), and ACA (AUC, p=0.006), and decreased flow in the OphA (peak and AUC, p=0.013 and p=0.005, respectively) and AChA (peak and subtracted TTP, p=0.023 and p=0.050, respectively) after flow diverter placement. Larger aneurysm volume was significantly correlated with decreased OphA flow after the procedure (peak and AUC, p=0.049 and p=0.037, respectively). Larger aneurysm volume also had a marginal correlation with increased distal ICA flow after the procedure, but this did not reach significance (peak and AUC, p=0.195 and p=0.060, respectively). Without using extra contrast medium or radiation dosages, color-coded DSA enables quantitative monitoring of the cerebral circulation after flow-diverting treatment. 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/.

  4. Disease gene prioritization using network and feature.

    Science.gov (United States)

    Xie, Bingqing; Agam, Gady; Balasubramanian, Sandhya; Xu, Jinbo; Gilliam, T Conrad; Maltsev, Natalia; Börnigen, Daniela

    2015-04-01

    Identifying high-confidence candidate genes that are causative for disease phenotypes, from the large lists of variations produced by high-throughput genomics, can be both time-consuming and costly. The development of novel computational approaches, utilizing existing biological knowledge for the prioritization of such candidate genes, can improve the efficiency and accuracy of the biomedical data analysis. It can also reduce the cost of such studies by avoiding experimental validations of irrelevant candidates. In this study, we address this challenge by proposing a novel gene prioritization approach that ranks promising candidate genes that are likely to be involved in a disease or phenotype under study. This algorithm is based on the modified conditional random field (CRF) model that simultaneously makes use of both gene annotations and gene interactions, while preserving their original representation. We validated our approach on two independent disease benchmark studies by ranking candidate genes using network and feature information. Our results showed both high area under the curve (AUC) value (0.86), and more importantly high partial AUC (pAUC) value (0.1296), and revealed higher accuracy and precision at the top predictions as compared with other well-performed gene prioritization tools, such as Endeavour (AUC-0.82, pAUC-0.083) and PINTA (AUC-0.76, pAUC-0.066). We were able to detect more target genes (9/18/19/27) on top positions (1/5/10/20) compared to Endeavour (3/11/14/23) and PINTA (6/10/13/18). To demonstrate its usability, we applied our method to a case study for the prediction of molecular mechanisms contributing to intellectual disability and autism. Our approach was able to correctly recover genes related to both disorders and provide suggestions for possible additional candidates based on their rankings and functional annotations.

  5. The predictive value of the ratio of neck circumference to thyromental distance in comparison with four predictive tests for difficult laryngoscopy in obstetric patients scheduled for caesarean delivery

    Directory of Open Access Journals (Sweden)

    Anahita Hirmanpour

    2014-01-01

    Full Text Available Background: Preoperative assessment of anatomical landmarks andclinical factors help detect potentially difficult laryngoscopies. The aim of the present study was to compare the ability to predict difficult visualization of the larynx from thefollowing preoperative airway predictive indices, in isolation and combination: Neck circumference to thyromental distance (NC/TMD, neck circumference (NC, modified Mallampatitest (MMT, the ratio of height to thyromental distance (RHTMD, and the upper-lip-bite test (ULBT. Materials and Methods: We collected data on657 consecutive patients scheduled for elective caesarean delivery under general anesthesia requiring endotracheal intubation and then evaluated all five factors before caesarean. An experienced anesthesiologist, not informed of the recorded preoperative airway evaluation, performed the laryngoscopy and grading (as per Cormack and Lehane′s classification. Sensitivity, specificity, and positive and negative predictive values for each airway predictor in isolation and in combination were determined. Results: Difficult laryngoscopy (Grade 3 or 4 occurred in 53 (8.06% patients. There were significant differences in thyromental distance (TMD, RHTMD, NC, and NC/TMD between difficult visualization of larynx and easy visualization of larynx patients (P < 0.05.The main end-point area under curve (AUC of the receiver-operating characteristic (ROC was lower for MMT (AUC = 0.497; 95% Confidence Interval = CI,0.045-0.536 and ULBT (AUC = 0.500, 95% CI, 0.461-0.539 compared to RHTMD, NC, TMD, and NC/TMD score ([AUC = 0.627, 95% CI, 0.589-0.664], [AUC = 0.691; 95% CI, 0.654-0.726], [AUC = 0.606; 95% CI, 0.567-0.643], [AUC = 0.689;95% CI, 0.625-0.724], respectively, and the differences of six ROC curves were statistically significant (P < 0.05. Conclusion: The NC/TM Discomparable with NC, RHTMD, and ULBT for the prediction of difficult laryngoscopy in caes are an delivery.

  6. Evaluation of a 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation: A Randomized, 3-Way Crossover Pharmacokinetic and Safety Study in Healthy Volunteers.

    Science.gov (United States)

    Yue, Yong; Collaku, Agron; Liu, Dongzhou J

    2018-01-01

    Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (T C≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC 0-t ), AUC from 0 to infinity (AUC 0-inf ), and maximum plasma acetaminophen concentration (C max ). T C≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas T C≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC 0-12 , AUC 0-t , and AUC 0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.

  7. Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects.

    Science.gov (United States)

    Chong, Edward; Kalia, Veena; Willsie, Sandra; Winkle, Peter

    2014-12-01

    The novel iron-based phosphate binder sucroferric oxyhydroxide is being investigated for the treatment of hyperphosphatemia. Patients with chronic kidney disease often have multiple comorbidities that may necessitate the daily use of several types of medication. Therefore, the potential pharmacokinetic drug-drug interactions between sucroferric oxyhydroxide and selected drugs commonly taken by dialysis patients were investigated. Five Phase I, single-center, open-label, randomized, three-period crossover studies in healthy volunteers investigated the effect of a single dose of sucroferric oxyhydroxide 1 g (based on iron content) on the pharmacokinetics of losartan 100 mg, furosemide 40 mg, omeprazole 40 mg, digoxin 0.5 mg and warfarin 10 mg. Pharmacokinetic parameters [including area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinite time (AUC0-∞) and from 0 to 24 h (AUC0-24)] for these drugs were determined: alone in the presence of food; with sucroferric oxyhydroxide in the presence of food; 2 h after food and sucroferric oxyhydroxide administration. Systemic exposure based on AUC0-∞ for all drugs, and AUC0-24 for all drugs except omeprazole (for which AUC 0-8 h was measured), was unaffected to a clinically significant extent by the presence of sucroferric oxyhydroxide, irrespective of whether sucroferric oxyhydroxide was administered with the drug or 2 h earlier. There is a low risk of drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, digoxin and warfarin. There is also a low risk of drug-drug interaction with omeprazole (based on AUC0-∞ values). Therefore, sucroferric oxyhydroxide may be administered concomitantly without the need to adjust the dosage regimens of these drugs.

  8. Changes in hepatic perfusion assessed by dynamic contrast enhanced MRI, associated with morphologic evaluation, in patients with liver metastases from colorectal cancer treated with first-line chemotherapy.

    Science.gov (United States)

    Tampellini, Marco; Gned, Dario; Baratelli, Chiara; Brizzi, Maria Pia; Ottone, Azzurra; Alabiso, Irene; Bertaggia, Chiara; Di Maio, Massimo; Scagliotti, Giorgio Vittorio; Veltri, Andrea

    2016-12-01

    Blood perfusion of liver metastases can be non-invasively assessed by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The aim of this study was to explore whether the ratio of hepatic arterial to total liver blood flow (Hepatic Perfusion Index-HPI) and the area under the enhancement curve (AUC) of selected liver areas in patients with hepatic metastases from colorectal cancer treated with first-line chemotherapy could predict response and/or be a prognostic variable. Sequential liver DCE-MRI studies with morphological imaging reconstruction were performed in 43 consecutive patients at baseline and every 3 months during oxaliplatin-based first-line chemotherapy. Data about HPI of the whole liver, and AUC of metastatic and healthy areas were calculated at each time-point and compared both at baseline and sequentially during the treatment. Baseline HPI and AUC values did not discriminate patients responsive to chemotherapy, nor those with better survival outcomes. HPI and AUC values at 3 months decreased significantly more in responders than non-responders. AUCs calculated from areas of the liver with or without neoplastic lesions varied consistently, being increased in progressing patients and decreased in responding patients. Our results did not support the hypothesis of a predictive or prognostic role of HPI and AUCs calculated by DCE-MRI in liver metastatic CRC patients, thus the primary endpoint of the study was not reached. However, reduced arterial blood flow in metastatic liver can be obtained by chemotherapy alone, without any anti-angiogenic agent; interestingly, HPI and AUC data suggest a possible relationship between tumor metabolism and entire liver perfusion.

  9. Screening for depression in adolescent paediatric patients: validity of the new Depression Screener for Teenagers (DesTeen).

    Science.gov (United States)

    Pietsch, Kathrin; Allgaier, Antje-Kathrin; Frühe, Barbara; Rohde, Sabine; Hosie, Stuart; Heinrich, Martina; Schulte-Körne, Gerd

    2011-09-01

    Depression in adolescents is often hard to detect. In many cases paediatricians are the first point of contact. In order to increase recognition rates, screening instruments may be a helpful support for health care professionals. However, there is a lack of valid and economical screening instruments for primary care patients. Thus, the aim of the study was the development of the new Depression Screener for Teenagers (DesTeen) and its validation in a paediatric sample. 326 patients between 13 and 16 years old completed the DesTeen and a diagnostic interview, serving as gold standard. Prevalence rate for any depressive disorder (minor depression, major depression and dysthymia) was 12.6%. Psychometric properties were calculated. For validity measures, the area under the receiver operating characteristic curves (AUC) for any depressive disorder and the diagnostic subgroups was computed. DesTeen showed a high reliability (Cronbach's α=.87) and a high validity (AUC=.91). For the diagnostic subgroups AUC values did not significantly differ from overall accuracy of any depressive disorder (major depression: AUC=.95, p=.179; dysthymia: AUC=.88, p=.605; minor depression: AUC=.87, p=.327). The optimal cut-off point for any depressive disorder according to the Youden-Index yielded a sensitivity of .90 and a specificity of .80. An abbreviated 5-item version of DesTeen showed no loss in validity (AUC=.90, p=.695). Overall, DesTeen can be regarded as a valid screening instrument for adolescent paediatric patients. For practical use, the 5-item version is even more promising. A replication of these results is essential. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. MR-sequences for prostate cancer diagnostics: validation based on the PI-RADS scoring system and targeted MR-guided in-bore biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Schimmoeller, Lars; Quentin, Michael; Buchbender, Christian; Antoch, Gerald; Blondin, Dirk [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Dusseldorf (Germany); Arsov, Christian; Hiester, Andreas; Rabenalt, Robert; Albers, Peter [University Dusseldorf, Medical Faculty, Department of Urology, Dusseldorf (Germany)

    2014-10-15

    This study evaluated the accuracy of MR sequences [T2-, diffusion-weighted, and dynamic contrast-enhanced (T2WI, DWI, and DCE) imaging] at 3T, based on the European Society of Urogenital Radiology (ESUR) scoring system [Prostate Imaging Reporting and Data System (PI-RADS)] using MR-guided in-bore prostate biopsies as reference standard. In 235 consecutive patients [aged 65.7 ± 7.9 years; median prostate-specific antigen (PSA) 8 ng/ml] with multiparametric prostate MRI (mp-MRI), 566 lesions were scored according to PI-RADS. Histology of all lesions was obtained by targeted MR-guided in-bore biopsy. In 200 lesions, biopsy revealed prostate cancer (PCa). The area under the curve (AUC) for cancer detection was 0.70 (T2WI), 0.80 (DWI), and 0.74 (DCE). A combination of T2WI + DWI, T2WI + DCE, and DWI + DCE achieved an AUC of 0.81, 0.78, and 0.79. A summed PI-RADS score of T2WI + DWI + DCE achieved an AUC of 0.81. For higher grade PCa (primary Gleason pattern ≥ 4), the AUC was 0.85 for T2WI + DWI, 0.84 for T2WI + DCE, 0.86 for DWI + DCE, and 0.87 for T2WI + DWI + DCE. The AUC for T2WI + DWI + DCE for transitional-zone PCa was 0.73, and for the peripheral zone 0.88. Regarding higher-grade PCa, AUC for transitional-zone PCa was 0.88, and for peripheral zone 0.96. The combination of T2WI + DWI + DCE achieved the highest test accuracy, especially in patients with higher-grade PCa. The use of ≤2 MR sequences led to lower AUC in higher-grade and peripheral-zone cancers. (orig.)

  11. NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in Oral Cavity Squamous Cell Carcinoma tissues and saliva

    Science.gov (United States)

    Guerrero-Preston, R; Soudry, E; Acero, J; Orera, M; Moreno-López, L; Macía-Colón, Germán; Jaffe, A; Berdasco, M; Ili-Gangas, C; Brebi-Mieville, P; Fu, Y; Engstrom, C; Irizarry, R; Esteller, M; Westra, W; Koch, W; Califano, J; Sidransky, D

    2011-01-01

    Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage-design consisting of Discovery and Prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (κ = 0.64), HOXA9 (κ = 0.60), NID2 (κ = 0.60), and EDNRB (κ = 0.60) had a moderate to substantial agreement with clinical diagnosis in the Discovery screen. HOXA9 had 68% sensitivity, 100% specificity and a 0.81 AUC. NID2 had 71% sensitivity, 100% specificity and a 0.79 AUC. In the Prevalence screen HOXA9 (κ = 0.82) and NID2 (κ = 0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity and a 0.97 AUC. In saliva from OSCC cases and controls HOXA9 had 75% sensitivity, 53% specificity and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity and a 0.73 AUC. This Phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies. PMID:21558411

  12. Relationship between day 1 and day 2 Vancomycin area under the curve values and emergence of heterogeneous Vancomycin-intermediate Staphylococcus aureus (hVISA) by Etest® macromethod among patients with MRSA bloodstream infections: a pilot study.

    Science.gov (United States)

    Martirosov, Dmitriy M; Bidell, Monique R; Pai, Manjunath P; Scheetz, Marc H; Rosenkranz, Susan L; Faragon, Corey; Malik, M; Mendes, R E; Jones, R N; McNutt, Louise-Anne; Lodise, Thomas P

    2017-08-02

    In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. However, no clinical studies have evaluated the relationship between initial vancomycin exposure and emergence of hVISA. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a non-hVISA BSI at baseline. This was a retrospective cohort study of patients with methicillin-resistant Staphylococcus aureus (MRSA) BSIs at Albany Medical Center Hospital (AMCH) between January 2005 and June 2009. The vancomycin AUC exposure variables on day 1 (AUC0-24h) and day 2 (AUC24-48h) were estimated using the maximal a posteriori probability (MAP) procedure in ADAPT 5. There were 238 unique episodes of MRSA BSIs during the study period, 119 of which met inclusion criteria. Overall, hVISA emerged in 7/119 (5.9%) of patients. All 7 cases of hVISA involved patients who did not achieve area under the curve over broth microdilution minimum inhibitory concentration (AUC0-24h/MICBMD) ratio of 521 or an AUC24-48h/MICBMD ratio of 650. No associations between other day 1 and day 2 AUC variables and emergence of hVISA were noted. Although more data are needed to draw definitive conclusions, these findings suggest that hVISA emergence among patients with non-hVISA MRSA BSIs at baseline may be partially explained by suboptimal exposure to vancomycin in the first 1 to 2 days of therapy. At a minimum, these findings support further study of the relationship between initial vancomycin exposure and hVISA emergence among patients with MRSA BSIs in a well-powered, multi-center, prospective trial.

  13. Therapeutic drug monitoring of cyclosporine Neoral in de novo Chinese cardiac transplant recipients treated with an everolimus-cyclosporine immunosuppressive regimen.

    Science.gov (United States)

    Wang, C-H; Chou, N-K; Wu, F-L L; Ko, W-J; Tsao, C-I; Chi, N-H; Hsu, R-B; Wang, S-S

    2006-09-01

    This study determined cyclosporine Neoral (CsA) pharmacokinetics and the accuracy of a limited sampling strategy to predict the 12-hour CsA area-under-the-curve (AUC) to provide a practical method for more accurate therapeutic drug monitor of CsA among de novo Chinese heart transplant recipients treated with an everolimus-CsA immunosuppressive regimen. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours after oral administration of CsA in six de novo heart recipients receiving a CsA, everolimus, and methylprenisolone immunosuppressive regimen after rabbit antithymoglobulin sequential immuno-induction. We analyzed the pharmacokinetics of the first dose (PK-1) and steady state dose (PK-2) at 1 month after transplantation. The accuracy of a single-point sampling method to predict the AUC was generated by linear regression analyses. The t(max) and dose-normalized C(max) of PK-1 and PK-2 were similar. The correlations in single-point blood levels of PK-1 to predict the AUC(0-infinity) were much lower than the corresponding sampling times in PK-2. In PK-2 study, C4 had the best correlation (r(2) = 0.913, P = .003) to predict AUC(0-12). In addition, the trough concentrations, C(0) (r(2) = 0.875, P = .006) and C(12) (r(2) = 0.783, P = .02) also showed good correlations. C2 had insufficient correlation to predict AUC(0-infinity) in PK-1 or AUC(0-12) in the PK-2 study. In conclusion, the absorption of CsA was similar during PK-1 and PK-2. At steady dose, C4 had the best single-point correlation to predict AUC(0-12). Trough blood levels may be more practical in clinical use to monitor CsA.

  14. The Concave Shape of the Forced Expiratory Flow-Volume Curve in 3 Seconds Is a Practical Surrogate of FEV1/FVC for the Diagnosis of Airway Limitation in Inadequate Spirometry.

    Science.gov (United States)

    Li, Hao; Liu, Chunhong; Zhang, Yi; Xiao, Wei

    2017-03-01

    Spirometry is important for the differential diagnosis of dyspnea. However, some patients cannot exhale for ≥6 s to achieve the American Thoracic Society/European Respiratory Society criteria. The aim of this study was to demonstrate the reliability of a new parameter that quantifies the degree of concavity in the first 3 s to define airway limitation as a surrogate for the FEV 1 /FVC. Four hundred spirometry test results were selected through complete random sampling. The new parameter, termed the AUC 3 /AT 3 , was calculated as the area under the descending limb of the expiratory flow-volume curve before the end of the first 3 s (AUC 3 ) divided by the area of the triangle before the end of the first 3 s (AT 3 ). The AUC 3 /AT 3 was compared with the FEV 1 /FVC using Pearson's correlation analysis. The level of agreement between the AUC 3 /AT 3 and the FEV 1 /FVC in the detection of airway obstruction was analyzed using the kappa statistic. We also compared the diagnostic accuracy of the new index with that of the FEV 1 /forced expiratory volume in the first 3 s (FEV 3 ). There was a strong correlation (r = 0.88, P < .001) between the AUC 3 /AT 3 and the FEV 1 /FVC. There was also strong agreement between the AUC 3 /AT 3 and the FEV 1 /FVC in the detection of obstruction with kappa indices of 0.72 (Global Initiative for Chronic Obstructive Lung Disease [GOLD] criterion) and 0.67 (lower limit of normal criterion), and these values were greater than those obtained for the FEV 1 /FEV 3 . The AUC 3 /AT 3 also exhibited acceptable sensitivity, specificity, positive predictive value, and negative predictive value. The diagnostic accuracies of the AUC 3 /AT 3 were 86.3% (GOLD criterion) and 83.8% (lower limit of normal criterion), which were greater than the 76.0 and 74.0% obtained for the FEV 1 /FEV 3 , respectively. The AUC 3 /AT 3 can be utilized as a surrogate parameter for the FEV 1 /FVC when patients cannot complete a 6-s expiratory effort. Additionally, the

  15. Functional Regions of Interest in Electrical Impedance Tomography: A Secondary Analysis of Two Clinical Studies.

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    Tobias Becher

    Full Text Available Patients with acute respiratory distress syndrome (ARDS typically show a high degree of ventilation inhomogeneity, which is associated with morbidity and unfavorable outcomes. Electrical impedance tomography (EIT is able to detect ventilation inhomogeneity, but it is unclear which method for defining the region of interest (ROI should be used for this purpose. The aim of our study was to compare the functional region of interest (fROI method to both the lung area estimation method (LAEM and no ROI when analysing global parameters of ventilation inhomogeneity. We assumed that a good method for ROI determination would lead to a high discriminatory power for ventilation inhomogeneity, as defined by the area under the receiver operating characteristics curve (AUC, comparing patients suffering from ARDS and control patients without pulmonary pathologies.We retrospectively analysed EIT data from 24 ARDS patients and 12 control patients without pulmonary pathology. In all patients, a standardized low-flow-pressure volume maneuver had been performed and was used for EIT image generation. We compared the AUC for global inhomogeneity (GI index and coefficient of variation (CV between ARDS and control patients using all EIT image pixels, the fROI method and the LAEM for ROI determination.When analysing all EIT image pixels, we found an acceptable AUC both for the GI index (AUC = 0.76; 95% confidence interval (CI 0.58-0.94 and the CV (AUC = 0.74; 95% CI 0.55-0.92. With the fROI method, we found a deteriorating AUC with increasing threshold criteria. With the LAEM, we found the best AUC both for the GI index (AUC = 0.89; 95% CI 0.78-1.0 and the CV (AUC = 0.89; 95% CI 0.78-1.0 using a threshold criterion of 50% of the maximum tidal impedance change.In the assessment of ventilation inhomogeneity with EIT, functional regions of interest obscure the difference between patients with ARDS and control patients without pulmonary pathologies. The LAEM is preferable

  16. MO-DE-207B-01: JACK FOWLER JUNIOR INVESTIGATOR COMPETITION WINNER: Between Somatic Mutations and PET-Based Radiomic Features in Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yip, S; Coroller, T; Rios Velazquez, E; Parmar, C; Mak, R; Aerts, H [Brigham and Women’s Hospital, Dana Farber Cancer Institute, and Harvard Medical School, Boston, MA (United States); Kim, J [Brigham and Women’s Hospital, Boston Children’s Hospital and Harvard Medical School, Boston, MA (United States)

    2016-06-15

    Purpose: Although PET-based radiomic features have been proposed to quantify tumor heterogeneity and shown promise in outcome prediction, little is known about their relationship with tumor genetics. This study assessed the association of [{sup 18}F]fluorodeoxyglucose (FDG)-PET-based radiomic features with non-small cell lung cancer (NSCLC) mutations. Methods: 348 NSCLC patients underwent FDG-PET/CT scans before treatment and were tested for genetic mutations. 13% (44/348) and 28% (96/348) patients were found to harbor EGFR (EGFR+) and KRAS (KRAS+) mutations, respectively. We evaluated nineteen PET-based radiomic features quantifying phenotypic traits, and compared them with conventional PET features (metabolic tumor volume (MTV) and maximum-SUV). The association between the feature values and mutation status was evaluated using the Wilcoxcon-rank-sum-test. The ability of each measure to predict mutations was assessed by the area under the receiver operating curve (AUC). Noether’s test was used to determine if the AUCs were significantly from random (AUC=0.50). All p-values were corrected for multiple testing by controlling the false discovery rate (FDR{sub Wilcoxon} and FDR{sub Noether}) of 10%. Results: Eight radiomic features, MTV, and maximum-SUV, were significantly associated with the EGFR mutation (FDR{sub Wilcoxon}=0.01–0.10). However, KRAS+ demonstrated no significantly distinctive imaging features compared to KRAS− (FDR{sub Wilcoxon}≥0.92). EGFR+ and EGFR− were significantly discriminated by conventional PET features (AUC=0.61, FDR{sub Noether}=0.04 for MTV and AUC=0.64, FDR{sub Noether}=0.01 for maximum-SUV). Eight radiomic features were significantly predictive for EGFR+ compared to EGFR− (AUC=0.59–0.67, FDR{sub Noether}=0.0032–0.09). Normalized-inverse-difference-moment outperformed all features in predicting EGFR mutation (AUC=0.67, FDR{sub Noether}=0.0032). Moreover, only the radiomic feature normalized-inverse-difference-moment could

  17. Selective CNS Uptake of the GCP-II Inhibitor 2-PMPA following Intranasal Administration.

    Directory of Open Access Journals (Sweden)

    Rana Rais

    Full Text Available Glutamate carboxypeptidase II (GCP-II is a brain metallopeptidase that hydrolyzes the abundant neuropeptide N-acetyl-aspartyl-glutamate (NAAG to NAA and glutamate. Small molecule GCP-II inhibitors increase brain NAAG, which activates mGluR3, decreases glutamate, and provide therapeutic utility in a variety of preclinical models of neurodegenerative diseases wherein excess glutamate is presumed pathogenic. Unfortunately no GCP-II inhibitor has advanced clinically, largely due to their highly polar nature resulting in insufficient oral bioavailability and limited brain penetration. Herein we report a non-invasive route for delivery of GCP-II inhibitors to the brain via intranasal (i.n. administration. Three structurally distinct classes of GCP-II inhibitors were evaluated including DCMC (urea-based, 2-MPPA (thiol-based and 2-PMPA (phosphonate-based. While all showed some brain penetration following i.n. administration, 2-PMPA exhibited the highest levels and was chosen for further evaluation. Compared to intraperitoneal (i.p. administration, equivalent doses of i.n. administered 2-PMPA resulted in similar plasma exposures (AUC0-t, i.n./AUC0-t, i.p. = 1.0 but dramatically enhanced brain exposures in the olfactory bulb (AUC0-t, i.n./AUC0-t, i.p. = 67, cortex (AUC0-t, i.n./AUC0-t, i.p. = 46 and cerebellum (AUC0-t, i.n./AUC0-t, i.p. = 6.3. Following i.n. administration, the brain tissue to plasma ratio based on AUC0-t in the olfactory bulb, cortex, and cerebellum were 1.49, 0.71 and 0.10, respectively, compared to an i.p. brain tissue to plasma ratio of less than 0.02 in all areas. Furthermore, i.n. administration of 2-PMPA resulted in complete inhibition of brain GCP-II enzymatic activity ex-vivo confirming target engagement. Lastly, because the rodent nasal system is not similar to humans, we evaluated i.n. 2-PMPA also in a non-human primate. We report that i.n. 2-PMPA provides selective brain delivery with micromolar concentrations. These studies

  18. Pharmacokinetics/Pharmacodynamics of Peptide Deformylase Inhibitor GSK1322322 against Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in Rodent Models of Infection.

    Science.gov (United States)

    Hoover, Jennifer; Lewandowski, Thomas; Straub, Robert J; Novick, Steven J; DeMarsh, Peter; Aubart, Kelly; Rittenhouse, Stephen; Zalacain, Magdalena

    2015-10-19

    GSK1322322 is a novel inhibitor of peptide deformylase (PDF) with good in vitro activity against bacteria associated with community-acquired pneumonia and skin infections. We have characterized the in vivo pharmacodynamics (PD) of GSK1322322 in immunocompetent animal models of infection with Streptococcus pneumoniae and Haemophilus influenzae (mouse lung model) and with Staphylococcus aureus (rat abscess model) and determined the pharmacokinetic (PK)/PD index that best correlates with efficacy and its magnitude. Oral PK studies with both models showed slightly higher-than-dose-proportional exposure, with 3-fold increases in area under the concentration-time curve (AUC) with doubling doses. GSK1322322 exhibited dose-dependent in vivo efficacy against multiple isolates of S. pneumoniae, H. influenzae, and S. aureus. Dose fractionation studies with two S. pneumoniae and S. aureus isolates showed that therapeutic outcome correlated best with the free AUC/MIC (fAUC/MIC) index in S. pneumoniae (R(2), 0.83), whereas fAUC/MIC and free maximum drug concentration (fCmax)/MIC were the best efficacy predictors for S. aureus (R(2), 0.9 and 0.91, respectively). Median daily fAUC/MIC values required for stasis and for a 1-log10 reduction in bacterial burden were 8.1 and 14.4 for 11 S. pneumoniae isolates (R(2), 0.62) and 7.2 and 13.0 for five H. influenzae isolates (R(2), 0.93). The data showed that for eight S. aureus isolates, fAUC correlated better with efficacy than fAUC/MIC (R(2), 0.91 and 0.76, respectively), as efficacious AUCs were similar for all isolates, independent of their GSK1322322 MIC (range, 0.5 to 4 μg/ml). Median fAUCs of 2.1 and 6.3 μg · h/ml were associated with stasis and 1-log10 reductions, respectively, for S. aureus. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Postprandial Glycemic and Insulinemic Responses to Common Breakfast Beverages Consumed with a Standard Meal in Adults Who Are Overweight and Obese

    Directory of Open Access Journals (Sweden)

    Jia Li

    2017-01-01

    Full Text Available Breakfast beverages with different nutrient compositions may affect postprandial glycemic control differently. We assessed the effects of consuming (1 common breakfast beverages (water, sugar-sweetened coffee, reduced-energy orange juice (OJ, and low-fat milk (LFM; and (2 fat-free, low-fat, and whole milk with breakfast on postprandial plasma glucose and insulin responses in adults who were overweight/obese. Forty-six subjects (33F/13M, body mass index: 32.5 ± 0.7 kg/m2, age: 50 ± 1 years, mean ± SEMs consumed a standard sandwich with one of the six beverages on separate mornings in randomized order. The test beverages (except water each contained 12 g digestible carbohydrate. Plasma glucose and insulin concentrations were measured from blood obtained pre- and post-meal at 30-min intervals for 4 h and incremental areas under the curve (AUC were computed. We found (1 among different beverage types, glucose AUC was higher for coffee versus water, OJ, and LFM. Insulin AUC was higher for coffee and LFM versus OJ and water; (2 Glucose AUCs were not different among water and milks while insulin AUC was higher for milks versus water. In conclusion, consumption of water, reduced-energy OJ, or milk (irrespective of fat content with a meal may be preferable to consuming sugar-sweetened coffee for glucose control in middle-aged adults who are overweight and obese.

  20. A Pharmacokinetic Study Comparing Eslicarbazepine Acetate Administered Orally as a Crushed or Intact Tablet in Healthy Volunteers.

    Science.gov (United States)

    Sunkaraneni, Soujanya; Kharidia, Jahnavi; Schutz, Ralph; Blum, David; Cheng, Hailong

    2016-07-01

    The relative bioequivalence of crushed versus intact eslicarbazepine acetate (ESL) tablets (800 mg) administered orally in healthy adults was evaluated in an open-label, randomized, 2-period crossover study with a 5-day washout between treatments. Sample blood levels of eslicarbazepine and (R)-licarbazepine were determined; pharmacokinetic parameters were derived for eslicarbazepine. Bioequivalence was established if the 90% confidence intervals (CIs) for the geometric mean treatment ratios of eslicarbazepine AUC(0-∞) and Cmax were within the prespecified 80%-125% range. Twenty-seven subjects in the intent-to-treat population (n = 28) completed both treatment periods. Eslicarbazepine exposure measures were similar for crushed versus intact ESL tablets: average Cmax , 11 700 versus 11 500 ng/mL; AUC(0-∞) , 225 000 versus 234 000 ng·h/mL; AUC(0-last) , 222 000 versus 231 000 ng·h/mL, respectively. Geometric least squares mean ratios (90%CIs) comparing eslicarbazepine exposure measures were within the 80%-125% range (Cmax , 102.63% [97.07%-108.51%]; AUC(0-∞) , 96.72% [94.36%-99.13%]; AUC0-last , 96.69% [94.24%-99.21%]). In conclusion, ESL administered orally as a crushed tablet sprinkled on applesauce, or intact were bioequivalent in healthy subjects. Eslicarbazepine bioavailability was not significantly altered by crushing, indicating that ESL tablets can be administered intact or crushed. © 2016, The American College of Clinical Pharmacology.

  1. A quantified risk-scoring system and rating model for postsurgical gastroparesis syndrome in gastric cancer patients.

    Science.gov (United States)

    Chen, Xiao-Dong; Mao, Chen-Chen; Zhang, Wei-Teng; Lin, Ji; Wu, Rui-Sen; Zhang, Feng-Min; Sun, Xiang-Wei; Chi, Chu-Huai; Shen, Xian; Wang, Peng-Fei

    2017-09-01

    The study aimed to investigate the relationship between obesity and postsurgical gastroparesis syndrome (PGS), and to construct a scoring system and a risk model to identify patients at high risk. A total of 634 patients were retrospectively analyzed. Clinical characteristics were evaluated via receiver operating characteristic (ROC) curve analysis. Logistic analysis was performed to determine the independent predictive indicators of PGS. A scoring system consisting of these indicators and a risk-rating model were constructed and evaluated via ROC curve analysis. Based on the ROC curves, the visceral fat area (VFA) cutoff value for PGS was 94.00. Logistic analysis showed that visceral obesity (VFA ≥ 94.00 cm(2) ), the reconstruction technique, and tumor size were independent prognostic factors for PGS. The scoring system could predict PGS reliably with a high area under the ROC curve ([AUC] = 0.769). A high-risk rating had a high AUC (AUC I = 0.56, AUC II = 0.65, and AUC III = 0.77), indicating that the risk-rating model could effectively screen patients at high risk of PGS. Visceral obesity defined by VFA effectively predicted PGS. Our scoring system may be a reliable instrument for identifying patients most at risk of PGS. © 2017 Wiley Periodicals, Inc.

  2. Hip fracture risk estimation based on principal component analysis of QCT atlas: a preliminary study

    Science.gov (United States)

    Li, Wenjun; Kornak, John; Harris, Tamara; Lu, Ying; Cheng, Xiaoguang; Lang, Thomas

    2009-02-01

    We aim to capture and apply 3-dimensional bone fragility features for fracture risk estimation. Using inter-subject image registration, we constructed a hip QCT atlas comprising 37 patients with hip fractures and 38 age-matched controls. In the hip atlas space, we performed principal component analysis to identify the principal components (eigen images) that showed association with hip fracture. To develop and test a hip fracture risk model based on the principal components, we randomly divided the 75 QCT scans into two groups, one serving as the training set and the other as the test set. We applied this model to estimate a fracture risk index for each test subject, and used the fracture risk indices to discriminate the fracture patients and controls. To evaluate the fracture discrimination efficacy, we performed ROC analysis and calculated the AUC (area under curve). When using the first group as the training group and the second as the test group, the AUC was 0.880, compared to conventional fracture risk estimation methods based on bone densitometry, which had AUC values ranging between 0.782 and 0.871. When using the second group as the training group, the AUC was 0.839, compared to densitometric methods with AUC values ranging between 0.767 and 0.807. Our results demonstrate that principal components derived from hip QCT atlas are associated with hip fracture. Use of such features may provide new quantitative measures of interest to osteoporosis.

  3. How many studies are necessary to compare niche-based models for geographic distributions? Inductive reasoning may fail at the end

    Directory of Open Access Journals (Sweden)

    LC Terribile

    Full Text Available The use of ecological niche models (ENM to generate potential geographic distributions of species has rapidly increased in ecology, conservation and evolutionary biology. Many methods are available and the most used are Maximum Entropy Method (MAXENT and the Genetic Algorithm for Rule Set Production (GARP. Recent studies have shown that MAXENT perform better than GARP. Here we used the statistics methods of ROC - AUC (area under the Receiver Operating Characteristics curve and bootstrap to evaluate the performance of GARP and MAXENT in generate potential distribution models for 39 species of New World coral snakes. We found that values of AUC for GARP ranged from 0.923 to 0.999, whereas those for MAXENT ranged from 0.877 to 0.999. On the whole, the differences in AUC were very small, but for 10 species GARP outperformed MAXENT. Means and standard deviations for 100 bootstrapped samples with sample sizes ranging from 3 to 30 species did not show any trends towards deviations from a zero difference in AUC values of GARP minus AUC values of MAXENT. Ours results suggest that further studies are still necessary to establish under which circumstances the statistical performance of the methods vary. However, it is also important to consider the possibility that this empirical inductive reasoning may fail in the end, because we almost certainly could not establish all potential scenarios generating variation in the relative performance of models.

  4. Comparison of the performance of log-logistic regression and artificial neural networks for predicting breast cancer relapse.

    Science.gov (United States)

    Faradmal, Javad; Soltanian, Ali Reza; Roshanaei, Ghodratollah; Khodabakhshi, Reza; Kasaeian, Amir

    2014-01-01

    Breast cancer is the most common cancers in female populations. The exact cause is not known, but is most likely to be a combination of genetic and environmental factors. Log-logistic model (LLM) is applied as a statistical method for predicting survival and it influencing factors. In recent decades, artificial neural network (ANN) models have been increasingly applied to predict survival data. The present research was conducted to compare log-logistic regression and artificial neural network models in prediction of breast cancer (BC) survival. A historical cohort study was established with 104 patients suffering from BC from 1997 to 2005. To compare the ANN and LLM in our setting, we used the estimated areas under the receiver-operating characteristic (ROC) curve (AUC) and integrated AUC (iAUC). The data were analyzed using R statistical software. The AUC for the first, second and third years after diagnosis are 0.918, 0.780 and 0.800 in ANN, and 0.834, 0.733 and 0.616 in LLM, respectively. The mean AUC for ANN was statistically higher than that of the LLM (0.845 vs. 0.744). Hence, this study showed a significant difference between the performance in terms of prediction by ANN and LLM. This study demonstrated that the ability of prediction with ANN was higher than with the LLM model. Thus, the use of ANN method for prediction of survival in field of breast cancer is suggested.

  5. Postprandial Glycemic and Insulinemic Responses to Common Breakfast Beverages Consumed with a Standard Meal in Adults Who Are Overweight and Obese.

    Science.gov (United States)

    Li, Jia; Janle, Elsa; Campbell, Wayne W

    2017-01-04

    Breakfast beverages with different nutrient compositions may affect postprandial glycemic control differently. We assessed the effects of consuming (1) common breakfast beverages (water, sugar-sweetened coffee, reduced-energy orange juice (OJ), and low-fat milk (LFM)); and (2) fat-free, low-fat, and whole milk with breakfast on postprandial plasma glucose and insulin responses in adults who were overweight/obese. Forty-six subjects (33F/13M, body mass index: 32.5 ± 0.7 kg/m², age: 50 ± 1 years, mean ± SEMs) consumed a standard sandwich with one of the six beverages on separate mornings in randomized order. The test beverages (except water) each contained 12 g digestible carbohydrate. Plasma glucose and insulin concentrations were measured from blood obtained pre- and post-meal at 30-min intervals for 4 h and incremental areas under the curve (AUC) were computed. We found (1) among different beverage types, glucose AUC was higher for coffee versus water, OJ, and LFM. Insulin AUC was higher for coffee and LFM versus OJ and water; (2) Glucose AUCs were not different among water and milks while insulin AUC was higher for milks versus water. In conclusion, consumption of water, reduced-energy OJ, or milk (irrespective of fat content) with a meal may be preferable to consuming sugar-sweetened coffee for glucose control in middle-aged adults who are overweight and obese.

  6. Relationship between acute rejection and cyclosporine or mycophenolic acid levels in Japanese heart transplantation.

    Science.gov (United States)

    Wada, Kyoichi; Takada, Mitsutaka; Ueda, Takashi; Ochi, Hiroyuki; Kotake, Takeshi; Morishita, Hideki; Hanatani, Akihisa; Nakatani, Takeshi

    2007-03-01

    Cyclosporine (CsA), Mycophenolate mofetil (MMF) and prednisolone (PSL) are widely used for the prevention of acute rejection after heart transplantation. Recently, the serum concentration - time curves (AUC) of CsA and MMF have been demonstrated to be precise predictors of acute rejection. Fourteen heart transplant patients were treated concomitantly with CsA, MMF, and PSL between May 1999 and November 2005 at the National Cardiovascular Center and of them 3 had acute rejection episodes [International Society for Heart & Lung Transplantation grade 3a]. Two patients (man in his 30 s; woman in her 40 s) had acute rejection with a mycophenolic acid (MPA) AUC(0-12 h) cardiac allograft rejection even if the MMF was temporarily stopped. These 3 patients were investigated to evaluate the relationship between acute rejection and pharmacokinetic parameters, including the CsA C0, C2, AUC(0-4 h) and MPA AUC(0-12 h). The findings suggest that a high CsA AUC(0-4 h) may prevent rejection of a cardiac allograft, even if MMF is stopped or drastically reduced.

  7. Feature selection in computer-aided breast cancer diagnosis via dynamic contrast-enhanced magnetic resonance images.

    Science.gov (United States)

    Rakoczy, Megan; McGaughey, Donald; Korenberg, Michael J; Levman, Jacob; Martel, Anne L

    2013-04-01

    The accuracy of computer-aided diagnosis (CAD) for early detection and classification of breast cancer in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is dependent upon the features used by the CAD classifier. Here, we show that fast orthogonal search (FOS), which provides a more efficient iterative manner of computing stepwise regression feature selection, can select features with predictive value from a set of kinetic and texture candidate features computed from dynamic contrast-enhanced magnetic resonance images. FOS can in minutes search candidate feature sets of millions of terms, which may include cross-products of features up to second-, third- or fourth-order. This method is tested on a set of 83 DCE-MRI images, of which 20 are for cancerous and 63 for benign cases, using a leave-one-out trial. The features selected by FOS were used in a FOS predictor and nearest-neighbour predictor and had an area under the receiver operating curve (AUC) of 0.889 and 0.791 respectively. The FOS predictor AUC is significantly improved over the signal enhancement ratio predictor with an AUC of 0.706 (p = 0.0035 for the difference in the AUCs). Moreover, using FOS-selected features in a support vector machine increased the AUC over that resulting when the features were manually selected.

  8. Using the Disease State Fingerprint Tool for Differential Diagnosis of Frontotemporal Dementia and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Muñoz-Ruiz

    2016-07-01

    Full Text Available Background: Disease State Index (DSI and its visualization, Disease State Fingerprint (DSF, form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. Aims: To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD and Alzheimer's disease (AD. Methods: The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases. We utilized data from neuropsychological tests, volumetric magnetic resonance imaging, single-photon emission tomography, cerebrospinal fluid biomarkers and the APOE genotype. The DSI classification results were calculated with a combination of leave-one-out cross-validation and bootstrapping. A DSF visualization of a FTD patient is presented as an example. Results: The DSI distinguishes controls from FTD (area under the receiver-operator curve, AUC = 0.99 and AD (AUC = 1.00 very well and achieves a good differential diagnosis between AD and FTD (AUC = 0.89. In subsamples of autopsy-confirmed cases (AUC = 0.97 and clinically diagnosed cases (AUC = 0.94, differential diagnosis of AD and FTD performs very well. Conclusions: DSI is a promising computer-assisted biomarker approach for aiding in the diagnostic process of dementing diseases. Here, DSI separates controls from dementia and differentiates between AD and FTD.

  9. Adaptive spectral window sizes for feature extraction from optical spectra

    Science.gov (United States)

    Kan, Chih-Wen; Lee, Andy Y.; Pham, Nhi; Nieman, Linda T.; Sokolov, Konstantin; Markey, Mia K.

    2008-02-01

    We propose an approach to adaptively adjust the spectral window size used to extract features from optical spectra. Previous studies have employed spectral features extracted by dividing the spectra into several spectral windows of a fixed width. However, the choice of spectral window size was arbitrary. We hypothesize that by adaptively adjusting the spectral window sizes, the trends in the data will be captured more accurately. Our method was tested on a diffuse reflectance spectroscopy dataset obtained in a study of oblique polarization reflectance spectroscopy of oral mucosa lesions. The diagnostic task is to classify lesions into one of four histopathology groups: normal, benign, mild dysplasia, or severe dysplasia (including carcinoma). Nine features were extracted from each of the spectral windows. We computed the area (AUC) under Receiver Operating Characteristic curve to select the most discriminatory wavelength intervals. We performed pairwise classifications using Linear Discriminant Analysis (LDA) with leave-one-out cross validation. The results showed that for discriminating benign lesions from mild or severe dysplasia, the adaptive spectral window size features achieved AUC of 0.84, while a fixed spectral window size of 20 nm had AUC of 0.71, and an AUC of 0.64 is achieved with a large window size containing all wavelengths. The AUCs of all feature combinations were also calculated. These results suggest that the new adaptive spectral window size method effectively extracts features that enable accurate classification of oral mucosa lesions.

  10. The average receiver operating characteristic curve in multireader multicase imaging studies.

    Science.gov (United States)

    Chen, W; Samuelson, F W

    2014-08-01

    In multireader, multicase (MRMC) receiver operating characteristic (ROC) studies for evaluating medical imaging systems, the area under the ROC curve (AUC) is often used as a summary metric. Owing to the limitations of AUC, plotting the average ROC curve to accompany the rigorous statistical inference on AUC is recommended. The objective of this article is to investigate methods for generating the average ROC curve from ROC curves of individual readers. We present both a non-parametric method and a parametric method for averaging ROC curves that produce a ROC curve, the area under which is equal to the average AUC of individual readers (a property we call area preserving). We use hypothetical examples, simulated data and a real-world imaging data set to illustrate these methods and their properties. We show that our proposed methods are area preserving. We also show that the method of averaging the ROC parameters, either the conventional bi-normal parameters (a, b) or the proper bi-normal parameters (c, da), is generally not area preserving and may produce a ROC curve that is intuitively not an average of multiple curves. Our proposed methods are useful for making plots of average ROC curves in MRMC studies as a companion to the rigorous statistical inference on the AUC end point. The software implementing these methods is freely available from the authors. METHODS for generating the average ROC curve in MRMC ROC studies are formally investigated. The area-preserving criterion we defined is useful to evaluate such methods.

  11. The precision--recall curve overcame the optimism of the receiver operating characteristic curve in rare diseases.

    Science.gov (United States)

    Ozenne, Brice; Subtil, Fabien; Maucort-Boulch, Delphine

    2015-08-01

    Compare the area under the receiver operating characteristic curve (AUC) vs. the area under the precision-recall curve (AUPRC) in summarizing the performance of a diagnostic biomarker according to the disease prevalence. A simulation study was performed considering different sizes of diseased and nondiseased groups. Values of a biomarker were sampled with various variances and differences in mean values between the two groups. The AUCs and the AUPRCs were examined regarding their agreement and vs. the positive predictive value (PPV) and the negative predictive value (NPV) of the biomarker. With a disease prevalence of 50%, the AUC and the AUPRC showed high correlations with the PPV and the NPV (ρ > 0.95). With a prevalence of 1%, small PPV and AUPRC values (0.9) were found. The AUPRC reflected better than the AUC the discriminant ability of the biomarker; it had a higher correlation with the PPV (ρ = 0.995 vs. 0.724; P < 0.001). In uncommon and rare diseases, the AUPRC should be preferred to the AUC because it summarizes better the performance of a biomarker. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Limited-sampling strategy models for estimating the pharmacokinetic parameters of 4-methylaminoantipyrine, an active metabolite of dipyrone

    Directory of Open Access Journals (Sweden)

    Suarez-Kurtz G.

    2001-01-01

    Full Text Available Bioanalytical data from a bioequivalence study were used to develop limited-sampling strategy (LSS models for estimating the area under the plasma concentration versus time curve (AUC and the peak plasma concentration (Cmax of 4-methylaminoantipyrine (MAA, an active metabolite of dipyrone. Twelve healthy adult male volunteers received single 600 mg oral doses of dipyrone in two formulations at a 7-day interval in a randomized, crossover protocol. Plasma concentrations of MAA (N = 336, measured by HPLC, were used to develop LSS models. Linear regression analysis and a "jack-knife" validation procedure revealed that the AUC0-¥ and the Cmax of MAA can be accurately predicted (R²>0.95, bias 0.85 of the AUC0-¥ or Cmax for the other formulation. LSS models based on three sampling points (1.5, 4 and 24 h, but using different coefficients for AUC0-¥ and Cmax, predicted the individual values of both parameters for the enrolled volunteers (R²>0.88, bias = -0.65 and -0.37%, precision = 4.3 and 7.4% as well as for plasma concentration data sets generated by simulation (R²>0.88, bias = -1.9 and 8.5%, precision = 5.2 and 8.7%. Bioequivalence assessment of the dipyrone formulations based on the 90% confidence interval of log-transformed AUC0-¥ and Cmax provided similar results when either the best-estimated or the LSS-derived metrics were used.

  13. Reproducibility of postprandial lipemia tests and validity of an abbreviated 4-hour test

    Science.gov (United States)

    Weiss, Edward P.; Fields, David A.; Mittendorfer, Bettina; Haverkort, M. A. Dorien; Klein, Samuel

    2008-01-01

    Postprandial lipemia test (PPLT) results are predictive of cardiovascular disease risk. However, their reproducibility must be established before they can be clinically useful. Therefore, we investigated PPLT reproducibility by testing nine men and women (BMI, 20–41 kg/m2; age=21–40y) on four separate occasions (n=36 PPLTs total) separated by 1 week. Furthermore, because PPLTs are time consuming, we assessed the validity of an abbreviated PPLT. During the PPLT, venous blood was obtained before and every hour for 8h after a high fat meal, which consisted of ice cream and heavy cream (~800 kcal, 71% fat calories). Total and triglyceride-rich lipoprotein (TRL) triglyceride concentrations were measured in plasma. Total area under the curve (AUC) for total triglycerides was highly reproducible [within-subject coefficient of variation (WCV): 8%; intraclass correlation coefficient (ICC): 0.82]; however, reproducibility was low for total triglyceride incremental AUC and both total and incremental TRL triglyceride AUCs (WCVs: 20–31%; ICCs: 0.28–0.54). Four-hour lipemic responses were highly predictive of 8-hr responses (R2: 0.89–0.96, p≤0.0001). In conclusion, PPLTs are highly reproducible when lipemic responses are determined as the total AUC for total triglycerides. However, large variability in incremental AUC and TRL triglyceride responses may preclude their clinical utility. Furthermore, abbreviated 4-hr PPLTs are a valid surrogate for longer tests and may make PPLTs more feasible in a clinical setting. PMID:18803956

  14. Prognosis prediction of non-enhancing T2 high signal intensity lesions in glioblastoma patients after standard treatment: application of dynamic contrast-enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Rihyeon; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho [Seoul National University Hospital, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Choi, Seung Hong [Seoul National University Hospital, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, 103 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University, Center for Nanoparticle Research, Institute for Basic Science (IBS), Daehak-dong, Gwanak-gu, Seoul (Korea, Republic of); Seoul National University, School of Chemical and Biological Engineering, Daehak-dong, Gwanak-gu, Seoul (Korea, Republic of); Lee, Soon-Tae [Seoul National University Hospital, Department of Neurology, Seoul (Korea, Republic of); Park, Chul-Kee [Seoul National University Hospital, Department of Neurosurgery, Seoul (Korea, Republic of); Kim, Tae Min [Seoul National University Hospital, Department of Internal Medicine, Seoul (Korea, Republic of); Park, Sun-Won [Seoul National University College of Medicine, Department of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Park, Sung-Hye [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Kim, Il Han [Seoul National University Hospital, Department of Radiation Oncology, Seoul (Korea, Republic of)

    2017-03-15

    To identify candidate imaging biomarkers for early disease progression in glioblastoma multiforme (GBM) patients by analysis of dynamic contrast-enhanced (DCE) MR parameters of non-enhancing T2 high signal intensity (SI) lesions. Forty-nine GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. According to the Response Assessment in Neuro-Oncology criteria, patients were classified into progression (n = 21) or non-progression (n = 28) groups. We analysed the pharmacokinetic parameters of Ktrans, Ve and Vp within non-enhancing T2 high SI lesions of each tumour. The best percentiles of each parameter from cumulative histograms were identified by the area under the receiver operating characteristic curve (AUC) and were compared using multivariate stepwise logistic regression. For the differentiation of early disease progression, the highest AUC values were found in the 99th percentile of Ktrans (AUC 0.954), the 97th percentile of Ve (AUC 0.815) and the 94th percentile of Vp (AUC 0.786) (all p < 0.05). The 99th percentile of Ktrans was the only significant independent variable from the multivariate stepwise logistic regression (p = 0.002). We found that the Ktrans of non-enhancing T2 high SI lesions in GBM patients holds potential as a candidate prognostic marker in future prospective studies. (orig.)

