Probing the electronic structure and Au–C chemical bonding in AuC2− and AuC2 using high-resolution photoelectron spectroscopy

International Nuclear Information System (INIS)

León, Iker; Yang, Zheng; Wang, Lai-Sheng

2014-01-01

We report photoelectron spectroscopy (PES) and high-resolution PE imaging of AuC 2 − at a wide range of photon energies. The ground state of AuC 2 − is found to be linear (C ∞v , 1 Σ + ) with a …8π 4 4δ 4 17σ 2 9π 4 18σ 2 valence configuration. Detachments from all the five valence orbitals of the ground state of AuC 2 − are observed at 193 nm. High-resolution PE images are obtained in the energy range from 830 to 330 nm, revealing complicated vibronic structures from electron detachment of the 18σ, 9π, and 17σ orbitals. Detachment from the 18σ orbital results in the 2 Σ + ground state of neutral AuC 2 , which, however, is bent due to strong vibronic coupling with the nearby 2 Π state from detachment of a 9π electron. The 2 Σ + – 2 Π vibronic and spin-orbit coupling results in complicated vibronic structures for the 2 Σ + and 2 Π 3/2 states with extensive bending excitations. The electron affinity of AuC 2 is measured accurately to be 3.2192(7) eV with a ground state bending frequency of 195(6) cm −1 . The first excited state ( 2 A′) of AuC 2 , corresponding to the 2 Π 3/2 state at the linear geometry, is only 0.0021 eV above the ground state ( 2 A′) and has a bending frequency of 207(6) cm −1 . The 2 Π 1/2 state, 0.2291 eV above the ground state, is linear with little geometry change relative to the anion ground state. The detachment of the 17σ orbital also results in complicated vibronic structures, suggesting again a bent state due to possible vibronic coupling with the lower 2 Π state. The spectrum at 193 nm shows the presence of a minor species with less than 2% intensity relative to the ground state of AuC 2 − . High-resolution data of the minor species reveal several vibrational progressions in the Au–C stretching mode, which are assigned to be from the metastable 3 Π 2,1,0 spin-orbit excited states of AuC 2 − to the 2 Π 3/2,1/2 spin-orbit states of neutral AuC 2 . The spin-orbit splittings of the 3 Π and 2 �

Purification of ADU and high-molybdenum AUC by recrystallization

International Nuclear Information System (INIS)

Tan Huanchang; Wen Jinfeng

1995-01-01

The ADU was converted to AUC by preparing pulp with (NH 4 ) 2 CO 3 concentrated solution, and then the prepared AUC (high-molybdenum AUC) crystals were dissolved with hot soft water for dissolution, and after filtration or clarification and scrubbing of the residue, and the clarified solution was digested and the obtained pulp was thickened and the thickened pulp was converted and recrystallized by adding (NH 4 ) 2 CO 3 concentrated solution. The crystals were washed and filtrated, and then the high-purity AUC crystals were prepared. The laboratory and pilot-plant scale experiments showed that the presented purification process was feasible with the solvent extraction step eliminated, so the chemicals consumption would be considerably decreased and the environmental pollution would be lowered. It is easy to realize the process in practice

[Atypical urothelial cells (AUC): A Bethesda-derived wording applicable to urinary cytopathology].

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Piaton, Eric; Advenier, Anne-Sophie; Benaïm, Gilles; Petrucci, Myriam Decaussin; Lechevallier, Florence Mege; Ruffion, Alain

2011-02-01

To investigate (1) whether sparse nuclear atypias involving deep urothelial cells have a diagnostic or prognostic value in urinary cytology, and (2) whether the terms atypical urothelial cells "of undetermined significance" (AUC-US) or "cannot exclude high grade" (AUC-H) might be used to standardize urinary cytology reports. Atypical urothelial cells (AUC) were defined as deep cells with nuclear abnormalities (increased N/C ratio, eccentric nucleus, hyperchromatism and/or irregular shape) in small number not allowing their categorization as malignant, high grade. We studied 435 urinary samples from 126 patients with AUC at any step of their clinical history, followed up over a 10-year period (1999-2009). Every case was compared with histopathology within 6 months and to long term follow-up including cystoscopy and histopathology combined. A total of 183 AUC was recorded. AUC were associated with negative, benign or low grade histological results in 36 of 106 cases (33.9 %) within 6 months, but a high grade was simultaneously documented in 70 cases (66 %). AUC preceded high-grade lesions in 66 cases (36.1 % of all AUC) in a mean interval of 10.5±12.0 months. Overall, AUC were associated with or predictive of high-grade lesions in 135 cases (73.8 %). AUC have a diagnostic and prognostic value. Applying the terms AUC-US and AUC-H to urinary cytopathology reports would allow, as for the Bethesda system for cervical or vaginal cytologic diagnoses, better appreciation of the risk of progression to high grade tumours in cases with atypias. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

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

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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.

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

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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.

Efficient AUC optimization for classification

NARCIS (Netherlands)

Calders, T.; Jaroszewicz, S.; Kok, J.N.; Koronacki, J.; Lopez de Mantaras, R.; Matwin, S.; Mladenic, D.; Skowron, A.

2007-01-01

In this paper we show an efficient method for inducing classifiers that directly optimize the area under the ROC curve. Recently, AUC gained importance in the classification community as a mean to compare the performance of classifiers. Because most classification methods do not optimize this

Study On Precipitation Of UO2 Ex-AUC Powder. Part I: Precipitation Of AUC By (NH4)2CO3 From Uranyl Fluoride Solution

International Nuclear Information System (INIS)

Nguyen Trong Hung; Le Ba Thuan; Do Van Khoai; Nguyen Thanh Thuy; Nguyen Van Tung

2011-01-01

In this paper, Ammonium Uranyl Carbonate (AUC) powders were prepared by precipitation method in solution. UO 2 F 2 /HF, ammonium carbonate (AC), and ammonium hydroxide solution were used as precursors for precipitation. The influence of C/U ratio (mol/mol), AC concentration (g/L), reaction temperature ( o C), on characteristics of AUC powders was also investigated. Then, the synthesized AUC powders were analyzed (to define) phase composition (X-ray), fluorine content, morphology (by SEM), and specific surface area (BET). (author)

CA-125 AUC as a predictor for epithelial ovarian cancer relapse.

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Mano, António; Falcão, Amílcar; Godinho, Isabel; Santos, Jorge; Leitão, Fátima; de Oliveira, Carlos; Caramona, Margarida

2008-01-01

The aim of the present work was to evaluate the usefulness of CA-125 normalized in time area under the curve (CA-125 AUC) to signalise epithelial ovarian cancer relapse. Data from a hundred and eleven patients were submitted to two different approaches based on CA-125 AUC increase values to predict patient relapse. In Criterion A total CA-125 AUC normalized in time value (AUC(i)) was compared with the immediately previous one (AUC(i-1)) using the formulae AUC(i) > or = F * AUC(i-1) (several F values were tested) to find the appropriate close related increment associated to patient relapse. In Criterion B total CA-125 AUC normalised in time was calculated and several cut-off values were correlated with patient relapse prediction capacity. In Criterion A the best accuracy was achieved with a factor (F) of 1.25 (increment of 25% from the previous status), while in Criterion B the best accuracies were achieved with cut-offs of 25, 50, 75 and 100 IU/mL. The mean lead time to relapse achieved with Criterion A was 181 days, while with Criterion B they were, respectively, 131, 111, 63 and 11 days. Based on our results we believe that conjugation and sequential application of both criteria in patient relapse detection should be highly advisable. CA-125 AUC rapid burst in asymptomatic patients should be firstly evaluated using Criterion A with a high accuracy (0.85) and with a substantial mean lead time to relapse (181 days). If a negative answer was obtained then Criterion B should performed to confirm the absence of relapse.

Limited Sampling Strategy for the Prediction of Area Under the Curve (AUC) of Statins: Reliability of a Single Time Point for AUC Prediction for Pravastatin and Simvastatin.

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Srinivas, N R

2016-02-01

Statins are widely prescribed medicines and are also available in fixed dose combinations with other drugs to treat several chronic ailments. Given the safety issues associated with statins it may be important to assess feasibility of a single time concentration strategy for prediction of exposure (area under the curve; AUC). The peak concentration (Cmax) was used to establish relationship with AUC separately for pravastatin and simvastatin using published pharmacokinetic data. The regression equations generated for statins were used to predict the AUC values from various literature references. The fold difference of the observed divided by predicted values along with correlation coefficient (r) were used to judge the feasibility of the single time point approach. Both pravastatin and simvastatin showed excellent correlation of Cmax vs. AUC values with r value ≥ 0.9638 (pAUC predictions and >81% of the predicted values were in a narrower range of >0.75-fold but AUC values showed excellent correlation for pravastatin (r=0.9708, n=115; pAUC predictions. On the basis of the present work, it is feasible to develop a single concentration time point strategy that coincides with Cmax occurrence for both pravastatin and simvastatin from a therapeutic drug monitoring perspective. © Georg Thieme Verlag KG Stuttgart · New York.

AUC-Maximized Deep Convolutional Neural Fields for Protein Sequence Labeling.

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Wang, Sheng; Sun, Siqi; Xu, Jinbo

2016-09-01

Deep Convolutional Neural Networks (DCNN) has shown excellent performance in a variety of machine learning tasks. This paper presents Deep Convolutional Neural Fields (DeepCNF), an integration of DCNN with Conditional Random Field (CRF), for sequence labeling with an imbalanced label distribution. The widely-used training methods, such as maximum-likelihood and maximum labelwise accuracy, do not work well on imbalanced data. To handle this, we present a new training algorithm called maximum-AUC for DeepCNF. That is, we train DeepCNF by directly maximizing the empirical Area Under the ROC Curve (AUC), which is an unbiased measurement for imbalanced data. To fulfill this, we formulate AUC in a pairwise ranking framework, approximate it by a polynomial function and then apply a gradient-based procedure to optimize it. Our experimental results confirm that maximum-AUC greatly outperforms the other two training methods on 8-state secondary structure prediction and disorder prediction since their label distributions are highly imbalanced and also has similar performance as the other two training methods on solvent accessibility prediction, which has three equally-distributed labels. Furthermore, our experimental results show that our AUC-trained DeepCNF models greatly outperform existing popular predictors of these three tasks. The data and software related to this paper are available at https://github.com/realbigws/DeepCNF_AUC.

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

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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.

Use of partial AUC to demonstrate bioequivalence of Zolpidem Tartrate Extended Release formulations.

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Lionberger, Robert A; Raw, Andre S; Kim, Stephanie H; Zhang, Xinyuan; Yu, Lawrence X

2012-04-01

FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times. Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations. The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test. In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien CR: onset of sleep and sleep maintenance.

The production of sinterable UO2 from AUC

International Nuclear Information System (INIS)

Chang, I.S.; Do, J.B.; Choi, Y.D.; Park, M.H.; Yun, H.H.; Kim, E.H.; Kim, Y.W.

1982-01-01

Fluidization, feeding and discharging, and mixing of fine particles (-up to 40μ in diameter) in fluidized bed reactor has been examined. The degree of conversion has been estimated using the kinetic data differential scanning colorimetry(DSC) and thermogravimetic analysis (TGA) of ammonium uranyl carbonate (AUC) and residence time distribution data. Satisfactory operation is obtained with a sintered ceramic distributor and filters. The reactor equilvalent to approximately 1.1-1.3 stages. Thermal analysis of AUC in hydrogen atmosphere shows that the decomposition of AUC to UO 3 at 200degC is followed by reduction of UO 3 to UO 2 in two steps in the range between 400degC and 500degC and the complete conversion to UO 2 takes two minutes at 550degC. The overall conversion of above 99.5% in the fluidized bed reactor is estimated with 40 minutes of a mean particle residence time at 600degC. (Author)

Clinical usefulness of limited sampling strategies for estimating AUC of proton pump inhibitors.

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Niioka, Takenori

2011-03-01

Cytochrome P450 (CYP) 2C19 (CYP2C19) genotype is regarded as a useful tool to predict area under the blood concentration-time curve (AUC) of proton pump inhibitors (PPIs). In our results, however, CYP2C19 genotypes had no influence on AUC of all PPIs during fluvoxamine treatment. These findings suggest that CYP2C19 genotyping is not always a good indicator for estimating AUC of PPIs. Limited sampling strategies (LSS) were developed to estimate AUC simply and accurately. It is important to minimize the number of blood samples because of patient's acceptance. This article reviewed the usefulness of LSS for estimating AUC of three PPIs (omeprazole: OPZ, lansoprazole: LPZ and rabeprazole: RPZ). The best prediction formulas in each PPI were AUC(OPZ)=9.24 x C(6h)+2638.03, AUC(LPZ)=12.32 x C(6h)+3276.09 and AUC(RPZ)=1.39 x C(3h)+7.17 x C(6h)+344.14, respectively. In order to optimize the sampling strategy of LPZ, we tried to establish LSS for LPZ using a time point within 3 hours through the property of pharmacokinetics of its enantiomers. The best prediction formula using the fewest sampling points (one point) was AUC(racemic LPZ)=6.5 x C(3h) of (R)-LPZ+13.7 x C(3h) of (S)-LPZ-9917.3 x G1-14387.2×G2+7103.6 (G1: homozygous extensive metabolizer is 1 and the other genotypes are 0; G2: heterozygous extensive metabolizer is 1 and the other genotypes are 0). Those strategies, plasma concentration monitoring at one or two time-points, might be more suitable for AUC estimation than reference to CYP2C19 genotypes, particularly in the case of coadministration of CYP mediators.

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

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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.

The cross-validated AUC for MCP-logistic regression with high-dimensional data.

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Jiang, Dingfeng; Huang, Jian; Zhang, Ying

2013-10-01

We propose a cross-validated area under the receiving operator characteristic (ROC) curve (CV-AUC) criterion for tuning parameter selection for penalized methods in sparse, high-dimensional logistic regression models. We use this criterion in combination with the minimax concave penalty (MCP) method for variable selection. The CV-AUC criterion is specifically designed for optimizing the classification performance for binary outcome data. To implement the proposed approach, we derive an efficient coordinate descent algorithm to compute the MCP-logistic regression solution surface. Simulation studies are conducted to evaluate the finite sample performance of the proposed method and its comparison with the existing methods including the Akaike information criterion (AIC), Bayesian information criterion (BIC) or Extended BIC (EBIC). The model selected based on the CV-AUC criterion tends to have a larger predictive AUC and smaller classification error than those with tuning parameters selected using the AIC, BIC or EBIC. We illustrate the application of the MCP-logistic regression with the CV-AUC criterion on three microarray datasets from the studies that attempt to identify genes related to cancers. Our simulation studies and data examples demonstrate that the CV-AUC is an attractive method for tuning parameter selection for penalized methods in high-dimensional logistic regression models.

Discrimination measures for survival outcomes: connection between the AUC and the predictiveness curve.

Science.gov (United States)

Viallon, Vivian; Latouche, Aurélien

2011-03-01

Finding out biomarkers and building risk scores to predict the occurrence of survival outcomes is a major concern of clinical epidemiology, and so is the evaluation of prognostic models. In this paper, we are concerned with the estimation of the time-dependent AUC--area under the receiver-operating curve--which naturally extends standard AUC to the setting of survival outcomes and enables to evaluate the discriminative power of prognostic models. We establish a simple and useful relation between the predictiveness curve and the time-dependent AUC--AUC(t). This relation confirms that the predictiveness curve is the key concept for evaluating calibration and discrimination of prognostic models. It also highlights that accurate estimates of the conditional absolute risk function should yield accurate estimates for AUC(t). From this observation, we derive several estimators for AUC(t) relying on distinct estimators of the conditional absolute risk function. An empirical study was conducted to compare our estimators with the existing ones and assess the effect of model misspecification--when estimating the conditional absolute risk function--on the AUC(t) estimation. We further illustrate the methodology on the Mayo PBC and the VA lung cancer data sets. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Science.gov (United States)

2013-08-21

... NUCLEAR REGULATORY COMMISSION [Docket No. 040-09092; [NRC-2013-0164] AUC, LLC Reno Creek, In Situ..., AUC, LLC (AUC) submitted to the U.S. Nuclear Regulatory Commission (NRC) an application for a new... and operation, and decommissioning of AUC's proposed in-situ uranium recovery (ISR, also known as in...

Application of the piecewise rational quadratic interpolant to the AUC calculation in the bioavailability study.

Science.gov (United States)

Akhter, Khalid P; Ahmad, Mahmood; Khan, Shujaat Ali; Ramzan, Munazza; Shafi, Ishrat; Muryam, Burhana; Javed, Zafar; Murtaza, Ghulam

2012-01-01

This study presents an application of the piecewise rational quadratic interpolant to the AUC calculation in the bioavailability study. The objective of this work is to find an area under the plasma concentration-time curve (AUC) for multiple doses of salbutamol sulfate sustained release tablets (Ventolin oral tablets SR 8 mg, GSK, Pakistan) in the group of 24 healthy adults by using computational mathematics techniques. Following the administration of 4 doses of Ventolin tablets 12 hourly to 24 healthy human subjects and bioanalysis of obtained plasma samples, plasma drug concentration-time profile was constructed. The approximated AUC was computed by using computational mathematics techniques such as extended rectangular, extended trapezium and extended Simpson's rule and compared with exact value of AUC calculated by using software - Kinetica to find best computational mathematics method that gives AUC values closest to exact. The exact values of AUC for four consecutive doses of Ventolin oral tablets were 150.58, 157.81, 164.41 and 162.78 ngxh/mL while the closest approximated AUC values were 149.24, 157.33, 164.25 and 162.28 ngxh/mL, respectively, as found by extended rectangular rule. The errors in the approximated values of AUC were negligible. It is concluded that all computational tools approximated values of AUC accurately but the extended rectangular rule gives slightly better approximated values of AUC as compared to extended trapezium and extended Simpson's rules.

Guidance to Achieve Accurate Aggregate Quantitation in Biopharmaceuticals by SV-AUC.

Science.gov (United States)

Arthur, Kelly K; Kendrick, Brent S; Gabrielson, John P

2015-01-01

The levels and types of aggregates present in protein biopharmaceuticals must be assessed during all stages of product development, manufacturing, and storage of the finished product. Routine monitoring of aggregate levels in biopharmaceuticals is typically achieved by size exclusion chromatography (SEC) due to its high precision, speed, robustness, and simplicity to operate. However, SEC is error prone and requires careful method development to ensure accuracy of reported aggregate levels. Sedimentation velocity analytical ultracentrifugation (SV-AUC) is an orthogonal technique that can be used to measure protein aggregation without many of the potential inaccuracies of SEC. In this chapter, we discuss applications of SV-AUC during biopharmaceutical development and how characteristics of the technique make it better suited for some applications than others. We then discuss the elements of a comprehensive analytical control strategy for SV-AUC. Successful implementation of these analytical control elements ensures that SV-AUC provides continued value over the long time frames necessary to bring biopharmaceuticals to market. © 2015 Elsevier Inc. All rights reserved.

Carboplatin AUC 10 for IGCCCG good prognosis metastatic seminoma.

Science.gov (United States)

Tookman, Laura; Rashid, Sukaina; Matakidou, Athena; Phillips, Melissa; Wilson, Peter; Ansell, Wendy; Jamal-Hanjani, Mariam; Chowdhury, Simon; Harland, Stephen; Sarwar, Naveed; Oliver, Timothy; Powles, Thomas; Shamash, Jonathan

2013-06-01

Metastatic seminoma is a highly curable disease. Standard treatment comprises of combination chemotherapy. The short- and long-term toxicities of this treatment are increasingly recognised and the possibility of over treatment in such a curable disease should be considered. We have therefore assessed the use of single agent carboplatin at a dose of AUC 10 in patients with good prognosis metastatic seminoma. Patients with good prognosis metastatic seminoma treated with carboplatin (AUC 10) were identified at our institution and affiliated institutions. Treatment was three weekly for a total of three or four cycles. Outcome and toxicities were analysed. With a median follow-up of 36 months, 61 patients in total were treated with carboplatin AUC 10, all good prognosis by the IGCCCG criteria. Forty-eight percent had stage IIA/IIB disease and 52% had greater than stage IIB disease. Thirty-one patients (51%) had a complete response following treatment. Three-year survival was 96.3% with a three-year progression free survival of 93.2%. The main treatment toxicity was haematological with 46% having grade 3, 24% having grade 4 neutropenia and 54% experiencing grade 3/4 thrombocytopenia. There were no treatment related deaths. Single agent carboplatin at a dose of AUC 10 is an effective treatment for good prognosis metastatic seminoma. The outcome compares favourably to previously published outcomes of combination chemotherapy. Although haematological toxicity is a concern, single agent carboplatin treatment for good prognosis metastatic seminoma could be considered a treatment option and is associated with less toxicity than combination regimens currently used.

An AUC-based permutation variable importance measure for random forests.

Science.gov (United States)

Janitza, Silke; Strobl, Carolin; Boulesteix, Anne-Laure

2013-04-05

The random forest (RF) method is a commonly used tool for classification with high dimensional data as well as for ranking candidate predictors based on the so-called random forest variable importance measures (VIMs). However the classification performance of RF is known to be suboptimal in case of strongly unbalanced data, i.e. data where response class sizes differ considerably. Suggestions were made to obtain better classification performance based either on sampling procedures or on cost sensitivity analyses. However to our knowledge the performance of the VIMs has not yet been examined in the case of unbalanced response classes. In this paper we explore the performance of the permutation VIM for unbalanced data settings and introduce an alternative permutation VIM based on the area under the curve (AUC) that is expected to be more robust towards class imbalance. We investigated the performance of the standard permutation VIM and of our novel AUC-based permutation VIM for different class imbalance levels using simulated data and real data. The results suggest that the new AUC-based permutation VIM outperforms the standard permutation VIM for unbalanced data settings while both permutation VIMs have equal performance for balanced data settings. The standard permutation VIM loses its ability to discriminate between associated predictors and predictors not associated with the response for increasing class imbalance. It is outperformed by our new AUC-based permutation VIM for unbalanced data settings, while the performance of both VIMs is very similar in the case of balanced classes. The new AUC-based VIM is implemented in the R package party for the unbiased RF variant based on conditional inference trees. The codes implementing our study are available from the companion website: http://www.ibe.med.uni-muenchen.de/organisation/mitarbeiter/070_drittmittel/janitza/index.html.

Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia.

Science.gov (United States)

Holmes, Natasha E; Turnidge, John D; Munckhof, Wendy J; Robinson, J Owen; Korman, Tony M; O'Sullivan, Matthew V N; Anderson, Tara L; Roberts, Sally A; Warren, Sanchia J C; Gao, Wei; Howden, Benjamin P; Johnson, Paul D R

2013-04-01

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥ 400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P AUC/MIC of ≥ 400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P = 0.132 and P = 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P = 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥ 400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.

Study of stripping cristallization processus of AUC with ammonium carbonate

International Nuclear Information System (INIS)

Chegrouche, Salah.

1987-09-01

This study is concerned with direct crystallization of ammonium uranyl carbonate (AUC) from a uranium loaded organic phase (30% TBP in kerosene), with ammonium carbonate (NH 4 ) 2 CO 3 . The effects of operating conditions ((NH 4 ) 2 CO 3 concentration, flow-ratio, residence time, temperature) on the physical properties of AUC crystals (particle size distribution, specific surface, density...) are reported. All products were identified (both by chemical analysis, X-Ray diffraction) as being ammonium uranyl carbonate crystals (AUC). The results show that a high phase ratio and (NH 4 ) 2 CO 3 concentration favor the formation of fine AUC grains and aggregates. This is due mainly to the high concentration of NH + 4 in the system which leads to a high solution supersaturation and consequently to a rapid formation rate of crystal (germination). The reverse phenomenon is observed at low phase ratio and (NH 4 ) 2 CO 3 concentration, where germination and crystal growth are slow and the product is mainly monocrystal. In the intermediate range, a mixture of polycrystal and aggregates is obtained. Residence and temperature are also shown to have an effect on the processes (the effect of time being more important than temperature). In the course of this study a bench-scale stripper-crystallizer was developped and operated successfully. (author). tables, graphs

AUC-based biomarker ensemble with an application on gene scores predicting low bone mineral density.

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Zhao, X G; Dai, W; Li, Y; Tian, L

2011-11-01

The area under the receiver operating characteristic (ROC) curve (AUC), long regarded as a 'golden' measure for the predictiveness of a continuous score, has propelled the need to develop AUC-based predictors. However, the AUC-based ensemble methods are rather scant, largely due to the fact that the associated objective function is neither continuous nor concave. Indeed, there is no reliable numerical algorithm identifying optimal combination of a set of biomarkers to maximize the AUC, especially when the number of biomarkers is large. We have proposed a novel AUC-based statistical ensemble methods for combining multiple biomarkers to differentiate a binary response of interest. Specifically, we propose to replace the non-continuous and non-convex AUC objective function by a convex surrogate loss function, whose minimizer can be efficiently identified. With the established framework, the lasso and other regularization techniques enable feature selections. Extensive simulations have demonstrated the superiority of the new methods to the existing methods. The proposal has been applied to a gene expression dataset to construct gene expression scores to differentiate elderly women with low bone mineral density (BMD) and those with normal BMD. The AUCs of the resulting scores in the independent test dataset has been satisfactory. Aiming for directly maximizing AUC, the proposed AUC-based ensemble method provides an efficient means of generating a stable combination of multiple biomarkers, which is especially useful under the high-dimensional settings. lutian@stanford.edu. Supplementary data are available at Bioinformatics online.

Optimal Combinations of Diagnostic Tests Based on AUC.

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Huang, Xin; Qin, Gengsheng; Fang, Yixin

2011-06-01

When several diagnostic tests are available, one can combine them to achieve better diagnostic accuracy. This article considers the optimal linear combination that maximizes the area under the receiver operating characteristic curve (AUC); the estimates of the combination's coefficients can be obtained via a nonparametric procedure. However, for estimating the AUC associated with the estimated coefficients, the apparent estimation by re-substitution is too optimistic. To adjust for the upward bias, several methods are proposed. Among them the cross-validation approach is especially advocated, and an approximated cross-validation is developed to reduce the computational cost. Furthermore, these proposed methods can be applied for variable selection to select important diagnostic tests. The proposed methods are examined through simulation studies and applications to three real examples. © 2010, The International Biometric Society.

The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative Systematic Review.

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Tkachuk, Stacey; Collins, Kyle; Ensom, Mary H H

2018-04-01

In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC ≥ 400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC. This review aimed to determine the relationship between vancomycin trough concentrations and AUC/MIC in pediatric patients. We searched the MEDLINE and Embase databases, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials using the medical subject heading (MeSH) terms vancomycin and AUC and pediatric* or paediatric*. Articles were included if they were published in English and reported a relationship between vancomycin trough concentrations and AUC/MIC. Of 122 articles retrieved, 11 met the inclusion criteria. One trial reported a relationship between vancomycin trough concentrations, AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found troughs 6-10 mg/l were sufficient to attain an AUC/MIC > 400 in most general hospitalized pediatric patients. One study in patients undergoing cardiothoracic surgery found a trough of 18.4 mg/l achieved an AUC/MIC > 400. Two oncology studies reported troughs ≥ 15 mg/l likely attained an AUC/MIC ≥ 400. In critical care patients: one study found a trough of 9 mg/l did not attain the AUC/MIC target; another found 7 mg/l corresponded to an AUC/MIC of 400. Potential vancomycin targets varied based on the population studied but, for general hospitalized pediatric patients, troughs of 6-10 mg/l are likely sufficient to achieve AUC/MIC ≥ 400. For MIC ≥ 2 mg/l, higher troughs are likely necessary to achieve an AUC/MIC ≥ 400. More

Support for higher ciprofloxacin AUC 24/MIC targets in treating Enterobacteriaceae bloodstream infection.

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Zelenitsky, Sheryl A; Ariano, Robert E

2010-08-01

Given concerns regarding optimal therapy for serious Gram-negative infections, the goal was to characterize the pharmacodynamics of ciprofloxacin in the context of treating bloodstream infection. Data were collected from the medical records of 178 clinical cases. Blood isolates were retrieved and ciprofloxacin MICs were measured. Forty-two cases in which ciprofloxacin was initiated within 24 h of the positive blood culture were used in the pharmacodynamic analysis. Significant factors with regard to treatment failure were low ciprofloxacin AUC(24)/MIC (P AUC(24) (P = 0.01). AUC(24)/MIC (P = 0.012) and MIC (P = 0.019) were significant variables in multivariate analyses; however, only the former remained significant (P = 0.038) after excluding two cases with ciprofloxacin-resistant isolates. An AUC(24)/MIC breakpoint of 250 was most significant, with cure rates of 91.4% (32/35) and 28.6% (2/7) in patients with values above and below this threshold, respectively (P = 0.001). The risk of ciprofloxacin treatment failure was 27.8 times (95% confidence interval, 2.1-333) greater in those not achieving an AUC(24)/MIC >or=250 (P = 0.011). Monte Carlo simulation of 5000 study subjects predicted that 0.88 of the population would achieve an AUC(24)/MIC >or=250 with standard-dose ciprofloxacin (400 mg intravenously every 12 h). This study confirms the pharmacodynamic parameters of ciprofloxacin that are important for optimizing the treatment of serious infections, particularly the benefits of achieving an AUC(24)/MIC >or=250, rather than the conventional target of >or=125. It also shows the relevance of dose selection in optimizing target attainment, with important differences among pathogens, even those with MICs within the susceptible range.

Analysis of flux standards in a fluized bed for AUC - UO2 convertion

International Nuclear Information System (INIS)

Juanico, L.E.; Clausse, A.; Guido Lavalle, G.

1990-01-01

One of the fuel cycle stages is the convertion (reduction) of ammonium uranyl carbonate (AUC) in UO 2 which, after being directly compacted, allows pellet obtainment acquire the correct density to be used as nuclear fuel during sintering. AUC's reduction in UO 2 is made on a fluidized bed in which AUC powder going into the upper part at a countercurrent to the gas flux (superheated steam), is converted into UO 2 ; after the reaction, UO 2 is collected at the lower part of the reactor. (Author) [es

Why Does Rebalancing Class-Unbalanced Data Improve AUC for Linear Discriminant Analysis?

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Xue, Jing-Hao; Hall, Peter

2015-05-01

Many established classifiers fail to identify the minority class when it is much smaller than the majority class. To tackle this problem, researchers often first rebalance the class sizes in the training dataset, through oversampling the minority class or undersampling the majority class, and then use the rebalanced data to train the classifiers. This leads to interesting empirical patterns. In particular, using the rebalanced training data can often improve the area under the receiver operating characteristic curve (AUC) for the original, unbalanced test data. The AUC is a widely-used quantitative measure of classification performance, but the property that it increases with rebalancing has, as yet, no theoretical explanation. In this note, using Gaussian-based linear discriminant analysis (LDA) as the classifier, we demonstrate that, at least for LDA, there is an intrinsic, positive relationship between the rebalancing of class sizes and the improvement of AUC. We show that the largest improvement of AUC is achieved, asymptotically, when the two classes are fully rebalanced to be of equal sizes.

Different truncation methods of AUC between Japan and the EU for bioequivalence assessment: influence on the regulatory judgment.

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Oishi, Masayo; Chiba, Koji; Fukushima, Takashi; Tomono, Yoshiro; Suwa, Toshio

2012-01-01

In regulatory guidelines for bioequivalence (BE) assessment, the definitions of AUC for primary assessment are different in ICH countries, i.e., AUC from zero to the last sampling point (AUCall) in Japan, AUC from zero to infinity (AUCinf) or AUC from zero to the last measurable point (AUClast) in the US, and AUClast in the EU. To assure sufficient accuracy of truncated AUC for BE assessment, the ratio of truncated AUC (AUCall or AUClast) to AUCinf should be more than 80% both in Japanese and EU guidelines. We investigated how the difference in the definition of truncated AUC affects BE assessment of sustained release (SR) formulation. Our simulation result demonstrated that AUCall/AUCinf could be ≥80% despite AUClast/AUCinf being AUC affected the judgment of validity of truncated AUC for BE assessment, and AUCall could fail to detect the substantially different in vivo dissolution profile of generic drugs with SR formulation from the original drug.

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

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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.

AUC versus peak-trough dosing of vancomycin: applying new pharmacokinetic paradigms to an old drug.

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Brown, Daniel L; Lalla, Christina D; Masselink, Andrew J

2013-08-01

To compare and contrast the pharmacokinetic/pharmacodynamic foundations of traditional "peak-trough" vancomycin dosing methods versus newer "area under the curve" (AUC) strategies. To propose a new AUC-based dosing chart for empirically determining an initial vancomycin dosing regimen designed to achieve a desired AUC24 using the minimum inhibitory concentration (MIC), creatinine clearance (CrCl), and vancomycin clearance (ClVanco). Peak-trough vancomycin dosing is designed to achieve a Cpeak of 20-40 mg/L and a Ctrough of 10-15 or 15-20 mg/L, depending on the severity of the infection and the nature of the pathogen. New treatment guidelines for vancomycin suggest that therapy should achieve an AUC24/MIC of ≥400. AUC-based vancomycin dosing derives the daily dose from ClVanco, MIC, and the desired AUC24/MIC, without consideration of the patient's weight. A vancomycin dosing chart is proposed that estimates ClVanco using the following formula developed by Matzke et al: ClVanco in L/h = [(CrClmL/min × 0.689) + 3.66] × 0.06, which simplifies to (CrClmL/min × 0.41) + 0.22. Two levels of dosing are included-high dose (Ctrough: 15-20 mg/L) and moderate dose (Ctrough: 10-15 mg/L). Although the chart has not been validated clinically, it represents the product of standard dosing equations that are used to determine a starting dosing regimen based on well-established vancomycin pharmacokinetic parameters. An understanding of pharmacokinetic and pharmacodynamic principles, including the relevance of AUC in relation to MIC, enables clinicians to make the best use of vancomycin dosing options. The proposed dosing chart is pharmacokinetically valid but has yet to be applied clinically. It provides a foundation for further study of how clinicians can determine an optimal AUC-based starting vancomycin dosing regimen without having to derive ClVanco or AUC24.

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

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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.

Higher capecitabine AUC in elderly patients with advanced colorectal cancer (SWOGS0030).

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Louie, S G; Ely, B; Lenz, H-J; Albain, K S; Gotay, C; Coleman, D; Raghavan, D; Shields, A F; Gold, P J; Blanke, C D

2013-10-01

The aging process is accompanied by physiological changes including reduced glomerular filtration and hepatic function, as well as changes in gastric secretions. To investigate what effect would aging have on the disposition of capecitabine and its metabolites, the pharmacokinetics between patients ≥70 years and AUC) was accompanied by reduction in capecitabine clearance in ≥70 years patients (PAUCs between the two age groups, suggesting that carboxylesterase and cytidine deaminase (CDA) activity was similar between the two age groups. These results suggest that metabolic enzymes involved in converting capecitabine metabolites are not altered by age. An elevation in capecitabine Cmax and reduction in clearance was seen in females, where capecitabine AUC was 40.3% higher in women. Elevation of DFUR Cmax (45%) and AUC (46%) (PAUC was observed in patients ≥70 years when compared with younger patients who were >60 years.

The Impact of AUC-Based Monitoring on Pharmacist-Directed Vancomycin Dose Adjustments in Complicated Methicillin-Resistant Staphylococcus aureus Infection.

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Stoessel, Andrew M; Hale, Cory M; Seabury, Robert W; Miller, Christopher D; Steele, Jeffrey M

2018-01-01

This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution. A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L. Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation ( P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107). The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

Balancing vancomycin efficacy and nephrotoxicity: should we be aiming for trough or AUC/MIC?

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Patel, Karisma; Crumby, Ashley S; Maples, Holly D

2015-04-01

Sixty years later, the question that still remains is how to appropriately utilize vancomycin in the pediatric population. The Infectious Diseases Society of America published guidelines in 2011 that provide guidance for dosing and monitoring of vancomycin in adults and pediatrics. However, goal vancomycin trough concentrations of 15-20 μg/mL for invasive infections caused by methicillin-resistant Staphylococcus aureus were based primarily on adult pharmacokinetic and pharmacodynamic data that achieved an area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of ≥400. Recent pediatric literature shows that vancomycin trough concentrations needed to achieve the target AUC/MIC are different than the adult goal troughs cited in the guidelines. This paper addresses several thoughts, including the role of vancomycin AUC/MIC in dosing strategies and safety monitoring, consistency in laboratory reporting, and future directions for calculating AUC/MIC in pediatrics.