  15. Composition specification of teicoplanin based on its estimated relative bioavailability.

    Science.gov (United States)

    Boix-Montañes, Antonio; Garcia-Arieta, Alfredo

    2015-02-01

    Teicoplanin is a fermentative antibiotic consisting of several active components that contribute similarly to the antibacterial activity, but exhibit different pharmacokinetic properties. Differences in systemic exposure between batches of teicoplanin are possible within pharmacopeial specifications as the proportion of subcomponents may vary from batch to batch. The aim of this paper is to study the possible modification of the present pharmacopeial specification for teicoplanin composition to ensure an a priori pharmacokinetic equivalence between all pharmacopoeial-compliant batches. The expectable whole Area Under the Curve (AUC) of plasma levels of teicoplanin was predicted for different experimental batches and also for the theoretical extreme batches within pharmacopeial specifications. Calculations were done based on the AUC of each teicoplanin active subcomponent. Subsequently, the equivalence between a generic teicoplanin and a reference drug product was investigated by means of the ratio of AUCs. Batches under study, complying with current pharmacopoeial specifications, showed a maximum predicted difference in AUC slightly larger than 40%. The observed variability in teicoplanin compositions surpasses the conventional ±5% specification used for drugs obtained by chemical synthesis, but no 5% differences have been observed for any of the AUC means of the reference product when compared with the whole pooled data. Alternative specifications of actives composition can be defined to ensure that all batches complying with the pharmacopoeia are inside ±10% interval between them.

  16. Innate biology versus lifestyle behaviour in the aetiology of obesity and type 2 diabetes: the GLACIER Study.

    Science.gov (United States)

    Poveda, Alaitz; Koivula, Robert W; Ahmad, Shafqat; Barroso, Inês; Hallmans, Göran; Johansson, Ingegerd; Renström, Frida; Franks, Paul W

    2016-03-01

    We compared the ability of genetic (established type 2 diabetes, fasting glucose, 2 h glucose and obesity variants) and modifiable lifestyle (diet, physical activity, smoking, alcohol and education) risk factors to predict incident type 2 diabetes and obesity in a population-based prospective cohort of 3,444 Swedish adults studied sequentially at baseline and 10 years later. Multivariable logistic regression analyses were used to assess the predictive ability of genetic and lifestyle risk factors on incident obesity and type 2 diabetes by calculating the AUC. The predictive accuracy of lifestyle risk factors was similar to that yielded by genetic information for incident type 2 diabetes (AUC 75% and 74%, respectively) and obesity (AUC 68% and 73%, respectively) in models adjusted for age, age(2) and sex. The addition of genetic information to the lifestyle model significantly improved the prediction of type 2 diabetes (AUC 80%; p = 0.0003) and obesity (AUC 79%; p diabetes and 64% for obesity. These findings illustrate that lifestyle and genetic information separately provide a similarly high degree of long-range predictive accuracy for obesity and type 2 diabetes.

  17. Tumour tropism and anti-cancer efficacy of polymer-based doxorubicin prodrugs in the treatment of subcutaneous murine B16F10 melanoma.

    Science.gov (United States)

    Seymour, L. W.; Ulbrich, K.; Steyger, P. S.; Brereton, M.; Subr, V.; Strohalm, J.; Duncan, R.

    1994-01-01

    Doxorubicin (5 mg kg-1) was administered intravenously to C57 mice bearing subcutaneous B16F10 melanomas, distributing into the tumour with an area under the concentration-time curve (0-48 h; AUC) of 8.7 micrograms h g-1. Injection of doxorubicin-N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugate, containing 5 mg of doxorubicin equivalent per kg, mediated an AUC for free doxorubicin (i.e. doxorubicin released from the conjugate) of 15.2 micrograms h g-1 and for total doxorubicin (i.e. free plus conjugated) of 149.1 micrograms h g-1. An increased dose of doxorubicin-HPMA copolymer conjugate (18 mg of doxorubicin equivalent per kg) produced AUC values of 40.1 micrograms h g-1 and 671.7 micrograms h g-1 for free and total doxorubicin respectively. Hence administration of doxorubicin-HPMA copolymer conjugate achieved rises of 1.7- to 4.6-fold in tumour AUC (free doxorubicin) and 17.19 to 77.0-fold in tumour AUC (total doxorubicin). HPMA copolymers bearing fluorescein isothiocyanate accumulated in vascularised stromal regions, particularly in new growth sites at the tumour periphery. Treatment of mice with doxorubicin-HPMA copolymer conjugate achieved treated/control lifespans up to 320% (three doses of 27 mg of doxorubicin equivalent per kg) compared with only 133% using aggressive regimens of free doxorubicin (3 x 5 mg kg-1). Images Figure 4 PMID:7917909

  18. Correlation between leukocyte count and infarct size in ST segment elevation myocardial infarction.

    Science.gov (United States)

    Ferrari, Júlia Peixoto; Lueneberg, Maria Emília; da Silva, Roberto Leo; Fattah, Tammuz; Gottschall, Carlos Antônio Mascia; Moreira, Daniel Medeiros

    2016-01-01

    Regarding the inflammatory mechanisms involved in ischemic heart disease, currently the leukocyte count is the subject of studies related to its association with the prognosis and mortality of ST segment elevation myocardial infarction (STEMI). Our aim is correlate the leukocyte count rise with the size of STEMI, evaluated with the area under the curve (AUC) and the peak of necrosis markers release. This study is a sub-analysis of the TETHYS trial, a clinical trial that evaluated the effects of methotrexate in STEMI. We evaluated the correlation between quantitative variables with Pearson's correlation, and the variables that did not follow a normal distribution were subjected to logarithmic transformation to base 10. The value of p leukocyte count at hospital admission was significantly correlated with the AUC creatine kinase (CK) ( r = 0.256, p = 0.021), troponin AUC ( r = 0.247, p = 0.026), peak CK ( r = 0.270, p = 0.015) and troponin peak ( r = 0.233, p = 0.037). The leukocyte count at 72 h was significantly correlated with CK AUC ( r = 0.238, p = 0.032), AUC of MB portion of CK ( r = 0.240, p = 0.031) and peak CK ( r = 0.224, p = 0.045). White blood cell count correlates with STEMI size assessed by serial cardiac biomarker levels.

  19. Comparison between the story recall test and the word-list learning test in Korean patients with mild cognitive impairment and early stage of Alzheimer's disease.

    Science.gov (United States)

    Baek, Min Jae; Kim, Hyun Jung; Kim, Sangyun

    2012-01-01

    Among verbal memory tests, two that are commonly used to measure the ability of verbal memory function in cognitive impairment are story recall tests and word-list learning tests. However, research is limited regarding which test might be more sensitive in discriminating between normal cognitive aging and patients with Alzheimer's disease (AD) in the Korean population. The purpose of the current study was to compare the word-list learning test (Seoul Verbal Learning Test; SVLT) and the story recall test (Korean Story Recall Test; KSRT) to determine which test is more sensitive in discriminating between individuals with normal cognitive aging and patients with mild cognitive impairment (MCI) and early stage of AD in Korea. A total of 53 healthy adults, 127 patients with MCI, and 72 patients with early stage of AD participated in this study. The receiver-operating characteristic (ROC) curve and area under the curve (AUC) were evaluated to compare these two tests. The results showed that the AUC of the SVLT was significantly larger than the AUC of the KSRT in all three groups (healthy adults vs. MCI and early stage of AD; healthy adults vs. MCI; healthy adults vs. early stage of AD). However, in comparison of patients with MCI and early stage of AD, the AUC of SVLT and the AUC of KSRT were not significant. The word-list learning test is a more useful tool for examining verbal memory function for older adults in Korea than the story recall test.

  20. Variability in Estimated Glomerular Filtration Rate by Area under the Curve Predicts Renal Outcomes in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Szu-Chia Chen

    2014-01-01

    Full Text Available Greater variability in renal function is associated with mortality in patients with chronic kidney disease (CKD. However, few studies have demonstrated the predictive value of renal function variability in relation to renal outcomes. This study investigates the predictive ability of different methods of determining estimated glomerular filtration rate (eGFR variability for progression to renal replacement therapy (RRT in CKD patients. This was a prospective observational study, which enrolled 1,862 CKD patients. The renal end point was defined as commencement of RRT. The variability in eGFR was measured by the area under the eGFR curve (AUC%. A significant improvement in model prediction was based on the −2 log likelihood ratio statistic. During a median 28.7-month follow-up, there were 564 (30.3% patients receiving RRT. In an adjusted Cox model, a smaller initial eGFR AUC%_12M (P<0.001, a smaller peak eGFR AUC%_12M (P<0.001, and a larger negative eGFR slope_12M (P<0.001 were associated with a higher risk of renal end point. Two calculated formulas: initial eGFR AUC%_12M and eGFR slope_12M were the best predictors. Our results demonstrate that the greater eGFR variability by AUC% is associated with the higher risk of progression to RRT.

  1. Estimation of haplotype associated with several quantitative phenotypes based on maximization of area under a receiver operating characteristic (ROC) curve.

    Science.gov (United States)

    Kamitsuji, Shigeo; Kamatani, Naoyuki

    2006-01-01

    An algorithm for estimating haplotypes associated with several quantitative phenotypes is proposed. The concept of a receiver operating characteristic (ROC) curve was introduced, and a linear combination of the quantitative phenotypic values was considered. This set of values was divided into two parts: values for subjects with and without a particular haplotype. The goodness of its partition was evaluated by the area under the ROC curve (AUC). The AUC value varied from 0 to 1; this value was close to 1 when the partition had high accuracy. Therefore, the strength of association between phenotypes and haplotypes was considered to be proportional to the AUC value. In our algorithm, the parameters representing a degree of association between the haplotypes and phenotypes were estimated so as to maximize the AUC value; further, the haplotype with the maximum AUC value was considered to be the best haplotype associated with the phenotypes. This algorithm was implemented by using R language. The effectiveness of our algorithm was evaluated by applying it to real genotype data of the Calpine-10 gene obtained from diabetics. The results showed that our algorithm was more reasonable and advantageous for use with several quantitative phenotypes than the generalized linear model or the neural network model.

  2. Pharmacokinetic and Bioequivalence Studies of a Newly Developed Branded Generic of Candesartan Cilexetil Tablets in Healthy Volunteers.

    Science.gov (United States)

    Patel, Rajesh; Palmer, Jonathan L; Joshi, Shashidhar; Di Ció Gimena, Alejandro; Esquivel, Florencia

    2017-09-01

    Two bioavailability/bioequivalence studies were carried out to evaluate the pharmacokinetics of candesartan cilexetil 16-mg tablet formulations. A pilot study was used to optimize the formulation and manufacturing process prior to conducting the definitive study. The pilot study was a single-dose, randomized, 2-period crossover, and the definitive study was a single-dose, randomized, 3-period, 6-sequence crossover study in healthy adults. In the pilot study the test formulation was 24% and 18% greater for Cmax and AUC, respectively, compared with the innovator product. Following optimization two 16-mg candesartan cilexetil tablet formulations were taken forward into the second bioavailability study.  Eighteen healthy fasted adult subjects were dosed with either the test formulations or the innovator. The pharmacokinetic parameters Cmax , AUC0-t , and AUC0-∞ of candesartan were investigated together with safety and tolerability. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for candesartan, Cmax , AUC0-t , and AUC0-∞ were within the boundary of 0.8-1.25 for one of the test formulations (formulation 2). For test formulation 3 the 90%CI of GMR for Cmax was above (133%) the upper limit of 125% for bioequivalence. Test formulation 2 was found to be bioequivalent and met internationally acceptable regulatory requirements. © 2016, The American College of Clinical Pharmacology.

  3. How many studies are necessary to compare niche-based models for geographic distributions? Inductive reasoning may fail at the end.

    Science.gov (United States)

    Terribile, L C; Diniz-Filho, J A F; De Marco jr, P

    2010-05-01

    The use of ecological niche models (ENM) to generate potential geographic distributions of species has rapidly increased in ecology, conservation and evolutionary biology. Many methods are available and the most used are Maximum Entropy Method (MAXENT) and the Genetic Algorithm for Rule Set Production (GARP). Recent studies have shown that MAXENT perform better than GARP. Here we used the statistics methods of ROC - AUC (area under the Receiver Operating Characteristics curve) and bootstrap to evaluate the performance of GARP and MAXENT in generate potential distribution models for 39 species of New World coral snakes. We found that values of AUC for GARP ranged from 0.923 to 0.999, whereas those for MAXENT ranged from 0.877 to 0.999. On the whole, the differences in AUC were very small, but for 10 species GARP outperformed MAXENT. Means and standard deviations for 100 bootstrapped samples with sample sizes ranging from 3 to 30 species did not show any trends towards deviations from a zero difference in AUC values of GARP minus AUC values of MAXENT. Ours results suggest that further studies are still necessary to establish under which circumstances the statistical performance of the methods vary. However, it is also important to consider the possibility that this empirical inductive reasoning may fail in the end, because we almost certainly could not establish all potential scenarios generating variation in the relative performance of models.

  4. Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging

    DEFF Research Database (Denmark)

    Falk, Anna; Fahlström, Markus; Rostrup, Egill

    2014-01-01

    grade II and grade III gliomas in histogram perfusion parameters was performed, and the areas under the curves (AUC) from the ROC analyses were evaluated. RESULTS: In DCE, the skewness of transfer constant (k(trans)) was found superior for differentiating grade II from grade III in all gliomas (AUC 0.......76). In DSC, the standard deviation of relative cerebral blood flow (rCBF) was found superior for differentiating grade II from grade III gliomas (AUC 0.80). CONCLUSIONS: Histogram parameters from k(trans) (DCE) and rCBF (DSC) could most efficiently discriminate between grade II and grade III gliomas....... that could best discriminate between grade II and III gliomas. METHODS: MRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after...

  5. Short Term Survival after Admission for Heart Failure in Sweden

    DEFF Research Database (Denmark)

    Ghith, Nermin; Wagner, Philippe; Frølich, Anne

    2016-01-01

    . METHODS: We analyzed 36,943 patients aged 45-80 treated in 565 wards at 71 hospitals during 2007-2009. We applied single and multilevel logistic regression analyses to calculate the odds ratios and the area under the receiver-operating characteristic (AUC). We evaluated general hospital and ward effects...... by quantifying the intra-class correlation coefficient (ICC) and the increment in the AUC obtained by adding random effects in a multilevel regression analysis (MLRA). Finally, the Odds Ratios (ORs) for specific ward and hospital characteristics were interpreted jointly with the proportional change in variance...... (PCV) and the proportion of ORs in the opposite direction (POOR). FINDINGS: Overall, the average 30-day mortality was 9%. Using only patient information on age and previous hospitalizations for different diseases we obtained an AUC = 0.727. This value was almost unchanged when adding sex, country...

  6. Activated carbon from sugarcane bagasse ash for melanoidins recovery.

    Science.gov (United States)

    Kaushik, A; Basu, S; Singh, K; Batra, V S; Balakrishnan, M

    2017-09-15

    This work investigates the value added utilization of two sugar-distillery wastes: (i) melanoidins, which are complex Maillard reaction products in molasses distillery wastewater, and (ii) unburnt carbon in sugarcane bagasse ash. Activated unburnt carbon (AUC), prepared by deashing and steam activation, had properties comparable to commercial activated carbon (CAC). Both carbons are suitable for melanoidins adsorption followed by desorption using 25% pyridine solution. For AUC, the equilibrium adsorption data is well described by Langmuir isotherm up to 35 °C while Freundlich model fits better at higher temperature. Adsorption using CAC followed Freundlich isotherm at all temperatures. Both carbons followed pseudo second order kinetics and displayed endothermic physisorption. Recovery of melanoidins from AUC (78%) was close to that observed with CAC (80%). Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Human puberty: salivary melatonin profiles in constant conditions.

    Science.gov (United States)

    Crowley, Stephanie J; Acebo, Christine; Carskadon, Mary A

    2012-05-01

    This analysis examined the relative contributions of sex, age, body mass index (BMI), and puberty (Tanner) stage on salivary melatonin amplitude. Sixty-nine children and adolescents (30 females; 9.6-17.8 years) were examined for Tanner stage. Serial salivary melatonin samples were collected in controlled conditions, from which these melatonin amplitude measures were derived: area under the curve (AUC) and maximum value (MAX). AUC declined with advancing Tanner stage. This melatonin decline was similar between boys and girls, but girls secreted more melatonin compared to boys. Tanner stage and sex explained AUC variability, but age and BMI did not; similar results emerged for MAX. These results indicate that puberty stage may either mediate the decline of melatonin, or the decrease in melatonin amplitude may be an indicator of pubertal progression. These findings also indicate that the melatonin decline during puberty is not entirely accounted for by body mass or by age. Copyright © 2011 Wiley Periodicals, Inc.

  8. [Omeprazol and ezomeprazol pharmacokinetics, duration of antisecretory effect, and reasons for their probable changes in duodenal ulcer].

    Science.gov (United States)

    Serebrova, S Iu; Starodubtsev, A K; Pisarev, V V; Kondratenko, S N; Vasilenko, G F; Dobrovol'skiĭ, O V

    2009-01-01

    There were authentic distinctions between the groups of healthy volunteers and patients with a peptic ulcer disease in Cmax, Tmax, AUC(0-t), AUC(0-infinity), CIt, Vd of omeprazole and Cmax of esomeprazole (Nexium, AstraZeneca). When the pharmacokinetics of omeprazole and ezomeprazole were compared in both groups, there were authentic distinctions in Cmax, AU(0-t), AUC(0-infinity), CIt, T1/2. The patients who had taken omeprazole the time of hypoacide condition was much shorter than in other groups. Disintegration test modeling pHmax for pH oscillation with large amplitude, that is typical for ulcer disease, demonstrated a possibility of early partial release of omeprazole, its acid-depended degradation and reduction of its bioavailability.

  9. The diagnostic value of three sacroiliac joint pain provocation tests for sacroiliitis identified by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Arnbak, B; Jurik, A G; Jensen, R K

    2017-01-01

    was 33 (range 18-40) years and 241 (53%) were women. The prevalence of SI joints with sacroiliitis was 5%. In the whole study group, only the thigh trust test was associated with sacroiliitis, the area under the receiver operating characteristic (ROC) curve (AUC) was 0.58 [95% confidence interval (CI) 0......OBJECTIVES: The aim of the current study was to investigate the diagnostic value of three sacroiliac (SI) joint pain provocation tests for sacroiliitis identified by magnetic resonance imaging (MRI) and stratified by gender. METHOD: Patients without clinical signs of nerve root compression were.......51-0.65], sensitivity 31% (95% CI 18-47), and specificity 85% (95% CI 82-87). In men, sacroiliitis was associated with all the SI joint tests assessed and multi-test regimens, with the greatest AUC found for at least one positive out of three tests [AUC 0.68 (95% CI 0.56-0.80), sensitivity 56% (95% CI 31...

  10. Cyclosporine A monitoring in children: abbreviated area under curve formulas and C2 level.

    Science.gov (United States)

    Dello Strologo, L; Campagnano, P; Federici, G; Rizzoni, G

    1999-02-01

    Cyclosporine A (CsA) is the most commonly used drug in organ transplantation. To evaluate exposure the gold standard is area under curve (AUC), but this is expensive and requires many blood samples. For this reason, abbreviated formulae have been developed in adults. Data in children are scanty. Formulae cannot be applied in patients taking CsA every 8 h. We tested the abbreviated AUC formula published for adults in renal transplant children on twice daily therapy and we propose a method, requiring three blood samples, for those taking CsA every 8 h. A very good correlation was obtained for both groups. Furthermore, we studied the correlation between CsA concentration 2 h after administration and AUC. A good correlation was found supporting the possible use of this parameter for monitoring CsA therapy.

  11. Analytical ultracentrifugation of polymers and nanoparticles

    CERN Document Server

    Maechtle, Walter

    2014-01-01

    Analytical ultracentrifugation (AUC) is a powerful method for the characterization of polymers, biopolymers, polyelectrolytes, nanoparticles, dispersions, and other colloidal systems. The method is able to determine the molar mass, the particle size, the particle density and interaction parameters like virial coefficients and association constants. Because AUC is also a fractionation method, the determination of the molar mass distribution, the particle size distribution, and the particle density distribution is possible. A special technique, the density gradient method, allows fractionating heterogeneous samples according to their chemical nature that means being able to detect chemical heterogeneity. The book is divided into chapters concerning instrumentation, sedimentation velocity runs, density gradient runs, application examples and future developments. In particular, the detailed application chapter demonstrates the versatility and power of AUC by means of many interesting and important industrial exam...

  12. Coronary artery calcium score and N-terminal pro-B-type natriuretic peptide as potential gatekeepers for myocardial perfusion imaging

    DEFF Research Database (Denmark)

    Haarmark, Christian; Andersen, Kim Francis; Madsen, Claus

    2017-01-01

    -proBNP as potential gatekeepers for MPI. Patients with intermediate risk of CHD referred for standard MPI were included. CAC score and NT-proBNP were both assessed at the day of the stress study. Sensitivity, specificity and NPV for prediction of abnormal MPI scans were calculated for CAC, NT......-proBNP and the combination hereof. A total of 190 patients were included (mean age 61 ± 12 years, 55% female) of whom 24% had known CHD. In all 30% of the scans were abnormal. CAC score achieved the highest AUC regardless of whether patients with known CHD were included or not [AUC 0·75 95% CI (0·66-0·84) and AUC 0·79 (0...

  13. Bioequivalence evaluation of epinephrine autoinjectors with attention to rapid delivery.

    Science.gov (United States)

    Sclar, David Alexander

    2013-01-01

    Timely and proper injection of epinephrine is critical to prevent serious consequences relating to anaphylaxis. In a recent bioavailability study comparing epinephrine delivery from the Auvi-Q™ and EpiPen(®) epinephrine autoinjectors, the Auvi-Q failed to meet the bioequivalence threshold when using partial area under the curve (AUC) analyses based on zero to Tmax recommended for highly variable drugs such as epinephrine. Peak plasma epinephrine concentrations for the EpiPen occurred 10 minutes (median Tmax) after dosing, while peak concentrations for the Auvi-Q occurred 20 minutes after dosing. Though bioequivalence may be concluded for Cmax, AUCinf, and AUC0-t, for fast-acting therapeutics used to treat life-threatening conditions, such as epinephrine, additional pharmacokinetic parameters such as AUC zero to Tmax may be important to evaluate when assessing bioequivalence.

  14. Validation of the fatigue scale for motor and cognitive functions in a danish multiple sclerosis cohort

    DEFF Research Database (Denmark)

    Oervik, M. S.; Sejbaek, T.; Penner, I. K.

    2017-01-01

    . The area under the curve (AUC) for the ROC curves represented excellent accuracy (Danish MS cohort, AUC = 0.9190; German MS cohort, AUC = 0.9034). Conclusion The Danish translation of the FSMC has a high convergent validity with another measure of fatigue as well as excellent internal consistency......Background Our objective was to validate the Danish translation of the Fatigue Scale for Motor and Cognitive Functions (FSMC) in multiple sclerosis (MS) patients. Materials and methods A Danish MS cohort (n = 84) was matched and compared to the original German validation cohort (n = 309......) and a healthy control cohort (n = 147). The Modified Fatigue Impact Scale (MFIS) was used as reference scale and Becks Depression Inventory-Fast Screen (BDI-FS) and Expanded Disability Status Scale (EDSS) for confounding factors. We assessed internal consistencies; convergent, divergent, and predictive validity...

  15. Early warning of diarrhea and pen fouling in growing pigs using sensor-based monitoring

    DEFF Research Database (Denmark)

    Jensen, D. B.; Toft, N.; Kristensen, A. R.

    as the area under the receiver operating characteristics curve (AUC). Results: We achieved an AUC of 0.83 when all variables were included. Omitting live weight and humidity had no effect. Omitting drinking behavior, temperature, and feed usage reduced the AUC to 0.70, 0.81, and 0.82 respectively. Conclusion...... then identify specific pens in need of extra attention. Here we evaluate the value of monitoring live weight, feed usage, humidity, drinking behavior and pen temperature in relation to early warnings of diarrhea and pen fouling in slaughter pigs. Materials and methods: We used data collected in 16 pens (8...... double-pens) between November 2013 and December 2014 at a commercial Danish farm. During this time, three new batches were inserted. We monitored the mean live weight of the pigs per pen (weekly, only in 4 pens), feed usage per double-pen (daily), humidity per section (daily), temperature at two...

  16. International multicenter tool to predict the risk of nonsentinel node metastases in breast cancer

    DEFF Research Database (Denmark)

    Meretoja, Tuomo J; Leidenius, Marjut H K; Heikkilä, Päivi S

    2012-01-01

    predicting nonsentinel node involvement were identified in logistic regression analysis. A multivariable predictive model was developed and validated by area under the receiver operating characteristics curve (AUC), first internally in 500 additional patients and then externally in 1068 patients from other...... centers. All statistical tests were two-sided. Results Nine tumor- and sentinel node-specific variables were identified as statistically significant factors predicting nonsentinel node involvement in logistic regression analysis. A resulting predictive model applied to the internal validation series...... resulted in an AUC of 0.714 (95% confidence interval [CI] = 0.665 to 0.763). For the external validation series, the AUC was 0.719 (95% CI = 0.689 to 0.750). The model was well calibrated in the external validation series. Conclusions We present a novel, international, multicenter, predictive tool...

  17. Pharmacokinetic interaction between ϵ-acetamidocaproic acid (AACA) and cimetidine in indomethacin-induced acute gastric ulcer and control rats: inhibition of active renal secretion of AACA by cimetidine.

    Science.gov (United States)

    Choi, Y H; Lee, U; Suh, J H; Kim, Y G; Lee, M; Oh, E; Lee, M G

    2011-05-01

    After both the intravenous and oral administration of zinc acexamate [ZAC; ion-pairing between zinc and ϵ-acetamidocaproic acid (AACA)] and cimetidine together, the areas under the curve (AUCs) of AACA were significantly greater [by 28.2 and 98.9% after the intravenous and oral administration, respectively, for control rats and 13.5 and 16.9% for indomethacin-induced acute gastric ulcer (IAGU) rats, respectively] than those of ZAC alone due to the significantly slower renal clearance (CL(R)). The significantly greater AUCs of AACA after both the intravenous and oral administration of ZAC and cimetidine together in control and IAGU rats could have been due to the inhibition of active renal tubular secretion of AACA by cimetidine. After the intravenous and oral administration of both drugs together, the AUCs of cimetidine in control and IAGU rats were not different compared with those with cimetidine alone.

  18. Pharmacokinetic Comparison of Inhaled Fixed Combination vs. the Free Combination of Beclomethasone and Formoterol pMDIs in Asthmatic Children

    DEFF Research Database (Denmark)

    Chawes, Bl; Piccinno, A; Kreiner-Møller, Eskil

    2012-01-01

    17MP (active metabolite of BDP) and Formoterol after single inhalation of Foster® pMDI 50/6μg vs. the free combination of BDP and Formoterol pMDIs in asthmatic children. METHODS: 5-11-year-old children inhaled BDP 200μg and Formoterol 24μg as fixed vs. free combination in an open label, randomized, 2......-way crossover single dose study. Blood was collected pre-dose up to 8h post-dose for pharmacokinetic evaluation (AUC(0-t) , AUC(0-∞) , AUC(0-0.5h) , C(max) , t(max) , t(1/2) ). Pharmacodynamics included heart rate, plasma potassium, urinary glucose and cortisol excretion. Peak expiratory flow......-superior after administration of the two actives as fixed vs. the free combination in 5-11-year-old asthmatic children....

  19. Latent information in fluency lists predicts functional decline in persons at risk for Alzheimer disease.

    Science.gov (United States)

    Clark, D G; Kapur, P; Geldmacher, D S; Brockington, J C; Harrell, L; DeRamus, T P; Blanton, P D; Lokken, K; Nicholas, A P; Marson, D C

    2014-06-01

    We constructed random forest classifiers employing either the traditional method of scoring semantic fluency word lists or new methods. These classifiers were then compared in terms of their ability to diagnose Alzheimer disease (AD) or to prognosticate among individuals along the continuum from cognitively normal (CN) through mild cognitive impairment (MCI) to AD. Semantic fluency lists from 44 cognitively normal elderly individuals, 80 MCI patients, and 41 AD patients were transcribed into electronic text files and scored by four methods: traditional raw scores, clustering and switching scores, "generalized" versions of clustering and switching, and a method based on independent components analysis (ICA). Random forest classifiers based on raw scores were compared to "augmented" classifiers that incorporated newer scoring methods. Outcome variables included AD diagnosis at baseline, MCI conversion, increase in Clinical Dementia Rating-Sum of Boxes (CDR-SOB) score, or decrease in Financial Capacity Instrument (FCI) score. Receiver operating characteristic (ROC) curves were constructed for each classifier and the area under the curve (AUC) was calculated. We compared AUC between raw and augmented classifiers using Delong's test and assessed validity and reliability of the augmented classifier. Augmented classifiers outperformed classifiers based on raw scores for the outcome measures AD diagnosis (AUC .97 vs. .95), MCI conversion (AUC .91 vs. .77), CDR-SOB increase (AUC .90 vs. .79), and FCI decrease (AUC .89 vs. .72). Measures of validity and stability over time support the use of the method. Latent information in semantic fluency word lists is useful for predicting cognitive and functional decline among elderly individuals at increased risk for developing AD. Modern machine learning methods may incorporate latent information to enhance the diagnostic value of semantic fluency raw scores. These methods could yield information valuable for patient care and clinical

  20. Comparative bioavailability of two oral formulations of levofloxacin in healthy Mexican volunteers.

    Science.gov (United States)

    M; Flores-Murrieta, F J

    2009-04-01

    To assess the bioequivalence of two levofloxacin 500 mg tablets marketed in Mexico. The clinical investigation was designed as a randomized, open-labeled, two-part, two-treatment, two-period crossover study, in 27 healthy male volunteers. 1 tablet of each formulation was administered with 200 ml of water after 10 h overnight fast. After dosing, serial blood samples were collected for a period of 24 h. Plasma concentrations were determined by a validated high-performance liquid chromatographic method and pharmacokinetic parameters were obtained by non-compartmental approach. Analysis of variance (ANOVA) was carried out using log-transformed AUClast, AUC yen and Cmax and untransformed tmax, and 90% confidence intervals for AUClast, AUC yen and Cmax were calculated. If the 90% confidence intervals (CI) for AUClast, AUC yen and Cmax fell fully within the interval 80 - 125%, the bioequivalence of the two formulations was established. The means (test and reference) for AUClast were 58.869 and 56.297 microg x h/ml, for AUC yen were 63.456 and 60.748 microg x h/ml and for Cmax were 8.691 and 8.445 microg/ml. The geometric mean ratios of the test formulation to reference formulation for AUClast, AUC yen and Cmax (CI) were 104.53% (102.73 - 106.36%), 104.37% (102.04 - 106.75%) and 103.45% (95.57 - 111.97%), respectively. All 90% CI for AUClast, AUC yen and Cmax fell within the Mexican Federal Commission for Prevention of Sanitary Risks (COFEPRIS) accepted bioequivalence range of 80 - 125%. Based on the results, the formulations tested are bioequivalent.

  1. Leptin and adiponectin during the first week after kidney transplantation: biomarkers of graft dysfunction?

    Science.gov (United States)

    Fonseca, Isabel; Oliveira, José Carlos; Santos, Josefina; Malheiro, Jorge; Martins, La Salete; Almeida, Manuela; Dias, Leonídio; Pedroso, Sofia; Lobato, Luísa; Henriques, António Castro; Mendonça, Denisa

    2015-02-01

    Based on evidence that leptin and adiponectin are removed from circulation primarily by the kidney, we designed a study to examine the longitudinal changes of these adipokines during the first week after kidney transplantation (KTx) and to test the hypothesis that higher levels of leptin and/or adiponectin could be early biomarkers of delayed graft function (DGF=dialysis requirement during the first post-transplant week) and acute rejection. Repeated-measures prospective study. Forty consecutive adult patients with end-stage renal disease who were undergoing KTx. Leptin and adiponectin were measured in blood samples that were collected before (day-0) and after KTx (days-1, 2, 4 and 7). Linear mixed-models, receiver operating characteristic and area under curve (AUC-ROC) were used. At post-transplant day-1, leptinemia and adiponectinemia declined 43% and 47%, respectively. At all times studied after KTx, the median leptin levels were significantly higher in patients developing DGF (n=18), but not adiponectin levels. Shortly after KTx (day-1), leptin values were significantly higher in DGF recipients in contrast to patients with promptly functioning kidneys, approximately two times higher when controlling for gender and BMI. The leptin reduction rate between pre-tranplant and one-day after KTx moderately predicted DGF (AUC=0.73). On day-1, serum leptin predicted DGF (AUC-ROC=0.76) with a performance slightly better than serum creatinine (AUC-ROC=0.72), even after correcting for BMI (AUC-ROC=0.73). Separating this analysis by gender showed that the performance of leptin in predicting DGF for male gender (AUC-ROC=0.86) improved. Kidney graft function is an independent determinant of leptin levels, but not of adiponectin. Leptin levels at day-1 slightly outperformed serum creatinine in predicting the occurrence of DGF, and more accurately in male gender. No significant association was detected with acute rejection. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Prognostic factors in adults with knee pain in general practice.

    Science.gov (United States)

    Belo, J N; Berger, M Y; Koes, B W; Bierma-Zeinstra, S M A

    2009-02-15

    To predict the 1-year outcome of incident nontraumatic knee symptoms in adults presenting in general practice. Adults age >35 years with nontraumatic knee symptoms (n = 480) were followed for 1 year. At baseline, data on knee symptoms and demographics were collected and a physical examination performed. Knee symptoms were assessed by self-report questionnaires at 3-month intervals. After 1 year the physical examination was repeated. Multivariate prognostic regression models of patient characteristics, symptom characteristics, and physical examination were used to predict persisting knee symptoms after 1 year. Areas under receiving operating characteristic curves (AUCs) were used to determine the predictive value of the model. To assess the added predictive value of symptom characteristics and physical examination, these models were added to the model of patient characteristics. The improvement was expressed as the difference between the 2 AUCs. In the multivariate prognostic model of patient characteristics, age >60 years, educational level, kinesophobia, and comorbidity of the skeletal system were associated with persistent knee symptoms after 1 year (AUC 0.67). Of the symptom characteristics, history of nontraumatic knee symptoms, bilateral symptoms, and duration of symptoms >3 months were associated (AUC 0.73). For determinants of physical examination, crepitus of passive extension was associated (AUC 0.55). The added value of the symptom characteristics model to the patient characteristics model was 0.09 (AUC 0.76). Physical examination added no further value. Symptom characteristics are the strongest predictors of persisting knee symptoms at 1-year followup. Physical examination has no added value in predicting persistent knee symptoms in general practice.

  3. CYP2B6 genotype-directed dosing is required for optimal efavirenz exposure in children 3-36 months with HIV infection.

    Science.gov (United States)

    Bolton Moore, Carolyn; Capparelli, Edmund V; Samson, Pearl; Bwakura-Dangarembizi, Mutsa; Jean-Philippe, Patrick; Worrell, Carol; Heckman, Barbara; Purdue, Lynette; Spector, Stephen A; Benns, Alex; Borkowsky, William; Loftis, Amy; Hawkins, Elizabeth; Wallis, Carole; Chadwick, Ellen G

    2017-05-15

    To determine safety-specific, efficacy-specific and genotypic-specific dose requirements of efavirenz (EFV) in children aged 3 to less than 36 months with HIV infection. IMPAACT P1070 was a 24-week prospective cohort trial of EFV (as open capsules) and two nucleoside reverse transcriptase inhibitors in children with HIV infection 3 to less than 36 months without tuberculosis (Cohort 1). CYP2B6 G516T genotype was determined, and intensive pharmacokinetics was performed at week 2. EFV dose was adjusted if outside the target area under the curve (AUC) 35-180 μg*h/ml. Pharmacokinetic and CYP2B6 G516T genotype data were used to model EFV exposures based on Food and Drug Administration (FDA)-approved doses. Forty-seven participants, median age 19 months, initiated the study regimen with 24 weeks median follow-up; 38 516GG/GT and 9 516TT genotypes. Initially, median EFV AUC was higher in 516TT vs. 516GG/GT (median 490 vs. 107 μg*h/ml; P = 0.0001) with all 516TT above AUC target. Following an amendment that reduced the 516TT EFV dose by 75%, pharmacokinetic modeling predicted that 83% of participants met the AUC target (31/38 516GG/GT, 8/9 516TT). In contrast, modeling using P1070 data predicted that FDA-approved doses would produce subtherapeutic AUCs in almost one-third of participants with 516GG/GT and excessive AUCs in more than 50% with 516TT genotypes. CYP2B6 G516T genotype strongly influences EFV exposures in this age group. Genotype-directed dosing yields therapeutic EFV concentrations and appears to outperform other dosing approaches.

  4. Effects of Cytochrome P450 3A4 Inhibitors-Ketoconazole and Erythromycin-on Bitopertin Pharmacokinetics and Comparison with Physiologically Based Modelling Predictions.

    Science.gov (United States)

    Boetsch, Christophe; Parrott, Neil; Fowler, Stephen; Poirier, Agnes; Hainzl, Dominik; Banken, Ludger; Martin-Facklam, Meret; Hofmann, Carsten

    2016-02-01

    To assess the effect of strong and moderate cytochrome P450 (CYP) 3A4 inhibition on exposure of bitopertin, a glycine reuptake inhibitor primarily metabolized by CYP3A4, and to compare the results with predictions based on physiologically based pharmacokinetic (PBPK) modelling. The effects of ketoconazole and erythromycin were assessed in two male volunteer studies with open-label, two-period, fixed-sequence designs. Twelve subjects were enrolled in each of the studies. In period 1, a single dose of bitopertin was administered; in period 2, 400 mg ketoconazole was administered once daily for 17 days or 500 mg erythromycin was administered twice daily for 21 days. A single dose of bitopertin was coadministered on day 5. Pharmacokinetic parameters were derived by non-compartmental methods. Simulated bitopertin profiles using dynamic PBPK modelling for a typical healthy volunteer in GastroPlus(®) were used to predict changes in pharmacokinetic parameters. In healthy volunteers, coadministration of ketoconazole increased the bitopertin area under the plasma concentration-time curve (AUC) from 0 to 312 h (AUC0-312h) 4.2-fold (90 % confidence interval [CI] 3.5-5.0) and erythromycin increased the AUC from time zero to infinity (AUC0-inf) 2.1-fold (90 % CI 1.9-2.3). The peak concentration (C max) increased by erythromycin were 7.7 and 1.9, respectively. Strong CYP3A4 inhibitors increase AUC0-inf of bitopertin 7- to 8-fold and hence should not be administered concomitantly with bitopertin. Moderate CYP3A4 inhibitors double AUC0-inf.

  5. Modelling the habitat suitability of cetaceans: Example of the sperm whale in the northwestern Mediterranean Sea

    Science.gov (United States)

    Praca, Emilie; Gannier, Alexandre; Das, Krishna; Laran, Sophie

    2009-04-01

    Cetaceans are mobile and spend long periods underwater. Because of this, modelling their habitat could be subject to a serious problem of false absence. Furthermore, extensive surveys at sea are time and money consuming, and presence-absence data are difficult to apply. This study compares the ability of two presence-absence and two presence-only habitat modelling methods and uses the example of the sperm whale ( Physeter macrocephalus) in the northwestern Mediterranean Sea. The data consist of summer visual and acoustical detections of sperm whales, compiled between 1998 and 2005. Habitat maps were computed using topographical and hydrological eco-geographical variables. Four methods were compared: principal component analysis (PCA), ecological niche factor analysis (ENFA), generalized linear model (GLM) and multivariate adaptive regression splines (MARS). The evaluation of the models was achieved by calculating the receiver operating characteristic (ROC) of the models and their respective area under the curve (AUC). Presence-absence methods (GLM, AUC=0.70, and MARS, AUC=0.79) presented better AUC than presence-only methods (PCA, AUC=0.58, and ENFA, AUC=0.66), but this difference was not statistically significant, except between the MARS and the PCA models. The four models showed an influence of both topographical and hydrological factors, but the resulting habitat suitability maps differed. The core habitat on the continental slope was well highlighted by the four models, while GLM and MARS maps also showed a suitable habitat in the offshore waters. Presence-absence methods are therefore recommended for modelling the habitat suitability of cetaceans, as they seem more accurate to highlight complex habitat. However, the use of presence-only techniques, in particular ENFA, could be very useful for a first model of the habitat range or when important surveys at sea are not possible.

  6. Accuracy of the Audio Computer Assisted Self Interview version of the Alcohol, Smoking and Substance Involvement Screening Test (ACASI ASSIST) for identifying unhealthy substance use and substance use disorders in primary care patients.

    Science.gov (United States)

    Kumar, Pritika C; Cleland, Charles M; Gourevitch, Marc N; Rotrosen, John; Strauss, Shiela; Russell, Linnea; McNeely, Jennifer

    2016-08-01

    An Audio Computer-assisted Self Interview (ACASI) version of the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) could reduce barriers to substance use screening and assessment in primary care settings. This study evaluated the diagnostic accuracy of an ACASI ASSIST for identification of unhealthy substance use and substance use disorders (SUD). 399 adult patients were consecutively recruited from an urban safety-net primary care clinic. ACASI ASSIST scores for tobacco, alcohol, marijuana, and cocaine were compared against reference standard measures to assess the instrument's diagnostic accuracy for identifying unhealthy use and SUD, first using empirically-derived optimal cutoffs, and second using the currently recommended ASSIST cutoffs. For identifying any unhealthy use, at the empirically-derived cutoffs the ACASI ASSIST had 93.6% sensitivity and 85.8% specificity (AUC=0.90) for tobacco, 85.9% sensitivity and 60.3% specificity (AUC=0.73), for alcohol in men, 100% sensitivity and 62.4% specificity (AUC=0.81) for alcohol in women, 94.6% sensitivity and 81.6% specificity (AUC=0.88) for marijuana, and 86.1% sensitivity, 84.0% specificity (AUC=0.85) for cocaine. For SUD, sensitivity ranged from 79% (for alcohol in males), to 100% (for tobacco), and specificity was 83% or higher (AUCs ranged 0.83-0.91). For substances other than tobacco, empirically-derived cutoff scores were lower than the standard cutoffs, and resulted in higher sensitivity and lower specificity for identifying unhealthy substance use. The ACASI ASSIST is a valid measure of unhealthy use and SUD for substances that are commonly used by primary care patients, and could facilitate effective and efficient screening for substance use in medical settings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Dynamic contrast-enhanced case-control analysis in 3T MRI of prostate cancer can help to characterize tumor aggressiveness.

    Science.gov (United States)

    Sanz-Requena, Roberto; Martí-Bonmatí, Luis; Pérez-Martínez, Rosario; García-Martí, Gracián

    2016-11-01

    The aim of this work is to establish normality and tumor tissue ranges for perfusion parameters from dynamic contrast-enhanced (DCE) MR of the peripheral prostate at 3T and to compare the diagnostic performance of quantitative and semi-quantitative parameters. Thirty-six patients with prostate carcinomas (18 Gleason-6, 15 Gleason-7, and 3 Gleason-8) and 33 healthy subjects were included. Image analysis workflow comprised four steps: manual segmentation of whole prostate and lesions, series registration, voxelwise T1 mapping and calculation of pharmacokinetic and semi-quantitative parameters. K(trans), ve, upslope and AUC60 showed statistically significant differences between healthy peripheral areas and tumors. Curve type showed no association with healthy/tumor peripheral areas (chi-square=0.702). Areas under the ROC curves were 0.64 (95% CI: 0.54-0.75), 0.70 (0.60-0.80), 0.62 (0.51-0.72) and 0.63 (0.52-0.74) for K(trans), ve, upslope and AUC60, respectively. The optimal cutoff values were: K(trans)=0.21min(-1) (sensitivity=0.61, specificity=0.64), ve=0.36 (0.63, 0.71), upslope=0.59 (0.59, 0.59) and AUC60=2.4 (0.63, 0.64). Significant differences were found between Gleason scores 6 and 7 for normalized K(trans), upslope and AUC60, with good diagnostic accuracy (area under ROC curve 0.80, 95% CI: 0.60-1.00). Quantitative (K(trans) and ve) and semi-quantitative (upslope and AUC60) perfusion parameters showed significant differences between tumors and control areas in the peripheral prostate. Normalized K(trans), upslope and AUC60 values might characterize tumor aggressiveness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration.

    Science.gov (United States)

    Davit, Barbara M; Nwakama, Patrick E; Buehler, Gary J; Conner, Dale P; Haidar, Sam H; Patel, Devvrat T; Yang, Yongsheng; Yu, Lawrence X; Woodcock, Janet

    2009-10-01

    In the US, manufacturers seeking approval to market a generic drug product must submit data demonstrating that the generic formulation provides the same rate and extent of absorption as (ie, is bioequivalent to) the innovator drug product. Thus, most orally administered generic drug products in the US are approved based on results of one or more clinical bioequivalence studies. To evaluate how well the bioequivalence measures of generic drugs approved in the US over a 12-year period compare with those of their corresponding innovator counterparts. This retrospective analysis compared the generic and innovator bioequivalence measures from 2070 single-dose clinical bioequivalence studies of orally administered generic drug products approved by the Food and Drug Administration (FDA) from 1996 to 2007 (12 y). Bioequivalence measures evaluated were drug peak plasma concentration (C(max)) and area under the plasma drug concentration versus time curve (AUC), representing drug rate and extent of absorption, respectively. The generic/innovator C(max) and AUC geometric mean ratios (GMRs) were determined from each of the bioequivalence studies, which used from 12 to 170 subjects. The GMRs from the 2070 studies were averaged. In addition, the distribution of differences between generic means and innovator means was determined for both C(max) and AUC. The mean +/- SD of the GMRs from the 2070 studies was 1.00 +/- 0.06 for C(max) and 1.00 +/- 0.04 for AUC. The average difference in C(max) and AUC between generic and innovator products was 4.35% and 3.56%, respectively. In addition, in nearly 98% of the bioequivalence studies conducted during this period, the generic product AUC differed from that of the innovator product by less than 10%. The criteria used to evaluate generic drug bioequivalence studies support the FDA's objective of approving generic drug formulations that are therapeutically equivalent to their innovator counterparts.

  9. Patients with Acute Myeloid Leukemia Admitted to Intensive Care Units: Outcome Analysis and Risk Prediction.

    Directory of Open Access Journals (Sweden)

    Michele Pohlen

    Full Text Available This retrospective, multicenter study aimed to reveal risk predictors for mortality in the intensive care unit (ICU as well as survival after ICU discharge in patients with acute myeloid leukemia (AML requiring treatment in the ICU.Multivariate analysis of data for 187 adults with AML treated in the ICU in one institution revealed the following as independent prognostic factors for death in the ICU: arterial oxygen partial pressure below 72 mmHg, active AML and systemic inflammatory response syndrome upon ICU admission, and need for hemodialysis and mechanical ventilation in the ICU. Based on these variables, we developed an ICU mortality score and validated the score in an independent cohort of 264 patients treated in the ICU in three additional tertiary hospitals. Compared with the Simplified Acute Physiology Score (SAPS II, the Logistic Organ Dysfunction (LOD score, and the Sequential Organ Failure Assessment (SOFA score, our score yielded a better prediction of ICU mortality in the receiver operator characteristics (ROC analysis (AUC = 0.913 vs. AUC = 0.710 [SAPS II], AUC = 0.708 [LOD], and 0.770 [SOFA] in the training cohort; AUC = 0.841 for the developed score vs. AUC = 0.730 [SAPSII], AUC = 0.773 [LOD], and 0.783 [SOFA] in the validation cohort. Factors predicting decreased survival after ICU discharge were as follows: relapse or refractory disease, previous allogeneic stem cell transplantation, time between hospital admission and ICU admission, time spent in ICU, impaired diuresis, Glasgow Coma Scale <8 and hematocrit of ≥25% at ICU admission. Based on these factors, an ICU survival score was created and used for risk stratification into three risk groups. This stratification discriminated distinct survival rates after ICU discharge.Our data emphasize that although individual risks differ widely depending on the patient and disease status, a substantial portion of critically ill patients with AML benefit from intensive care.

  10. Genome-wide association study for biomarker identification of Rapamycin and Everolimus using a lymphoblastoid cell line system

    Directory of Open Access Journals (Sweden)

    Jing eJiang

    2013-08-01

    Full Text Available The mammalian target of rapamycin (mTOR inhibitors, a set of promising potential anti-cancer agents, has shown response variability among individuals. This study aimed to identify novel biomarkers and mechanisms that might influence the response to Rapamycin and Everolimus. Genome-wide association (GWA analyses involving single nucleotide polymorphisms (SNPs, mRNA and microRNAs microarray data were assessed for association with area under the cytotoxicity dose response curve (AUC of two mTOR inhibitors in 272 human lymphoblastoid cell lines (LCLs. Integrated analysis among SNPs, expression data, microRNA data and AUC values were also performed to help select candidate genes for further functional characterization. Functional validation of candidate genes using siRNA screening in multiple cell lines followed by MTS assays for the two mTOR inhibitors were performed. We found that 16 expression probe sets (genes that overlapped between the two drugs were associated with AUC values of two mTOR inhibitors. 127 and 100 SNPs had P<10-4, while 8 and 10 SNPs had P<10-5 with Rapamycin and Everolimus AUC, respectively. Functional studies indicated that 13 genes significantly altered cell sensitivity to either one or both drugs in at least one cell line. Additionally, one microRNA, miR-10a, was significantly associated with AUC values for both drugs and was shown to repress expression of genes that were associated with AUC and desensitize cells to both drugs. In summary, this study identified genes and a microRNA that might contribute to response to mTOR inhibitors.

  11. Exposure-response relationship of AMG 386 in combination with weekly paclitaxel in recurrent ovarian cancer and its implication for dose selection.

    Science.gov (United States)

    Lu, Jian-Feng; Rasmussen, Erik; Karlan, Beth Y; Vergote, Ignace B; Navale, Lynn; Kuchimanchi, Mita; Melara, Rebeca; Stepan, Daniel E; Weinreich, David M; Sun, Yu-Nien

    2012-05-01

    To characterize exposure-response relationships of AMG 386 in a phase 2 study in advanced ovarian cancer for the facilitation of dose selection in future studies. A population pharmacokinetic model of AMG 386 (N = 141) was developed and applied in an exposure-response analysis using data from patients (N = 160) with recurrent ovarian cancer who received paclitaxel plus AMG 386 (3 or 10 mg/kg once weekly) or placebo. Reduction in the risk of progression or death with increasing exposure (steady-state area under the concentration-versus-time curve [AUC(ss)]) was assessed using Cox regression analyses. Confounding factors were tested in multivariate analysis. Alternative AMG 386 doses were explored with Monte Carlo simulations using population pharmacokinetic and parametric survival models. There was a trend toward increased PFS with increased AUC(ss) (hazard ratio [HR] for each one-unit increment in AUC(ss), 0.97; P = 0.097), suggesting that the maximum effect on prolonging PFS was not achieved at the highest dose tested (10 mg/kg). Among patients with AUC(ss) ≥ 9.6 mg h/mL, PFS was 8.1 months versus 5.7 months for AUC(ss) AMG 386 15 mg/kg once weekly would result in an AUC(ss) ≥ 9.6 mg h/mL in > 90% of patients with median PFS of 8.2 months versus 5.0 months for placebo (HR [15 mg/kg vs. placebo], 0.56). Increased exposure to AMG 386 was associated with improved clinical outcomes in recurrent ovarian cancer, supporting the evaluation of a higher dose in future studies.