Characterisation and compaction behaviour of UO2 powder prepared from ADU and AUC

International Nuclear Information System (INIS)

Rachmawati, M.

2000-01-01

UO 2 powder prepared from ADU and AUC route process are characterised primarily in terms of compaction and sintering behaviour. Scientific understanding of the phenomena will give useful information leading to processing and product improvement. The investigation has been done by characterising the particle size/shape distribution using SEM and compacting the powder at 4 and 5.4 tons/cm 2 . The behaviour of the powder under compaction is observed by characterizing the pellet length, green density, microstructure, and the compression strength using micrometer SEM, and Universal Testing Machine. The results of the experiment show that the UO 2 powder ex-AUC has particles of spherical type and separate individually which provide the flowable characteristic, important for the die filling aspect during compaction step. The UO 2 powder ex-ADU is more or less agglomerated and contains very fine particles causing the difficulty in pressing. Therefore the green density resulted from UO 2 ex-AUC (6.415 g/cm 3 ) is higher than UO 2 powder of UO 2 ex-ADU (6.117 g/cm 3 . UO 2 at lower pressure (4 tons/cm 3 ) the compression strength ex-AUC green pellet (47.144 kgf) is lower than UO 2 ex-ADU (63,364 kgf), and at higher temperature the compression strength of ex-AUC (92.86 kgf) is higher than UO 2 ex-ADU (82.664 kgf). It is suggested that UO 2 ex-ADU has to be precompacted and granulated in order to increase its flowability so that the pellet length can easily be controlled during pressing (improve reproducibility). (author)

Peak Measurement for Vancomycin AUC Estimation in Obese Adults Improves Precision and Lowers Bias.

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Pai, Manjunath P; Hong, Joseph; Krop, Lynne

2017-04-01

Vancomycin area under the curve (AUC) estimates may be skewed in obese adults due to weight-dependent pharmacokinetic parameters. We demonstrate that peak and trough measurements reduce bias and improve the precision of vancomycin AUC estimates in obese adults ( n = 75) and validate this in an independent cohort ( n = 31). The precision and mean percent bias of Bayesian vancomycin AUC estimates are comparable between covariate-dependent ( R 2 = 0.774, 3.55%) and covariate-independent ( R 2 = 0.804, 3.28%) models when peaks and troughs are measured but not when measurements are restricted to troughs only ( R 2 = 0.557, 15.5%). Copyright © 2017 American Society for Microbiology.

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

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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).

An alternative approach to calculating Area-Under-the-Curve (AUC) in delay discounting research.

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Borges, Allison M; Kuang, Jinyi; Milhorn, Hannah; Yi, Richard

2016-09-01

Applied to delay discounting data, Area-Under-the-Curve (AUC) provides an atheoretical index of the rate of delay discounting. The conventional method of calculating AUC, by summing the areas of the trapezoids formed by successive delay-indifference point pairings, does not account for the fact that most delay discounting tasks scale delay pseudoexponentially, that is, time intervals between delays typically get larger as delays get longer. This results in a disproportionate contribution of indifference points at long delays to the total AUC, with minimal contribution from indifference points at short delays. We propose two modifications that correct for this imbalance via a base-10 logarithmic transformation and an ordinal scaling transformation of delays. These newly proposed indices of discounting, AUClog d and AUCor d, address the limitation of AUC while preserving a primary strength (remaining atheoretical). Re-examination of previously published data provides empirical support for both AUClog d and AUCor d . Thus, we believe theoretical and empirical arguments favor these methods as the preferred atheoretical indices of delay discounting. © 2016 Society for the Experimental Analysis of Behavior.

Bayesian approach to estimate AUC, partition coefficient and drug targeting index for studies with serial sacrifice design.

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Wang, Tianli; Baron, Kyle; Zhong, Wei; Brundage, Richard; Elmquist, William

2014-03-01

The current study presents a Bayesian approach to non-compartmental analysis (NCA), which provides the accurate and precise estimate of AUC 0 (∞) and any AUC 0 (∞) -based NCA parameter or derivation. In order to assess the performance of the proposed method, 1,000 simulated datasets were generated in different scenarios. A Bayesian method was used to estimate the tissue and plasma AUC 0 (∞) s and the tissue-to-plasma AUC 0 (∞) ratio. The posterior medians and the coverage of 95% credible intervals for the true parameter values were examined. The method was applied to laboratory data from a mice brain distribution study with serial sacrifice design for illustration. Bayesian NCA approach is accurate and precise in point estimation of the AUC 0 (∞) and the partition coefficient under a serial sacrifice design. It also provides a consistently good variance estimate, even considering the variability of the data and the physiological structure of the pharmacokinetic model. The application in the case study obtained a physiologically reasonable posterior distribution of AUC, with a posterior median close to the value estimated by classic Bailer-type methods. This Bayesian NCA approach for sparse data analysis provides statistical inference on the variability of AUC 0 (∞) -based parameters such as partition coefficient and drug targeting index, so that the comparison of these parameters following destructive sampling becomes statistically feasible.

Determination of uranium content and its impurities in the AUC and UO2 powders

International Nuclear Information System (INIS)

Boybul; Arif Nugroho

2012-01-01

The analysis of uranium (U) content and its impurities in the ammonium uranyl carbonate (AUC) and uranium dioxide (UO 2 ) produced from research reactor fuel element production installation, PT. BATAN Teknologi have been carried out. Uranium content in the powders was analyzed by potentiometric titration methods and impurity contents was analyzed by atomic absorption spectrophotometer (AAS) and by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The purpose of this study was to determine of impurity elements in the AUC and UO 2 powder resulting from the production process if it meets the required specifications. It is reported that U content in the AUC is 48.62 wt% and that in the UO 2 is 88.08 wt%. The precision and accuracy analysis of the U content is 0,235% and 0,151%. In case of impurities in the AUC powders, it is reported that the analytical results of Zn, Ni, Cd, Co, Mn, Mg, Fe, Cu and Cr at 10.15 ppm, 1.12 ppm, not detection, not detection, not detection, 0.30 ppm, 216.07 ppm, not detection, and 31.36 ppm, respectively, while that UO 2 are 11.31 ppm, 72.14 ppm, not detection, not detection, 6.25 ppm, 8.65 ppm, 298.24 ppm, 12.75 ppm and 32, 23 ppm. The U and impurity contents in both the AUC and UO 2 fulfill the specification of nuclear fuel for RSG-GAS research reactor. (author)

Utility of the AAOS Appropriate Use Criteria (AUC) for Pediatric Supracondylar Humerus Fractures in Clinical Practice.

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Ibrahim, Talal; Hegazy, Abdelsalam; Abulhail, Safa I S; Ghomrawi, Hassan M K

2017-01-01

The American Academy of Orthopaedic Surgeons (AAOS) recently developed an Appropriate Use Criteria (AUC) for pediatric supracondylar humerus fractures (PSHF). The AUC is intended to improve quality of care by informing surgeon decision making. The aim of our study was to cross-reference the management of operatively treated PSHF with the AAOS-published AUC. The AUC for PSHF include 220 patient scenarios, based on different combinations of 6 factors. For each patient scenario, 8 treatment options are evaluated as "appropriate," "maybe appropriate," and "rarely appropriate." We retrospectively reviewed the medical charts and radiographs of all operatively treated PSHF at our hospital from January 2013 to December 2014 and determined the appropriateness of the treatment. Over the study period, 94 children (mean age: 5.2 y; 51 male, 43 female) were admitted with PSHF and underwent a surgical procedure (type IIA: 7, type IIB: 14, type III: 70, flexion type: 3). Only 8 of the 220 scenarios were observed in our patient cohort. The most frequent scenario was represented by a type III fracture, palpable distal pulse, no nerve injury, closed soft-tissue envelope, no radius/ulna fracture, and typical swelling. Of the 94 fractures, the AUC was "appropriate" for 84 cases and "maybe appropriate" for 9 cases. There was only 1 case of "rarely appropriate" management. Closed reduction with lateral pinning and immobilization was the most prevalent treatment option (58.5%). The rate of appropriateness was not affected by the operating surgeon. However, the definition of a case as emergent had a significant impact on the rate of appropriateness. Application of the AUC to actual clinical data was relatively simple. The majority of operatively treated PSHF (89.4%) were managed appropriately. With the introduction of electronic medical charts, an AUC application becomes attractive and easy for orthopaedic surgeons to utilize in clinical practice. However, validity studies of the AUC in

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.

Direct AUC optimization of regulatory motifs.

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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. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Study of secular equilibrium reinstatement on UO2 pellets manufactured by AUC route

International Nuclear Information System (INIS)

Carnaval, João Paulo R.; Beltran, Dalton J.M.C.; Oliveira, Carlos A.

2017-01-01

The fuel assemblies manufactured by INB for Angra-1 power plant has axial blanket fuel rods which must be inspected due the columns formed by different enrichment pellets. The equipment used for inspection is built with a group of BGO scintillators detectors which measurement principle is based on the absorption of gamma rays emitted from Uranium decay. The commercial grade UF 6 used by INB is stored into cylinders type 30B. The uranium inside these cylinders is in secular equilibrium before the processing. It has been found that the AUC route causes the loss of that equilibrium because the UF 6 is volatilized from the cylinder and the uranium daughters remain in the container. As AUC is converted to powder and pellets, the secular equilibrium is restored through time. The purpose of this work is to present a study of the secular equilibrium reinstatement on UO 2 pellets manufactured by AUC route before being inspected on Rod Scanner. (author)

A modified Wald interval for the area under the ROC curve (AUC) in diagnostic case-control studies.

Science.gov (United States)

Kottas, Martina; Kuss, Oliver; Zapf, Antonia

2014-02-19

The area under the receiver operating characteristic (ROC) curve, referred to as the AUC, is an appropriate measure for describing the overall accuracy of a diagnostic test or a biomarker in early phase trials without having to choose a threshold. There are many approaches for estimating the confidence interval for the AUC. However, all are relatively complicated to implement. Furthermore, many approaches perform poorly for large AUC values or small sample sizes. The AUC is actually a probability. So we propose a modified Wald interval for a single proportion, which can be calculated on a pocket calculator. We performed a simulation study to compare this modified Wald interval (without and with continuity correction) with other intervals regarding coverage probability and statistical power. The main result is that the proposed modified Wald intervals maintain and exploit the type I error much better than the intervals of Agresti-Coull, Wilson, and Clopper-Pearson. The interval suggested by Bamber, the Mann-Whitney interval without transformation and also the interval of the binormal AUC are very liberal. For small sample sizes the Wald interval with continuity has a comparable coverage probability as the LT interval and higher power. For large sample sizes the results of the LT interval and of the Wald interval without continuity correction are comparable. If individual patient data is not available, but only the estimated AUC and the total sample size, the modified Wald intervals can be recommended as confidence intervals for the AUC. For small sample sizes the continuity correction should be used.

Preparation and characterization of Fe3O4@Au-C225 composite targeted nanoparticles for MRI of human glioma.

Science.gov (United States)

Ge, Yaoqi; Zhong, Yuejiao; Ji, Guozhong; Lu, Qianling; Dai, Xinyu; Guo, Zhirui; Zhang, Peng; Peng, Gang; Zhang, Kangzhen; Li, Yuntao

2018-01-01

To study the characterization of Fe3O4@Au-C225 composite targeted MNPs. Fe3O4@Au-C225 was prepared by the absorption method. The immunosorbent assay was used to evaluate its absorption efficiency at C225 Fc. ZETA SIZER3000 laser particle size analyzer, ultraviolet photometer and its characteristics were analyzed by VSM. the targeting effect of Fe3O4@Au-C225 composite targeted MNPs on U251 cells in vitro were detected by 7.0 Tesla Micro-MR; and subcutaneous transplanted human glioma in nude mice were performed the targeting effect in vivo after tail vein injection of Fe3O4@Au-C225 composite targeted MNPs by MRI. The self-prepared Fe3O4@Au composite MNPs can adsorb C225 with high efficiency of adsorption so that Fe3O4@Au-C225 composite targeted MNPs were prepared successfully. Fe3O4@Au-C225 composite targeted MNPs favorably targeted human glioma cell line U251 in vitro; Fe3O4@Au-C225 composite targeted MNPs have good targeting ability to xenografted glioma on nude mice in vivo, and can be traced by MRI. The Fe3O4@Au-C225 composite targeted MNPs have the potential to be used as a tracer for glioma in vivo.

Simple Decision-Analytic Functions of the AUC for Ruling Out a Risk Prediction Model and an Added Predictor.

Science.gov (United States)

Baker, Stuart G

2018-02-01

When using risk prediction models, an important consideration is weighing performance against the cost (monetary and harms) of ascertaining predictors. The minimum test tradeoff (MTT) for ruling out a model is the minimum number of all-predictor ascertainments per correct prediction to yield a positive overall expected utility. The MTT for ruling out an added predictor is the minimum number of added-predictor ascertainments per correct prediction to yield a positive overall expected utility. An approximation to the MTT for ruling out a model is 1/[P (H(AUC model )], where H(AUC) = AUC - {½ (1-AUC)} ½ , AUC is the area under the receiver operating characteristic (ROC) curve, and P is the probability of the predicted event in the target population. An approximation to the MTT for ruling out an added predictor is 1 /[P {(H(AUC Model:2 ) - H(AUC Model:1 )], where Model 2 includes an added predictor relative to Model 1. The latter approximation requires the Tangent Condition that the true positive rate at the point on the ROC curve with a slope of 1 is larger for Model 2 than Model 1. These approximations are suitable for back-of-the-envelope calculations. For example, in a study predicting the risk of invasive breast cancer, Model 2 adds to the predictors in Model 1 a set of 7 single nucleotide polymorphisms (SNPs). Based on the AUCs and the Tangent Condition, an MTT of 7200 was computed, which indicates that 7200 sets of SNPs are needed for every correct prediction of breast cancer to yield a positive overall expected utility. If ascertaining the SNPs costs $500, this MTT suggests that SNP ascertainment is not likely worthwhile for this risk prediction.

Comparison of 3 estimation methods of mycophenolic acid AUC based on a limited sampling strategy in renal transplant patients.

Science.gov (United States)

Hulin, Anne; Blanchet, Benoît; Audard, Vincent; Barau, Caroline; Furlan, Valérie; Durrbach, Antoine; Taïeb, Fabrice; Lang, Philippe; Grimbert, Philippe; Tod, Michel

2009-04-01

A significant relationship between mycophenolic acid (MPA) area under the plasma concentration-time curve (AUC) and the risk for rejection has been reported. Based on 3 concentration measurements, 3 approaches have been proposed for the estimation of MPA AUC, involving either a multilinear regression approach model (MLRA) or a Bayesian estimation using either gamma absorption or zero-order absorption population models. The aim of the study was to compare the 3 approaches for the estimation of MPA AUC in 150 renal transplant patients treated with mycophenolate mofetil and tacrolimus. The population parameters were determined in 77 patients (learning study). The AUC estimation methods were compared in the learning population and in 73 patients from another center (validation study). In the latter study, the reference AUCs were estimated by the trapezoidal rule on 8 measurements. MPA concentrations were measured by liquid chromatography. The gamma absorption model gave the best fit. In the learning study, the AUCs estimated by both Bayesian methods were very similar, whereas the multilinear approach was highly correlated but yielded estimates about 20% lower than Bayesian methods. This resulted in dosing recommendations differing by 250 mg/12 h or more in 27% of cases. In the validation study, AUC estimates based on the Bayesian method with gamma absorption model and multilinear regression approach model were, respectively, 12% higher and 7% lower than the reference values. To conclude, the bicompartmental model with gamma absorption rate gave the best fit. The 3 AUC estimation methods are highly correlated but not concordant. For a given patient, the same estimation method should always be used.

Limited sampling strategy models for estimating the AUC of gliclazide in Chinese healthy volunteers.

Science.gov (United States)

Huang, Ji-Han; Wang, Kun; Huang, Xiao-Hui; He, Ying-Chun; Li, Lu-Jin; Sheng, Yu-Cheng; Yang, Juan; Zheng, Qing-Shan

2013-06-01

The aim of this work is to reduce the cost of required sampling for the estimation of the area under the gliclazide plasma concentration versus time curve within 60 h (AUC0-60t ). The limited sampling strategy (LSS) models were established and validated by the multiple regression model within 4 or fewer gliclazide concentration values. Absolute prediction error (APE), root of mean square error (RMSE) and visual prediction check were used as criterion. The results of Jack-Knife validation showed that 10 (25.0 %) of the 40 LSS based on the regression analysis were not within an APE of 15 % using one concentration-time point. 90.2, 91.5 and 92.4 % of the 40 LSS models were capable of prediction using 2, 3 and 4 points, respectively. Limited sampling strategies were developed and validated for estimating AUC0-60t of gliclazide. This study indicates that the implementation of an 80 mg dosage regimen enabled accurate predictions of AUC0-60t by the LSS model. This study shows that 12, 6, 4, 2 h after administration are the key sampling times. The combination of (12, 2 h), (12, 8, 2 h) or (12, 8, 4, 2 h) can be chosen as sampling hours for predicting AUC0-60t in practical application according to requirement.

Study of secular equilibrium reinstatement on UO{sub 2} pellets manufactured by AUC route

Energy Technology Data Exchange (ETDEWEB)

Carnaval, João Paulo R.; Beltran, Dalton J.M.C.; Oliveira, Carlos A., E-mail: joaocarnaval@inb.gov.br, E-mail: daltonbeltran@inb.gov.br, E-mail: carlossilva@inb.gov.br [Indústrias Nucleares do Brasil S.A. (INB), Resende, RJ (Brazil)

2017-07-01

The fuel assemblies manufactured by INB for Angra-1 power plant has axial blanket fuel rods which must be inspected due the columns formed by different enrichment pellets. The equipment used for inspection is built with a group of BGO scintillators detectors which measurement principle is based on the absorption of gamma rays emitted from Uranium decay. The commercial grade UF{sub 6} used by INB is stored into cylinders type 30B. The uranium inside these cylinders is in secular equilibrium before the processing. It has been found that the AUC route causes the loss of that equilibrium because the UF{sub 6} is volatilized from the cylinder and the uranium daughters remain in the container. As AUC is converted to powder and pellets, the secular equilibrium is restored through time. The purpose of this work is to present a study of the secular equilibrium reinstatement on UO{sub 2} pellets manufactured by AUC route before being inspected on Rod Scanner. (author)

Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation.

Science.gov (United States)

Cheung, Chi Yuen; van der Heijden, Jaques; Hoogtanders, Karin; Christiaans, Maarten; Liu, Yan Lun; Chan, Yiu Han; Choi, Koon Shing; van de Plas, Afke; Shek, Chi Chung; Chau, Ka Foon; Li, Chun Sang; van Hooff, Johannes; Stolk, Leo

2008-02-01

Dried blood spot (DBS) sampling and high-performance liquid chromatography tandem-mass spectrometry have been developed in monitoring tacrolimus levels. Our center favors the use of limited sampling strategy and abbreviated formula to estimate the area under concentration-time curve (AUC(0-12)). However, it is inconvenient for patients because they have to wait in the center for blood sampling. We investigated the application of DBS method in tacrolimus level monitoring using limited sampling strategy and abbreviated AUC estimation approach. Duplicate venous samples were obtained at each time point (C(0), C(2), and C(4)). To determine the stability of blood samples, one venous sample was sent to our laboratory immediately. The other duplicate venous samples, together with simultaneous fingerprick blood samples, were sent to the University of Maastricht in the Netherlands. Thirty six patients were recruited and 108 sets of blood samples were collected. There was a highly significant relationship between AUC(0-12), estimated from venous blood samples, and fingerprick blood samples (r(2) = 0.96, P AUC(0-12) strategy as drug monitoring.

Relationship between the clinical efficacy and AUC/MIC of intravenous ciprofloxacin in Japanese patients with intraabdominal infections.

Science.gov (United States)

Ohki, Emiko; Yamagishi, Yuka; Mikamo, Hiroshige

2013-10-01

The efficacy of fluoroquinolones (FQs) correlates with the pharmacokinetic/pharmacodynamic (PK-PD) parameter, AUC/MIC. To our knowledge, however, no prospective studies have reported the relationship between FQ efficacy and PK-PD parameters in intraabdominal infection; therefore, we prospectively investigated the relationship between the efficacy of intravenous ciprofloxacin (CPFX IV) and PK-PD parameters. The study included 16 patients diagnosed with peritonitis between 2006 and 2008: 14 patients infected with a single organism and 2 patients infected with more than one organism. Each patient was treated with CPFX IV (300 mg twice daily). The response rate was 56% (9 responders and 7 non-responders). Non-responders were infected with Escherichia coli, Pseudomonas aeruginosa, and Bacteroides fragilis (6 patients were infected with a single organism and 1 with more than one organism). Plasma drug concentrations were measured 1 h and 2 or 4 h after administration of CPFX IV. AUC for 24 h (AUC(0-24))/MIC values was calculated. The range of AUC(0-24)/MIC values in responders [95.3-3628.4 (geometric mean, 521.6)] was significantly different from that in non-responders [7.0-45.2 (geometric mean, 16.5)] (p = 0.001). The target AUC/MIC value of CPFX IV would be considered to be 45-95 in patients with peritonitis.

Combining large number of weak biomarkers based on AUC.

Science.gov (United States)

Yan, Li; Tian, Lili; Liu, Song

2015-12-20

Combining multiple biomarkers to improve diagnosis and/or prognosis accuracy is a common practice in clinical medicine. Both parametric and non-parametric methods have been developed for finding the optimal linear combination of biomarkers to maximize the area under the receiver operating characteristic curve (AUC), primarily focusing on the setting with a small number of well-defined biomarkers. This problem becomes more challenging when the number of observations is not order of magnitude greater than the number of variables, especially when the involved biomarkers are relatively weak. Such settings are not uncommon in certain applied fields. The first aim of this paper is to empirically evaluate the performance of existing linear combination methods under such settings. The second aim is to propose a new combination method, namely, the pairwise approach, to maximize AUC. Our simulation studies demonstrated that the performance of several existing methods can become unsatisfactory as the number of markers becomes large, while the newly proposed pairwise method performs reasonably well. Furthermore, we apply all the combination methods to real datasets used for the development and validation of MammaPrint. The implication of our study for the design of optimal linear combination methods is discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Sintering of uranium dioxide obtained by continuous precipitation of AUC

International Nuclear Information System (INIS)

Amaya, C.D.; Sterba, M.E.; Russo, D.O.

1993-01-01

The Nuclear Materials Division in Bariloche Atomic Center evaluates the ceramic behaviour of UO 2 powders obtained from continuously precipitated and reduced AUC (Ammonium Uranyl Tri Carbonate). An analysis is made of powder characteristics (particle morphology and size distribution and specific area) on behaviour of UO 2 during sintering (compaction, sintering, pore and grain microstructure, etc.). 1 ref

Traffic days '95 at AUC. Conference report. Vol. 1

International Nuclear Information System (INIS)

Lohmann-Hansen, A.

1995-01-01

Volume one of Traffic days '95 at AUC (Aalborg University, Denmark) contains 28 papers presented at the conference held on August 21 - 22, 1995, at Aalborg University in Jutland, Denmark. The papers in this volume are ranged under the general headings of: The road to sustainable transport, the evaluation of traffic and infrastructure planning - decision-making procedures, traffic and the environment in towns, railways, traffic information + signals, and environmental conditions relative to shipping

The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens.

Science.gov (United States)

Haeseker, Michiel; Stolk, Leo; Nieman, Fred; Hoebe, Christian; Neef, Cees; Bruggeman, Cathrien; Verbon, Annelies

2013-01-01

The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated. In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400-1200 mg day(-1) i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\\PHARM 3.60). A two compartment open model was used. Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h(-1) kg(-1) and the mean AUC was 49 mg l(-1) h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l(-1), respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively. A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Predictive value of modeled AUC(AFP-hCG), a dynamic kinetic parameter characterizing serum tumor marker decline in patients with nonseminomatous germ cell tumor.

Science.gov (United States)

You, Benoit; Fronton, Ludivine; Boyle, Helen; Droz, Jean-Pierre; Girard, Pascal; Tranchand, Brigitte; Ribba, Benjamin; Tod, Michel; Chabaud, Sylvie; Coquelin, Henri; Fléchon, Aude

2010-08-01

The early decline profile of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in patients with nonseminomatous germ cell tumors (NSGCT) treated with chemotherapy may be related to the risk of relapse. We assessed the predictive values of areas under the curve of hCG (AUC(hCG)) and AFP (AUC(AFP)) of modeled concentration-time equations on progression-free survival (PFS). Single-center retrospective analysis of hCG and AFP time-points from 65 patients with IGCCCG intermediate-poor risk NSGCT treated with 4 cycles of bleomycin-etoposide-cisplatin (BEP). To determine AUC(hCG) and AUC(AFP) for D0-D42, AUCs for D0-D7 were calculated using the trapezoid rule and AUCs for D7-D42 were calculated using the mathematic integrals of equations modeled with NONMEM. Combining AUC(AFP) and AUC(hCG) enabled us to define 2 predictive groups: namely, patients with favorable and unfavorable AUC(AFP-hCG). Survival analyses and ROC curves assessed the predictive values of AUC(AFP-hCG) groups regarding progression-free survival (PFS) and compared them with those of half-life (HL) and time-to-normalization (TTN). Mono-exponential models best fit the patterns of marker decreases. Patients with a favorable AUC(AFP-hCG) had a significantly better PFS (100% vs 71.5%, P = .014). ROC curves confirmed the encouraging predictive accuracy of AUC(AFP-hCG) against HL or TTN regarding progression risk (ROC AUCs = 79.6 vs 71.9 and 70.2 respectively). Because of the large number of patients with missing data, multivariate analysis could not be performed. AUC(AFP-hCG) is a dynamic parameter characterizing tumor marker decline in patients with NSGCT during BEP treatment. Its value as a promising predictive factor should be validated. Copyright 2010 Elsevier Inc. All rights reserved.

Max-AUC feature selection in computer-aided detection of polyps in CT colonography.

Science.gov (United States)

Xu, Jian-Wu; Suzuki, Kenji

2014-03-01

We propose a feature selection method based on a sequential forward floating selection (SFFS) procedure to improve the performance of a classifier in computerized detection of polyps in CT colonography (CTC). The feature selection method is coupled with a nonlinear support vector machine (SVM) classifier. Unlike the conventional linear method based on Wilks' lambda, the proposed method selected the most relevant features that would maximize the area under the receiver operating characteristic curve (AUC), which directly maximizes classification performance, evaluated based on AUC value, in the computer-aided detection (CADe) scheme. We presented two variants of the proposed method with different stopping criteria used in the SFFS procedure. The first variant searched all feature combinations allowed in the SFFS procedure and selected the subsets that maximize the AUC values. The second variant performed a statistical test at each step during the SFFS procedure, and it was terminated if the increase in the AUC value was not statistically significant. The advantage of the second variant is its lower computational cost. To test the performance of the proposed method, we compared it against the popular stepwise feature selection method based on Wilks' lambda for a colonic-polyp database (25 polyps and 2624 nonpolyps). We extracted 75 morphologic, gray-level-based, and texture features from the segmented lesion candidate regions. The two variants of the proposed feature selection method chose 29 and 7 features, respectively. Two SVM classifiers trained with these selected features yielded a 96% by-polyp sensitivity at false-positive (FP) rates of 4.1 and 6.5 per patient, respectively. Experiments showed a significant improvement in the performance of the classifier with the proposed feature selection method over that with the popular stepwise feature selection based on Wilks' lambda that yielded 18.0 FPs per patient at the same sensitivity level.

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

Science.gov (United States)

Eum, Seenae; Bergsbaken, Robert L; Harvey, Craig L; Warren, J Bryan; Rotschafer, John C

2016-09-27

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 AUC of 450 mg∙h/L or greater was required to achieve 100% target attainment using either Vitek 2 or E-test MIC results.

The Goodness of Covariance Selection Problem from AUC Bounds

OpenAIRE

Khajavi, Navid Tafaghodi; Kuh, Anthony

2016-01-01

We conduct a study of graphical models and discuss the quality of model selection approximation by formulating the problem as a detection problem and examining the area under the curve (AUC). We are specifically looking at the model selection problem for jointly Gaussian random vectors. For Gaussian random vectors, this problem simplifies to the covariance selection problem which is widely discussed in literature by Dempster [1]. In this paper, we give the definition for the correlation appro...

Determination of parameters dissolution of yellow-cake. Production of uranyl nitrate - Gas precipitation of AUC

International Nuclear Information System (INIS)

Mellah, A.

1987-07-01

The different stages of the purification cycle of yellow-cakes have been studied thoroughly in order to obtain an ammonium uranyl carbonate (AUC) as an intermediate product of uranium dioxide (UO 2 ). The optimal parameters of yellow-cake dissolution, filtration, extraction by solvent, scrubbing and stripping were determined. An original program of thermodynamic calculation was developed for the determination of the free energies of yellow-cake dissolution reactions. Different numerical methods were used to determine the kinetic constant, the reaction order and correlation equations of uranyl nitrate density as a function of U and H + concentrations, before and after the extraction cycle. For the first time, Algerian filteraids were used for the filtration of uranyl nitrate solutions with satisfactory results. A laboratory designed installation enabled the precipitation of AUC by injection of ammonia and carbon dioxide gases. Interesting results have been obtained and further investigations should be carried out in order to optimize all the paremeters of the gas precipitation of AUC

[Successful cyclosporine treatment in 2 patients with refractory CIDP, involving monitoring of both AUC(0-4h) and trough levels].

Science.gov (United States)

Takeuchi, Akiko; Shirai, Shinichi; Horiuchi, Kazuhiro; Takahashi, Ikuko; Matsushima, Masaaki; Hirotani, Makoto; Kano, Takahiro; Yabe, Ichiro; Matumoto, Akihisa; Sasaki, Hidenao

2012-01-01

Cyclosporine A (CYA) treatment has been reported to be probably useful for patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) that is resistant to conventional treatment. Although several studies have shown that appropriate area under the concentration-time curve (AUC) monitoring of CYA levels results in improved outcomes for refractory nephrotic syndrome patients, the importance of using AUC analysis for CIDP remains unclear. In this study, we measured both trough and AUC from 0 to 4 h (AUC(0-4 h)) levels of CYA in 2 patients with CIDP and compared the findings for the clinical parameters. On the basis of the CYA dosing recommendations for patients with nephrotic syndrome, we used a CYA concentration of 150 ng/ml for the trough level and an AUC(0-4 h) value of 2,500 ng/(ml·h). Patient 1 showed a significant increase in grip strength and a prolonged remission period. Patient 2 showed improvement in the modified Rankin scale and manual muscle test (MMT) scores. Monitoring both AUC(0-4 h) and trough levels of CYA seems to be a better option than monitoring the trough level alone because it leads to improved estimation of the efficacy and safety of CYA treatment in the case of CIDP patients.

How to interpret a small increase in AUC with an additional risk prediction marker: decision analysis comes through

NARCIS (Netherlands)

Baker, Stuart G.; Schuit, Ewoud; Steyerberg, Ewout W.; Pencina, Michael J.; Vickers, Andrew; Vickers, Andew; Moons, Karel G. M.; Mol, Ben W. J.; Lindeman, Karen S.

2014-01-01

An important question in the evaluation of an additional risk prediction marker is how to interpret a small increase in the area under the receiver operating characteristic curve (AUC). Many researchers believe that a change in AUC is a poor metric because it increases only slightly with the

An effect of re-extraction crystallization parameters on physical and chemical properties of AUC

International Nuclear Information System (INIS)

Yahi, Boussad

1990-07-01

This study is concerned with direct cristallization of ammonium uranyl carbonate (AUC) from a uranium loaded organic phase (30% TBP in kerosene), with ammonium carbonate (NH4)2 CO3. The effects of operating conditions (NH4)2 CO3 concentration, flowration residence time, temperature on the physical properties of AUC crystals (particle size distribution, specific area, density..) are reported. All products were identified (both by chemical analysis, X-Ray diffraction) as being ammonium uranyl ratio and (NH4)2 CO3 concentration favor the formation of fine AUC grains and aggregates. This is due mainly to the high concentration of (NH4)+ in the system which leads to a high solution supersaturation and consequently to a rapid formation rate of crystal (germination). The reverse phenomenon is observed at low phase ratio and (NH4)2 CO3 concentration, where germination and crystal growth ara slow and the product is mainly monocrystal. In the intermediate range, a mixture of polycrystal and aggregates is obtained. Residence time and temperature are also shown to have an effect on the processes (the effect of time being more important than temperature)

What is the evidence status of Appropriate Use Criteria (AUC)? Insight from a matching exercise with the guidelines for echocardiography.

Science.gov (United States)

Fonseca, R; Negishi, K; Marwick, T H

2015-08-01

There is interest in adapting the American Appropriate Use Criteria (AUC) for transthoracic echocardiography to Australian practice. We matched 90 of 98 AUC with the guidelines (53 appropriate, 12 sometimes appropriate, 25 rarely appropriate), but eight lacked any match. Among the matched criteria, 76 (82%) indications were concordant with the guidelines. A stronger evidence base would be desirable to settle these discrepancies before Australian adoption of AUC. © 2015 Royal Australasian College of Physicians.

Nitrofurantoin safety and effectiveness in treating acute uncomplicated cystitis (AUC) in hospitalized adults with renal insufficiency: antibiotic stewardship implications.

Science.gov (United States)

Cunha, B A; Cunha, C B; Lam, B; Giuga, J; Chin, J; Zafonte, V F; Gerson, S

2017-07-01

Nitrofurantoin remains a key oral antibiotic stewardship program (ASP) option in the treatment of acute uncomplicated cystitis (AUC) due to multi-drug resistant (MDR) Gram negative bacilli (GNB). However, there have been concerns regarding decreased nitrofurantoin efficacy with renal insufficiency. In our experience over the past three decades, nitrofurantoin has been safe and effective in treating AUC in hospitalized adults with renal insufficiency. Accordingly, we retrospectively reviewed our recent experience treating AUC in hospitalized adults with decreased renal function (CrCl AUC due to MDR GNB uropathogens, these results have important ASP implications. Currently, nitfurantoin is not recommended if CrCl < 60 ml/min. In our experience, used appropriately against susceptible uropathogens, nitrofurantoin was highly effective in nearly all patients with CrCl = 30-60 ml/min., and only failed in two patients due to renal insufficiency (CrCl < 30 ml/ml).

Mathematical modeling of antibody drug conjugates with the target and tubulin dynamics to predict AUC.

Science.gov (United States)

Byun, Jong Hyuk; Jung, Il Hyo

2018-04-14

Antibody drug conjugates (ADCs)are one of the most recently developed chemotherapeutics to treat some types of tumor cells. They consist of monoclonal antibodies (mAbs), linkers, and potent cytotoxic drugs. Unlike common chemotherapies, ADCs combine selectively with a target at the surface of the tumor cell, and a potent cytotoxic drug (payload) effectively prevents microtubule polymerization. In this work, we construct an ADC model that considers both the target of antibodies and the receptor (tubulin) of the cytotoxic payloads. The model is simulated with brentuximab vedotin, one of ADCs, and used to investigate the pharmacokinetic (PK) characteristics of ADCs in vivo. It also predicts area under the curve (AUC) of ADCs and the payloads by identifying the half-life. The results show that dynamical behaviors fairly coincide with the observed data and half-life and capture AUC. Thus, the model can be used for estimating some parameters, fitting experimental observations, predicting AUC, and exploring various dynamical behaviors of the target and the receptor. Copyright © 2018 Elsevier Ltd. All rights reserved.

New graphic AUC-based method to estimate overall survival benefit: pomalidomide reanalysis.

Science.gov (United States)

Fenix-Caballero, S; Diaz-Navarro, J; Prieto-Callejero, B; Rios-Sanchez, E; Alegre-del Rey, E J; Borrero-Rubio, J M

2016-02-01

Difference in median survival is an erratic measure and sometimes does not provide a good assessment of survival benefit. The aim of this study was to reanalyse the overall survival benefit of pomalidomide from pivotal clinical trial using a new area under curve (AUC)-based method. In the pivotal trial, pomalidomide plus low-dose dexamethasone showed a significant survival benefit over high-dose dexamethasone, with a difference between medians of 4.6 months. The new AUC method applied to the survival curves, obtained an overall survival benefit of 2.6 months for the pomalidomide treatment. This average difference in OS was calculated for the 61.5% of patients for whom the time to event is reliable enough. This 2-month differential would have major clinical and pharmacoeconomic implications, on both cost-effectiveness studies and on the willingness of the healthcare systems to pay for this treatment. © 2015 John Wiley & Sons Ltd.

Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx who received concurrent chemoradiation therapy with carboplatin (CBDCA) - AUC 1.5 vs AUC 2.0.

Science.gov (United States)

Furusaka, Tohru; Matsuda, Hiroshi; Saito, Tsutomu; Katsura, Yoshihisa; Ikeda, Minoru

2012-11-01

Patients who received concurrent chemoradiation therapy with carboplatin were followed up on a long-term basis. In 25 patients treated with carboplatin at an AUC of 2.0 mg/ml, the complete response (CR), 10-year survival, and 10-year larynx preservation rates were 96.0%, 91.1%, and 75.2%, respectively, and the safety margin for partial laryngectomy was 4 mm from the gross tumor. To perform long-term follow-up of the therapeutic outcomes of concurrent chemoradiation therapy and salvage surgery to determine the additive and synergistic effects of anticancer drugs combined with chemoradiotherapy. Fifty male patients (aged 33-76 years) with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included. Carboplatin was intravenously administered once a week for 4 weeks. Radiotherapy was delivered by an external beam of 4 MV linac X-ray (total = 66 Gy). The AUC 1.5 combination group showed overall response, CR, 5-year survival, 10-year survival, 5-year larynx preservation, and 10-year larynx preservation rates of 100.0%, 68.0%, 83.4%, 77.0%, 75.2%, and 75.2%, respectively. The AUC 2.0 combination group showed corresponding rates of 100%, 96.0%, 95.7%, 91.1%, 82.9%, and 72.7%, respectively. The most common side effects of grade 3 or more were leukopenia, neutropenia, and mucositis (stomatitis), and all were reversible. Thirteen patients (52.0%) in the AUC 1.5 combination group and nine patients (36.0%) in the AUC 2.0 combination group required salvage surgery. Histologically, concurrent chemoradiation therapy with carboplatin caused more severe cancer tissue degeneration. Pathological examinations indicated that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

AUC-Guided Vancomycin Dosing in Adolescent Patients With Suspected Sepsis.

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Lanke, Shankar; Yu, Tian; Rower, Joseph E; Balch, Alfred H; Korgenski, E Kent; Sherwin, Catherine M

2017-01-01

Vancomycin is a first-line treatment for β-lactam-resistant Gram-positive bacterial infections. Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of vancomycin in an adolescent population is of clinical importance in this often overlooked pediatric population. This retrospective study investigated vancomycin PK-PD in an adolescent cohort (12 to 18 years of age) of 463 patients (57% male, 81% white) admitted to the Intermountain Healthcare System between January 2006 and December 2013. Population PK modeling was performed in NONMEM 7.3. Vancomycin PK was well described with a 1-compartment model that identified both body weight (WT) and creatinine clearance (CRCL) as covariates significantly impacting vancomycin disposition. The model was then utilized to determine dosing strategies that achieved the targeted area under the 24-hour time curve vs minimum inhibitory concentration (AUC 0-24 /MIC) ratio of ≥400. Additionally, these data were correlated with minimum steady-state concentrations (C ss,min ) to find an acceptable target trough concentration range in adolescents. This analysis demonstrated that C ss,min ranging from 10 to 12.5 mg/L were highly predictive of achieving an AUC 0-24 /MIC ≥400 when the MIC was ≤1 mg/L. These results suggest that the target trough concentration for adolescents may be lower than that for adults. © 2016, The American College of Clinical Pharmacology.

Mycophenolic acid AUC in Thai kidney transplant recipients receiving low dose mycophenolate and its association with UGT2B7 polymorphisms.

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Pithukpakorn, Manop; Tiwawanwong, Tiwat; Lalerd, Yupaporn; Assawamakin, Anunchai; Premasathian, Nalinee; Tasanarong, Adis; Thongnoppakhun, Wanna; Vongwiwatana, Attapong

2014-01-01

Despite use of a lower mycophenolate dose in Thai kidney transplant patients, acceptable graft and patient outcomes can be achieved. We therefore examined the pharmacokinetics of mycophenolic acid (MPA) by area under the curve (AUC) and investigated genetic contribution in mycophenolate metabolism in this population. Kidney transplant recipients with stable graft function who were receiving mycophenolate mofetil 1,000 mg/d in combination with either cyclosporine or tacrolimus, and prednisolone were studied. The MPA concentration was measured by fluorescence polarization immunoassay (FPIA), at predose and 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing. Genetic polymorphisms in UGT1A8, UGT1A9, and UGT2B7 were examined by denaturing high-performance liquid chromatography (DHPLC)-based single-base extension (SBE) analysis. A total 138 patients were included in study. The mean AUC was 39.49 mg-h/L (28.39-89.58 mg-h/L), which was in the therapeutic range. The correlation between the predose MPA concentration and AUC was poor. The mean AUC in the tacrolimus group was higher than that in the cyclosporine group. Polymorphisms in UGT2B7 showed significant association with AUC. Most of our patients with reduced mycophenolate dose had the AUC within the therapeutic range. Genetic polymorphisms in UGT2B7 may play a role in MPA metabolism in Thai kidney transplant patients.

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

Czech Academy of Sciences Publication Activity Database

Chutora, Taras; López, Roso Redondo Jesús 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 OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 3.127, year: 2016

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.

Science.gov (United States)

Srinivas, Nuggehally R; Syed, Muzeeb

2016-01-01

Limited pharmacokinetic sampling strategy may be useful for predicting the area under the curve (AUC) for triptans and may have clinical utility as a prospective tool for prediction. Using appropriate intranasal pharmacokinetic data, a Cmax vs. AUC relationship was established by linear regression models for sumatriptan and zolmitriptan. The predictions of the AUC values were performed using published mean/median Cmax data and appropriate regression lines. The quotient of observed and predicted values rendered fold-difference calculation. The mean absolute error (MAE), mean positive error (MPE), 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 AUCs (83%-85%) were within 0.76-1.25-fold difference using the regression model. The prediction of AUC values for sumatriptan or zolmitriptan using the concentration data that reflected the Tmax occurrence were in the proximity of the reported values. In summary, the Cmax vs. AUC models exhibited strong correlations for sumatriptan and zolmitriptan. The usefulness of the prediction of the AUC values was established by a rigorous statistical approach.

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.

[Safe and effective administration of carboplatin-based chemotherapy in a patient undergoing hemodialysis with cancer of unknown primary by monitoring observed AUC of carboplatin-a case report].

Science.gov (United States)

Kondo, Masahiro; Kuroda, Junko; Ikai, Yoshitomo; Hayashi, Rumiko; Uegaki, Shiori; Yoshida, Tatsuya; Yoshida, Atsuhiro; Komatsu, Hirokazu; Kimura, Kazunori

2012-11-01

Here we report a case of successful treatment with combination chemotherapy of carboplatin(CBDCA)and paclitaxel for a patient undergoing hemodialysis(HD)with cancer of unknown primary, conducted by monitoring the observed AUC of ultrafilterable CBDCA. CBDCA was administered at a dose of 125 mg on day 1 in each course, an amount which had been calculated by the Calvert formula(GFR: 0, target AUC: 5). HD was started at a point in time one hour after the completion of each CBDCA administration, and performed for 5 hours in each course. Blood samples were collected during the first 3 courses of chemotherapy to measure the plasma concentration of free-platinum. The observed AUCs(o-AUC)of CBDCA in the first, second and third courses were 3. 03, 3. 44 and 3. 50mg·min/mL, respectively. The o-AUC in the first course was lower than that in the second course. The o-AUC in the second course was nearly equal to that in the third course, while each o-AUC was below the target AUC(t-AUC). Partial response was achieved after two courses of the CBDCA and paclitaxel combination chemotherapy, with adverse events of Grade 3 neutropenia and Grade 3 peripheral neuropathy observed in each course after the second course of chemotherapy. o-AUC of CBDCA administered to HD patients can not only be below t-AUC, as in this case, but also oppositely above t-AUC in cases with different doses of CBDCA or HD settings. Our results suggest that the monitoring of o-AUC of CBDCA is useful when practicing CBDCA-based chemotherapy safely and effectively in cancer patients undergoing HD.

Precise determination of protein extinction coefficients under native and denaturing conditions using SV-AUC.

Science.gov (United States)

Hoffmann, Andreas; Grassl, Kerstin; Gommert, Janine; Schlesak, Christian; Bepperling, Alexander

2018-04-17

The accurate determination of protein concentration is an important though non-trivial task during the development of a biopharmaceutical. The fundamental prerequisite for this is the availability of an accurate extinction coefficient. Common approaches for the determination of an extinction coefficient for a given protein are either based on the theoretical prediction utilizing the amino acid sequence or the photometric determination combined with a measurement of absolute protein concentration. Here, we report on an improved SV-AUC based method utilizing an analytical ultracentrifuge equipped with absorbance and Rayleigh interference optics. Global fitting of datasets helped to overcome some of the obstacles encountered with the traditional method employing synthetic boundary cells. Careful calculation of dn/dc values taking glycosylation and solvent composition into account allowed the determination of the extinction coefficients of monoclonal antibodies and an Fc-fusion protein under native as well as under denaturing conditions. An intra-assay precision of 0.9% and an accuracy of 1.8% compared to the theoretical value was achieved for monoclonal antibodies. Due to the large number of data points of a single dataset, no meaningful difference between the ProteomeLab XL-I and the new Optima AUC platform could be observed. Thus, the AUC-based approach offers a precise, convenient and versatile alternative to conventional methods like total amino acid analysis (AAA).

Development of AUC-based process at BARC for production of free-flowing and sinterable UO2 powder

International Nuclear Information System (INIS)

Keni, V.S.; Ghosh, S.K.; Ganguly, C.; Majumdar, S.

1994-01-01

Ammonium uranium carbonate (AUC) process has been developed and industrially used in Germany for preparation of free-flowing and sinterable UO 2 powder for fabrication of UO 2 fuel pellets for light water reactors (LWR). Efforts are underway at Bhabha Atomic Research Centre (BARC) for developing AUC-based process which would yield free-flowing UO 2 powder suitable for direct pelletisation and sintering to very high density (> 96% T.D.) UO 2 fuel pellets for pressurised heavy water reactors (PHWRs) in India. The first phase of this work has been completed jointly by Chemical Engineering Division (ChED) and Radiometallurgy Division (RMD) in batches of 1.5 kg. It was possible to fabricate UO 2 pellets of density 93-95% T.D. on a reproducible basis. At ChED, process parameters have been optimised for fabrication of AUC with suitable physical properties in batches of 1.5 kg (U), starting with nuclear pure uranyl nitrate solution. At RMD calcination parameters of AUC was optimised in batches of 500 g for obtaining free-flowing UO 2 powder, suitable for direct pelletisation and sintering. The pelletisation and sintering have been carried out at Radiometallurgy Division in batches of 1-1.5 kg. The maximum achievable density of UO 2 pellets has been in the range of 95.5-96% T.D. (author). 11 refs

[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

Novel HPTLC and UV-AUC analyses: For simple, economical, and rapid determination of Zileuton racemate

Directory of Open Access Journals (Sweden)

Saurabh B. Ganorkar

2017-03-01

Full Text Available Novel, simple, rapid and reliable High-Performance Thin-Layer Chromatographic (HPTLC and UV-spectroscopic area under curve (UV-AUC methods were developed and validated for the analysis of zileuton racemate in bulk and in in-house tablet formulation. HPTLC quantitation of zileuton was done by UV detection at 260 nm and analysis was performed on (20 × 10 cm aluminium sheets precoated with silica gel 60-F254 (E. Merck as stationary phase and toluene–methanol–glacial acetic acid (3.5:1.5:0.1 v/v as mobile phase. Quantitation by HPTLC method was performed over the concentration range of 200–1200 ng/band. The HPTLC method resulted into a compact and well resolved band for zileuton at retention factor (Rf of 0.51 ± 0.02. Linear regression analysis data for calibration of HPTLC method represented a good linear relationship with regression coefficient; r2 = 0.997. UV-AUC method was developed using sodium lauryl sulphate (0.05 M as a hydrotropic agent to enhance water solubility and area was determined at a wavelength range in between 248.40 and 271.0 nm. Correlation coefficient for UV-AUC analysis was found to be r2 = 0.999. The developed UV-AUC method depicted a fine linear relationship for zileuton racemate in a concentration range of 2–12 μg/mL. Both the developed methods were validated for precision, robustness, ruggedness, accuracy, sensitivity as per guidelines laid by the International Conference on Harmonisation (ICH. Statistical analysis proved that the developed methods were precise, robust, sensitive and accurate and can be used effectively for the analysis of zileuton in bulk and pharmaceutical formulations.

The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

Science.gov (United States)

Boily, Michaël; Dussault, Catherine; Massicotte, Julie; Guibord, Pascal; Lefebvre, Marc

2015-01-23

To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Local epidemiology and resistance profiles in acute uncomplicated cystitis (AUC) in women: a prospective cohort study in an urban urological ambulatory setting.

Science.gov (United States)

Seitz, Michael; Stief, Christian; Waidelich, Raphaela

2017-10-16

Acute uncomplicated cystitis (AUC) is a common ailment in the urological setting. Guidelines for urinary tract infections are based on large-scale multi-centre, epidemiological and international studies. The objective of this observational study was to establish whether the results of a multi-centre study on the resistance profile of Escherichia coli (E. coli) in patients with AUC could be directly applied to an urological practice in a major European city or whether there are divergences in the resistance profile. An observational study was applied prospectively to 502 patients with AUC between January 2015 and January 2017). Personal data were anonymised. Exclusion criteria were the patient's age (AUC should therefore only be treated with TRS, CIP and AMC after a susceptibility test has been carried out.

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.

Spectroscopic Identification of the Au-C Bond Formation upon Electroreduction of an Aryl Diazonium Salt on Gold.

Science.gov (United States)

Guo, Limin; Ma, Lipo; Zhang, Yelong; Cheng, Xun; Xu, Ye; Wang, Jin; Wang, Erkang; Peng, Zhangquan

2016-11-08

Electroreduction of aryl diazonium salts on gold can produce organic films that are more robust than their analogous self-assembled monolayers formed from chemical adsorption of organic thiols on gold. However, whether the enhanced stability is due to the Au-C bond formation remains debated. In this work, we report the electroreduction of an aryl diazonium salt of 4,4'-disulfanediyldibenzenediazonium on gold forming a multilayer of Au-(Ar-S-S-Ar) n , which can be further degraded to a monolayer of Au-Ar-S - by electrochemical cleavage of the S-S moieties within the multilayer. By conducting an in situ surface-enhanced Raman spectroscopic study of both the multilayer formation/degradation and the monolayer reduction/oxidation processes, coupled to density functional theory calculations, we provide compelling evidence that an Au-C bond does form upon electroreduction of aryl diazonium salts on gold and that the enhanced stability of the electrografted organic films is due to the Au-C bond being intrinsically stronger than the Au-S bond for a given phenylthiolate compound by ca. 0.4 eV.

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

International Nuclear Information System (INIS)

Carnaval, Joao Paulo R.; Santos, Rafael D. dos; Barbosa, Rodrigo A.; Lauer, Sergio

2013-01-01

In the INB nuclear fuel cycle, the pellets production is based on UO 2 powder made by AUC (Ammonium-Uranyl-Carbonate) route. AUC formation occurs by fluidising of UF 6 , NH 3 and CO 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 2 powder. At this point, the dried AUC decompounds to UO 3 , NH 3 and C0 2 , these 2 gases are absorbed at the gases washer, formin go the carbonated water (CW), whit is basically a (NH 4 ) 2 CO 3 solution. The UO 2+x is reduced and stabilized to UO 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 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)

Obtainment of UO{sub 2} ex AUC (ammonium uranyl carbonate) from uranyl fluoride; Obtencion de UO{sub 2} ex AUC (carbonato de uranil amonio) partiendo de fluoruro de uranilo

Energy Technology Data Exchange (ETDEWEB)

Fuente, M de la; Gonzalez, A G; Gonzalez Scardaone, S; Perez de Perel, L; Marajofsky, A [Comision Nacional de Energia Atomica, San Martin (Argentina). Unidad de Actividad Combustibles Nucleares

1997-12-31

It is proposed the production of enriched UO{sub 2} powder starting from UF6 with the desired isotopic concentration in order to avoid the possible segregation inconveniences that take place in the mixture of enriched and natural UO{sub 2} powders. In this work is shown the feasibility of obtaining powders with direct sinterability, through the precipitation of uranyl fluoride solutions (UF{sub 6} hydrolysis). The AUC is a crystalline forerunner used in the powder production line. A simulated hydrolyzed UF{sub 6} solution was obtained by means of the dissolution of UO{sub 3} with FH acid. The precipitation operation was carried out in a discontinuous operation device, with simultaneous pumping. The precipitating media is achieved by adding simultaneously NH{sub 3} (g) and CO{sub 2} (g), using ejector nozzles during precipitation. Mother waters pH during precipitation stay between 8.5 and 9.2 and the temperature of operation is around 323 K. The AUC calcination, reduction and passivation took place during the same operation. The reduction was carried out at three different temperatures, 823 K, 933 K and 1003 K in H{sub 2} reducing atmosphere. The passivation was carried out at 343 K. The main problem of this process is free fluorine that could remain in the powder. It would inhibit its use as nuclear fuel, since the international specifications do not tolerate more than 20 mg/kg. However, the determinations carried out in all the cases, showed that it was completely eliminated during calcination. The ex AUC UO{sub 2} powders obtained from solution of F{sub 2} (UO{sub 2}) were fluoride free, showed specific areas within specification and good sinterability. Therefore it is possible to fabricate enriched powders using a humid process from F{sub 6}U, to be used without problems of segregation due to the origin of the powder mix in PWR fuels type (CAREM). (author). 3 figs.

Evaluation of limited sampling models for prediction of oral midazolam AUC for CYP3A phenotyping and drug interaction studies.

Science.gov (United States)

Mueller, Silke C; Drewelow, Bernd

2013-05-01

The area under the concentration-time curve (AUC) after oral midazolam administration is commonly used for cytochrome P450 (CYP) 3A phenotyping studies. The aim of this investigation was to evaluate a limited sampling strategy for the prediction of AUC with oral midazolam. A total of 288 concentration-time profiles from 123 healthy volunteers who participated in four previously performed drug interaction studies with intense sampling after a single oral dose of 7.5 mg midazolam were available for evaluation. Of these, 45 profiles served for model building, which was performed by stepwise multiple linear regression, and the remaining 243 datasets served for validation. Mean prediction error (MPE), mean absolute error (MAE) and root mean squared error (RMSE) were calculated to determine bias and precision The one- to four-sampling point models with the best coefficient of correlation were the one-sampling point model (8 h; r (2) = 0.84), the two-sampling point model (0.5 and 8 h; r (2) = 0.93), the three-sampling point model (0.5, 2, and 8 h; r (2) = 0.96), and the four-sampling point model (0.5,1, 2, and 8 h; r (2) = 0.97). However, the one- and two-sampling point models were unable to predict the midazolam AUC due to unacceptable bias and precision. Only the four-sampling point model predicted the very low and very high midazolam AUC of the validation dataset with acceptable precision and bias. The four-sampling point model was also able to predict the geometric mean ratio of the treatment phase over the baseline (with 90 % confidence interval) results of three drug interaction studies in the categories of strong, moderate, and mild induction, as well as no interaction. A four-sampling point limited sampling strategy to predict the oral midazolam AUC for CYP3A phenotyping is proposed. The one-, two- and three-sampling point models were not able to predict midazolam AUC accurately.

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)

A new mathematical approach for the estimation of the AUC and its variability under different experimental designs in preclinical studies.

Science.gov (United States)

Navarro-Fontestad, Carmen; González-Álvarez, Isabel; Fernández-Teruel, Carlos; Bermejo, Marival; Casabó, Vicente Germán

2012-01-01

The aim of the present work was to develop a new mathematical method for estimating the area under the curve (AUC) and its variability that could be applied in different preclinical experimental designs and amenable to be implemented in standard calculation worksheets. In order to assess the usefulness of the new approach, different experimental scenarios were studied and the results were compared with those obtained with commonly used software: WinNonlin® and Phoenix WinNonlin®. The results do not show statistical differences among the AUC values obtained by both procedures, but the new method appears to be a better estimator of the AUC standard error, measured as the coverage of 95% confidence interval. In this way, the new proposed method demonstrates to be as useful as WinNonlin® software when it was applicable. Copyright © 2011 John Wiley & Sons, Ltd.

The impact of composite AUC estimates on the prediction of systemic exposure in toxicology experiments.

Science.gov (United States)

Sahota, Tarjinder; Danhof, Meindert; Della Pasqua, Oscar

2015-06-01

Current toxicity protocols relate measures of systemic exposure (i.e. AUC, Cmax) as obtained by non-compartmental analysis to observed toxicity. A complicating factor in this practice is the potential bias in the estimates defining safe drug exposure. Moreover, it prevents the assessment of variability. The objective of the current investigation was therefore (a) to demonstrate the feasibility of applying nonlinear mixed effects modelling for the evaluation of toxicokinetics and (b) to assess the bias and accuracy in summary measures of systemic exposure for each method. Here, simulation scenarios were evaluated, which mimic toxicology protocols in rodents. To ensure differences in pharmacokinetic properties are accounted for, hypothetical drugs with varying disposition properties were considered. Data analysis was performed using non-compartmental methods and nonlinear mixed effects modelling. Exposure levels were expressed as area under the concentration versus time curve (AUC), peak concentrations (Cmax) and time above a predefined threshold (TAT). Results were then compared with the reference values to assess the bias and precision of parameter estimates. Higher accuracy and precision were observed for model-based estimates (i.e. AUC, Cmax and TAT), irrespective of group or treatment duration, as compared with non-compartmental analysis. Despite the focus of guidelines on establishing safety thresholds for the evaluation of new molecules in humans, current methods neglect uncertainty, lack of precision and bias in parameter estimates. The use of nonlinear mixed effects modelling for the analysis of toxicokinetics provides insight into variability and should be considered for predicting safe exposure in humans.

Best single time point correlations with AUC for cyclosporine and tacrolimus in HIV-infected kidney and liver transplant recipients.

Science.gov (United States)

Frassetto, Lynda A; Tan-Tam, Clara C; Barin, Burc; Browne, Matt; Wolfe, Alan R; Stock, Peter G; Roland, Michelle; Benet, Leslie Z

2014-03-27

Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, tacrolimus (TAC) trough levels (C0) or cyclosporine (CsA) drawn at C0 or 2 hours after dosing (C2) correlate with drug exposure (area under the curve [AUC]/dose) and outcomes. Because of ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, this study investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels. This study prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS in 150 studies over time after transplantation (weeks 2 to 4, 12, 28, 52, and 104). IS levels were measured with liquid chromatography-tandem mass spectrometry and AUC calculated using WinNonlin 9.0. Correlation analyses were run on SAS 9.2. CsA concentration at C4 correlated better with AUC than C0 or C2, and over time TAC concentration correlated better at C0 or C2. It is suggested that C0 is acceptable for TAC monitoring, but poor predictability will occur at C0 with CsA. The low correlation of C0 with CsA AUC could be responsible for the higher rejection rates on CsA that has been reported in these subjects.

How to interpret a small increase in AUC with an additional risk prediction marker: decision analysis comes through.

Science.gov (United States)

Baker, Stuart G; Schuit, Ewoud; Steyerberg, Ewout W; Pencina, Michael J; Vickers, Andrew; Vickers, Andew; Moons, Karel G M; Mol, Ben W J; Lindeman, Karen S

2014-09-28

An important question in the evaluation of an additional risk prediction marker is how to interpret a small increase in the area under the receiver operating characteristic curve (AUC). Many researchers believe that a change in AUC is a poor metric because it increases only slightly with the addition of a marker with a large odds ratio. Because it is not possible on purely statistical grounds to choose between the odds ratio and AUC, we invoke decision analysis, which incorporates costs and benefits. For example, a timely estimate of the risk of later non-elective operative delivery can help a woman in labor decide if she wants an early elective cesarean section to avoid greater complications from possible later non-elective operative delivery. A basic risk prediction model for later non-elective operative delivery involves only antepartum markers. Because adding intrapartum markers to this risk prediction model increases AUC by 0.02, we questioned whether this small improvement is worthwhile. A key decision-analytic quantity is the risk threshold, here the risk of later non-elective operative delivery at which a patient would be indifferent between an early elective cesarean section and usual care. For a range of risk thresholds, we found that an increase in the net benefit of risk prediction requires collecting intrapartum marker data on 68 to 124 women for every correct prediction of later non-elective operative delivery. Because data collection is non-invasive, this test tradeoff of 68 to 124 is clinically acceptable, indicating the value of adding intrapartum markers to the risk prediction model. Copyright © 2014 John Wiley & Sons, Ltd.

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...

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

Limited pharmacokinetic sampling strategy may be useful for predicting the area under the curve (AUC) for triptans and may have clinical utility as a prospective tool for prediction. Using appropriate intranasal pharmacokinetic data, a Cmax vs. AUC relationship was established by linear regression...... models for sumatriptan and zolmitriptan. The predictions of the AUC values were performed using published mean/median Cmax data and appropriate regression lines. The quotient of observed and predicted values rendered fold-difference calculation. The mean absolute error (MAE), mean positive error (MPE......), 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...

Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

Science.gov (United States)

Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

2012-02-01

There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Rocker: Open source, easy-to-use tool for AUC and enrichment calculations and ROC visualization.

Science.gov (United States)

Lätti, Sakari; Niinivehmas, Sanna; Pentikäinen, Olli T

2016-01-01

Receiver operating characteristics (ROC) curve with the calculation of area under curve (AUC) is a useful tool to evaluate the performance of biomedical and chemoinformatics data. For example, in virtual drug screening ROC curves are very often used to visualize the efficiency of the used application to separate active ligands from inactive molecules. Unfortunately, most of the available tools for ROC analysis are implemented into commercially available software packages, or are plugins in statistical software, which are not always the easiest to use. Here, we present Rocker, a simple ROC curve visualization tool that can be used for the generation of publication quality images. Rocker also includes an automatic calculation of the AUC for the ROC curve and Boltzmann-enhanced discrimination of ROC (BEDROC). Furthermore, in virtual screening campaigns it is often important to understand the early enrichment of active ligand identification, for this Rocker offers automated calculation routine. To enable further development of Rocker, it is freely available (MIT-GPL license) for use and modifications from our web-site (http://www.jyu.fi/rocker).

Treatment of the effluent generated in conversion process of auc by precipitation

International Nuclear Information System (INIS)

Carvalho, E.F.U. de; Santos, L.R. dos; Riella, H.G.

1988-01-01

The purpose of this study is to provide a description for the treatment of generating effluent from Ammonium Uranyl Carbonate-AUC IPEN/CNEN-SP. This procedure describes the uranium recovery (200 mlU/1) by means of its precipitation with hidrogen peroxide at 50 0 C, pH 8,5 where results a yellow powder thought to be UO 4 2NH 3 2HF and a NH 4 F solution with an uranium concentration of 6-7mgU/1. The powder resulted was characterized by chemical analysis and X- Ray difraction techniques. (author) [pt

Development of a high-throughput in vitro assay using a novel Caco-2/rat hepatocyte system for the prediction of oral plasma area under the concentration versus time curve (AUC) in rats.

Science.gov (United States)

Cheng, K-C; Li, Cheng; Hsieh, Yunsheng; Montgomery, Diana; Liu, Tongtong; White, Ronald E

2006-01-01

Previously, we have shown that a novel Caco-2/human hepatocyte system is a useful model for the prediction of oral bioavailability in humans. In this study, we attempted to use a similar system in a high-throughput screening mode for the selection of new compound entities (NCE) in drug discovery. A total of 72 compounds randomly selected from three different chemotypes were dosed orally in rats. In vivo plasma area under the concentration versus time curve (AUC) from 0-6 h of the parent compound was determined. The same compounds were also tested in the Caco-2/rat hepatocyte system. In vitro AUC from 0-3 h in the Caco-2 rat hepatocyte system was determined. The predictive usefulness of the Caco-2/rat hepatocyte system was evaluated by comparing the in vivo plasma AUC and the in vitro AUC. Linear regression analysis showed a reasonable correlation (R2 = 0.5) between the in vivo AUC and the in vitro AUC. Using 0.4 microM h in vivo AUC as a cut-off, compounds were categorized as either low or high AUC. The in vitro AUC successfully matched the corresponding in vivo category for sixty-three out of seventy-two compounds. The results presented in this study suggest that the Caco-2/rat hepatocyte system may be used as a high-throughput screen in drug discovery for pharmacokinetic behaviors of compounds in rats.

Abbreviated AUC monitoring of cyclosporine more adequately identified patients at risk for acute rejection during induction of immunosuppressive therapy after kidney transplantation than recommended C2 concentration values.

Science.gov (United States)

Troncoso, P; Ortiz, A M; Jara, A; Vilches, S

2009-01-01

Monitoring of cyclosporine (CsA) is critical during the induction of immunosuppressive therapy. Although most centers have incorporated C2 levels, our unit still uses an abbreviated AUC model which includes concentrations at C1, C2, and C6 post-dose (AUC(1-6)). The objective of this study was to compare both strategies of CsA monitoring during the first 30 days after kidney transplantation. The study included 89 recipients induced with CsA microemulsion and steroids. AUC(1-6) profiles were performed around days 3, 10, and 30 after transplantation with a target of 5500 to 6000 ng*h/mL considered therapeutic. For comparison purposes, a value of C2 >/= 1500 ng/mL was also considered therapeutic. Mean C2 and AUC(1-6) values were low dated with biopsy-proven acute rejection episodes (BPAR) during the study period. Twenty patients received living donor kidneys and overall there were 46 females. During this period, 253 AUC(1-6) were performed including 44 (17.4%) below the therapeutic range. When the analysis included only C2, 171 (67.6%) were below the therapeutic target (P AUC(1-6) at day 10 discriminated rejectors versus nonrejectors (5645 +/- 1390 and 8221 +/- 2502, respectively; P = .008). C2 was not significantly different at any time in either group. In this study, abbreviated AUC monitoring more adequately identified patients at risk for acute rejection than C2. Recommended C2 concentration levels need to be redefined in our patients.

Proposing the Use of Partial AUC as an Adjunctive Measure in Establishing Bioequivalence Between Deltoid and Gluteal Administration of Long-Acting Injectable Antipsychotics.

Science.gov (United States)

Lee, Lik Hang N; Choi, Charles; Gershkovich, Pavel; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M

2016-12-01

The maximum plasma concentration (C max ) and the area under the plasma concentration-time curve (AUC) are commonly used to establish bioequivalence between two formulations of the same oral medication. Similarly, these pharmacokinetic parameters have also been used to establish bioequivalence between two sites of administration for the same injectable formulation. However, these conventional methods of establishing bioequivalence are of limited use when comparing modified-release formulations of a drug, particularly those with rates of absorption that are amenable to change with the site of injection. Inherent differences in the rate of absorption can result in clinically significant differences in early exposure and drug response. Here, we propose the use of the partial AUC (pAUC) as a measure of early exposure to aid in the assessment of bioequivalence between the gluteal and the deltoid site of administration for long-acting injectable antipsychotics.

Are Vancomycin Trough Concentrations of 15 to 20 mg/L Associated With Increased Attainment of an AUC/MIC ≥ 400 in Patients With Presumed MRSA Infection?

Science.gov (United States)

Hale, Cory M; Seabury, Robert W; Steele, Jeffrey M; Darko, William; Miller, Christopher D

2017-06-01

To determine whether there is an association between higher vancomycin trough concentrations and attainment of a calculated area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ≥400. A retrospective analysis was conducted among vancomycin-treated adult patients with a positive methicillin-resistant Staphylococcus aureus (MRSA) culture. Attainment of a calculated AUC/MIC ≥400 was compared between patients with troughs in the reference range of 15 to 20 mg/L and those with troughs in the following ranges: 20 mg/L. Nephrotoxicity was assessed as a secondary outcome based on corrected average vancomycin troughs over 10 days of treatment. Overall, 226 patients were reviewed and 100 included. Relative to troughs ≥10, patients with vancomycin troughs AUC/MIC ≥400 (odds ratio [OR] 0.27, 95% confidence interval [CI]: 0.01-0.75). No difference was found in the attainment of an AUC/MIC ≥400 in patients with troughs of 10 to 14.9 mg/L and >20 mg/L when compared to patients with troughs of 15 to 20 mg/L. The mean corrected average vancomycin trough was higher in patients developing nephrotoxicity compared to those who did not (19.5 vs 14.5 mg/L, P AUC/MIC target relative to troughs of 10 to 14.9 mg/L but may increase nephrotoxicity risk.

Hidden Hydride Transfer as a Decisive Mechanistic Step in the Reactions of the Unligated Gold Carbide [AuC]+ with Methane under Ambient Conditions.

Science.gov (United States)

Li, Jilai; Zhou, Shaodong; Schlangen, Maria; Weiske, Thomas; Schwarz, Helmut

2016-10-10

The reactivity of the cationic gold carbide [AuC] + (bearing an electrophilic carbon atom) towards methane has been studied using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The product pairs generated, that is, Au + /C 2 H 4 , [Au(C 2 H 2 )] + /H 2 , and [C 2 H 3 ] + /AuH, point to the breaking and making of C-H, C-C, and H-H bonds under single-collision conditions. The mechanisms of these rather efficient reactions have been elucidated by high-level quantum-chemical calculations. As a major result, based on molecular orbital and NBO-based charge analysis, an unprecedented hydride transfer from methane to the carbon atom of [AuC] + has been identified as a key step. Also, the origin of this novel mechanistic scenario has been addressed. The mechanistic insights derived from this study may provide guidance for the rational design of carbon-based catalysts. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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, respe......, 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....

Alternative methods for CYP2D6 phenotyping: comparison of dextromethorphan metabolic ratios from AUC, single point plasma, and urine.

Science.gov (United States)

Chen, Rui; Wang, Haotian; Shi, Jun; Hu, Pei

2016-05-01

CYP2D6 is a high polymorphic enzyme. Determining its phenotype before CYP2D6 substrate treatment can avoid dose-dependent adverse events or therapeutic failures. Alternative phenotyping methods of CYP2D6 were compared to aluate the appropriate and precise time points for phenotyping after single-dose and ultiple-dose of 30-mg controlled-release (CR) dextromethorphan (DM) and to explore the antimodes for potential sampling methods. This was an open-label, single and multiple-dose study. 21 subjects were assigned to receive a single dose of CR DM 30 mg orally, followed by a 3-day washout period prior to oral administration of CR DM 30 mg every 12 hours for 6 days. Metabolic ratios (MRs) from AUC∞ after single dosing and from AUC0-12h at steady state were taken as the gold standard. The correlations of metabolic ratios of DM to dextrorphan (MRDM/DX) values based on different phenotyping methods were assessed. Linear regression formulas were derived to calculate the antimodes for potential sample methods. In the single-dose part of the study statistically significant correlations were found between MRDM/DX from AUC∞ and from serial plasma points from 1 to 30 hours or from urine (all p-values < 0.001). In the multiple-dose part, statistically significant correlations were found between MRDM/DX from AUC0-12h on day 6 and MRDM/DX from serial plasma points from 0 to 36 hours after the last dosing (all p-values < 0.001). Based on reported urinary antimode and linear regression analysis, the antimodes of AUC and plasma points were derived to profile the trend of antimodes as the drug concentrations changed. MRDM/DX from plasma points had good correlations with MRDM/DX from AUC. Plasma points from 1 to 30 hours after single dose of 30-mg CR DM and any plasma point at steady state after multiple doses of CR DM could potentially be used for phenotyping of CYP2D6.

Dual Incorporation of the in vitro Data (IC50) and in vivo (Cmax) Data for the Prediction of Area Under the Curve (AUC) for Statins using Regression Models Developed for Either Pravastatin or Simvastatin.