  12. A simplified score to quantify comorbidity in COPD.

    Directory of Open Access Journals (Sweden)

    Nirupama Putcha

    Full Text Available Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes.Using the COPDGene study (GOLD II-IV COPD, we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1 simple count, 2 weighted score, and 3 weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC and calibration statistics to validate scores internally with outcomes of respiratory disease-specific quality of life (St. George's Respiratory Questionnaire, SGRQ, six minute walk distance (6MWD, modified Medical Research Council (mMRC dyspnea score and exacerbation risk, ultimately choosing one score for external validation in SPIROMICS.Associations between comorbidities and all outcomes were comparable across the three scores. All scores added predictive ability to models including age, gender, race, current smoking status, pack-years smoked and FEV1 (p<0.001 for all comparisons. Area under the curve (AUC was similar between all three scores across outcomes: SGRQ (range 0·7624-0·7676, MMRC (0·7590-0·7644, 6MWD (0·7531-0·7560 and exacerbation risk (0·6831-0·6919. Because of similar performance, the comorbidity count was used for external validation. In the SPIROMICS cohort, the comorbidity count performed well to predict SGRQ (AUC 0·7891, MMRC (AUC 0·7611, 6MWD (AUC 0·7086, and exacerbation risk (AUC 0·7341.Quantifying comorbidity provides a more thorough understanding of the risk for patient-centered outcomes in COPD. A comorbidity count performs well to quantify comorbidity in a diverse population with COPD.

  13. Different effects of (+)‑borneol and (‑)‑borneol on the pharmacokinetics of osthole in rats following oral administration.

    Science.gov (United States)

    Luo, Dan-Dan; Chen, Xiao-Ying; Zhang, Zhen-Biao; Sun, Chao-Yue; Zheng, Yi-Feng; Liu, Yu-Hong; Wang, Xiu-Fen; Wang, Qi; Zhan, Janis Ya-Xian; Su, Zi-Ren

    2017-06-01

    Osthole is the primary active component of a number of herbal plants such as the Cnidium monnieri fruit. In traditional Chinese herb medicine, osthole is commonly used in combination with borneol to obtain improved pharmacological effects. The aim of the present study was to investigate the effect of borneol enantiomers on the pharmacokinetics of osthole. An appropriate high‑performance liquid chromatography (HPLC) method was applied to determine the concentrations of osthole in plasma. Following oral administration of osthole alone or combined with borneol in rats, blood samples were collected and analyzed by HPLC. The results demonstrated that there were statistically significant differences in the pharmacokinetic parameters of osthole between osthole administration alone and co‑administration with borneol. When combined with synthetic borneol, the AUC0‑t, AUC0‑∞ and Cmax of osthole increased by 48.153, 104.708 and 92.630%, respectively, while the CL/F decreased by 51.251%. When combined with (+)‑borneol, the AUC0‑t, AUC0‑∞ and Cmax of osthole were increased by 61.561, 78.167, and 51.769%, respectively, while the CL/F decreased by 44.174% (P<0.01). In addition, when combined with (‑)‑borneol, the AUC0‑t, AUC0‑∞ and Cmax of osthole increased by 115.856, 167.786 and 271.289%, respectively, while the CL/F decreased by 60.686% (P<0.01). These results indicated that borneol may enhance gastrointestinal absorption and inhibit the metabolism of osthole. In addition, the promotional effect of (‑)‑borneol on the pharmacokinetic parameters of osthole was greater than that of (+)‑borneol.

  14. Emtricitabine Seminal Plasma and Blood Plasma Population Pharmacokinetics in HIV-Infected Men in the EVARIST ANRS-EP 49 Study

    Science.gov (United States)

    Tréluyer, Jean-Marc; Illamola, Silvia M.; Bouazza, Naïm; Foissac, Frantz; De Sousa Mendes, Maïlys; Lui, Gabrielle; Chenevier-Gobeaux, Camille; Suzan-Monti, Marie; Rouzioux, Christine; Assoumou, Lambert; Viard, Jean-Paul; Hirt, Déborah; Urien, Saïk; Ghosn, Jade

    2015-01-01

    We aimed to describe blood plasma (BP) and seminal plasma (SP) pharmacokinetics of emtricitabine (FTC) in HIV-1-infected men, assess its penetration in the male genital tract, and evaluate its impact on seminal plasma HIV load (spVL) detection. Men from the EVARIST ANRS EP49 study receiving combined antiretroviral therapy with FTC and with suppressed BP viral load were included in the study. A total of 236 and 209 FTC BP and SP concentrations, respectively, were available. A population pharmacokinetic model was developed with Monolix 4.1.4. The impact of FTC seminal exposure on spVL detection was explored by receiver operating characteristic (ROC) curves and mixed-effects logistic regressions. FTC BP pharmacokinetics was described by a two-compartment model. The addition of an effect compartment with different input and output constants best described FTC SP pharmacokinetics. No covariates were found to explain the variability in SP. FTC exposures (area under the concentration-time curve from 0 to 24 h [AUC0–24]) were higher in SP than in BP (median AUC0–24, 38.04 and 12.95 mg · liter−1 · h, respectively). The median (range) SP-to-BP AUC0–24 ratio was 2.91 (0.84 to 10.08). Less than 1% of FTC AUC0–24 ratios were lower than 1. The impact of FTC SP AUC0–24 or FTC SP-to-BP AUC0–24 ratio on spVL detection was not significant (P = 0.943 or 0.893, respectively). This is the first population model describing FTC pharmacokinetics simultaneously in both BP and SP. FTC distributes well in the male genital tract with higher FTC concentrations in SP than in BP. FTC seminal plasma exposures were considered efficient in the majority of men. PMID:26282407

  15. Injectable dexamethasone sodium phosphate administered orally? A pharmacokinetic analysis of a common emergency department practice.

    Science.gov (United States)

    Toledo, Alexander; Amato, Christopher S; Clarke, Nigel; Reitz, Richard E; Salo, David

    2015-01-01

    The injectable formulation of dexamethasone has been administered orally, for the treatment of pediatric asthma and croup. The practice is followed in emergency departments around the country, but pharmacokinetic data supporting this practice are lacking. This study evaluated the relative bioavailability and pharmacokinetics of dexamethasone sodium phosphate for injection (DSPI) administered orally compared to dexamethasone oral concentrate (DOC) in healthy adults. This was an open label, crossover study of 11 healthy adults 18 to 45 years of age. All subjects received 8 mg of dexamethasone oral concentrate initially. After a 1-week wash-out period, subjects received 8 mg of DSPI administered orally. Dexamethasone levels were measured by liquid chromatography in tandem mass spectrometry. Cmax and area under the curve (AUC (0-t) and AUC (0-∞)) were calculated and compared between groups using the paired t test. The mean ± SD AUC(0-t) for dexamethasone oral concentrate and DSPI were 5497.23 ± 1649 and 4807.82 ± 1971) ng/dL/hr, respectively; 90% confidence interval (CI) was 78.8%-96.9%. The mean ± SD AUC(0-∞) for dexamethasone oral concentrate and DSPI were 6136.43 ± 2577 and 5591.48 ± 3075 ng/dL/hr, respectively; 90% CI was 79.0% -105.2%. Mean Cmax ± SD for DOC and DSPI were 942.94 ± 151 and 790.92 ± 229 ng/dL, respectively; 90% CI 76.8%-91.7%. The relative bioavailability of DSPI administered orally was 87.4% when using AUC(0-t) and 91.1% when using AUC(0-∞). The calculated absolute bioavailability was 75.9%. DSPI is not bioequivalent to dexamethasone oral concentrate when administered orally. The existing literature supports the efficacy of DSPI despite this. Dosing adjustments may be considered.

  16. In vitro Dynamic Pharmacokinetic/Pharmacodynamic (PK/PD) study and COPD of Marbofloxacin against Haemophilus parasuis.

    Science.gov (United States)

    Sun, Jian; Xiao, Xia; Huang, Rui-Juan; Yang, Tao; Chen, Yi; Fang, Xi; Huang, Ting; Zhou, Yu-Feng; Liu, Ya-Hong

    2015-12-01

    Haemophilus parasuis (H. parasuis) can invade the body and cause systemic infection under stress conditions. Marbofloxacin has been recommended for the treatment of swine infections. However, few studies have investigated the PK/PD characteristics and PK/PD cutoff (COPD) of this drug against H. parasuis. MICs of marbofloxacin against 198 H. parasuis isolates were determined. The MIC50 and MIC90 were 2 and 8 mg/L, respectively. An in vitro dynamic PK/PD model was established to study the PK/PD relationship of marbofloxacin against H. parasuis. The PK/PD surrogate markers Cmax/MIC, Cmax/MPC (the maximum concentration divided by MIC or mutant prevention concentration (MPC)) and AUC 24h/MIC, AUC 24h/MPC (the area under the curve during the first 24 h divided by MIC or MPC) simulated the antimicrobial effect of marbofloxacin successfully with the R(2) of 0.9928 and 0.9911, respectively. The target values of 3-log10-unit and 4-log10-unit reduction for AUC 24h/MPC were 33 and 42, while the same efficacy for AUC 24h/MIC were 88 and 110. The COPD deduced from Monte Carlo simulation (MCS) for marbofloxacin against H. parasuis was 0.5 mg/L. The recommended dose of marbofloxacin against H. parasuis with MIC ≤ 2 mg/L was 16 mg/kg body weight (BW). The PK/PD surrogate markers AUC 24h/MIC, Cmax/MIC and AUC 24h/MPC, Cmax/MPC properly described the effects of marbofloxacin. Marbofloxacin can achieve the best efficacy at dosage of 16 mg/kg BW for strains with MIC values ≤ 2 mg/L, therefore, it is obligatory to know the sensitivity of the pathogen and to treat animals as early as possible. The very first COPD provide fundamental data for marbofloxacin breakpoint determination.

  17. A Two-Period Open-Label, Single-Dose Crossover Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Between Cimetidine and Inhaled Extrafine CHF 5993.

    Science.gov (United States)

    Mariotti, Fabrizia; Ciurlia, Giorgia; Spaccapelo, Luca; Muraro, Annamaria; Acerbi, Daniela

    2017-04-01

    CHF 5993 is an extrafine 'triple therapy' combination of the long-acting muscarinic antagonist glycopyrronium bromide (GB), the long-acting β2-agonist formoterol fumarate (FF), and the inhaled corticosteroid beclometasone dipropionate (BDP). It is in development for chronic obstructive pulmonary disease and asthma delivered via pressurised metered-dose inhaler. This two-period, open-label, crossover study examined the drug-drug interaction of CHF 5993 and cimetidine. In one period, subjects received cimetidine 800 mg twice daily for 6 days; on the fourth day they also received CHF 5993 (BDP/FF/GB 400/24/100 µg). In the other, they received CHF 5993 alone. Primary objective was to compare the area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUC0-t) of GB, with and without cimetidine. Secondary endpoints included GB AUC0-12h, maximum concentration (C max), time to C max (t max), elimination half-life (t ½) and urinary excretion. Pharmacokinetic parameters of BDP, beclometasone-17-monopropionate (B17MP; active metabolite of BDP) and formoterol were also evaluated. Twenty-six subjects were randomised; 25 completed. Co-administration of CHF 5993 and cimetidine resulted in small, statistically significant increases in GB AUC0-t, AUC0-12h and C max vs CHF 5993 (ratios 1.16, 1.21 and 1.26, respectively); t ½, t max and urinary excretion were unaffected. There were small, statistically significant increases in formoterol AUC0-t, AUC0-24h and t ½ following co-administration of cimetidine and CHF 5993; urinary excretion was unaffected. There were no significant differences for either BDP or B17MP. There were few adverse events (AEs), and no serious AEs. Overall, this study indicates that there is no clinically relevant drug-drug interaction between CHF 5993 and cimetidine.

  18. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers

    Science.gov (United States)

    Hanley, Michael J; Masse, Gina; Harmatz, Jerold S; Cancalon, Paul F; Dolnikowski, Gregory G; Court, Michael H; Greenblatt, David J

    2013-01-01

    Aim The present study evaluated the possibility of drug interactions involving blueberry juice (BBJ) and substrate drugs whose clearance is dependent on cytochromes P4503A (CYP3A) and P4502C9 (CYP2C9). Methods A 50:50 mixture of lowbush and highbush BBJ was evaluated in vitro as an inhibitor of CYP3A activity (hydroxylation of triazolam and dealkylation of buspirone) and of CYP2C9 activity (flurbiprofen hydroxylation) using human liver microsomes. In clinical studies, clearance of oral buspirone and oral flurbiprofen was studied in healthy volunteers with and without co-treatment with BBJ. Results BBJ inhibited CYP3A and CYP2C9 activity in vitro, with 50% inhibitory concentrations (IC50) of less than 2%, but without evidence of mechanism-based (irreversible) inhibition. Grapefruit juice (GFJ) also inhibited CYP3A activity, but inhibitory potency was increased by pre-incubation, consistent with mechanism-based inhibition. In clinical studies, GFJ significantly increased area under the plasma concentration−time curve (AUC) for the CYP3A substrate buspirone. The geometric mean ratio (GMR = AUC with GFJ divided by AUC with water) was 2.12. In contrast, the effect of BBJ (GMR = 1.39) was not significant. In the study of flurbiprofen (CYP2C9 substrate), the positive control inhibitor fluconazole significantly increased flurbiprofen AUC (GMR = 1.71), but BBJ had no significant effect (GMR = 1.03). Conclusion The increased buspirone AUC associated with BBJ is quantitatively small and could have occurred by chance. BBJ has no effect on flurbiprofen AUC. The studies provide no evidence for concern about clinically important pharmacokinetic drug interactions of BBJ with substrate drugs metabolized by CYP3A or CYP2C9. PMID:22943633

  19. A comparison of the ratio of patient′s height to thyromental distance with the modified Mallampati and the upper lip bite test in predicting difficult laryngoscopy

    Directory of Open Access Journals (Sweden)

    Mohammadreza Safavi

    2011-01-01

    Full Text Available Background: The aim of the present study was to compare the ability to predict difficult visualization of the larynx from the following preoperative airway predictive indices, in isolation and combination: modified Mallampati test (MMT, the ratio of height to thyromental distance (RHTMD and the Upper-Lip-Bite test (ULBT. Methods: We collected data on 603 consecutive patients scheduled for elective surgery under general anesthesia requiring endotracheal intubation and then evaluated all three factors before surgery. An experienced anesthesiologist, not informed of the recorded preoperative airway evaluation, performed the laryngoscopy and grading (as per Cormack and Lehane′s classification. Sensitivity, specificity, and positive and negative predictive value, Receiver operating characteristic (ROC Curve and the area under ROC curve (AUC for each airway predictor in isolation and in combination were determined. Results: Difficult laryngoscopy (Grade 3 or 4 occurred in 41 (6.8% patients. The main endpoint of the present study, the AUC of the ROC, was significantly lower for the MMT (AUC, 0.511; 95% CI, 0.470-0.552 than the ULBT (AUC, 0.709; 95% CI, 0.671-0.745, P=0.002 and the RHTMD score (AUC, 0.711; 95% CI, 0.673-0.747, P=0.001. There was no significant difference between the AUC of the ROC for the ULBT and the RHTMD score. By using discrimination analysis, the optimal cutoff point for the RHTMD for predicting difficult laryngoscopy was 21.06 (sensitivity, 75.6%; specificity, 58.5%. Conclusion: The RHTMD is comparable with ULBT for prediction of difficult laryngoscopy in general population.

  20. Accuracy of ultrasound imaging technique for assessing lipoatrophy in HIV-infected subjects.

    Science.gov (United States)

    Ferraioli, Giovanna; Tinelli, Carmine; Scudeller, Luigia; Filice, Gaetano; Filice, Carlo

    2011-07-01

    To compare the accuracy of ultrasound imaging technique to that of clinical diagnosis in evaluating subcutaneous fat changes in HIV-infected subjects. HIV-uninfected control subjects (Group A), HIV-infected subjects with clinically assessed lipoatrophy (Group B), and HIV-infected subjects without clinical lipoatrophy (Group C) underwent ultrasound measurements of subcutaneous fat thickness at facial, brachial and thigh regions. ROC curve analyses were used to estimate ultrasound prediction accuracy and cut-off values of subcutaneous fat thickness. 228 subjects were enrolled: 78 in Group A, 73 in Group B, and 77 in Group C. Facial lipoatrophy: ROC curve analysis identified optimal cut-off value of 13.3 mm [sensitivity, 96.0%; specificity, 76.9% AUC 0.92], 5.0 mm [sensitivity, 71.4%; specificity, 92.3%; AUC 0.90] and 11.2 mm [sensitivity, 95.8%; specificity, 89.7%; AUC 0.97] for females and 12.05 mm [sensitivity, 51.2%; specificity, 87.2%; AUC 0.74], 4.1 mm [sensitivity, 76.2%; specificity, 89.7%; AUC 0.85] and 4.35 mm [sensitivity, 60.0%; specificity, 89.7%; AUC 0.82] for males in assessing facial, brachial and crural lipoatrophy respectively. Using this cut-off values, 12/25 (48%) females and 17/49 (34.7%) males, 12/28 (42.9%) females and 23/49 (46.9%) males, 19/28 (67.9%) females and 12/49 (24.5%) males in Group C would be classified as "sub-clinical" facial, brachial and crural lipoatrophy respectively. The results of our study show that in the assessment of subtle subcutaneous fat changes ultrasound is more accurate than clinical evaluation and confirm the usefulness of ultrasound imaging technique in identifying lipoatrophy at an early stage.

  1. Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

    Science.gov (United States)

    Liu, Dongzhou J; Collaku, Agron

    2018-01-01

    Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

  2. Residual Convolutional Neural Network for the Determination ofIDHStatus in Low- and High-Grade Gliomas from MR Imaging.

    Science.gov (United States)

    Chang, Ken; Bai, Harrison X; Zhou, Hao; Su, Chang; Bi, Wenya Linda; Agbodza, Ena; Kavouridis, Vasileios K; Senders, Joeky T; Boaro, Alessandro; Beers, Andrew; Zhang, Biqi; Capellini, Alexandra; Liao, Weihua; Shen, Qin; Li, Xuejun; Xiao, Bo; Cryan, Jane; Ramkissoon, Shakti; Ramkissoon, Lori; Ligon, Keith; Wen, Patrick Y; Bindra, Ranjit S; Woo, John; Arnaout, Omar; Gerstner, Elizabeth R; Zhang, Paul J; Rosen, Bruce R; Yang, Li; Huang, Raymond Y; Kalpathy-Cramer, Jayashree

    2017-11-22

    Purpose: Isocitrate dehydrogenase ( IDH ) mutations in glioma patients confer longer survival and may guide treatment decision making. We aimed to predict the IDH status of gliomas from MR imaging by applying a residual convolutional neural network to preoperative radiographic data. Experimental Design: Preoperative imaging was acquired for 201 patients from the Hospital of University of Pennsylvania (HUP), 157 patients from Brigham and Women's Hospital (BWH), and 138 patients from The Cancer Imaging Archive (TCIA) and divided into training, validation, and testing sets. We trained a residual convolutional neural network for each MR sequence (FLAIR, T2, T1 precontrast, and T1 postcontrast) and built a predictive model from the outputs. To increase the size of the training set and prevent overfitting, we augmented the training set images by introducing random rotations, translations, flips, shearing, and zooming. Results: With our neural network model, we achieved IDH prediction accuracies of 82.8% (AUC = 0.90), 83.0% (AUC = 0.93), and 85.7% (AUC = 0.94) within training, validation, and testing sets, respectively. When age at diagnosis was incorporated into the model, the training, validation, and testing accuracies increased to 87.3% (AUC = 0.93), 87.6% (AUC = 0.95), and 89.1% (AUC = 0.95), respectively. Conclusions: We developed a deep learning technique to noninvasively predict IDH genotype in grade II-IV glioma using conventional MR imaging using a multi-institutional data set. Clin Cancer Res; 1-9. ©2017 AACR. ©2017 American Association for Cancer Research.

  3. Temperature cycling during platelet cold storage improves in vivo recovery and survival in healthy volunteers.

    Science.gov (United States)

    Vostal, Jaroslav G; Gelderman, Monique P; Skripchenko, Andrey; Xu, Fei; Li, Ying; Ryan, Johannah; Cheng, Chunrong; Whitley, Pam; Wellington, Michael; Sawyer, Sherrie; Hanley, Shalene; Wagner, Stephen J

    2018-01-01

    Room temperature (RT) storage of platelets (PLTs) can support bacterial proliferation in contaminated units, which can lead to transfusion-transmitted septic reactions. Cold temperature storage of PLTs could reduce bacterial proliferation but cold exposure produces activation-like changes in PLTs and leads to their rapid clearance from circulation. Cold-induced changes are reversible by warming and periodic rewarming during cold storage (temperature cycling [TC]) has been proposed to alleviate cold-induced reduction in PLT circulation. A clinical trial in healthy human volunteers was designed to compare in vivo recovery, survival, and area under the curve (AUC) of radiolabeled autologous apheresis PLTs stored for 7 days at RT or under TC or cold conditions. Paired comparisons of RT versus TC and TC versus cold PLTs were conducted. Room temperature PLTs had in vivo recovery of 55.7 ± 13.9%, survival of 161.3 ± 28.8 hours, and AUC of 5031.2 ± 1643.3. TC PLTs had recovery of 42.6 ± 16.4%, survival of 48.1 ± 14.4% hours, and AUC of 1331.3 ± 910.2 (n = 12, p cold PLTs had recovery of 23.1 ± 8.8%, survival of 33.7 ± 14.7 hours, and AUC of 540.2 ± 229.6 while TC PLTs had recovery of 36.5 ± 12.9%, survival of 49.0 ± 17.3 hours, and AUC of 1164.3 ± 622.2 (n = 4, AUC had p cold storage but is not equivalent to RT storage. © 2017 AABB.

  4. Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

    Science.gov (United States)

    Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

    2013-11-01

    An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variabilitybioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Does arterial shear explain the magnitude of flow-mediated dilation?: a comparison between young and older humans.

    Science.gov (United States)

    Thijssen, Dick H J; Bullens, Lauren M; van Bemmel, Marieke M; Dawson, Ellen A; Hopkins, Nicola; Tinken, Toni M; Black, Mark A; Hopman, Maria T E; Cable, N Timothy; Green, Daniel J

    2009-01-01

    Flow-mediated dilatation (FMD) has become a commonly applied approach for the assessment of vascular function and health in humans. Recent studies emphasize the importance of normalizing the magnitude of FMD to its apparent eliciting stimulus, the postdeflation arterial shear. However, the relationship between shear stress and the magnitude of FMD may differ between groups. The aim of this study was to examine the relationship between the brachial FMD and four different indexes of postdeflation shear rate (SR) in healthy children (n = 51, 10 +/- 1 yr) and young (n = 57, 27 +/- 6 yr) and older (n = 27, 58 +/- 4 yr) adults. SR was calculated from deflation (time 0) until 9 s (peak), 30 s (0-30), 60 s (0-60), or until the time-to-peak diameter in each individual (0-ttp). Edge detection and wall tracking of high resolution B-mode arterial ultrasound images were used to calculate the conduit artery diameter. In young adults, the brachial artery FMD demonstrated a significant correlation with the area under the SR curve (SR(AUC)) 0-30 s (r(2) = 0.12, P = 0.009), 0-60 s (r(2) = 0.14, P = 0.005), and 0-ttp (r(2) = 0.14, P = 0.005) but not for the peak SR(AUC) 0-9 s (r(2) = 0.04, P = 0.12). In children and older adults, the magnitude of the brachial artery FMD did not correlate with any of the four SR(AUC) stimuli. These findings suggest that in young subjects, postdeflation SR(AUC) correlates moderately with the magnitude of the FMD response. However, the relationship between FMD and postdeflation shear appears to be age dependent, with less evidence for an association in younger and older subjects. Therefore, we support presenting SR(AUC) stimuli but not normalizing FMD responses for the SR(AUC) when using this technique.

  6. Pharmacokinetics and bioequivalence study of three oral formulations of ambroxol 30 mg: a randomized, three-period crossover comparison in healthy volunteers.

    Science.gov (United States)

    Jiang, Bo; Chen, Jin-Liang; Lou, Hong-Gang; Yu, Ling-Yan; Shen, Hua-Hao; Ruan, Zou-Rong

    2014-10-01

    To compare the pharmacokinetic properties of two newly developed generic ambroxol formulations with a branded innovator product in healthy Chinese male volunteers. This was a single-dose, randomized, open-label, three-period crossover study in healthy volunteers aged 18 - 45 years under fasting conditions. Subjects were assigned to receive 1 of 2 test formulations or a reference tablet of ambroxol 30 mg. Each study period was separated by a 1-week washout phase. Blood samples were collected at pre-specified times. A non-compartmental method was employed to determine pharmacokinetic properties (C(max), t(max), AUC(0-tlast), AUC(0-∞)) to test for bioequivalence. The predetermined regulatory range of 90% CI for bioequivalence was 80 - 125%. 24 subjects were enrolled in and completed the study. The geometric mean C(max) values for the test tablet, test capsule, and reference product were 82.73, 85.36, 84.56 ng/mL, and their geometric mean AUC(0-tlast) (AUC(0-∞)) were 660.87 (753.49), 678.98 (756.79), and 639.41 (712.14) ng x h/mL, respectively. For test tablet vs. reference, the 90% CIs of the least squares mean test/reference ratios of C(max), AUC(0-tlast), and AUC(0-∞) were 91.2% to 104.9%, 96.5% to 110.7%, and 98.8% to 113.4%, respectively. For test capsule, the corresponding values were 94.1% to 108.3%, 99.2% to 113.7%, and 99.2% to 113.9%, respectively. No adverse events occurred during the study. The ambroxol 30 mg tablets and capsules were considered bioequivalent to the reference formulation in accordance with predetermined regulatory criteria.

  7. Medical and surgical treatments for obesity have opposite effects on peptide YY and appetite: a prospective study controlled for weight loss.

    Science.gov (United States)

    Valderas, Juan P; Irribarra, Verónica; Boza, Camilo; de la Cruz, Rolando; Liberona, Yessica; Acosta, Ana Maria; Yolito, Macarena; Maiz, Alberto

    2010-03-01

    The effects of medical and surgical treatments for obesity on peptide YY (PYY) levels, in patients with similar weight loss, remain unclear. The objective of the study was to assess PYY and appetite before and after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and medical treatment (MED). This was a prospective, controlled, nonrandomized study. The study was conducted at the Departments of Nutrition and Digestive Surgery at a university hospital. PARTICIPANTS included three groups of eight patients with similar body mass indexes (RYGB 37.8 +/- 0.8, SG 35.3 +/- 0.7, and MED 39.1 +/- 1.7 kg/m(2), P = NS) and eight lean controls (body mass index 21.7 +/- 0.7 kg/m(2)). Total plasma PYY, hunger, and satiety visual analog scales in fasting and after ingestion of a standard test meal were measured. At baseline there were no differences in the area under the curve (AUC) of PYY, hunger, or satiety in obese groups. Two months after the interventions, RYGB, SG, and MED groups achieved similar weight loss (17.7 +/- 3, 14.9 +/- 2.4, 16.6 +/- 4%, respectively, P = NS). PYY AUC increased in RYGB (P < 0.001) and SG (P < 0.05) and did not change in MED. PYY levels decreased at fasting, 30 min, and 180 min after a standard test meal in MED (P < 0.05). Hunger AUC decreased in RYGB (P < 0.05). Satiety AUC increased in RYGB (P < 0.05) and SG (P < 0.05). Appetite did not change in MED. PYY AUC correlated with satiety AUC (r = 0.35, P < 0.05). RYGB and SG increased PYY and reduced appetite. MED failed to produce changes. Different effects occur despite similar weight loss. This suggests that the weight-loss effects of these procedures are enhanced by an increase in PYY and satiety.

  8. Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [13C8]‐evacetrapib as a tracer

    Science.gov (United States)

    Aburub, Aktham; Ward, Chris; Hinds, Chris; Czeskis, Boris; Ruterbories, Kenneth; Suico, Jeffrey G.; Royalty, Jane; Ortega, Demetrio; Pack, Brian W.; Begum, Syeda L.; Annes, William F.; Lin, Qun; Small, David S.

    2015-01-01

    This open‐label, single‐period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130‐mg evacetrapib oral dose and 4‐h intravenous (IV) infusion of 175 µg [13C8]‐evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [13C8]‐evacetrapib using high‐performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration‐time curve (AUC) from zero to infinity (AUC[0‐∞]) and to the last measureable concentration (AUC[0‐tlast]), were calculated. Bioavailability was calculated as the ratio of least‐squares geometric mean of dose‐normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2–47.6%) for AUC(0‐∞) and 44.3% (90% CI: 41.8–46.9%) for AUC(0‐tlast). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a 13C‐labeled IV microdose tracer at about 1/1000th the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability. PMID:26639670

  9. Diagnostic value of quantitative ultrasound and Osteoporosis self-assessment tool in comparison with DXA in detecting low bone mineral density in post-menopausal women in Riyadh, Kingdom of Saudi Arabia

    Directory of Open Access Journals (Sweden)

    AlJohara M AlQuaiz

    2015-11-01

    Full Text Available The objective of this study was to assess the diagnostic value of quantitative ultrasound (QUS and Osteoporosis self-assessment tool (OST compared with Dual Energy x-ray absorptiometry (DXA, and to identify the best cut-off value for determining low bone mineral density (BMD among postmenopausal women in Riyadh, Saudi Arabia. We conducted a community based cross-sectional study on 224 randomly selected post-menopausal women. Women visited primary heath care centers for answering self-administered questionnaireand screening for low BMD using QUS technique. OST was calculated based on age and weight. DXA scanwas performedforlumbar spine and femur neck at King Khalid University Hospital, Riyadh. Mean age of participants was 58.05(±8.97 years. The prevalence of low BMD at lumbar spine and femur neck was 56% and 28% respectively. The best cut-off value for QUS and OST was ≤-1 and ≤2 respectively. QUS yielded sensitivity and specificity of 73% vs 47% for lumbar spine (area under curve (AUC 0.56 and 84% vs 43% for femur neck (AUC 0.61. OST yielded sensitivity and specificity of 38% vs 84% for lumbar spine (AUC 0.62 and 48% vs 78% for femur neck (AUC 0.68. On combining the results, sensitivity and specificity were81% vs 41% (AUC 0.61 for lumbar spine and 89% vs 35% for femur neck (AUC 0.68 respectively. QUS and OST separately have limited diagnostic value, however on combining both instruments there is improvement in sensitivity to detect low BMD for both lumbar spine and femur neck.

  10. Anthropometric and central obesity indices as predictors of long-term cardiometabolic risk among Saudi young and middle-aged men and women.

    Science.gov (United States)

    Abulmeaty, Mahmoud M A; Almajwal, Ali M; Almadani, Najwa K; Aldosari, Mona S; Alnajim, Ahmed A; Ali, Saeed B; Hassan, Heba M; Elkatawy, Hany A

    2017-04-01

    To investigate the prediction of long-term cardiometabolic risk using anthropometric and central obesity parameters.  Methods: A total of 390 Saudi subjects (men 42.8%) aged 18-50 years were enrolled in a cross-sectional study in King Saud University, Riyadh, Kingdom of Saudi Arabia between August 2014 and  January 2016. All   participants were instructed to fast for 12 hours before taking blood samples for glucose and lipid panel analyses. A full anthropometric measurement and bioelectric impedance analysis was performed. The anthropometric and central obesity parameters were used for correlation with 30-year Framingham and life-time American College of Cardiology/American Heart Association risk scores. We used receiver operator characteristic curves to select the best predictors with the highest sensitivity and specificity. Results: The best discriminators of the long-term cardiometabolic risk among all the studied variables in men were the visceral adiposity index (VAI) (AUC=0.767), conicity index (CI) (AUC=0.817), and mid-arm muscular area (MAMA) (AUC=0.639). The best predictors for women were body mass index (AUC=0.912), waist circumference (AUC=0.752), and lipid accumulation product (AUC=0.632). The Kappa coefficient and 95% confidence interval ranged from 0.1 to 0.35, which suggests that there is a poor to fair agreement between these indices and cardiovascular risk scores.   Conclusion: Long-term cardiometabolic risk can be predicted using simple anthropometric and central obesity indices, and these discriminators were not the same in Saudi men and women.

  11. Incremental Value of Platelet Reactivity Over a Risk Score of Clinical and Procedural Variables in Predicting Bleeding After Percutaneous Coronary Intervention via the Femoral Approach: Development and Validation of a New Bleeding Risk Score.

    Science.gov (United States)

    Mangiacapra, Fabio; Ricottini, Elisabetta; Barbato, Emanuele; Demartini, Chiara; Peace, Aaron; Patti, Giuseppe; Vizzi, Vincenzo; De Bruyne, Bernard; Wijns, William; Di Sciascio, Germano

    2015-05-01

    Growing evidence suggests that platelet reactivity (PR) may predict bleeding. We investigate the incremental value of PR in predicting bleeding after percutaneous coronary intervention (PCI) via the femoral approach over a validated bleeding risk score (BRS) of clinical and procedural variables. A total of 800 patients undergoing elective PCI via the femoral approach were included. PR was measured before PCI with the VerifyNow P2Y12 assay and low PR was defined as a P2Y12 reaction unit value ≤ 178. Calculation of the BRS included the following: age, sex, intra-aortic balloon pump, glycoprotein IIb/IIIa inhibitors, chronic kidney disease, anemia, and low-molecular-weight heparin within 48-hour pre-PCI. A new risk score including low PR (BRS-PR) was developed and validated in an independent cohort of patients (n = 310). Bleeding events at 30 days after PCI were defined according to the thrombolysis in myocardial infarction, Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2, and Bleeding Academic Research Consortium criteria. Both BRS and PR showed high discriminatory power for bleeding (area under the curve [AUC] > 0.7 for all definitions). Discriminatory power of BRS-PR (AUC = 0.809 for thrombolysis in myocardial infarction bleeding; AUC = 0.814 for Bleeding Academic Research Consortium class ≥ 2 bleeding; AUC = 0.708 for Bleeding Academic Research Consortium class ≥ 3 bleeding; and AUC = 0.813 for REPLACE-2 bleeding) was significantly higher than that of BRS alone (P validation set, BRS-PR showed higher discriminatory power for thrombolysis in myocardial infarction bleeding than BRS alone (AUC = 0.788 versus 0.709; P = 0.036). PR has incremental predictive value on bleeding events after elective PCI via the femoral approach over a validated risk score of clinical and procedural variables. A risk score including PR yields significantly better prognostic performance compared with the original BRS. © 2015 American Heart

  12. Pulse Oximetry: A Non-Invasive, Novel Marker for the Quality of Chest Compressions in Porcine Models of Cardiac Arrest.

    Directory of Open Access Journals (Sweden)

    Jun Xu

    Full Text Available Pulse oximetry, which noninvasively detects the blood flow of peripheral tissue, has achieved widespread clinical use. We have noticed that the better the quality of cardiopulmonary resuscitation (CPR, the better the appearance of pulse oximetry plethysmographic waveform (POP. We investigated whether the area under the curve (AUC and/or the amplitude (Amp of POP could be used to monitor the quality of CPR.Prospective, randomized controlled study.Animal experimental center in Peking Union Medical Collage Hospital, Beijing, China.Healthy 3-month-old male domestic swine.34 local pigs were enrolled in this study. After 4 minutes of untreated ventricular fibrillation, animals were randomly assigned into two resuscitation groups: a "low quality" group (with a compression depth of 3cm and a "high quality" group (with a depth of 5cm. All treatments between the two groups were identical except for the depth of chest compressions. Hemodynamic parameters [coronary perfusion pressure (CPP, partial pressure of end-tidal carbon dioxide (PETCO2] as well as AUC and Amp of POP were all collected and analyzed.There were statistical differences between the "high quality" group and the "low quality" group in AUC, Amp, CPP and PETCO2 during CPR (P<0.05. AUC, Amp and CPP were positively correlated with PETCO2, respectively (P<0.01. There was no statistical difference between the heart rate calculated according to the POP (FCPR and the frequency of mechanical CPR at the 3rd minute of CPR. The FCPR was lower than the frequency of mechanical CPR at the 6th and the 9th minute of CPR.Both the AUC and Amp of POP correlated well with CPP and PETCO2 in animal models. The frequency of POP closely matched the CPR heart rate. AUC and Amp of POP might be potential noninvasive quality monitoring markers for CPR.

  13. Multiparametric 3T MRI for the prediction of pathological downgrading after radical prostatectomy in patients with biopsy-proven Gleason score 3 + 4 prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gondo, Tatsuo [Memorial Sloan-Kettering Cancer Center, Urology Service, Department of Surgery, New York, NY (United States); Tokyo Medical University, Department of Urology, Tokyo (Japan); Hricak, Hedvig; Sala, Evis; Vargas, Hebert Alberto [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Zheng, Junting; Moskowitz, Chaya S. [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Bernstein, Melanie; Eastham, James A. [Memorial Sloan-Kettering Cancer Center, Urology Service, Department of Surgery, New York, NY (United States)

    2014-12-15

    The aim of this study was to assess the diagnostic performance of pre-treatment 3-Tesla (3T) multiparametric magnetic resonance imaging (mpMRI) for predicting Gleason score (GS) downgrading after radical prostatectomy (RP) in patients with GS 3 + 4 prostate cancer (PCa) on biopsy. We retrospectively reviewed 304 patients with biopsy-proven GS 3 + 4 PCa who underwent mpMRI before RP. On T2-weighted imaging and three mpMRI combinations (T2-weighted imaging + diffusion-weighted imaging [DWI], T2-weighted imaging + dynamic contrast-enhanced-MRI [DCE-MRI], and T2-weighted imaging + DWI + DCE-MRI), two radiologists (R1/R2) scored the presence of a dominant tumour using a 5-point Likert scale (1 = definitely absent to 5 = definitely present). Diagnostic performance in identifying downgrading was evaluated via areas under the curves (AUCs). Predictive accuracies of multivariate models were calculated. In predicting downgrading, T2-weighted imaging + DWI (AUC = 0.89/0.85 for R1/R2) performed significantly better than T2-weighted imaging alone (AUC = 0.72/0.73; p < 0.001/p = 0.02 for R1/R2), while T2-weighted imaging + DWI + DCE-MRI (AUC = 0.89/0.84 for R1/R2) performed no better than T2-weighted imaging + DWI (p = 0.48/p > 0.99 for R1/R2). On multivariate analysis, the clinical + mpMRI model incorporating T2-weighted imaging + DWI (AUC = 0.92/0.88 for R1/R2) predicted downgrading significantly better than the clinical model (AUC = 0.73; p < 0.001 for R1/R2). mpMRI improves the ability to identify a subgroup of patients with Gleason 3 + 4 PCa on biopsy who are candidates for active surveillance. DCE-MRI (compared to T2 + DWI) offered no additional benefit to the prediction of downgrading. (orig.)

  14. Assessment of three risk evaluation systems for patients aged ≥70 in East China: performance of SinoSCORE, EuroSCORE II and the STS risk evaluation system.

    Science.gov (United States)

    Shan, Lingtong; Ge, Wen; Pu, Yiwei; Cheng, Hong; Cang, Zhengqiang; Zhang, Xing; Li, Qifan; Xu, Anyang; Wang, Qi; Gu, Chang; Zhang, Yangyang

    2018-01-01

    To assess and compare the predictive ability of three risk evaluation systems (SinoSCORE, EuroSCORE II and the STS risk evaluation system) in patients aged ≥70, and who underwent coronary artery bypass grafting (CABG) in East China. Three risk evaluation systems were applied to 1,946 consecutive patients who underwent isolated CABG from January 2004 to September 2016 in two hospitals. Patients were divided into two subsets according to their age: elderly group (age ≥70) with a younger group (age evaluation system were 0.78(0.64)%, 1.43(1.14)% and 0.78(0.77)%, respectively. SinoSCORE achieved the best discrimination (the area under the receiver operating characteristic curve (AUC) = 0.829), followed by the STS risk evaluation system (AUC = 0.790) and EuroSCORE II (AUC = 0.769) in the entire cohort. In the elderly group, the observed mortality rate was 4.82% while it was 1.38% in the younger group. SinoSCORE (AUC = .829) also achieved the best discrimination in the elderly group, followed by the STS risk evaluation system (AUC = .730) and EuroSCORE II (AUC = 0.640) while all three risk evaluation systems all had good performances in the younger group. SinoSCORE, EuroSCORE II and the STS risk evaluation system all achieved positive calibrations in the entire cohort and subsets. The performance of the three risk evaluation systems was not ideal in the entire cohort. In the elderly group, SinoSCORE appeared to achieve better predictive efficiency than EuroSCORE II and the STS risk evaluation system.

  15. Big Data, Predictive Analytics, and Quality Improvement in Kidney Transplantation: A Proof of Concept.

    Science.gov (United States)

    Srinivas, T R; Taber, D J; Su, Z; Zhang, J; Mour, G; Northrup, D; Tripathi, A; Marsden, J E; Moran, W P; Mauldin, P D

    2017-03-01

    We sought proof of concept of a Big Data Solution incorporating longitudinal structured and unstructured patient-level data from electronic health records (EHR) to predict graft loss (GL) and mortality. For a quality improvement initiative, GL and mortality prediction models were constructed using baseline and follow-up data (0-90 days posttransplant; structured and unstructured for 1-year models; data up to 1 year for 3-year models) on adult solitary kidney transplant recipients transplanted during 2007-2015 as follows: Model 1: United Network for Organ Sharing (UNOS) data; Model 2: UNOS & Transplant Database (Tx Database) data; Model 3: UNOS, Tx Database & EHR comorbidity data; and Model 4: UNOS, Tx Database, EHR data, Posttransplant trajectory data, and unstructured data. A 10% 3-year GL rate was observed among 891 patients (2007-2015). Layering of data sources improved model performance; Model 1: area under the curve (AUC), 0.66; (95% confidence interval [CI]: 0.60, 0.72); Model 2: AUC, 0.68; (95% CI: 0.61-0.74); Model 3: AUC, 0.72; (95% CI: 0.66-077); Model 4: AUC, 0.84, (95 % CI: 0.79-0.89). One-year GL (AUC, 0.87; Model 4) and 3-year mortality (AUC, 0.84; Model 4) models performed similarly. A Big Data approach significantly adds efficacy to GL and mortality prediction models and is EHR deployable to optimize outcomes. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. Area under the curve as a novel metric of behavioral economic demand for alcohol.

    Science.gov (United States)

    Amlung, Michael; Yurasek, Ali; McCarty, Kayleigh N; MacKillop, James; Murphy, James G

    2015-06-01

    Behavioral economic purchase tasks can be readily used to assess demand for a number of addictive substances, including alcohol, tobacco, and illicit drugs. However, several methodological limitations associated with the techniques used to quantify demand may reduce the utility of demand measures. In the present study, we sought to introduce area under the curve (AUC), commonly used to quantify degree of delay discounting, as a novel index of demand. A sample of 207 heavy-drinking college students completed a standard alcohol purchase task and provided information about typical weekly drinking patterns and alcohol-related problems. Level of alcohol demand was quantified using AUC--which reflects the entire amount of consumption across all drink prices--as well as the standard demand indices (e.g., intensity, breakpoint, Omax, Pmax, and elasticity). Results indicated that AUC was significantly correlated with each of the other demand indices (rs = .42-.92), with particularly strong associations with Omax (r = .92). In regression models, AUC and intensity were significant predictors of weekly drinking quantity, and AUC uniquely predicted alcohol-related problems, even after controlling for drinking level. In a parallel set of analyses, Omax also predicted drinking quantity and alcohol problems, although Omax was not a unique predictor of the latter. These results offer initial support for using AUC as an index of alcohol demand. Additional research is necessary to further validate this approach and to examine its utility in quantifying demand for other addictive substances such as tobacco and illicit drugs. (c) 2015 APA, all rights reserved).

  17. Radiomic Machine Learning Classifiers for Prognostic Biomarkers of Head & Neck Cancer

    Directory of Open Access Journals (Sweden)

    Chintan eParmar

    2015-12-01

    Full Text Available Introduction: Radiomics extracts and mines large number of medical imaging features in a non-invasive and cost-effective way. The underlying assumption of radiomics is that these imaging features quantify phenotypic characteristics of entire tumor. In order to enhance applicability of radiomics in clinical oncology, highly accurate and reliable machine learning approaches are required. In this radiomic study, thirteen feature selection methods and eleven machine learning classification methods were evaluated in terms of their performance and stability for predicting overall survival in head and neck cancer patients. Methods: Two independent head and neck cancer cohorts were investigated. Training cohort HN1 consisted 101 HNSCC patients. Cohort HN2 (n=95 was used for validation. A total of 440 radiomic features were extracted from the segmented tumor regions in CT images. Feature selection and classification methods were compared using an unbiased evaluation framework. Results: We observed that the three feature selection methods MRMR (AUC = 0.69, Stability = 0.66, MIFS (AUC = 0.66, Stability = 0.69, and CIFE (AUC = 0.68, Stability = 0.7 had high prognostic performance and stability. The three classifiers BY (AUC = 0.67, RSD = 11.28, RF (AUC = 0.61, RSD = 7.36, and NN (AUC = 0.62, RSD = 10.52 also showed high prognostic performance and stability. Analysis investigating performance variability indicated that the choice of classification method is the major factor driving the performance variation (29.02% of total variance. Conclusions: Our study identified prognostic and reliable machine learning methods for the prediction of overall survival of head and neck cancer patients. Identification of optimal machine-learning methods for radiomics based prognostic analyses could broaden the scope of radiomics in precision oncology and cancer care.

  18. Relation of Left Ventricular Mass and Infarct Size in Anterior Wall ST-Segment Elevation Acute Myocardial Infarction (from the EMBRACE STEMI Clinical Trial).

    Science.gov (United States)

    Daaboul, Yazan; Korjian, Serge; Weaver, W Douglas; Kloner, Robert A; Giugliano, Robert P; Carr, Jim; Neal, Brandon J; Chi, Gerald; Cochet, Madeleine; Goodell, Laura; Michalak, Nathan; Rusowicz-Orazem, Luke; Alkathery, Turky; Allaham, Haytham; Routray, Sujit; Szlosek, Donald; Jain, Purva; Gibson, C Michael

    2016-09-01

    Biomarker measures of infarct size and myocardial salvage index (MSI) are important surrogate measures of clinical outcomes after a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post hoc analysis of Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE) ST-Segment Elevation Myocardial Infarction (STEMI) trial evaluates the association between left ventricular (LV) mass and infarct size as assessed by areas under the curve for creatine kinase-MB (CK-MB) and troponin I release over the first 72 hours (CK-MB area under the curve [AUC] and troponin I [TnI] AUC) and the MSI. Patients with first anterior STEMI, occluded left anterior descending artery, and available LV mass measurement in EMBRACE STEMI trial were included (n = 100) (ClinicalTrials.govNCT01572909). MSI, end-diastolic LV mass on day 4 cardiac magnetic resonance, and CK-MB and troponin I concentrations were evaluated by a core laboratory. After saturated multivariate analysis, dominance analysis was performed to estimate the contribution of each independent variable to the predicted variance of each outcome. In multivariate models that included age, gender, body surface area, lesion location, smoking, and ischemia time, LV mass remained independently associated with biomarker measures of infarct size (CK-MB AUC p = 0.02, TnI AUC p = 0.03) and MSI (p = 0.003). Dominance analysis demonstrated that LV mass accounted for 58%, 47%, and 60% of the predicted variances for CK-MB AUC, TnI AUC, and MSI, respectively. In conclusion, LV mass accounts for approximately half of the predicted variance in biomarker measures of infarct size. It should be considered as an adjustment variable in studies evaluating infarct size. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: an inter-species extrapolation approach.

    Science.gov (United States)

    Motwani, Hitesh V; Törnqvist, Margareta

    2014-12-15

    1,3-Butadiene (BD) is a rodent and human carcinogen. In the cancer tests, mice have been much more susceptible than rats with regard to BD-induced carcinogenicity. The species-differences are dependent on metabolic formation/disappearance of the genotoxic BD epoxy-metabolites that lead to variations in the respective in vivo doses, i.e. "area under the concentration-time curve" (AUC). Differences in AUC of the most gentoxic BD epoxy-metabolite, diepoxybutane (DEB), are considered important with regard to cancer susceptibility. The present work describes: the application of cob(I)alamin for accurate measurements of in vitro enzyme kinetic parameters associated with BD epoxy-metabolites in human, mouse and rat; the use of published data on hemoglobin (Hb) adduct levels of BD epoxides from BD exposure studies on the three species to calculate the corresponding AUCs in blood; and a parallelogram approach for extrapolation of AUC of DEB based on the in vitro metabolism studies and adduct data from in vivo measurements. The predicted value of AUC of DEB for humans from the parallelogram approach was 0.078 nM · h for 1 ppm · h of BD exposure compared to 0.023 nM · h/ppm · h as calculated from Hb adduct levels observed in occupational exposure. The corresponding values in nM · h/ppm · h were for mice 41 vs. 38 and for rats 1.26 vs. 1.37 from the parallelogram approach vs. experimental exposures, respectively, showing a good agreement. This quantitative inter-species extrapolation approach will be further explored for the clarification of metabolic rates/pharmacokinetics and the AUC of other genotoxic electrophilic compounds/metabolites, and has a potential to reduce and refine animal experiments. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Can machine-learning improve cardiovascular risk prediction using routine clinical data?

    Science.gov (United States)

    Weng, Stephen F; Reps, Jenna; Kai, Joe; Garibaldi, Jonathan M; Qureshi, Nadeem

    2017-01-01

    Current approaches to predict cardiovascular risk fail to identify many people who would benefit from preventive treatment, while others receive unnecessary intervention. Machine-learning offers opportunity to improve accuracy by exploiting complex interactions between risk factors. We assessed whether machine-learning can improve cardiovascular risk prediction. Prospective cohort study using routine clinical data of 378,256 patients from UK family practices, free from cardiovascular disease at outset. Four machine-learning algorithms (random forest, logistic regression, gradient boosting machines, neural networks) were compared to an established algorithm (American College of Cardiology guidelines) to predict first cardiovascular event over 10-years. Predictive accuracy was assessed by area under the 'receiver operating curve' (AUC); and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to predict 7.5% cardiovascular risk (threshold for initiating statins). 24,970 incident cardiovascular events (6.6%) occurred. Compared to the established risk prediction algorithm (AUC 0.728, 95% CI 0.723-0.735), machine-learning algorithms improved prediction: random forest +1.7% (AUC 0.745, 95% CI 0.739-0.750), logistic regression +3.2% (AUC 0.760, 95% CI 0.755-0.766), gradient boosting +3.3% (AUC 0.761, 95% CI 0.755-0.766), neural networks +3.6% (AUC 0.764, 95% CI 0.759-0.769). The highest achieving (neural networks) algorithm predicted 4,998/7,404 cases (sensitivity 67.5%, PPV 18.4%) and 53,458/75,585 non-cases (specificity 70.7%, NPV 95.7%), correctly predicting 355 (+7.6%) more patients who developed cardiovascular disease compared to the established algorithm. Machine-learning significantly improves accuracy of cardiovascular risk prediction, increasing the number of patients identified who could benefit from preventive treatment, while avoiding unnecessary treatment of others.

  1. Advances toward fully automated in vivo assessment of oral epithelial dysplasia by nuclear endomicroscopy-A pilot study.