Science.gov (United States)

Srinivas, N R

2016-08-01

Linear regression models utilizing a single time point (Cmax) has been reported for pravastatin and simvastatin. A new model was developed for the prediction of AUC of statins that utilized the slopes of the above 2 models, with pharmacokinetic (Cmax) and a pharmacodynamic (IC50 value) components for the statins. The prediction of AUCs for various statins (pravastatin, atorvastatin, simvastatin and rosuvastatin) was carried out using the newly developed dual pharmacokinetic and pharmacodynamic model. Generally, the AUC predictions were contained within 0.5 to 2-fold difference of the observed AUC suggesting utility of the new models. The root mean square error predictions wereAUC for statins. Such a new concept as described in the work may have utility in both drug discovery and development stages. © Georg Thieme Verlag KG Stuttgart · New York.

Estimation of chloroform inhalation dose by other routes based on the relationship of area under the blood concentration-time curve (AUC)-inhalation dose to chloroform distribution in the blood of rats.

Science.gov (United States)

Take, Makoto; Takeuchi, Tetsuya; Haresaku, Mitsuru; Matsumoto, Michiharu; Nagano, Kasuke; Yamamoto, Seigo; Takamura-Enya, Takeji; Fukushima, Shoji

2014-01-01

The present study investigated the time-course changes of concentration of chloroform (CHCl3) in the blood during and after exposure of male rats to CHCl3 by inhalation. Increasing the dose of CHCl3 in the inhalation exposed groups caused a commensurate increase in the concentration of CHCl3 in the blood and the area under the blood concentration-time curve (AUC). There was good correlation (r = 0.988) between the inhalation dose and the AUC/kg body weight. Based on the AUC/kg body weight-inhalation dose curve and the AUC/kg body weight after oral administration, inhalation equivalent doses of orally administered CHCl3 were calculated. Calculation of inhalation equivalent doses allows the body burden due to CHCl3 by inhalation exposure and oral exposure to be directly compared. This type of comparison facilitates risk assessment in humans exposed to CHCl3 by different routes. Our results indicate that when calculating inhalation equivalent doses of CHCl3, it is critical to include the AUC from the exposure period in addition to the AUC after the end of the exposure period. Thus, studies which measure the concentration of volatile organic compounds in the blood during the inhalation exposure period are crucial. The data reported here makes an important contribution to the physiologically based pharmacokinetic (PBPK) database of CHCl3 in rodents.

Validation of limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring - is a separate validation group required?

NARCIS (Netherlands)

Proost, J. H.

Objective: Limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring are usually validated in a separate group of patients, according to published guidelines. The aim of this study is to evaluate the validation of LSM by comparing independent validation with cross-validation

Statement to commencement ceremony at American University in Cairo (AUC). 9 February 2006, Cairo, Egypt

Energy Technology Data Exchange (ETDEWEB)

ElBaradei, M

2006-02-09

In its statement to Commencement Ceremony At American University in Cairo (AUC) the Director General of the IAEA reminisced about his life - the twists and turns it had taken, and the lessons he had learned along the way. His messages to the students was to keep thinking and learning, be ready for opportunity when it comes, treat others with the understanding that we are all part of one human family, live your own life, and take joy in it, be proud of your heritage and engage fully in the future of Egypt.

Statement to commencement ceremony at American University in Cairo (AUC). 9 February 2006, Cairo, Egypt

International Nuclear Information System (INIS)

ElBaradei, M.

2006-01-01

In its statement to Commencement Ceremony At American University in Cairo (AUC) the Director General of the IAEA reminisced about his life - the twists and turns it had taken, and the lessons he had learned along the way. His messages to the students was to keep thinking and learning, be ready for opportunity when it comes, treat others with the understanding that we are all part of one human family, live your own life, and take joy in it, be proud of your heritage and engage fully in the future of Egypt

AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis.

Science.gov (United States)

Castañeda, Ximena; García-de-la-Mària, Cristina; Gasch, Oriol; Pericas, Juan M; Armero, Yolanda; Soy, Dolors; García-González, Javier; Falces, Carlos; Ninot, Salvador; Almela, Manel; Ambrosioni, Juan; Quintana, Eduardo; Vidal, Barbara; Fuster, David; Llopis, Jaume; Soto, Sara; Moreno, Asuncion; Marco, Francesc; Miró, Jose M

2017-06-01

The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) ( P = 0.343), while the medians (interquartile ranges [IQRs]) for log 10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) ( P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis. Copyright © 2017 American Society for Microbiology.

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

Excellent AUC for joint fluid cytology in the detection/exclusion of hip and knee prosthetic joint infection.

Science.gov (United States)

Gallo, Jiri; Juranova, Jarmila; Svoboda, Michal; Zapletalova, Jana

2017-09-01

The aim of this study was to evaluate the characteristics of synovial fluid (SF) white cell count (SWCC) and neutrophil/lymphocyte percentage in the diagnosis of prosthetic joint infection (PJI) for particular threshold values. This was a prospective study of 391 patients in whom SF specimens were collected before total joint replacement revisions. SF was aspirated before joint capsule incision. The PJI diagnosis was based only on non-SF data. Receiver operating characteristic plots were constructed for the SWCC and differential counts of leukocytes in aspirated fluid. Logistic binomic regression was used to distinguish infected and non-infected cases in the combined data. PJI was diagnosed in 78 patients, and aseptic revision in 313 patients. The areas (AUC) under the curve for the SWCC, the neutrophil and lymphocyte percentages were 0.974, 0.962, and 0.951, respectively. The optimal cut-off for PJI was 3,450 cells/μL, 74.6% neutrophils, and 14.6% lymphocytes. Positive likelihood ratios for the SWCC, neutrophil and lymphocyte percentages were 19.0, 10.4, and 9.5, respectively. Negative likelihood ratios for the SWCC, neutrophil and lymphocyte percentages were 0.06, 0.076, and 0.092, respectively. Based on AUC, the present study identified cut-off values for the SWCC and differential leukocyte count for the diagnosis of PJI. The likelihood ratio for positive/negative SWCCs can significantly change the pre-test probability of PJI.

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.

Ammonium uranyl carbonate (AUC) based process of simultaneous partitioning and reconversion for uranium and plutonium in fast breeder reactors (FBRs) fuel reprocessing

International Nuclear Information System (INIS)

Govindan, P.; Palamalai, A.; Vijayan, K.S.; Subba Rao, R.V.; Venkataraman, M.; Natarajan, R.

2013-01-01

Ammonium uranyl carbonate (AUC) based process of simultaneous partitioning and reconversion for uranium and plutonium is developed for the recovery of uranium and plutonium present in spent fuel of fast breeder reactors (FBRs). Effect of pH on the solubility of carbonates of uranium and plutonium in ammonium carbonate medium is studied. Effect of mole ratios of uranium and plutonium as a function of uranium and plutonium concentration at pH 8.0-8.5 for effective separation of uranium and plutonium to each other is studied. Feasibility of reconversion of plutonium in carbonate medium is also studied. The studies indicate that uranium is selectively precipitated as AUC at pH 8.0-8.5 by adding ammonium carbonate solution leaving plutonium in the filtrate. Plutonium in the filtrate after acidified with concentrated nitric acid could also be precipitated as carbonate at pH 6.5-7.0 by adding ammonium carbonate solution. A flow sheet is proposed and evaluated for partitioning and reconversion of uranium and plutonium simultaneously in the FBR fuel reprocessing. (author)

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.

An exposure-response analysis based on rifampin suggests CYP3A4 induction is driven by AUC: an in vitro investigation.

Science.gov (United States)

Chang, Cheng; Yang, Xin; Fahmi, Odette A; Riccardi, Keith A; Di, Li; Obach, R Scott

2017-08-01

1. Induction is an important mechanism contributing to drug-drug interactions. It is most commonly evaluated in the human hepatocyte assay over 48-h or 72-h incubation period. However, whether the overall exposure (i.e. Area Under the Curve (AUC) or C ave ) or maximum exposure (i.e. C max ) of the inducer is responsible for the magnitude of subsequent induction has not been thoroughly investigated. Additionally, in vitro induction assays are typically treated as static systems, which could lead to inaccurate induction potency estimation. Hence, European Medicines Agency (EMA) guidance now specifies quantitation of drug levels in the incubation. 2. This work treated the typical in vitro evaluation of rifampin induction as an in vivo system by generating various target engagement profiles, measuring free rifampin concentration over 3 d of incubation and evaluating the impact of these factors on final induction response. 3. This rifampin-based analysis demonstrates that the induction process is driven by time-averaged target engagement (i.e. AUC-driven). Additionally, depletion of rifampin in the incubation medium over 3 d as well as non-specific/specific binding were observed. 4. These findings should help aid the discovery of clinical candidates with minimal induction liability and further expand our knowledge in the quantitative translatability of in vitro induction assays.

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

International Nuclear Information System (INIS)

Liao, C.-M.; Liang, H.-M.; Chen, B.-C.; Singh Sher; Tsai, J.-W.; Chou, Y.-H.; Lin, W.-T.

2005-01-01

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

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.

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.

Increased oral AUC of baicalin in streptozotocin-induced diabetic rats due to the increased activity of intestinal beta-glucuronidase.

Science.gov (United States)

Liu, Li; Deng, Yuan-Xiong; Liang, Yan; Pang, Xiao-Yan; Liu, Xiao-Dong; Liu, Yao-Wu; Yang, Jian-Song; Xie, Lin; Wang, Guang-Ji

2010-01-01

The purpose of the study was to investigate the pharmacokinetics of baicalin, a major bioactive component of Scutellariae radix, in diabetic conditions. The 4-week diabetic rats were induced by intraperitoneal administration of streptozotocin. Plasma concentrations of baicalin were measured following oral (200 mg/kg) or intravenous (12 mg/kg) administration. Everted intestinal transport, intestinal mucosal metabolism of baicalin and intestinal beta-glucuronidase activity were also investigated. It was found that the diabetic condition significantly increased the exposure of baicalin following oral doses (AUC 100.77 +/- 4.16 microg x h/mL in diabetic rats vs. 48.48 +/- 7.94 microg x h/mL in normal rats). In contrast, the diabetic condition significantly decreased the exposure of baicalin following intravenous doses (AUC 11.20 +/- 2.28 microg x h/mL in diabetic rats vs. 18.02 +/- 3.45 microg x h/mL in normal rats). We also found lower apparent permeability coefficients of baicalin in the ileum of diabetic rats (8.43 x 10 (-6) +/- 2.40 x 10 (-6) cm/s in diabetic rats vs. 5.21 x 10 (-5) +/- 1.55 x 10 (-5) cm/s in normal rats). Further studies showed that the diabetic condition enhanced the hydrolysis of baicalin to baicalein in intestinal mucosal, accompanied by an increase of beta-glucuronidase activity. All these results suggested that the higher oral exposure of baicalin in diabetic rats did not result from the decreased hepatic metabolism or increased intestinal absorption of baicalin. The enhancement of intestinal beta-glucuronidase activity may partly account for the higher exposure of baicalin in diabetic rats after oral administration. Copyright Georg Thieme Verlag KG Stuttgart . New York.

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)

Modeling the UO2 ex-AUC pellet process and predicting the fuel rod temperature distribution under steady-state operating condition

Science.gov (United States)

Hung, Nguyen Trong; Thuan, Le Ba; Thanh, Tran Chi; Nhuan, Hoang; Khoai, Do Van; Tung, Nguyen Van; Lee, Jin-Young; Jyothi, Rajesh Kumar

2018-06-01

Modeling uranium dioxide pellet process from ammonium uranyl carbonate - derived uranium dioxide powder (UO2 ex-AUC powder) and predicting fuel rod temperature distribution were reported in the paper. Response surface methodology (RSM) and FRAPCON-4.0 code were used to model the process and to predict the fuel rod temperature under steady-state operating condition. Fuel rod design of AP-1000 designed by Westinghouse Electric Corporation, in these the pellet fabrication parameters are from the study, were input data for the code. The predictive data were suggested the relationship between the fabrication parameters of UO2 pellets and their temperature image in nuclear reactor.

A phase I study of PRO131921, a novel anti-CD20 monoclonal antibody in patients with relapsed/refractory CD20+ indolent NHL: correlation between clinical responses and AUC pharmacokinetics.

Science.gov (United States)

Casulo, Carla; Vose, Julie M; Ho, William Y; Kahl, Brad; Brunvand, Mark; Goy, Andre; Kasamon, Yvette; Cheson, Bruce; Friedberg, Jonathan W

2014-09-01

PRO131921 is a third-generation, humanized anti-CD20 monoclonal antibody with increased antibody-dependent cytotoxicity and complement-dependent cytotoxicity compared to rituximab. In this phase I study, PRO131921 was administered as a single agent to patients with CD20+, relapsed or refractory, indolent non-Hodgkin lymphoma (NHL) who had been treated with a prior rituximab-containing regimen. The primary aim of this study was safety and tolerability of PRO131921. The secondary aim of the study, and focus of this report, was to determine the pharmacokinetics (PK) profile of PRO131921 and establish a correlation between drug exposure and clinical efficacy. Patients were treated with PRO131921 by intravenous infusion weekly for 4 weeks and the dose was escalated based on safety in a 3+3 design. Twenty-four patients were treated with PRO131921 at doses from 25mg/m(2) to 800 mg/m(2). Analysis of PK data demonstrated a correlation between higher normalized drug exposure (normalized AUC) and tumor shrinkage (p = .0035). Also, normalized AUC levels were higher among responders and subjects displaying tumor shrinkage versus subjects progressing or showing no regression (p = 0.030). In conclusion, PRO131921 demonstrated clinical activity in rituximab-relapsed and refractory indolent NHL patients. The observation that higher normalized AUC may be associated with improved clinical responses has potential implications in future trials of monoclonal antibody-based therapies, and emphasizes the importance of early PK studies to optimize antibody efficacy. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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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.

Predictive performance of three practical approaches for grapefruit juice-induced 2-fold or greater increases in AUC of concomitantly administered drugs.

Science.gov (United States)

Takahashi, M; Onozawa, S; Ogawa, R; Uesawa, Y; Echizen, H

2015-02-01

Clinical pharmacists have a challenging task when answering patients' question about whether they can take specific drugs with grapefruit juice (GFJ) without risk of drug interaction. To identify the most practicable method for predicting clinically relevant changes in plasma concentrations of orally administered drugs caused by the ingestion of GFJ, we compared the predictive performance of three methods using data obtained from the literature. We undertook a systematic search of drug interactions associated with GFJ using MEDLINE and the Metabolism & Transport Drug Interaction Database (DIDB version 4.0). We considered an elevation of the area under the plasma concentration-time curve (AUC) of 2 or greater relative to the control value [AUC ratio (AUCR) ≥ 2.0] as a clinically significant interaction. The data from 74 drugs (194 data sets) were analysed. When the reported information of CYP3A involvement in the metabolism of a drug of interest was adopted as a predictive criterion for GFJ-drug interaction, the performance assessed by positive predictive value (PPV) was low (0.26), but that assessed by negative predictive value (NPV) and sensitivity was high (1.00 for both). When the reported oral bioavailability of ≤ 0.1 was used as a criterion, the PPV improved to 0.50 with an acceptable NPV of 0.81, but sensitivity was reduced to 0.21. When the reported AUCR was ≥ 10 after co-administration of a typical CYP3A inhibitor, the corresponding values were 0.64, 0.79 and 0.19, respectively. We consider that an oral bioavailability of ≤ 0.1 or an AUCR of ≥ 10 caused by a CYP3A inhibitor of a drug of interest may be a practical prediction criterion for avoiding significant interactions with GFJ. Information about the involvement of CYP3A in their metabolism should also be taken into account for drugs with narrow therapeutic ranges. © 2014 John Wiley & Sons Ltd.

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

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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

Long Term Measurement of the Vapor Pressure of Gold in the Au-C System

Science.gov (United States)

Copland, Evan H.

2009-01-01

Incorporating the {Au(s,l) + graphite} reference in component activity measurements made with the multiple effusion-cell vapor source mass spectrometry (multicell KEMS) technique provides a fixed temperature defining ITS-90 (T(sub mp)(Au) = 1337.33K) and a systematic method to check accuracy. Over a 2 year period delta H sub(298)Au was determined by the 2nd and 3rd law methods in 25 separate experiments and were in the ranges 362.2 plus or minus 3.3 kJmol(sup -1) and 367.8 plus or minus 1.1 kJmol(sup -1), respectively. This 5 kJmol-1 discrepancy is transferred directly to the measured activities. This is unacceptable and the source of this discrepancy needs to be understood and corrected. Accepting the 2nd law value increases p(Au) by about 50 percent, brings the 2nd and 3rd law values into agreement and removes the T dependence in the 3rd law values. While compelling, there is no way to independently determine instrument sensitivities, S(sub Au), with T in a single experiment with KEMS. This lack of capability is stopping a deeper understanding of this problem. In addition, the Au-C phase diagram suggests a eutectic invariant reaction: L-Au(4.7at%C) = FCC-Au(0.08at%C) + C(graphite) at T(sub e) approximately 1323K. This high C concentration in Au(l) must reduce p(Au) in equilibrium with {Au(s,l) + graphite} and raises some critical questions about the Gibbs free energy functions of Au(s,l) and the Au fixed point (T(sub mp)(Au) = 1337.33K) which is always measured in graphite.

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

International Nuclear Information System (INIS)

Silva, Dionisio F.; Geraldes, Adriana N.; Cardoso, Elisangela S.Z.; Gomes, Thiago B.; Linardi, Marcelo; Oliveira Neto, Almir; Spinace, Estevam V.

2011-01-01

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)

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)

Probing the electronic structure and Au—C chemical bonding in AuCn− and AuCnH− (n = 2, 4, and 6) using high-resolution photoelectron spectroscopy

International Nuclear Information System (INIS)

León, Iker; Ruipérez, Fernando; Ugalde, Jesus M.; Wang, Lai-Sheng

2016-01-01

We report a joint photoelectron spectroscopy and theoretical study on AuC 4 − , AuC 6 − , and AuC n H − (n = 2, 4, and 6) using high-resolution photoelectron imaging and ab initio calculations. The ground state of AuC 2 H − , AuC 4 H − , and AuC 6 H − is found to be linear, while that of AuC 4 − and AuC 6 − is bent. All the species are found to be linear in their neutral ground states. The electron affinities (EAs) are measured to be 3.366(1) and 3.593(1) eV for AuC 4 and AuC 6 , respectively. Both bending and stretching frequencies are resolved in the spectra of AuC 4 − and AuC 6 − . High-resolution data of AuC n H − reveal major vibrational progressions in the Au—C stretching and bending modes. AuC 2 H − has a ground state stretching frequency of 445(10) cm −1 and a bending frequency of 260(10) cm −1 ; AuC 4 H − has a ground state stretching frequency of 340(10) cm −1 ; AuC 6 H − has a ground state stretching frequency of 260(10) cm −1 and a bending frequency of 55(10) cm −1 . The EAs are measured to be 1.475(1), 1.778(1), and 1.962(1) eV for AuC 2 H, AuC 4 H, and AuC 6 H, respectively. The strength of the Au—C bond decreases as the number of carbon atoms increases. The current study provides a wealth of electronic structure information about AuC 4 − , AuC 6 − , and AuC n H − (n = 2, 4, and 6) and their corresponding neutrals.

Evaluation of postprandial glucose excursion using a novel minimally invasive glucose area-under-the-curve monitoring system.

Science.gov (United States)

Kuranuki, Sachi; Sato, Toshiyuki; Okada, Seiki; Hosoya, Samiko; Seko, Akinobu; Sugihara, Kaya; Nakamura, Teiji

2013-01-01

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. 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. 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). 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.

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

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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.

On the validity of time-dependent AUC estimators.

Science.gov (United States)

Schmid, Matthias; Kestler, Hans A; Potapov, Sergej

2015-01-01

Recent developments in molecular biology have led to the massive discovery of new marker candidates for the prediction of patient survival. To evaluate the predictive value of these markers, statistical tools for measuring the performance of survival models are needed. We consider estimators of discrimination measures, which are a popular approach to evaluate survival predictions in biomarker studies. Estimators of discrimination measures are usually based on regularity assumptions such as the proportional hazards assumption. Based on two sets of molecular data and a simulation study, we show that violations of the regularity assumptions may lead to over-optimistic estimates of prediction accuracy and may therefore result in biased conclusions regarding the clinical utility of new biomarkers. In particular, we demonstrate that biased medical decision making is possible even if statistical checks indicate that all regularity assumptions are satisfied. © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Predictive Validity of the HKT-R Risk Assessment Tool: Two and 5-Year Violent Recidivism in a Nationwide Sample of Dutch Forensic Psychiatric Patients.

Science.gov (United States)

Bogaerts, Stefan; Spreen, Marinus; Ter Horst, Paul; Gerlsma, Coby

2018-06-01

This study has examined the predictive validity of the Historical Clinical Future [ Historisch Klinisch Toekomst] Revised risk assessment scheme in a cohort of 347 forensic psychiatric patients, which were discharged between 2004 and 2008 from any of 12 highly secure forensic centers in the Netherlands. Predictive validity was measured 2 and 5 years after release. Official reconviction data obtained from the Dutch Ministry of Security and Justice were used as outcome measures. Violent reoffending within 2 and 5 years after discharge was assessed. With regard to violent reoffending, results indicated that the predictive validity of the Historical domain was modest for 2 (area under the curve [AUC] = .75) and 5 (AUC = .74) years. The predictive validity of the Clinical domain was marginal for 2 (admission: AUC = .62; discharge: AUC = .63) and 5 (admission: AUC = .69; discharge: AUC = .62) years after release. The predictive validity of the Future domain was modest (AUC = .71) for 2 years and low for 5 (AUC = .58) years. The total score of the instrument was modest for 2 years (AUC = .78) and marginal for 5 (AUC = .68) years. Finally, the Final Risk Judgment was modest for 2 years (AUC = .78) and marginal for 5 (AUC = .63) years time at risk. It is concluded that this risk assessment instrument appears to be a satisfactory instrument for risk assessment.

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

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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.

Sedation and mechanical antinociception after intravenous administration of detomidine in donkeys: a dosage-effect study.

Science.gov (United States)

Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Varner, Kelley M; Robinson, Lauren S

2015-02-21

There is limited, useful, scientific information on detomidine in donkeys. This study compared the effects of intravenous saline, detomidine (10, 13.5, 17 and 20 μg/kg) and acepromazine (50 μg/kg) in donkeys by computing areas under the curve for 0-30, 30-60 and 60-120 minutes (AUC0-30, AUC30-60 and AUC60-120) for sedation scores, head heights and mechanical nociceptive thresholds (MNTs). For sedation scores, all detomidine treatments, except 10 μg/kg, increased AUC0-30 values compared with saline, and AUC0-30 values were larger for 17 μg/kg detomidine than for acepromazine. All head height AUC values were lower for detomidine than for saline (except AUC60-120 for 10 μg/kg detomidine) and acepromazine (except AUC0-30 for 10 and 20 μg/kg detomidine, and AUC60-120 for 10 μg/kg detomidine). For MNTs, all detomidine treatments increased AUC0-30 and AUC30-60 values compared with saline and acepromazine; AUC30-60 values were smaller for 10 μg/kg than for 17 and 20 μg/kg detomidine. MNT AUC60-120 values were larger for 20 μg/kg detomidine than for saline, 10 μg/kg detomidine and acepromazine. Detomidine induced sedation and antinociception, but only antinociception was dosage dependent. Selection of detomidine dosage for donkeys may depend on the required duration of sedation and/or degree of analgesia. British Veterinary Association.

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

Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome.

Science.gov (United States)

Cheang, Kai I; Sistrun, Sakita N; Morel, Kelley S; Nestler, John E

2016-01-01

Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS ( n = 16) and normal ( n = 15) women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUC DCI-IPG ), AUC insulin , and AUC DCI-IPG /AUC insulin were measured during a 2 hr OGTT at baseline and 8 weeks. Results. PCOS women had lower AUC DCI-IPG /AUC insulin at baseline and a significant relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0003), which was not present in controls. Weight loss was similar between PCOS (-4.08 kg) and normal women (-4.29 kg, p = 0.6281). Weight loss in PCOS women did not change the relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0100), and this relationship remained absent in control women. Conclusion. The association between AUC DCI-IPG /AUC insulin and insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity.

Predicting pathologic tumor response to chemoradiotherapy with histogram distances characterizing longitudinal changes in 18F-FDG uptake patterns

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Tan, Shan; Zhang, Hao; Zhang, Yongxue; Chen, Wengen; D’Souza, Warren D.; Lu, Wei

2013-01-01

Purpose: A family of fluorine-18 (18F)-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) features based on histogram distances is proposed for predicting pathologic tumor response to neoadjuvant chemoradiotherapy (CRT). These features describe the longitudinal change of FDG uptake distribution within a tumor. Methods: Twenty patients with esophageal cancer treated with CRT plus surgery were included in this study. All patients underwent PET/CT scans before (pre-) and after (post-) CRT. The two scans were first rigidly registered, and the original tumor sites were then manually delineated on the pre-PET/CT by an experienced nuclear medicine physician. Two histograms representing the FDG uptake distribution were extracted from the pre- and the registered post-PET images, respectively, both within the delineated tumor. Distances between the two histograms quantify longitudinal changes in FDG uptake distribution resulting from CRT, and thus are potential predictors of tumor response. A total of 19 histogram distances were examined and compared to both traditional PET response measures and Haralick texture features. Receiver operating characteristic analyses and Mann-Whitney U test were performed to assess their predictive ability. Results: Among all tested histogram distances, seven bin-to-bin and seven crossbin distances outperformed traditional PET response measures using maximum standardized uptake value (AUC = 0.70) or total lesion glycolysis (AUC = 0.80). The seven bin-to-bin distances were: L2 distance (AUC = 0.84), χ2 distance (AUC = 0.83), intersection distance (AUC = 0.82), cosine distance (AUC = 0.83), squared Euclidean distance (AUC = 0.83), L1 distance (AUC = 0.82), and Jeffrey distance (AUC = 0.82). The seven crossbin distances were: quadratic-chi distance (AUC = 0.89), earth mover distance (AUC = 0.86), fast earth mover distance (AUC = 0.86), diffusion distance (AUC = 0.88), Kolmogorov-Smirnov distance (AUC = 0.88), quadratic form distance

Diagnostic efficiency of truncated area under the curve from 0 to 2 h (AUC₀₋₂) of mycophenolic acid in kidney transplant recipients receiving mycophenolate mofetil and concomitant tacrolimus.

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Lampón, Natalia; Tutor-Crespo, María J; Romero, Rafael; Tutor, José C

2011-07-01

Recently, the use of the truncated area under the curve from 0 to 2 h (AUC(0-2)) of mycophenolic acid (MPA) has been proposed for therapeutic monitoring in liver transplant recipients. The aim of our study was the evaluation of the clinical usefulness of truncated AUC(0-2) in kidney transplant patients. Plasma MPA was measured in samples taken before the morning dose of mycophenolate mofetil, and one-half and 2 h post-dose, completing 63 MPA concentration-time profiles from 40 adult kidney transplant recipients. The AUC from 0 to 12 h (AUC(0-12)) was calculated using the validated algorithm of Pawinski et al. The truncated AUC(0-2) was calculated using the linear trapezoidal rule, and extrapolated to 0-12 h (trapezoidal extrapolated AUC(0-12)) as previously described. Algorithm calculated and trapezoidal extrapolated AUC(0-12) values showed high correlation (r=0.995) and acceptable dispersion (ma68=0.71 μg·h/mL), median prediction error (6.6%) and median absolute prediction error (12.6%). The truncated AUC(0-2) had acceptable diagnostic efficiency (87%) in the classification of subtherapeutic, therapeutic or supratherapeutic values with respect to AUC(0-12). However, due to the high inter-individual variation of the drug absorption-rate, the dispersion between both pharmacokinetic variables (ma68=6.9 μg·h/mL) was unacceptable. The substantial dispersion between truncated AUC(0-2) and AUC(0-12) values may be a serious objection for the routine use of MPA AUC(0-2) in clinical practice.

A minimally invasive system for glucose area under the curve measurement using interstitial fluid extraction technology: evaluation of the accuracy and usefulness with oral glucose tolerance tests in subjects with and without diabetes.

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Sakaguchi, Kazuhiko; Hirota, Yushi; Hashimoto, Naoko; Ogawa, Wataru; Sato, Toshiyuki; Okada, Seiki; Hagino, Kei; Asakura, Yoshihiro; Kikkawa, Yasuo; Kojima, Junko; Maekawa, Yasunori; Nakajima, Hiromu

2012-06-01

Recent studies have highlighted the importance of managing postprandial hyperglycemia, but adequate monitoring of postprandial glucose remains difficult because of wide variations in levels. We have therefore developed a minimally invasive system to monitor postprandial glucose area under the curve (AUC). This system involves no blood sampling and uses interstitial fluid glucose (IG) AUC (IG-AUC) as a surrogate marker of postprandial glucose. This study aimed to evaluate the usefulness of this system by comparing data with the findings of oral glucose tolerance tests (OGTTs) in subjects with and without diabetes. The glucose AUC monitoring system was validated by OGTTs in 37 subjects with and 10 subjects without diabetes. A plastic microneedle array was stamped on the forearm to extract IG. A hydrogel patch was then placed on the pretreated area to accumulate IG. Glucose and sodium ion concentrations in the hydrogel were measured to calculate IG-AUC at 2-h postload glucose. Plasma glucose (PG) levels were measured every 30 min to calculate reference PG-AUC. IG-AUC correlated strongly with reference PG-AUC (r=0.93) over a wide range. The level of correlation between IG-AUC and maximum PG level was also high (r=0.86). The painless nature of the technique was confirmed by the response of patients to questionnaires. The glucose AUC monitoring system using IG provided good estimates of reference PG-AUC and maximum PG level during OGTTs in subjects with and without diabetes. This system provides easy-to-use monitoring of glucose AUC, which is a good indicator of postprandial glucose.

Assessment of diagnostic value of various tumors markers (CEA, CA199, CA50) for colorectal neoplasm with logistic regression and ROC curve

International Nuclear Information System (INIS)

Gu Ping; Huang Gang; Han Yuan

2007-01-01

Objective: To assess the diagnostic value of CEA, CA199 and CA50 for colorectal neoplasm by logistic regression and ROC curve. Methods: Serum CEA (with CLIA), CA199 (with ECLIA) and CA50 (with IRMA) levels were measured in 75 patients with colorectal cancer, 35 patients with benign colorectal disorders and 49 controls. The area under the ROC curve (AUC)s of CEA, CA199, CA50 from logistic regression results were compared. Results: In the cancer-benign disorder group, the AUC of CA50 was larger than the AUC of CA199. AUC of combined CEA, CA50 was largest: not only larger than any AUC of CEA, CA50, CA199 alone but also larger than the AUC of the combined three markers (0.875 vs 0.604). In cancer-control group, the AUC of combination of CEA, CA199 and CA50 was larger than any AUC of CEA, CA199 or CA50 alone. Both in the cancer-benign disorder group or cancer-control group, the AUC of CEA was larger than the AUC of CA199 or CA50. Conclusion: CEA is of definite value in the diagnosis of colorectal cancer. For differential diagnosis, the combination of CEA and CA50 can give more information, while the combination of three tumor markers is less helpful. As an advanced statistical method, logistic regression can improve the diagnostic sensitivity and specificity. (authors)

A strategy to calculate cyclosporin A area under the time-concentration curve in pediatric renal transplantation.

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David-Neto, Elias; Araujo, Lilian Pereira; Feres Alves, Cristiane; Sumita, Nairo; Romano, Pascoalina; Yagyu, Elisa Midori; Nahas, William Carlos; Ianhez, Luiz Estevam

2002-08-01

The complete area under the time-concentration curve (AUC) is considered the gold standard for cyclosporin A (CsA) monitoring, particularly in pediatric kidney graft recipients who have great absorption and drug clearance variability. However, complete AUC is time-consuming and expensive. For this reason, we retrospectively reviewed 131 complete 4-h AUC (AUC0-4) performed in 34 children (mean age 10.6 +/- 2 yr) in order to construct an equation to calculate AUC0-4. The median time after transplantation was 540 (range: 247-1,358) days. Multiple regression analysis was performed either with a single variable or with a combination of two variables. CsA blood concentration at the second hour after the oral morning dose (C2) was the best predictor of AUC0-4, where AUC0-4 = 424 + (2.65 x C2), R2 = 0.81, p time-periods, C2 was the best parameter to use to calculate AUC0-4. The equations obtained during these two time-periods were very close to the one for the whole population. Our data shows that C2 can be safely used to estimate AUC0-4. However, for values above 4,000 ng/h/mL, the formula overestimates the trapezoidal AUC0-4. The C2 equation simplifies the CsA monitoring as a result of its high predictive value and clinical feasibility.

Is the area under blood pressure curve the best parameter to evaluate 24-h ambulatory blood pressure monitoring data?

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Nobre, Fernando; Mion, Décio

2005-10-01

Ambulatory blood pressure monitoring (ABPM) provides relevant data about blood pressure over a 24-h period. The analysis of parameters to determine the blood pressure profile from these data is of great importance. To calculate areas under systolic and diastolic blood pressure curves (SBP-AUC/DBP-AUC) and compare with systolic and diastolic blood pressure load (SBPL/DBPL) and 24-h systolic and diastolic blood pressure (24-h SBP/24-h DBP) in order to determine which provides the best correlation with left ventricular mass index (LVMI). ABPM measurements (1143 individuals) were analyzed to obtain 24-h SBP/24-h DBP, SBPL/DBPL, and SBP-AUC/ DBP-AUC, using Spacelabs (90207) and CardioSistemas devices. Left ventricular mass was determined using an echocardiograph HP Sonos 5500 and LVMI was calculated. The correlations between all possible pairs within the group 24-h SBP/SBPL/SBP-AUC and 24-h DBP/DBPL/DBP-AUC were high and statistically significant. The correlations between 24-h SBP/24-h DBP and SBP-AUC/DBP-AUC with SBPL/DBPL close to 100%, were lower than those mentioned above. The correlations of the parameters obtained by ABPM with LVMI were also high and statistically significant, except for blood pressure load between 90 and 100%, and for 24-h SBP of 135 mmHg or less and SBPL higher than 50%. SBPL/DBPL and SBP-AUC/DBP-AUC can be used for the evaluation of ABPM data owing to the strong correlation with 24-h SBP/24-h DBP and with LVMI, except when SBPL is close to 100% or 24-h SBP is below 135 mmHg but SBPL is above 50%. SBP-AUC/DBP-AUC, however, are a better alternative because they do not have the limitations of blood pressure load or even of 24-h blood pressure present.

Development of a reconversion method for uranyl nitrate to oxide in the reconversion step of reprocessing of irradiated fuel

International Nuclear Information System (INIS)

Govindan, P.; Palamalai, A.; Vijayan, K.S.; Subbuthai, S.; Murugesan, S.; Mohan, S.V.; Subba Rao, R.V.

2002-01-01

Ammonium uranyl carbonate (AUC) precipitation is developed for the conversion of uranyl nitrate to oxide in the uranium reconversion step of reprocessing of irradiated fuel by the addition of ammonium carbonate salt. Different precipitation conditions of AUC are studied. The solubility of AUC as a function of uranium concentration in the feed at different temperatures using ammonium carbonate salt as precipitant is studied. This study indicates that 95-99.8% of uranium is recovered as AUC by precipitating 5-125 g/l of uranium with loss of uranium (250-10 ppm) in the filtrate by adding ammonium carbonate salt. It is also observed that the solubility of AUC increased as the concentration of uranium decreased. Thermal decomposition is carried out by thermogravimetry/differential thermal analysis (TG/DTA) and evolved gas analysis-mass spectrometry (EGA-MS) to find out AUC decomposition and gases evolved during decomposition. Studies are also carried out to characterize AUC by using X-ray diffraction (XRD). The data show that AUC obtained by the above conditions is very much consistent with published information. (author)

Effects of short-term therapy with glibenclamide and repaglinide on incretin hormones and oxidative damage associated with postprandial hyperglycaemia in people with type 2 diabetes mellitus

DEFF Research Database (Denmark)

Stephens, J W; Bodvarsdottir, T B; Wareham, K

2011-01-01

glucose load at baseline and after eight weeks of treatment. The areas under the curve were analysed at 45, 60 and 120 min (AUC45, AUC60, AUC120). Results: Significant improvements in glucose were observed with repaglinide (HBA1c: 1.5%, fasting glucose: 2.8 mmol/L, 2-h glucose: 3.7 mmol/L, AUC120: 18...