    Science.gov (United States)

    Liese, Jan; Winter, Karsten; Glass, Änne; Bertolini, Julia; Kämmerer, Peer Wolfgang; Frerich, Bernhard; Schiefke, Ingolf; Remmerbach, Torsten W

    2017-11-01

    Uncertainties in detection of oral epithelial dysplasia (OED) frequently result from sampling error especially in inflammatory oral lesions. Endomicroscopy allows non-invasive, "en face" imaging of upper oral epithelium, but parameters of OED are unknown. Mucosal nuclei were imaged in 34 toluidine blue-stained oral lesions with a commercial endomicroscopy. Histopathological diagnosis showed four biopsies in "dys-/neoplastic," 23 in "inflammatory," and seven in "others" disease groups. Strength of different assessment strategies of nuclear scoring, nuclear count, and automated nuclear analysis were measured by area under ROC curve (AUC) to identify histopathological "dys-/neoplastic" group. Nuclear objects from automated image analysis were visually corrected. Best-performing parameters of nuclear-to-image ratios were the count of large nuclei (AUC=0.986) and 6-nearest neighborhood relation (AUC=0.896), and best parameters of nuclear polymorphism were the count of atypical nuclei (AUC=0.996) and compactness of nuclei (AUC=0.922). Excluding low-grade OED, nuclear scoring and count reached 100% sensitivity and 98% specificity for detection of dys-/neoplastic lesions. In automated analysis, combination of parameters enhanced diagnostic strength. Sensitivity of 100% and specificity of 87% were seen for distances of 6-nearest neighbors and aspect ratios even in uncorrected objects. Correction improved measures of nuclear polymorphism only. The hue of background color was stronger than nuclear density (AUC=0.779 vs 0.687) to detect dys-/neoplastic group indicating that macroscopic aspect is biased. Nuclear-to-image ratios are applicable for automated optical in vivo diagnostics for oral potentially malignant disorders. Nuclear endomicroscopy may promote non-invasive, early detection of dys-/neoplastic lesions by reducing sampling error. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Proteomic biomarkers predicting lymph node involvement in serum of cervical cancer patients. Limitations of SELDI-TOF MS

    Directory of Open Access Journals (Sweden)

    Van Gorp Toon

    2012-06-01

    Full Text Available Abstract Background Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. We investigated whether lymph node status can be predicted with proteomic profiling. Material & methods Serum samples of 60 cervical cancer patients (FIGO I/II were obtained before primary treatment. Samples were run through a HPLC depletion column, eliminating the 14 most abundant proteins ubiquitously present in serum. Unbound fractions were concentrated with spin filters. Fractions were spotted onto CM10 and IMAC30 surfaces and analyzed with surface-enhanced laser desorption time of flight (SELDI-TOF mass spectrometry (MS. Unsupervised peak detection and peak clustering was performed using MASDA software. Leave-one-out (LOO validation for weighted Least Squares Support Vector Machines (LSSVM was used for prediction of lymph node involvement. Other outcomes were histological type, lymphvascular space involvement (LVSI and recurrent disease. Results LSSVM models were able to determine LN status with a LOO area under the receiver operating characteristics curve (AUC of 0.95, based on peaks with m/z values 2,698.9, 3,953.2, and 15,254.8. Furthermore, we were able to predict LVSI (AUC 0.81, to predict recurrence (AUC 0.92, and to differentiate between squamous carcinomas and adenocarcinomas (AUC 0.88, between squamous and adenosquamous carcinomas (AUC 0.85, and between adenocarcinomas and adenosquamous carcinomas (AUC 0.94. Conclusions Potential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer. However, identification of the potential biomarkers was hampered by the technical limitations of SELDI-TOF MS.

  3. The impact of reliable prebolus T{sub 1} measurements or a fixed T{sub 1} value in the assessment of glioma patients with dynamic contrast enhancing MRI

    Energy Technology Data Exchange (ETDEWEB)

    Tietze, Anna [Aarhus University Hospital, Dept. of Neuroradiology, Aarhus (Denmark); Aarhus University, Center of Functionally Integrative Neuroscience, Aarhus (Denmark); Mouridsen, Kim; Mikkelsen, Irene Klaerke [Aarhus University, Center of Functionally Integrative Neuroscience, Aarhus (Denmark)

    2015-03-06

    Accurate quantification of hemodynamic parameters using dynamic contrast enhanced (DCE) MRI requires a measurement of tissue T{sub 1} prior to contrast injection (T{sub 1}). We evaluate (i) T{sub 1} estimation using the variable flip angle (VFA) and the saturation recovery (SR) techniques and (ii) investigate if accurate estimation of DCE parameters outperform a time-saving approach with a predefined T{sub 1} value when differentiating high- from low-grade gliomas. The accuracy and precision of T{sub 1} measurements, acquired by VFA and SR, were investigated by computer simulations and in glioma patients using an equivalence test (p > 0.05 showing significant difference). The permeability measure, K{sub trans}, cerebral blood flow (CBF), and - volume, V{sub p}, were calculated in 42 glioma patients, using fixed T{sub 1} of 1500 ms or an individual T{sub 1} measurement, using SR. The areas under the receiver operating characteristic curves (AUCs) were used as measures for accuracy to differentiate tumor grade. The T{sub 1} values obtained by VFA showed larger variation compared to those obtained using SR both in the digital phantom and the human data (p > 0.05). Although a fixed T{sub 1} introduced a bias into the DCE calculation, this had only minor impact on the accuracy differentiating high-grade from low-grade gliomas, (AUC{sub fix} = 0.906 and AUC{sub ind} = 0.884 for K{sub trans}; AUC{sub fix} = 0.863 and AUC{sub ind} = 0.856 for V{sub p;} p for AUC comparison > 0.05). T{sub 1} measurements by VFA were less precise, and the SR method is preferable, when accurate parameter estimation is required. Semiquantitative DCE values, based on predefined T{sub 1} values, were sufficient to perform tumor grading in our study. (orig.)

  4. In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

    Energy Technology Data Exchange (ETDEWEB)

    Motwani, Hitesh V., E-mail: hitesh.motwani@mmk.su.se; Törnqvist, Margareta

    2014-12-15

    1,3-Butadiene (BD) is a rodent and human carcinogen. In the cancer tests, mice have been much more susceptible than rats with regard to BD-induced carcinogenicity. The species-differences are dependent on metabolic formation/disappearance of the genotoxic BD epoxy-metabolites that lead to variations in the respective in vivo doses, i.e. “area under the concentration-time curve” (AUC). Differences in AUC of the most gentoxic BD epoxy-metabolite, diepoxybutane (DEB), are considered important with regard to cancer susceptibility. The present work describes: the application of cob(I)alamin for accurate measurements of in vitro enzyme kinetic parameters associated with BD epoxy-metabolites in human, mouse and rat; the use of published data on hemoglobin (Hb) adduct levels of BD epoxides from BD exposure studies on the three species to calculate the corresponding AUCs in blood; and a parallelogram approach for extrapolation of AUC of DEB based on the in vitro metabolism studies and adduct data from in vivo measurements. The predicted value of AUC of DEB for humans from the parallelogram approach was 0.078 nM · h for 1 ppm · h of BD exposure compared to 0.023 nM · h/ppm · h as calculated from Hb adduct levels observed in occupational exposure. The corresponding values in nM · h/ppm · h were for mice 41 vs. 38 and for rats 1.26 vs. 1.37 from the parallelogram approach vs. experimental exposures, respectively, showing a good agreement. This quantitative inter-species extrapolation approach will be further explored for the clarification of metabolic rates/pharmacokinetics and the AUC of other genotoxic electrophilic compounds/metabolites, and has a potential to reduce and refine animal experiments. - Highlights: • In vitro metabolism to in vivo dose extrapolation of butadiene metabolites was proposed. • A parallelogram approach was introduced to estimate dose (AUC) in humans and rodents. • AUC of diepoxybutane predicted in humans was 0.078 nM h/ppm h

  5. Fluconazole bioequivalence study: quantification by tandem mass spectrometry.

    Science.gov (United States)

    Moraes, L A; Lerner, F E; Moraes, M E; Moraes, M O; Corso, G; De Nucci, G

    1999-04-01

    To develop a new method for quantifying fluoconazole in human plasma and to compare the bioavailability of two fluconazole capsule formulations, an open, randomized, two-period crossover study with a one-week washout interval was conducted in 24 healthy volunteers. Plasma samples were obtained up to 168 hours after drug administration and the serum fluconazole concentrations were analyzed using electrospray tandem mass spectrometry coupled to liquid chromatography using multiple reaction monitoring mode. The pharmacokinetic parameters obtained for fluconazole after the administration of each formulation included the Area under the curve (AUC)(0-168h), AUC(0-infinity), Cmax, Cmax/AUC(0-168h), Tmax, elimination rate constant (Ke), and half-life (T1/2). Within- and between-run imprecision was less than 2.3% and 8.2%, respectively. Inaccuracy within and between runs was -1.5% and -9.7%, respectively. The pharmacokinetic parameters for bioequivalence showed a normal distribution, and the variance of AUC(0-168h), AUC(0-infinity), and Cmax were homoscedastic. The geometric mean for the Fluconal/Zoltec (Fluconal; Libbs Farmacêutica Ltda, São Paulo, Brazil; Zoltec; Laboratórios Pfizer Ltda., São Paulo, Brazil) individual percent ratio was 94.9% for AUC(0-168h), 94.7% for AUC(0-infinity), 80.1% for Cmax, 102.6% for Ke, 97.5% for T1/2, and 0.93 for Tmax (arithmetic mean of individual differences). We have developed a method in which liquid chromatography is coupled with electrospray tandem mass spectrometry to improve the pharmacokinetic analysis of fluconazole. Because the 90% CI AUC is within the interval proposed for the Food and Drug Administration, we concluded that Fluconal is bioequivalent to Zoltec in terms of absorption. The CV was 27.5% for the Cmax parameter, indicating that fluconazole's absorption rate is highly variable. The European Union Regulatory Agency accepts an interval of 70-143%, and because the 90% CI for Cmax is within the interval proposed for

  6. Effect of polymer type and drug dose on the in vitro and in vivo behavior of amorphous solid dispersions

    DEFF Research Database (Denmark)

    Knopp, Matthias Manne; Chourak, Nabil; Khan, Fauzan

    2016-01-01

    This study investigated the non-sink in vitro dissolution behavior and in vivo performance in rats of celecoxib (CCX) amorphous solid dispersions with polyvinyl acetate (PVA), polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) at different drug doses. Both in vitro and in vivo...... showed a lower AUC both in vitro and in vivo than crystalline CCX. For crystalline CCX and CCX:PVA, the in vitro AUC was limited by the low solubility of the drug and the slow release of the drug from the hydrophobic polymer, respectively. For the supersaturating formulations, amorphous CCX, CCX...

  7. Apparent diffusion coefficient ratio correlates significantly with prostate cancer gleason score at final pathology

    DEFF Research Database (Denmark)

    Boesen, Lars; Chabanova, Elizaveta; Løgager, Vibeke

    2015-01-01

    PURPOSE: To evaluate the correlation between apparent diffusion coefficient measurements (ADCtumor and ADCratio ) and the Gleason score from radical prostatectomy specimens. MATERIALS AND METHODS: Seventy-one patients with clinically localized prostate cancer scheduled for radical prostatectomy...... between ADC measurements and the Gleason score for all tumors (P = 0.001). Receiver operating characteristic curve analysis showed an overall area under the curve (AUC) of 0.73 (ADCtumor ) to 0.80 (ADCratio ) in discriminating Gleason score 6 from Gleason score ≥7 tumors. The AUC changed to 0.72 (ADCtumor...

  8. Pharmacokinetics of concentration-controlled mycophenolate mofetil in proliferative lupus nephritis: an observational cohort study.

    Science.gov (United States)

    Alexander, Suceena; Fleming, Denise H; Mathew, Binu S; Varughese, Santosh; Jeyaseelan, Visalakshi; Tamilarasi, Veerasamy; Jacob, Chakko K; John, George T

    2014-08-01

    Mycophenolate mofetil (MMF) has variable pharmacokinetics. This study examines the pharmacokinetic and clinical correlations in proliferative lupus nephritis. Thirty-four patients were started on MMF, and the area under the concentration-time curve (AUC) was measured by limited sampling strategies, and dosing was adjusted to achieve an AUC of 30-60 mg·h·L. Twenty-seven patients had at least 2 measurements, and renal response was assessed within 1 year. About 61.8% of patients had mycophenolic acid (MPA) AUC <30 mg·h·L with an empiric starting dose of 30 mg/kg. About 79.4% of patients achieved renal response by 1 year, and the median time to renal response was 111 days. MMF dose per body weight had a weak correlation with the AUC and did not correlate with trough concentrations. The median dose was 1.5 g/d at entry and 2 g/d after dose modification during the induction phase. Trough concentrations had a weak correlation with AUC. Patients with serum albumin ≥35 g/L had a greater chance of having an AUC ≥30 mg·h·L. The between-patient coefficient of variability for dose-normalized AUC was 37.9% at entry and 31% within 1 year, whereas repeated measurements over time in an individual had a good intraclass correlation of 0.78. Infections occurred in 11.8% and toxicities in 5.9%. MPA exposure was not significantly associated with adverse events. Patients with an AUC ≥30 mg·h·L had greater renal response at 1 year. Lupus nephritis patients induced with concentration-controlled MMF had excellent renal response and fewer adverse events with lower than usual dosing. MPA exposure had high interpatient variability, requiring measurements for personalized dosing, and fewer adverse events. Long-term cost reduction is achievable with lower doses and good renal response in the majority of patients.

  9. Abdominal mesotherapy injection extended the absorption of follicle-stimulating hormone.

    Science.gov (United States)

    Hsu, Chao-Chin; Kuo, Hsin-Chih; Hsu, Chao-Tien; Gu, Qing

    2011-05-01

    Abdominal mesotherapy injection of recombinant human FSH (rhFSH) was well tolerated with increased net absorption (AUC0-∞ 4,655.3 IU·h/L and t1/2 247.6 h) up to 360 hours compared with those of 120 hours (AUC0-∞ 1,915.7 IU·h/L and t1/2 101.8 h). The extended absorption of rhFSH suggests that abdominal mesotherapy injection mode be considered for future administration of rhFSH in controlled ovarian hyperstimulation. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Effects of erythromycin at steady-state concentrations on the pharmacokinetics of ulipristal acetate.

    Science.gov (United States)

    Pohl, O; Osterloh, I; Gotteland, J-P

    2013-12-01

    Ulipristal acetate (UPA) is a novel selective progesterone receptor modulator for the treatment of benign gynaecological conditions such as uterine myoma. In vitro, it is mainly metabolized by the cytochrome P450 isoenzyme CYP3A4 and to a small extent by CYP1A2 and CYP2D6. Erythromycin, a macrolide antibiotic, has been shown to be a moderate CYP3A4 inhibitor. Thus, the aim of this study was to determine the effects of erythromycin at steady-state concentrations on the pharmacokinetics of UPA. Effects on the pharmacokinetics of the mono-demethylated metabolite of UPA (PGL4002) were also evaluated. This was a non-randomized, single-sequence, two-period, open, single-dose study in 18 healthy female subjects. Subjects received oral UPA (20 mg) once daily on days 1 and 13 and twice-daily erythromycin propionate administrations (500 mg) from days 9 through 17. Geometric mean Cmax and AUCs of UPA were increased by 24% [geometric mean ratio point estimate (90% CI): 1·24 (1·01-1·52)] and +224% and +227% [geometric mean ratio point estimates (90% CI): AUC0-t 3·24 (2·75-3·83) and AUC0-∞ (3·27 (2·79-3·83)], respectively, with no effect on median tmax or t1/2. Geometric mean Cmax of PGL4002 was decreased by 47% [geometric mean ratio point estimate (90% CI): 0·523 (0·44-0·62)], but AUCs were increased by +62% and +66% [geometric mean ratio point estimates (90% CI): AUC0-t 1·62 (1·43-1·85) and AUC0-∞ by 1·66 (1·47-1·88)], respectively, with no effect on median tmax. However, geometric mean t1/2.doubled from 24 h to 48 h. No subject was discontinued from the study due to adverse events. Concomitant use of ulipristal acetate with erythromycin at therapeutic concentrations led to a limited increase in Cmax and a 3-fold increase in AUCs for UPA and to a decrease in Cmax and an increase in AUCs and prolonged elimination for PGL4002. This indicates that inhibition of CYP3A4 impacted rate and extent of absorption of UPA and also its metabolism by slowing the

  11. Dynamic contrast-enhanced case-control analysis in 3T MRI of prostate cancer can help to characterize tumor aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Sanz-Requena, Roberto, E-mail: roberto.sanz@quironsalud.es [Biomedical Engineering, Hospital Quirónsalud Valencia, Valencia (Spain); Radiology Department, Hospital Quirónsalud Valencia, Valencia (Spain); GIBI230, Instituto de Investigación Sanitaria y Hospital Universitari i Politècnic La Fe, Valencia (Spain); Martí-Bonmatí, Luis [Radiology Department, Hospital Quirónsalud Valencia, Valencia (Spain); GIBI230, Instituto de Investigación Sanitaria y Hospital Universitari i Politècnic La Fe, Valencia (Spain); Pérez-Martínez, Rosario [Radiology Department, Hospital Quirónsalud Valencia, Valencia (Spain); García-Martí, Gracián [Biomedical Engineering, Hospital Quirónsalud Valencia, Valencia (Spain); Radiology Department, Hospital Quirónsalud Valencia, Valencia (Spain); GIBI230, Instituto de Investigación Sanitaria y Hospital Universitari i Politècnic La Fe, Valencia (Spain); CIBER-SAM, Instituto de Salud Carlos III, Madrid (Spain)

    2016-11-15

    Highlights: • Curve types showed no statistical association with healthy/tumor peripheral areas. • K{sup trans}, v{sub e}, upslope and AUC showed significant differences in controls vs. tumors. • The global diagnostic performance of standard MRI perfusion parameters is poor. • Normalized K{sup trans}, upslope and AUC had good diagnostic accuracy for tumor grading. - Abstract: Purpose: The aim of this work is to establish normality and tumor tissue ranges for perfusion parameters from dynamic contrast-enhanced (DCE) MR of the peripheral prostate at 3T and to compare the diagnostic performance of quantitative and semi-quantitative parameters. Materials and methods: Thirty-six patients with prostate carcinomas (18 Gleason-6, 15 Gleason-7, and 3 Gleason-8) and 33 healthy subjects were included. Image analysis workflow comprised four steps: manual segmentation of whole prostate and lesions, series registration, voxelwise T1 mapping and calculation of pharmacokinetic and semi-quantitative parameters. Results: K{sup trans}, v{sub e}, upslope and AUC60 showed statistically significant differences between healthy peripheral areas and tumors. Curve type showed no association with healthy/tumor peripheral areas (chi-square = 0.702). Areas under the ROC curves were 0.64 (95% CI: 0.54–0.75), 0.70 (0.60–0.80), 0.62 (0.51–0.72) and 0.63 (0.52–0.74) for K{sup trans}, v{sub e}, upslope and AUC60, respectively. The optimal cutoff values were: K{sup trans} = 0.21 min{sup −1} (sensitivity = 0.61, specificity = 0.64), v{sub e} = 0.36 (0.63, 0.71), upslope = 0.59 (0.59, 0.59) and AUC60 = 2.4 (0.63, 0.64). Significant differences were found between Gleason scores 6 and 7 for normalized K{sup trans}, upslope and AUC60, with good diagnostic accuracy (area under ROC curve 0.80, 95% CI: 0.60–1.00). Conclusion: Quantitative (K{sup trans} and v{sub e}) and semi-quantitative (upslope and AUC60) perfusion parameters showed significant differences between tumors and control

  12. Relative bioavailability of griseofulvin lyophilized dry emulsion tablet vs. immediate release tablet: a single-dose, randomized, open-label, six-period, crossover study in healthy adult volunteers in the fasted and fed states.

    Science.gov (United States)

    Ahmed, Iman Saad; Aboul-Einien, Mona Hassan; Mohamed, Osama Hussein; Farid, Samar Farghali

    2008-10-02

    The oral bioavailability of griseofulvin (GF) formulated as a fast disintegrating lyophilized dry emulsion (LDE) tablet was studied and compared to the commercially available immediate release (IR) tablet, as a reference, in both the fasted and fed states in nine healthy volunteers after a single oral dose (125 mg) in a crossover design. Furthermore the LDE tablets were ingested with and without water under both the fasted and fed states. In the fasted state, the rate of absorption was found to be significantly faster from LDE tablets, in the presence and absence of water, as shown by a higher C(max) (more than two times higher, p=0.0001) and a shorter t(max) (by more than 3h, p=0.0001) compared to IR tablets. The extent of absorption, expressed as AUC, from LDE tablets in the presence and absence of water was 65% and 77% larger and statistically significantly different relative to the mean AUC from IR tablets (p=0.006). In the fed state, C(max) from LDE tablets ingested with and without water was found to be about 30% and 50% higher, respectively, than the immediate release tablets. A shorter t(max) was also shown whether LDE tablets were ingested with or without water in the fed state as compared to immediate release tablets. The mean AUC from LDE tablets under fed conditions in the presence of water was about 21% larger and was not statistically significantly different from AUC from immediate release tablets (p=0.517). When ingested without water, AUC from LDE tablets was about 43% larger and statistically significantly different relative to AUC from IR tablets (p=0.033). The mean AUC from the LDE tablet ingested with water under fed conditions relative to AUC from LDE tablet ingested without water was not statistically significantly different (p=0.454). Results show that the food effect of the high fat meal is very pronounced in case of the immediate release tablets, Fulvin, than in case of LDE tablets whether given with or without water.

  13. The inflammatory marker suPAR after cardiac arrest

    DEFF Research Database (Denmark)

    Rundgren, Malin; Lyngbaek, Stig; Fisker, Helle

    2015-01-01

    BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is released in response to inflammatory stimuli, and plasma levels are associated with long-term outcomes. The ischemia/reperfusion injury caused by cardiac arrest (CA) and resuscitation triggers an inflammatory response...... analysis shoved an AUC of 0.76 at 6 hours. In the subgroup of CA of cardiac cause, the AUC was 0.84. CONCLUSION: suPAR levels at 6 and 36 hours after CA were significantly higher in nonsurviving patients compared with survivors; however, the overlap in suPAR levels between the outcome groups...

  14. The use of molecular analyses in voided urine for the assessment of patients with hematuria

    DEFF Research Database (Denmark)

    Beukers, Willemien; Kandimalla, Raju; van Houwelingen, Diandra

    2013-01-01

    variables into a logistic regression model. Results Logistic regression analysis based on the five methylation markers, age, gender and type of hematuria resulted in an area under the curve (AUC) of 0.88 and an optimism corrected AUC of 0.84 after internal validation by bootstrapping. Using a cut-off value...... examination of low risk patients and thereby, reducing patient burden and costs. Further validation in a large prospective patient cohort is necessary to prove the true clinical value of this model....

  15. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...... different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging....

  16. Ocular kinetics of pefloxacin after intramuscular administration in albino and pigmented rabbits.

    OpenAIRE

    Cochereau-Massin, I; Bauchet, J; Faurisson, F; Vallois, J M; Lacombe, P.; Pocidalo, J J

    1991-01-01

    We determined the ocular kinetics of pefloxacin, a new fluoroquinolone, when administered by the intramuscular route to albino and pigmented rabbits. In serum of albino rabbits, the area under the concentration-time curve (AUC) for the experimental period was 31.4 +/- 1.07 micrograms.h/ml (mean +/- standard deviation); the AUCs in the aqueous and vitreous humors were high (10.5 +/- 1.90 and 12.4 +/- 3.79 micrograms.h/ml, respectively). Pefloxacin was found in the avascular ocular tissues (30....

  17. Textural features of {sup 18}F-fluorodeoxyglucose positron emission tomography scanning in diagnosing aortic prosthetic graft infection

    Energy Technology Data Exchange (ETDEWEB)

    Saleem, Ben R.; Zeebregts, Clark J. [University of Groningen, University Medical Center Groningen, Department of Surgery, Division of Vascular Surgery, P.O. Box 30 001, Groningen (Netherlands); Beukinga, Roelof J.; Slart, Riemer H.J.A. [University of Groningen, University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Twente, Department of Biomedical Photonic Imaging (BMPI), Enschede (Netherlands); Boellaard, Ronald; Glaudemans, Andor W.J.M. [University of Groningen, University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Reijnen, Michel M.P.J. [Rijnstate Hospital, Department of Surgery, Arnhem (Netherlands)

    2017-05-15

    The clinical problem in suspected aortoiliac graft infection (AGI) is to obtain proof of infection. Although {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography scanning (PET) has been suggested to play a pivotal role, an evidence-based interpretation is lacking. The objective of this retrospective study was to examine the feasibility and utility of {sup 18}F-FDG uptake heterogeneity characterized by textural features to diagnose AGI. Thirty patients with a history of aortic graft reconstruction who underwent {sup 18}F-FDG PET/CT scanning were included. Sixteen patients were suspected to have an AGI (group I). AGI was considered proven only in the case of a positive bacterial culture. Positive cultures were found in 10 of the 16 patients (group Ia), and in the other six patients, cultures remained negative (group Ib). A control group was formed of 14 patients undergoing {sup 18}F-FDG PET for other reasons (group II). PET images were assessed using conventional maximal standardized uptake value (SUVmax), tissue-to-background ratio (TBR), and visual grading scale (VGS). Additionally, 64 different {sup 18}F-FDG PET based textural features were applied to characterize {sup 18}F-FDG uptake heterogeneity. To select candidate predictors, univariable logistic regression analysis was performed (α = 0.16). The accuracy was satisfactory in case of an AUC > 0.8. The feature selection process yielded the textural features named variance (AUC = 0.88), high grey level zone emphasis (AUC = 0.87), small zone low grey level emphasis (AUC = 0.80), and small zone high grey level emphasis (AUC = 0.81) most optimal for distinguishing between groups I and II. SUVmax, TBR, and VGS were also able to distinguish between these groups with AUCs of 0.87, 0.78, and 0.90, respectively. The textural feature named short run high grey level emphasis was able to distinguish group Ia from Ib (AUC = 0.83), while for the same task the TBR and VGS were not found to be predictive

  18. Efficacy and tolerability of a new ibuprofen 200mg plaster in patients with acute sports-related traumatic blunt soft tissue injury/contusion.

    Science.gov (United States)

    Predel, Hans-Georg; Giannetti, Bruno; Connolly, Mark P; Lewis, Fraser; Bhatt, Aomesh

    2018-01-01

    Ibuprofen is used for the treatment of non-serious pain. This study assessed the efficacy and safety of a new ibuprofen plaster for the treatment of pain associated with acute sports impact injuries/contusions. In this randomised, double-blind, multi-centre, placebo controlled, parallel group study, adults (n = 130; 18-58 years of age) diagnosed with acute sports-related blunt soft tissue injury/contusion were randomized to receive either ibuprofen 200 mg plaster or placebo plaster. Plasters were administered once daily for five consecutive days. The primary assessment was area under the visual analogue scale (VAS) of pain on movement (POM) over 0 to three days (VAS AUC0-3d). Other endpoints included algometry AUC from 0 to three days (AUC0-3d) and 0 to five days (AUC0-5d), to evaluate improvement of sensitivity at the injured site, and patient and investigator global assessment of efficacy. Safety was monitored throughout the study. The ibuprofen plaster resulted in superior reduction in AUC0-3d compared with placebo; the Least Squares (LS) mean difference was 662.82 mm*h in favour of the ibuprofen 200mg plaster (P = 0.0011). The greater improvement in VAS AUC of POM was also observed after 12 h, 24 h, and five days of therapy. Tenderness also significantly improved with the ibuprofen plaster compared with placebo; LS mean difference in algometry/tenderness AUC0-3d was 1.87 N/cm2*d and AUC0-5d was 1.87 N/cm2*d (P values ≤0.0004). At all study timepoints, a greater percentage of patients and investigators rated the effectiveness of the ibuprofen 200 mg plaster as good/excellent than the placebo plaster. Treatment-emergent adverse events for the ibuprofen plaster were few (≤1.5%) and were mild in severity. The results of this study indicate 200 mg plaster is effective and safe for the treatment of pain due to acute sports-related traumatic blunt soft tissue injury/contusion in adults.

  19. A program for computing the prediction probability and the related receiver operating characteristic graph.

    Science.gov (United States)

    Jordan, Denis; Steiner, Marcel; Kochs, Eberhard F; Schneider, Gerhard

    2010-12-01

    Prediction probability (P(K)) and the area under the receiver operating characteristic curve (AUC) are statistical measures to assess the performance of anesthetic depth indicators, to more precisely quantify the correlation between observed anesthetic depth and corresponding values of a monitor or indicator. In contrast to many other statistical tests, they offer several advantages. First, P(K) and AUC are independent from scale units and assumptions on underlying distributions. Second, the calculation can be performed without any knowledge about particular indicator threshold values, which makes the test more independent from specific test data. Third, recent approaches using resampling methods allow a reliable comparison of P(K) or AUC of different indicators of anesthetic depth. Furthermore, both tests allow simple interpretation, whereby results between 0 and 1 are related to the probability, how good an indicator separates the observed levels of anesthesia. For these reasons, P(K) and AUC have become popular in medical decision making. P(K) is intended for polytomous patient states (i.e., >2 anesthetic levels) and can be considered as a generalization of the AUC, which was basically introduced to assess a predictor of dichotomous classes (e.g., consciousness and unconsciousness in anesthesia). Dichotomous paradigms provide equal values of P(K) and AUC test statistics. In the present investigation, we introduce a user-friendly computer program for computing P(K) and estimating reliable bootstrap confidence intervals. It is designed for multiple comparisons of the performance of depth of anesthesia indicators. Additionally, for dichotomous classes, the program plots the receiver operating characteristic graph completing information obtained from P(K) or AUC, respectively. In clinical investigations, both measures are applied for indicator assessment, where ambiguous usage and interpretation may be a consequence. Therefore, a summary of the concepts of P(K) and

  20. Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3-<36 months

    DEFF Research Database (Denmark)

    NN, NN; Valerius, Niels Henrik

    2010-01-01

    the plasma concentration-time curve over 24 h (AUC(0-24)) and the maximum concentration (C(max)) were compared using geometric mean ratios (GMRs); 90% confidence intervals (CIs) within the range of 0.80-1.25 were considered bioequivalent. RESULTS: A total of 18 children (4, 6 and 8 in the 3-...-daily dosing: abacavir and lamivudine GMRs were 2.04 (90% CI 1.73-2.42) and 1.78 (90% CI 1.52-2.09), respectively. At baseline, 12, 24 and 48 weeks, 89%, 94%, 100% and 89% of children had HIV-1 RNABioequivalence was demonstrated on AUC(0-24) between twice...

  1. Evaluation of Diagnostic Accuracy and its Standard Error using Constant Shape Weibull Mixture ROC Curve

    Directory of Open Access Journals (Sweden)

    Sudesh Pundir

    2016-12-01

    Full Text Available Receiver Operating Characteristic (ROC Curve is a widely used classification technique in Medical Diagnosis which classifies the healthy and diseased individuals on the basis of optimal cut off value of the biomarker. In this article, we have proposed Constant Shape Weibull Mixture ROC (CSWMROC model. The properties of CSWMROC Curve are discussed and expressions for AUC, its variance and confidence interval are derived. The estimates of AUC of CSWMROC curve are obtained using Method of Moments (MOM. Numerical example is considered to support the proposed theory.

  2. Short-Term Effects of Lupin vs. Whey Supplementation on Glucose and Insulin Responses to a Standardized Meal in a Randomized Cross-Over Trial.

    Science.gov (United States)

    Schopen, Kathrin; Ewald, Ann C; Johannes, Bernd W; Bloch, Wilhelm; Rittweger, Jörn; Frings-Meuthen, Petra

    2017-01-01

    Background: Whey protein is known to reduce postprandial glycaemia in people with type 2 diabetes mellitus. Lupin as a vegetable source of protein could be considered as an alternative, as the percentage of vegetarian and vegan consumers is raising. The present study compares the acute glycemic effects of whey and lupin in healthy volunteers following a carbohydrate-rich reference meal. Methods In cross-over design, three standardized meals (reference meal; reference meal + whey; reference meal + lupin) were provided to 12 healthy male and female volunteers, aged between 23 and 33, in a balanced, randomized order. Volunteers' blood glucose and insulin concentrations were analyzed at baseline and at seven time points following the ingestion of the meals. Results: The supplementation of whey or lupin significantly blunted the postprandial increase in blood glucose concentrations compared to the reference meal (p < 0.001). In the overall statistical analysis, this effect was comparable for whey and lupin [Δ AUC whey-lupin = 8%, 0-60 min area under the curve (0-60 min AUC), p = 0.937], with a blunting effect of -46% by whey (p = 0.005, 0-60 min AUC) and of -54% by lupin (p < 0.001, 0-60 min AUC). When comparing whey and lupin data only, the insulin increase was found to be more pronounced for whey protein than for lupin supplementation (Δ AUC whey-lupin = 39%, 0-60 min AUC, p = 0.022). However, when comparing the insulin response of each supplementation to the one of the reference meal, no differences could be detected (whey p = 0.259, 0-60 min AUC; lupin p = 0.275, 0-60 min AUC). Conclusions: Results suggest that lupin and whey can both lower the increase of postprandial blood glucose concentrations to a comparable extent, implying the usability of lupin to reduce postprandial glycaemia. However, the insulin response following the supplementations to a carbohydrate-rich meal seems to differ for these two protein sources.

  3. Pharmacokinetics of single oral dose trazodone : a randomized, two-period, cross-over trial in healthy, adult, human volunteers under fed condition

    Directory of Open Access Journals (Sweden)

    PRASHANT eKALE

    2015-10-01

    Full Text Available Objective To assess the bioequivalence of single dose trazodone hydrochloride USP 100 mg tablets administered as an oral dose under fed condition. Methods This study was an open-label, balanced, randomized, two-sequence, two-treatment, two-period, single oral dose, crossover bioequivalence study in healthy, adult, human subjects under fed conditions. After an overnight fast of at least 10 hours, the subjects were served a high fat and high calorie vegetarian breakfast, which they were required to consume within 30 minutes. A single oral dose (100 mg of either the test or the reference product was administered to the subjects. The primary pharmacokinetic parameters, maximum plasma concentration (Cmax and area under the plasma concentration–time curve (AUC from time zero to last measurable concentration (AUC0-t and extrapolated to infinity (AUC0- were compared by an analysis of variance using log-transformed data. Bioequivalence was concluded if the 90% confidence intervals (CIs of the adjusted geometric mean (gMean ratios for Cmax and AUC were within the predetermined range of 80%-125%, in accordance with regulatory requirements. Results For the test formulation, the trazodone gMean Cmax was 1480.9 ng/mL (vs. 1520.2 ng/mL for reference, AUC0-t was 18193.0 ng·h/mL (vs. 18209.8 ng·h/mL and AUC0- was 19346.3 ng·h/mL (vs. 19393.4 ng·h/mL. The 90% CIs for the ratio (test/reference were 93.0-102.0% for Cmax, 96.7-103.2% for AUC0-t and 96.1-103.5% for AUC0-. There were no deaths or serious adverse events during the conduct of the study. Conclusion Test product when compared with the Reference product meets the bioequivalence criteria with respect to the rate and extent of absorption of Trazodone under fed condition.

  4. Comparison of different models for susceptibility mapping of earthquake triggered landslides related with the 2008 Wenchuan earthquake in China

    Science.gov (United States)

    Xu, Chong; Xu, Xiwei; Dai, Fuchu; Saraf, Arun K.

    2012-09-01

    The main purpose of this study is to compare the following six GIS-based models for susceptibility mapping of earthquake triggered landslides: bivariate statistics (BS), logistic regression (LR), artificial neural networks (ANN), and three types of support vector machine (SVM) models that use the three different kernel functions linear, polynomial, and radial basis. The models are applied in a tributary watershed of the Fu River, a tributary of the Jialing River, which is part of the area of China affected by the May 12, 2008 Wenchuan earthquake. For this purpose, eleven thematic data layers are used: landslide inventory, slope angle, aspect, elevation, curvature, distance from drainages, topographic wetness index (TWI), distance from main roads, distance from surface rupture, peak ground acceleration (PGA), and lithology. The data layers were specifically constructed for analysis in this study. In the subsequent stage of the study, susceptibility maps were produced using the six models and the same input for each one. The validations of the resulting susceptibility maps were performed and compared by means of two values of area under curve (AUC) that represent the respective success rates and prediction rates. The AUC values obtained from all six results showed that the LR model provides the highest success rate (AUC=80.34) and the highest prediction rate (AUC=80.27). The SVM (radial basis function) model generates the second-highest success rate (AUC=80.302) and the second-highest prediction rate (AUC=80.151), which are close to the value from the LR model. The results using the SVM (linear) model show the lowest AUC values. The AUC values from the SVM (linear) model are only 72.52 (success rates) and 72.533 (prediction rates). Furthermore, the results also show that the radial basis function is the most appropriate kernel function of the three kernel functions applied using the SVM model for susceptibility mapping of earthquake triggered landslides in the study

  5. Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency.

    Science.gov (United States)

    Rousseau, Elise; Joubert, Michael; Trzepla, Géraldine; Parienti, Jean Jacques; Freret, Thomas; Vanthygem, Marie Christine; Desailloud, Rachel; Lefebvre, Hervé; Coquerel, Antoine; Reznik, Yves

    2015-01-01

    Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated. Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients' cortisol AUC in the control range. Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement. Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone

  6. Pharmacokinetics and bioequivalence of a pregabalin 150-mg capsule in healthy Thai subjects.

    Science.gov (United States)

    Prompila, Nantaporn; Eiamart, Wanna; Jumroen, Yaowatree; Sayankuldilok, Nonlanee; Chariyavilaskul, Pajaree; Ketchat, Wannarasami; Wittayalertpanya, Supeecha

    2017-10-01

    The purpose of the study was to evaluate the pharmacokinetics and bioequivalence of pregabalin following administration of a 150-mg capsule of test and reference products. The study was designed as a randomized, two-treatment, two-period, two-sequence, single-dose crossover with 1-week washout period between period I and period II dosing. 20 healthy male and female Thai subjects were enrolled in the study. Each subject was in fasted state for ~ 10 hours prior to receiving a single oral 150-mg pregabalin capsule. Serial blood samples were collected at pre-dose until 32 hours after drug administration. Plasma samples were extracted by protein precipitation and derivatized with 4-chloro-7-nitrobenzofurazan. Pregabalin plasma concentrations were determined by HPLC method, and pharmacokinetic parameters were calculated. For bioequivalence assessment, the differences of Cmax, AUC0-t, and AUC0-inf means based on ln-transformed data were assessed by the 90% confidence interval (CI). Pharmacokinetic parameters were determined that test and reference products showed 0.96 ± 0.35 and 1.04 ± 0.96 hours for tmax, 4,594.217 ± 834.195 and 4,568.68 ± 573.963 ng/mL for Cmax, 30,048.150 ± 2,998.920 and 29,315.722 ± 2,747.396 ng×h/mL for AUC0-t, 30,594.210 ± 2,872.317 and 29,831.454 ± 2,688.020 ng×h/mL for AUC0-inf, respectively. The 90% CIs of Cmax, AUC0-t, and AUC0-inf for test and reference products were assessed at 95.356 - 104.630%, 99.303 - 105.751%, and 99.373 - 105.788%, respectively. The results were within the acceptance criteria of 80 - 125%. Pharmacokinetic parameters of a single oral 150-mg pregabalin capsule in healthy Thai subjects were evaluated and showed rapid absorption. 90% CI for the differences of Cmax, AUC0-t, and AUC0-inf were within the acceptable range of the criteria so that bioequivalence of the test and reference products of pregabalin 150-mg capsule could be concluded.
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  7. A pharmacokinetic comparison of single doses of once-daily cyclobenzaprine extended-release 15 mg and 30 mg: a randomized, double-blind, two-period crossover study in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Chang, Steven; Hellriegel, Edward T

    2009-01-01

    The purpose of this study was to compare the pharmacokinetics and tolerability of single oral doses of cyclobenzaprine extended-release (CER) 15- and 30-mg capsules. This was a randomized, double-blind, 2-period crossover study in healthy adults aged 18 to 40 years. Subjects were assigned to receive a single dose of either CER 15 mg or 30 mg on days 1 and 15, separated by a 14-day washout. Study comparisons included the plasma cyclobenzaprine AUC to 168 hours after dosing (AUC(0-168)), AUC(0-infinity), and C(max). Plasma cyclobenzaprine T(max), terminal elimination t(1/2), and adverse events (AEs) were also assessed. Sixteen subjects (9 women, 7 men) were randomized to receive cyclobenzaprine 15 mg or 30 mg; 13 (81.3%) were white and 3 (18.8%) were black. Mean age and weight were 30.2 years and 70.7 kg, respectively. The shapes of the pharmacokinetic profiles for CER 15 and 30 mg were parallel. Mean observed values for dose-dependent pharmacokinetic parameters of CER 15 and 30 mg were as follows: AUC(0-168), 318.3 and 736.6 ng . h/mL, respectively; AUC(0-infinity)), 354.1 and 779.9 ng . h/mL; and C(max), 8.3 and 19.9 ng/mL. Dose-independent parameters were comparable across doses. Median observed Tmax was 6.0 hours for both CER doses; mean t(1/2) was 33.4 hours for CER 15 mg and 32.0 hours for CER 30 mg. The bioavailability of the 2 doses, as indicated by the least squares mean AUC(0-infinity), was 330.3 ng . h/mL for CER 15 mg and 755.1 ng . h/mL for CER 30 mg. During the CER 15-mg treatment sequence, 5 subjects experienced 5 AEs (headache, dizziness, musculoskeletal pain, dermatitis, and glossodynia); during the CER 30-mg treatment sequence, 2 subjects experienced 2 AEs (somnolence and dysmenorrhea). All AEs were mild in intensity. No serious AEs occurred during the study. Once-daily CER 15 and 30 mg exhibited similarly shaped pharmacokinetic profiles. AUC(0-168), AUC(0-infinity)), and C(max) values for the 30-mg dose were approximately double those for the 15-mg

  8. Separate Evaluation of the Ipsilateral and Contralateral MR Fetal Lung Volume in Patients With Congenital Diaphragmatic Hernia.

    Science.gov (United States)

    Hagelstein, Claudia; Burger-Scheidlin, Stefan; Weis, Meike; Weiss, Christel; Schoenberg, Stefan O; Schaible, Thomas; Neff, K Wolfgang

    2016-08-01

    Our study had two objectives. First, we separately evaluated observed-to-expected MR fetal lung volume (FLV) of lungs ipsilateral and contralateral to a congenital diaphragmatic hernia (CDH). Second, we compared the prognostic value of observed-to-expected MR FLV of the ipsilateral and contralateral lungs with that of observed-to-expected MR FLV of both lungs with respect to survival, need for extracorporeal membrane oxygenation (ECMO), and development of chronic lung disease (CLD). We evaluated observed-to-expected MR FLV of the lung ipsilateral to the diaphragmatic defect as well as in the contralateral lung in 107 fetuses with isolated CDH. ROC analysis and logistic regression analysis were performed to assess the prognostic value of the observed-to-expected MR FLV for association with outcome. In all fetuses with CDH, values in the ipsilateral (mean observed-to-expected MR FLV ± SD, 9.4% ± 9.6%) and the contralateral lung (mean observed-to-expected MR FLV, 48.9% ± 18.5%; p lungs and of the contralateral and ipsilateral lung revealed significant differences regarding survival (p lungs, the observed-to-expected MR FLV of the contralateral lung showed a slightly higher prognostic accuracy regarding survival (AUC = 0.859 vs 0.825) and development of CLD (AUC = 0.734 vs 0.732) and a similar prognostic accuracy regarding need for ECMO (AUC = 0.805 vs 0.826). Observed-to-expected MR FLV of the ipsilateral lung did not show good prognostic value regarding survival (AUC = 0.617), need for ECMO (AUC = 0.673), and development of CLD (AUC = 0.636). These AUCs were significantly smaller than the AUCs resulting from the observed-to-expected MR FLV of both lungs (each p lung (each p lungs compared with healthy fetuses. The observed-to-expected MR FLV of both lungs as well as of the lung contralateral to the CDH were reliable prenatal predictors of survival, need for ECMO, and development of CLD.

  9. Venlafaxine and oxycodone effects on human spinal and supraspinal pain processing

    DEFF Research Database (Denmark)

    Lelic, D; Fischer, I W D; Olesen, A E

    2016-01-01

    Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids, the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine...... and AUCs were computed for the major EP peaks and brain source analysis was done. The NWR was decreased in venlafaxine arm (P = 0.02), but the EP parameters did not change. Oxycodone increased the AUC of the EP response (P = 0.04). Oxycodone also shifted the cingulate activity anteriorly in the mid......-cingulate-operculum network (P

  10. Association of osteolytic lesions, bone mineral loss and trabecular sclerosis with prevalent vertebral fractures in patients with multiple myeloma.

    Science.gov (United States)

    Borggrefe, J; Giravent, S; Campbell, G; Thomsen, F; Chang, D; Franke, M; Günther, A; Heller, M; Wulff, A

    2015-11-01

    In patients with multiple myeloma (MM), computed tomography is widely used for staging and to detect fractures. Detecting patients at severe fracture risk is of utmost importance. However the criteria for impaired stability of vertebral bodies are not yet clearly defined. We investigated the performance of parameters that can be detected by the radiologist for discrimination of patients with and without fractures. We analyzed 128 whole body low-dose CT of MM patients. In all scans a QCT calibration phantom was integrated into the positioning mat (Image Analysis Phantom(®)). A QCT-software (Structural Insight) performed the volumetric bone mineral density (vBMD) measurements. Description of fracture risk was provided from the clinical radiological report. Suspected progressive disease (PD) was reported by the referring clinicians. Two radiologists that were blinded to study outcome reported on the following parameters based on predefined criteria: reduced radiodensity in the massa lateralis of the os sacrum (RDS), trabecular thickening and sclerosis of three or more vertebrae (TTS), extraosseous MM manifestations (EOM), visible small osteolytic lesions up to a length of 8mm (SO) and osteolytic lesions larger than 8mm (LO). Prevalent vertebral fractures (PVF) were defined by Genant criteria. Age-adjusted standardized odds ratios (sOR) per standard deviation change were derived from logistic regression analysis and area under the curve (AUC) from receiver operating characteristics (ROC) analyses were calculated. ROC curves were compared using the DeLong method. 45% of the 128 patients showed PVF (29 of 75 men, 24 of 53 women). Patients with PVF were not significantly older than patients without fractures (64.6 ± 9.2 vs. 63.3 ± 12.3 years: mean ± SD, p=0.5). The prevalence of each parameter did not differ significantly by sex. Significant fracture discrimination for age adjusted single models was provided by the parameters vBMD (OR 3.5 [1.4-8.8], AUC=0.64 ± 0

  11. Assessment of CT image quality using a Bayesian approach

    Science.gov (United States)

    Reginatto, M.; Anton, M.; Elster, C.

    2017-08-01

    One of the most promising approaches for evaluating CT image quality is task-specific quality assessment. This involves a simplified version of a clinical task, e.g. deciding whether an image belongs to the class of images that contain the signature of a lesion or not. Task-specific quality assessment can be done by model observers, which are mathematical procedures that carry out the classification task. The most widely used figure of merit for CT image quality is the area under the ROC curve (AUC), a quantity which characterizes the performance of a given model observer. In order to estimate AUC from a finite sample of images, different approaches from classical statistics have been suggested. The goal of this paper is to introduce task-specific quality assessment of CT images to metrology and to propose a novel Bayesian estimation of AUC for the channelized Hotelling observer (CHO) applied to the task of detecting a lesion at a known image location. It is assumed that signal-present and signal-absent images follow multivariate normal distributions with the same covariance matrix. The Bayesian approach results in a posterior distribution for the AUC of the CHO which provides in addition a complete characterization of the uncertainty of this figure of merit. The approach is illustrated by its application to both simulated and experimental data.

  12. Diagnostic value of soluble CD163 serum levels in patients suspected of meningitis: comparison with CRP and procalcitonin

    DEFF Research Database (Denmark)

    Knudsen, Troels Bygum; Larsen, Klaus; Kristiansen, Thomas Birk

    2007-01-01

    The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected of meningi......The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected...... marker for distinguishing bacterial infection from non-bacterial disease (specificity 0.91; sensitivity 0.47). However, the overall diagnostic accuracy of CRP (AUC =0.91) and PCT (AUC =0.87) were superior (p... infection, the AUC of sCD163 (0.83) did not differ significantly from those of CRP or PCT. All markers had AUCs CRP and PCT had high diagnostic value and were superior as markers of bacterial infection compared to s...

  13. Bug bites and stings: When to see a dermatologist

    Medline Plus

    Full Text Available ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ... it’s important to take steps to reduce your risk. To help prevent bug bites, dermatologists recommend the ...

  14. Evaluation of the bioequivalence of capsules containing 150 mg of fluconazole.

    Science.gov (United States)

    Porta, V; Chang, K H; Storpirtis, S

    2005-01-06

    Fluconazole is an antifungal agent. The purpose of this study was to evaluate bioequivalence of two commercial 150 mg capsule formulations of fluconazole available in the Brazilian market. The study was an open, randomized, two-period, two-group crossover trial with a 2-week washout interval. Blood samples were collected throughout a 96-h period after administration of reference product (R) and test product (T) to 28 fasting volunteers. A simple, accurate, precise and sensitive high-performance liquid chromatographic (HPLC) method with ultraviolet detection was developed and validated for quantification of fluconazole in plasma samples after liquid-liquid extraction. Bioequivalence between the products was determined by calculating 90% confidence intervals (90% C.I.) for the ratio of C(max), AUC(0-t) and AUC(0-infinity) values for the test and reference products, using logarithmic transformed data. The 90% confidence intervals for the ratio of C(max) (101.06-105.45%), AUC(0-t) (97.11-104.69%) and AUC(0-infinity) (97.96-103.36%) values for the test and reference products are within the 80-125% interval, proposed by FDA and EMEA. It was concluded that the two fluconazole formulations are bioequivalent in their rate and extent of absorption.

  15. Procalcitonin is a strong predictor of urine culture results in patients with obstructing ureteral stones: A prospective, pilot study

    Directory of Open Access Journals (Sweden)

    Dimitri Papagiannopoulos

    2016-01-01

    Conclusions: This proof-of-concept pilot study gives encouraging results, in that PCT was a good predictor of positive cultures (P = 0.02, AUC 0.812. Given, the small sample size, one cannot directly compare PCT to other markers of infection. However, PCT shows promise in this arena and warrants future investigation.

  16. Bug bites and stings: When to see a dermatologist

    Medline Plus

    Full Text Available ... Grant Young Investigator Awards Volunteer opportunities Academy councils, committees, and task forces AccessDerm Camp Discovery Diversity Mentorship ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ...

  17. Limited sampling strategy for determining metformin area under the plasma concentration-time curve

    DEFF Research Database (Denmark)

    Santoro, Ana Beatriz; Stage, Tore Bjerregaard; Struchiner, Claudio José

    2016-01-01

    AIM: The aim was to develop and validate limited sampling strategy (LSS) models to predict the area under the plasma concentration-time curve (AUC) for metformin. METHODS: Metformin plasma concentrations (n = 627) at 0-24 h after a single 500 mg dose were used for LSS development, based on all su...