Assessment of diagnostic value of tumor markers for colorectal neoplasm by logistic regression and ROC curve

International Nuclear Information System (INIS)

Ping, G.

2007-01-01

Full text: Objective: To assess the diagnostic value of CEA CA199 and CA50 for colorectal neoplasm by logistic regression and ROC curve. Methods: The subjects include 75 patients of colorectal cancer, 35 patients of benign intestinal disease and 49 health controls. CEA CA199 and CA50 are measured by CLIA ECLIA and IRMA respectively. The area under the curve (AUC) of CEA CA 199 CA50 and logistic regression results are compared. [Result] In the cancer-benign group, the AUC of CA50 is larger than the AUC of CA199 Compared with the AUC of combination of CEA CA199 and CA50 (0.604),the AUC of combination of CEA and CA50 (0.875) is larger and it is also larger than any other AUC of CEA CA199 or CA50 alone. In the cancerhealth group, the AUC of combination of CEA CA199 and CA50 is larger than any other AUC of CEA CA199 or CA50 alone. No matter in the cancer-benign group or cancerhealth group. The AUC of CEA is larger than the AUC of CA199 or CA50. Conclusion: CEA is useful in the diagnosis of colorectal cancer. In the process of differential diagnosis, the combination of CEA and CA50 can give more information, while the combination of three tumor markers does not perform well. Furthermore, as a statistical method, logistic regression can improve the diagnostic sensitivity and specificity. (author)

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.

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.

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma.

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Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-03-30

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration-time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters ( ABCB1 and ABCG2 ), UGT1A , and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate ( P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC ( P treatment precisely predicted actual AUC after axitinib treatment ( P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC.

Secretion of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes

DEFF Research Database (Denmark)

Calanna, Salvatore; Christensen, Mikkel; Holst, Jens Juul

2013-01-01

lower GIP responses as evaluated from iAUC (weighted mean difference, -648 pmol/L×min; 95% CI, -1,276 to -21). Fixed-effects models meta-analyses confirmed most of the results of the primary meta-analysis but showed iAUC×min(-1) to be reduced and showed tAUC and tAUC×min(-1) to be higher in diabetic...... of Science. Data were retrieved and random-effects models for the primary meta-analysis, random-effects meta-regression, and subgroup and regression analyses were applied. RESULTS: Random-effects meta-analysis of GIP responses in 23 trials during 28 different stimulation tests showed that patients with type...... patients. Random-effects meta-regression of the primary meta-analysis showed that age (peak GIP, tAUC, iAUC, and iAUC×min(-1)), BMI (tAUC, iAUC, and iAUC×min(-1)), and HbA1c (iAUC and iAUC×min(-1)) predicted some of the GIP outcomes. Post hoc subgroup analysis showed a negative influence of age and of HbA1...

HEAPA Filter Bank In-Place Leak Test for ACUs of Advanced Fuel Science Building in 2010

Energy Technology Data Exchange (ETDEWEB)

Ji, Chul Goo; Bae, Sang Oh [KAERI, Daejeon (Korea, Republic of)

2010-12-15

Air cleaning units installed in the Advanced Fuel Science Building were performed visual inspection, airflow capacity test, and HEAPA filter bank in-place leak test in accordance with ASME N-510-1989. All the above inspections was acceptable. Visual inspection was satisfied to AUC-556 and AUC-557. Airflow capacity was 96%(30,240 m{sup 3}/h) of design airflow capacity(31,500 m{sup 3}/h) for AUC-556 and was 97%(22,800 m{sup 3}/h) of design airflow capacity(22,800 m{sup 3}/h) for AUC-557, and was maintained within {+-}10% of the specified value. Penetration of HEAPA filter bank in-place leak test was 0.009% for AUC-556 and was 0.013% for AUC-557 and these values were maintained less than the acceptance criteria(0.05%)

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

OpenAIRE

Kuranuki, Sachi; Sato, Toshiyuki; Okada, Seiki; Hosoya, Samiko; Seko, Akinobu; Sugihara, Kaya; Nakamura, Teiji

2013-01-01

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 are...

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

Waist-to-Height Ratio and Triglycerides/High-Density Lipoprotein Cholesterol Were the Optimal Predictors of Metabolic Syndrome in Uighur Men and Women in Xinjiang, China.

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Chen, Bang-Dang; Yang, Yi-Ning; Ma, Yi-Tong; Pan, Shuo; He, Chun-Hui; Liu, Fen; Ma, Xiang; Fu, Zhen-Yan; Li, Xiao-Mei; Xie, Xiang; Zheng, Ying-Ying

2015-06-01

This study aimed to identify the best single predictor of metabolic syndrome by comparing the predictive ability of various anthropometric and atherogenic parameters among a Uighur population in Xinjiang, northwest China. A total of 4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS), which was carried out from October, 2007, to March, 2010. Anthropometric data, blood pressure, serum concentration of serum total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and fasting glucose were documented. Prevalence of metabolic syndrome and its individual components were confirmed according to International Diabetes Federation (IDF) criteria. Area under the receiver operating characteristic curve (AUC) of each variable for the presence of metabolic syndrome was compared. The sensitivity (Sen), specificity (Spe), distance in the receiver operating characteristic (ROC) curve, and cutoffs of each variable for the presence of metabolic syndrome were calculated. In all, 23.7% of men had the metabolic syndrome, whereas 40.1% of women had the metabolic syndrome in a Uighur population in Xinjiang; the prevalence of metabolic syndrome in women was significantly higher than that in men (PAUC value (AUC=0.838); it was followed by TGs/HDL-C (AUC=0.826), body mass index (BMI) (AUC=0.812), waist-to-hip ratio (WHR) (AUC=0.781), and body adiposity index (BAI) (AUC=0.709). In women, the TGs/HDL-C had the highest AUC value (AUC=0.815); it was followed by WHtR (AUC=0.780), WHR (AUC=0.730), BMI (AUC=0.719), and BAI (AUC=0.699). Similarly, among all five anthropometric and atherogenic parameters, the WHtR had the shortest ROC distance of 0.32 (Sen=85.40%, Spe=71.6%), and the optimal cutoff for WHtR was 0.55 in men. In women, TGs/HDL-C had the shortest ROC distance of 0.35 (Sen=75.29%, Spe=75.18%), and the optimal cutoff of TGs/HDL-C was 1.22. WHtR was the best predictor of metabolic

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

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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.

Sedative and mechanical antinociceptive effects of four dosages of romifidine administered intravenously to donkeys.

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Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Robinson, Lauren S

2017-06-01

Although romifidine is commonly used to provide sedation and analgesia for the facilitation of clinical procedures in donkeys, limited scientific information is available for this drug in this species. This randomized, controlled, crossover, Latin-square, blinded study compared the sedative and antinociceptive effects of four dosages of romifidine (40, 60, 80, and 100μg/kg IV; R40, R60, R80, and R100, respectively), acepromazine (0.1mg/kg IV; ACE) and saline (0.9%, 5mL IV) by assigning sedation scores (SS) and measuring head heights above ground (HHAG) and mechanical nociceptive thresholds (MNT) in donkeys. Areas under the curve (AUC) from 0 to 30, 30-60, 60-120, and 120-180min after administration were computed for SS, HHAG, and MNT and compared among treatments. Romifidine and ACE, but not saline, induced clinical signs of sedation. SS-AUC 0-30 for R60, R80 and R100, and SS-AUC 30-60 for R100 were higher than corresponding values for saline. HHAG-AUC 30-60 for R40 and R80, and HHAG-AUC 60-120 for R40, R60, R80 and R100 were smaller than for saline. HHAG-AUC 60-120 for R100 were also smaller than those for ACE. Romifidine, but not saline or ACE, increased MNT. MNT-AUC 0-30 and MNT-AUC 30-60 for R40, R60, R80 and R100, and MNT-AUC 60-120 for R80 and R100 were higher than corresponding values for saline and ACE. MNT-AUC 60-120 for R100 were higher than for all other romifidine treatments. In donkeys, the degree of sedation was similar for the four dosages of romifidine, but antinociception was dose-dependent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamics of Nampt/visfatin and high molecular weight adiponectin in response to oral glucose load in obese and lean women.

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Unlütürk, Uğur; Harmanci, Ayla; Yildiz, Bülent Okan; Bayraktar, Miyase

2010-04-01

High molecular weight adiponectin (HMWA) is the active circulating form of adiponectin. Nampt/visfatin is the enzyme secreted from adipocytes in an active form and is one of the putative regulators of insulin secretion. To investigate the dynamics of total adiponectin (TA), HMWA and Nampt/visfatin in obese and lean women during oral glucose tolerance test (OGTT). We studied normal glucose-tolerant (NGT), age-matched, 30 obese and 30 lean women. All subjects underwent a standard 75 g, 2-h OGTT, and area under the curve (AUC) during OGTT for glucose, insulin, Nampt/visfatin, TA and HMWA was calculated. Body fat mass was assessed by bioimpedance analysis. Results Obese women had significantly higher basal and AUC values for insulin and Nampt/visfatin, whereas basal and AUC-HMWA were significantly lower in this group. Alternatively, obese and lean groups had similar basal and AUC values for glucose and TA. Basal insulin levels were negatively correlated with HMWA levels, but not with basal Nampt/visfatin. AUC-insulin was correlated positively with AUC-visfatin, and negatively with AUC-HMWA. Total and truncal body fat mass showed positive correlation with basal and AUC-visfatin, and negative correlation with basal and AUC-HMWA. In the NGT state, obese women have higher Nampt/visfatin and lower HMWA levels, both basally and in response to oral glucose challenge. The dynamics of Nampt/visfatin and HMWA during OGTT appear to be linked with insulin and adiposity. Counter-regulatory adaptations in HMWA and Nampt/visfatin might have an impact on suggested adipoinsular axis, contributing to maintenance of normal glucose tolerance.

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

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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.

The role of stress hormones in the relationship between resting blood pressure and coagulation activity.

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Wirtz, Petra H; Ehlert, Ulrike; Emini, Luljeta; Rüdisüli, Katharina; Groessbauer, Sara; Mausbach, Brent T; von Känel, Roland

2006-12-01

Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress. We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress. At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI. MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.

Comparison of Paired ROC Curves through a Two-Stage Test.

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Yu, Wenbao; Park, Eunsik; Chang, Yuan-Chin Ivan

2015-01-01

The area under the receiver operating characteristic (ROC) curve (AUC) is a popularly used index when comparing two ROC curves. Statistical tests based on it for analyzing the difference have been well developed. However, this index is less informative when two ROC curves cross and have similar AUCs. In order to detect differences between ROC curves in such situations, a two-stage nonparametric test that uses a shifted area under the ROC curve (sAUC), along with AUCs, is proposed for paired designs. The new procedure is shown, numerically, to be effective in terms of power under a wide range of scenarios; additionally, it outperforms two conventional ROC-type tests, especially when two ROC curves cross each other and have similar AUCs. Larger sAUC implies larger partial AUC at the range of low false-positive rates in this case. Because high specificity is important in many classification tasks, such as medical diagnosis, this is an appealing characteristic. The test also implicitly analyzes the equality of two commonly used binormal ROC curves at every operating point. We also apply the proposed method to synthesized data and two real examples to illustrate its usefulness in practice.

Process for obtaining ammonium uranyl tri carbonate

International Nuclear Information System (INIS)

Santos, L.R. dos; Riella, H.G.

1992-01-01

The procedure adopted for obtaining Ammonium Uranyl Carbonate (AUC) from uranium hexafluoride (U F 6 ) in a aqueous solutions of ammonium hydrogen carbonate is described in this work. The precipitation is made in temperature and pH controlled. This process consists of three steps: evaporation of U F 6 , AUC precipitation and filtration of the AUC slurry. An attempt is made of correlate the parameters involved in the precipitation process of AUC with its and U O 2 characteristics. (author)

Limited-sampling strategies for anidulafungin in critically ill patients

NARCIS (Netherlands)

van Wanrooy, Marjolijn J.P.; Proost, Johannes H.; Rodgers, Michael G. G.; Zijlstra, Jan G.; Uges, Donald R.A.; Kosterink, Jos G.W.; van der Werf, Tjip S.; Alffenaar, Jan-Willem C.

2015-01-01

Efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Determination of the anidulafungin AUC along with MIC values can therefore be useful. Since obtaining a full concentration-time curve to determine an AUC is not always feasible or appropriate,

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

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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.

Comparative analysis of anthropometric indices of obesity as correlates and potential predictors of risk for hypertension and prehypertension in a population in Nigeria.

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Ononamadu, Chimaobi James; Ezekwesili, Chinwe Nonyelum; Onyeukwu, Onyemaechi Faith; Umeoguaju, Uchenna Francis; Ezeigwe, Obiajulu Christian; Ihegboro, Godwin Okwudiri

Obesity is a well-established independent risk factor for hypertension and other cardiometabolic disorders. However, the best anthropometric index of obesity that predicts or associates strongly with hypertension and related conditions remains controversial and inconclusive. This study compared the performance of eight anthropometric indices of obesity: body mass index (BMI), ponderal index (PI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), waist-height ratio (WHtR), body adiposity index (BAI) and conicity index (CI) as correlates and potential predictors of risk of hypertension and prehypertension in a Nigerian population, and also the possible effect of combining two or more indices in that regard. This church-based, cross-sectional study was conducted in Anambra state, south-eastern Nigeria from 2012 to 2013. A total of 912 persons (436 male and 476 female) drawn randomly from three major cities (Awka, Onitsha and Nnewi) in the state participated in the study. Information on demography, medical history and lifestyle were obtained using a well-structured and validated questionnaire. The systolic/diastolic blood pressure and anthropometric measurements were taken by well-trained personnel. The resulting data were analysed using descriptive statistics, logistic regression, Poisson regression and receiver operating characteristic curve analysis. The mean values of all the anthropometric indices studied increased from normotension, through prehypertension to hypertension in both genders. BMI, WC, HC and CI were significantly higher (p blood pressure. BMI, WHtR, WC and PI (with higher correlation coefficients for blood pressure) showed the best potential to predict hypertension and prehypertension in the study: BMI (cut-off = 24.49, AUC = 0.698; cut-off = 23.62, AUC = 0.659), WHtR (cut-off = 0.55, AUC = 0.682; cut-off = 0.5, AUC = 0.636), WC (cut-off = 91.44, AUC = 0.692; cut-off = 82.55, AUC = 0.645), PI (cut-off = 14.45, AUC = 0.670; cut

Immunological and cardiometabolic risk factors in the prediction of type 2 diabetes and coronary events: MONICA/KORA Augsburg case-cohort study.

Directory of Open Access Journals (Sweden)

Christian Herder

Full Text Available BACKGROUND: This study compares inflammation-related biomarkers with established cardiometabolic risk factors in the prediction of incident type 2 diabetes and incident coronary events in a prospective case-cohort study within the population-based MONICA/KORA Augsburg cohort. METHODS AND FINDINGS: Analyses for type 2 diabetes are based on 436 individuals with and 1410 individuals without incident diabetes. Analyses for coronary events are based on 314 individuals with and 1659 individuals without incident coronary events. Mean follow-up times were almost 11 years. Areas under the receiver-operating characteristic curve (AUC, changes in Akaike's information criterion (ΔAIC, integrated discrimination improvement (IDI and net reclassification index (NRI were calculated for different models. A basic model consisting of age, sex and survey predicted type 2 diabetes with an AUC of 0.690. Addition of 13 inflammation-related biomarkers (CRP, IL-6, IL-18, MIF, MCP-1/CCL2, IL-8/CXCL8, IP-10/CXCL10, adiponectin, leptin, RANTES/CCL5, TGF-β1, sE-selectin, sICAM-1; all measured in nonfasting serum increased the AUC to 0.801, whereas addition of cardiometabolic risk factors (BMI, systolic blood pressure, ratio total/HDL-cholesterol, smoking, alcohol, physical activity, parental diabetes increased the AUC to 0.803 (ΔAUC [95% CI] 0.111 [0.092-0.149] and 0.113 [0.093-0.149], respectively, compared to the basic model. The combination of all inflammation-related biomarkers and cardiometabolic risk factors yielded a further increase in AUC to 0.847 (ΔAUC [95% CI] 0.044 [0.028-0.066] compared to the cardiometabolic risk model. Corresponding AUCs for incident coronary events were 0.807, 0.825 (ΔAUC [95% CI] 0.018 [0.013-0.038] compared to the basic model, 0.845 (ΔAUC [95% CI] 0.038 [0.028-0.059] compared to the basic model and 0.851 (ΔAUC [95% CI] 0.006 [0.003-0.021] compared to the cardiometabolic risk model, respectively. CONCLUSIONS: Inclusion of multiple

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

International Nuclear Information System (INIS)

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

2015-01-01

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.)

Digital image analysis supports a nuclear-to-cytoplasmic ratio cutoff value of 0.5 for atypical urothelial cells.

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Hang, Jen-Fan; Charu, Vivek; Zhang, M Lisa; VandenBussche, Christopher J

2017-09-01

An elevated nuclear-to-cytoplasmic (N:C) ratio of ≥0.5 is a required criterion for the diagnosis of atypical urothelial cells (AUC) in The Paris System for Reporting Urinary Cytology. To validate the N:C ratio cutoff value and its predictive power for high-grade urothelial carcinoma (HGUC), the authors retrospectively reviewed the urinary tract cytology specimens of 15 cases of AUC with HGUC on follow-up (AUC-HGUC) and 33 cases of AUC without HGUC on follow-up (AUC-N-HGUC). The number of atypical cells in each case was recorded, and each atypical cell was photographed and digitally examined to calculate the nuclear size and N:C ratio. On average, the maximum N:C ratios of atypical cells were significantly different between the AUC-HGUC and AUC-N-HGUC cohorts (0.53 vs 0.43; P =.00009), whereas the maximum nuclear sizes of atypical cells (153.43 μM 2 vs 201.47 μM 2 ; P = .69) and the number of atypical cells per case (10.13 vs 7.88; P = .12) were not found to be significantly different. Receiver operating characteristic analysis demonstrated that the maximum N:C ratio alone had high discriminatory capacity (area under the curve, 79.19%; 95% confidence interval, 64.19%-94.19%). The optimal maximum N:C ratio threshold was 0.486, giving a sensitivity of 73.3% and a specificity of 84.8% for predicting HGUC on follow-up. The identification of AUC with an N:C ratio >0.486 has a high predictive power for HGUC on follow-up in AUC specimens. This justifies using the N:C ratio as a required criterion for the AUC category. Individual laboratories using different cytopreparation methods may require independent validation of the N:C ratio cutoff value. Cancer Cytopathol 2017;125:710-6. © 2017 American Cancer Society. © 2017 American Cancer Society.

Comparison of sedation and mechanical antinociception induced by intravenous administration of acepromazine and four dose rates of dexmedetomidine in donkeys.

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Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Robinson, Lauren S

2017-05-01

To assess and compare the sedative and antinociceptive effects of four dosages of dexmedetomidine in donkeys. Randomized, controlled, crossover, Latin-square, blinded study. Six healthy, castrated, adult, standard donkeys. Dexmedetomidine (2, 3, 4 and 5 μg kg -1 ; D2, D3, D4 and D5), acepromazine (0.1 mg kg -1 ) and saline were administered intravenously to each donkey and a 1 week interval was allowed between successive trials on each animal. Sedation scores (SS) and head heights above ground (HHAG) were used to assess sedation and mechanical nociceptive threshold (MNT) testing to assess antinociception over 120 minutes post-treatment. Areas under the curve (AUC) for 0-30, 30-60 and 60-120 minutes were computed to compare the effect of treatments. SS-AUC 0-30 values were larger for D4 and D5, and SS-AUC 30-60 values were larger for D5 than for saline. All dexmedetomidine treatments produced lower HHAG-AUC 0-30 and HHAG-AUC 30-60 values, and acepromazine produced lower HHAG AUC 60-120 values than did saline. For MNT, D3, D4 and D5 increased AUC 0-30 and AUC 30-60 values compared with saline and also AUC 0-30 values compared with D2 and acepromazine. Smaller MNT-AUC 30-60 values were obtained with D2 than with D4 and D5, with D3 than with D5, and with acepromazine than with D4 and D5. Dexmedetomidine induced sedation and dosage-dependent mechanical antinociception. Larger dexmedetomidine dose rates were required to induce antinociception than sedation. Furthermore, the antinociception induced by dexmedetomidine was of shorter duration than its sedation. For minor painful procedures on standing donkeys, D5 may be clinically useful to provide sedation and analgesia. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

A comparison of the accuracy of film-screen mammography, full-field digital mammography, and digital breast tomosynthesis

International Nuclear Information System (INIS)

Michell, M.J.; Iqbal, A.; Wasan, R.K.; Evans, D.R.; Peacock, C.; Lawinski, C.P.; Douiri, A.; Wilson, R.; Whelehan, P.

2012-01-01

Aim: To measure the change in diagnostic accuracy of conventional film-screen mammography and full-field digital mammography (FFDM) with the addition of digital breast tomosynthesis (DBT) in women recalled for assessment following routine screening. Materials and methods: Ethics approval for the study was granted. Women recalled for assessment following routine screening with screen-film mammography were invited to participate. Participants underwent bilateral, two-view FFDM and two-view DBT. Readers scored each lesion separately for probability of malignancy on screen-film mammography, FFDM, and then DBT. The scores were compared with the presence or absence of malignancy based on the final histopathology outcome. Results: Seven hundred and thirty-eight women participated (93.2% recruitment rate). Following assessment 204 (26.8%) were diagnosed as malignant (147 invasive and 57 in-situ tumours), 286 (37.68%) as benign, and 269 (35.4%) as normal. The diagnostic accuracy was evaluated by using receiving operating characteristic (ROC) and measurement of area under the curve (AUC). The AUC values demonstrated a significant (p = 0.0001) improvement in the diagnostic accuracy with the addition of DBT combined with FFDM and film-screen mammography (AUC = 0.9671) when compared to FFDM plus film-screen mammography (AUC = 0.8949) and film-screen mammography alone (AUC = 0.7882). The effect was significantly greater for soft-tissue lesions [AUC was 0.9905 with the addition of DBT and AUC was 0.9201 for FFDM with film-screen mammography combined (p = 0.0001)] compared to microcalcification [with the addition of DBT (AUC = 0.7920) and for FFDM with film-screen mammography combined (AUC = 0.7843; p = 0.3182)]. Conclusion: The addition of DBT increases the accuracy of mammography compared to FFDM and film-screen mammography combined and film-screen mammography alone in the assessment of screen-detected soft-tissue mammographic abnormalities.

Hyperglycemic clamp and oral glucose tolerance test for 3-year prediction of clinical onset in persistently autoantibody-positive offspring and siblings of type 1 diabetic patients.

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Balti, Eric V; Vandemeulebroucke, Evy; Weets, Ilse; Van De Velde, Ursule; Van Dalem, Annelien; Demeester, Simke; Verhaeghen, Katrijn; Gillard, Pieter; De Block, Christophe; Ruige, Johannes; Keymeulen, Bart; Pipeleers, Daniel G; Decochez, Katelijn; Gorus, Frans K

2015-02-01

In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb(+)) offspring and siblings of patients with type 1 diabetes (T1D). The design is a registry-based study. Functional tests were performed in a hospital setting. Persistently autoAb(+) first-degree relatives of patients with T1D (n = 81; age 5-39 years). We assessed 3-year predictive ability of OGTT- and clamp-derived markers using receiver operating characteristics (ROC) and Cox regression analysis. Area under the curve of clamp-derived first-phase C-peptide release (AUC(5-10 min); min 5-10) was determined in all relatives and second-phase release (AUC(120-150 min); min 120-150) in those aged 12-39 years (n = 62). Overall, the predictive ability of AUC(5-10 min) was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80-0.98] vs 0.81 [0.70-0.93]). Fasting blood glucose (FBG) and AUC(5-10 min) provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84-1.00]). In multivariate Cox regression analysis, AUC(5-10 min)) (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC(5-10 min) below percentile 10 of controls was associated with 50-70% progression to T1D regardless of age. Similar results were obtained for AUC(120-150 min). Clamp-derived first-phase C-peptide release can be used as an efficient and simple screening strategy in persistently autoAb(+) offspring and siblings of T1D patients to predict impending diabetes.

Anthropometric Indicators as Body Fat Discriminators in Children and Adolescents: A Systematic Review and Meta-Analysis.

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Alves Junior, Carlos As; Mocellin, Michel C; Gonçalves, Eliane C Andrade; Silva, Diego As; Trindade, Erasmo Bsm

2017-09-01

We analyzed the discriminatory capacity of anthropometric indicators for body fat in children and adolescents. This systematic review and meta-analysis included cross-sectional and clinical studies comprising children and adolescents aged 2-19 y that tested the discriminatory value for body fat measured by anthropometric methods or indexes generated by anthropometric variables compared with precision methods in the diagnosis of body fat [dual-energy X-ray absorptiometry (DXA), computed tomography, air displacement plethysmography (ADP), or MRI]. Five studies met the eligibility criteria and presented high methodologic quality. The anthropometric indicators that had high discriminatory power to identify high body fat were body mass index (BMI) in males [area under the curve (AUC): 0.975] and females (AUC: 0.947), waist circumference (WC) in males (AUC: 0.975) and females (AUC: 0.959), and the waist-to-height ratio (WTHR) in males (AUC: 0.897) and females (AUC: 0.914). BMI, WC, and WTHR can be used by health professionals to assess body fat in children and adolescents. © 2017 American Society for Nutrition.

Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoural FDG uptake in non-small cell lung cancer PET studies

International Nuclear Information System (INIS)

Velden, Floris H.P. van; Cheebsumon, Patsuree; Yaqub, Maqsood; Hoekstra, Otto S.; Lammertsma, Adriaan A.; Boellaard, Ronald; Smit, Egbert F.

2011-01-01

Standardized uptake values (SUV) are commonly used for quantification of whole-body [ 18 F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) studies. Changes in SUV following therapy, however, only provide a proper measure of response in case of homogeneous FDG uptake in the tumour. The purpose of this study was therefore to implement and characterize a method that enables quantification of heterogeneity in tumour FDG uptake. Cumulative SUV-volume histograms (CSH), describing % of total tumour volume above % threshold of maximum SUV (SUV max ), were calculated. The area under a CSH curve (AUC) is a quantitative index of tumour uptake heterogeneity, with lower AUC corresponding to higher degrees of heterogeneity. Simulations of homogeneous and heterogeneous responses were performed to assess the value of AUC-CSH for measuring uptake and/or response heterogeneity. In addition, partial volume correction and image denoising was applied prior to calculating AUC-CSH. Finally, the method was applied to a number of human FDG scans. Partial volume correction and noise reduction improved CSH curves. Both simulations and clinical examples showed that AUC-CSH values corresponded with level of tumour heterogeneity and/or heterogeneity in response. In contrast, this correspondence was not seen with SUV max alone. The results indicate that the main advantage of AUC-CSH above other measures, such as 1/COV (coefficient of variation), is the possibility to measure or normalize AUC-CSH in different ways. AUC-CSH might be used as a quantitative index of heterogeneity in tracer uptake. In response monitoring studies it can be used to address heterogeneity in response. (orig.)

Features of time–intensity curve parameters of colorectal adenocarcinomas evaluated by double-contrast enhanced ultrasonography: Initial observation

International Nuclear Information System (INIS)

Zhuang Hua; Yang Zhigang; Wang Ziqiang; Wang Xiaodong; Chen Huijiao; Zhang Yuanchuan; Luo Yan

2012-01-01

Purpose: This study is to investigate the value of double contrast-enhanced ultrasonography (DCEU) in assessing microcirculation of colorectal adenocarcinomas and to describe the perfusion features of the tumours. Material and methods: DCEUS was performed in 42 patients with adenocarcinoma. The time–intensity curve parameters (arrival time (AT), time-to-peak (TTP), peak intensity (PI) and area under the curve (AUC)) within the tumours were extracted. The parameters were compared among the tumours with different CEUS features and stages. Results: The mean values of AT, TTP, PI and AUC of the colorectal adenocarcinomas were 13.68 ± 13.36 s, 32.61 ± 19.56 s, 19.82 ± 16.54 dB and 271.10 ± 159.19 dB s, respectively. In the adenocarcinomas with necrosis, the mean values of AUC was significantly lower than that of the adenocarcinomas without (231.10 ± 219.27 dB s, 278.10 ± 123.20 dB s, p = 0.004). In the adenocarcinomas with necrosis, the AUC and PI of the non-necrotic part were significantly higher than that of the necrotic part (p = 0.007, 0.0025, respectively). AUC increased progressively in the subgroups of T2, T3 and T4 and the difference of AUC between T2 and T4 subgroup was significant (p = 0.008). Conclusions: Double contrast-enhanced ultrasonography is a valuable technique for quantifying tumour vascularity of colorectal adenocarcinomas. AUC was significantly different in the subgroups of different T stage. AUC and PI could reflect the different perfusion status of tumours with or without necrosis.

Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.

Science.gov (United States)

Hammami, Muhammad M; Yusuf, Ahmed; Shire, Faduma S; Hussein, Rajaa; Al-Swayeh, Reem

2017-05-23

Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug bioavailability; it was previously observed that being aware of caffeine ingestion may prolong caffeine plasma half-life. This study was set to evaluate such concept using different drugs. Balanced single-dose, two-period, two-group, cross-over design was used to compare the pharmacokinetics of oral cephalexin, ibuprofen, and paracetamol, each described by its name (overt) or as placebo (covert). Volunteers and study coordinators were deceived as to study aim. Drug concentrations were determined blindly by in-house, high performance liquid chromatography assays. Terminal-elimination half-life (t ½ ) (primary outcome), maximum concentration (C max ), C max first time (T max ), terminal-elimination-rate constant (λ), area-under-the-concentration-time-curve, to last measured concentration (AUC T ), extrapolated to infinity (AUC I ), or to T max of overt drug (AUC Overttmax ), and C max /AUC I were calculated blindly using standard non-compartmental method. Covert-vs-overt effect on drug pharmacokinetics was evaluated by analysis-of-variance (ANOVA, primary analysis), 90% confidence interval (CI) using the 80.00-125.00% bioequivalence range, and percentage of individual pharmacokinetic covert/overt ratios that are outside the +25% range. Fifty, 30, and 50 healthy volunteers (18%, 10%, and 6% females, mean (SD) age 30.8 (6.2), 31.4 (6.6), and 31.2 (5.4) years) participated in 3 studies on cephalexin, ibuprofen, and paracetamol, respectively. Withdrawal rate was 4%, 0%, and 4%, respectively. Eighteen blood samples were obtained over 6, 10, and 14 h in each study period of the three drugs, respectively. ANOVA showed no significant difference in any pharmacokinetic parameter for any of the drugs. The 90% CIs for AUC T , AUC I , C max , AUC Overttmax , and C max /AUC I were within the bioequivalence range, except

Optimized approach to decision fusion of heterogeneous data for breast cancer diagnosis

International Nuclear Information System (INIS)

Jesneck, Jonathan L.; Nolte, Loren W.; Baker, Jay A.; Floyd, Carey E.; Lo, Joseph Y.

2006-01-01

As more diagnostic testing options become available to physicians, it becomes more difficult to combine various types of medical information together in order to optimize the overall diagnosis. To improve diagnostic performance, here we introduce an approach to optimize a decision-fusion technique to combine heterogeneous information, such as from different modalities, feature categories, or institutions. For classifier comparison we used two performance metrics: The receiving operator characteristic (ROC) area under the curve [area under the ROC curve (AUC)] and the normalized partial area under the curve (pAUC). This study used four classifiers: Linear discriminant analysis (LDA), artificial neural network (ANN), and two variants of our decision-fusion technique, AUC-optimized (DF-A) and pAUC-optimized (DF-P) decision fusion. We applied each of these classifiers with 100-fold cross-validation to two heterogeneous breast cancer data sets: One of mass lesion features and a much more challenging one of microcalcification lesion features. For the calcification data set, DF-A outperformed the other classifiers in terms of AUC (p 0.10), the DF-P did significantly improve specificity versus the LDA at both 98% and 100% sensitivity (p<0.04). In conclusion, decision fusion directly optimized clinically significant performance measures, such as AUC and pAUC, and sometimes outperformed two well-known machine-learning techniques when applied to two different breast cancer data sets

Area under the curve predictions of dalbavancin, a new lipoglycopeptide agent, using the end of intravenous infusion concentration data point by regression analyses such as linear, log-linear and power models.

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Bhamidipati, Ravi Kanth; Syed, Muzeeb; Mullangi, Ramesh; Srinivas, Nuggehally

2018-02-01

1. Dalbavancin, a lipoglycopeptide, is approved for treating gram-positive bacterial infections. Area under plasma concentration versus time curve (AUC inf ) of dalbavancin is a key parameter and AUC inf /MIC ratio is a critical pharmacodynamic marker. 2. Using end of intravenous infusion concentration (i.e. C max ) C max versus AUC inf relationship for dalbavancin was established by regression analyses (i.e. linear, log-log, log-linear and power models) using 21 pairs of subject data. 3. The predictions of the AUC inf were performed using published C max data by application of regression equations. The quotient of observed/predicted values rendered fold difference. The mean absolute error (MAE)/root mean square error (RMSE) and correlation coefficient (r) were used in the assessment. 4. MAE and RMSE values for the various models were comparable. The C max versus AUC inf exhibited excellent correlation (r > 0.9488). The internal data evaluation showed narrow confinement (0.84-1.14-fold difference) with a RMSE models predicted AUC inf with a RMSE of 3.02-27.46% with fold difference largely contained within 0.64-1.48. 5. Regardless of the regression models, a single time point strategy of using C max (i.e. end of 30-min infusion) is amenable as a prospective tool for predicting AUC inf of dalbavancin in patients.

Muscle stiffness at different force levels measured with two myotonometric devices

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Jarocka, Ewa; Marusiak, Jarosław; Kumorek, Martyna; Jaskólska, Anna; Jaskólski, Artur

2012-01-01

Myotonometric measurements are quantitative methods of muscle tone assessment and may be used as an alternative for palpation evaluation. The objective of the study was to compare the measurements of brachioradialis muscle tone and stiffness using the Myoton-3 and the Myotonometer. The participants were young males (N = 17, mean age 21 ± 1 years). The skeletal muscle state was expressed by the Myoton-3 parameters stiffness (N m −1 ), frequency (Hz) and decrement (no unit) and the Myotonometer's area under the curve (AUC) parameter (area under the curve, no unit), when muscle was at rest and during activity at 25%, 50%, 80% and 100% of maximal voluntary contraction for elbow flexors. Pearson's correlation between AUC and stiffness is r = −0.89, AUC and frequency r = −0.84 and AUC and decrement r = 0.79, p < 0.01. When comparing the results from each experimental condition separately for frequency and AUC, the correlation was from −0.63 to −0.80, for stiffness and AUC it ranged from −0.25 to −0.75 and for decrement and AUC from 0.27 to 0.74. The degree of correlation between myotonometric measurements depends on whether the measured muscle is at rest or during contraction. The correlation is diverse among related parameters. (paper)

Short-term glucagon stimulation test of C-peptide effect on glucose utilization in patients with type 1 diabetes mellitus.

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Mojto, Viliam; Rausova, Zuzana; Chrenova, Jana; Dedik, Ladislav

2015-12-01

This work aimed to evaluate the use of a four-point glucagon stimulation test of C-peptide effect on glucose utilization in type 1 diabetic patients using a new mathematical model. A group of 32 type 1 diabetic patients and a group of 10 healthy control subjects underwent a four-point glucagon stimulation test with blood sampling at 0, 6, 15 and 30 min after 1 mg glucagon bolus intravenous administration. Pharmacokinetic and pharmacokinetic/pharmacodynamic models of C-peptide effect on glucose utilization versus area under curve (AUC) were used. A two-sample t test and ANOVA with Bonferroni correction were used to test the significance of differences between parameters. A significant difference between control and patient groups regarding the coefficient of whole-body glucose utilization and AUC C-peptide/AUC glucose ratio (p ≪ 0.001 and p = 0.002, respectively) was observed. The high correlation (r = 0.97) between modeled coefficient of whole-body glucose utilization and numerically calculated AUC C-peptide/AUC glucose ratio related to entire cohort indicated the stability of used method. The short-term four-point glucagon stimulation test allows the numerically calculated AUC C-peptide/AUC glucose ratio and/or the coefficient of whole-body glucose utilization calculated from model to be used to diagnostically identify type 1 diabetic patients.