  18. Dose-dependent pharmacokinetics of delavirdine in combination with amprenavir in healthy volunteers

    DEFF Research Database (Denmark)

    Justesen, Ulrik S; Klitgaard, Niels A; Brosen, Kim

    2004-01-01

    . The combinations were taken at least 2 weeks apart. RESULTS: Differences in median delavirdine Cmax, C12 and AUC0-12 were seen when comparing the three combinations (3 > 2>1) (Pimportant higher median C12 was seen with combination 3 when compared to combination 1 (835 to 3944...

  19. Use of multiple metabolic and genetic markers to improve the prediction of type 2 diabetes: the EPIC-Potsdam Study.

    Science.gov (United States)

    Schulze, Matthias B; Weikert, Cornelia; Pischon, Tobias; Bergmann, Manuela M; Al-Hasani, Hadi; Schleicher, Erwin; Fritsche, Andreas; Häring, Hans-Ulrich; Boeing, Heiner; Joost, Hans-Georg

    2009-11-01

    We investigated whether metabolic biomarkers and single nucleotide polymorphisms (SNPs) improve diabetes prediction beyond age, anthropometry, and lifestyle risk factors. A case-cohort study within a prospective study was designed. We randomly selected a subcohort (n = 2,500) from 26,444 participants, of whom 1,962 were diabetes free at baseline. Of the 801 incident type 2 diabetes cases identified in the cohort during 7 years of follow-up, 579 remained for analyses after exclusions. Prediction models were compared by receiver operatoring characteristic (ROC) curve and integrated discrimination improvement. Case-control discrimination by the lifestyle characteristics (ROC-AUC: 0.8465) improved with plasma glucose (ROC-AUC: 0.8672, P < 0.001) and A1C (ROC-AUC: 0.8859, P < 0.001). ROC-AUC further improved with HDL cholesterol, triglycerides, gamma-glutamyltransferase, and alanine aminotransferase (0.9000, P = 0.002). Twenty SNPs did not improve discrimination beyond these characteristics (P = 0.69). Metabolic markers, but not genotyping for 20 diabetogenic SNPs, improve discrimination of incident type 2 diabetes beyond lifestyle risk factors.

  20. Preliminary Investigation of Beagle Dog as Substitute for Humans in ...

    African Journals Online (AJOL)

    Pharmacokinetic parameters were calculated using non-compartmental analysis while bioavailability was assessed using an analysis of variance (ANOVA) model ... under plasma concentration curve extrapolated to infinity (AUC0-‡ ) and maximum plasma concentration (Cmax), calculated for the dogs were comparable to ...

  1. Continuous infusion of vancomycin : Effective, efficient and safe

    NARCIS (Netherlands)

    Van Maarseveen, E.; Touw, D.; Bouma, A.; Van Zanten, A.

    Aims: Vancomycin is an antibiotic which is used in (suspected or proven) bacteriaemia, peritonitis or osteomyelitis with grampositive micro-organisms. Currently in most Dutch hospitals vancomycin is administered as an intermittent infusion. As the killing of vancomycin is dependent of the AUC/MIC

  2. A patient-centered methodology that improves the accuracy of prognostic predictions in cancer.

    Directory of Open Access Journals (Sweden)

    Mohammed Kashani-Sabet

    Full Text Available Individualized approaches to prognosis are crucial to effective management of cancer patients. We developed a methodology to assign individualized 5-year disease-specific death probabilities to 1,222 patients with melanoma and to 1,225 patients with breast cancer. For each cancer, three risk subgroups were identified by stratifying patients according to initial stage, and prediction probabilities were generated based on the factors most closely related to 5-year disease-specific death. Separate subgroup probabilities were merged to form a single composite index, and its predictive efficacy was assessed by several measures, including the area (AUC under its receiver operating characteristic (ROC curve. The patient-centered methodology achieved an AUC of 0.867 in the prediction of 5-year disease-specific death, compared with 0.787 using the AJCC staging classification alone. When applied to breast cancer patients, it achieved an AUC of 0.907, compared with 0.802 using the AJCC staging classification alone. A prognostic algorithm produced from a randomly selected training subsample of 800 melanoma patients preserved 92.5% of its prognostic efficacy (as measured by AUC when the same algorithm was applied to a validation subsample containing the remaining patients. Finally, the tailored prognostic approach enhanced the identification of high-risk candidates for adjuvant therapy in melanoma. These results describe a novel patient-centered prognostic methodology with improved predictive efficacy when compared with AJCC stage alone in two distinct malignancies drawn from two separate populations.

  3. External validation of the Practical Risk Chart for the prediction of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Foreman, Paul M; Chua, Michelle H; Harrigan, Mark R; Fisher, Winfield S; Tubbs, R Shane; Shoja, Mohammadali M; Griessenauer, Christoph J

    2017-05-01

    OBJECTIVE Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) occurs in approximately 30% of patients. The Practical Risk Chart was developed to predict DCI based on admission characteristics; the authors seek to externally validate and critically appraise this prediction tool. METHODS A prospective cohort of aSAH patients was used to externally validate the previously published Practical Risk Chart. The model consists of 4 variables: clinical condition on admission, amount of cisternal and intraventricular blood on CT, and age. External validity was assessed using logistic regression. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS In a cohort of 125 patients with aSAH, the Practical Risk Chart adequately predicted DCI, with an AUC of 0.66 (95% CI 0.55-0.77). Clinical grade on admission and amount of intracranial blood on CT were the strongest predictors of DCI and clinical vasospasm. The best-fit model used a combination of the Hunt and Hess grade and the modified Fisher scale to yield an AUC of 0.76 (95% CI 0.675-0.85) and 0.70 (95% CI 0.602-0.8) for the prediction of DCI and clinical vasospasm, respectively. CONCLUSIONS The Practical Risk Chart adequately predicts the risk of DCI following aSAH. However, the best-fit model represents a simpler stratification scheme, using only the Hunt and Hess grade and the modified Fisher scale, and produces a comparable AUC.

  4. Morphologic and Hemodynamic Analysis in the Patients with Multiple Intracranial Aneurysms: Ruptured versus Unruptured.

    Science.gov (United States)

    Jing, Linkai; Fan, Jixing; Wang, Yang; Li, Haiyun; Wang, Shengzhang; Yang, Xinjian; Zhang, Ying

    2015-01-01

    The authors evaluated the impact of morphologic and hemodynamic factors on multiple intracranial aneurysms and aimed to identify which parameters can be reliable indexes as one aneurysm ruptured, and the others did not. Between June 2011 and May 2014, 69 patients harboring multiple intracranial aneurysms (69 ruptured and 86 unruptured) were analyzed from 3D-digital subtraction angiography (DSA) images and computational fluid dynamics (CFD). Morphologic and hemodynamic parameters were evaluated for significance with respect to rupture. Receiver operating characteristic (ROC) analysis identified area under the curve (AUC) and optimal thresholds separating ruptured from unruptured intracranial aneurysms for each parameter. Significant parameters were examined by binary logistic regression analysis to identify independent discriminators. Nine morphologic (size, neck width, surface area, volume, diameter of parent arteries, aspect ratio, size ratio, lateral/bifurcation type and regular/irregular type) and 6 hemodynamic (WSSmean, WSSmin, OSI, LSA, flow stability and flow complexity) parameters achieved statistical significance (pflow stability and flow complexity) parameters had high AUC values (AUC>0.7). By binary logistic regression analysis, large aspect ratio and low WSSmean were the independently significant rupture factors (AUC, 0.924; 95% CI, 0.883-0.965). Large aspect ratio and low WSSmean were independently associated with the rupture status of multiple intracranial aneurysms.

  5. [Predisposition of citizens to use Internet-based channels to communicate with doctors in Spain].

    Science.gov (United States)

    Herrera-Usagre, Manuel; Reyes-Alcázar, Víctor; Valverde, José A

    2014-01-01

    Analyze factors affecting the predisposition of Spanish citizens to use Internet-based communication channels (E-mail, blogs, social networks, and online recommendations). Secondary data were analyzed by applying a boosted regression tree (BRT) to the results obtained from the survey "Use and Applications of Information and Communications Technology in Health," administered to a representative sample of the Spanish population between 16 and 85 years of age who use the Internet. Model forecasts achieved different degrees of precision for each of the communication channels: for E-mail, AUC (area under the curve) = 0.79; for the physician's blog or personal website, AUC = 0.736; for social networks, AUC = 0.73; for recommendations of websites related to health problems, AUC = 0.768. Being young was the most important parameter in citizen predisposition to communicate through social networks (relative influence; RI = 21.05%), while population density was the most important parameter in likelihood that the physician would have a blog or personal health-related website (RI = 19.48%). Having a positive perception of the technology when facilitating health-related transactions was the most important characteristic in wanting to receive recommendations on health-related Internet resources (RI = 18.66%), while having a higher level of education was the best predictor of wanting to establish E-mail communication (RI = 18.98%). Many of Spanish people are open to using physician-patient interaction channels on the Internet.

  6. Activated Leukocyte Cell Adhesion Molecule: a Novel Biomarker for Breast Cancer

    Science.gov (United States)

    Kulasingam, Vathany; Zheng, Yingye; Soosaipillai, Antoninus; Leon, Antonette E.; Gion, Massimo; Diamandis, Eleftherios P.

    2013-01-01

    Activated leukocyte cell adhesion molecule (ALCAM) has been implicated in tumorigenesis. Our goal was to examine the levels of ALCAM, in addition to the classical breast cancer tumor markers carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA), in serum by quantitative ELISA for diagnosis in breast cancer patients. The three proteins were measured in serum of 100 healthy women, 50 healthy men and 150 breast carcinoma patients. The diagnostic sensitivity and specificity of the tests were calculated and the association of serum marker concentrations with various clinicopathologic variables was examined using nonparametric Kruskal-Wallis tests. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the biomarkers. ALCAM, with area under the curve (AUC) of 0.78 [95% CI: 0.73, 0.84] outperformed CA15-3 (AUC= 0.70 [95% CI: 0.64, 0.76]) and CEA (AUC= 0.63 [95% CI: 0.56, 0.70]). The incremental values of AUC for ALCAM over that for CA15-3 were statistically significant (Delong test, p breast cancer and may have value for disease diagnosis. PMID:19322904

  7. Pharmacokinetic Modeling and Optimal Sampling Strategies for Therapeutic Drug Monitoring of Rifampin in Patients with Tuberculosis

    NARCIS (Netherlands)

    Sturkenboom, M.G.; Mulder, L.W.; Jager, A de; Altena, R. van; Aarnoutse, R.E.; Lange, W.C. de; Proost, J.H.; Kosterink, J.G.W.; Werf, T.S. van der; Alffenaar, J.W.C.

    2015-01-01

    Rifampin, together with isoniazid, has been the backbone of the current first-line treatment of tuberculosis (TB). The ratio of the area under the concentration-time curve from 0 to 24 h (AUC0-24) to the MIC is the best predictive pharmacokinetic-pharmacodynamic parameter for determinations of

  8. Pharmacokinetic Study of Nifedipine in Healthy Adult Male Human ...

    African Journals Online (AJOL)

    Conclusion: This study confirms the rapid absorption of nifedipine in humans. AUC was similar to that previously reported for Nigerians but slightly lower than that stated in the literature for other south Asian races. Further studies on large segments of the local population using the non-compartmental model for

  9. Pharmacokinetic Study of Nifedipine in Healthy Adult Male Human ...

    African Journals Online (AJOL)

    Erah

    Conclusion: This study confirms the rapid absorption of nifedipine in humans. AUC was similar to that previously reported for Nigerians but slightly lower than that stated in the literature for other south Asian races. Further studies on large segments of the local population using the non-compartmental model for.

  10. Pharmacokinetic Modeling and Optimal Sampling Strategies for Therapeutic Drug Monitoring of Rifampin in Patients with Tuberculosis

    NARCIS (Netherlands)

    Sturkenboom, Marieke G. G.; Mulder, Leonie W.; de Jager, Arthur; van Altena, Richard; Aarnoutse, Rob E.; de Lange, Wiel C. M.; Proost, Johannes H.; Kosterink, Jos G. W.; van der Werf, Tjip S.; Alffenaar, Jan-Willem C.

    Rifampin, together with isoniazid, has been the backbone of the current first-line treatment of tuberculosis (TB). The ratio of the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) to the MIC is the best predictive pharmacokinetic-pharmacodynamic parameter for determinations of

  11. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... for members Chronic urticaria—for public Dermatology World Dialogues in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient ... notes Image library 3-D animated image library Dialogues in Dermatology Dialogues in Dermatology quizzes JAAD quizzes ...

  12. Summer and winter habitat suitability of Marco Polo argali in southeastern Tajikistan: A modeling approach.

    Science.gov (United States)

    Salas, Eric Ariel L; Valdez, Raul; Michel, Stefan

    2017-11-01

    We modeled summer and winter habitat suitability of Marco Polo argali in the Pamir Mountains in southeastern Tajikistan using these statistical algorithms: Generalized Linear Model, Random Forest, Boosted Regression Tree, Maxent, and Multivariate Adaptive Regression Splines. Using sheep occurrence data collected from 2009 to 2015 and a set of selected habitat predictors, we produced summer and winter habitat suitability maps and determined the important habitat suitability predictors for both seasons. Our results demonstrated that argali selected proximity to riparian areas and greenness as the two most relevant variables for summer, and the degree of slope (gentler slopes between 0° to 20°) and Landsat temperature band for winter. The terrain roughness was also among the most important variables in summer and winter models. Aspect was only significant for winter habitat, with argali preferring south-facing mountain slopes. We evaluated various measures of model performance such as the Area Under the Curve (AUC) and the True Skill Statistic (TSS). Comparing the five algorithms, the AUC scored highest for Boosted Regression Tree in summer (AUC = 0.94) and winter model runs (AUC = 0.94). In contrast, Random Forest underperformed in both model runs.

  13. Summer and winter habitat suitability of Marco Polo argali in southeastern Tajikistan: A modeling approach

    Directory of Open Access Journals (Sweden)

    Eric Ariel L. Salas

    2017-11-01

    Full Text Available We modeled summer and winter habitat suitability of Marco Polo argali in the Pamir Mountains in southeastern Tajikistan using these statistical algorithms: Generalized Linear Model, Random Forest, Boosted Regression Tree, Maxent, and Multivariate Adaptive Regression Splines. Using sheep occurrence data collected from 2009 to 2015 and a set of selected habitat predictors, we produced summer and winter habitat suitability maps and determined the important habitat suitability predictors for both seasons. Our results demonstrated that argali selected proximity to riparian areas and greenness as the two most relevant variables for summer, and the degree of slope (gentler slopes between 0° to 20° and Landsat temperature band for winter. The terrain roughness was also among the most important variables in summer and winter models. Aspect was only significant for winter habitat, with argali preferring south-facing mountain slopes. We evaluated various measures of model performance such as the Area Under the Curve (AUC and the True Skill Statistic (TSS. Comparing the five algorithms, the AUC scored highest for Boosted Regression Tree in summer (AUC = 0.94 and winter model runs (AUC = 0.94. In contrast, Random Forest underperformed in both model runs. Keywords: Ecology, Evolution, Zoology, Environmental science, Geography, Biological sciences

  14. Flanking region sequence information to refine microRNA target ...

    Indian Academy of Sciences (India)

    Our methodology attained a higher average accuracy of 0.88, average sensitivity and specificity of 0.81 and 0.94, respectively, and areas under the curves (AUCs) for all the four models scored above 0.9, suggesting better performance by our methodology and a possible role of flanking regions in microRNA targeting ...

  15. The Pedagogy of Failure in the Global Market

    Science.gov (United States)

    Silk, Janet

    2011-01-01

    An American artist and art educator discusses her experience teaching at the American University in Cairo, Egypt (AUC). Students are confronted by local and international discourse about authenticity, integrity and influence. They express their frustration and anxiety about their chances for success in the global art market. The author questions…

  16. Salivary cortisol in two professions: daily cortisol profiles in school teachers and firefighters.

    Science.gov (United States)

    Susoliakova, Olga; Smejkalova, Jindra; Bicikova, Marie; Potuznikova, Dana; Hodacova, Lenka; Grimby-Ekman, Anna; Fiala, Zdenek

    2014-01-01

    It's indicated negative-perceived stress could induce worse health status and change of cortisol secretion. To assess salivary cortisol levels in two occupations with a high psychosocial workload, but different features, teachers and firefighters. The study population consisted of 142 school teachers and 136 firefighters. Four saliva samples were collected from pedagogical participants during their busiest workday. The cortisol measures used were: morning values, evening values, slope of decline, ratio (evening value divided by morning value), and area under the curve (AUC). The salivary cortisol measurements in both genders were almost equal regarding morning values, slope, and AUC increase. Evening values were lower and the relative reactivity was higher (lower ratio) for female teachers, compared to male teachers. There was a tendency of a lower total daytime output of cortisol (AUC ground) among female teachers. Firefighters had lower levels of cortisol, lower total daytime output, and higher relative reactivity (lower ratio), but lower absolute reactivity, regarding both slope and AUC increase. Overall, male teachers might be the group most affected by stress in this study, even if some of their cortisol values were almost equal to the female teachers' values. Male teachers also seemed to be more affected by stress, according to salivary cortisol, compared to male firefighters, even if there were some inconsistencies.

  17. Automatic REM Sleep Detection Associated with Idiopathic REM Sleep Behavior Disorder

    DEFF Research Database (Denmark)

    Kempfner, Jacob; Sørensen, Gertrud Laura; Sørensen, Helge Bjarup Dissing

    2011-01-01

    , an automatic computerized REM detection algorithm has been implemented, using wavelet packet combined with artificial neural network. Results: When using the EEG, EOG and EMG modalities, it was possible to correctly classify REM sleep with an average Area Under Curve (AUC) equal to 0:900:03 for normal subjects...

  18. The Heathen Obama

    DEFF Research Database (Denmark)

    Christensen, Rune Reimer

    2008-01-01

    Om faren ved brugen af satire i fremstillinger af race i amerikansk kultur.  Forskningsbaseret bidrag til akademisk blog om amerikansk historie, kultur, og samfundsforhold. I samarbejde med bl.a. forskere fra KUA, RUC, AUC. Udgivelsesdato: 15.07...

  19. From hybrid swarms to swarms of hybrids

    Science.gov (United States)

    Stohlgren, Thomas J.; Szalanski, Allen L; Gaskin, John F.; Young, Nicholas E.; West, Amanda; Jarnevich, Catherine S.; Tripodi, Amber

    2014-01-01

    Science has shown that the introgression or hybridization of modern humans (Homo sapiens) with Neanderthals up to 40,000 YBP may have led to the swarm of modern humans on earth. However, there is little doubt that modern trade and transportation in support of the humans has continued to introduce additional species, genotypes, and hybrids to every country on the globe. We assessed the utility of species distributions modeling of genotypes to assess the risk of current and future invaders. We evaluated 93 locations of the genus Tamarix for which genetic data were available. Maxent models of habitat suitability showed that the hybrid, T. ramosissima x T. chinensis, was slightly greater than the parent taxa (AUCs > 0.83). General linear models of Africanized honey bees, a hybrid cross of Tanzanian Apis mellifera scutellata and a variety of European honey bee including A. m. ligustica, showed that the Africanized bees (AUC = 0.81) may be displacing European honey bees (AUC > 0.76) over large areas of the southwestern U.S. More important, Maxent modeling of sub-populations (A1 and A26 mitotypes based on mDNA) could be accurately modeled (AUC > 0.9), and they responded differently to environmental drivers. This suggests that rapid evolutionary change may be underway in the Africanized bees, allowing the bees to spread into new areas and extending their total range. Protecting native species and ecosystems may benefit from risk maps of harmful invasive species, hybrids, and genotypes.

  20. Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.

    Science.gov (United States)

    Wang, Chang-Yu; Lee, Tsair-Fwu; Fang, Chun-Hsiung; Chou, Jyh-Horng

    2012-11-01

    Given the poor prognosis of esophageal cancer and the invasiveness of combined modality treatment, improved prognostic scoring systems are needed. We developed a fuzzy logic-based system to improve the predictive performance of a risk score based on the serum concentrations of C-reactive protein (CRP) and albumin in a cohort of 271 patients with esophageal cancer before radiotherapy. Univariate and multivariate survival analyses were employed to validate the independent prognostic value of the fuzzy risk score. To further compare the predictive performance of the fuzzy risk score with other prognostic scoring systems, time-dependent receiver operating characteristic curve (ROC) analysis was used. Application of fuzzy logic to the serum values of CRP and albumin increased predictive performance for 1-year overall survival (AUC=0.773) compared with that of a single marker (AUC=0.743 and 0.700 for CRP and albumin, respectively), where the AUC denotes the area under curve. This fuzzy logic-based approach also performed consistently better than the Glasgow Prognostic Score (GPS) (AUC=0.745). Thus, application of fuzzy logic to the analysis of serum markers can more accurately predict the outcome for patients with esophageal cancer.

  1. Reliability and validity of a continuous pain registration procedure

    NARCIS (Netherlands)

    van Wijk, A.J.; Lobbezoo, F.; Hoogstraten, J.

    2013-01-01

    Background Conventional pain rating scales [i.e. visual analogue scales (VAS) or numerical rating scales (NRS)] only provide a summary for different levels of pain felt, while the duration of these levels is not accounted for. If pain can be rated continuously, the area under the curve (AUC) of

  2. Concurrent carboplatin with radiotherapy in T2 laryngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Hitoshi; Suzuki, Mamoru; Yoshida, Tomoyuki [Tokyo Medical Coll. (Japan); Kida, Akinori; Endo, Sohei [Nihon Univ., Tokyo (Japan). Itabashi Hospital; Furusaka, Tohru; Nakai, Takahisa [Nihon Univ., Tokyo (Japan). Surugadai Hospital

    2002-03-01

    A combination of carboplatin (CBDCA) therapy and radiotherapy was used in T2 laryngeal cancer. The subjects were 34 untreated patients with T2 laryngeal cancer, who were enrolled during the period from May 1998 to April 2000. All the patients were male, and their average age was 64.4 years. The dose of CBDCA was properly adjusted so that the AUC would be either 1.5 or 2.0. CBDCA therapy was conducted once a week for four weeks. As a rule, radiotherapy was administered at a dose of 2 Gy, with a total of 60 Gy to be given to each patient. Of the 34 patients, 29 were eligible for evaluation. Twenty-five of the 29 patients demonstrated complete response (CR) (86.2%). The larynx was preserved in 25 of these 29 patients (86.2%). The complete response rate was 81.8% in those who were placed on CBDCA therapy with an AUC of 1.5, and 88.9% in those with an AUC of 2.0. Regarding hematological toxicity, grade 3 leukocytopenia was recognized in three patients, while symptoms of thrombocytopenia severer than grade 3 were rarely observed. Accordingly, CBDCA therapy with an AUC of 2.0 reflects the optimum dose of CBDCA. The combination of CBDCA therapy and radiology is considered to be an effective treatment for T2 laryngeal cancer. (author)

  3. Effects of tomato juice on the pharmacokinetics of CYP3A4-substrate drugs

    Directory of Open Access Journals (Sweden)

    Atsuko Ohkubo

    2017-09-01

    Full Text Available We previously demonstrated that tomato juice (TJ contains potent mechanism-based inhibitor(s of CYP3A4. In this study, we investigated the effects of TJ and grapefruit juice (GFJ on the pharmacokinetics of the CYP3A4-substrate drugs, nifedipine (NFP and midazolam (MDZ, in male Wistar rats. Oral administration of GFJ 90 min before the intraduodenal administration of NFP or MDZ increased the area under the concentration–time curves (AUCs of NFP and MDZ by 32.4% and 89.4%, respectively. TJ increased MDZ blood concentrations and AUC after intraduodenal MDZ administration; however, it had no effect on NFP. When MDZ and NFP were intravenously administered, GFJ significantly increased the AUC of MDZ, but only slightly increased that of NFP. In contrast, TJ only slightly increased the AUC of MDZ. These results suggest that, similar to GFJ, TJ influences the pharmacokinetics of CYP3A4-substrate drugs; however, it may be a drug-dependent partial effect.

  4. Intestinal first pass metabolism of midazolam in liver cirrhosis --effect of grapefruit juice

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Pedersen, Natalie; Larsen, Niels-Erik

    2002-01-01

    subjects after ingestion of grapefruit juice. However, this interaction has not been studied in patients with impaired liver function. Accordingly, the effect of grapefruit juice on the AUC of midazolam and the metabolite alpha-hydroxymidazolam was studied in patients with cirrhosis of the liver....

  5. Effect of food on the pharmacokinetics of oral MMI270B (CGS 27023A), a novel matrix metalloproteinase inhibitor

    NARCIS (Netherlands)

    F.A.L.M. Eskens (Ferry); N.C. Levitt; A. Sparreboom (Alex); L. Choi; R. Mather; J. Verweij (Jaap); A.L. Harris

    2000-01-01

    textabstractMMI270B is a matrix metalloproteinase inhibitor (MMPI) with in vitro and in vivo activity. To exert optimal target inhibition, MMPI must be given chronically, and therefore, oral bioavailability is important. We analyzed the effect of food intake on AUC0-8

  6. An assessment on the use of bivariate, multivariate and soft ...

    Indian Academy of Sciences (India)

    However, Area Under Curve (AUC) values obtained from all three models showed that the map obtained from .... an extra value to the literature of the collapse sus- ceptibility mapping as a comparative study of very ...... Negnevitsky M 2002 Artificial Intelligence – A Guide to. Intelligent Systems; Addison – Wesley Co., Great ...

  7. Circulating levels of GH predict mortality and complement prognostic scores in critically ill medical patients.

    Science.gov (United States)

    Schuetz, Philipp; Müller, Beat; Nusbaumer, Charly; Wieland, Melanie; Christ-Crain, Mirjam

    2009-02-01

    Circulating levels of GH are increased during critical illness and correlate with outcome in children with meningococcal sepsis. We assessed the prognostic implications of GH on admission and during follow-up in critically ill adult patients admitted to a medical intensive care unit. We measured GH, IGF1 and IGF-binding protein3 (IGFBP-3) plasma concentrations in 103 consecutive critically ill patients and compared it with two clinical severity scores (APACHE II, SAPS II). Median GH levels on admission were similar in septic (n=53) and non-septic (n=50) patients and about 7-fold increased in the 24 non-survivors as compared with survivors (9.50 (interquartile ranges (IQR) 3.53-18.40) vs 1.4 (IQR 0.63-5.04), PAPACHE II: AUC 0.71 (95% CI, 0.58-0.83), P=0.16, SAPS II: AUC 0.75 (95% CI, 0.63-0.86, P=0.36)). GH improved the prognostic accuracy of the APACHE II score to an AUC of 0.78 (95% CI, 0.66-090, P=0.04) and tended to improve the SAPS II score to an AUC of 0.79 (95% CI, 0.67-0.90, P=0.09). GH plasma concentrations on admission are independent predictors for mortality in adult critically ill patients and may complement existing risk prediction scores, namely the APACHE II and the SAPS II score.

  8. Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I to ADH 3 (Class III in Mouse

    Directory of Open Access Journals (Sweden)

    Takeshi Haseba

    2012-01-01

    Full Text Available ADH 1 and ADH 3 are major two ADH isozymes in the liver, which participate in systemic alcohol metabolism, mainly distributing in parenchymal and in sinusoidal endothelial cells of the liver, respectively. We investigated how these two ADHs contribute to the elimination kinetics of blood ethanol by administering ethanol to mice at various doses, and by measuring liver ADH activity and liver contents of both ADHs. The normalized AUC (AUC/dose showed a concave increase with an increase in ethanol dose, inversely correlating with β. CLT (dose/AUC linearly correlated with liver ADH activity and also with both the ADH-1 and -3 contents (mg/kg B.W.. When ADH-1 activity was calculated by multiplying ADH-1 content by its Vmax⁡/mg (4.0 and normalized by the ratio of liver ADH activity of each ethanol dose to that of the control, the theoretical ADH-1 activity decreased dose-dependently, correlating with β. On the other hand, the theoretical ADH-3 activity, which was calculated by subtracting ADH-1 activity from liver ADH activity and normalized, increased dose-dependently, correlating with the normalized AUC. These results suggested that the elimination kinetics of blood ethanol in mice was dose-dependently changed, accompanied by a shift of the dominant metabolizing enzyme from ADH 1 to ADH 3.

  9. Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma.

    Science.gov (United States)

    Gauvreau, Gail M; Boulet, Louis-Philippe; Cockcroft, Donald W; Fitzgerald, J Mark; Carlsten, Chris; Davis, Beth E; Deschesnes, Francine; Duong, MyLinh; Durn, Billie L; Howie, Karen J; Hui, Linda; Kasaian, Marion T; Killian, Kieran J; Strinich, Tara X; Watson, Richard M; Y, Nathalie; Zhou, Simon; Raible, Donald; O'Byrne, Paul M

    2011-04-15

    Extensive evidence in animal models supports a role for IL-13 in the pathobiology of asthma. IMA-638 and IMA-026 are fully humanized IgG(1) antibodies that bind to different epitopes and neutralize IL-13 bioactivity. We hypothesized that anti-IL-13 treatment would inhibit allergen-induced late-phase asthmatic responses, airway hyperresponsiveness, and inflammation in subjects with asthma. Fifty-six subjects with mild, atopic asthma were recruited for two double-blind, randomized, placebo-controlled, parallel group trials to compare IMA-638 and IMA-026 IL-13 antibody treatments with placebo treatment. Drug was administered on Days 1 and 8, and allergen challenges were performed on Days 14 and 35. The primary outcome variable was the late-phase area under the curve (AUC), and secondary outcome variables were the early- and late-phase maximum percent fall in FEV(1), early AUC, allergen-induced shift in airway hyperresponsiveness, and sputum eosinophils. The treatment difference with IMA-638 on Day 14 was -19.1 FEV(1) × hour (95% confidence interval: -36.2, -1.9) for the allergen-induced early AUC and -23.8 FEV(1) × hour (95% confidence interval: -46.4, -1.2) for the late AUC (both P humans. Further study is required to determine whether anti-IL-13 monoclonal antibodies will be beneficial clinically.

  10. Bug bites and stings: When to see a dermatologist

    Medline Plus

    Full Text Available ... Rotation PICMED Grant Professionalism Award Resident-Fellow QI Project Award Resident International Grant Resident Scholarship to Legislative ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ...

  11. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Rotation PICMED Grant Professionalism Award Resident-Fellow QI Project Award Resident International Grant Resident Scholarship to Legislative ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ...

  12. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... Rotation PICMED Grant Professionalism Award Resident-Fellow QI Project Award Resident International Grant Resident Scholarship to Legislative ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ...

  13. The Score Model Containing Chinese Medicine Syndrome Element of Blood Stasis Presented a Better Performance Compared to APRI and FIB-4 in Diagnosing Advanced Fibrosis in Patients with Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Xiao-Ling Chi

    2016-01-01

    Full Text Available This study aims to explore a useful noninvasive assessment containing TCM syndrome elements for liver fibrosis in CHB patients. The demographic, clinical, and pathological data were retrospectively collected from 709 CHB patients who had ALT less than 2 times the upper limit of normal from April 2009 to October 2012. Logistical regression and area under receiver-operator curve (AUROC were used to determine the diagnostic performances of simple tests for advanced fibrosis (Scheuer stage, F ≥ 3. Results showed that the most common TCM syndrome element observed in this CHB population was dampness and Qi stagnation, followed by blood stasis, by heat, and less by Qi deficiency and Yin deficiency. The logistical regression analysis identified AST ≥ 35 IU/L, PLT ≤ 161 × 109/L, and TCM syndrome element of blood stasis as the independent risk factors for advanced fibrosis. Therefore, a score model containing these three factors was established and tested. The score model containing blood stasis resulted in a higher AUC (AUC = 0.936 compared with APRI (AUC = 0.731 and FIB-4 (AUC = 0.709. The study suggested that the score model containing TCM syndrome element of blood stasis could be used as a useful diagnostic tool for advanced fibrosis in CHB patients and presented a better performance compared to APRI and FIB-4.

  14. Comparing rat and rabbit embryo-fetal developmental toxicity studies for 379 pharmaceuticals: On systemic dose and developmental effects (Critical Reviews in Toxicology)

    Science.gov (United States)

    A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse ef...

  15. Limited sampling strategies for therapeutic drug monitoring of mycophenolate mofetil therapy in patients with autoimmune disease

    NARCIS (Netherlands)

    de Winter, Brenda C. M.; Neumann, Irmgard; van Hest, Reinier M.; van Gelder, Teun; Mathot, Ron A. A.

    2009-01-01

    Mycophenolate mofetil (MMF) is increasingly used for the treatment of autoimmune diseases (AID). In renal transplant recipients, it has been demonstrated that adjustment of the MMF dose according to the area under the plasma concentration versus time curve (AUC) of mycophenolic acid (MPA), the

  16. In vivo antimicrobial activity of marbofloxacin against Pasteurella multocida in a tissue cage model in calves

    Directory of Open Access Journals (Sweden)

    Changfu eCao

    2015-07-01

    Full Text Available Marbofloxacin is a fluoroquinolone specially developed for use in veterinary medicine with broad-spectrum antibacterial activity. The objective of our study was to re-evaluate in vivo antimicrobial activity of marbofloxacin against Pasteurella multocida using subcutaneously implanted tissue cages in calves. Calves were infected by direct injection into tissue cages with Pasteurella multocida(type B, serotype 2, then intramuscularly received a range of marbofloxacin doses 24h after inoculation. The ratio of 24h area under the concentration-time curve divided by the minimum inhibitory concentration or the mutant prevention concentration (AUC24h/MIC or AUC24h/MPC was the pharmacokinetic-pharmacodynamic (PK/PD index that best described the effectiveness of marbofloxacin against Pasteurella multocida (R2=0.8514 by nonlinear regression analysis. Marbofloxacin exhibited a good antimicrobial activity in vivo. The levels of AUC24h/MIC and AUC24h/MPC that produced 50% (1.5log10CFU/mL reduction and 90% (3log10CFU/mL reduction of maximum response were 18.60h and 50.65h, 4.67h and 12.89h by using sigmoid Emax model WINNONLIN software, respectively. The in vivo PK/PD integrated methods by tissue cage model display the advantage of the evaluation of antimicrobial activity and the optimization of the dosage regimen for antibiotics in the presence of the host defenses, especially in target animal of veterinary interest.

  17. Effect of an oral contraceptive preparation containing ethinylestradiol and gestodene on CYP3A4 activity as measured by midazolam 1'-hydroxylation.

    Science.gov (United States)

    Palovaara, S; Kivistö, K T; Tapanainen, P; Manninen, P; Neuvonen, P J; Laine, K

    2000-10-01

    To characterize the effect of an oral contraceptive (OC) containing ethinylestradiol and gestodene on the activity of CYP3A4 in vivo as measured by the 1'-hydroxylation of midazolam. In this randomised, double-blind, cross-over trial nine healthy female subjects received either a combined OC (30 microg ethinylestradiol and 75 microg gestodene) or placebo once daily for 10 days. On day 10, a single 7.5 mg dose of midazolam was given orally. Plasma concentrations of midazolam and 1'-hydroxymidazolam were determined up to 24 h and the effects of midazolam were measured with three psychomotor tests up to 8 h. The combined OC increased the mean AUC of midazolam by 21% (95% CI 2% to 40%; P = 0.03) and decreased that of 1'-hydroxymidazolam by 25% (95% CI 10% to 41%; P = 0.01), compared with placebo. The metabolic ratio (AUC of 1'-hydroxymidazolam/AUC of midazolam) was 36% smaller (95% CI 19% to 53%; P = 0.01) in the OC phase than in the placebo phase. There were no significant differences in the Cmax, tmax, t(1/2) or effects of midazolam between the phases. A combined OC preparation caused a modest reduction in the activity of CYP3A4, as measured by the 1'-hydroxylation of midazolam, and slightly increased the AUC of oral midazolam. This study suggests that, at the doses used, ethinylestradiol and gestodene have a relatively small effect on CYP3A4 activity in vivo.

  18. The effect of breakfast type and frequency of consumption on glycemic response in overweight/obese late adolescent girls.

    Science.gov (United States)

    Alwattar, A Y; Thyfault, J P; Leidy, H J

    2015-08-01

    The primary aim was to examine the daily glycemic response to normal-protein (NP) vs higher-protein (HP) breakfasts in overweight adolescents who habitually skip breakfast (H-BS). The secondary aim examined whether the glycemic response to these meals differed in H-BS vs habitual breakfast consumers (H-BC). Thirty-five girls (age: 19 ± 1 year; body mass index: 28.4 ± 0.7 kg/m(2)) participated in the semi-randomized crossover-design study. The participants were grouped according to habitual breakfast frequency. H-BS (n = 20) continued to skip breakfast (BS) or consumed a NP (12 g protein) or HP (32 g protein) breakfast for 3 days, whereas the H-BC (n = 15) completed the NP and HP breakfast conditions for 3 days. On day 4 of each pattern, an 8 h testing day was completed. The respective breakfast and a standard lunch meal were provided, and plasma was collected to assess morning, afternoon, and total glucose and insulin area under the curves (AUC). In H-BS, the addition of a HP breakfast increased total glucose AUC vs BS (P breakfast increased total insulin AUC vs BS (P breakfast reduced morning, afternoon and total glucose AUCs vs NP (all, P breakfasts (both, Pbreakfasts were observed and were influenced by the frequency of habitual breakfast consumption in overweight adolescents.

  19. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... Member directory Publications JAAD JAAD Case Reports Dermatology World DW Weekly Member to Member Derm Coding Consult ... urticaria—for members Chronic urticaria—for public Dermatology World Dialogues in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis ...

  20. Bug bites and stings: When to see a dermatologist

    Medline Plus

    Full Text Available ... Member directory Publications JAAD JAAD Case Reports Dermatology World DW Weekly Member to Member Derm Coding Consult ... urticaria—for members Chronic urticaria—for public Dermatology World Dialogues in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis ...

  1. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Member directory Publications JAAD JAAD Case Reports Dermatology World DW Weekly Member to Member Derm Coding Consult ... urticaria—for members Chronic urticaria—for public Dermatology World Dialogues in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis ...

  2. Variations in predicted risks in personal genome testing for common complex diseases

    Science.gov (United States)

    Kalf, Rachel R.J.; Mihaescu, Raluca; Kundu, Suman; de Knijff, Peter; Green, Robert C.; Janssens, A. Cecile J.W.

    2013-01-01

    Purpose The promise of personalized genomics for common complex diseases depends, in part, on the ability to predict genetic risks on the basis of single nucleotide polymorphisms. We examined and compared the methods of three companies (23andMe, deCODEme, and Navigenics) that have offered direct-to-consumer personal genome testing. Methods We simulated genotype data for 100,000 individuals on the basis of published genotype frequencies and predicted disease risks using the methods of the companies. Predictive ability for six diseases was assessed by the AUC. Results AUC values differed among the diseases and among the companies. The highest values of the AUC were observed for age related macular degeneration, celiac disease, and Crohn disease. The largest difference among the companies was found for celiac disease: the AUC was 0.73 for 23andMe and 0.82 for deCODEme. Predicted risks differed substantially among the companies as a result of differences in the sets of single nucleotide polymorphisms selected and the average population risks selected by the companies, and in the formulas used for the calculation of risks. Conclusion Future efforts to design predictive models for the genomics of common complex diseases may benefit from understanding the strengths and limitations of the predictive algorithms designed by these early companies. PMID:23807614

  3. Impact of Diabetes-Specific Nutritional Formulas versus Oatmeal on Postprandial Glucose, Insulin, GLP-1 and Postprandial Lipidemia

    Directory of Open Access Journals (Sweden)

    Adham Mottalib

    2016-07-01

    Full Text Available Diabetes-specific nutritional formulas (DSNFs are frequently used as part of medical nutrition therapy for patients with diabetes. This study aims to evaluate postprandial (PP effects of 2 DSNFs; Glucerna (GL and Ultra Glucose Control (UGC versus oatmeal (OM on glucose, insulin, glucagon-like peptide-1 (GLP-1, free fatty acids (FFA and triglycerides (TG. After an overnight fast, 22 overweight/obese patients with type 2 diabetes were given 200 kcal of each of the three meals on three separate days in random order. Blood samples were collected at baseline and at 30, 60, 90, 120, 180 and 240 min. Glucose area under the curve (AUC0–240 after GL and UGC was lower than OM (p < 0.001 for both. Insulin positive AUC0–120 after UGC was higher than after OM (p = 0.02. GLP-1 AUC0–120 and AUC0–240 after GL and UGC was higher than after OM (p < 0.001 for both. FFA and TG levels were not different between meals. Intake of DSNFs improves PP glucose for 4 h in comparison to oatmeal of similar caloric level. This is achieved by either direct stimulation of insulin secretion or indirectly by stimulating GLP-1 secretion. The difference between their effects is probably related to their unique blends of amino acids, carbohydrates and fat.

  4. A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults.

    Science.gov (United States)

    Sikes, Carolyn; Stark, Jeffrey G; McMahen, Russ; Engelking, Dorothy

    2017-11-01

    The purpose of this study was to compare the pharmacokinetics of a new extended-release amphetamine oral suspension (AMP XR-OS) with a standard extended-release mixed amphetamine salts product, Adderall XR®. In this single-dose, open-label, randomized, two-period, two-treatment crossover study, 42 healthy adult volunteers received 15 mL of AMP XR-OS in one period and a 30 mg Adderall XR capsule in another period (both containing 18.8 mg of amphetamine base) under fasted conditions. Blood samples were analyzed for d- and l-amphetamine concentrations, and pharmacokinetic parameters Cmax, AUC0-5, AUC5-last, and AUCinf were calculated to determine bioequivalence. Safety was monitored throughout the study. The 90% confidence intervals (CIs) for the log-transformed Cmax, AUC0-5, AUC5-last, and AUCinf fell within the accepted 80% to 125% range for establishing bioequivalence for d- and l-amphetamine. The most common adverse events were nausea and decreased appetite. AMP XR-OS is bioequivalent to Adderall XR in healthy adult participants.

  5. Shear-wave elastography for breast masses: local shear wave speed (m/sec versus Young modulus (kPa

    Directory of Open Access Journals (Sweden)

    Ji Hyun Youk

    2014-01-01

    Conclusion:

    The quantitative elasticity values measured in kPa and m/sec on SWE showed good diagnostic performance. The specificity of the SD and AUC of the wSD measured in kPa were significantly higher than those measured in m/sec.

  6. Pittsburgh outcomes after stroke thrombectomy score predicts outcomes after endovascular therapy for anterior circulation large vessel occlusions.

    Science.gov (United States)

    Rangaraju, Srikant; Liggins, John T P; Aghaebrahim, Amin; Streib, Christopher; Sun, Chung-Huan; Gupta, Rishi; Nogueira, Raul; Frankel, Michael; Mlynash, Michael; Lansberg, Maarten; Albers, Gregory; Jadhav, Ashutosh; Jovin, Tudor G

    2014-08-01

    Prognostication tools that predict good outcome in patients with anterior circulation large vessel occlusions after endovascular therapy are lacking. We aim to develop a tool that incorporates clinical and imaging data to predict outcomes after endovascular therapy. In a derivation cohort of anterior circulation large vessel occlusion stroke patients treated with endovascular therapy within 8 hours from time last seen well (n=247), we performed logistic regression to identify independent predictors of good outcome (90-day modified Rankin Scale, 0-2). Factors were weighted based on β-coefficients to derive the Pittsburgh Outcomes After Stroke Thrombectomy (POST) score. POST was validated in an institutional endovascular database (University of Pittsburgh Medical Center, n=393) and the Diffusion-Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) data set (n=105), as well as in patients treated beyond 8 hours (n=194) and in octogenarians (n=111). In the derivation cohort, independent predictors (PPittsburgh Medical Center, AUC=0.81; DEFUSE-2, AUC=0.86), as well as in patients treated beyond 8 hours (AUC, 0.85) and octogenarians (AUC=0.76). POST had better predictive accuracy for good and poor outcome than the ischemic stroke predictive risk score (iSCORE). POST score is a validated predictor of outcome in patients with anterior circulation large vessel occlusions after endovascular therapy. © 2014 American Heart Association, Inc.

  7. Ocular kinetics of pefloxacin after intramuscular administration in albino and pigmented rabbits.

    Science.gov (United States)

    Cochereau-Massin, I; Bauchet, J; Faurisson, F; Vallois, J M; Lacombe, P; Pocidalo, J J

    1991-06-01

    We determined the ocular kinetics of pefloxacin, a new fluoroquinolone, when administered by the intramuscular route to albino and pigmented rabbits. In serum of albino rabbits, the area under the concentration-time curve (AUC) for the experimental period was 31.4 +/- 1.07 micrograms.h/ml (mean +/- standard deviation); the AUCs in the aqueous and vitreous humors were high (10.5 +/- 1.90 and 12.4 +/- 3.79 micrograms.h/ml, respectively). Pefloxacin was found in the avascular ocular tissues (30.15 +/- 3.79 micrograms.h/ml in the cornea and 6.98 +/- 1.06 micrograms.h/ml in the lens). In the vascularized tissues, the penetration ratio, defined as tissue AUC/serum AUC, was more than 1. The good intraocular diffusion of pefloxacin might be related to its low molecular weight and to its strong lipophilicity and could explain its clinical efficacy in the treatment of endophthalmitis. In pigmented rabbits, pefloxacin levels were high in the iris (1525 +/- 328 micrograms.h/ml, versus 40.2 +/- 5.08 micrograms.h/ml in albino rabbits) and chorioretina (2600 +/- 422 micrograms.h/ml, versus 48.3 +/- 7.52 micrograms.h/ml in albino rabbits), suggesting that it binds to the pigmentary apparatus.

  8. Oral bioavailability and pharmacokinetic study of cetrizine HCl in Iranian healthy volunteers

    Science.gov (United States)

    Derakhshandeh, K.; Mohebbi, M.

    2009-01-01

    The objective of the present study was to evaluate the pharmacokinetic parameters and bioavailability of a selective histamine (H1)-receptor antagonist, cetirizine hydrochloride (CTZ), following administration of a single oral dose of the drug. The properties of a test compound were compared with those of a reference product in a randomized cross-over study in 12 volunteers. Blood samples were collected at selected time intervals up to 24 h and plasma concentrations of CTZ were determined using a validated HPLC method. Pharmacokinetic parameters including T1/2, T1/2(abs), K, Ka, Tmax, Cmax, Vd/F, Cl/F, AUC0-24, AUC 0-∞ and MRT were determined from plasma concentration-time profiles for tested products and found to be in good agreement with previous reports. The analysis of variance did not show any significant differences between the test and reference products. The confidence intervals for the ratio of Cmax (95-110%), AUC0-24 (91-112%) and AUC0-∞ (92-109%) for the test and reference products were within the acceptable interval of 80-125%. ANOVA assessment of logarithmically transformed data did not reveal any significant subject, period or sequence effects. It was, therefore, concluded that the two products were bioequivalent and could be used interchangeably. PMID:21589806

  9. Comparative bioavailability study with two gemfibrozil tablet formulations in healthy volunteers.

    Science.gov (United States)

    Borges, Ney Carter do C; Mendes, Gustavo Duarte; Barrientos-Astigarraga, Rafael E; Zappi, Eduardo; Mendes, Fabiana Duarte; De Nucci, Gilberto

    2005-01-01

    To assess the bioequivalence of gemfibrozil (CAS 25812-30-0) 900 mg tablet formulation from EMS Farmaceutica as test formulation versus a 900 mg tablet formulation as reference in 36 healthy volunteers of both sexes. The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Plasma samples were obtained over a 24-h period. Plasma gemfibrozil concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). From the gemfibrozil plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUClast, AUC(0-inf) and Cmax. The limit of quantification was 0.05 microg/mL for plasma gemfibrozil analysis. The geometric mean and respective 90% confidence interval (CI) of Test/Reference percent ratios were 90.29 (81.39-100.17) for Cmax, 96.26 (90.33-102.59) for AUClast, 96.04 (90.21-102.23) for AUC(0-24 h) and 96.62 (90.82-102.78) for AUC(0-infinity). Since the 90% CI for AUClast, AUC(0-inf) and Cmax, ratios were within the 80-125% interval proposed by the U.S. FDA, it was concluded that gemfibrozil 900 mg tablet (test formulation) was bioequivalent to the 900 mg tablet reference formulation for both rate and extent of absorption.

  10. Dynamic contrast enhanced MR imaging for evaluation of angiogenesis of hepatocellular nodules in liver cirrhosis in N-nitrosodiethylamine induced rat model

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wei; Chen, Hui Juan; Huang, Wei; Zhang, Long Jiang [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Wang, Zhen J. [University of California, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2017-05-15

    To investigate whether dynamic contrast -enhanced MRI (DCE-MRI) can distinguish the type of liver nodules in a rat model with N-nitrosodiethylamine- induced cirrhosis. Liver nodules in cirrhosis were induced in 60 male Wistar rats via 0.01 % N-nitrosodiethylamine in the drinking water for 35-100 days. The nodules were divided into three groups: regenerative nodule (RN), dysplastic nodule (DN), and hepatocellular carcinoma (HCC). DCE-MRI was performed, and parameters including transfer constant (K{sup trans}), rate constant (K{sub ep}), extravascular extracellular space volume fraction (V{sub e}), and initial area under the contrast concentration versus time curve (iAUC) were measured and compared. The highest K{sup trans} and iAUC values were seen in HCC, followed by DN and RN (all P < 0.05). The area under the receiver operating characteristic curve (AUROC) for DN and HCC were 0.738 and 0.728 for K{sup trans} and iAUC, respectively. The AUROC for HCC were 0.850 and 0.840 for K{sup trans} and iAUC, respectively. Ordinal logistic regression analysis showed that K{sup trans} had a high goodness of fit (0.970, 95 % confidence interval, 13.751-24.958). DCE-MRI is a promising method to differentiate of liver nodules. Elevated K{sup trans} suggested that the nodules may be transformed into HCC. (orig.)

  11. Pharmacokinetic (PK) drug interaction studies of cabozantinib: Effect of CYP3A inducer rifampin and inhibitor ketoconazole on cabozantinib plasma PK and effect of cabozantinib on CYP2C8 probe substrate rosiglitazone plasma PK.

    Science.gov (United States)

    Nguyen, Linh; Holland, Jaymes; Miles, Dale; Engel, Caroline; Benrimoh, Natacha; O'Reilly, Terry; Lacy, Steven

    2015-09-01

    Cabozantinib is a small-molecule tyrosine kinase inhibitor that has been approved for the treatment of patients with progressive, metastatic medullary thyroid cancer. In vitro data indicate that (1) cytochrome P450 (CYP) 3A4 is the primary CYP isoenzyme involved in the metabolism of cabozantinib, and (2) CYP2C8 is the CYP isoenzyme most potently inhibited by cabozantinib with potential for in vivo inhibition at clinically relevant plasma exposures. Pharmacokinetic (PK) drug-drug interactions (DDIs) were evaluated clinically between cabozantinib and (1) a CYP3A inducer (rifampin) in healthy volunteers, (2) a CYP3A inhibitor (ketoconazole) in healthy volunteers, and (3) a CYP2C8 substrate (rosiglitazone) in patients with solid tumors. Compared with cabozantinib given alone, coadministration with rifampin resulted in a 4.3-fold higher plasma clearance (CL/F) of cabozantinib and a 77% decrease in cabozantinib plasma AUC0-inf , whereas coadministration with ketoconazole decreased cabozantinib CL/F by 29% and increased cabozantinib AUC0-inf by 38%. Chronic coadministration with cabozantinib resulted in no significant effect on rosiglitazone plasma Cmax , AUC0-24 , or AUC0-inf . In summary, chronic use of strong CYP3A inducers and inhibitors should be avoided when cabozantinib is administered, and cabozantinib at clinically relevant exposures is not anticipated to markedly affect the PK of concomitant medications via CYP enzyme inhibition. © 2015, The American College of Clinical Pharmacology.

  12. Bioequivalence of ciprofloxacin tablet formulations assessed in Indonesian volunteers.

    Science.gov (United States)

    Harahap, Y; Prasaja, B; Indriati, E; Lusthom, W; Lipin

    2007-06-01

    Determination of the bioequivalence of two ciprofloxacin tablet formulations (test formulation manufactured by Novell Pharmaceutical Laboratories, Indonesia, reference formulation from Quimica Farmaceutica Bayer, Spain). 24 healthy volunteers received each of the two ciprofloxacin formulations at a dose of 500 mg in a 2-way crossover design. Blood samples were obtained prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and24h after drug administration. Plasma concentrations of ciprofloxacin were monitored using high-performance liquid chromatography over a period of 24 h after administration. The pharmacokinetics parameter AUC0-24h, AUC0-infinity and Cmax were tested for bioequivalence after log-transformation of data and ratios of tmax were evaluated non-parametrically. The point estimates and 90% confidence intervals for AUC0-24h, AUC0-infinity and Cmax were 97.55% (92.71 - 102.6%), 97.63% (92.90 - 102.59%) and 95.84% (89.95 - 102.10%), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. These results indicate that two medications of ciprofloxacin are bioequivalent and, thus, may be prescribed interchangeably.

  13. Influence of Fructooligosaccharide on Pharmacokinetics of Isoflavones in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Supanimit Teekachunhatean

    2012-01-01

    Full Text Available The objective of the present paper was to determine the influence of fructooligosaccharide (FOS on the pharmacokinetics of isoflavones in healthy postmenopausal women. The study was a fixed-sequence, two-phase, crossover study. Twelve subjects received a single oral dose of 300 mL of a soy beverage. Blood samples were collected before the dose and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, and 32 h after the administration of the soy beverage. After a washout period of at least 1 week, subjects were assigned to receive oral doses of FOS, 5 g each time, twice a day (after breakfast and dinner for 14 days, followed by a single oral dose of the same soy beverage on the next day. Blood samples were then collected at the same time points mentioned previously. Plasma isoflavone concentrations were determined by HPLC. Continuous oral administrations of FOS followed by a single oral administration of soy beverage caused significant increases in Cmax, AUC0–32, and AUC0–∞ of genistein and AUC0–32 of daidzein, comparing to those obtained following a single oral dose of soy beverage alone. Other pharmacokinetic parameters (Tmax and t1/2 of both aglycones and AUC0–∞ of daidzein between both regimens were not significantly different.

  14. [Acute coronary syndrome in nonagenarians: clinical evolution and validation of the main risk scores].

    Science.gov (United States)

    Gómez-Talavera, Sandra; Núñez-Gil, Iván; Vivas, David; Ruiz-Mateos, Borja; Viana-Tejedor, Ana; Martín-García, Agustín; Higueras-Nafría, Javier; Macaya, Carlos; Fernández-Ortiz, Antonio

    2014-01-01

    Several risk scores regarding the probability of death/complications in the acute setting and during the follow-up of patients admitted with acute coronary syndromes (ACS) have been published, such as the GRACE, TIMI and ZWOLLE risk score. Our objective was to assess the prognosis of nonagenarians admitted to a coronary care unit with an ACS, as well as the usefulness of each of these scores. A retrospective analysis was performed on nonagenarians with an ACS admitted between 2003 and 2011. Vital status was determined at 14, 30 days, and 6 months after the ACS, and later during the follow-up. The risk scores were evaluated by area under the curve ROC (AUC). A total of 45 patients with an ACS, 26 (57.8%) with ST-segment elevation and 19 (42.2%) with non-ST elevation. The GRACE- AUC for in-hospital mortality was excellent, 0.91, (95% CI: 0.82-1; PTIMI-AUC and ZWOLLE-AUC did not reach statistical significance. It is useful calculate the GRACE risk score in order to estimate risk and survival in the acute phase of ACS in nonagenarians. This can help appropriate in making invasive or conservative treatment decisions. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.

  15. Evidence of CYP3A Allosterism In Vivo: Analysis of Fluconazole and Midazolam Interaction

    Science.gov (United States)

    Yang, Jing; Atkins, William M.; Isoherranen, Nina; Paine, Mary F.; Thummel, Kenneth E.

    2013-01-01

    The allosteric effect of fluconazole (effector) on the formation of 1’-hydroxymidazolam (1’-OH-MDZ) and 4-hydroxymidazolam (4-OH-MDZ) from the CYP3A4/5 substrate, midazolam (MDZ), was examined in healthy volunteers. Following pre-treatment of fluconazole, AUC4-OH/AUCMDZ increased 35–62%, while AUC1’-OH/AUCMDZ decreased 5–37%; AUC1’-OH/AUC4-OH ratio decreased 46–58% by fluconazole and had no association with CYP3A5 genotype. 1’-OH-MDZ formation in vitro was more susceptible than 4-OH-MDZ formation to inhibition by fluconazole. Fluconazole decreased the intrinsic formation clearance ratio of 1’-OH-MDZ/4-OH-MDZ to an extent that was quantitatively comparable to in vivo observations. The elimination clearance of midazolam metabolites appeared unaffected by fluconazole. This study demonstrated that fluconazole alters midazolam product formation both in vivo and in vitro in a manner consistent with an allosteric interaction. The 1'-OH-MDZ/4-OH-MDZ ratio may serve as a biomarker of such interactions between midazolam, CYP3A4/5 and other putative effectors. PMID:22048224

  16. Applicability of a Single Time Point Strategy for the Prediction of Area Under the Concentration Curve of Linezolid in Patients

    DEFF Research Database (Denmark)

    Srinivas, Nuggehally R; Syed, Muzeeb

    2016-01-01

    models displayed excellent correlation, with r values of >0.9760. However, linezolid AUC values were predicted to be within the narrower boundary of 0.76 to 1.5-fold by a higher percentage by the Ctrough (78.3 %) versus Cmax model (48.2 %). The Ctrough model showed superior correlation of predicted...

  17. Development and Validation of the Juvenile Sexual Offense Recidivism Risk Assessment Tool-II.

    Science.gov (United States)

    Epperson, Douglas L; Ralston, Christopher A

    2015-12-01

    This article describes the development and initial validation of the Juvenile Sexual Offense Recidivism Risk Assessment Tool-II (JSORRAT-II). Potential predictor variables were extracted from case file information for an exhaustive sample of 636 juveniles in Utah who sexually offended between 1990 and 1992. Simultaneous and hierarchical logistic regression analyses were used to identify the group of variables that was most predictive of subsequent juvenile sexual recidivism. A simple categorical scoring system was applied to these variables without meaningful loss of accuracy in the development sample for any sexual (area under the curve [AUC] = .89) and sexually violent (AUC = .89) juvenile recidivism. The JSORRAT-II was cross-validated on an exhaustive sample of 566 juveniles who had sexually offended in Utah in 1996 and 1997. Reliability of scoring the tool across five coders was quite high (intraclass correlation coefficient [ICC] = .96). Relative to the development sample, however, there was considerable shrinkage in the indices of predictive accuracy for any sexual (AUC = .65) and sexually violent (AUC = .65) juvenile recidivism. The reduced level of accuracy was not explained by severity of the index sexual offense, time at risk, or missing data. Capitalization on chance and other explanations for the possible reduction in predictive accuracy are explored, and potential uses and limitations of the tool are discussed. © The Author(s) 2014.

  18. Preface and Program

    Directory of Open Access Journals (Sweden)

    Päivi Soppela

    2002-04-01

    Full Text Available A group of PhD students, post-doctoral scientists and senior scientists gathered together in Tromsø, August 1999 for the 1st CAES Workshop 'Reindeer 2000', in conjunction with the 10th Arctic Ungulate Conference (AUC. The purpose of the workshop was to stimulate the interdisciplinary approach and communication in studies relating to reindeer and reindeer husbandry.

  19. Research

    African Journals Online (AJOL)

    abp

    2017-06-28

    Jun 28, 2017 ... Clinical characteristics, PCT and CRP levels of neonates with positive blood culture are shown in Table 3. Diagnostic accuracy of PCT and CRP: The receiver operator characteristic curves (ROCs) of PCT and CRP are shown in Figure 1. The area under the receiver operating characteristic curve (AUC) for.

  20. Bayesian estimation of the receiver operating characteristic curve for a diagnostic test with a limit of detection in the absence of a gold standard.

    Science.gov (United States)

    Jafarzadeh, Seyed Reza; Johnson, Wesley O; Utts, Jessica M; Gardner, Ian A

    2010-09-10

    The receiver operating characteristic (ROC) curve is commonly used for evaluating the discriminatory ability of a biomarker. Measurements for a diagnostic test may be subject to an analytic limit of detection leading to immeasurable or unreportable test results. Ignoring the scores that are beyond the limit of detection of a test leads to a biased assessment of its discriminatory ability, as reflected by indices such as the associated area under the curve (AUC). We propose a Bayesian approach for the estimation of the ROC curve and its AUC for a test with a limit of detection in the absence of gold standard based on assumptions of normally and gamma-distributed data. The methods are evaluated in simulation studies, and a truncated gamma model with a point mass is used to evaluate quantitative real-time polymerase chain reaction data for bovine Johne's disease (paratuberculosis). Simulations indicated that estimates of diagnostic accuracy and AUC were good even for relatively small sample sizes (n=200). Exceptions were when there was a high per cent of unquantifiable results (60 per cent) or when AUC was < or =0.6, which indicated a marked overlap between the outcomes in infected and non-infected populations.

  1. Comparison of proteomic biomarker panels in urine and serum for ovarian cancer diagnosis

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Simonsen, Anja Hviid; Høgdall, Estrid

    2010-01-01

    The purposes of this study were to confirm previously found candidate epithelial ovarian cancer biomarkers in urine and to compare a paired serum biomarker panel and a urine biomarker panel from the same study cohort with regard to the receiver operating characteristic curve (ROC) area under...... the ROC curve (AUC) values....

  2. Download this PDF file

    African Journals Online (AJOL)

    therapeutic effectiveness of various brands index drugs (3) different brands has d with digoxin (4),. - nisolone (6), effect time curve were 83.91–100.7 and 31. /2–1 ... than after the d 13.8 min) and. Pharmacodynamic Bioeduivalence. N. Parvez et al. 65. -. The AUC did not differ following º Of the three formulations (1031, 879.

  3. Absorption kinetics of two highly concentrated preparations of growth hormone: 12 IU/ml compared to 56 IU/ml

    DEFF Research Database (Denmark)

    Laursen, Torben; Susgaard, Søren; Jensen, Flemming Steen

    1994-01-01

    in the interval 0.8-1.25, implying that the two preparations are bioequivalent. Neither AUC (P = 0.90), Cmax (p = 0.47) or Tmax (P = 0.86) for the two formulations of growth hormone were significantly different. Similar levels of serum IGF-I, IGFBP-3, insulin and blood glucose were obtained.(ABSTRACT TRUNCATED...

  4. bioequivalence study on two 10% enrofloxacin oral formulations in ...

    African Journals Online (AJOL)

    AONDOVER

    Ratios of Cmax, and AUC0-24(T/R) were 0.91 and 1.29 respectively. These are within the bioequivalence acceptance range. conflox. ®. -vet and kenflox. ® are therefore bioequivalent and interchangeable. Key words: Antibacterial, Bioequivalence, Enrofloxacin, Plasma. INTRODUCTION. Enrofloxacin is a third generation,.

  5. Relation between peak and integral of the diaphragm electromyographic activity at different levels of support during weaning from mechanical ventilation: a physiologic study.

    Science.gov (United States)

    Muttini, Stefano; Villani, Pier Giorgio; Trimarco, Roberta; Bellani, Giacomo; Grasselli, Giacomo; Patroniti, Nicolò

    2015-02-01

    To investigate the relationship between peak (EAdipeak) and area under the curve (EAdiAUC) of diaphragm electrical activity, and to evaluate the validity of their ratio (P/I index) as a measure of the imbalance between drive and sustainability of effort demand at different support levels. Prospective physiological study on 18 ready-to-wean patients ventilated with neurally adjusted ventilatory assist (NAVA) undergoing 2 levels of NAVA (NAVA100% and NAVA50%) followed by a weaning trial with continuous positive airway pressure, according to which patients were classified as success or failure. Tidal volume (VT), respiratory rate, EAdipeak, EAdiAUC, rapid shallow breathing index (respiratory rate/VT), neuroventilatory index (VT/EAdipeak), and P/I index were obtained at the end of each step. The slopes of regression line between EAdipeak and EAdiAUC (a mathematical equivalent of P/I index) and P/I index were significantly higher in failures. At variance with other variables, P/I index did not vary with level of support. P/I index was inversely correlated with inspiratory time at all support levels. The relationship between EAdipeak and EAdiAUC and the P/I index may give important information on the balance between respiratory drive and inspiratory demand sustainability. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Procalcitonin Improves the Glasgow Prognostic Score for Outcome Prediction in Emergency Patients with Cancer: A Cohort Study

    Directory of Open Access Journals (Sweden)

    Anna Christina Rast

    2015-01-01

    Full Text Available The Glasgow Prognostic Score (GPS is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT, white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males, 81 (23.8% died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67 for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9, P<0.001, AUC 0.69 and significantly improved the GPS to a combined AUC of 0.74 (P=0.007. Considering all investigated biomarkers, the AUC increased to 0.76 (P<0.001. The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventional trials.

  7. Variations in predicted risks in personal genome testing for common complex diseases.

    Science.gov (United States)

    Kalf, Rachel R J; Mihaescu, Raluca; Kundu, Suman; de Knijff, Peter; Green, Robert C; Janssens, A Cecile J W

    2014-01-01

    The promise of personalized genomics for common complex diseases depends, in part, on the ability to predict genetic risks on the basis of single nucleotide polymorphisms. We examined and compared the methods of three companies (23andMe, deCODEme, and Navigenics) that have offered direct-to-consumer personal genome testing. We simulated genotype data for 100,000 individuals on the basis of published genotype frequencies and predicted disease risks using the methods of the companies. Predictive ability for six diseases was assessed by the AUC. AUC values differed among the diseases and among the companies. The highest values of the AUC were observed for age-related macular degeneration, celiac disease, and Crohn disease. The largest difference among the companies was found for celiac disease: the AUC was 0.73 for 23andMe and 0.82 for deCODEme. Predicted risks differed substantially among the companies as a result of differences in the sets of single nucleotide polymorphisms selected and the average population risks selected by the companies, and in the formulas used for the calculation of risks. Future efforts to design predictive models for the genomics of common complex diseases may benefit from understanding the strengths and limitations of the predictive algorithms designed by these early companies.

  8. Factors affecting intrasubject variability of PK exposure: absolute oral bioavailability and acidic nature of drugs.

    Science.gov (United States)

    Sato, Masahiko; Narukawa, Mamoru

    2015-11-01

    The aim of the present study is to investigate factors affecting intrasubject variability of pharmacokinetic (PK) exposure, which affect the results of bioequivalence (BE) studies. We focused on two factors: absolute oral bioavailability (BA) and acidic nature of drugs. Intrasubject coefficient of variation (CV) for Cmax and AUC was estimated based on the 90% confidence intervals (CIs) and the number of subjects from fasting BE study results for our investigation. Relationships between the intrasubject CV and the absolute oral BA as well as the acidic nature of the drugs were investigated. First, the relationship between absolute oral BA and intrasubject variability of PK exposure (Cmax and AUC) showed negative log-linear relationship in the BE studies following oral administration of 65 immediate-release drugs under fasted condition. Drugs with poor absolute oral BA of less than 5% showed high intrasubject CV in the range of 30-65%. In contrast, drugs with high absolute oral BA of more than 80% showed low intrasubject CV of less than 20%. Second, acidic drugs with pKadrugs. The intrasubject CV ratios of Cmax to AUC for acidic drugs with pKadrugs. Results show that absolute oral BA is one of the major factors that predict the extent of intrasubject variability of PK exposure. Acidic nature of drugs is thought to be an additional factor increasing intrasubject variability of Cmax as compared to AUC.

  9. Bioavailability of a crushed pantoprazole tablet after buffering with sodium hydrogencarbonate or magaldrate relative to the intact enteric coated pantoprazole tablet.

    Science.gov (United States)

    Ley, L M; Stahlheber-Dilg, B; Sander, P; Huber, R; Mascher, H; Lücker, P W

    2001-01-01

    The aim of this study was to determine the bioavailability of orally administered, crushed pantoprazole tablets after buffering with either 1.4% sodium hydrogencarbonate or 1600 mg magaldrate relative to the intact enteric coated pantoprazole tablet. A single dose, three-period crossover study was performed with 18 healthy male volunteers. The crushed pantoprazole suspension, together with either sodium hydrogencarbonate or magaldrate, was administered via a nasogastral tube. Tmax of crushed pantoprazole was earlier as compared to the intact tablet (0.5 h vs. 3 h) and Cmax was approximately 10% higher due to faster absorption. The bioavailability of the crushed pantoprazole tablet relative to the intact pantoprazole tablet was 93% when using sodium hydrogencarbonate as the buffering agent, and 88% when using magaldrate. Based on the internationally approved confidence intervals for AUC (0.80-1.20) and Cmax (0.70-1.43), the crushed tablet buffered with sodium hydrogencarbonate was shown to be bioequivalent with the intact tablet (point estimates for AUC or Cmax: 0.93 or 1.10). For the crushed tablet buffered with magaldrate (point estimates for AUC or Cmax: 0.88 or 1.12) bioequivalence with the intact tablet could not be formally demonstrated, although the lower confidence limit for AUC of 0.78 was only slightly below the lower limit of the equivalence range of 0.80.

  10. Artificial neural network for predicting pathological stage of clinically localized prostate cancer in a Taiwanese population

    Directory of Open Access Journals (Sweden)

    Chih-Wei Tsao

    2014-10-01

    Conclusion: ANN was superior to LR at predicting OCD in prostate cancer. Compared with the validation of current Partin Tables for the Taiwanese population, the ANN model resulted in larger AUCs and more accurate prediction of the pathologic stage of prostate cancer.

  11. Vom work Book Journal 2010 6b

    African Journals Online (AJOL)

    USER

    highest concentration of calcium ions in medicated water (as seen in group c ) level of the absorption .of ciprofloxacin will be reduced , hence reduced bioavailability There was also a direct linear relationship between the AUC values for tissue and the level of calcium hardness of water. This study therefore suggests a need ...

  12. Effect of Calcium (Hardness of Water) on the Uptake of Ciprofloxacin ...

    African Journals Online (AJOL)

    L respectively, showing that at the highest concentration of calcium ions in medicated water (as seen in group c ) level of the absorption .of ciprofloxacin will be reduced , hence reduced bioavailability There was also a direct linear relationship between the AUC values for tissue and the level of calcium hardness of water.

  13. Predictors of severity and survival in acute pancreatitis: validation of the efficacy of early warning scores.

    Science.gov (United States)

    Garcea, Giuseppe; Gouda, Mohammed; Hebbes, Christopher; Ong, Seok Ling; Neal, Christopher P; Dennison, Ashley R; Berry, David Paul

    2008-10-01

    Early Warning Scores (EWS) is a widely used scoring system monitoring patient progress, which we have previously shown to predict outcome from acute pancreatitis. This study examined EWS from a larger group of patients to confirm if this predictive value held true. The EWS scores were compared with the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, modified organ dysfunction scores, Imrie scores, computed tomography grading scores, and Ranson criteria for 181 admissions with acute pancreatitis. The accuracy of EWS in predicting outcome was determined by receiver operator characteristics. A total of 181 patients were identified with acute pancreatitis. On day 1 of admission, APACHE II scores were the most accurate predictor of mortality with an area under curve (AUC) values of 0.876, closely followed by EWS (AUC, 0.827). By day 2 and 3 after admission, the EWS was the most accurate predictor of mortality (AUC, 0.910 and 0.934, respectively). The APACHE II was the second most accurate scoring system at 48 and 72 hours (AUC, 0.892 and 0.911, respectively). The EWSs on days 2 and 3 after admission are sensitive and specific in predicting mortality from acute pancreatitis. It is as accurate as the APACHE II scores and easier to implement in daily practice.

  14. Diagnostic Value of the Updated Diamond and Forrester Score to Predict Coronary Artery Disease in Patients with Acute-Onset Chest Pain

    DEFF Research Database (Denmark)

    Sørgaard, Mathias; Linde, Jesper James; Kofoed, Klaus Fuglsang

    2016-01-01

    compared the diagnostic accuracy of PTP and stress testing assessed by the area under the receiver operating characteristic curve (AUC) to identify significant CAD, defined as at least 1 coronary artery branch with >70% diameter stenosis identified by CCTA. RESULTS: The diagnostic accuracy of PTP...

  15. Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

    DEFF Research Database (Denmark)

    Kristensen, Gitte; Berg, Kasper Drimer; Lippert, Solvej

    2017-01-01

    analysis and quantified using the areas under the ROC curve (AUC).Results: All soluble uPAR levels were significantly (p=0.03) higher in patients with N1 disease compared with patients with N0/x disease. ROC curves including clinical tumour stage, biopsy Gleason score, prostate-specific antigen and percent...

  16. Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects.

    Science.gov (United States)

    Qayyum, Aisha; Najmi, Muzammil Hasan; Abbas, Mateen

    2013-11-01

    Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen (100mg) either generic or branded product according to randomization scheme on each of 2 periods. Blood samples were collected and plasma flurbiprofen concentration was determined by a validated HPLC method. Pharmacokinetic parameters like AUC(0-t), AUC(0-oo), Cmax, Tmax, t½, Vd and clearance were determined. The 90% CI for the ratio of geometric means of test to reference product's pharmacokinetic variables was calculated. Pharmacokinetic parameters for two formulations were comparable. Ratio of means of AUC(0-24), AUC(0-oo) and Cmax for test to reference products and 90% CI for these ratios were within the acceptable range. The p-values calculated by TOST were much less than the specified value (p-0.05). ANOVA gave p-values which were more than the specified value (p-0.05) for sequence, subject, period and formulation. Test formulation of flurbiprofen (tablet Flurso) was found to meet the criteria for bioequivalence to branded product (tablet Ansaid) based on pharmacokinetic parameters.

  17. Development and evaluation of Korean version of Quality of Sexual Function (QSF-K) in healthy Korean women.

    Science.gov (United States)

    Lee, Yumi; Lim, Myong Cheol; Son, Yedong; Joo, Jungnam; Park, KiByung; Kim, Jung-Sup; Lee, Dong Ock; Park, Sang-Yoon

    2014-06-01

    This study was done to develop a Korean version of the Quality of Sexual Function (QSF-K) and evaluate the validity and reliability of the QSF-K. The participants were 220 women who visited the Center for Uterine Cancer at the National Cancer Center in Korea. Participants completed the scale once and then again at a two to four week interval. The QSF-K, Female Sexual Function Index (FSFI) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) were used in this study. Receiver operating characteristics (ROC) curve, area under the ROC curve (AUC), intraclass correlation coefficients (ICC), and Cronbach's alpha were analyzed. In the analysis of the reliability, Cronbach's alpha was 0.83 and the ICC was 0.70. The validity measured with the AUC of the QSF-K comparing the FSFI and Global Health/QOL of the EORTC-QLQ-C30 was 0.717 and 0.728, respectively. Specifically, the AUC of the sexual activity level of the QSF-K was 0.838 in the FSFI comparison. The AUC of the psycho-somatic QOL of the QSF-K was 0.758 in the Global Health/QOL of the EORTC-QLQ-C30 comparison. Approximately half of the women (51.8%) had mild complaints/problems. The Korean version of the QSF was developed and validated.

  18. Cross Validation of the Current Opioid Misuse Measure (COMM) to Monitor Chronic Pain Patients on Opioid Therapy

    Science.gov (United States)

    Butler, Stephen F.; Budman, Simon H.; Fanciullo, Gilbert J.; Jamison, Robert N.

    2010-01-01

    Objectives The Current Opioid Misuse Measure (COMM) is a self-report measure of risk for aberrant medication related behavior among persons with chronic pain who are prescribed opioids for pain. It was developed to complement predictive screeners of opioid misuse potential and improve a clinician's ability to periodically assess a patient's risk for opioid misuse. The aim of this study was to cross validate the COMM with a new sample of chronic noncancer pain patients. Methods Two hundred and twenty six (N=226) participants prescribed opioids for pain were recruited from five pain management centers in the US. Subjects completed the 17-item COMM and a series of self-report measures. Patients were rated by their treating physician, had a urine toxicology screen, and were classified on the Aberrant Drug Behavior index. Results The reliability and predictive validity in this cross validation as measured by the area under the curve (AUC) were found to be highly significant (AUC =.79) and not significantly different from the AUC obtained in the original validation study (AUC =.81). Reliability (coefficient α) was .83, which is comparable to the .86 obtained in the original sample. Discussion Results of the cross validation suggest that the psychometric parameters of the COMM are not based solely on unique characteristics of the initial validation sample. The COMM appears to be a reliable and valid screening tool to help detect current aberrant drug-related behavior among chronic pain patients. PMID:20842012

  19. Bug bites and stings: When to see a dermatologist

    Medline Plus

    Full Text Available ... programs 2018 AAD election Call for nominations Member benefits Become a member DermCare Team Professionalism and ethics ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding ...

  20. Dandruff: How to Treat

    Medline Plus

    Full Text Available ... programs 2018 AAD election Call for nominations Member benefits Become a member DermCare Team Professionalism and ethics ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding ...

  1. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... programs 2018 AAD election Call for nominations Member benefits Become a member DermCare Team Professionalism and ethics ... in Dermatology JAAD Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding ...

  2. Pharmacokinetics of Levofloxacin in Multidrug-and Extensively Drug-Resistant Tuberculosis Patients

    NARCIS (Netherlands)

    Boveneind - Vrubleuskaya ,van 't Natasha; Seuruk, Tatiana; van Hateren, Kai; van der Laan, Tridia; Kosterink, Jos G W; van der Werf, Tjip S; van Soolingen, Dick; van den Hof, Susan; Skrahina, Alena; Alffenaar, Jan-Willem C

    Pharmacodynamics are important in treatment of especially multidrug- and extensively resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to minimal inhibitory concentration (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter

  3. Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant Tuberculosis Patients

    NARCIS (Netherlands)

    Boveneind-Vrubleuskaya, N. Van't; Seuruk, T.; Hateren, K. van; Laan, T. van der; Kosterink, J.G.W.; Werf, T.S. van der; Soolingen, D. van; Hof, S. van den; Skrahina, A.; Alffenaar, J.C.

    2017-01-01

    Pharmacodynamics are especially important in the treatment of multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to MIC (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter for predicting the

  4. Predictive Dose-Based Estimation of Systemic Exposure Multiples in Mouse and Monkey Relative to Human for Antisense Oligonucleotides With 2′-O-(2-Methoxyethyl Modifications

    Directory of Open Access Journals (Sweden)

    Rosie Z Yu

    2015-01-01

    Full Text Available Evaluation of species differences and systemic exposure multiples (or ratios in toxicological animal species versus human is an ongoing exercise during the course of drug development. The systemic exposure ratios are best estimated by directly comparing area under the plasma concentration-time curves (AUCs, and sometimes by comparing the dose administered, with the dose being adjusted either by body surface area (BSA or body weight (BW. In this study, the association between AUC ratio and the administered dose ratio from animals to human were studied using a retrospective data-driven approach. The dataset included nine antisense oligonucleotides (ASOs with 2′-O-(2-methoxyethyl modifications, evaluated in two animal species (mouse and monkey following single and repeated parenteral administrations. We found that plasma AUCs were similar between ASOs within the same species, and are predictable to human exposure using a single animal species, either mouse or monkey. Between monkey and human, the plasma exposure ratio can be predicted directly based on BW-adjusted dose ratios, whereas between mouse and human, the exposure ratio would be nearly fivefold lower in mouse compared to human based on BW-adjusted dose values. Thus, multiplying a factor of 5 for the mouse BW-adjusted dose would likely provide a reasonable AUC exposure estimate in human at steady-state.

  5. Comfortable with Chaos: Operational Design in the Naval Special Warfare Planning Process

    Science.gov (United States)

    2011-05-08

    Nacional or ELN (National Liberation Army) conducted subversive attacks on Colombian institutions and organizations to further their Marxist cause...alternative approaches. Lastly, the Autodefensas Unidas de Colombia or AUC (Self-defense Forces of Colombia) was a home grown paramilitary movement that

  6. Interpreting incremental value of markers added to risk prediction models.

    Science.gov (United States)

    Pencina, Michael J; D'Agostino, Ralph B; Pencina, Karol M; Janssens, A Cecile J W; Greenland, Philip

    2012-09-15

    The discrimination of a risk prediction model measures that model's ability to distinguish between subjects with and without events. The area under the receiver operating characteristic curve (AUC) is a popular measure of discrimination. However, the AUC has recently been criticized for its insensitivity in model comparisons in which the baseline model has performed well. Thus, 2 other measures have been proposed to capture improvement in discrimination for nested models: the integrated discrimination improvement and the continuous net reclassification improvement. In the present study, the authors use mathematical relations and numerical simulations to quantify the improvement in discrimination offered by candidate markers of different strengths as measured by their effect sizes. They demonstrate that the increase in the AUC depends on the strength of the baseline model, which is true to a lesser degree for the integrated discrimination improvement. On the other hand, the continuous net reclassification improvement depends only on the effect size of the candidate variable and its correlation with other predictors. These measures are illustrated using the Framingham model for incident atrial fibrillation. The authors conclude that the increase in the AUC, integrated discrimination improvement, and net reclassification improvement offer complementary information and thus recommend reporting all 3 alongside measures characterizing the performance of the final model.

  7. Toward a model-based patient selection strategy for proton therapy: External validation of photon-derived normal tissue complication probability models in a head and neck proton therapy cohort.

    Science.gov (United States)

    Blanchard, Pierre; Wong, Andrew J; Gunn, G Brandon; Garden, Adam S; Mohamed, Abdallah S R; Rosenthal, David I; Crutison, Joseph; Wu, Richard; Zhang, Xiaodong; Zhu, X Ronald; Mohan, Radhe; Amin, Mayankkumar V; Fuller, C David; Frank, Steven J

    2016-12-01

    To externally validate head and neck cancer (HNC) photon-derived normal tissue complication probability (NTCP) models in patients treated with proton beam therapy (PBT). This prospective cohort consisted of HNC patients treated with PBT at a single institution. NTCP models were selected based on the availability of data for validation and evaluated by using the leave-one-out cross-validated area under the curve (AUC) for the receiver operating characteristics curve. 192 patients were included. The most prevalent tumor site was oropharynx (n=86, 45%), followed by sinonasal (n=28), nasopharyngeal (n=27) or parotid (n=27) tumors. Apart from the prediction of acute mucositis (reduction of AUC of 0.17), the models overall performed well. The validation (PBT) AUC and the published AUC were respectively 0.90 versus 0.88 for feeding tube 6months PBT; 0.70 versus 0.80 for physician-rated dysphagia 6months after PBT; 0.70 versus 0.68 for dry mouth 6months after PBT; and 0.73 versus 0.85 for hypothyroidism 12months after PBT. Although a drop in NTCP model performance was expected for PBT patients, the models showed robustness and remained valid. Further work is warranted, but these results support the validity of the model-based approach for selecting treatment for patients with HNC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Teicoplanin Dosing Strategy for Treatment of Staphylococcus aureus in Korean Patients with Neutropenic Fever

    Science.gov (United States)

    Ahn, Byung-Jin; Yim, Dong-Seok; Kwon, Jae-Cheol; Kim, Si-Hyun; Choi, Su-Mi

    2011-01-01

    Purpose The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (Ctrough) and microorganism-specific (AUC24/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever. Materials and Methods One thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC24/MIC >125 [or 345] using logistic analysis. Results The standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L, respectively. Conclusion The current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered. PMID:21623604

  9. Using quantitative image analysis to classify axillary lymph nodes on breast MRI: A new application for the Z 0011 Era

    Energy Technology Data Exchange (ETDEWEB)

    Schacht, David V., E-mail: dschacht@radiology.bsd.uchicago.edu; Drukker, Karen, E-mail: kdrukker@uchicago.edu; Pak, Iris, E-mail: irisgpak@gmail.com; Abe, Hiroyuki, E-mail: habe@radiology.bsd.uchicago.edu; Giger, Maryellen L., E-mail: m-giger@uchicago.edu

    2015-03-15

    Highlights: •Quantitative image analysis showed promise in evaluating axillary lymph nodes. •13 of 28 features performed better than guessing at metastatic status. •When all features were used in together, a considerably higher AUC was obtained. -- Abstract: Purpose: To assess the performance of computer extracted feature analysis of dynamic contrast enhanced (DCE) magnetic resonance images (MRI) of axillary lymph nodes. To determine which quantitative features best predict nodal metastasis. Methods: This institutional board-approved HIPAA compliant study, in which informed patient consent was waived, collected enhanced T1 images of the axilla from patients with breast cancer. Lesion segmentation and feature analysis were performed on 192 nodes using a laboratory-developed quantitative image analysis (QIA) workstation. The importance of 28 features were assessed. Classification used the features as input to a neural net classifier in a leave-one-case-out cross-validation and evaluated with receiver operating characteristic (ROC) analysis. Results: The area under the ROC curve (AUC) values for features in the task of distinguishing between positive and negative nodes ranged from just over 0.50 to 0.70. Five features yielded AUCs greater than 0.65: two morphological and three textural features. In cross-validation, the neural net classifier obtained an AUC of 0.88 (SE 0.03) for the task of distinguishing between positive and negative nodes. Conclusion: QIA of DCE MRI demonstrated promising performance in discriminating between positive and negative axillary nodes.

  10. A comparison of the clinical usefulness of neck circumference and waist circumference in individuals with severe obesity.

    Science.gov (United States)

    Assyov, Yavor; Gateva, Antoaneta; Tsakova, Adelina; Kamenov, Zdravko

    2017-02-01

    Purpose/Aim: Neck circumference (NC) is an emerging anthropometric parameter that has been proposed to reflect metabolic health. The aim of the current study was to compare its clinical usefulness to waist circumference (WC) in the assessment of individuals with severe obesity. A total of 255 subjects participated in the study. All anthropometric measurements were done by a single medical professional. Biochemical measurements included oral glucose-tolerance tests (OGTTs), fasting insulin, lipids, and hepatic enzymes. The mean age of the participants was 49 ± 12 years with the mean body mass index (BMI) of 36.9 ± 6.2 kg/m(2). Correlation analyses revealed that while WC was better associated with adiposity parameters, it was of little use in comparison to NC with regard to metabolic outcomes. In men, NC was positively associated with fasting plasma glucose, fasting insulin, FINDRISC scores. ROC analyses showed NC was better in distinguishing type 2 diabetes (AUC = 0.758; p < 0.001), insulin resistance (AUC = 0.757; p = 0.001), metabolic syndrome (AUC = 0.724; p < 0.001), and hypertension (AUC = 0.763; p = 0.001). Similar correlations were observed in women. Using binary logistic regression, we determined that a NC of ≥35 cm in women and ≥38 cm in men are valuable cut-off values to use in the everyday practice. In individuals with severe obesity, NC performs better than WC in the assessment of metabolic health.

  11. Predicting Bleeding Risk by Platelet Function Testing in Patients Undergoing Heart Surgery.

    Science.gov (United States)

    Kuliczkowski, Wiktor; Sliwka, Joanna; Kaczmarski, Jacek; Zysko, Dorota; Zembala, Michal; Steter, Damian; Zembala, Marian; Fortmann, Seth; Serebruany, Victor

    2015-11-01

    Predicting bleeding events in patients with coronary artery bypass grafting (CABG) represents an unmet medical need that may improve CABG outcomes. To assess the potential link between platelet function testing and bleeding risk in patients undergoing CABG. Platelet aggregation and clinical outcomes in 478 patients treated with aspirin and/or clopidogrel were retrospectively analyzed. Platelet activity was assessed prior to CABG with arachidonic acid (ASPI Test), and adenosine diphosphate(ADP Test) utilizing multiple-electrode aggregometry. In the study group of 478 patients, mean age was 65.2±15.2 years; 138 were women. The majority of patients (n = 198) underwent on-pump surgery, with 162 undergoing off-pump and 30 undergoing minimally invasive surgery. Forty-eight patients received artificial valve implantation alone, and 40 received valve implantation in combination with CABG. The analysis of the entire pool revealed that an ASPI test value <407 area under curve per minute (AUC*min) may be useful in predicting postoperative drainage. In CABG patients only, an ASPI test value <271 AUC*min predicted the need for red blood cell concentrate transfusion following surgery. In patients who stopped clopidogrel for up to 5 days before surgery, the ADP test failed to exhibit prognostic utility for predicting bleeding risk. In patients undergoing heart surgery, an ASPI test value <407 AUC*min may predict higher postoperative drainage, whereas <271 AUC*min may be linked to postoperative use of red blood cell concentrate. © 2015 Wiley Periodicals, Inc.

  12. Validation of the Seven Up Seven Down Inventory in bipolar offspring: screening and prediction of mood disorders. Findings from the Dutch Bipolar Offspring Study.

    Science.gov (United States)

    Mesman, E; Youngstrom, E A; Juliana, N K; Nolen, W A; Hillegers, M H J

    2017-01-01

    To validate the Seven Up Seven Down (7U7D), an abbreviated version of the General Behavior Inventory (GBI), as screener for mood disorders and test its ability to predict mood disorders over time in individuals at risk for bipolar disorder (BD). Bipolar offspring (n=108) were followed from adolescence into adulthood and assessed at baseline, 1-, 5- and 12 years follow-up (T1-T4 respectively). Offspring were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children--Present and Lifetime Version, Structured Clinical Interview for DSM-IV Axis I Disorders and the GBI. Performance of the GBI and 7U7D was functionally similar for the depression (7D) scale, but variable for the mania (7U) scale. As screener for mood disorders (T4), the 7D showed fair diagnostic efficiency (area under the curve (AUC) 0.68, pdisorder was only close to significant (7D AUC 0.66, p=0.078; 7U AUC 0.67, p=0.067). In terms of prediction of mood disorder onset between T1 and T4, the 7D, but not the 7U, was associated with new onset (AUC 0.67, pmood disorders in bipolar offspring. The clinical utility of the 7U7D needs further exploration for use in clinical and research settings. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Urine biomarkers of acute kidney injury in noncritically ill, hospitalized children treated with chemotherapy.

    Science.gov (United States)

    Sterling, Maya; Al-Ismaili, Zubaida; McMahon, Kelly R; Piccioni, Melissa; Pizzi, Michael; Mottes, Theresa; Lands, Larry C; Abish, Sharon; Fleming, Adam J; Bennett, Michael R; Palijan, Ana; Devarajan, Prasad; Goldstein, Stuart L; O'Brien, Maureen M; Zappitelli, Michael

    2017-10-01

    Cisplatin (Cis), carboplatin (Carb), and ifosfamide (Ifos) are common nephrotoxic chemotherapies. Biomarkers of tubular injury may allow for early acute kidney injury (AKI) diagnosis. We performed a two-center (Canada, United States) pilot study to prospectively measure serum creatinine (SCr), urine neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) in children receiving Cis/Carb (27 episodes), Ifos (30 episodes), and in 15 hospitalized, nonchemotherapy patients. We defined AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition. We compared postchemotherapy infusion NGAL and IL-18 concentrations (immediate postdose to 3 days later) to pre-infusion concentrations. We calculated area under the receiver operating characteristic curve (AUC) for postinfusion biomarkers to discriminate for AKI. Prechemotherapy infusion NGAL and IL-18 concentrations were not higher than nonchemotherapy control concentrations. Increasing chemotherapy dose was associated with increasing postinfusion (0-4 hr after infusion) NGAL (P 0.05). NGAL and IL-18 measured immediately after Ifos infusion discriminated for AKI with AUCs is 0.80 (standard error = 0.13) and 0.73 (standard error = 0.16), respectively. NGAL and IL-18 were not diagnostic of Cis-Carb-associated AKI. When AUCs were adjusted for age, all biomarker AUCs (Cis-Carb and Ifos) improved. Urine NGAL and IL-18 show promise as early AKI diagnostic tests in children treated with ifosfamide and may have a potential role in drug toxicity monitoring. © 2017 Wiley Periodicals, Inc.

  14. Low but Sufficient Anidulafungin Exposure in Critically Ill Patients

    NARCIS (Netherlands)

    van Wanrooy, Marjolijn J. P.; Rodgers, Michael G. G.; Uges, Donald R. A.; Arends, Jan P.; Zijlstra, Jan G.; Werf, van der Tjip S.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    The efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Patients in intensive care may be at risk for underexposure. In critically ill patients with an invasive Candida infection, the anidulafungin exposure and a possible correlation with disease

  15. Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

    Directory of Open Access Journals (Sweden)

    Susanna K. P. Lau

    2016-02-01

    Full Text Available To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6, lysophosphatidylethanolamine (LysoPE (n = 3, sphingomyelins (SM (n = 2 and phosphatidylcholine (PC (n = 1, with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0 possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%, and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%. Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0 representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.

  16. Toxicokinetics of 2-nitropropane in the rat

    NARCIS (Netherlands)

    Derks HJGM; Heinignen A van; Klaassen R; Olling M

    1989-01-01

    De toxicokinetiek van 2-nitropropaan na intraveneuze en orale toediening (in water en in olie) werd onderzocht. Uit de plasma-concentratie profielen werden farmacokinetische paramters berekend waarbij een open een-compartiment model werd gebruikt. Door AUC-waarden verkregen bij varierende

  17. Cerebrospinal fluid eosinophilia is a sensitive and specific test for the diagnosis of Parelaphostrongylus tenuis in camelids in the northeastern United States.

    Science.gov (United States)

    Pinn, Toby L; Bender, Hannah S; Stokol, Tracy; Erb, Hollis N; Schlafer, Donald H; Perkins, Gillian A

    2013-01-01

    Aberrant migration of Parelaphostrongylus tenuis in camelids results in neurologic deficits, recumbency, and sometimes death. An antemortem diagnosis of P. tenuis in camelids is typically based upon the presence of characteristic asymmetric neurologic deficits, known exposure to white-tailed deer, cerebrospinal fluid (CSF) eosinophilia, and response to treatment. The diagnostic accuracy of CSF eosinophil percentage for the diagnosis of P. tenuis in camelids has not been critically examined. The objective of the current study was to determine the sensitivity (Se) and specificity (Sp) of CSF eosinophil percentage, CSF eosinophil concentration, total nucleated cell concentration, and protein concentration for the antemortem diagnosis of P. tenuis. Medical records of camelids admitted to Cornell University with clinical signs of neurologic disease, CSF analysis, and necropsy were examined from January 2000 through December 2009. Se and Sp were determined by receiver operating characteristic curves in camelids diagnosed with P. tenuis (n = 13) or other conditions (n = 24) based on postmortem examination. More than 17% of eosinophils in CSF had a Se of 85% and Sp of 92% for P. tenuis diagnosis (area under the curve [AUC]: 0.87; SE AUC: 0.07; P 1.4 eosinophils/µl of CSF had a Se of 85% and Sp of 96% (AUC: 0.9; SE AUC: 0.06; P camelids residing in regions endemic to white-tailed deer.

  18. Development of an online, publicly accessible naive Bayesian decision support tool for mammographic mass lesions based on the American College of Radiology (ACR) BI-RADS lexicon

    Science.gov (United States)

    Benndorf, Matthias; Kotter, Elmar; Langer, Mathias; Herda, Christoph; Wu, Yirong; Burnside, Elizabeth S.

    2015-01-01

    Purpose To develop and validate a decision support tool for mammographic mass lesions based on a standardized descriptor terminology (BI-RADS lexicon) to reduce variability of practice. Materials and Methods We used separate training data (1276 lesions, 138 malignant) and validation data (1177 lesions, 175 malignant). We created naïve Bayes (NB) classifiers from the training data with 10-fold cross validation. Our “inclusive model” comprised BI-RADS categories, BI-RADS descriptors and age as predictive variables, our “descriptor model” comprised BI-RADS descriptors and age. The resulting NB classifiers were applied to the validation data. We evaluated and compared classifier performance with ROC-analysis. Results In the training data, the inclusive model yields an AUC of 0.959, the descriptor model yields an AUC of 0.910 (P<0.001). The inclusive model is superior to the clinical performance (BI-RADS categories alone, P<0.001), the descriptor model performs similarly. When applied to the validation data, the inclusive model yields an AUC of 0.935, the descriptor model yields an AUC of 0.876 (P<0.001). Again, the inclusive model is superior to the clinical performance (P<0.001), the descriptor model performs similarly. Conclusion We consider our classifier a step towards a more uniform interpretation of combinations of BI-RADS descriptors. We provide our classifier at www.ebm-radiology.com/nbmm/index.html. PMID:25576230

  19. Development of an online, publicly accessible naive Bayesian decision support tool for mammographic mass lesions based on the American College of Radiology (ACR) BI-RADS lexicon

    Energy Technology Data Exchange (ETDEWEB)

    Benndorf, Matthias; Kotter, Elmar; Langer, Mathias [University Hospital Freiburg, Department of Radiology, Freiburg (Germany); Herda, Christoph [Kantonsspital Graubuenden, Chur (Switzerland); Wu, Yirong; Burnside, Elizabeth S. [University of Wisconsin-Madison School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

    2015-06-01

    To develop and validate a decision support tool for mammographic mass lesions based on a standardized descriptor terminology (BI-RADS lexicon) to reduce variability of practice. We used separate training data (1,276 lesions, 138 malignant) and validation data (1,177 lesions, 175 malignant). We created naive Bayes (NB) classifiers from the training data with tenfold cross-validation. Our ''inclusive model'' comprised BI-RADS categories, BI-RADS descriptors, and age as predictive variables; our ''descriptor model'' comprised BI-RADS descriptors and age. The resulting NB classifiers were applied to the validation data. We evaluated and compared classifier performance with ROC-analysis. In the training data, the inclusive model yields an AUC of 0.959; the descriptor model yields an AUC of 0.910 (P < 0.001). The inclusive model is superior to the clinical performance (BI-RADS categories alone, P < 0.001); the descriptor model performs similarly. When applied to the validation data, the inclusive model yields an AUC of 0.935; the descriptor model yields an AUC of 0.876 (P < 0.001). Again, the inclusive model is superior to the clinical performance (P < 0.001); the descriptor model performs similarly. We consider our classifier a step towards a more uniform interpretation of combinations of BI-RADS descriptors. We provide our classifier at www.ebm-radiology.com/nbmm/index.html. (orig.)

  20. Application of contrast-enhanced ultrasonography in the diagnosis of skeletal muscle crush injury in rabbits

    Science.gov (United States)

    Zhang, C-D; Lv, F-Q; Li, Q-Y; Zhang, Y; Shi, X-Q; Li, X-Y

    2014-01-01

    Objective: To explore the diagnostic value of quantitative contrast-enhanced (CE) ultrasonography for crush injury in the hind limb muscles of rabbits. Methods: A total of 120 New Zealand white rabbits were randomized to receive compression on the left hind limb for either 2 h (n = 56) or 4 h (n = 56) to induce muscle crush injury. Another eight animals were not injured and served as normal controls. CE ultrasonography parameters such as peak intensity (PI), ascending slop, descending slop and area under curve (AUC) were measured at 0.5, 2, 6 and 24 h and 3, 7 and 14 days after decompression. Results: Compared with the uninjured muscles, reperfusion of the injured muscles showed early and high enhancement in CE ultrasonography images. The time-intensity curve showed a trend of rapid lift and gradual drop. The PI and AUC values differed significantly among the three groups and were positively correlated with serum and tissue biomarkers. Rabbits of the 4-h compression group showed significantly higher PI and AUC values, and serum and tissue parameters than the 2-h compression group at each time points. Conclusion: CE ultrasonography can effectively detect muscle crush injury and monitor dynamic changes of the injured muscles in rabbits. PI and AUC are promising diagnostic parameters for this disease. Advances in knowledge: CE ultrasonography might play an important role in the pre-hospital and bedside settings for the diagnosis of muscle crush injury. PMID:25026985

  1. A deep feature fusion methodology for breast cancer diagnosis demonstrated on three imaging modality datasets.

    Science.gov (United States)

    Antropova, Natalia; Huynh, Benjamin Q; Giger, Maryellen L

    2017-10-01

    Deep learning methods for radiomics/computer-aided diagnosis (CADx) are often prohibited by small datasets, long computation time, and the need for extensive image preprocessing. We aim to develop a breast CADx methodology that addresses the aforementioned issues by exploiting the efficiency of pre-trained convolutional neural networks (CNNs) and using pre-existing handcrafted CADx features. We present a methodology that extracts and pools low- to mid-level features using a pretrained CNN and fuses them with handcrafted radiomic features computed using conventional CADx methods. Our methodology is tested on three different clinical imaging modalities (dynamic contrast enhanced-MRI [690 cases], full-field digital mammography [245 cases], and ultrasound [1125 cases]). From ROC analysis, our fusion-based method demonstrates, on all three imaging modalities, statistically significant improvements in terms of AUC as compared to previous breast cancer CADx methods in the task of distinguishing between malignant and benign lesions. (DCE-MRI [AUC = 0.89 (se = 0.01)], FFDM [AUC = 0.86 (se = 0.01)], and ultrasound [AUC = 0.90 (se = 0.01)]). We proposed a novel breast CADx methodology that can be used to more effectively characterize breast lesions in comparison to existing methods. Furthermore, our proposed methodology is computationally efficient and circumvents the need for image preprocessing. © 2017 American Association of Physicists in Medicine.

  2. Carbamazepine induces bioactivation of cyclophosphamide and thiotepa

    NARCIS (Netherlands)

    Ekhart, Corine; Rodenhuis, Sjoerd; Beijnen, Jos H.; Huitema, Alwin D. R.

    2009-01-01

    PURPOSE: We report a patient with metastatic breast cancer who received three cycles of high-dose chemotherapy with cyclophosphamide [1,000 mg/(m(2) day)], thiotepa (80 mg/(m(2) day) and carboplatin (dose calculated based on modified Calvert formula with 3.25 mg min/ml as daily target AUC) over 4

  3. Predictive Accuracy of Calf Circumference Measurements to Detect Decreased Skeletal Muscle Mass and European Society for Clinical Nutrition and Metabolism-Defined Malnutrition in Hospitalized Older Patients.

    Science.gov (United States)

    Maeda, Keisuke; Koga, Takayuki; Nasu, Tomomi; Takaki, Miki; Akagi, Junji

    2017-01-01

    The ability to readily diagnose sarcopenia and malnutrition in a clinical setting is essential. This study is aimed at clarifying the calf circumference (CC) cut-off values for decreased skeletal muscle mass (SMM), according to the Asian Work Group for Sarcopenia's criteria definition of sarcopenia, and those for European Society for Clinical Nutrition and Metabolism-defined malnutrition, in hospitalized Japanese patients. The study involved 1,164 patients aged ≥65 years. Predictive CC cut-off values were determined using receiver operating curve (ROC) analyses. The predictive validity of the cut-off values was confirmed against in-hospital mortality. There were 654 females and 510 males (mean age, 83.5 ± 8.2 years). Decreased SMM and malnutrition were observed in 80.4 and 32.8% of all patients, respectively. ROC analyses identified CCs of ≤29 cm (female, area under the curve [AUC] 0.791) and ≤30 cm (male, AUC 0.832) as cut-off values for decreased SMM, and CCs of ≤26 cm (female, AUC 0.798) and ≤28 cm (male, AUC 0.837) for malnutrition. CC cut-off values for SMM and malnutrition were independently correlated with in-hospital mortality. The study determined appropriate cut-off values for CC to identify decreased SMM and malnutrition according to the relevant guidelines. © 2017 S. Karger AG, Basel.