Severity of Carpal Tunnel Syndrome and Diagnostic Accuracy of Hand and Body Anthropometric Measures.

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Mauro Mondelli

Full Text Available To study the diagnostic properties of hand/wrist and body measures according to validated clinical and electrophysiological carpal tunnel syndrome (CTS severity scales.We performed a prospective case-control study. For each case, two controls were enrolled. Two five-stage clinical and electrophysiological scales were used to evaluate CTS severity. Anthropometric measurements were collected and obesity indicators and hand/wrist ratios were calculated. Area under the receiver operating characteristic curves (AUC, sensitivity, specificity, and likelihood ratios were calculated separately by gender.We consecutively enrolled 370 cases and 747 controls. The wrist-palm ratio, waist-hip-height ratio and waist-stature ratio showed the highest proportion of cases with abnormal values in the severe stages of CTS for clinical and electrophysiological severity scales in both genders. Accuracy tended to increase with CTS severity for females and males. In severe stage, most of the indexes presented moderate accuracy in both genders. Among subjects with severe CTS, the wrist-palm ratio presented the highest AUC for hand measures in the clinical and electrophysiological severity scales both in females (AUC 0.83 and 0.76, respectively and males (AUC 0.91 and 0.82, respectively. Among subjects with severe CTS, the waist-stature ratio showed the highest AUC for body measures in the clinical and electrophysiological severity scales both in females (AUC 0.78 and 0.77, respectively and males (AUC 0.84 and 0.76, respectively. The results of waist-hip-height ratio AUC were similar.Wrist-palm ratio, waist-hip-height ratio and waist-stature ratio could contribute to support the diagnostic hypothesis of severe CTS that however has to be confirmed by nerve conduction study.

Applicability of a Single Time Point Strategy for the Prediction of Area Under the Concentration Curve of Linezolid in Patients: Superiority of Ctrough- over Cmax-Derived Linear Regression Models.

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Srinivas, Nuggehally R; Syed, Muzeeb

2016-03-01

Linezolid, a oxazolidinone, was the first in class to be approved for the treatment of bacterial infections arising from both susceptible and resistant strains of Gram-positive bacteria. Since overt exposure of linezolid may precipitate serious toxicity issues, therapeutic drug monitoring (TDM) may be required in certain situations, especially in patients who are prescribed other co-medications. Using appropriate oral pharmacokinetic data (single dose and steady state) for linezolid, both maximum plasma drug concentration (Cmax) versus area under the plasma concentration-time curve (AUC) and minimum plasma drug concentration (Cmin) versus AUC relationship was established by linear regression models. The predictions of the AUC values were performed using published mean/median Cmax or Cmin data and appropriate regression lines. The quotient of observed and predicted values rendered fold difference calculation. The mean absolute error (MAE), root mean square error (RMSE), correlation coefficient (r), and the goodness of the AUC fold prediction were used to evaluate the two models. The Cmax versus AUC and trough plasma concentration (Ctrough) versus AUC 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 versus observed values and RMSE (r = 0.9031; 28.54%, respectively) compared with the Cmax model (r = 0.5824; 61.34%, respectively). A single time point strategy of using Ctrough level is possible as a prospective tool to measure the AUC of linezolid in the patient population.

Relationship between the cortisol awakening response and other features of the diurnal cortisol rhythm: the Multi-Ethnic Study of Atherosclerosis.

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Golden, Sherita Hill; Sánchez, Brisa N; Wu, Meihua; Champaneri, Shivam; Diez Roux, Ana V; Seeman, Teresa; Wand, Gary S

2013-11-01

Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and Black individuals (mean age 65 ± 9.8 years) in the Multi-Ethnic Study of Atherosclerosis. Outcome measures included awakening cortisol, CAR (awakening to 30 min post-awakening), early decline (30 min to 2h post-awakening), late decline (2h post-awakening to bedtime), and the corresponding AUCs. Total cortisol AUC was a summary measure of cumulative cortisol exposure. Higher CAR was associated with significantly lower wake-up cortisol (β=-0.56; 95% CI: -0.59 to -0.53) and a higher early decline AUC (β=0.38; 95% CI: 0.34-0.42) but was not associated with total cortisol AUC (β=0.04; 95% CI: -0.01 to 0.09), or other diurnal cortisol curve components following multivariable adjustment. Total cortisol AUC was significantly and positively associated with wake-up cortisol (β=0.36; 95% CI: 0.32-0.40), bedtime cortisol (β=0.61; 95% CI: 0.58-0.64), and other AUC measures, following multivariable adjustment. Associations were similar by sex, race/ethnicity, and age categories. We conclude that bedtime cortisol showed the strongest correlation with total cortisol AUC, suggesting it may be a marker of daily cortisol exposure. Copyright © 2013 Elsevier Ltd. All rights reserved.

Slow recovery of blood glucose in the insulin tolerance test during the prepartum transition period negatively impacts the nutritional status and reproductive performance postpartum of dairy cows.

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Lee, Hsu-Hsun; Kida, Katsuya; Miura, Ryotaro; Inokuma, Hisashi; Miyamoto, Akio; Kawashima, Chiho; Haneda, Shingo; Miyake, Yoh-Ichi; Matsui, Motozumi

2012-04-01

In peripartum dairy cows, insulin resistance (IR) increases to adjust the direction of energy to lactation after calving. To investigate the effect of prepartum IR on postpartum reproductive performance, the insulin tolerance test (ITT) was applied to 15 cows at 3 weeks (Pre21) and 10 days (Pre10) before the predicted calving date. Blood glucose area under the curve (AUC(glu)) within 120 min after administration of 0.05 IU/kg-BW insulin was calculated. The occurrence of first ovulation, days to first artificial insemination (AI) and first AI conception rate were recorded. Nutritional status postpartum was evaluated by blood chemical analysis. Based on AUC(glu) changes from Pre21 to Pre10, cows were classified into either the AUC-up group (AUC(glu) increase, n=5) or the AUC-down group (AUC(glu) decrease, n=10). There was no difference in the decrease in blood glucose at 30 min after insulin injection between groups, although glucose recovery from 30 to 60 min during the ITT was slow at Pre10 in the AUC-up group. The AUC-up group had a higher number of days to first AI and high glucose, total protein, globulin, γ-glutamyltransferase, triacylglycerol levels and a low albumin-globulin ratio at the 14th day postpartum. The present study infers that prepartum slow glucose recovery rather than insulin sensitivity might increase the potential for subclinical health problems postpartum and thus suppress reproductive performance. During the prepartum transition period, glucose dynamics in the ITT can be considered as a new indicator for the postpartum metabolic status and reproductive performance of dairy cows.

Association of Anthropometric Measurement Methods with Cardiovascular Disease Risk in Turkey

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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.

Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoural FDG uptake in non-small cell lung cancer PET studies

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Velden, Floris H.P. van; Cheebsumon, Patsuree; Yaqub, Maqsood; Hoekstra, Otto S.; Lammertsma, Adriaan A.; Boellaard, Ronald [VU University Medical Center, Department of Nuclear Medicine and PET Research, PO Box 7057, Amsterdam (Netherlands); Smit, Egbert F. [VU University Medical Center, Department of Pulmonary Diseases, Amsterdam (Netherlands)

2011-09-15

Standardized uptake values (SUV) are commonly used for quantification of whole-body [{sup 18}F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) studies. Changes in SUV following therapy, however, only provide a proper measure of response in case of homogeneous FDG uptake in the tumour. The purpose of this study was therefore to implement and characterize a method that enables quantification of heterogeneity in tumour FDG uptake. Cumulative SUV-volume histograms (CSH), describing % of total tumour volume above % threshold of maximum SUV (SUV{sub max}), were calculated. The area under a CSH curve (AUC) is a quantitative index of tumour uptake heterogeneity, with lower AUC corresponding to higher degrees of heterogeneity. Simulations of homogeneous and heterogeneous responses were performed to assess the value of AUC-CSH for measuring uptake and/or response heterogeneity. In addition, partial volume correction and image denoising was applied prior to calculating AUC-CSH. Finally, the method was applied to a number of human FDG scans. Partial volume correction and noise reduction improved CSH curves. Both simulations and clinical examples showed that AUC-CSH values corresponded with level of tumour heterogeneity and/or heterogeneity in response. In contrast, this correspondence was not seen with SUV{sub max} alone. The results indicate that the main advantage of AUC-CSH above other measures, such as 1/COV (coefficient of variation), is the possibility to measure or normalize AUC-CSH in different ways. AUC-CSH might be used as a quantitative index of heterogeneity in tracer uptake. In response monitoring studies it can be used to address heterogeneity in response. (orig.)

Effects of oatmeal and corn flakes cereal breakfasts on satiety, gastric emptying, glucose, and appetite-related hormones.

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Geliebter, Allan; Grillot, Charlotte L; Aviram-Friedman, Roni; Haq, Sakeena; Yahav, Eric; Hashim, Sami A

2015-01-01

The extent to which different types of breakfasts affect appetite and food intake is unclear. To assess the satiety effects of a high-fiber cereal, we compared oatmeal, isocaloric corn flakes, and water. Thirty-six subjects (18 lean, 18 overweight) were assigned to three conditions in a randomized sequence on different days. Ratings of hunger and fullness were obtained concurrently with blood samples for measuring concentrations of glucose, insulin, glucagon, leptin, and acetaminophen (gastric emptying tracer). Appetite was assessed by calculating the area under the curve (AUC) for fullness and hunger, and by measuring food intake of an ad libitum lunch meal at 180 min. Lunch meal intake was lowest after consuming oatmeal (p AUC was greatest (p = 0.00001), and hunger AUC lowest (p blood glucose was lowest after the corn flakes (p = 0.0001). Insulin AUC was greater for both cereals than water (p AUC and glucagon AUC values did not differ between conditions. Acetaminophen concentrations peaked latest after consuming oatmeal (p = 0.046), reflecting slower gastric emptying. Satiety was greater and ad libitum test meal intake lower after consuming oatmeal than after corn flakes, especially in the overweight subjects. © 2015 S. Karger AG, Basel.

Manufacture of uranium dioxide powder

International Nuclear Information System (INIS)

Becker, M.

1976-01-01

Uranium dioxide powder is prepared by the AUC (ammonium uranyl carbonate) method. Supplementing the known process steps, the AUC, after separation from the mother liquor, is washed with an ammonium hydrogen carbonate or an NH 4 OH solution and is subsequently post-treated with a liquid which reduces the surface tension of the residual water in an AUC. Such a liquid is, for instance, alcohol

Second-meal effects of pulses on blood glucose and subjective appetite following a standardized meal 2 h later.

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Mollard, Rebecca C; Wong, Christina L; Luhovyy, Bohdan L; Cho, France; Anderson, G Harvey

2014-07-01

This study investigated whether pulses (chickpeas, yellow peas, navy beans, lentils) have an effect on blood glucose (BG) and appetite following a fixed-size meal 2 h later. Over the following 2 h, all pulses lowered BG area under the curve (AUC) and lentils reduced appetite AUC compared with white bread (p AUC was lower after lentils compared with white bread (p < 0.05).

Accuracy of Four Imaging Techniques for Diagnosis of Posterior Pelvic Floor Disorders.

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van Gruting, Isabelle M A; Stankiewicz, Aleksandra; Kluivers, Kirsten; De Bin, Riccardo; Blake, Helena; Sultan, Abdul H; Thakar, Ranee

2017-11-01

To establish the diagnostic test accuracy of evacuation proctography, magnetic resonance imaging (MRI), transperineal ultrasonography, and endovaginal ultrasonography for detecting posterior pelvic floor disorders (rectocele, enterocele, intussusception, and anismus) in women with obstructed defecation syndrome and secondarily to identify the most patient-friendly imaging technique. In this prospective cohort study, 131 women with symptoms of obstructed defecation syndrome underwent evacuation proctogram, MRI, and transperineal and endovaginal ultrasonography. Images were analyzed by two blinded observers. In the absence of a reference standard, latent class analysis was used to assess diagnostic test accuracy of multiple tests with area under the curve (AUC) as the primary outcome measure. Secondary outcome measures were interobserver agreement calculated as Cohen's κ and patient acceptability using a visual analog scale. No significant differences in diagnostic accuracy were found among the imaging techniques for all the target conditions. Estimates of diagnostic test accuracy were highest for rectocele using MRI (AUC 0.79) or transperineal ultrasonography (AUC 0.85), for enterocele using transperineal (AUC 0.73) or endovaginal ultrasonography (AUC 0.87), for intussusception using evacuation proctography (AUC 0.76) or endovaginal ultrasonography (AUC 0.77), and for anismus using endovaginal (AUC 0.95) or transperineal ultrasonography (AUC 0.78). Interobserver agreement for the diagnosis of rectocele (κ 0.53-0.72), enterocele (κ 0.54-0.94) and anismus (κ 0.43-0.81) was moderate to excellent, but poor to fair for intussusception (κ -0.03 to 0.37) with all techniques. Patient acceptability was better for transperineal and endovaginal ultrasonography as compared with MRI and evacuation proctography (P<.001). Evacuation proctography, MRI, and transperineal and endovaginal ultrasonography were shown to have similar diagnostic test accuracy. Evacuation proctography

Characterization of adsorption uptake curves for both intraparticle diffusion and liquid film mass transfer controlling systems

International Nuclear Information System (INIS)

Sonetaka, Noriyoshi; Fan, Huan-Jung; Kobayashi, Seiji; Su, Yang-Chih; Furuya, Eiji

2009-01-01

In general, the adsorption uptake curve (AUC) can be easily determined in either intraparticle diffusion or liquid film mass transfer dominating systems. However, for both intraparticle diffusion and liquid film mass transfer controlling systems, the characterization of AUC is much more complicated, for example, when relatively small adsorbent particles are employed. In addition, there is no analytical solution available for both intraparticle diffusion and liquid film mass transfer controlling systems. Therefore, this paper is trying to characterize AUC for both intraparticle diffusion and liquid film mass transfer controlling adsorption systems using the shallow bed reactor technique. Typical parameters influencing AUC include liquid film mass transfer coefficient (k F ), effective intraparticle diffusivity (D S ), influent concentration (c 0 ) and equilibrium parameters (such as Freundlich isotherm constants k and 1/n). These parameters were investigated in this research and the simulated results indicated that the ratio of k F /D S and Freundlich constant 1/n had impact on AUC. Biot number (Bi) was used to replace the ratio of k F /D S in this study. Bi represents the ratio of the rate of transport across the liquid layer to the rate of intraparticle diffusion. Furthermore, Bi is much more significant than that of 1/n for AUC. Therefore, AUC can be characterized by Bi. In addition, the obtained Bi could be used to determine D S and k F simultaneously. Both parameters (D S and k F ) are important for designing and operating fixed bed reactors.

BMI or BIA: Is Body Mass Index or Body Fat Mass a Better Predictor of Cardiovascular Risk in Overweight or Obese Children and Adolescents?

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Bohn, Barbara; Müller, Manfred James; Simic-Schleicher, Gunter; Kiess, Wieland; Siegfried, Wolfgang; Oelert, Monika; Tuschy, Sabine; Berghem, Stefan; Holl, Reinhard W.

2015-01-01

Background Body fat (BF) percentiles for German children and adolescents have recently been published. This study aims to evaluate the association between bioelectrical impedance analysis(BIA)-derived BF and cardiovascular risk factors and to investigate whether BF is better suited than BMI in children and adolescents. Methods Data of 3,327 children and adolescents (BMI > 90th percentile) were included. Spearman's correlation and receiver operating characteristics (ROCs) were applied determining the associations between BMI or BF and cardiovascular risk factors (hypertension, dyslipidemia, elevated liver enzymes, abnormal carbohydrate metabolism). Area under the curve (AUC) was calculated to predict cardiovascular risk factors. Results A significant association between both obesity indices and hypertension was present (all p correlation with BMI was stronger (r = 0.22) compared to BF (r = 0.13). There were no differences between BMI and BF regarding their correlation with other cardiovascular risk factors. BF significantly predicted hypertension (AUC = 0.61), decreased HDL-cholesterol (AUC = 0.58), elevated LDL-cholesterol (AUC = 0.59), elevated liver enzymes (AUC = 0.61) (all p < 0.0001), and elevated triglycerides (AUC = 0.57, p < 0.05), but not abnormal carbohydrate metabolism (AUC = 0.54, p = 0.15). For the prediction of cardiovascular risk factors, no significant differences between BMI and BF were observed. Conclusion BIA-derived BF was not superior to BMI to predict cardiovascular risk factors in overweight or obese children and adolescents. PMID:26087841

A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent

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Fleming D

2006-01-01

Full Text Available Background : Therapeutic drug monitoring for mycophenolic acid (MPA is increasingly being advocated. Thepresent therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC.However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this samplingperiod? Aim : To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. Settings and Design : Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paireddata. Materials and Methods : Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept ® wereevaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the timeafter transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factorapplied. These two AUCs were then compared. Statistical Analysis : Linear regression, intra-class correlations (ICC and a two-tailed paired t-test were appliedto the data. Results : Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2 were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. Nobias was seen with a Bland Altman plot or by calculation. Conclusion : For patients on Cellcept ® with prednisolone ± cyclosporine the 6-hour corrected is an accuratemeasure of the full 12-hour AUC.

Is 'gut feeling' by medical staff better than validated scores in estimation of mortality in a medical intensive care unit? - The prospective FEELING-ON-ICU study.

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Radtke, Anne; Pfister, Roman; Kuhr, Kathrin; Kochanek, Matthias; Michels, Guido

2017-10-01

The aim of the FEELING-ON-ICU study was to compare mortality estimations of critically ill patients based on 'gut feeling' of medical staff and by Acute Physiology And Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure Assessment (SOFA). Medical staff estimated patients' mortality risks via questionnaires. APACHE II, SAPS II and SOFA were calculated retrospectively from records. Estimations were compared with actual in-hospital mortality using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). 66 critically ill patients (60.6% male, mean age 63±15years (range 30-86)) were evaluated each by a nurse (n=66, male 32.4%) and a physician (n=66, male 67.6%). 15 (22.7%) patients died on the intensive care unit. AUC was largest for estimations by physicians (AUC 0.814 (95% CI 0.705-0.923)), followed by SOFA (AUC 0.749 (95% CI 0.629-0.868)), SAPS II (AUC 0.723 (95% CI 0.597-0.849)), APACHE II (AUC 0.721 (95% CI 0.595-0.847)) and nursing staff (AUC 0.669 (95% CI 0.529-0.810)) (p<0.05 for all results). The concept of physicians' 'gut feeling' was comparable to classical objective scores in mortality estimations of critically ill patients. Concerning practicability physicians' evaluations were advantageous to complex score calculation. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of postural steadiness before and after sedation: comparison of four nonlinear and three conventional measures

International Nuclear Information System (INIS)

Tietäväinen, A; Hæggström, E; Mandel, J E

2014-01-01

Sedative drugs decrease postural steadiness and increase the risk of injury from falls and accidents. The recovery rate is individual, making it hard to predict the patient's steadiness and hence safe discharge time. 103 outpatients sedated with midazolam and fentanyl were measured posturographically, before (PRE) and after (POST) endoscopy. The ability of conventional and nonlinear sway measures to separate the PRE and POST conditions were compared, and the area under the receiver operating characteristics curve (AUC) was used to quantify the significance of the separation. A nonlinear measure, fuzzy sample entropy, scored the largest AUC (AUC FSE  = 0.83, p < 0.0001). While the AUC FSE  was not significantly larger than the AUCs of conventional sway measures which offer easy quantification of postural steadiness, nonlinear measures provide more insight into the structure of postural control, which may help understand the effect of sedation on postural steadiness. This study is a step toward developing a tester that indicates a safe discharge time. (paper)

Pharmacokinetics and Biliary Excretion of Fisetin in Rats.

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Huang, Miao-Chan; Hsueh, Thomas Y; Cheng, Yung-Yi; Lin, Lie-Chwen; Tsai, Tung-Hu

2018-06-14

The hypothesis of this study is that fisetin and phase II conjugated forms of fisetin may partly undergo biliary excretion. To investigate this hypothesis, male Sprague-Dawley rats were used for the experiment, and their bile ducts were cannulated with polyethylene tubes for bile sampling. The pharmacokinetic results demonstrated that the average area-under-the-curve (AUC) ratios ( k (%) = AUC conjugate /AUC free-form ) of fisetin, its glucuronides, and its sulfates were 1:6:21 in plasma and 1:4:75 in bile, respectively. Particularly, the sulfated metabolites were the main forms that underwent biliary excretion. The biliary excretion rate ( k BE (%) = AUC bile /AUC plasma ) indicates the amount of fisetin eliminated by biliary excretion. The biliary excretion rates of fisetin, its glucuronide conjugates, and its sulfate conjugates were approximately 144, 109, and 823%, respectively, after fisetin administration (30 mg/kg, iv). Furthermore, biliary excretion of fisetin is mediated by P-glycoprotein.

Physiologic Waveform Analysis for Early Detection of Hemorrhage during Transport and Higher Echelon Medical Care of Combat Casualties

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2014-03-01

area under the curve (ROC AUC ) values. (ROC AUC values range from 0 and 1 and indicate the probability of correct detection/discrimination...training set of the human LBNP data. Values are receiver operating characteristic area under the curves (ROC AUCs ) comparing the relative SV change...detection of hemorrhage is crucial for managing combat casualties. However, mean arterial blood pressure (ABP) and other vital signs are late indicators of

Severity of Carpal Tunnel Syndrome and Diagnostic Accuracy of Hand and Body Anthropometric Measures

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Mondelli, Mauro; Farioli, Andrea; Mattioli, Stefano; Aretini, Alessandro; Ginanneschi, Federica; Greco, Giuseppe; Curti, Stefania

2016-01-01

Objective To study the diagnostic properties of hand/wrist and body measures according to validated clinical and electrophysiological carpal tunnel syndrome (CTS) severity scales. Methods We performed a prospective case-control study. For each case, two controls were enrolled. Two five-stage clinical and electrophysiological scales were used to evaluate CTS severity. Anthropometric measurements were collected and obesity indicators and hand/wrist ratios were calculated. Area under the receiver operating characteristic curves (AUC), sensitivity, specificity, and likelihood ratios were calculated separately by gender. Results We consecutively enrolled 370 cases and 747 controls. The wrist-palm ratio, waist-hip-height ratio and waist-stature ratio showed the highest proportion of cases with abnormal values in the severe stages of CTS for clinical and electrophysiological severity scales in both genders. Accuracy tended to increase with CTS severity for females and males. In severe stage, most of the indexes presented moderate accuracy in both genders. Among subjects with severe CTS, the wrist-palm ratio presented the highest AUC for hand measures in the clinical and electrophysiological severity scales both in females (AUC 0.83 and 0.76, respectively) and males (AUC 0.91 and 0.82, respectively). Among subjects with severe CTS, the waist-stature ratio showed the highest AUC for body measures in the clinical and electrophysiological severity scales both in females (AUC 0.78 and 0.77, respectively) and males (AUC 0.84 and 0.76, respectively). The results of waist-hip-height ratio AUC were similar. Conclusions Wrist-palm ratio, waist-hip-height ratio and waist-stature ratio could contribute to support the diagnostic hypothesis of severe CTS that however has to be confirmed by nerve conduction study. PMID:27768728

A Pharmacokinetic Bioequivalence Study Comparing Pirfenidone Tablet and Capsule Dosage Forms in Healthy Adult Volunteers.

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Pan, Lin; Belloni, Paula; Ding, Han Ting; Wang, Jianshuang; Rubino, Christopher M; Putnam, Wendy S

2017-09-01

Pirfenidone film-coated tablets were developed to offer an alternative to the marketed capsule formulation. This study assessed the bioequivalence of the tablet and capsule formulations under fed and fasted states. A Phase I, open-label, randomized, four-treatment-period, four-sequence, crossover pharmacokinetics study (NCT02525484) was conducted. Each subject received an 801-mg single dose of pirfenidone as three 267-mg capsules or one 801-mg tablet under fasted and fed conditions. Pirfenidone plasma C max , AUC 0-t and AUC 0-∞ were used to assess bioequivalence. Forty-four subjects were randomized to treatment. The 801-mg tablet in the fasted state met bioequivalence criteria [90% confidence intervals (CI) 80.00-125.00%] for the GLSM ratios of natural log-transformed C max , AUC 0-t and AUC 0-∞ . Under fed conditions, the 801-mg tablet met the bioequivalence criteria for AUC 0-t and AUC 0-∞ , but slightly exceeded the bioequivalence criteria for the C max (90% CI of 108.26-125.60%). The tablet C max was approximately 17% higher than that of the capsules. In the fed state, the tablet C max , and both AUC 0-t and AUC 0-∞ were reduced by 39% and 17%, respectively, relative to the fasted state. The tablet and capsules had acceptable tolerability profiles. The pirfenidone 801-mg tablet met bioequivalence criteria when compared with three 267-mg capsules in the fasted state. The tablet C max was slightly higher relative to capsules in the fed state, but this is not expected to have a clinically meaningful impact on the benefit-risk profile of pirfenidone. This work was supported by F. Hoffmann-La Roche Ltd.

Measurement of serum isoform [-2]proPSA derivatives shows superior accuracy to magnetic resonance imaging in the diagnosis of prostate cancer in patients with a total prostate-specific antigen level of 2-10 ng/ml.

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Furuya, Kazuhiro; Kawahara, Takashi; Narahara, Masaki; Tokita, Takashi; Fukui, Sachi; Imano, Masashi; Mitome, Taku; Ito, Yusuke; Izumi, Koji; Osaka, Kimito; Yokomizo, Yumiko; Hayashi, Narihiko; Hasumi, Hisashi; Nawata, Shintaro; Kawano, Tsuyoshi; Yao, Masahiro; Uemura, Hiroji

2017-08-01

More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer. The subjects were 50 consecutive men with a PSA level of 2.0-10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer. In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%). PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer.

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

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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 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 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.

Effects of breaking up sitting on adolescents' postprandial glucose after consuming meals varying in energy: a cross-over randomised trial.

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Fletcher, Elly A; Salmon, Jo; McNaughton, Sarah A; Orellana, Liliana; Wadley, Glenn D; Bruce, Clinton; Dempsey, Paddy C; Lacy, Kathleen E; Dunstan, David W

2018-03-01

To explore the impact of uninterrupted sitting versus sitting with resistance-type activity breaks on adolescents' postprandial glucose responses while consuming a diet varying in energy. Cross-over randomised trial. Thirteen healthy participants (16.4±1.3years) completed a four-treatment cross-over trial: (1) uninterrupted sitting+high-energy diet; (2) sitting with breaks+high-energy diet; (3) uninterrupted sitting+standard-energy diet; and (4) sitting with breaks+standard-energy diet. For all four conditions, two identical meals were consumed; at 0h and 3h. A continuous glucose monitoring system (CGM) recorded interstitial glucose concentrations every five minutes. Linear mixed models examined differences in glucose positive incremental area under the curve (iAUC) and total AUC between the sitting and diet conditions for the first meal, second meal and entire trial period. Compared to the uninterrupted sitting conditions, the breaks condition elicited a 36.0mmol/L/h (95%CI 6.6-65.5) and 35.9mmol/L/h (95%CI 6.6-65.5) lower iAUC response after the first and second meal, respectively, but not for the entire trial period or for total AUC. Compared to the standard-energy diet, the high-energy diet elicited a 55.0mmol/L/h (95%CI 25.8-84.2) and 75.7mmol/L/h (95%CI 8.6-142.7) higher iAUC response after the first meal and entire trial, respectively. Similar response to the high-energy diet were observed for total AUC. According to iAUC, interrupting sitting had a significant effect on lowering postprandial glucose for both dietary conditions, however, it was not significant when examining total AUC. Larger studies are needed to confirm these findings. ACTRN12615001145594. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

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

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

2018-05-01

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.

A comparative bioavailability study of two formulations of pregabalin in healthy Chilean volunteers.

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Quiñones, Luis; Sasso, Jaime; Tamayo, Evelyn; Catalán, Johanna; González, Juan Paplo; Escala, Mario; Varela, Nelson; León, Jorge; Cáceres, Dante Daniel; Saavedra, Iván

2010-07-01

The aim of this study was to compare the pharmacokinetic parameters between two brands of pregabalin in healthy Chilean volunteers. A randomized, single-dose, two-period, two-sequence, crossover study design with a 2-week washout period was conducted in healthy Chilean males. Plasma samples were collected over a 12-hour period after administration of 150 mg pregabalin in each period. A validated ultra-performance liquid chromatography with positive ionization mass spectrometric detection method was used to analyze pregabalin concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products was determined when the ratio for the 90% confidence intervals (CIs) of the difference in the means of the log-transformed area under the curve (AUC)(0-t), AUC(0-∞), and maximum concentration (C(max)) of the two products were within 0.80 and 1.25. The study was carried out on 22 healthy Chilean volunteers. The mean (SD) C(max), AUC(0-t) and AUC(0-∞) of the test formulation (Pregobin™) of pregabalin were 2.10 (0.56) μg/ml, 10.35 (2.00) μgxh/ml and 13.92 (2.74) μgxh/ml, respectively. The mean (SD) C(max), AUC(0-t) and AUC(0-∞) of the reference formulation (Lyrica™) of pregabalin were 2.15 (0.52) μg/ml, 10.31 (1.85) μgxh/ml and 13.78 (2.25) μgxh/ml, respectively. The parametric 90% CIs for C(max), AUC(0-t), and AUC(0-∞) were 0.97-1.13, 1.01-1.04, and 0.98-1.02, respectively. These results suggest that both products are bioequivalent and can be used as interchangeable options in the clinical setting.

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.

The effect of oral and intravenous dextrose on C-peptide secretion in ponies.

Science.gov (United States)

de Laat, M A; van Haeften, J J; Sillence, M N

2016-02-01

Managing equine hyperinsulinemia is crucial for preventing laminitis, but our understanding of the mechanisms involved in insulin dysregulation in this species is incomplete. C-peptide is co-secreted with insulin but is resistant to hepatic metabolism and can be used to study insulin dysregulation. This study examined C-peptide secretion in serial blood samples collected after oral and i.v. dextrose (0.75 g/kg) administration to 9 ponies (BCS, 7.1 ± 0.5). The ponies were designated as hyperinsulinemic (HI) or normoinsulinemic (NI) responders before the study, using oral glucose tests and fasted glucose-to-insulin ratios, and responses were compared between the 2 groups. C-peptide concentrations increased ( dextrose, with similar area under the concentration-time curve (AUC) for both tests and a significant correlation with AUC. The AUC was similar in HI and NI ponies after i.v. dextrose, indicating similar pancreatic capacity for both groups. However, for oral dextrose, the AUC and the AUC were markedly higher ( < 0.05) in the HI ponies, indicating a greater secretion rate of these peptides. Slower insulin clearance might have also contributed to the larger AUC in HI ponies, but this hypothesis requires further investigation with specific measures of hepatic insulin clearance.

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

The New Injury Severity Score Versus the Injury Severity Score in Predicting Patient Outcome: A Comparative Evaluation on Trauma Service Patients of the Auckland Hospital

OpenAIRE

Samin, Oliver A.; Civil, Ian D.

1999-01-01

Retrospectively calculated NISS was compared with the prospectively calculated ISS from data derived from the trauma registry of the Trauma Services of the Auckland Hospital as to which test is a better predictor of patient outcome, which is defined as the likelihood of death. The area under the curve (AUC) for ISS and NISS were computed using the non-parametric approach. AUC for ISS = 0.95835, and AUC for NISS = 0.97350, p

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.

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

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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.)

Maximum a posteriori Bayesian estimation of mycophenolic Acid area under the concentration-time curve: is this clinically useful for dosage prediction yet?

Science.gov (United States)

Staatz, Christine E; Tett, Susan E

2011-12-01

This review seeks to summarize the available data about Bayesian estimation of area under the plasma concentration-time curve (AUC) and dosage prediction for mycophenolic acid (MPA) and evaluate whether sufficient evidence is available for routine use of Bayesian dosage prediction in clinical practice. A literature search identified 14 studies that assessed the predictive performance of maximum a posteriori Bayesian estimation of MPA AUC and one report that retrospectively evaluated how closely dosage recommendations based on Bayesian forecasting achieved targeted MPA exposure. Studies to date have mostly been undertaken in renal transplant recipients, with limited investigation in patients treated with MPA for autoimmune disease or haematopoietic stem cell transplantation. All of these studies have involved use of the mycophenolate mofetil (MMF) formulation of MPA, rather than the enteric-coated mycophenolate sodium (EC-MPS) formulation. Bias associated with estimation of MPA AUC using Bayesian forecasting was generally less than 10%. However some difficulties with imprecision was evident, with values ranging from 4% to 34% (based on estimation involving two or more concentration measurements). Evaluation of whether MPA dosing decisions based on Bayesian forecasting (by the free website service https://pharmaco.chu-limoges.fr) achieved target drug exposure has only been undertaken once. When MMF dosage recommendations were applied by clinicians, a higher proportion (72-80%) of subsequent estimated MPA AUC values were within the 30-60 mg · h/L target range, compared with when dosage recommendations were not followed (only 39-57% within target range). Such findings provide evidence that Bayesian dosage prediction is clinically useful for achieving target MPA AUC. This study, however, was retrospective and focussed only on adult renal transplant recipients. Furthermore, in this study, Bayesian-generated AUC estimations and dosage predictions were not compared

Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study

Science.gov (United States)

O’Connell, Philip J; Zhang, Weijia; Menon, Madhav C; Yi, Zhengzi; Schröppel, Bernd; Gallon, Lorenzo; Luan, Yi; Rosales, Ivy A; Ge, Yongchao; Losic, Bojan; Xi, Caixia; Woytovich, Christopher; Keung, Karen L; Wei, Chengguo; Greene, Ilana; Overbey, Jessica; Bagiella, Emilia; Najafian, Nader; Samaniego, Milagros; Djamali, Arjang; Alexander, Stephen I; Nankivell, Brian J; Chapman, Jeremy R; Smith, Rex Neal; Colvin, Robert; Murphy, Barbara

2016-01-01

Summary Background Chronic injury in kidney transplants remains a major cause of allograft loss. The aim of this study was to identify a gene set capable of predicting renal allografts at risk of progressive injury due to fibrosis. Methods This Genomics of Chronic Allograft Rejection (GoCAR) study is a prospective, multicentre study. We prospectively collected biopsies from renal allograft recipients (n=204) with stable renal function 3 months after transplantation. We used microarray analysis to investigate gene expression in 159 of these tissue samples. We aimed to identify genes that correlated with the Chronic Allograft Damage Index (CADI) score at 12 months, but not fibrosis at the time of the biopsy. We applied a penalised regression model in combination with permutation-based approach to derive an optimal gene set to predict allograft fibrosis. The GoCAR study is registered with ClinicalTrials.gov, number NCT00611702. Findings We identified a set of 13 genes that was independently predictive for the development of fibrosis at 1 year (ie, CADI-12 ≥2). The gene set had high predictive capacity (area under the curve [AUC] 0·967), which was superior to that of baseline clinical variables (AUC 0·706) and clinical and pathological variables (AUC 0·806). Furthermore routine pathological variables were unable to identify which histologically normal allografts would progress to fibrosis (AUC 0·754), whereas the predictive gene set accurately discriminated between transplants at high and low risk of progression (AUC 0·916). The 13 genes also accurately predicted early allograft loss (AUC 0·842 at 2 years and 0·844 at 3 years). We validated the predictive value of this gene set in an independent cohort from the GoCAR study (n=45, AUC 0·866) and two independent, publically available expression datasets (n=282, AUC 0·831 and n=24, AUC 0·972). Interpretation Our results suggest that this set of 13 genes could be used to identify kidney transplant recipients at

BMI or BIA: Is Body Mass Index or Body Fat Mass a Better Predictor of Cardiovascular Risk in Overweight or Obese Children and Adolescents? A German/Austrian/Swiss Multicenter APV Analysis of 3,327 Children and Adolescents.