  4. The use of real-time optical feedback to improve outcomes

    Science.gov (United States)

    Magaña, Isidro B.; Adhikari, Pratik; Yendluri, Raghuvara B.; Goodrich, Glenn P.; Schwartz, Jon A.; O'Neal, D. P.

    2014-03-01

    More than a decade into the development of gold nanoparticles for cancer therapies, with multiple clinical trials underway, ongoing pre-clinical research continues towards better understanding in vivo interactions with the goal of treatment optimization through improved best practices. In an effort to collect information for healthcare providers, enabling informed decisions in a relevant time frame, instrumentation for real-time plasma concentration (multi-wavelength pulse photometry) and protocols for rapid elemental analysis (energy dispersive X-Ray fluorescence) of biopsied tumor tissue have been developed in a murine model. An initial analysis, designed to demonstrate the robust nature and utility of the techniques, revealed that area under the bioavailability curve (AUC) alone does not currently inform tumor accumulation with a high degree of accuracy (R2=0.32), This finding suggests that the control of additional experimental and physiological variables may yield more predictable tumor accumulation. Subject core temperature are blood pressure were monitored, but did not demonstrate clear trends. An effort to modulate AUC has produced an adjuvant therapy which is employed to enhance circulation parameters, including the AUC, of nanorods and gold nanoshells. Preliminary studies demonstrated a greater than 300% increase in average AUC through the use of a reticuloendothelial blockade agent versus control groups. Given a better understanding of the relative importance of the physiological factors which impact rates of tumor accumulation, a proposed set of experimental best practices is presented.

  5. A Comparison of Intensive Care Unit Mortality Prediction Models through the Use of Data Mining Techniques.

    Science.gov (United States)

    Kim, Sujin; Kim, Woojae; Park, Rae Woong

    2011-12-01

    The intensive care environment generates a wealth of critical care data suited to developing a well-calibrated prediction tool. This study was done to develop an intensive care unit (ICU) mortality prediction model built on University of Kentucky Hospital (UKH)'s data and to assess whether the performance of various data mining techniques, such as the artificial neural network (ANN), support vector machine (SVM) and decision trees (DT), outperform the conventional logistic regression (LR) statistical model. The models were built on ICU data collected regarding 38,474 admissions to the UKH between January 1998 and September 2007. The first 24 hours of the ICU admission data were used, including patient demographics, admission information, physiology data, chronic health items, and outcome information. Only 15 study variables were identified as significant for inclusion in the model development. The DT algorithm slightly outperformed (AUC, 0.892) the other data mining techniques, followed by the ANN (AUC, 0.874), and SVM (AUC, 0.876), compared to that of the APACHE III performance (AUC, 0.871). With fewer variables needed, the machine learning algorithms that we developed were proven to be as good as the conventional APACHE III prediction.

  6. Limited sampling pharmacokinetics of subcutaneous ondansetron in healthy geriatric cats, cats with chronic kidney disease, and cats with liver disease.

    Science.gov (United States)

    Fitzpatrick, R L; Wittenburg, L A; Hansen, R J; Gustafson, D L; Quimby, J M

    2016-08-01

    Ondansetron, a 5-HT3 receptor antagonist, is an effective anti-emetic in cats. The purpose of this study was to compare pharmacokinetics of subcutaneous (SQ) ondansetron in healthy geriatric cats to cats with chronic kidney disease (CKD) or liver disease using a limited sampling strategy. 60 cats participated; 20 per group. Blood was drawn 30 and 120 min following one 2 mg (mean 0.49 mg/kg, range 0.27-1.05 mg/kg) SQ dose of ondansetron. Ondansetron concentrations were measured by liquid chromatography coupled to tandem mass spectrometry. Drug exposure represented as area under the curve (AUC) was predicted using a limited sampling approach based on multiple linear regression analysis from previous full sampling studies, and clearance (CL/F) estimated using noncompartmental methods. Kruskal-Wallis anova was used to compare parameters between groups. Mean AUC (ng/mL·h) of subcutaneous ondansetron was 301.4 (geriatric), 415.2 (CKD), and 587.0 (liver). CL/F (L/h/kg) of SQ ondansetron was 1.157 (geriatric), 0.967 (CKD), and 0.795 (liver). AUC was significantly higher in liver and CKD cats when compared to geriatric cats (P cats was significantly decreased (P cats. In age-matched subset analysis, AUC and CL/F in liver cats remained significantly different from geriatric cats. © 2015 John Wiley & Sons Ltd.

  7. Colombia: Issues for Congress

    Science.gov (United States)

    2007-11-09

    proyectos /justicia_y_paz.htm] on August 30, 2006; “Presidencia de la República de Colombia, “Listado de Privados de Libertad de las AUC Remitidos a...extradición: 8,” August 29, 2006, at [http://www.presidencia.gov.co/prensa_new/ proyectos /justicia_y_paz.htm

  8. In vivo release of bupivacaine from subcutaneously administered oily solution. Comparison with in vitro release

    DEFF Research Database (Denmark)

    Larsen, Dorrit Bjerg; Joergensen, Stig; Olsen, Niels Vidiendal

    2002-01-01

    administration of oily solution showed a prolonged bupivacaine release with lower peak plasma levels as compared to administration of an aqueous formulation applied in the same compartment. t(1/2), t(max), C(max) and AUC(0-infinity) for the aqueous solution were 63+/-8 min, 19+/-16 min, 194+/-46 ng x ml(-1...

  9. Bioavailability of high dose methotrexate in patients with rheumatoid arthritis : A pharmacokinetic analysis

    NARCIS (Netherlands)

    Hoekstra, Monique; Neef, C; Knuijf, T; Proost, H; van de Laar, M; Haagsma, C

    Background: Although a clear relation between the pharmacokinetics of methotrexate (MTX) and its efficacy is difficult to establish, a relation between dose and efficacy was proven. For doses up to 15-20 mg week there is an increasing area under the serum concentration curve (AUC), and the

  10. Comparison of Simple Versus Performance-Based Fall Prediction Models

    Directory of Open Access Journals (Sweden)

    Shekhar K. Gadkaree BS

    2015-05-01

    Full Text Available Objective: To compare the predictive ability of standard falls prediction models based on physical performance assessments with more parsimonious prediction models based on self-reported data. Design: We developed a series of fall prediction models progressing in complexity and compared area under the receiver operating characteristic curve (AUC across models. Setting: National Health and Aging Trends Study (NHATS, which surveyed a nationally representative sample of Medicare enrollees (age ≥65 at baseline (Round 1: 2011-2012 and 1-year follow-up (Round 2: 2012-2013. Participants: In all, 6,056 community-dwelling individuals participated in Rounds 1 and 2 of NHATS. Measurements: Primary outcomes were 1-year incidence of “ any fall ” and “ recurrent falls .” Prediction models were compared and validated in development and validation sets, respectively. Results: A prediction model that included demographic information, self-reported problems with balance and coordination, and previous fall history was the most parsimonious model that optimized AUC for both any fall (AUC = 0.69, 95% confidence interval [CI] = [0.67, 0.71] and recurrent falls (AUC = 0.77, 95% CI = [0.74, 0.79] in the development set. Physical performance testing provided a marginal additional predictive value. Conclusion: A simple clinical prediction model that does not include physical performance testing could facilitate routine, widespread falls risk screening in the ambulatory care setting.

  11. A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

    DEFF Research Database (Denmark)

    Zhao, Huaying; Ghirlando, Rodolfo; Alfonso, Carlos

    2015-01-01

    Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish ...

  12. Collaborative Knowledge Building in Web-based Learning: Assessing the Quality of Dialogue

    DEFF Research Database (Denmark)

    Sorensen, Elsebeth Korsgaard; Takle, E. S.

    2001-01-01

    The conference was held in Tampera, Finland. [Online]. Available: http://dl.aace.org/8875 . {*Selected through double peer review by the International Program Committee and final blind review by the Conference Program Chairs from over 1100 papers from 60 countries to receive the ED-MEDIA 2001 Best...... Paper Award}. http://www.hum.auc.dk/ansatte/es/publikationer/collaborative.pdf...

  13. Comparison of the pharmacokinetics of erlotinib administered in complete fasting and 2 h after a meal in patients with lung cancer.

    Science.gov (United States)

    Katsuya, Yuki; Fujiwara, Yutaka; Sunami, Kuniko; Utsumi, Hirofumi; Goto, Yasushi; Kanda, Shintaro; Horinouchi, Hidehito; Nokihara, Hiroshi; Yamamoto, Noboru; Takashima, Yuki; Osawa, Satoko; Ohe, Yuichiro; Tamura, Tomohide; Hamada, Akinobu

    2015-07-01

    The recommended dose of erlotinib is 150 mg daily either 1 h before a meal (complete fasting) or 2 h after a meal (2 h post-meal), because of the food effect. We conducted a cross-over pharmacokinetic study to compare the fed bioequivalence in the two conditions. Twenty-three patients with non-small cell lung cancer were included in the analysis. AUC0-24 and C max in the 2-h post-meal status were significantly higher than in the complete fasting status (GMR = 1.33, P fasting state, we conducted analyses only on day 14, which showed no significant difference in AUC0-24 or C max between the two conditions. The more rapid increase in AUC0-24 and C min did not produce any earlier and more severe toxic events. The AUC0-24 increased significantly faster (48-53 % greater) in the 2-h post-meal status than in complete fasting status, which suggested that the two gastric emptying states might differ in their absorption. However, there was no clinically significant difference in bioavailability or toxicity between the two clinically used fed conditions at least in 14 days.

  14. New parameters available on Sysmex XE-5000 hematology analyzers contribute to differentiating dengue from leptospirosis and enteric fever.

    Science.gov (United States)

    Oehadian, A; Michels, M; de Mast, Q; Prihatni, D; Puspita, M; Hartantri, Y; Sinarta, S; van der Ven, A J A M; Alisjahbana, B

    2015-12-01

    Distinguishing dengue virus infection from other febrile thrombocytopenic illnesses such as leptospirosis or enteric fever is important but difficult, due to the unavailability of reliable diagnostic tests. Sysmex XE-5000 hematology analyzers use fluorescence flow cytometry to quantitate new parameters including cells in the atypical lymphocyte area (AL), high-fluorescent lymphocyte counts (HFLC), immature granulocytes (IG), and immature platelets (IPF). This study aimed to investigate whether these parameters can help to discriminate between the diseases. We compared hematocytometry performed by a Sysmex XE-5000 analyzer in Indonesian adults with dengue (n = 93), leptospirosis (n = 11), and enteric fever (n = 6) infection, and in healthy controls (n = 28). Receiver operating characteristic curves comparing dengue and leptospirosis showed that dengue was characterized by increased %AL (AUC 0.87; 95% CI 0.70-1.03), %HFLC (AUC 0.89; 95% CI 0.78-0.99), and %IPF (AUC 0.81; 95% CI 0.65-0.97), while patients with leptospirosis had increased %IG (AUC 0.86; 95% CI 0.71-1.02). Low %AL, %HFLC, and %IG supported a diagnosis of enteric fever. The detection of AL, HFLC, IG, and IPF by Sysmex XE-5000 hematology analyzers can help to differentiate between common causes of febrile illnesses with thrombocytopenia in dengue endemic areas. We recommend further investigating the discriminatory value of these parameters in clinical practice. © 2015 John Wiley & Sons Ltd.

  15. Comparing rat and rabbit embryo-fetal developmental toxicity ...

    Science.gov (United States)

    A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n=283), dLOAELs in rats and rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and rabbit were equally sensitive. The relative extent of embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and rabbit studies. Individual rat and rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects betwe

  16. How does pain experience relate to the need for pain relief?

    DEFF Research Database (Denmark)

    Johnsen, Anna Thit; Petersen, Morten A; Snyder, Claire F

    2016-01-01

    -C30 discriminated between patients with and without a need for pain relief to an acceptable degree (area under the curve (AUC) 0.73-0.77). The cut-point a little gave a sensitivity of 84 % and specificity of 59 % for the item "Have you had pain?" and a sensitivity of 72 % and a specificity of 72...

  17. ε-Acetamidocaproic acid pharmacokinetics in rats with gastric ulcer or small bowel inflammation.

    Science.gov (United States)

    Lee, U; Choi, Y H; Kim, Y G; Lee, B K; Oh, E; Lee, M G

    2012-03-01

    The pharmacokinetics of ϵ-acetamidocaproic acid (AACA) were evaluated after the intravenous and oral administration of an antiulcer agent, zinc acexamate (ZAC) at a dose of 20 mg kg⁻¹ (ion pairing between zinc and AACA) in rats with indomethacin-induced acute gastric ulcer (IAGU) or indomethacin-induced small bowel inflammation (ISBI). In IAGU rats, the area under the curves (AUCs) of AACA were significantly smaller after both the intravenous (551 versus 1270 μg min ml⁻¹) and oral (397 versus 562 μg min ml⁻¹) administration of ZAC than controls, possible due to the significantly faster CL(R) of AACA. In ISBI rats, however, the AUCs of AACA were comparable with controls after both the intravenous and oral administration of ZAC. In IAGU rats, the significantly smaller AUCs of AACA were due to the significantly faster CL(R) (due to the decreased urinary pH by indomethacin treatment) than controls. AACA has a basic secondary amine group. On the other hand, the comparable AUCs of AACA in ISBI rats were due to the comparable CL(R)s between ISBI and control rats. AACA was excreted in the urine via active renal tubular secretion in all rats studied.

  18. Unsupervised Behavior-Specific Dictionary Learning for Abnormal Event Detection

    DEFF Research Database (Denmark)

    Ren, Huamin; Liu, Weifeng; Olsen, Søren Ingvor

    2015-01-01

    dictionaries, but also on non zero distribution in coefficients. Experimental results on Anomaly Stairs dataset and UCSD Anomaly dataset show the effectiveness of our algorithm. Remarkably, our BSD algorithm can improve AUC significantly by 10% on the stricter pixel-level evaluation, compared to the best...

  19. Improving alcohol screening for college students: Screening for alcohol misuse amongst college students with a simple modification to the CAGE questionnaire.

    Science.gov (United States)

    Taylor, Purcell; El-Sabawi, Taleed; Cangin, Causenge

    2016-07-01

    To improve the CAGE (Cut down, Annoyed, Guilty, Eye opener) questionnaire's predictive accuracy in screening college students. The sample consisted of 219 midwestern university students who self-administered a confidential survey. Exploratory factor analysis, confirmatory factor analysis, receiver operating characteristics (ROC), and Cronbach's alpha were used to analyze factor structure, validity, and reliability. The modified CAGE correctly classified students with alcohol abuse ("AA students"; area under the curve [AUC] = 0.7765) and students with alcohol dependency ("AD students"; AUC = 0.8392) more often than CAGE (AA students: AUC = 0.6977; AD students: AUC = 0.7437), and these differences are statistically significant (AA students: χ(2)(1) = 14.72, p students: χ(2)(1) = 7.71, p students as AD, whereas the modified CAGE correctly identified 87% of AD students as AD. Using 1-point cut scores, CAGE correctly identified 65% AA students, whereas the modified CAGE identified 85.29%. The modified CAGE has better accuracy than CAGE in predicting AA and AD among college populations.

  20. Pharmacokinetics of cyclosporine in monkeys after oral and intramuscular administration : relation to efficacy in kidney allografting

    NARCIS (Netherlands)

    Schuurman, HJ; Slingerland, W; Mennninger, K; Ossevoort, M; Hengy, JC; Dorobek, B; Vouderscher, J; Ringers, J; Odeh, M; Jonker, Margreet

    In cynomolgus and rhesus monkeys, the dose-normalized exposure of cyclosporine administered orally as microemulsion preconcentrate (Neoral) was lower than that upon intramuscular administration. For oral administration, mean values (+/- SD) of C-max, 24-h area-under-the curve (AUC) and 24-h trough

  1. Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents

    Science.gov (United States)

    Schell, Ryan F.; Sidone, Brian J.; Caron, Whitney P.; Walsh, Mark D.; Zamboni, Beth A.; Ramanathan, Ramesh K.; Zamboni, William C.

    2013-01-01

    Purpose A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents. Methods Inter-patient PK variability of 9 liposomal and SM formulations of the same drug were evaluated. PK variability was measured as coefficient of variance (CV%) of area under the plasma concentration versus time curve (AUC) and the fold-difference between AUCmax and AUCmin (AUC range). Results CV% of AUC and AUC ranges were 2.7-fold (P<0.001) and 16.7-fold (P=0.13) greater, respectively, for liposomal compared with SM drugs. There was an inverse linear relationship between the clearance (CL) of liposomal agents and PK variability with a lower CL associated with greater PK variability (R2 = 0.39). PK variability of liposomal agents was greater when evaluated from 0–336 h compared with 0–24 h. Conclusion PK variability of liposomes is significantly greater than SM. The factors associated with the PK variability of liposomal agents needs to be evaluated. PMID:23891988

  2. Effect Of Different Degrees Of Hepatic Dysfunction On The ...

    African Journals Online (AJOL)

    Main outcome measures: Cmax, tmax, t 1/2, MRT, AUC0-∞, Cl/F and Vdss Results: The pharmacokinetic profile of telmisartan was characterized by rapid absorption kinetics and a slow terminal elimination phase with mean half life of 25 hours. The maximum plasma concentration and area under the telmisartan plasma ...

  3. Monochromatic Pupillometry in Unilateral Glaucoma Discloses no Adaptive Changes Subserved by the ipRGCs

    DEFF Research Database (Denmark)

    Nissen, Claus; Sander, Birgit Agnes; Milea, Dan

    2014-01-01

    , employing red (660 nm) or blue (470 nm) light, and by optical coherence tomography of the peripapillary retinal nerve fiber layer. The main outcome measure in pupillometry, the area under the curve (AUC), i.e., the product of pupillary contraction amplitude and time, was determined during and after light...... exposure in glaucomatous and unafflicted fellow eyes and compared to the AUCs of a healthy, age-matched control group. RESULTS: The AUC to stimulation with blue light was significantly reduced in glaucomatous eyes, both during and after stimulus, compared with that of fellow, unafflicted eyes (p ≤ 0.......014). The AUC to red light stimulation was reduced during (p = 0.035), but not after (p ≥ 0.072), exposure in glaucomatous eyes. In the unafflicted fellow eyes, the pupillary response to blue light did not differ from that of healthy controls. CONCLUSION: The pupillary response to blue light was decreased...

  4. Performance of Two Bioelectrical Impedance Analyses in the Diagnosis of Overweight and Obesity in Children and Adolescents: The FUPRECOL Study

    Directory of Open Access Journals (Sweden)

    Robinson Ramírez-Vélez

    2016-10-01

    Full Text Available This study aimed to determine thresholds for percentage of body fat (BF% corresponding to the cut-off values for overweight/obesity as recommended by the International Obesity Task Force (IOTF, using two bioelectrical impedance analyzers (BIA, and described the likelihood of increased cardiometabolic risk in our cohort defined by the IOTF and BF% status. Participants included 1165 children and adolescents (54.9% girls from Bogotá (Colombia. Body mass index (BMI was calculated from height and weight. BF% of each youth was assessed first using the Tanita BC-418® followed by a Tanita BF-689®. The sensitivity and specificity of both devices and their ability to correctly classify children as overweight/obesity (≥2 standard deviation, as defined by IOTF, was investigated using receiver operating characteristic (ROC by sex and age groups (9–11, 12–14, and 13–17 years old; Area under curve (AUC values were also reported. For girls, the optimal BF% threshold for classifying into overweight/obesity was found to be between 25.2 and 28.5 (AUC = 0.91–0.97 and 23.9 to 26.6 (AUC = 0.90–0.99 for Tanita BC-418® and Tanita BF-689®, respectively. For boys, the optimal threshold was between 16.5 and 21.1 (AUC = 0.93–0.96 and 15.8 to 20.6 (AUC = 0.92–0.94 by Tanita BC-418® and Tanita BF-689®, respectively. All AUC values for ROC curves were statistically significant and there were no differences between AUC values measured by both BIA devices. The BF% values associated with the IOTF-recommended BMI cut-off for overweight/obesity may require age- and sex-specific threshold values in Colombian children and adolescents aged 9–17 years and could be used as a surrogate method to identify individuals at risk of excess adiposity.

  5. Bioequivalence study of two formulations of flupirtine maleate capsules in healthy male Chinese volunteers under fasting and fed conditions

    Directory of Open Access Journals (Sweden)

    Liu YF

    2017-12-01

    Full Text Available Yanfang Liu, Hua Huo, Zhibo Zhao, Wenli Hu, Yujia Sun, Yunbiao Tang Technical Center for Clinical Pharmacy, Department of Drug Clinical Trail Management Agency, General Hospital of Shenyang Military Area Command, Shenyang, China Aim: This study developed a high-performance liquid chromatography–tandem mass spectrometry method to simultaneously determine the concentrations of flupirtine and its major active metabolite D-13223 in human plasma in order to assess the bioequivalence (BE of two flupirtine maleate capsules among healthy male Chinese volunteers under fasting and fed conditions. Materials and methods: There were two single-center, randomized, single-dose, open-label, laboratory-blinded, two-period, cross-over studies which included 24 healthy male Chinese volunteers under fasting and fed conditions, respectively. Plasma samples were collected prior to and up to 48 h after dosing. The concentrations of flupirtine and its major active metabolite D-13223 in plasma samples were determined by a validated method, that is, high-performance liquid chromatography coupled with a tandem mass spectrometry detector. Pharmacokinetic metrics of area from time zero to the last measurable concentration (AUC0-t, area under the plasma concentration–time curve from administration to infinite time (AUC0-∞, and Cmax were used for BE assessment. Results: Forty-eight healthy volunteers who met the criteria were enrolled and completed the study. According to the observation of vital signs and laboratory measurement, no volunteers had any adverse reactions. Under fasting condition, the geometric mean ratios (90% CI of the test/reference drug for flupirtine were 103.0% (98.1%–108.2% for AUC0-t, 102.9% (98.2%–107.9% for AUC0-∞, and 97.0% (85.9%–109.5% for Cmax. Under fed condition, the geometric mean ratios (90% CI of the test/reference drug for flupirtine were 101.7% (98.4%–105.1% for AUC0-t, 101.6% (98.5%–104.8% for AUC0-∞, and 103.5% (94.7%

  6. Pharmacokinetic profile of defibrotide in patients with renal impairment.

    Science.gov (United States)

    Tocchetti, Paola; Tudone, Elena; Marier, Jean-Francois; Marbury, Thomas C; Zomorodi, Katie; Eller, Mark

    2016-01-01

    Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable, potentially life-threatening complication of hematopoietic stem cell transplant conditioning. Severe VOD/SOS, generally associated with multiorgan dysfunction (pulmonary or renal dysfunction), may be associated with >80% mortality. Defibrotide, recently approved in the US, has demonstrated efficacy treating hepatic VOD/SOS with multiorgan dysfunction. Because renal impairment is prevalent in patients with VOD/SOS, this Phase I, open-label, two-part study in adults examined the effects of hemodialysis and severe or end-stage renal disease (ESRD) on defibrotide pharmacokinetics (PK). Part 1 compared defibrotide PK during single 6.25 mg/kg doses infused with and without dialysis. Part 2 assessed defibrotide plasma PK after multiple 6.25 mg/kg doses in nondialysis-dependent subjects with severe/ESRD versus healthy matching subjects. Among six subjects enrolled in Part 1, percent ratios of least-squares mean and 90% confidence intervals (CIs) on dialysis and nondialysis days were 109.71 (CI: 97.23, 123.78) for maximum observed plasma concentration (Cmax); 108.39 (CI: 97.85, 120.07) for area under the concentration-time curve to the time of the last quantifiable plasma concentration (AUC0-t); and 109.98 (CI: 99.39, 121.70) for AUC extrapolated to infinity (AUC0-∞). These ranges were within 80%-125%, indicating no significant effect of dialysis on defibrotide exposure/clearance. In Part 2, defibrotide exposure parameters in six subjects with severe/ESRD after multiple doses (AUC0-t, 113 µg·h/mL; AUC over dosing interval, 113 µg·h/mL; Cmax, 53.8 µg/mL) were within 5%-8% of parameters after the first dose (AUC0-t, 117 µg·h/mL; AUC0-∞, 118 µg·h/mL; Cmax, 54.9 µg/mL), indicating no accumulation. Defibrotide peak and extent of exposures in those with severe/ESRD were ~35%-37% and 50%-60% higher, respectively, versus controls, following single and multiple

  7. Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer

    Science.gov (United States)

    2014-01-01

    Introduction Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of everolimus also known as RAD001 (oral mammalian target of rapamycin (mTOR) inhibitor) and carboplatin may have activity in metastatic triple-negative breast cancer (TNBC). Methods The primary objective of this study was to determine clinical benefit rate (CBR), that is (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting ≥6 months) and the toxicity of everolimus/carboplatin in women with metastatic TNBC. Prior carboplatin was allowed. Treatment consisted of intravenous carboplatin area under the curve (AUC) 6 (later decreased to AUC 5 and subsequently to AUC 4) every 3 weeks with daily 5 mg everolimus. Results We enrolled 25 patients in this study. Median age was 58 years. There were one CR, six PRs, seven SDs and eight PDs (progression of disease). CBR was 36% (95% confidence interval (CI) 21.1 to 57.4%). One SD was achieved in a patient progressing on single agent carboplatin. The median progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) and overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached). There were seven patients (28%) with ≥ grade 3 thrombocytopenia; three (12%) with grade 3 neutropenia (no bleeding/febrile neutropenia) and one (4%) with grade 3 anemia. Greater hematological toxicity was seen in the first seven patients treated with carboplatin AUC5/6. After the amendment for starting dose of carboplatin to AUC 4, the regimen was well tolerated with only one out of 18 patients with grade 3 neutropenia and two patients with grade 3 thrombocytopenia. There was only one case of mucositis. Conclusion Everolimus-carboplatin was efficacious in metastatic TNBC. Dose limiting hematological toxicity was observed when AUC5/6 of carboplatin was combined with everolimus. However, carboplatin AUC 4 was well tolerated in

  8. Comparison of consumption behavior and appetite sensations among patients with type 2 diabetes mellitus after bariatric surgery

    Science.gov (United States)

    Yeh, Chun; Huang, Hsien-Hao; Chen, Shu-Chun; Chen, Tung-Fang

    2017-01-01

    Background The promising postsurgical weight loss and remission of type 2 diabetes (T2D) from bariatric surgery can be attributed to modified eating physiology after surgical procedures. We sought to investigate the changes in the parameters of consumption behaviors and appetite sensations induced by a mixed meal tolerance test, and to correlate these alterations with age, body mass index, C-peptide levels, and duration of T2D 1 year after bariatric surgery. Methods A total of 16 obese patients with T2D who underwent mini-gastric bypass (GB) and 16 patients who underwent sleeve gastrectomy (SG) were enrolled in this study and evaluated using a mixed meal tolerance test one year after surgery. A visual analogue scale was used for scoring appetite sensation at different time points. The area under the curve (AUC) and the incremental or decremental AUCAUC) were compared between the two groups. Results One year after surgery, a decreasing trend in the consumption time was observed in the GB group compared to the SG group, while the duration of T2D before surgery was negatively correlated with the post-operative consumed time in those after GB. Patients who underwent GB had significantly higher fasting scores for fullness and desire to eat, higher AUC0′–180′ of scores for desire to eat, as well as more effective post-meal suppression of hunger and desire to eat compared with those undergoing SG one year after surgery. Post-operative C-peptide levels were negatively correlated with ΔAUC0′–180′ for hunger and ΔAUC0′–180′ for desire to eat in the GB group, while negatively correlated with ΔAUC0′–180′ for fullness in the SG group. Discussion Patients with T2D after either GB or SG exhibit distinct nutrient-induced consumption behaviors and appetite sensations post-operatively, which may account for the differential effects on weight loss and glycemic control after different surgery. PMID:28344903

  9. Reconsidering lactate as a sepsis risk biomarker.

    Directory of Open Access Journals (Sweden)

    John L Moran

    Full Text Available There has been renewed interest in lactate as a risk biomarker in sepsis and septic shock. However, the ability of the odds ratio (OR and change in the area under the receiver operator characteristic curve (AUC-ROC to assess biomarker added-value has been questioned.A sepsis cohort was identified from the ICU database of an Australian tertiary referral hospital using APACHE III diagnostic codes. Demographic information, APACHE III scores, 24-hour post-admission patient lactate levels, and hospital mortality were accessed.Hospital mortality was modelled using a base predictive logistic regression model and sequential addition of admission lactate, lactate clearance ([lactateadmission-lactatefinal]/lactateadmission, and area under the lactate-time curve (LTC. Added-value was assessed using lactate index OR; AUC-ROC difference (base-model versus lactate index addition; net (mortality reclassification index (NRI; range -2 to +2; and net benefit (NB, the number of true positives per patient adjusted for the number of false positives. The data set comprised 717 patients with mean(SD age and APACHE III score 61.1(16.5 years and 68.3(28.2 respectively; 59.2% were male. Admission lactate was 2.3(2.5 mmol/l; with lactate of ≥ 4 mmol/L (37% hospital mortality in 17% and patients with lactate < 4 mmol/L having 18% hospital mortality. The admission base-model had an AUC-ROC = 0.81 with admission lactate OR = 1.127 (95%CI: 1.038, 1.224, AUC-ROC difference of 0.0032 (-0.0037, 0.01615; P = 0.61, and NRI 0.240(0.030, 0.464. The over-time model had an AUC-ROC = 0.86 with (i clearance OR = 0.771, 95%CI: 0.578, 1.030; P = 0.08; AUC-ROC difference 0.001 (-0.003, 0.014; P = 0.78, and NRI 0.109(-0.193, 0.425 and (ii LTC OR = 0.997, 95%CI: 0.989, 1.005, P = 0.49; AUC-ROC difference 0.004 (-0.002, 0.004; P = 0.34, and NRI 0.111(-0.222, 0.403. NB was not incremented by any lactate index.Lactate added-value assessment is dependent upon the performance of the underlying

  10. Pharmacokinetic and bioequivalence comparison of a single 100-mg dose of cefteram pivoxil powder suspension and tablet formulations: a randomized-sequence, open-label, two-period crossover study in healthy Chinese adult male volunteers.

    Science.gov (United States)

    Zou, Jianjun; Di, Bin; Wu, Chun Yong; Hu, Qin; Li, Jian Hua; Zhu, Yubing; Fan, Hongwei; Xiao, DaWei; Wang, Guang Ji

    2008-04-01

    Cefteram pivoxil (CFTM-PI) is an oral antibiotic available in powder suspension and tablet formulations indicated in China for the treatment of bacterial infections. Although these 2 formulations are marketed in China, published information regarding their pharmacokinetics and bioequivalence in the Chinese population is not available. The aim of this study was to compare the pharmacokinetics and bioequivalence of the powder suspension (test) and tablet (reference) formulations of CFTM-PI 100 mg available in China. This single-dose, randomized-sequence, open-label, 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 100-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Plasma was assayed using a high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to 6 hours (AUC(0-6)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were obtained at intervals over the 6-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (80%-125%) as established by the US Food and Drug Administration (FDA). Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). Twenty-four Chinese male subjects (mean [range] age,24.2 [23-32] years;weight,64.3 [58-67] kg; height, 172 [167-185] cm) enrolled; all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-6;), and

  11. Bioequivalence of two formulations of glucosamine sulfate 500-mg capsules in healthy male Chinese volunteers: an open-label, randomized-sequence, single-dose, fasting, two-way crossover study.

    Science.gov (United States)

    Zhu, YuBing; Zou, JianJun; Xiao, DaWei; Fan, HongWei; Yu, CuiXia; Zhang, JingJing; Yang, Jing; Guo, DaQing

    2009-07-01

    Glucosamine sulfate is used for the treatment of arthrosis, especially osteoarthritis of the knee joint. The available evidence suggests differences in its pharmacokinetics in Chinese subjects compared with non-Chinese subjects. The aim of this study was to compare the pharmacokinetics and relative bioavailability of a test and reference formulation of glucosamine sulfate 500 mg after single oral administration in healthy Chinese volunteers. This open-label, randomized-sequence, single-dose, 2-way crossover study was performed at the First Hospital of Nanjing Medical University, Nanjing, China. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 500-mg dose of the test or reference capsule formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Glucosamine sulfate was assayed using a liquid-chromatography tandem mass spectrometry method. For analysis of pharmacokinetic properties, including C(max), AUC(0-t), and AUC(0-infinity)), blood samples were obtained at intervals over a 14-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (70%-143% for C(max) and 80%-125% for AUC) as established by the State Food and Drug Administration (SFDA) of China. Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). Twenty-two healthy male Chinese subjects were enrolled (mean [range] age, 24 [22-26] years; weight, 63.9 [58.5-69.3] kg; height, 172 [167-177] cm); all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-t), and AUC(0-infinity)) were 93.4 to 127.3, 92.4 to 114

  12. Prognostic Value of Non-Invasive Fibrosis and Steatosis Tools, Hepatic Venous Pressure Gradient (HVPG and Histology in Nonalcoholic Steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Giada Sebastiani

    Full Text Available Non-invasive diagnostic methods for liver fibrosis predict clinical outcomes in viral hepatitis and nonalcoholic fatty liver disease (NAFLD. We specifically evaluated prognostic value of non-invasive fibrosis methods in nonalcoholic steatohepatitis (NASH against hepatic venous pressure gradient (HVPG and liver histology.This was a retrospective cohort study of 148 consecutive patients who met the following criteria: transjugular liver biopsy with HVPG measurement; biopsy-proven NASH; absence of decompensation; AST-to-Platelets Ratio Index (APRI, fibrosis-4 (FIB-4, NAFLD fibrosis score, ultrasound, hepatic steatosis index and Xenon-133 scan available within 6 months from biopsy; a minimum follow-up of 1 year. Outcomes were defined by death, liver transplantation, cirrhosis complications. Kaplan-Meier and Cox regression analyses were employed to estimate incidence and predictors of outcomes, respectively. Prognostic value was expressed as area under the curve (AUC.During a median follow-up of 5 years (interquartile range 3-8, 16.2% developed outcomes, including 7.4% who died or underwent liver transplantation. After adjustment for age, sex, diabetes, the following fibrosis tools predicted outcomes: HVPG >10mmHg (HR=9.60; 95% confidence interval [CI] 3.07-30.12, histologic fibrosis F3-F4 (HR=3.14; 1.41-6.95, APRI >1.5 (HR=5.02; 1.6-15.7, FIB-4 >3.25 (HR=6.33; 1.98-20.2, NAFLD fibrosis score >0.676 (HR=11.9; 3.79-37.4. Prognostic value was as follows: histologic fibrosis stage, AUC=0.85 (95% CI 0.76-0.93; HVPG, AUC=0.81 (0.70-0.91; APRI, AUC=0.89 (0.82-0.96; FIB-4, AUC=0.89 (0.83-0.95; NAFLD fibrosis score, AUC=0.79 (0.69-0.91. Neither histologic steatosis nor non-invasive steatosis methods predicted outcomes (AUC<0.50.Non-invasive methods for liver fibrosis predict outcomes of patients with NASH. They could be used for serial monitoring, risk stratification and targeted interventions.

  13. Comparison of consumption behavior and appetite sensations among patients with type 2 diabetes mellitus after bariatric surgery.

    Science.gov (United States)

    Yeh, Chun; Huang, Hsien-Hao; Chen, Shu-Chun; Chen, Tung-Fang; Ser, Kong-Han; Chen, Chih-Yen

    2017-01-01

    The promising postsurgical weight loss and remission of type 2 diabetes (T2D) from bariatric surgery can be attributed to modified eating physiology after surgical procedures. We sought to investigate the changes in the parameters of consumption behaviors and appetite sensations induced by a mixed meal tolerance test, and to correlate these alterations with age, body mass index, C-peptide levels, and duration of T2D 1 year after bariatric surgery. A total of 16 obese patients with T2D who underwent mini-gastric bypass (GB) and 16 patients who underwent sleeve gastrectomy (SG) were enrolled in this study and evaluated using a mixed meal tolerance test one year after surgery. A visual analogue scale was used for scoring appetite sensation at different time points. The area under the curve (AUC) and the incremental or decremental AUCAUC) were compared between the two groups. One year after surgery, a decreasing trend in the consumption time was observed in the GB group compared to the SG group, while the duration of T2D before surgery was negatively correlated with the post-operative consumed time in those after GB. Patients who underwent GB had significantly higher fasting scores for fullness and desire to eat, higher AUC 0'-180' of scores for desire to eat, as well as more effective post-meal suppression of hunger and desire to eat compared with those undergoing SG one year after surgery. Post-operative C-peptide levels were negatively correlated with ΔAUC 0'-180' for hunger and ΔAUC 0'-180' for desire to eat in the GB group, while negatively correlated with ΔAUC 0'-180' for fullness in the SG group. Patients with T2D after either GB or SG exhibit distinct nutrient-induced consumption behaviors and appetite sensations post-operatively, which may account for the differential effects on weight loss and glycemic control after different surgery.

  14. MR-sequences for prostate cancer diagnostics: validation based on the PI-RADS scoring system and targeted MR-guided in-bore biopsy.

    Science.gov (United States)

    Schimmöller, Lars; Quentin, Michael; Arsov, Christian; Hiester, Andreas; Buchbender, Christian; Rabenalt, Robert; Albers, Peter; Antoch, Gerald; Blondin, Dirk

    2014-10-01

    This study evaluated the accuracy of MR sequences [T2-, diffusion-weighted, and dynamic contrast-enhanced (T2WI, DWI, and DCE) imaging] at 3T, based on the European Society of Urogenital Radiology (ESUR) scoring system [Prostate Imaging Reporting and Data System (PI-RADS)] using MR-guided in-bore prostate biopsies as reference standard. In 235 consecutive patients [aged 65.7 ± 7.9 years; median prostate-specific antigen (PSA) 8 ng/ml] with multiparametric prostate MRI (mp-MRI), 566 lesions were scored according to PI-RADS. Histology of all lesions was obtained by targeted MR-guided in-bore biopsy. In 200 lesions, biopsy revealed prostate cancer (PCa). The area under the curve (AUC) for cancer detection was 0.70 (T2WI), 0.80 (DWI), and 0.74 (DCE). A combination of T2WI + DWI, T2WI + DCE, and DWI + DCE achieved an AUC of 0.81, 0.78, and 0.79. A summed PI-RADS score of T2WI + DWI + DCE achieved an AUC of 0.81. For higher grade PCa (primary Gleason pattern ≥ 4), the AUC was 0.85 for T2WI + DWI, 0.84 for T2WI + DCE, 0.86 for DWI + DCE, and 0.87 for T2WI + DWI + DCE. The AUC for T2WI + DWI + DCE for transitional-zone PCa was 0.73, and for the peripheral zone 0.88. Regarding higher-grade PCa, AUC for transitional-zone PCa was 0.88, and for peripheral zone 0.96. The combination of T2WI + DWI + DCE achieved the highest test accuracy, especially in patients with higher-grade PCa. The use of ≤2 MR sequences led to lower AUC in higher-grade and peripheral-zone cancers. • T2WI + DWI + DCE achieved the highest accuracy in patients with higher grade PCa • T2WI + DWI + DCE was more accurate for peripheral- than for transitional-zone PCa • DCE increased PCa detection accuracy in the peripheral zone • DWI was the leading sequence in the transitional zone.

  15. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria for Coronary Revascularization in Patients With Stable Ischemic Heart Disease : A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons.

    Science.gov (United States)

    Patel, Manesh R; Calhoon, John H; Dehmer, Gregory J; Grantham, James Aaron; Maddox, Thomas M; Maron, David J; Smith, Peter K

    2017-10-01

    The American College of Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, and American Association for Thoracic Surgery, along with key specialty and subspecialty societies, have completed a 2-part revision of the appropriate use criteria (AUC) for coronary revascularization. In prior coronary revascularization AUC documents, indications for revascularization in acute coronary syndromes and stable ischemic heart disease (SIHD) were combined into 1 document. To address the expanding clinical indications for coronary revascularization, and to align the subject matter with the most current American College of Cardiology/American Heart Association guidelines, the new AUC for coronary artery revascularization were separated into 2 documents addressing SIHD and acute coronary syndromes individually. This document presents the AUC for SIHD.Clinical scenarios were developed to mimic patient presentations encountered in everyday practice. These scenarios included information on symptom status; risk level as assessed by noninvasive testing; coronary disease burden; and, in some scenarios, fractional flow reserve testing, presence or absence of diabetes, and SYNTAX score. This update provides a reassessment of clinical scenarios that the writing group felt were affected by significant changes in the medical literature or gaps from prior criteria. The methodology used in this update is similar to the initial document but employs the recent modifications in the methods for developing AUC, most notably, alterations in the nomenclature for appropriate use categorization.A separate, independent rating panel scored the clinical scenarios on a scale of 1 to 9. Scores of 7 to 9 indicate that revascularization is considered appropriate for the clinical scenario presented. Scores of 1 to 3 indicate that revascularization is considered rarely appropriate for the clinical scenario, whereas scores in the mid-range of 4 to 6 indicate that

  16. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2016 Appropriate Use Criteria for Coronary Revascularization in Patients With Acute Coronary Syndromes : A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and the Society of Thoracic Surgeons.

    Science.gov (United States)

    Patel, Manesh R; Calhoon, John H; Dehmer, Gregory J; Grantham, James Aaron; Maddox, Thomas M; Maron, David J; Smith, Peter K

    2017-04-01

    The American College of Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, and American Association for Thoracic Surgery, along with key specialty and subspecialty societies, have completed a 2-part revision of the appropriate use criteria (AUC) for coronary revascularization. In prior coronary revascularization AUC documents, indications for revascularization in acute coronary syndromes (ACS) and stable ischemic heart disease were combined into 1 document. To address the expanding clinical indications for coronary revascularization, and in an effort to align the subject matter with the most current American College of Cardiology/American Heart Association guidelines, the new AUC for coronary artery revascularization were separated into 2 documents addressing ACS and stable ischemic heart disease individually. This document presents the AUC for ACS. Clinical scenarios were developed to mimic patient presentations encountered in everyday practice and included information on symptom status, presence of clinical instability or ongoing ischemic symptoms, prior reperfusion therapy, risk level as assessed by noninvasive testing, fractional flow reserve testing, and coronary anatomy. This update provides a reassessment of clinical scenarios that the writing group felt to be affected by significant changes in the medical literature or gaps from prior criteria. The methodology used in this update is similar to the initial document but employs the recent modifications in the methods for developing AUC, most notably, alterations in the nomenclature for appropriate use categorization. A separate, independent rating panel scored the clinical scenarios on a scale of 1 to 9. Scores of 7 to 9 indicate that revascularization is considered appropriate for the clinical scenario presented. Scores of 1 to 3 indicate that revascularization is considered rarely appropriate for the clinical scenario, whereas scores in the mid-range (4 to 6

  17. Combined 3 Tesla MRI Biomarkers Improve the Differentiation between Benign vs Malignant Single Ring Enhancing Brain Masses.

    Directory of Open Access Journals (Sweden)

    Simone Salice

    Full Text Available To evaluate whether the combination of imaging biomarkers obtained by means of different 3 Tesla (3T Magnetic Resonance Imaging (MRI advanced techniques can improve the diagnostic accuracy in the differentiation between benign and malignant single ring-enhancing brain masses.14 patients presenting at conventional 3T MRI single brain mass with similar appearance as regard ring enhancement, presence of peri-lesional edema and absence of hemorrhage signs were included in the study. All lesions were histologically proven: 5 pyogenic abscesses, 6 glioblastomas, and 3 metastases. MRI was performed at 3 Tesla and included Diffusion Weighted Imaging (DWI, Dynamic Susceptibility Contrast -Perfusion Weighted Imaging (DSC-PWI, Magnetic Resonance Spectroscopy (MRS, and Diffusion Tensor Imaging (DTI. Imaging biomarkers derived by those advanced techniques [Cerebral Blood Flow (CBF, relative Cerebral Blood Volume (rCBV, relative Main Transit Time (rMTT, Choline (Cho, Creatine (Cr, Succinate, N-Acetyl Aspartate (NAA, Lactate (Lac, Lipids, relative Apparent Diffusion Coefficient (rADC, and Fractional Anisotropy (FA] were detected by two experienced neuroradiologists in joint session in 4 areas: Internal Cavity (IC, Ring Enhancement (RE, Peri-Lesional edema (PL, and Contralateral Normal Appearing White Matter (CNAWM. Significant differences between benign (n = 5 and malignant (n = 9 ring enhancing lesions were tested with Mann-Withney U test. The diagnostic accuracy of MRI biomarkers taken alone and MRI biomarkers ratios were tested with Receiver Operating Characteristic (ROC analysis with an Area Under the Curve (AUC ≥ 0.9 indicating a very good diagnostic accuracy of the variable.Five MRI biomarker ratios achieved excellent accuracy: IC-rADC/PL-NAA (AUC = 1, IC-rADC/IC-FA (AUC = 0.978, RE-rCBV/RE-FA (AUC = 0.933, IC-rADC/RE-FA (AUC = 0.911, and IC-rADC/PL-FA (AUC = 0.911. Only IC-rADC achieved a very good diagnostic accuracy (AUC = 0.909 among MRI biomarkers

  18. How many studies are necessary to compare niche-based models for geographic distributions? Inductive reasoning may fail at the end Quantos estudos ainda serão necessários para avaliar modelos de distribuição geográfica baseados em modelagem do nicho? Um pensamento indutivo pode estar fadado ao fracasso

    Directory of Open Access Journals (Sweden)

    LC Terribile

    2010-05-01

    Full Text Available The use of ecological niche models (ENM to generate potential geographic distributions of species has rapidly increased in ecology, conservation and evolutionary biology. Many methods are available and the most used are Maximum Entropy Method (MAXENT and the Genetic Algorithm for Rule Set Production (GARP. Recent studies have shown that MAXENT perform better than GARP. Here we used the statistics methods of ROC - AUC (area under the Receiver Operating Characteristics curve and bootstrap to evaluate the performance of GARP and MAXENT in generate potential distribution models for 39 species of New World coral snakes. We found that values of AUC for GARP ranged from 0.923 to 0.999, whereas those for MAXENT ranged from 0.877 to 0.999. On the whole, the differences in AUC were very small, but for 10 species GARP outperformed MAXENT. Means and standard deviations for 100 bootstrapped samples with sample sizes ranging from 3 to 30 species did not show any trends towards deviations from a zero difference in AUC values of GARP minus AUC values of MAXENT. Ours results suggest that further studies are still necessary to establish under which circumstances the statistical performance of the methods vary. However, it is also important to consider the possibility that this empirical inductive reasoning may fail in the end, because we almost certainly could not establish all potential scenarios generating variation in the relative performance of models.A utilização de modelos de nicho ecológico (ENM para gerar distribuições geográficas potenciais de espécies tem aumentado rapidamente nas áreas de ecologia, biologia da conservação e biologia evolutiva. O Método de Máxima Entropia (MAXENT e o Algoritmo Genético para Produção de Conjunto de Regras (GARP estão entre os métodos mais utilizados, e estudos recentes têm atribuído ao MAXENT um melhor desempenho no processo de modelagem com relação ao GARP. Neste trabalho, foram utilizados os m

  19. Correlations between A1c, fasting glucose, 2h postload glucose, and β-cell function in the Chinese population.

    Science.gov (United States)

    Li, Cuiliu; Yang, Huijie; Tong, Guoyu; Shen, Shanmei; Feng, Wenhuan; Bi, Yan; Zhu, Dalong

    2014-08-01

    This study was aimed to assess the associations of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and 2h postload plasma glucose (2hPG) with β-cell function in the Chinese population. A total of 913 subjects underwent 75-g oral glucose tolerance test (OGTT) and HbA1c testing. According to OGTT, isolated impaired fasting glucose (i-IFG) was defined as 5.6 mmol/l ≤ FPG < 7.0 mmol/l and 2hPG < 7.8 mmol/l; isolated impaired glucose tolerance (i-IGT) was defined as FPG < 5.6 mmol/l and 7.8 mmol/l ≤ 2hPG < 11.1 mmol/l. HbA1c 5.7-6.4 % was used to identify subjects with prediabetes. Insulin release was calculated by basal homeostasis model assessment of insulin secretion (HOMA-β), early-phase InsAUC30/GluAUC30, and total-phase InsAUC120/GluAUC120. β-cell function relative to insulin sensitivity was expressed as disposition index (DI). All indices of insulin sensitivity and β-cell function gradually decreased with increasing HbA1c, FPG, and 2hPG (all p < 0.01). β-cell function decreased precipitously when HbA1c exceeded 5.5 %. Compared with HbA1c, FPG showed stronger correlations with HOMA-β, InsAUC30/GluAUC30, InsAUC120/GluAUC120, DI30, and DI120 (all p < 0.05), and 2hPG was more closely related to DI30 and DI120 (all p < 0.01). Moreover, FPG was more strongly related to HOMA-β and InsAUC30/GluAUC30 than 2hPG (all p < 0.05). The combination of i-IFG and HbA1c 5.7-6.4 % showed the greatest reduction in DI30 and DI120 compared with HbA1c 5.7-6.4 % alone, i-IGT, or i-IFG (p < 0.05). In conclusion, HbA1c could be used as a marker to identify subjects with impaired β-cell function, but OGTT performs better than HbA1c. The combination of HbA1c and FPG is a simple and sensitive method to evaluate β-cell function.

  20. Plasma Pentraxin 3 Is Closely Associated with Peripheral Arterial Disease in Hemodialysis Patients and Predicts Clinical Outcome: A 6-Year Follow-Up.

    Science.gov (United States)

    Zhou, Yijun; Zhang, Jiwei; Zhu, Mingli; Lu, Renhua; Wang, Yongmei; Ni, Zhaohui

    2015-01-01

    The aim of this study is to investigate the value of plasma PTX3 level for assessing peripheral artery disease (PAD) and clinical outcome in hemodialysis (HD) patients. The ankle-brachial index (ABI) was measured in HD patients. PTX3 levels in 116 HD patients were measured by ELISA. Overall, 116 HD patients were enrolled; 21 (18%) patients had PAD. Using the ROC curve analysis for PAD, PTX3 (cut-off value 4.06 ng/ml, AUC 0.901, p < 0.0001) showed a significantly better positive predictive value than hsCRP (cut-off value 3.33 ng/ml, AUC 0.640, p < 0.05). During follow-up (mean 57 ± 26 months), 40 deaths (34%) occurred. Kaplan-Meier analysis found that those patients with elevated PTX3 had a significantly poor outcome (p < 0.0001), and Cox analysis further confirmed that PTX3 was an independent predictor of overall mortality (HR, 1.105, p = 0.03). For prediction of overall mortality, the AUC for PTX3 (cut-off value 3.22 ng/ml, AUC 0.690, p < 0.0001) was close to hsCRP (cut-off value 5.84 ng/ml, AUC 0.620, p < 0.001). For the prediction of PAD in HD patients, the diagnostic sensitivity and specificity of PTX3 were higher than those of hsCRP. Furthermore, PTX3 was also a predictor of all-cause mortality in HD patients. PTX3 may be considered a novel biomarker of inflammation in HD patients. © 2015 S. Karger AG, Basel.

  1. Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa.