Science.gov (United States)

Bohn, Barbara; Müller, Manfred James; Simic-Schleicher, Gunter; Kiess, Wieland; Siegfried, Wolfgang; Oelert, Monika; Tuschy, Sabine; Berghem, Stefan; Holl, Reinhard W

2015-01-01

Body fat (BF) percentiles for German children and adolescents have recently been published. This study aims to evaluate the association between bioelectrical impedance analysis (BIA)-derived BF and cardiovascular risk factors and to investigate whether BF is better suited than BMI in children and adolescents. Data of 3,327 children and adolescents (BMI > 90th percentile) were included. Spearman's correlation and receiver operating characteristics (ROCs) were applied determining the associations between BMI or BF and cardiovascular risk factors (hypertension, dyslipidemia, elevated liver enzymes, abnormal carbohydrate metabolism). Area under the curve (AUC) was calculated to predict cardiovascular risk factors. A significant association between both obesity indices and hypertension was present (all p risk factors. BF significantly predicted hypertension (AUC = 0.61), decreased HDL-cholesterol (AUC = 0.58), elevated LDL-cholesterol (AUC = 0.59), elevated liver enzymes (AUC = 0.61) (all p risk factors, no significant differences between BMI and BF were observed. BIA-derived BF was not superior to BMI to predict cardiovascular risk factors in overweight or obese children and adolescents.

Accuracy of Blood Pressure-to-Height Ratio to Define Elevated Blood Pressure in Children and Adolescents: The CASPIAN-IV Study.

Science.gov (United States)

Kelishadi, Roya; Bahreynian, Maryam; Heshmat, Ramin; Motlagh, Mohammad Esmail; Djalalinia, Shirin; Naji, Fatemeh; Ardalan, Gelayol; Asayesh, Hamid; Qorbani, Mostafa

2016-02-01

The aim of this study was to propose a simple practical diagnostic criterion for pre-hypertension (pre-HTN) and hypertension (HTN) in the pediatric age group. This study was conducted on a nationally representative sample of 14,880 students, aged 6-18 years. HTN and pre-HTN were defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ 95 and 90-95th percentile for age, gender, and height, respectively. By using the area under the curve (AUC) of the receiver operator characteristic curves, we estimated the diagnostic accuracy of two indexes of SBP-to-height ratio (SBPHR) and DBP-to-height (DBPHR) to define pre-HTN and HTN. Overall, SBPHR performed relatively well in classifying subjects to HTN (AUC 0.80-0.85) and pre-HTN (AUC 0.84-0.90). Likewise, DBPHR performed relatively well in classifying subjects to HTN (AUC 0.90-0.97) and pre-HTN (AUC 0.70-0.83). Two indexes of SBPHR and DBPHR are considered as valid, simple, inexpensive, and accurate tools to diagnose pre-HTN and HTN in pediatric age group.

Prediction model of ammonium uranyl carbonate calcination by microwave heating using incremental improved Back-Propagation neural network

Energy Technology Data Exchange (ETDEWEB)

Li Yingwei [Faculty of Metallurgical and Energy Engineering, Kunming University of Science and Technology, Kunming, Yunnan Province 650093 (China); Key Laboratory of Unconventional Metallurgy, Ministry of Education, Kunming University of Science and Technology, Kunming, Yunnan Province 650093 (China); Peng Jinhui, E-mail: jhpeng@kmust.edu.c [Faculty of Metallurgical and Energy Engineering, Kunming University of Science and Technology, Kunming, Yunnan Province 650093 (China); Key Laboratory of Unconventional Metallurgy, Ministry of Education, Kunming University of Science and Technology, Kunming, Yunnan Province 650093 (China); Liu Bingguo [Faculty of Metallurgical and Energy Engineering, Kunming University of Science and Technology, Kunming, Yunnan Province 650093 (China); Key Laboratory of Unconventional Metallurgy, Ministry of Education, Kunming University of Science and Technology, Kunming, Yunnan Province 650093 (China); Li Wei [Key Laboratory of Unconventional Metallurgy, Ministry of Education, Kunming University of Science and Technology, Kunming, Yunnan Province 650093 (China); Huang Daifu [No. 272 Nuclear Industry Factory, China National Nuclear Corporation, Hengyang, Hunan Province 421002 (China); Zhang Libo [Faculty of Metallurgical and Energy Engineering, Kunming University of Science and Technology, Kunming, Yunnan Province 650093 (China); Key Laboratory of Unconventional Metallurgy, Ministry of Education, Kunming University of Science and Technology, Kunming, Yunnan Province 650093 (China)

2011-05-15

Research highlights: The incremental improved Back-Propagation neural network prediction model using the Levenberg-Marquardt algorithm based on optimizing theory is put forward. The prediction model of the nonlinear system is built, which can effectively predict the experiment of microwave calcining of ammonium uranyl carbonate (AUC). AUC can accept the microwave energy and microwave heating can quickly decompose AUC. In the experiment of microwave calcining of AUC, the contents of U and U{sup 4+} increased with increasing of microwave power and irradiation time, and decreased with increasing of the material average depth. - Abstract: The incremental improved Back-Propagation (BP) neural network prediction model was put forward, which was very useful in overcoming the problems, such as long testing cycle, high testing quantity, difficulty of optimization for process parameters, many training data probably were offered by the way of increment batch and the limitation of the system memory could make the training data infeasible, which existed in the process of calcinations for ammonium uranyl carbonate (AUC) by microwave heating. The prediction model of the nonlinear system was built, which could effectively predict the experiment of microwave calcining of AUC. The predicted results indicated that the contents of U and U{sup 4+} were increased with increasing of microwave power and irradiation time, and decreased with increasing of the material average depth.

The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates.

Science.gov (United States)

Meany, Holly J; Fox, Elizabeth; McCully, Cynthia; Tucker, Chris; Balis, Frank M

2008-08-01

Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model. Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUC(CSF):AUC(plasma). Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma was 30% (range 12-59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUC(CSF):AUC(plasma)) of erlotinib and OSI-420 was OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.

MicroRNA Biomarkers in Whole Blood for Detection of Pancreatic Cancer

DEFF Research Database (Denmark)

Schultz, Nicolai A; Dehlendorff, Christian; Jensen, Benny V

2014-01-01

in index II (miR-26b, miR-34a, miR-122, miR-126*, miR-145, miR-150, miR-223, miR-505, miR-636, miR-885.5p). The test characteristics for the training cohort were index I area under the curve (AUC) of 0.86 (95% CI, 0.82-0.90), sensitivity of 0.85 (95% CI, 0.79-0.90), and specificity of 0.64 (95% CI, 0.......57-0.71); index II AUC of 0.93 (95% CI, 0.90-0.96), sensitivity of 0.85 (95% CI, 0.79-0.90), and specificity of 0.85 (95% CI, 0.80-0.85); and CA19-9 AUC of 0.90 (95% CI, 0.87-0.94), sensitivity of 0.86 (95% CI, 0.80-0.90), and specificity of 0.99 (95% CI, 0.96-1.00). Performances were strengthened...... in the validation cohort by combining panels and CA19-9 (index I AUC of 0.94 [95% CI, 0.90-0.98] and index II AUC of 0.93 [95% CI, 0.89-0.97]). Compared with CA19-9 alone, the AUC for the combination of index I and CA19-9 was significantly higher (P = .01). The performance of the panels in patients with stage IA...

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.

Correlation of continuous glucose monitoring profiles with pregnancy outcomes in nondiabetic women.

Science.gov (United States)

Sung, Joyce F; Kogut, Elizabeth A; Lee, Henry C; Mannan, Jana L; Navabi, Kasra; Taslimi, M Mark; El-Sayed, Yasser Y

2015-04-01

To determine whether hyperglycemic excursions detected by continuous glucose monitoring (CGM) correlate with birth weight percentile and other pregnancy outcomes, and whether CGM correlates better with these outcomes than a single glucose value from a 1-hour glucose challenge test (GCT). This was a prospective observational study of 55 pregnant patients without preexisting diabetes, who wore a CGM device for up to 7 days, between 24 and 28 weeks' gestation. The area under the curve (AUC) of hyperglycemic excursions above various thresholds (110, 120, 130, 140, and 180 mg/dL) was calculated. These AUC values, and results from a standard 50-g GCT, were correlated with our primary outcome of birth weight percentile, and secondary outcomes of unplanned operative delivery, pregnancy complications, delivery complications, fetal complications, and neonatal complications. A consistent correlation was seen between all AUC thresholds and birth weight percentile (r = 0.29, p AUC-110, -120, -130, and -140; r = 0.25, p = 0.07 for AUC-180). This correlation was stronger than that of 1-hour oral GCT (r = -0.02, p = 0.88). There was no association between AUC values and other outcomes. Among nondiabetic pregnant patients, hyperglycemic excursions detected by CGM show a stronger correlation to birth weight percentile than blood glucose values obtained 1-hour after a 50-g oral GCT. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prediction model of ammonium uranyl carbonate calcination by microwave heating using incremental improved Back-Propagation neural network

International Nuclear Information System (INIS)

Li Yingwei; Peng Jinhui; Liu Bingguo; Li Wei; Huang Daifu; Zhang Libo

2011-01-01

Research highlights: → The incremental improved Back-Propagation neural network prediction model using the Levenberg-Marquardt algorithm based on optimizing theory is put forward. → The prediction model of the nonlinear system is built, which can effectively predict the experiment of microwave calcining of ammonium uranyl carbonate (AUC). → AUC can accept the microwave energy and microwave heating can quickly decompose AUC. → In the experiment of microwave calcining of AUC, the contents of U and U 4+ increased with increasing of microwave power and irradiation time, and decreased with increasing of the material average depth. - Abstract: The incremental improved Back-Propagation (BP) neural network prediction model was put forward, which was very useful in overcoming the problems, such as long testing cycle, high testing quantity, difficulty of optimization for process parameters, many training data probably were offered by the way of increment batch and the limitation of the system memory could make the training data infeasible, which existed in the process of calcinations for ammonium uranyl carbonate (AUC) by microwave heating. The prediction model of the nonlinear system was built, which could effectively predict the experiment of microwave calcining of AUC. The predicted results indicated that the contents of U and U 4+ were increased with increasing of microwave power and irradiation time, and decreased with increasing of the material average depth.

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients.

Science.gov (United States)

Uemura, Mei; Yano, Yutaka; Suzuki, Toshinari; Yasuma, Taro; Sato, Toshiyuki; Morimoto, Aya; Hosoya, Samiko; Suminaka, Chihiro; Nakajima, Hiromu; Gabazza, Esteban C; Takei, Yoshiyuki

2017-08-01

Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day. Copyright © 2017 Korean Diabetes Association

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients

Directory of Open Access Journals (Sweden)

Mei Uemura

2017-07-01

Full Text Available BackgroundContinuous glucose monitoring (CGM is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET. Here we evaluated the accuracy of interstitial fluid glucose (IG AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference.MethodsThirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. ResultsA significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76 and nighttime (r=0.82. The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity.ConclusionWe showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day.

Investigating Cortisol Production and Pattern as Mediators in the Relationship Between Shift Work and Cardiometabolic Risk.

Science.gov (United States)

Ritonja, Jennifer; Aronson, Kristan J; Day, Andrew G; Korsiak, Jill; Tranmer, Joan

2018-05-01

Shift work is a risk factor for many diseases, including cardiovascular disease. Although the biological pathways are still unclear, it is hypothesized that cortisol disruption during night work is an intermediate. The objective of this study is to determine whether total cortisol production and cortisol pattern mediate the relationship between current shift work and cardiometabolic risk (CMR) among female hospital employees. A cross-sectional study was conducted among 326 female employees (166 rotating shift workers, 160 day workers), recruited from a hospital in Southeastern Ontario, Canada, during 2011 to 2014. Participants completed a baseline interview, questionnaire, and clinical exam. Urine samples were collected over two 24-hour periods and used to analyze creatinine-adjusted cortisol, which was then used to calculate total cortisol production (AUC G ), and pattern (AUC I ). Mediation analysis was performed to test the mediating effect of cortisol in the relationship between shift work and a continuous CMR score. Current shift work is associated with a 0.52 higher CMR score (95% CI: 0.15, 0.89), a lower cortisol output (AUC G ), and a flatter pattern (AUC I ) over a 2-day period. AUC G is a partial mediator in the relationship between shift work and CMR, whereas AUC I is not. AUC G is also associated with CMR while controlling for shift work, suggesting that lower total cortisol production is also linked to CMR in non-shift workers. Total cortisol production is a partial mediator in the relationship between rotating shift work and CMR among female hospital employees, whereas cortisol pattern is not a mediator. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

A study of dose-proportionality in the pharmacokinetics of the oral direct renin inhibitor aliskiren in healthy subjects.

Science.gov (United States)

Limoges, D; Dieterich, H A; Yeh, C-M; Vaidyanathan, S; Howard, D; Dole, W P

2008-05-01

To evaluate the dose-proportionality of the pharmacokinetics of aliskiren, the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension. This was an open-label, single-center, single-dose, randomized, 4-period crossover study. Following a 21-day screening period, 32 healthy male or female subjects (ages 18 - 45 years) were randomized to 1 of 4 aliskiren dosing sequence groups (8 subjects per group): 75, 150, 300 and 600 mg. Blood samples were obtained for determination of plasma aliskiren concentrations (HPLC/MS/MS) for 96 h post dose. Log-transformed pharmacokinetic parameters AUC and C(max) were analyzed to determine dose-proportionality using the power model, parameter = A*(Dose)(beta), where A = intercept and beta = dose-proportionality coefficient. The predefined dose-proportionality criteria over the dose range 75 â 600 mg were 90% confidence intervals (CI) for beta contained within the range 0.89 - 1.11. AUC and Cmax values increased with increasing doses of aliskiren. Both AUC and C(max) were associated with high variability (coefficient of variation 55 - 64% for AUC and 59 - 117% for C(max)). The estimated proportionality coefficients (beta) for AUC(0-infiniti), AUC(0-t) and C(max) were 1.18 (90% CI 1.10, 1.25), 1.29 (90% CI 1.22, 1.36) and 1.42 (90% CI 1.31, 1.52), respectively. Dose-proportionality was, therefore, not demonstrated across the entire 8-fold dose range. For the clinical dose range of 150 â 300 mg, increases of 2.3- and 2.6-fold were observed for AUC and C(max), respectively. All doses of aliskiren were well tolerated. Exposure to aliskiren was greater than proportional over the dose range of 75 - 600 mg. Over the therapeutic dose range of 150 â 300 mg approved for the treatment of hypertension, AUC and Cmax increased by 2.3- and 2.6-fold, respectively. The pharmacokinetics of aliskiren show relatively high intersubject variability.

Intentions to perform non-pharmaceutical protective behaviors during influenza outbreaks in Sweden: a cross-sectional study following a mass vaccination campaign.

Science.gov (United States)

Timpka, Toomas; Spreco, Armin; Gursky, Elin; Eriksson, Olle; Dahlström, Örjan; Strömgren, Magnus; Ekberg, Joakim; Pilemalm, Sofie; Karlsson, David; Hinkula, Jorma; Holm, Einar

2014-01-01

Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45-85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non

Intentions to perform non-pharmaceutical protective behaviors during influenza outbreaks in Sweden: a cross-sectional study following a mass vaccination campaign.

Directory of Open Access Journals (Sweden)

Toomas Timpka

Full Text Available Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443 of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8, sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a an influenza with low case fatality and mild lifestyle impact; b severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0% reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45-85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89, severe outbreaks AUC 0.82 (95% CI 0.77;0.85 and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82, AUC 0.77 (0.72;0.82, using handwash products (AUC 0.70 (0.65;0.75, AUC 0.76 (0.71;0.80, and frequently washing hands (AUC 0.71 (0.66;0.76, AUC 0.75 (0.71;0.80. We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non

The value of intratumoral heterogeneity of (18)F-FDG uptake to differentiate between primary benign and malignant musculoskeletal tumours on PET/CT.

Science.gov (United States)

Nakajo, Masatoyo; Nakajo, Masayuki; Jinguji, Megumi; Fukukura, Yoshihiko; Nakabeppu, Yoshiaki; Tani, Atsushi; Yoshiura, Takashi

2015-01-01

The cumulative standardized uptake value (SUV)-volume histogram (CSH) was reported to be a novel way to characterize heterogeneity in intratumoral tracer uptake. This study investigated the value of fluorine-18 fludeoxyglucose ((18)F-FDG) intratumoral heterogeneity in comparison with SUV to discriminate between primary benign and malignant musculoskeletal (MS) tumours. The subjects comprised 85 pathologically proven MS tumours. The area under the curve of CSH (AUC-CSH) was used as a heterogeneity index, with lower values corresponding with increased heterogeneity. As 22 tumours were indiscernible on (18)F-FDG positron emission tomography, maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and AUC-CSH were obtained in 63 positive tumours. The Mann-Whitney U test and receiver operating characteristic (ROC) analysis were used for analyses. The difference between benign (n = 35) and malignant tumours (n = 28) was significant in AUC-CSH (p = 0.004), but not in SUVmax (p = 0.168) and SUVmean (p = 0.879). The sensitivity, specificity and accuracy for diagnosing malignancy were 61%, 66% and 64% for SUVmax (optical threshold value, >6.9), 54%, 60% and 57% for SUVmean (optical threshold value, >3) and 61%, 86% and 75% for AUC-CSH (optical threshold value, ≤0.42), respectively. The area under the ROC curve was significantly higher in AUC-CSH (0.71) than SUVmax (0.60) (p = 0.018) and SUVmean (0.51) (p = 0.005). The heterogeneity index, AUC-CSH, has a higher diagnostic accuracy than SUV analysis in differentiating between primary benign and malignant MS tumours, although it is not sufficiently high enough to obviate histological analysis. AUC-CSH can assess the heterogeneity of (18)F-FDG uptake in primary benign and malignant MS tumours, with significantly greater heterogeneity associated with malignant MS tumours. AUC-CSH is more diagnostically accurate than SUV analysis in differentiating between benign and

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

[Impact of area under the curve of oral glucose tolerance test on pregnant woman with gestational diabetes mellitus].

Science.gov (United States)

Zhang, Congyue; Su, Shiping; Liu, Chunhong; Zhang, Li; Yang, Huixia

2015-09-01

To investigate whether area under the curve (AUC) of oral glucose tolerance test (OGTT) could work as a predictor of outcomes of gestational diabetes mellitus (GDM) on condition that blood glucose is controlled. A total of 1 796 women who had a standard antenatal care in Peking University First Hospital and gave single live births from July 1, 2011 to December 31, 2 013 were included. They should be diagnosed of GDM by the diagnosis criteria of gestational diabetes published by the Ministry of Health of PRC and diabetes pre-pregnancy excluded. Data were analyzed with SPSS 17.0, grouping by AUC. (1) Women with higher AUC had a rising trend of age and a downward trend of gestational weight gain, however, not statistically significant [specifically, in the four group of less than 15.00 mmol · L⁻¹ · h⁻¹, 15.00 to 16.79 mmol · L⁻¹ · h⁻¹, 16.80 to 17.99 mmol · L⁻¹ · h⁻¹ and 18.00 mmol · L⁻¹ · h⁻¹ or more, gestational weight gain was (15.3 ± 5.2), (14.1 ± 4.8), (13.5 ± 4.7) and (13.1 ± 4.8) kg]. The prevalence of macrosomia raised while AUC increased. Those with an AUC of lower than 15.00 (mmol · L⁻¹ · h⁻¹) had a lower risk of macrosomia (P = 0.04). But those with an AUC of 18.00 (mmol · L⁻¹ · h⁻¹) or more had a higher risk of macrosomia (P = 0.02). There was a rising trend in premature birth and preeclampsia with AUC increasing but not significant (the prevalence of premature birth was 4.38%, 5.36%, 7.71% and 7.94% while that of preeclampsia was 2.85%, 4.69%, 4.67% and 5.08% in these four groups). (2) The prevalence of macrosomia was 12.76% (54/423) when overweight pre-pregnancy, significantly higher compared with 5.87% (65/1 107) in normal group. The prevalence of preeclampsia was 5.91% (25/423) and 3.34% (37/1 107) in those two groups, which was also significantly different. The obese group had a statistically highest prevalence of preeclampsia of 9.23% (12/130). (3) AUC (P AUC, as well as pre-pregnancy BMI and

Pilot scale for preparation of ammonium uranyl carbonate

International Nuclear Information System (INIS)

Santos, L.R. dos.

1989-01-01

The procedure adopted for obtaining Ammonium Uranyl Carbonate (AUC) from uranium hexafluoride (UF sub(6)) or aqueous solutions of uranylnitrate (UO sub(2)(NO sub(3)) sub(2)) is described in the present work. This procedure involves the precipitation of AUC in a chemical reactor by the addition of gaseous UF sub(6) or solutions of uranylnitrate to NH sub(3) and CO sub(2) gases in a solution containing ammonium bicarbonate, where pH and temperature are controlled. Details regarding the characterization and quality control methods in the preparation of AUC are presented along with their physical and chemical properties. Some informations about effluents generated during the process are presented too. An attempt is made to correlate the parameters involved in the precipitation process of AUC and their characteristics. (author)

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

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

On the analysis of glycomics mass spectrometry data via the regularized area under the ROC curve

Directory of Open Access Journals (Sweden)

Lebrilla Carlito B

2007-12-01

Full Text Available Abstract Background Novel molecular and statistical methods are in rising demand for disease diagnosis and prognosis with the help of recent advanced biotechnology. High-resolution mass spectrometry (MS is one of those biotechnologies that are highly promising to improve health outcome. Previous literatures have identified some proteomics biomarkers that can distinguish healthy patients from cancer patients using MS data. In this paper, an MS study is demonstrated which uses glycomics to identify ovarian cancer. Glycomics is the study of glycans and glycoproteins. The glycans on the proteins may deviate between a cancer cell and a normal cell and may be visible in the blood. High-resolution MS has been applied to measure relative abundances of potential glycan biomarkers in human serum. Multiple potential glycan biomarkers are measured in MS spectra. With the objection of maximizing the empirical area under the ROC curve (AUC, an analysis method was considered which combines potential glycan biomarkers for the diagnosis of cancer. Results Maximizing the empirical AUC of glycomics MS data is a large-dimensional optimization problem. The technical difficulty is that the empirical AUC function is not continuous. Instead, it is in fact an empirical 0–1 loss function with a large number of linear predictors. An approach was investigated that regularizes the area under the ROC curve while replacing the 0–1 loss function with a smooth surrogate function. The constrained threshold gradient descent regularization algorithm was applied, where the regularization parameters were chosen by the cross-validation method, and the confidence intervals of the regression parameters were estimated by the bootstrap method. The method is called TGDR-AUC algorithm. The properties of the approach were studied through a numerical simulation study, which incorporates the positive values of mass spectrometry data with the correlations between measurements within person

Role of MRI and added value of diffusion-weighted and gadolinium-enhanced MRI for the diagnosis of local recurrence from rectal cancer.

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Molinelli, Valeria; Angeretti, Maria Gloria; Duka, Ejona; Tarallo, Nicola; Bracchi, Elena; Novario, Raffaele; Fugazzola, Carlo

2018-03-14

To evaluate whether the addition of gadolinium-enhanced MRI and diffusion-weighted imaging (DWI) improves T2 sequence performance for the diagnosis of local recurrence (LR) from rectal cancer and to assess which approach is better at formulating this diagnosis among readers with different experience. Forty-three patients with suspected LR underwent pelvic MRI with T2 weighted (T2) sequences, gadolinium fat-suppressed T1 weighted sequences (post-contrast T1), and DWI sequences. Three readers (expert: G, intermediate: E, resident: V) scored the likelihood of LR on T2, T2 + post-contrast T1, T2 + DWI, and T2 + post-contrast T1 + DWI. In total, 18/43 patients had LR; on T2 images, the expert reader achieved an area under the ROC curve (AUC) of 0.916, sensitivity of 88.9%, and specificity of 76%; the intermediate reader achieved values of 0.890, 88.9%, and 48%, respectively, and the resident achieved values of 0.852, 88.9%, and 48%, respectively. DWI significantly improved the AUC value for the expert radiologist by up to 0.999 (p = 0.04), while post-contrast T1 significantly improved the AUC for the resident by up to 0.950 (p = 0.04). For the intermediate reader, both the T2 + DWI AUC and T2 + post-contrast T1 AUC were better than the T2 AUC (0.976 and 0.980, respectively), but with no statistically significant difference. No statistically significant difference was achieved by any of the three readers by comparing either the T2 + DWI AUCs to the T2 + post-contrast T1 AUCs or the AUCs of the two pairs of sequences to those of the combined three sequences. Furthermore, using the T2 sequences alone, all of the readers achieved a fair number of "equivocal" cases: they decreased with the addition of either DWI or post-contrast T1 sequences and, for the two less experienced readers, they decreased even more with the three combined sequences. Both DWI and T1 post-contrast MRI increased diagnostic performance for LR diagnosis compared to T2; however, no

Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets

International Nuclear Information System (INIS)

Kessler, Winfried; Numtip, Wanwiwa; Grote, Konstanze; Csanady, Gyoergy A.; Chahoud, Ibrahim; Filser, Johannes G.

2004-01-01

A comparison of the dose-dependent blood burden of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in pregnant and nonpregnant rats and marmosets is presented. Sprague-Dawley rats and marmosets were treated orally with 30 or 500 mg DEHP/kg per day, nonpregnant animals on 7 (rats) and 29 (marmosets) consecutive days, pregnant animals on gestation days 14-19 (rats) and 96-124 (marmosets). In addition, rats received a single dose of 1000 mg DEHP/kg. Blood was collected up to 48 h after dosing. Concentrations of DEHP and MEHP in blood were determined by GC/MS. In rats, normalized areas under the concentration-time curves (AUCs) of DEHP were two orders of magnitude smaller than the normalized AUCs of the first metabolite MEHP. Metabolism of MEHP was saturable. Repeated DEHP treatment and pregnancy had only little influence on the normalized AUC of MEHP. In marmosets, most of MEHP concentration-time courses oscillated. Normalized AUCs of DEHP were at least one order of magnitude smaller than those of MEHP. In pregnant marmosets, normalized AUCs of MEHP were similar to those in nonpregnant animals with the exception that at 500 mg DEHP/kg per day, the normalized AUCs determined on gestation days 103, 117, and 124 were distinctly smaller. The maximum concentrations of MEHP in blood of marmosets were up to 7.5 times and the normalized AUCs up to 16 times lower than in rats receiving the same daily oral DEHP dose per kilogram of body weight. From this toxicokinetic comparison, DEHP can be expected to be several times less effective in the offspring of marmosets than in that of rats if the blood burden by MEHP in dams can be regarded as a dose surrogate for the MEHP burden in their fetuses

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.

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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.

Pharmacokinetic Effects of Isavuconazole Coadministration With the Cytochrome P450 Enzyme Substrates Bupropion, Repaglinide, Caffeine, Dextromethorphan, and Methadone in Healthy Subjects.

Science.gov (United States)

Yamazaki, Takao; Desai, Amit; Goldwater, Ronald; Han, David; Howieson, Corrie; Akhtar, Shahzad; Kowalski, Donna; Lademacher, Christopher; Pearlman, Helene; Rammelsberg, Diane; Townsend, Robert

2017-01-01

This report describes phase 1 clinical trials performed to assess interactions of oral isavuconazole at the clinically targeted dose (200 mg, administered as isavuconazonium sulfate 372 mg, 3 times a day for 2 days; 200 mg once daily [QD] thereafter) with single oral doses of the cytochrome P450 (CYP) substrates: bupropion hydrochloride (CYP2B6; 100 mg; n = 24), repaglinide (CYP2C8/CYP3A4; 0.5 mg; n = 24), caffeine (CYP1A2; 200 mg; n = 24), dextromethorphan hydrobromide (CYP2D6/CYP3A4; 30 mg; n = 24), and methadone (CYP2B6/CYP2C19/CYP3A4; 10 mg; n = 23). Compared with each drug alone, coadministration with isavuconazole changed the area under the concentration-time curves (AUC ∞ ) and maximum concentrations (C max ) as follows: bupropion, AUC ∞ reduced 42%, C max reduced 31%; repaglinide, AUC ∞ reduced 8%, C max reduced 14%; caffeine, AUC ∞ increased 4%, C max reduced 1%; dextromethorphan, AUC ∞ increased 18%, C max increased 17%; R-methadone, AUC ∞ reduced 10%, C max increased 3%; S-methadone, AUC ∞ reduced 35%, C max increased 1%. In all studies, there were no deaths, 1 serious adverse event (dextromethorphan study; perioral numbness, numbness of right arm and leg), and adverse events leading to study discontinuation were rare. Thus, isavuconazole is a mild inducer of CYP2B6 but does not appear to affect CYP1A2-, CYP2C8-, or CYP2D6-mediated metabolism. © 2016 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

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

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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.)

Bladder cancer treatment response assessment in CT urography using two-channel deep-learning network

Science.gov (United States)

Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Samala, Ravi K.; Cohan, Richard H.; Caoili, Elaine M.; Weizer, Alon Z.; Alva, Ajjai

2018-02-01

We are developing a CAD system for bladder cancer treatment response assessment in CT. We trained a 2- Channel Deep-learning Convolution Neural Network (2Ch-DCNN) to identify responders (T0 disease) and nonresponders to chemotherapy. The 87 lesions from 82 cases generated 18,600 training paired ROIs that were extracted from segmented bladder lesions in the pre- and post-treatment CT scans and partitioned for 2-fold cross validation. The paired ROIs were input to two parallel channels of the 2Ch-DCNN. We compared the 2Ch-DCNN with our hybrid prepost- treatment ROI DCNN method and the assessments by 2 experienced abdominal radiologists. The radiologist estimated the likelihood of stage T0 after viewing each pre-post-treatment CT pair. Receiver operating characteristic analysis was performed and the area under the curve (AUC) and the partial AUC at sensitivity AUC0.9) were compared. The test AUCs were 0.76+/-0.07 and 0.75+/-0.07 for the 2 partitions, respectively, for the 2Ch-DCNN, and were 0.75+/-0.08 and 0.75+/-0.07 for the hybrid ROI method. The AUCs for Radiologist 1 were 0.67+/-0.09 and 0.75+/-0.07 for the 2 partitions, respectively, and were 0.79+/-0.07 and 0.70+/-0.09 for Radiologist 2. For the 2Ch-DCNN, the AUC0.9s were 0.43 and 0.39 for the 2 partitions, respectively, and were 0.19 and 0.28 for the hybrid ROI method. For Radiologist 1, the AUC0.9s were 0.14 and 0.34 for partition 1 and 2, respectively, and were 0.33 and 0.23 for Radiologist 2. Our study demonstrated the feasibility of using a 2Ch-DCNN for the estimation of bladder cancer treatment response in CT.

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).

Are patient-reported outcomes predictive of patient satisfaction 5 years after anterior cervical spine surgery?

Science.gov (United States)

Schroeder, Gregory D; Coric, Dom; Kim, Han Jo; Albert, Todd J; Radcliff, Kris E

2017-07-01

Patient satisfaction is becoming an increasing common proxy for surgical quality; however, the correlation between patient satisfaction and surgical outcomes 2 and 5 years after anterior cervical surgery has not been evaluated. The study aimed to determine if patient satisfaction is predicted by improvement in patient-reported outcomes (PRO) 2 and 5 years after anterior cervical spine surgery. This is a retrospective analysis of prospectively collected data. The sample included patients enrolled in the Food and Drug Administration investigational device exemption clinical trial comparing total disc replacement with Mobi-C cervical artificial disc and anterior cervical discectomy and fusion. The outcome measures were visual analog scale (VAS) neck pain score, Neck Disability Index (NDI), and Short-Form 12-Item scores, as well as patient satisfaction. Receiver operating characteristic curves were used to determine if improvement in different PRO metrics can accurately identify patient satisfaction. Additionally, a logistic regression analysis was performed on the results at 24 months and 60 months to identify independent predictors of patient satisfaction. This research was supported by LDR (Zimmer Biomet) 13785 Research Boulevard - Suite 200 Austin, TX 78750. Data were available for 512 patients at 60 months. At 24 months postoperatively, NDI score improvement (area under the curve [AUC]=0.806), absolute NDI score (AUC=0.823), and absolute VAS neck pain score (AUC=0.808) were all excellent predictors of patient satisfaction. At 60 months postoperatively, NDI score improvement (AUC=0.815), absolute NDI score (AUC=0.839), VAS neck pain score improvement (AUC=0.803), and absolute VAS neck pain score (AUC=0.861) were all excellent predictors of patient satisfaction. In patients undergoing one- and two-level anterior cervical spine surgery, between 2 and 5 years postoperatively, patient satisfaction is significantly predicted by PROs, including the VAS neck score and the

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

International Nuclear Information System (INIS)

Schimmoeller, Lars; Quentin, Michael; Buchbender, Christian; Antoch, Gerald; Blondin, Dirk; Arsov, Christian; Hiester, Andreas; Rabenalt, Robert; Albers, Peter

2014-01-01

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. (orig.)

Impact of long-term burden of excessive adiposity and elevated blood pressure from childhood on adulthood left ventricular remodeling patterns: the Bogalusa Heart Study.

Science.gov (United States)

Lai, Chin-Chih; Sun, Dianjianyi; Cen, Ruiqi; Wang, Jian; Li, Shengxu; Fernandez-Alonso, Camilo; Chen, Wei; Srinivasan, Sathanur R; Berenson, Gerald S

2014-10-14

Cardiovascular risk factors are associated with left ventricular hypertrophy (LVH), but little is known regarding related impact of longitudinal measures of childhood adiposity and LV hemodynamic variables. The aim of this study was to examine the impact of cumulative long-term burden and trends of excessive adiposity and elevated blood pressure (BP) during childhood on adulthood LVH and LV geometric remodeling patterns. This longitudinal study consisted of 1,061 adults, age 24 to 46 years, who had been examined 4 or more times for body mass index (BMI) and BP starting in childhood, with a mean follow-up of 28.0 years. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and BP from childhood to adulthood. Four LV geometric types were defined-normal, concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH)-all on the basis of LV mass indexed for body height (m(2.7)) and relative wall thickness. Higher values of BMI and systolic and diastolic BP in childhood and adulthood, as well as total AUC and incremental AUC, were all significantly associated with higher LV mass index and LVH, adjusted for race, sex, and age. In addition, higher values of BMI and BP in childhood and adulthood, total AUC, and incremental AUC were significantly associated with EH and CH but not with CR. Importantly, all of these measures of BMI had a consistently and significantly greater influence on EH than did measures of BP. These findings indicate that the adverse influence of excessive adiposity and elevated BP levels on LVH begins in childhood. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Postprandial Glucose Surges after Extremely Low Carbohydrate Diet in Healthy Adults.

Science.gov (United States)

Kanamori, Koji; Ihana-Sugiyama, Noriko; Yamamoto-Honda, Ritsuko; Nakamura, Tomoka; Sobe, Chie; Kamiya, Shigemi; Kishimoto, Miyako; Kajio, Hiroshi; Kawano, Kimiko; Noda, Mitsuhiko

2017-09-01

Carbohydrate-restricted diets are prevalent not only in obese people but also in the general population to maintain appropriate body weight. Here, we report that extreme carbohydrate restriction for one day affects the subsequent blood glucose levels in healthy adults. Ten subjects (median age 30.5 years, BMI 21.1 kg/m 2 , and HbA1c 5.5%), wearing with a continuous glucose monitoring device, were given isoenergetic test meals for 4 consecutive days. On day 1, day 2 (D2), and day 4 (D4), they consumed normal-carbohydrate (63-66% carbohydrate) diet, while on day 3, they took low-carbohydrate/high-fat (5% carbohydrate) diet. The daily energy intake was 2,200 kcal for males and 1,700 kcal for females. On D2 and D4, we calculated the mean 24-hr blood glucose level (MEAN/24h) and its standard deviation (SD/24h), the area under the curve (AUC) for glucose over 140 mg/dL within 4 hours after each meal (AUC/4h/140), the mean amplitude of the glycemic excursions (MAGE), the incremental AUC of 24-hr blood glucose level above the mean plus one standard deviation (iAUC/MEAN+SD). Indexes for glucose fluctuation on D4 were significantly greater than those on D2 (SD/24h; p = 0.009, MAGE; p = 0.013, AUC/4h/140 after breakfast and dinner; p = 0.006 and 0.005, and iAUC/MEAN+SD; p = 0.007). The value of MEAN/24h and AUC/4h/140 after lunch on D4 were greater than those on D2, but those differences were not statistically significant. In conclusion, consumption of low-carbohydrate/high-fat diet appears to cause higher postprandial blood glucose on subsequent normal-carbohydrate diet particularly after breakfast and dinner in healthy adults.