    Science.gov (United States)

    Lawson, Elizabeth A; Holsen, Laura M; Santin, McKale; DeSanti, Rebecca; Meenaghan, Erinne; Eddy, Kamryn T; Herzog, David B; Goldstein, Jill M; Klibanski, Anne

    2013-05-01

    Anorexia nervosa, a psychiatric disorder characterized by self-induced starvation, is associated with endocrine dysfunction and comorbid anxiety and depression. Animal data suggest that oxytocin may have anxiolytic and antidepressant effects. We have reported increased postprandial oxytocin levels in women with active anorexia nervosa and decreased levels in weight-recovered women with anorexia nervosa compared to healthy controls. A meal may represent a significant source of stress in patients with disordered eating. We therefore investigated the association between postprandial oxytocin secretion and symptoms of anxiety and depression in anorexia nervosa. We performed a cross-sectional study of 35 women (13 women with active anorexia nervosa, 9 with weight-recovered anorexia nervosa, and 13 healthy controls). Anorexia nervosa was diagnosed according to DSM-IV-TR criteria. Serum oxytocin and cortisol and plasma leptin levels were measured fasting and 30, 60, and 120 minutes after a standardized mixed meal. The area under the curve (AUC) and, for oxytocin, postprandial nadir and peak levels were determined. Anxiety and depressive symptoms were assessed using the Spielberger State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory II (BDI-II). The study was conducted from January 2009 to March 2011. In women with anorexia nervosa, oxytocin AUC and postprandial nadir and peak levels were positively associated with STAI trait and STAI premeal and postmeal state scores. Oxytocin AUC and nadir levels were positively associated with BDI-II scores. After controlling for cortisol AUC, all of the relationships remained significant. After controlling for leptin AUC, most of the relationships remained significant. Oxytocin secretion explained up to 51% of the variance in STAI trait and 24% of the variance in BDI-II scores. Abnormal postprandial oxytocin secretion in women with anorexia nervosa is associated with increased symptoms of anxiety and depression. This

  2. Oxytocin secretion is associated with severity of disordered eating psychopathology and insular cortex hypoactivation in anorexia nervosa.

    Science.gov (United States)

    Lawson, Elizabeth A; Holsen, Laura M; Santin, McKale; Meenaghan, Erinne; Eddy, Kamryn T; Becker, Anne E; Herzog, David B; Goldstein, Jill M; Klibanski, Anne

    2012-10-01

    Animal data suggest that oxytocin is a satiety hormone. We have demonstrated that anorexia nervosa (anorexia), a disorder characterized by food restriction, low weight, and hypoleptinemia, is associated with decreased nocturnal oxytocin secretion. We have also reported functional magnetic resonance imaging (fMRI) hypoactivation in anorexia in brain regions involved in food motivation. The relationships between oxytocin, food-motivation neurocircuitry, and disordered eating psychopathology have not been investigated in humans. The objective of the study was to determine whether the oxytocin response to feeding in anorexia differs from healthy women and to establish the relationship between oxytocin secretion and disordered eating psychopathology and food-motivation neurocircuitry. This was a cross-sectional study. The study was conducted at a clinical research center. Participants included 35 women: 13 anorexia (AN), nine weight-recovered anorexia (ANWR), and 13 healthy controls (HC). Peripheral oxytocin and leptin levels were measured fasting and 30, 60, and 120 min after a standardized mixed meal. The Eating Disorder Examination-Questionnaire was used to assess disordered eating psychopathology. fMRI was performed during visual processing of food and nonfood stimuli to measure brain activation before and after the meal. Mean oxytocin levels were higher in AN than HC at 60 and 120 min and lower in ANWR than HC at 0, 30, and 120 min and AN at all time points. Mean oxytocin area under the curve (AUC) was highest in AN, intermediate in HC, and lowest in ANWR. Mean leptin levels at all time points and AUC were lower in AN than HC and ANWR. Oxytocin AUC was associated with leptin AUC in ANWR and HC but not in AN. Oxytocin AUC was associated with the severity of disordered eating psychopathology in AN and ANWR, independent of leptin secretion, and was associated with between-group variance in fMRI activation in food motivation brain regions, including the hypothalamus

  3. Comparison of shear-wave and strain ultrasound elastography in the differentiation of benign and malignant breast lesions.

    Science.gov (United States)

    Chang, Jung Min; Won, Jae-Kyung; Lee, Kyoung-Bun; Park, In Ae; Yi, Ann; Moon, Woo Kyung

    2013-08-01

    The purpose of this article is to compare the diagnostic performances of shearwave and strain elastography for the differentiation of benign and malignant breast lesions. B-mode ultrasound and shear-wave and strain elastography were performed in 150 breast lesions; 71 were malignant. BI-RADS final assessment, elasticity values in kilopascals, and elasticity scores on a 5-point scale were assessed before biopsy. The results were compared using the area under the receiver operating characteristic curve (AUC). The AUC for shear-wave elastography was similar to that of strain elastography (0.928 vs 0.943). The combined use of B-mode ultrasound and either elastography technique improved diagnostic performance in the differentiation of benign and malignant breast lesions compared with the use of B-mode ultrasound alone (B-mode alone, AUC = 0.851; B-mode plus shear-wave elastography, AUC = 0.964; B-mode plus strain elastography, AUC = 0.965; p < 0.001). With the best cutoff points of 80 kPa on shear-wave elastography and a score between 3 and 4 on strain elastography, the sensitivity was higher in shear-wave elastography, and specificity was higher in strain elastography (95.8% vs 81.7%, p = 0.002; 93.7% vs 84.8%, p = 0.016). In cases of infiltrating ductal carcinoma, mean elasticity scores were lower in grade 3 than in grade 1 and 2 cancers (p = 0.017) with strain elastography causing false-negative findings. The diagnostic performance of shear-wave and strain elastography was similar. Either elastography technique can improve overall diagnostic performance in the differentiation of benign and malignant lesions when combined with B-mode ultrasound. However, the sensitivity and specificity of shear-wave and strain elastography were different according to lesion histologic profile, tumor grade, and breast thickness.

  4. Accuracy of cone-beam computed tomography and periapical radiography in detecting small periapical lesions.

    Science.gov (United States)

    Tsai, Patrick; Torabinejad, Mahmoud; Rice, Dwight; Azevedo, Bruno

    2012-07-01

    The aim of this study was to determine the diagnostic accuracy of 2 cone-beam computed tomography (CBCT) machines and periapical (PA) radiography in detecting simulated apical lesions created with the smallest dental burs available. By using mandibles from human cadavers, simulated apical lesions were created and then progressively enlarged in 16 roots by using sizes #1/4, #1/2, #1, #2, #4, and #6 round burs. Imaging was obtained after each enlargement with a Kodak 9000 3D (Kodak) CBCT, a Veraviewpocs 3De (Morita) CBCT, and intraoral digital PA radiography. Specificity and sensitivity at variable decision thresholds were calculated and plotted on receiver operator characteristic curves. The area under the curve (AUC) served as an estimate of diagnostic accuracy. The overall AUCs for Kodak, Morita, and PA radiography were 0.767 (95% confidence interval [CI], 0.743-0.792), 0.753 (95% CI, 0.728-0.779), and 0.584 (95% CI, 0.554-0.615), respectively. The AUCs for Kodak and Morita were both statistically significantly larger than the AUC for all corresponding simulated lesion sizes imaged with PA radiography. Between Kodak and Morita, there were no statistically significant differences in AUCs for any of the corresponding simulated lesion sizes. Both CBCT devices demonstrated poor accuracy in detecting simulated lesions smaller than 0.8 mm in diameter, fair to good accuracy when simulated lesion diameter was between 0.8-1.4 mm, and excellent accuracy when simulated lesions were larger than 1.4 mm in diameter. PA radiography, at best, demonstrated poor diagnostic accuracy for all simulated lesion sizes. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Pharmacokinetic/pharmacodynamic (PK/PD) Determinants of Vancomycin Efficacy in Enterococcal Bacteremia.

    Science.gov (United States)

    Jumah, Muhammed Taufiq Bin; Vasoo, Shawn; Menon, Sanjay R; De, Partha Pratim; Neely, Michael; Teng, Christine B

    2017-12-20

    Background. While pharmacokinetic-pharmacodynamic targets for vancomycin therapy are recognized for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections, scant data are available to guide therapy for other gram positive infections.Methods. A retrospective single-centre cohort of patients with Enterococcus spp. bacteremia hospitalized between 1st January 2009 and 31st May 2015 were studied. Average vancomycin AUC0-24hrs was computed using a Bayesian approach. MIC was determined by gradient diffusion (E-test, bioMerieux) and the average AUC0-24hrs/MIC over the initial 72 hours of therapy was calculated. We assessed 30-day all-cause mortality as the primary outcome. Classification and regression tree analysis (CART) was used to identify vancomycin AUC0-24hrs/MIC associated with 30-day mortality.Results. Fifty-seven patients with enterococcal bacteremia (32 E. faecium, 21 E. faecalis, 4 other Enteroccocusspp.) were studied. The median vancomycin MIC was 0.75 mg/L (range 0.38-3 mg/L). All-cause 30-day mortality occurred in 10 out of 57 patients (17.5%). A CART-derived vancomycin AUC/MICEtest of ≥389 was associated with reduced mortality (P= 0.017); failure to achieve this independently predicted 30-day mortality [OR 5.65 (95% CI 1.18-27.03), P= 0.03].Conclusion. We found that a vancomycin AUC/MICEtest (≥389), achieved within 72 hours, was associated with reduced mortality. Larger, prospective studies are warranted to verify the vancomycin pharmacodynamic targets associated with maximal clinical outcomes and acceptable safety. Copyright © 2017 American Society for Microbiology.

  6. Axial-shear strain elastography for breast lesion classification: further results from in vivo data.

    Science.gov (United States)

    Thittai, Arun K; Yamal, Jose-Miguel; Mobbs, Louise M; Kraemer-Chant, Christina M; Chekuri, Srinivasa; Garra, Brian S; Ophir, Jonathan

    2011-02-01

    The purpose of this work was to investigate the potential of the normalized axial-shear strain area (NASSA) feature, derived from axial-shear strain elastograms (ASSE), for breast lesion classification of fibroadenoma and cancer. This study consisted of previously acquired in vivo digital radiofrequency data of breast lesions. A total of 33 biopsy-proven malignant tumors and 30 fibroadenoma cases were included in the study, which involved three observers blinded to the original BIRADS-ultrasound scores. The observers outlined the lesions on the sonograms. The ASSEs were segmented and color-overlaid on the sonograms, and the NASSA feature from the ASSE was computed semi-automatically. Receiver operating characteristic (ROC) curves were then generated and the area under the curve (AUC) was calculated for each observer performance. A logistic regression classifier was built to compare the improvement in the AUC when using BIRADS scores plus NASSA values as opposed to BIRADS scores alone. BIRADS score ROC had an AUC of 0.89 (95% CI = 0.81 to 0.97). In comparison, the average of the AUC for all the three observers using ASSE feature alone was 0.84. However, the AUC increased to 0.94 (average of 3 observers) when BIRADS score and ASSE feature were combined. The results demonstrate that the NASSA feature derived from ASSE has the potential to improve BIRADS breast lesion classification of fibroadenoma and malignant tumors. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  7. A phase I pharmacokinetic study of intraperitoneal bortezomib and carboplatin in patients with persistent or recurrent ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study.

    Science.gov (United States)

    Jandial, Danielle A; Brady, William E; Howell, Stephen B; Lankes, Heather A; Schilder, Russell J; Beumer, Jan H; Christner, Susan M; Strychor, Sandra; Powell, Matthew A; Hagemann, Andrea R; Moore, Kathleen N; Walker, Joan L; DiSilvestro, Paul A; Duska, Linda R; Fracasso, Paula M; Dizon, Don S

    2017-05-01

    Intraperitoneal (IP) therapy improves survival compared to intravenous (IV) treatment for women with newly diagnosed, optimally cytoreduced, ovarian cancer. However, the role of IP therapy in recurrent disease is unknown. Preclinical data demonstrated IP administration of the proteasome inhibitor, bortezomib prior to IP carboplatin increased tumor platinum accumulation resulting in synergistic cytotoxicity. We conducted this phase I trial of IP bortezomib and carboplatin in women with recurrent disease. Women with recurrent ovarian cancer were treated with escalating doses of IP bortezomib - in combination with IP carboplatin (AUC 4 or 5) every 21days for 6cycles. Pharmacokinetics of both agents were evaluated in cycle 1. Thirty-three women participated; 32 were evaluable for safety. Two patients experienced dose-limiting toxicity (DLT) at the first dose level (carboplatin AUC 5, bortezomib 0.5mg/m2), prompting carboplatin reduction to AUC 4 for subsequent dose levels. With carboplatin dose fixed at AUC 4, bortezomib was escalated from 0.5 to 2.5mg/m2 without DLT. Grade 3/4 related toxicities included abdominal pain, nausea, vomiting, and diarrhea which were infrequent. The overall response rate in patients with measurable disease (n=21) was 19% (1 complete, 3 partial). Cmax and AUC in peritoneal fluid and plasma increased linearly with dose, with a favorable exposure ratio of the peritoneal cavity relative to peripheral blood plasma. IP administration of this novel combination was feasible and showed promising activity in this phase I trial of heavily pre-treated women with ovarian cancer. Further evaluation of this IP combination should be conducted. Copyright © 2017. Published by Elsevier Inc.

  8. Carboplatin therapeutic monitoring in preterm and full-term neonates.

    Science.gov (United States)

    Veal, Gareth J; Errington, Julie; Hayden, James; Hobin, David; Murphy, Dermot; Dommett, Rachel M; Tweddle, Deborah A; Jenkinson, Helen; Picton, Susan

    2015-09-01

    Administration of the most appropriate dose of chemotherapy to neonates is particularly challenging and frequently not standardised based on any scientific rationale. We report the clinical utility of carboplatin therapeutic drug monitoring in preterm and full-term neonates within the first month of life. Carboplatin therapeutic monitoring was performed to achieve target drug exposures area under the plasma concentration-time curve (AUC values) in nine preterm and full-term neonates diagnosed with retinoblastoma or neuroblastoma treated over an 8 year period. Carboplatin was administered over 3 days with therapeutic drug monitoring utilised to target cumulative AUC values of 5.2-7.8 mg/ml min. AUC values achieved were within 15% of target values for the individual courses of treatment in all but one patient (12/13 courses of treatment), with dose modifications of up to 215% required to achieve target AUC values, based on initial mg/kg dosing schedules. Carboplatin clearance determined across three consecutive chemotherapy courses in two patients increased from 3.4 to 7.1 ml/min and from 7.2 to 16.5 ml/min, representing increases of 210-230% over several weeks of treatment. Complete remission was observed in 8/9 patients, with no renal toxicity reported and only one patient experiencing ototoxicity. The study highlights the benefits of utilising therapeutic drug monitoring to achieve target carboplatin AUC values in preterm and full-term neonates treated within the first few weeks of life, particularly in view of marked increases in drug clearance observed over consecutive chemotherapy courses. In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform future treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Aggregation analysis of pharmaceutical human immunoglobulin preparations using size-exclusion chromatography and analytical ultracentrifugation sedimentation velocity.

    Science.gov (United States)

    Krayukhina, Elena; Uchiyama, Susumu; Nojima, Kiyoko; Okada, Yoshiaki; Hamaguchi, Isao; Fukui, Kiichi

    2013-01-01

    In the pharmaceutical industry, analysis of soluble aggregates in pharmaceutical formulations is most commonly performed using size-exclusion chromatography (SEC). However, owing to concerns that aggregates can be overlooked by SEC analysis, it has been suggested that its results should be confirmed with orthogonal methods. One of the main alternative methods for SEC is analytical ultracentrifugation sedimentation velocity (AUC-SV), which has been indicated as an important tool for the measurement of protein aggregation. The present study aimed to show that AUC-SV can be effectively applied for the characterization of marketed immunoglobulin pharmaceutical preparations to support the results obtained by SEC. In addition, the present research aimed to assess the appropriateness of two integration approaches for the quantitative analysis of the SEC results. Thus, the aggregates were measured in seven different preparations of human immunoglobulins by AUC-SV and SEC, and the acquired chromatographic data were processed by using either the vertical drop method or the Gaussian skim approach, implemented in the Empower II chromatography data software (Waters, Tokyo, Japan). The results of aggregation measurements performed using AUC-SV were in good agreement with those obtained using SEC. As expected, the Gaussian skim integration approach inherently provided lower estimates of aggregation content than the results of the vertical drop method. The finding of this study confirmed the complementary nature of AUC-SV to SEC for aggregate composition analysis and underscored the important role that the different integration methods can play in the quantitative interpretation of chromatographic results. Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  10. New serum biomarkers for prostate cancer diagnosis

    Science.gov (United States)

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  11. Comparison of the ability to identify cardiometabolic risk factors between two new body indices and waist-to-height ratio among Chinese adults with normal BMI and waist circumference.

    Science.gov (United States)

    Liu, Peng Ju; Ma, Fang; Lou, Hui Ping; Zhu, Yan Ning

    2017-04-01

    Waist-to-height ratio (WHtR) has been reported to be more strongly associated with cardiometabolic risk factors among non-obese individuals than BMI and waist circumference (WC). A body shape index (ABSI) and body roundness index (BRI) have been proposed recently to assess obesity-related disorders or mortalities. Our aim was to compare the ability of ABSI and BRI with that of WHtR to identify cardiometabolic risk factors in Chinese adults with normal BMI and WC. Receiver-operating characteristic curves and areas under the curve (AUC) were employed to evaluate the ability of the indices (WHtR, BRI, ABSI) to identify metabolic risk factors and to determine the indices' optimal cut-off values. The value of each index that resulted in maximization of the Youden index (sensitivity + specificity - 1) was defined as optimal. Differences in the AUC values between the indices were also evaluated. Individuals attending a voluntary health check-up in Beijing, China, July-December 2015, were recruited to the study. Non-obese adults (n 1596). Among both genders, ABSI exhibited the lowest AUC value for identifying each risk factor among the three indices; the AUC value of BRI for identifying each risk factor was very close to that of WHtR, and no significant differences were observed between the AUC values of the two new indices. When evaluating cardiometabolic risk factors among non-obese adults, WHtR was a simple and effective index in the assessment of cardiometabolic risk factors, BRI could be used as an alternative body index to WHtR, while ABSI could not.

  12. Nocturnal levels of chemerin and progranulin in adolescents: influence of sex, body mass index, glucose metabolism and sleep.

    Science.gov (United States)

    Daxer, Johann; Herttrich, Theresa; Zhao, Ying Y; Vogel, Mandy; Hiemisch, Andreas; Scheuermann, Kathrin; Körner, Antje; Kratzsch, Jürgen; Kiess, Wieland; Quante, Mirja

    2017-01-01

    Adipokines have been implicated in obesity, insulin resistance and sleep regulation. However, the role of chemerin and progranulin, two recently described adipokines, in the context of sleep remains unclear. The aim of this study was to compare nocturnal serum chemerin and progranulin levels between overweight/obese and normal-weight adolescents and to assess variations by sex, across different sleep stages and in relation to glucose metabolism. The study sample included 34 overweight/obese and 32 normal-weight adolescents from secondary schools and the Leipzig Research Center for Civilization Diseases (LIFE) Child study cohort. We obtained longitudinal serum adipokine levels during in-laboratory polysomnography followed by an oral glucose tolerance test. Overweight/obese adolescents had significantly higher mean nocturnal serum chemerin area under the curve (AUC) levels (348.2±133.3 vs. 241.7±67.7 vs. ng/mL×h, pweight controls. In detail, higher chemerin AUC levels in obese/overweight subjects were exclusively due to increased levels in females. No overall difference for serum progranulin AUC was found between the groups. However, when assessing sex-specific levels, serum progranulin AUC levels were ~30% higher in overweight/obese males compared to overweight/obese females. Of note, nocturnal serum chemerin and progranulin AUC did not exhibit a correlation with markers of glucose metabolism or sleep stages. Collectively, we report a sexual dimorphism in nocturnal progranulin and chemerin levels, which may help explain underlying differences in energy balance and body composition between males and females in the context of obesity.

  13. Effect of oral contraceptives and/or metformin on GLP-1 secretion and reactive hypoglycaemia in polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Dorte Glintborg

    2017-06-01

    Full Text Available Context: Insulin resistance in polycystic ovary syndrome (PCOS may increase the risk of reactive hypoglycaemia (RH and decrease glucagon-like peptide-1 (GLP-1 secretion. The possible effects of treatment with oral contraceptives (OCP and/or metformin on GLP-1 secretion and risk of RH in PCOS is undetermined. Setting: Outpatient clinic. Patients and interventions: Randomized, controlled clinical trial. Ninety women with PCOS were randomized to 12-month treatment with OCP (150 mg desogestrel + 30 mg ethinylestradiol, metformin (2 g/day or metformin + OCP. Five-hour oral glucose tolerance tests (5-h OGTT measuring fasting and area under the curve (AUC for GLP-1, glucose, insulin and C-peptide were performed before and after the intervention period. Sixty-five women completed the study and 34 weight-matched healthy women were included as controls. Main outcome measures: Changes in GLP-1, glucose, insulin and C-peptide during 5-h OGTT. Results: Fasting GLP-1 levels increased during metformin + OCP vs OCP treatment, whereas AUC GLP-1 levels were unchanged during medical treatment. The prevalence of reactive hypoglycemia increased from 9/65 to 14/65 after intervention (P < 0.01 and was more common after treatment with metformin + OCP (increase from 3/23 to 6/23, P = 0.01. Reactive hypoglycaemia was associated with higher insulin and C-peptide levels during 5-h OGTT, but was unassociated with BMI and AUC GLP-1. GLP-1 levels were comparable in PCOS vs controls. AUC GLP-1 levels were significantly lower in obese vs lean patients and were inversely associated with BMI. Conclusions: AUC GLP-1 levels were unchanged during treatment. Increased risk of hypoglycemia during metformin + OCP could be associated with increased insulin secretion.

  14. Highly sensitive alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxyprothrombin for hepatocellular carcinoma detection.

    Science.gov (United States)

    Caviglia, Gian Paolo; Abate, Maria Lorena; Petrini, Elisa; Gaia, Silvia; Rizzetto, Mario; Smedile, Antonina

    2016-03-01

    Hepatocellular carcinoma (HCC) develops with high incidence in patients with chronic liver disease (CLD), and particularly in those with cirrhosis. Currently, diagnosis and surveillance are mainly based on imaging methods. The aim of this study was to evaluate the diagnostic accuracy of highly sensitive measurement of α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxyprothrombin (DCP) alone and in combination, for HCC detection. In addition, a recently proposed statistical model, including these three biomarkers plus sex and age, the GALAD model, was applied. In a total of 98 patients (44 CLD patients without HCC [23 men, 21 women; mean age, 53.2 ± 13.4 years] and 54 patients with HCC [45 men, nine women; 69.5 ± 9.8 years]), AFP, AFP-L3 and DCP levels were determined using a highly sensitive assay on an μTASWako i30 immuno-analyzer. Areas under the curve (AUC), sensitivity and specificity were calculated and compared to assess diagnostic performance of the HCC biomarkers and of the GALAD model. AFP, AFP-L3 and DCP serum levels were significantly elevated in HCC compared with CLD patients (P < 0.0001). AUC values were 0.891, 0.867 and 0.870, respectively. The combination of the three biomarkers resulted in an AUC of 0.947, whereas the GALAD model showed an AUC of 0.976 with a difference between AUC values of 0.029 (P = 0.028). The combination of AFP, AFP-L3 and DCP is superior to a single biomarker in HCC detection. Furthermore, GALAD model performance is significantly higher than simple combination of these three biomarkers. © 2015 The Japan Society of Hepatology.

  15. IgG glycan patterns are associated with type 2 diabetes in independent European populations.

    Science.gov (United States)

    Lemmers, Roosmarijn F H; Vilaj, Marija; Urda, Daniel; Agakov, Felix; Šimurina, Mirna; Klaric, Lucija; Rudan, Igor; Campbell, Harry; Hayward, Caroline; Wilson, Jim F; Lieverse, Aloysius G; Gornik, Olga; Sijbrands, Eric J G; Lauc, Gordan; van Hoek, Mandy

    2017-09-01

    Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects. In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination. After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729. Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology. This work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. HIV-1 envelope sequence-based diversity measures for identifying recent infections.

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    Alexis Kafando

    Full Text Available Identifying recent HIV-1 infections is crucial for monitoring HIV-1 incidence and optimizing public health prevention efforts. To identify recent HIV-1 infections, we evaluated and compared the performance of 4 sequence-based diversity measures including percent diversity, percent complexity, Shannon entropy and number of haplotypes targeting 13 genetic segments within the env gene of HIV-1. A total of 597 diagnostic samples obtained in 2013 and 2015 from recently and chronically HIV-1 infected individuals were selected. From the selected samples, 249 (134 from recent versus 115 from chronic infections env coding regions, including V1-C5 of gp120 and the gp41 ectodomain of HIV-1, were successfully amplified and sequenced by next generation sequencing (NGS using the Illumina MiSeq platform. The ability of the four sequence-based diversity measures to correctly identify recent HIV infections was evaluated using the frequency distribution curves, median and interquartile range and area under the curve (AUC of the receiver operating characteristic (ROC. Comparing the median and interquartile range and evaluating the frequency distribution curves associated with the 4 sequence-based diversity measures, we observed that the percent diversity, number of haplotypes and Shannon entropy demonstrated significant potential to discriminate recent from chronic infections (p<0.0001. Using the AUC of ROC analysis, only the Shannon entropy measure within three HIV-1 env segments could accurately identify recent infections at a satisfactory level. The env segments were gp120 C2_1 (AUC = 0.806, gp120 C2_3 (AUC = 0.805 and gp120 V3 (AUC = 0.812. Our results clearly indicate that the Shannon entropy measure represents a useful tool for predicting HIV-1 infection recency.

  17. A rapid and sensitive HPLC method for the analysis of metronidazole in human plasma: application to single dose pharmacokinetic and bioequivalence studies

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    Jaber Emami

    2006-03-01

    Full Text Available A sensitive, accurate and rapid reverse phase HPLC method was developed to quantitate plasma levels of metronidazole in order to conduct a comparative bioavailability studies. The drug and internal standard were added to plasma samples, vortexed and then zinc sulfate solution was added in order to precipitate the plasma proteins. Samples were centrifuged at 3000 rpm for 10 min. The supernatant layer was separated and analyzed on a phenyl (300 × 4.6mm column, with 5% acetonitrile in 0.1 M KH2PO4 buffer (pH = 4.5 at 324 nm. The standard curve covering 0.15 – 30 μg/ml concentration range, was linear (r2 = 0.9999, relative errors were within 2.48 to 9.15 % and the CV% ranged from 2.999 to 10.796. The method is suitable for bioavailability, pharmacokinetic, and bioequivalent studies in human. The in-vivo study was carried out in 12 healthy volunteers according to a single dose, two-sequence, cross over randomized design. The bioavailability was compared using the total area under the plasma level versus time curve (AUC0-48, AUC0-, peak plasma concentration (Cmax and time to Cmax (Tmax. No statistically significant difference was found between the AUC0- , Cmax and Tmax values of the test and reference, Flagyl® (p > 0.05. The 90% CI for the ratio of the AUC0- (0.94-1.07 and Cmax (0.88-1.03 and the logarithmically transformed AUC0- (0.99-1.01 and Cmax (0.94-1.01 values of the generic product over those of Flagyl® was calculated to be within the acceptable limit of 0.80-1.20 and 0.80-1.25, respectively. It was, therefore, concluded that the generic metronidazole was bioequivalent with the innovator formulation.

  18. Urinary Biomarker Panel to Improve Accuracy in Predicting Prostate Biopsy Result in Chinese Men with PSA 4–10 ng/mL

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    Yongqiang Zhou

    2017-01-01

    Full Text Available This study aims to evaluate the effectiveness and clinical performance of a panel of urinary biomarkers to diagnose prostate cancer (PCa in Chinese men with PSA levels between 4 and 10 ng/mL. A total of 122 patients with PSA levels between 4 and 10 ng/mL who underwent consecutive prostate biopsy at three hospitals in China were recruited. First-catch urine samples were collected after an attentive prostate massage. Urinary mRNA levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR. The predictive accuracy of these biomarkers and prediction models was assessed by the area under the curve (AUC of the receiver-operating characteristic (ROC curve. The diagnostic accuracy of PCA3, PSGR, and MALAT-1 was superior to that of PSA. PCA3 performed best, with an AUC of 0.734 (95% CI: 0.641, 0.828 followed by MALAT-1 with an AUC of 0.727 (95% CI: 0.625, 0.829 and PSGR with an AUC of 0.666 (95% CI: 0.575, 0.749. The diagnostic panel with age, prostate volume, % fPSA, PCA3 score, PSGR score, and MALAT-1 score yielded an AUC of 0.857 (95% CI: 0.780, 0.933. At a threshold probability of 20%, 47.2% of unnecessary biopsies may be avoided whereas only 6.2% of PCa cases may be missed. This urinary panel may improve the current diagnostic modality in Chinese men with PSA levels between 4 and 10 ng/mL.

  19. Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.

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    Rosario López-Rodríguez

    Full Text Available Chronic hepatitis C (CHC is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC. CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA grade of CHC patients.NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80 or high grade (NIA = 3, n = 39. In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates.Seven SNPs located in IL-28B (rs12979860, JAK1 (rs11576173 and rs1497056, TYK2 (rs280519, OAS1 (rs2057778, SOCS1 (rs33932899 and RNASEL (rs3738579 genes were significantly related to severe NIA grade (p40 IU/L (p40 IU/L, TYK2 rs280519 (G allele and RNASEL rs3738579 (G allele were factors independently associated with elevated NIA (p<0.05. AST concentration showed a moderate AUC value (AUC = 0.63, similar to TYK2 (rs280519 and RNASEL (rs3738579 SNPs (AUC = 0.61, both in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74.The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.

  20. [Endemic heteroresistant glycopeptide intermediate Staphylcoccus aureus (hGISA) comprising unrelated clonal types and not associated with vancomycin therapy].

    Science.gov (United States)

    Lecaillon, E; Gueudet, P; Wooton, M; Walsh, T R; Macgowan, A P; Jones, M E

    2002-11-01

    The detection of methicillin-resistant S. aureus (SA) (MRSA) refractory to glycopeptides is a serious clinical issue. The prevalence of hetero-resistant GISA (hGISA) strains at H. Maréchal Joffre, France is reported.858 non-repeat SA were isolated during 1999. 367 (43%) of these, from 257 patients, were MRSA (mean incidence 11.9/1000 admissions). All MSRA detected during 1999 were screened for vancomycin (VAN) resistance (BHI+4 mg/l VAN). Isolates recovered were retested using Etest strips (2 McFarland inoculum on BHI) and population analysis profile/area under the curve (PAP-AUC) analysis with hGISA SA Mu3 as a comparator. 58 selected strains were screened for teicoplanin resistance(TEI) using SFM recommended screen (2 McFarland inoculum on MH+5 mg/L TEI) and MIC (0.5 MF inoculum swabbed on MH agar) methods. 188 (51.3%) grew on VAN screen agar (6.1/1000 admissions). 58 strains (7.6%) possessed Etest VAN MIC > 8 mg/l all others being VAN 8 mg/l). PAP-AUC showed 12 strains to have PAP-AUC ratios > 0.95 but < 1.5 (ie. hGISA, not GISA). All 7 isolates defined as hGISA by both Etest and PAP-AUC comprised 1 PFGE clone (< 3 bands difference). Additionally 2 distinct PFGE types were detected among the other 5 hGISA identified PAP-AUC. The 12 hGISAs, were derived from 12 patients with severe underlying disease. None were on glycopeptide therapy prior to hGISA isolation. This is the first report of endemic hGISA, comprising 3 clonal types. The isolation of hVISA seems not to be associated with patient-specific glycopeptide therapies.

  1. Diagnostic performance of on-site CT-derived fractional flow reserve versus CT perfusion.

    Science.gov (United States)

    Yang, Dong Hyun; Kim, Young-Hak; Roh, Jae Hyung; Kang, Joon-Won; Ahn, Jung-Min; Kweon, Jihoon; Lee, Jung Bok; Choi, Seong Hoon; Shin, Eun-Seok; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Lee, Cheol Whan; Park, Seong-Wook; Park, Seung-Jung; Lim, Tae-Hwan

    2017-04-01

    To compare the diagnostic accuracy of on-site computed tomography (CT)-derived fractional flow reserve (FFR) and stress CT myocardial perfusion (CTP) in patients with coronary artery disease. Using a prospective CTP registry, 72 patients with invasive FFR were enrolled. CT-derived FFR was computed on-site using rest-phase CTP data. The diagnostic accuracies of coronary CT angiography (CCTA), CT-derived FFR, and stress CTP were evaluated using an area under the receiver-operating characteristic curve (AUC) with invasive FFR as a reference standard. Logistic regression and the net reclassification index (NRI) were used to evaluate incremental differences in CT-derived FFR or CTP compared with CCTA alone. The per-vessel prevalence of haemodynamically significant stenosis (FFR ≤ 0.80) was 39% (54/138). Per-vessel sensitivity and specificity were 94 and 66% for CCTA, 87 and 77% for CT-derived FFR, and 79 and 91% for CTP, respectively. There was no significant difference in the AUC values of CT-derived FFR and CTP (P = 0.845). The diagnostic performance of CCTA (AUC = 0.856) was improved by combining it with CT-derived FFR (AUC = 0.919, P = 0.004, NRI = 1.01) or CTP (AUC = 0.913, P = 0.004, NRI = 0.66). CT-derived FFR values had a moderate correlation with invasive FFR (r = 0.671, P derived FFR combined with CCTA provides an incremental diagnostic improvement over CCTA alone in identifying haemodynamically significant stenosis defined by invasive FFR, with a diagnostic accuracy comparable with CTP.

  2. Growth hormone and sex steroid effects on serum glucose, insulin, and lipid concentrations in healthy older women and men.

    Science.gov (United States)

    Münzer, Thomas; Harman, S Mitchell; Sorkin, John D; Blackman, Marc R

    2009-10-01

    With aging, GH, IGF-I, and sex steroid concentrations and glucose tolerance decrease, and body fat and serum lipids increase. The aim of the study was to assess GH and/or sex steroid administration effects on serum glucose, insulin, insulin sensitivity, and lipids in older individuals. A double-masked, 2 x 2 factorial, placebo-controlled, double-dummy design was used for the study. GH and/or sex steroid [transdermal estradiol plus oral medroxyprogesterone acetate in women (HRT); testosterone enanthate (T) in men] were administered for 6 months. Healthy, community-dwelling women (n = 57) and men (n = 74) ages 65-88 yr (mean, 72 yr) participated in the study. We measured serum glucose, insulin, and insulin sensitivity [quantitative insulin sensitivity check index (QUICKI) and insulin sensitivity index (ISI)] before and during an oral glucose tolerance test and lipid profiles. In women, GH did not alter oral glucose tolerance test 120 min or 2-h area under the curve (AUC) glucose values, but it increased 120 min insulin and AUC insulin. There were no significant effects of HRT or GH+HRT. ISI and QUICKI decreased after GH. In men, GH increased 120 min and AUC glucose and insulin AUC. GH+T increased 120 min glucose and glucose and insulin AUCs. T alone did not affect glucose or insulin. ISI decreased after GH and GH+T, whereas QUICKI decreased after GH. GH in women and men and GH+T in men decreased QUICKI by 4 wk. In women, HRT decreased total cholesterol and low-density lipoprotein (LDL)-cholesterol, and GH decreased LDL-cholesterol. In men, total cholesterol decreased after T and GH+T. LDL-cholesterol decreased after GH and GH+T. GH increased serum triglycerides. GH administration to healthy older individuals for 6 months increased insulin resistance with moderately beneficial effects on lipids.

  3. Glycemic index predicts individual glucose responses after self-selected breakfasts in free-living, abdominally obese adults.

    Science.gov (United States)

    Kochan, Angela M; Wolever, Thomas M S; Chetty, V Tony; Anand, Sonia S; Gerstein, Hertzel C; Sharma, Arya M

    2012-01-01

    The degree to which an individual's glycemic response to a meal is determined by the glycemic index (GI) and other components of the meal remains unclear, especially when meals are not consumed in a highly controlled research setting. To address this question, we analyzed data collected during the run-in period of a clinical trial. Free-living, nondiabetic adults (n = 57) aged 53.9 ± 9.8 y (mean ± SD) with a BMI of 33.9 ± 5.3 kg/m(2) and waist circumference of 109 ± 11 cm underwent a 75-g oral glucose tolerance test (OGTT) and, on a separate day, wore a continuous glucose-monitoring system (CGMS) for 24 h during which time they recorded all foods consumed. The protein, fat, and available carbohydrate (avCHO) content and GI of the breakfast meals were calculated from the food records and the incremental areas under the glycemic response curves (iAUC) for 2 h after breakfast (iAUC(breakfast)) were calculated from CGMS data. Values for iAUC(breakfast), avCHO, fat, fiber, and BMI were normalized by log-transformation. The ability of participant characteristics and breakfast composition to predict individual iAUC(breakfast) responses was determined using step-wise multiple linear regression. A total of 56% of the variation in iAUC(breakfast) was explained by GI (30%; P fat, protein, dietary fiber, age, sex, and BMI were not significant. We concluded that, in free-living, abdominally obese adults, GI is a significant determinant of individual glycemic responses elicited by self-selected breakfast meals. In this study, GI was a more important determinant of glycemic response than carbohydrate intake.

  4. Multiparametric Evaluation of Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer Using Integrated PET/MR.

    Science.gov (United States)

    Wang, Jane; Shih, Tiffany Ting-Fang; Yen, Ruoh-Fang

    2017-07-01

    The aim of this study was to investigate whether integrated PET/MR system can predict the treatment response to neoadjuvant chemotherapy (NAC) early in the course of breast cancer treatment. Fourteen women with newly diagnosed invasive breast cancer (median age, 54.5 years) were recruited. Each participant underwent 2 PET/MR studies. Study 1 was pre-NAC; study 2 was early in NAC treatment (after the first or second cycle). PET parameters included SUVmax and total lesion glycolysis (TLG). MRI parameters included choline signal-to-noise ratio (ChoSNR), peak enhancement ratio (PER), and the minimum apparent diffusion coefficient (ADCmin). The pathologic response was categorized as a pathologic complete response or residual cellularity of less than 10% (group 1) and residual cellularity of 10% or greater (group 2). The accuracy of the NAC response prediction was obtained by receiver operating characteristic analysis. Group 1 showed a greater reduction of SUVmax (percentage change, [INCREMENT]% SUVmax, P = 0.013; area under the receiver operating characteristic curve [AUC], 0.898), TLG ([INCREMENT]%TLG, P = 0.018; AUC = 0.878), and PER ([INCREMENT]% PER, P = 0.035; AUC = 0.837) than did group 2. The ChoSNR, ADCmin, [INCREMENT]%ChoSNR, and [INCREMENT]%ADCmin did not differ significantly between the 2 groups. The hybrid markers, [INCREMENT]%SUVmax/[INCREMENT]%ADCmin (AUC = 0.976) and [INCREMENT]%TLG/[INCREMENT]%ADCmin (AUC = 0.905), showed greater accuracy in predicting NAC response than the individual PET/MR parameters. The PET/MR parameters can predict the NAC response early in the course of breast cancer treatment. The hybrid markers more accurately predicted treatment response than the individual PET/MR parameters.

  5. SU-F-R-04: Radiomics for Survival Prediction in Glioblastoma (GBM)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H; Molitoris, J; Bhooshan, N; Choi, W; Lu, W; Mehta, M; D’Souza, W [University of Maryland School of Medicine, Baltimore, MD (United States); Tan, S [Huazhong University of Science & Technology, Wuhan (China); Giacomelli, I; Scartoni, D [University of Florence, Florence (Italy); Gzell, C [Northern Sydney Cancer Centre, Sydney (Australia)

    2016-06-15

    Purpose: To develop a quantitative radiomics approach for survival prediction of glioblastoma (GBM) patients treated with chemoradiotherapy (CRT). Methods: 28 GBM patients who received CRT at our institution were retrospectively studied. 255 radiomic features were extracted from 3 gadolinium-enhanced T1 weighted MRIs for 2 regions of interest (ROIs) (the surgical cavity and its surrounding enhancement rim). The 3 MRIs were at pre-treatment, 1-month and 3-month post-CRT. The imaging features comprehensively quantified the intensity, spatial variation (texture), geometric property and their spatial-temporal changes for the 2 ROIs. 3 demographics features (age, race, gender) and 12 clinical parameters (KPS, extent of resection, whether concurrent temozolomide was adjusted/stopped and radiotherapy related information) were also included. 4 Machine learning models (logistic regression (LR), support vector machine (SVM), decision tree (DT), neural network (NN)) were applied to predict overall survival (OS) and progression-free survival (PFS). The number of cases and percentage of cases predicted correctly were collected and AUC (area under the receiver operating characteristic (ROC) curve) were determined after leave-one-out cross-validation. Results: From univariate analysis, 27 features (1 demographic, 1 clinical and 25 imaging) were statistically significant (p<0.05) for both OS and PFS. Two sets of features (each contained 24 features) were algorithmically selected from all features to predict OS and PFS. High prediction accuracy of OS was achieved by using NN (96%, 27 of 28 cases were correctly predicted, AUC = 0.99), LR (93%, 26 of 28 cases were correctly predicted, AUC = 0.95) and SVM (93%, 26 of 28 cases were correctly predicted, AUC = 0.90). When predicting PFS, NN obtained the highest prediction accuracy (89%, 25 of 28 cases were correctly predicted, AUC = 0.92). Conclusion: Radiomics approach combined with patients’ demographics and clinical parameters can

  6. Full Outline of Unresponsiveness score and the Glasgow Coma Scale in prediction of pediatric coma.

    Science.gov (United States)

    Jamal, Atahar; Sankhyan, Naveen; Jayashree, Murlidharan; Singhi, Sunit; Singhi, Pratibha

    2017-01-01

    This study was done to compare the admission Full Outline of Unresponsiveness (FOUR) score and Glasgow Coma Scale (GCS) as predictors of outcome in children with impaired consciousness. In this observational study, children (5-12 years) with impaired consciousness of <7 days were included. Children with traumatic brain injury, on sedatives or neuromuscular blockade; with pre-existing cerebral palsy, mental retardation, degenerative brain disease, vision/hearing impairment; and seizure within last 1 hour were excluded. Primary outcomes: comparison of area under curve (AUC) of receiver operating characteristic (ROC) curve for in-hospital mortality. Secondary outcomes: comparison of AUC of ROC curve for mortality and poor outcome on Pediatric Overall Performance Category Scale at 3 months. Of the 63 children, 20 died during hospital stay. AUC for in-hospital mortality for GCS was 0.83 (CI 0.7 to 0.9) and FOUR score was 0.8 (CI 0.7 to 0.9) [difference between areas -0.0250 (95%CI 0.0192 to 0.0692), Z statistic 1.109, P=0.2674]. AUC for mortality at 3 months for GCS was 0.78 (CI 0.67 to 0.90) and FOUR score was 0.74 (CI 0.62 to 0.87) (P=0.1102) and AUC for poor functional outcome for GCS was 0.82 (CI 0.72 to 0.93) and FOUR score was 0.79 (CI 0.68 to 0.9) (P=0.2377), which were also comparable. Inter-rater reliability for GCS was 0.96 and for FOUR score 0.98. FOUR score was as good as GCS in prediction of in-hospital and 3-month mortality and functional outcome at 3 months. FOUR score had a good inter-rater reliability.

  7. Cocoa extract intake for 4 weeks reduces postprandial systolic blood pressure response of obese subjects, even after following an energy-restricted diet

    Directory of Open Access Journals (Sweden)

    Idoia Ibero-Baraibar

    2016-03-01

    Full Text Available Background: Cardiometabolic profile is usually altered in obesity. Interestingly, the consumption of flavanol-rich foods might be protective against those metabolic alterations. Objective: To evaluate the postprandial cardiometabolic effects after the acute consumption of cocoa extract before and after 4 weeks of its daily intake. Furthermore, the bioavailability of cocoa extract was investigated. Design: Twenty-four overweight/obese middle-aged subjects participated in a 4-week intervention study. Half of the volunteers consumed a test meal enriched with 1.4 g of cocoa extract (415 mg flavanols, while the rest of the volunteers consumed the same meal without the cocoa extract (control group. Glucose and lipid profile, as well as blood pressure and cocoa metabolites in plasma, were assessed before and at 60, 120, and 180 min post-consumption, at the beginning of the study (Postprandial 1 and after following a 4-week 15% energy-restricted diet including meals containing or not containing the cocoa extract (Postprandial 2. Results: In the Postprandial 1 test, the area under the curve (AUC of systolic blood pressure (SBP was significantly higher in the cocoa group compared with the control group (p=0.007, showing significant differences after 120 min of intake. However, no differences between groups were observed at Postprandial 2. Interestingly, the reduction of postprandial AUC of SBP (AUC_Postprandial 2-AUC_Postprandial 1 was higher in the cocoa group (p=0.016. Furthermore, cocoa-derived metabolites were detected in plasma of the cocoa group, while the absence or significantly lower amounts of metabolites were found in the control group. Conclusions: The daily consumption of cocoa extract within an energy-restricted diet for 4 weeks resulted in a greater reduction of postprandial AUC of SBP compared with the effect of energy-restricted diet alone and independently of body weight loss. These results suggest the role of cocoa flavanols on

  8. Prediction model for knee osteoarthritis incidence, including clinical, genetic and biochemical risk factors.

    Science.gov (United States)

    Kerkhof, H J M; Bierma-Zeinstra, S M A; Arden, N K; Metrustry, S; Castano-Betancourt, M; Hart, D J; Hofman, A; Rivadeneira, F; Oei, E H G; Spector, Tim D; Uitterlinden, A G; Janssens, A C J W; Valdes, A M; van Meurs, J B J

    2014-12-01

    To develop and validate a prognostic model for incident knee osteoarthritis (KOA) in a general population and determine the value of different risk factor groups to prediction. The prognostic model was developed in 2628 individuals from the Rotterdam Study-I (RS-I). Univariate and multivariate analyses were performed for questionnaire/easily obtainable variables, imaging variables, genetic and biochemical markers. The extended multivariate model was tested on discrimination (receiver operating characteristic curve and area under the curve (AUC)) in two other population-based cohorts: Rotterdam Study-II and Chingford Study. In RS-I, there was moderate predictive value for incident KOA based on the genetic score alone in subjects aged <65 years (AUC 0.65), while it was only 0.55 for subjects aged ≥65 years. The AUC for gender, age and body mass index (BMI) in prediction for KOA was 0.66. Addition of the questionnaire variables, genetic score or biochemical marker urinary C-terminal cross-linked telopeptide of type II collagen to the model did not change the AUC. However, when adding the knee baseline KL score to the model the AUC increased to 0.79. Applying external validation, similar results were observed in the Rotterdam Study-II and the Chingford Study. Easy obtainable 'Questionnaire' variables, genetic markers, OA at other joint sites and biochemical markers add only modestly to the prediction of KOA incidence using age, gender and BMI in an elderly population. Doubtful minor radiographic degenerative features in the knee, however, are a very strong predictor of future KOA. This is an important finding, as many radiologists do not report minor degenerative changes in the knee. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. SU-D-207B-02: Early Grade Classification in Meningioma Patients Combining Radiomics and Semantics Data

    Energy Technology Data Exchange (ETDEWEB)

    Coroller, T; Bi, W; Abedalthagafi, M; Aizer, A; Wu, W; Greenwald, N; Beroukhim, R; Al-Mefty, O; Santagata, S; Dunn, I; Alexander, B; Huang, R; Aerts, H [Dana Farber Cancer Institute, Brigham and Womens Hospital, Harvard Medical School (United States)

    2016-06-15

    Purpose: The clinical management of meningioma is guided by its grade and biologic behavior. Currently, diagnosis of tumor grade follows surgical resection and histopathologic review. Reliable techniques for pre-operative determination of tumor behavior are needed. We investigated the association between imaging features extracted from preoperative gadolinium-enhanced T1-weighted MRI and meningioma grade. Methods: We retrospectively examined the pre-operative MRI for 139 patients with de novo WHO grade I (63%) and grade II (37%) meningiomas. We investigated the predictive power of ten semantic radiologic features as determined by a neuroradiologist, fifteen radiomic features, and tumor location. Conventional (volume and diameter) imaging features were added for comparison. AUC was computed for continuous and χ{sup 2} for discrete variables. Classification was done using random forest. Performance was evaluated using cross validation (1000 iterations, 75% training and 25% validation). All p-values were adjusted for multiple testing. Results: Significant association was observed between meningioma grade and tumor location (p<0.001) and two semantic features including intra-tumoral heterogeneity (p<0.001) and overt hemorrhage (p=0.01). Conventional (AUC 0.61–0.67) and eleven radiomic (AUC 0.60–0.70) features were significant from random (p<0.05, Noether test). Median AUC values for classification of tumor grade were 0.57, 0.71, 0.72 and 0.77 respectively for conventional, radiomic, location, and semantic features after using random forest. By combining all imaging data (semantic, radiomic, and location), the median AUC was 0.81, which offers superior predicting power to that of conventional imaging descriptors for meningioma as well as radiomic features alone (p<0.05, permutation test). Conclusion: We demonstrate a strong association between radiologic features and meningioma grade. Pre-operative prediction of tumor behavior based on imaging features offers

  10. Impact of PCI Appropriateness in the Long-Term Outcomes of Consecutive Patients Treated With Second-Generation Drug-Eluting Stents.

    Science.gov (United States)

    Seixas, Ana Cristina; Sousa, Amanda; de Ribamar Costa, Jose; Costa Moreira, Adriana; Costa, Ricardo; Damiani, Lucas; Campos Neto, Cantídio; Maldonado, Galo; Cano, Manuel; Sousa, J Eduardo

    2017-09-01

    Appropriate use criteria (AUC) for coronary revascularization were developed to deliver high-quality care; however, the prognostic impact of these criteria remains unclear. We sought to assess the outcomes of patients treated with second-generation drug-eluting stent (DES) classified according to the updated American College of Cardiology Foundation/American Heart Association/Society for Cardiac Angiography and Intervention AUC for percutaneous coronary intervention (PCI). Between January 2012 and December 2013, a total of 1108 consecutive patients treated only with second-generation DES were categorized according to the AUC in three groups, using the new proposed terminology: appropriate ("A"); uncertain ("U"); and inappropriate ("I"). Major adverse cardiac event (MACE, defined as cardiac death, non-fatal myocardial infarction, and ischemia-driven target-lesion revascularization) and stent thrombosis up to 3 years were compared. PCI was categorized as A in 33.8%, U in 46.8%, and I in 19.4% of all cases. PCI-A patients had a higher prevalence of acute coronary syndromes, while PCI-I involved the treatment of more diabetics and patients with stable coronary disease. There were no differences in procedural complications among the three groups, with comparable rates of in-hospital MACE (9.3% for A vs 9.0% for U vs 7.0% for I; P=.70) and 2-year MACE (13.9% for A vs 9.0% for U vs 8.6% for I; P=.40). In the multivariable analysis, AUC classification was not associated with adverse outcomes. In this contemporary cohort of patients treated with second-generation DES implantation, AUC did not impact 3-year clinical follow-up.

  11. On a fractional order calculus model in diffusion weighted breast imaging to differentiate between malignant and benign breast lesions detected on X-ray screening mammography.

    Science.gov (United States)

    Bickelhaupt, Sebastian; Steudle, Franziska; Paech, Daniel; Mlynarska, Anna; Kuder, Tristan Anselm; Lederer, Wolfgang; Daniel, Heidi; Freitag, Martin; Delorme, Stefan; Schlemmer, Heinz-Peter; Laun, Frederik Bernd

    2017-01-01

    To evaluate a fractional order calculus (FROC) model in diffusion weighted imaging to differentiate between malignant and benign breast lesions in breast cancer screening work-up using recently introduced parameters (βFROC, DFROC and μFROC). This retrospec