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.

Abbreviated kinetic profiles in area-under-the-curve monitoring of cyclosporine therapy.

Science.gov (United States)

Grevel, J; Kahan, B D

1991-11-01

Abbreviated kinetic profiles can reduce the number of phlebotomies and drug assays, and thereby the cost of area-under-the-curve (AUC) monitoring. In the present investigation, we used two independent data sets: group 1, 101 AUC profiles from 77 stable renal-transplant patients, which included a 5-h sample in addition to the usual 0-, 2-, 4-, 6-, 10-, 14-, and 24-h samples; and group 2, 100 profiles from 50 stable renal-transplant patients before and after a change in their daily oral dose of cyclosporine. Group I demonstrated a fair correlation between cyclosporine trough concentrations and the AUC calculated from a complete set of seven concentrations (r2 = 0.820 and 0.758 for the 24- and 0-h samples, respectively). Stepwise multiple linear-regression analysis revealed that the abbreviated set of three time points (2, 6, and 14 h) explained 96% of the variance in AUC values calculated from the full set of seven samples; additional time points increased the accuracy only slightly. For group 2, we examined the difference between the observed and the predicted concentrations by linear extrapolation; the error in the observed AUC value, compared with the predicted value calculated from seven time points (-13.2% to -1.2%), was similar to the error from just three time points (-11.5% to 4.5%). Abbreviated AUC profiles involving three time points used with a model equation seem to provide a reliable alternative to full seven-point profiles.

Comparison of Glasgow-Blatchford score and full Rockall score systems to predict clinical outcomes in patients with upper gastrointestinal bleeding.

Science.gov (United States)

Mokhtare, Marjan; Bozorgi, Vida; Agah, Shahram; Nikkhah, Mehdi; Faghihi, Amirhossein; Boghratian, Amirhossein; Shalbaf, Neda; Khanlari, Abbas; Seifmanesh, Hamidreza

2016-01-01

Various risk scoring systems have been recently developed to predict clinical outcomes in patients with upper gastrointestinal bleeding (UGIB). The two commonly used scoring systems include full Rockall score (RS) and the Glasgow-Blatchford score (GBS). Bleeding scores were assessed in terms of prediction of clinical outcomes in patients with UGIB. Two hundred patients (age >18 years) with obvious symptoms of UGIB in the emergency department of Rasoul Akram Hospital were enrolled. Full RS and GBS were calculated. We followed the patients for records of rebleeding and 1-month mortality. A receiver operating characteristic curve by using areas under the curve (AUCs) was used to statistically identify the best cutoff point. Eighteen patients were excluded from the study due to failure to follow-up. Rebleeding and mortality rate were 9.34% (n=17) and 11.53% (n=21), respectively. Regarding 1-month mortality, full RS was better than GBS (AUC, 0.648 versus 0.582; P =0.021). GBS was more accurate in terms of detecting transfusion need (AUC, 0.757 versus 0.528; P =0.001), rebleeding rate (AUC, 0.722 versus 0.520; P =0.002), intensive care unit admission rate (AUC, 0.648 versus 0.582; P =0.021), and endoscopic intervention rate (AUC, 0.771 versus 0.650; P <0.001). We found the full RS system is better for 1-month mortality prediction while GBS system is better for prediction of other outcomes.

Correlation of contrast-enhanced ultrasound parameters with oncogene expression and cell proliferation activity in breast cancer

Institute of Scientific and Technical Information of China (English)

Ce Zhang

2017-01-01

Objective: To study the correlation of contrast-enhanced ultrasound parameters with oncogene expression and cell proliferation activity in breast cancer. Methods: Breast cancer lesions and benign breast lesions surgically removed in Zigong Third People's Hospital between May 2014 and February 2017 were selected, contrast-enhanced ultrasound was done before operation to draw the time-intensity curve and calculate the area under the curve (AUC), and the expression of proliferation molecules and tumor suppressor genes were detected after operation. Results:The contrast-enhanced ultrasound parameter AUC of the breast cancer lesion was greatly higher than that of the benign breast lesion; ECT2, ZKSCAN3, USP39 and EphA2 mRNA expression in breast cancer lesions were obviously higher than those in benign breast lesions whereas HPK1, TCEAL17, CCN5, ATG2B and ATG4D mRNA expression were greatly lower than those in benign breast lesions; ECT2, ZKSCAN3, USP39 and EphA2 mRNA expression in breast cancer lesions with high AUC were greatly higher than those in breast cancer lesions with low AUC whereas HPK1, TCEAL17, CCN5, ATG2B and ATG4D mRNA expression were greatly lower than those in breast cancer lesions with low AUC. Conclusion: The contrast-enhanced ultrasound parameter AUC of breast cancer lesion significantly increases and is closely related to the higher expression of pro-proliferation molecules and the lower expression of tumor suppressor genes.

Bayesian modeling and inference for diagnostic accuracy and probability of disease based on multiple diagnostic biomarkers with and without a perfect reference standard.

Science.gov (United States)

Jafarzadeh, S Reza; Johnson, Wesley O; Gardner, Ian A

2016-03-15

The area under the receiver operating characteristic (ROC) curve (AUC) is used as a performance metric for quantitative tests. Although multiple biomarkers may be available for diagnostic or screening purposes, diagnostic accuracy is often assessed individually rather than in combination. In this paper, we consider the interesting problem of combining multiple biomarkers for use in a single diagnostic criterion with the goal of improving the diagnostic accuracy above that of an individual biomarker. The diagnostic criterion created from multiple biomarkers is based on the predictive probability of disease, conditional on given multiple biomarker outcomes. If the computed predictive probability exceeds a specified cutoff, the corresponding subject is allocated as 'diseased'. This defines a standard diagnostic criterion that has its own ROC curve, namely, the combined ROC (cROC). The AUC metric for cROC, namely, the combined AUC (cAUC), is used to compare the predictive criterion based on multiple biomarkers to one based on fewer biomarkers. A multivariate random-effects model is proposed for modeling multiple normally distributed dependent scores. Bayesian methods for estimating ROC curves and corresponding (marginal) AUCs are developed when a perfect reference standard is not available. In addition, cAUCs are computed to compare the accuracy of different combinations of biomarkers for diagnosis. The methods are evaluated using simulations and are applied to data for Johne's disease (paratuberculosis) in cattle. Copyright © 2015 John Wiley & Sons, Ltd.

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.

Diagnostic value of T1 and T2 * relaxation times and off-resonance saturation effects in the evaluation of Achilles tendinopathy by MRI at 3T.

Science.gov (United States)

Grosse, Ulrich; Syha, Roland; Hein, Tobias; Gatidis, Sergios; Grözinger, Gerd; Schabel, Christoph; Martirosian, Petros; Schick, Fritz; Springer, Fabian

2015-04-01

To evaluate and compare the diagnostic value of T1 , T2 * relaxation times and off-resonance saturation ratios (OSR) in healthy controls and patients with different clinical and morphological stages of Achilles tendinopathy. Forty-two healthy Achilles tendons and 34 tendons of 17 patients with symptomatic and asymptomatic tendinopathy were investigated clinically with conventional magnetic resonance imaging (MRI) sequences on a 3T whole-body MR scanner and a dynamic ultrasound examination. In addition, T1 and T2 * relaxation times were assessed using an ultrashort echo time (UTE) imaging sequence with flip angle and echo time variation. For the calculation of OSR values a Gaussian off-resonance saturation pulse (frequency offset: 750-5000 Hz) was used. The diagnostic value of the derived MR values was assessed and compared using receiver operating characteristic (ROC) curves. ROC curves demonstrate the highest overall test performance for OSR values at 2000 Hz off-resonance in differentiating slightly (OSR-2000 [AUC: 0.930] > T2 * [AUC: 0.884] > T1 [AUC: 0.737]) and more severe pathologically altered tendon areas (OSR-2000 [AUC: 0.964] > T2 * [AUC: 0.917] > T1 [AUC: 0.819]) from healthy ones. OSR values at a frequency offset of 2000 Hz demonstrated a better sensitivity and specificity for detecting mild and severe stages of tendinopathy compared to T2 * and particularly when compared to T1 relaxation times. © 2014 Wiley Periodicals, Inc.

Preparation of U3O8 powder for MTR type fuel from ammonium uranyl carbonate

International Nuclear Information System (INIS)

Marcondes, G.H.; Riella, H.G.

1990-08-01

In this paper it is described the research done at IPEN-CNEN/SP on the preparation of U 3 O 8 powder from calcination of the AUC, with appropriate characteristics to be used as dispersoid for MTR type fuel. The calcination in air of the AUC leads a U 3 O 8 powder that is further processed to obtain a powder with density and particle size as especifications. The important process parameters are here discussed with the variation AUC calcination temperature and sintering time of the U 3 O 8 powder. (author) [pt

The New Injury Severity Score Versus the Injury Severity Score in Predicting Patient Outcome: A Comparative Evaluation on Trauma Service Patients of the Auckland Hospital

Science.gov (United States)

Samin, Oliver A.; Civil, Ian D.

1999-01-01

Retrospectively calculated NISS was compared with the prospectively calculated ISS from data derived from the trauma registry of the Trauma Services of the Auckland Hospital as to which test is a better predictor of patient outcome, which is defined as the likelihood of death. The area under the curve (AUC) for ISS and NISS were computed using the non-parametric approach. AUC for ISS = 0.95835, and AUC for NISS = 0.97350, p <0.012. Misclassification rate for ISS was 2.77% and the value for NISS was 2.43%.

Therapeutic drug monitoring for the individualization of docetaxel dosing: a randomized pharmacokinetic study

NARCIS (Netherlands)

Engels, Frederike K.; Loos, Walter J.; van der Bol, Jessica M.; de Bruijn, Peter; Mathijssen, Ron H. J.; Verweij, Jaap; Mathot, Ron A. A.

2011-01-01

Docetaxel pharmacokinetic (PK) parameters, notably clearance and exposure (AUC), are characterized by large interindividual variability. The purpose of this study was to evaluate the effect of PK-guided [area under the plasma concentration versus time curve (AUC) targeted], individualized docetaxel

Limited-sampling strategies for anti-infective agents: systematic review.

Science.gov (United States)

Sprague, Denise A; Ensom, Mary H H

2009-09-01

Area under the concentration-time curve (AUC) is a pharmacokinetic parameter that represents overall exposure to a drug. For selected anti-infective agents, pharmacokinetic-pharmacodynamic parameters, such as AUC/MIC (where MIC is the minimal inhibitory concentration), have been correlated with outcome in a few studies. A limited-sampling strategy may be used to estimate pharmacokinetic parameters such as AUC, without the frequent, costly, and inconvenient blood sampling that would be required to directly calculate the AUC. To discuss, by means of a systematic review, the strengths, limitations, and clinical implications of published studies involving a limited-sampling strategy for anti-infective agents and to propose improvements in methodology for future studies. The PubMed and EMBASE databases were searched using the terms "anti-infective agents", "limited sampling", "optimal sampling", "sparse sampling", "AUC monitoring", "abbreviated AUC", "abbreviated sampling", and "Bayesian". The reference lists of retrieved articles were searched manually. Included studies were classified according to modified criteria from the US Preventive Services Task Force. Twenty studies met the inclusion criteria. Six of the studies (involving didanosine, zidovudine, nevirapine, ciprofloxacin, efavirenz, and nelfinavir) were classified as providing level I evidence, 4 studies (involving vancomycin, didanosine, lamivudine, and lopinavir-ritonavir) provided level II-1 evidence, 2 studies (involving saquinavir and ceftazidime) provided level II-2 evidence, and 8 studies (involving ciprofloxacin, nelfinavir, vancomycin, ceftazidime, ganciclovir, pyrazinamide, meropenem, and alpha interferon) provided level III evidence. All of the studies providing level I evidence used prospectively collected data and proper validation procedures with separate, randomly selected index and validation groups. However, most of the included studies did not provide an adequate description of the methods or

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

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

International Nuclear Information System (INIS)

Motwani, Hitesh V.; Törnqvist, Margareta

2014-01-01

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

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

Intentions to Perform Non-Pharmaceutical Protective Behaviors during Influenza Outbreaks in Sweden: A Cross-Sectional Study following a Mass Vaccination Campaign

Science.gov (United States)

Timpka, Toomas; Spreco, Armin; Gursky, Elin; Eriksson, Olle; Dahlström, Örjan; Strömgren, Magnus; Ekberg, Joakim; Pilemalm, Sofie; Karlsson, David; Hinkula, Jorma; Holm, Einar

2014-01-01

Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45–85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non

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 AUC 0-3d ). Other endpoints included algometry AUC from 0 to three days (AUC 0-3d ) and 0 to five days (AUC 0-5d ), 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 AUC 0-3d 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 AUC 0-3d was 1.87 N/cm 2 *d and AUC 0-5d was 1.87 N/cm 2 *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.

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

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...

Applying the J-optimal channelized quadratic observer to SPECT myocardial perfusion defect detection

Science.gov (United States)

Kupinski, Meredith K.; Clarkson, Eric; Ghaly, Michael; Frey, Eric C.

2016-03-01

To evaluate performance on a perfusion defect detection task from 540 image pairs of myocardial perfusion SPECT image data we apply the J-optimal channelized quadratic observer (J-CQO). We compare AUC values of the linear Hotelling observer and J-CQO when the defect location is fixed and when it occurs in one of two locations. As expected, when the location is fixed a single channels maximizes AUC; location variability requires multiple channels to maximize the AUC. The AUC is estimated from both the projection data and reconstructed images. J-CQO is quadratic since it uses the first- and second- order statistics of the image data from both classes. The linear data reduction by the channels is described by an L x M channel matrix and in prior work we introduced an iterative gradient-based method for calculating the channel matrix. The dimensionality reduction from M measurements to L channels yields better estimates of these sample statistics from smaller sample sizes, and since the channelized covariance matrix is L x L instead of M x M, the matrix inverse is easier to compute. The novelty of our approach is the use of Jeffrey's divergence (J) as the figure of merit (FOM) for optimizing the channel matrix. We previously showed that the J-optimal channels are also the optimum channels for the AUC and the Bhattacharyya distance when the channel outputs are Gaussian distributed with equal means. This work evaluates the use of J as a surrogate FOM (SFOM) for AUC when these statistical conditions are not satisfied.

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

Association of peak factor VIII levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic-guided prophylaxis.

Science.gov (United States)

Valentino, L A; Pipe, S W; Collins, P W; Blanchette, V S; Berntorp, E; Fischer, K; Ewenstein, B M; Oh, M; Spotts, G

2016-07-01

We previously showed that pharmacokinetic-guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been investigated. The aim of this study was to analyse data from the PKP arm to determine whether peak FVIII levels, AUC and time with FVIII levels in a haemostatically effective range are independent predictors of bleeding during prophylaxis. Post hoc analysis of the association of FVIII levels and AUC with annualized bleeding rate in 34 patients on PKP. During 1 year of PKP, 131 bleeding episodes occurred in 24/34 patients. Average peak FVIII levels ranged from 24 to 168 IU dL(-1) , with higher values associated with a decreased risk for all bleeding (joint and non-joint; P 20 IU dL(-1) was 22%; median AUC was 1363. Both values were significantly associated with a lower ABR when targeting a 1% trough at 72 h. When PKP was administered every third day, higher peak FVIII levels, higher AUC and more time spent per week with FVIII levels >20 IU dL(-1) provided increased protection from joint and non-joint bleeding. These data highlight the potential impact of variability in individual pharmacokinetic and bleeding risk and support the need for high peak levels and AUC in some patients treated every third day. The findings do not necessarily apply to alternate-day or other prophylactic dosing regimens. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Work Ability Index as tool to identify workers at risk of premature work exit.

Science.gov (United States)

Roelen, Corné A M; Heymans, Martijn W; Twisk, Jos W R; van der Klink, Jac J L; Groothoff, Johan W; van Rhenen, Willem

2014-12-01

To investigate the Work Ability Index (WAI) as tool for identifying workers at risk of premature work exit in terms of disability pension, unemployment, or early retirement. Prospective cohort study of 11,537 male construction workers (mean age 45.5 years), who completed the WAI at baseline and reported their work status (employed, unemployed, disability pension, or retired) after mean 2.3 years of follow-up. Associations between WAI scores and work status were investigated by multinomial logistic regression analysis. The ability of the WAI to discriminate between workers at high and low risk of premature work exit was analyzed by the area (AUC) under the receiver operating characteristic curve. 9,530 (83 %) construction workers had complete data for analysis. At follow-up, 336 (4 %) workers reported disability pension, 125 (1 %) unemployment, and 255 (3 %) retirement. WAI scores were prospectively associated with the risk of disability pension at follow-up, but not with the risk of unemployment and early retirement. The WAI showed fair discrimination to identify workers at risk of disability pension [AUC = 0.74; 95 % confidence interval (CI) 0.70-0.77]. The discriminative ability decreased with age from AUC = 0.78 in workers aged 30-39 years to AUC = 0.69 in workers ≥50 years of age. Discrimination failed for unemployment (AUC = 0.51; 95 % CI 0.47-0.55) and early retirement (AUC = 0.58; 95 % CI 0.53-0.61). The WAI can be used to identify construction workers <50 years of age at increased risk of disability pension and invite them for preventive interventions.

Novel Breast Imaging and Machine Learning: Predicting Breast Lesion Malignancy at Cone-Beam CT Using Machine Learning Techniques.

Science.gov (United States)

Uhlig, Johannes; Uhlig, Annemarie; Kunze, Meike; Beissbarth, Tim; Fischer, Uwe; Lotz, Joachim; Wienbeck, Susanne

2018-05-24

The purpose of this study is to evaluate the diagnostic performance of machine learning techniques for malignancy prediction at breast cone-beam CT (CBCT) and to compare them to human readers. Five machine learning techniques, including random forests, back propagation neural networks (BPN), extreme learning machines, support vector machines, and K-nearest neighbors, were used to train diagnostic models on a clinical breast CBCT dataset with internal validation by repeated 10-fold cross-validation. Two independent blinded human readers with profound experience in breast imaging and breast CBCT analyzed the same CBCT dataset. Diagnostic performance was compared using AUC, sensitivity, and specificity. The clinical dataset comprised 35 patients (American College of Radiology density type C and D breasts) with 81 suspicious breast lesions examined with contrast-enhanced breast CBCT. Forty-five lesions were histopathologically proven to be malignant. Among the machine learning techniques, BPNs provided the best diagnostic performance, with AUC of 0.91, sensitivity of 0.85, and specificity of 0.82. The diagnostic performance of the human readers was AUC of 0.84, sensitivity of 0.89, and specificity of 0.72 for reader 1 and AUC of 0.72, sensitivity of 0.71, and specificity of 0.67 for reader 2. AUC was significantly higher for BPN when compared with both reader 1 (p = 0.01) and reader 2 (p Machine learning techniques provide a high and robust diagnostic performance in the prediction of malignancy in breast lesions identified at CBCT. BPNs showed the best diagnostic performance, surpassing human readers in terms of AUC and specificity.

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.

Residual Convolutional Neural Network for the Determination of IDH Status 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

2018-03-01

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; 24(5); 1073-81. ©2017 AACR . ©2017 American Association for Cancer Research.

Statistical properties of a utility measure of observer performance compared to area under the ROC curve

Science.gov (United States)

Abbey, Craig K.; Samuelson, Frank W.; Gallas, Brandon D.; Boone, John M.; Niklason, Loren T.

2013-03-01

The receiver operating characteristic (ROC) curve has become a common tool for evaluating diagnostic imaging technologies, and the primary endpoint of such evaluations is the area under the curve (AUC), which integrates sensitivity over the entire false positive range. An alternative figure of merit for ROC studies is expected utility (EU), which focuses on the relevant region of the ROC curve as defined by disease prevalence and the relative utility of the task. However if this measure is to be used, it must also have desirable statistical properties keep the burden of observer performance studies as low as possible. Here, we evaluate effect size and variability for EU and AUC. We use two observer performance studies recently submitted to the FDA to compare the EU and AUC endpoints. The studies were conducted using the multi-reader multi-case methodology in which all readers score all cases in all modalities. ROC curves from the study were used to generate both the AUC and EU values for each reader and modality. The EU measure was computed assuming an iso-utility slope of 1.03. We find mean effect sizes, the reader averaged difference between modalities, to be roughly 2.0 times as big for EU as AUC. The standard deviation across readers is roughly 1.4 times as large, suggesting better statistical properties for the EU endpoint. In a simple power analysis of paired comparison across readers, the utility measure required 36% fewer readers on average to achieve 80% statistical power compared to AUC.

Optimizing area under the ROC curve using semi-supervised learning.

Science.gov (United States)

Wang, Shijun; Li, Diana; Petrick, Nicholas; Sahiner, Berkman; Linguraru, Marius George; Summers, Ronald M

2015-01-01

Receiver operating characteristic (ROC) analysis is a standard methodology to evaluate the performance of a binary classification system. The area under the ROC curve (AUC) is a performance metric that summarizes how well a classifier separates two classes. Traditional AUC optimization techniques are supervised learning methods that utilize only labeled data (i.e., the true class is known for all data) to train the classifiers. In this work, inspired by semi-supervised and transductive learning, we propose two new AUC optimization algorithms hereby referred to as semi-supervised learning receiver operating characteristic (SSLROC) algorithms, which utilize unlabeled test samples in classifier training to maximize AUC. Unlabeled samples are incorporated into the AUC optimization process, and their ranking relationships to labeled positive and negative training samples are considered as optimization constraints. The introduced test samples will cause the learned decision boundary in a multidimensional feature space to adapt not only to the distribution of labeled training data, but also to the distribution of unlabeled test data. We formulate the semi-supervised AUC optimization problem as a semi-definite programming problem based on the margin maximization theory. The proposed methods SSLROC1 (1-norm) and SSLROC2 (2-norm) were evaluated using 34 (determined by power analysis) randomly selected datasets from the University of California, Irvine machine learning repository. Wilcoxon signed rank tests showed that the proposed methods achieved significant improvement compared with state-of-the-art methods. The proposed methods were also applied to a CT colonography dataset for colonic polyp classification and showed promising results.

Insulin and GH secretion in adolescent girls with irregular cycles: polycystic vs multifollicular ovaries.

Science.gov (United States)

Villa, P; Rossodivita, A; Fulghesu, A M; Cucinelli, F; Barini, A; Apa, R; Belosi, C; Lanzone, A

2003-04-01

In the present study insulin (I) and GH secretion was studied in a group of twenty-five young adolescent girls (mean age: 15 +/- 0.23 yr) with cycle irregularity associated to clinical signs of hyperandrogenism in comparison with that observed in eleven normal matched subjects with regular menses. All patients underwent basal hormone measurements and, on two consecutive days, an oral glucose tolerance test (OGTT) and a GHRH iv test. Therefore, all subjects had a transabdominal US scan for the measurement of ovarian volume and the characterization of ovarian morphology. On the basis of the US examination we found patients with polycystic ovaries (PCO-like group) and subjects with multifollicular ovaries (MFO group). PCO-like group exhibited T (pirregular menses showed plasma concentrations of AUC for I (AUC-I) significantly higher in respect to control group (7359.4 +/- 709 vs 5447 +/- 431 microIU/ml x 180 min, p<0.01) as well as both PCO-like group and MFO group did (p<0.001 and p<0.01) respectively. MFO group showed higher values of the AUC for GH (AUC-GH) (2809 +/- 432 ng/ml x 120 min) in respect to controls (1708 +/- 208 ng/ml x 120 min, p<0.05) and PCO-like subjects (p<0.001), who on the contrary showed the lowest AUC-GH values (618 +/- 119 ng/ml x 120 min). In conclusion, PCO-like patients associated hyperinsulinemia with a blunted GH secretion while MFO patients had higher GH secretion associated with higher AUC-I values in a way suggesting an immature and still developing reproductive system.

Impact of insurance carrier, prior authorization, and socioeconomic status on appropriate use of SPECT myocardial perfusion imaging in private community-based office practice.

Science.gov (United States)

Doukky, Rami; Hayes, Kathleen; Frogge, Nathan; Nazir, Noreen T; Collado, Fareed M; Williams, Kim A

2015-05-01

The impact of health insurance carrier and socioeconomic status (SES) on the adherence to appropriate use criteria (AUC) for radionuclide myocardial perfusion imaging (MPI) is unknown. Health insurance carrier's prior authorization and patient's SES impact adherence to AUC for MPI in a fee-for-service setting. We conducted a prospective cohort study of 1511 consecutive patients who underwent outpatient MPI in a multi-site, office-based, fee-for-service setting. The patients were stratified according to the 2009 AUC into appropriate/uncertain appropriateness and inappropriate use groups. Insurance status was categorized as Medicare (does not require prior authorization) vs commercial (requires prior authorization). Socioeconomic status was determined by the median household income in the ZIP code of residence. The proportion of patients with Medicare was 33% vs 67% with commercial insurance. The rate of inappropriate use was higher among patients with commercial insurance vs Medicare (55% vs 24%; P impact AUC determination (odds ratio: 1.06, 95% confidence interval: 0.62-1.82, P = 0.82). The mean annual household income in the residential areas of patients with inappropriate use as compared to those with appropriate/uncertain use was $72 000 ± 21 000 vs $68 000 ± 20 000, respectively (P impact AUC determination, SES (top vs bottom quartile income area) was not independently predictive of inappropriate MPI use (odds ratio: 0.9, 95% confidence interval: 0.53-1.52, P = 0.69). Insurance carriers prior authorization and SES do not seem to play a significant role in determining physicians adherence to AUC for MPI. © 2015 Wiley Periodicals, Inc.

A single-dose, randomized, two-way crossover study comparing two olanzapine tablet products in healthy adult male volunteers under fasting conditions.

Science.gov (United States)

Elshafeey, Ahmed H; Elsherbiny, Mohamed A; Fathallah, Mohsen M

2009-03-01

Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepine class. The aim of this study was to assess the bioequivalence of 2 commercial 10-mg tablet formulations of olanzapine by statistical analysis of the pharmacokinetic parameters C(max), AUC from 0 to 72 hours after dosing (AUC(0-72)), and AUC(0-infinity) as required by the Egyptian health authority for the marketing of a generic product. This bioequivalence study was carried out in healthy male volunteers using a single-dose, randomized, 2-way crossover design under fasting conditions. Statistical analysis of the pharmacokinetic parameters C(max), AUC(0-72), and AUC(0-infinity) was conducted to determine bioequivalence (after log-transformation of data using analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The formulations were considered to be bioequivalent if the log-transformed ratios of the 3 pharmacokinetic parameters were within the predetermined bioequivalence range (ie, 80%-125%), as established by the US Food and Drug Administration (FDA). Both the test product (Trademark: Integrol((R)) [Global Napi Pharmaceuticals, Cairo, Egypt]) and the reference product (Trademark: Zyprexa((R)) [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom]) were administered as 10-mg tablets with 240 mL of water after an overnight fast on 2 treatment days, separated by a 2-week washout period. After dosing, serial blood samples were collected for 72 hours. Plasma samples were analyzed using a sensitive, reproducible, and accurate liquid chromatography-tandem mass spectrometry method capable of quantitating olanzapine in the range of 0.167 to 16.7 ng/mL, with a lower limit of quantitation of 0.167 ng/mL. Adverse events were reported by the volunteers as instructed or observed by the resident physician, and were recorded, tabulated, and evaluated. Twenty-four healthy adult male volunteers participated in this study. Their mean (SD) age was 24.7 (6.2) years (range, 19

Development of fluidized-bed furnace for thermal treatment of ammonium uranyl carbonate

Energy Technology Data Exchange (ETDEWEB)

Gupta, U C; Anuradha, M; Meena, R [Nuclear Fuel Complex, Hyderabad (India)

1994-06-01

At present the ammonium uranyl carbonate (AUC) route is developed at a scale of 10 kg/day of UO{sub 2}. This UO{sub 2} is directly compactible and sinterable to densities of 10.55-10.65 gm/cc. The equipment developed include precipitation tank with filtration and methanol washing and fluidized bed furnaces for thermal treatment of AUC and U{sub 3}O{sub 8}. During the design and development of these furnaces many experiments were conducted to study fluidization of AUC powder. In this paper the findings of these studies are presented. (author). 3 refs., 4 figs., 3 tabs.

Impact of cereal fibre on glucose-regulating factors

DEFF Research Database (Denmark)

Weickert, M O; Mohlig, M; Koebnick, C

2005-01-01

postprandial glucose response on the following day subsequent to ingestion of a control meal (AUC(C-C) 4,140+/-401, AUC(C-WF) 2,850+/-331 [p=0.007], AUC(C-OF) 2,830+/-277 [p=0.011]), with no difference in maximal concentration and T(max) of glucose responses. No differences in insulin responses were observed......AIMS/HYPOTHESIS: Insoluble dietary fibre intake is associated, by unknown mechanisms, with a reduced risk of type 2 diabetes. We investigated whether a short-term dietary intervention with purified insoluble fibres influences acute and delayed responses of glucose, insulin, glucose...

Genetic and Environmental Pathways in Type 1 Diabetes Complications

Science.gov (United States)

2010-09-01

Chicago, IL) at 5 g/kg body weight. Blood glucose levels were determined and plotted as a function of time. Area under the curve ( AUC ) of blood ... Blood glucose (mg/dL) 86 ± 12 101 ± 7 AUC (arbitrary unit) 1.0 ± 0.09 1.7 ± 0.13 ⁎ Plasma insulin (μU/mL) 0.17 ± 0.03 0.73 ± 0.13 ⁎ Plasma NEFA (mEq/L...was performed after 7 weeks of fructose feeding for the determination of AUC of blood glucose profiles in response to glucose challenge. Hamsters were

Tools to identify linear combination of prognostic factors which maximizes area under receiver operator curve.

Science.gov (United States)

Todor, Nicolae; Todor, Irina; Săplăcan, Gavril

2014-01-01

The linear combination of variables is an attractive method in many medical analyses targeting a score to classify patients. In the case of ROC curves the most popular problem is to identify the linear combination which maximizes area under curve (AUC). This problem is complete closed when normality assumptions are met. With no assumption of normality search algorithm are avoided because it is accepted that we have to evaluate AUC n(d) times where n is the number of distinct observation and d is the number of variables. For d = 2, using particularities of AUC formula, we described an algorithm which lowered the number of evaluations of AUC from n(2) to n(n-1) + 1. For d > 2 our proposed solution is an approximate method by considering equidistant points on the unit sphere in R(d) where we evaluate AUC. The algorithms were applied to data from our lab to predict response of treatment by a set of molecular markers in cervical cancers patients. In order to evaluate the strength of our algorithms a simulation was added. In the case of no normality presented algorithms are feasible. For many variables computation time could be increased but acceptable.

Cortisol stress response is positively correlated with central obesity in obese women with binge eating disorder (BED) before and after cognitive-behavioral treatment.

Science.gov (United States)

Gluck, Marci E; Geliebter, Allan; Lorence, Margarita

2004-12-01

Stress is the most commonly reported trigger of binge eating, and high cortisol levels are positively related to both central body fat and food intake after laboratory stress. We therefore examined waist circumference (WHR) and cortisol stress responsivity after a cold pressor stress test (CPT) in 22 obese (BMI > 27) women (11 BED, 11 non-BED). BMI and WHR did not differ between groups. The BED group had higher morning basal cortisol than the non-BED group (P = .03) and greater AUC cortisol after CPT, after controlling for AUC insulin (P = .04). In the BED group, WHR was related to AUC cortisol (P = .002) and peak cortisol stress responsivity (P = .003). Twenty (10 non-BED, 10 BED) were randomized to a 6-week treatment program (CBT + Diet) or Wait-List (WL) control group. There were no BED group or treatment-group differences in WHR, morning basal cortisol, or AUC cortisol after CPT. The relationship between WHR and both AUC cortisol (P = .002) and peak cortisol stress responsivity after CPT (P = .008) remained significant in the BED group. In BED, there is a hyperactive HPA axis related to abdominal obesity that persists even after treatment, suggesting that cortisol might be a primary factor in the disorder.

Tobacco smoking strengthens the association of elevated blood pressure with arterial stiffness: the Bogalusa Heart Study.

Science.gov (United States)

Yun, Miaoying; Li, Shengxu; Sun, Dianjianyi; Ge, Shaoqing; Lai, Chin-Chih; Fernandez, Camilo; Chen, Wei; Srinivasan, Sathanur R; Berenson, Gerald S

2015-02-01

The study assessed the hypothesis that smoking strengthens the association of adult arterial stiffness with long-term cumulative burden of blood pressure (BP) from childhood to adulthood. Tobacco smoking and elevated BPs are important risk factors of vascular stiffness. However, the synergistic effect of these two risk factors is not well established, especially for the long-term burden of elevated BP since childhood. The study cohort consisted of 945 adults (661 whites and 284 blacks, aged 24-43 years) who have BP measured 4-15 times since childhood (aged 4-17 years) in Bogalusa, Louisiana. The adult arterial stiffness was measured as aorta-femoral pulse wave velocity (afPWV); the total area under the curve (AUC) and incremental AUC were used as a measure of long-term burden and trends of BP, respectively. Increased adult afPWV was significantly associated with higher adulthood (P AUC (P AUC (P AUC (P = 0.007) were significantly greater among the current smokers than among the nonsmokers. DBP showed a similar pattern regarding the smoking-BP interaction on afPWV. These results, by showing the synergistic effect of tobacco smoking and long-term BP measures from childhood to adulthood on arterial stiffening process, underscore the importance of undertaking preventive strategies early in life and smoking behavior control.

Applying an Evidence-Based Assessment Model to Identify Students at Risk for Perceived Academic Problems following Concussion.

Science.gov (United States)

Ransom, Danielle M; Burns, Alison R; Youngstrom, Eric A; Vaughan, Christopher G; Sady, Maegan D; Gioia, Gerard A

2016-11-01

The aim of this study was to demonstrate the utility of an evidence-based assessment (EBA) model to establish a multimodal set of tools for identifying students at risk for perceived post-injury academic problems. Participants included 142 students diagnosed with concussion (age: M=14.95; SD=1.80; 59% male), evaluated within 4 weeks of injury (median=16 days). Demographics, pre-injury history, self- and parent-report measures assessing symptom severity and executive functions, and cognitive test performance were examined as predictors of self-reported post-injury academic problems. Latent class analysis categorized participants into "high" (44%) and "low" (56%) levels of self-reported academic problems. Receiver operating characteristic analyses revealed significant discriminative validity for self- and parent-reported symptom severity and executive dysfunction and self-reported exertional response for identifying students reporting low versus high academic problems. Parent-reported symptom ratings [area under the receiver operating characteristic curve (AUC)=.79] and executive dysfunction (AUC=.74), and self-reported ratings of executive dysfunction (AUC=.84), symptoms (AUC=.80), and exertional response (AUC=.70) each classified students significantly better than chance (psperspective in the management of concussion by applying traditional strengths of neuropsychological assessment to clinical decision making. (JINS, 2016, 22, 1038-1049).

The ACS NSQIP Risk Calculator Is a Fair Predictor of Acute Periprosthetic Joint Infection.

Science.gov (United States)

Wingert, Nathaniel C; Gotoff, James; Parrilla, Edgardo; Gotoff, Robert; Hou, Laura; Ghanem, Elie

2016-07-01

Periprosthetic joint infection (PJI) is a severe complication from the patient's perspective and an expensive one in a value-driven healthcare model. Risk stratification can help identify those patients who may have risk factors for complications that can be mitigated in advance of elective surgery. Although numerous surgical risk calculators have been created, their accuracy in predicting outcomes, specifically PJI, has not been tested. (1) How accurate is the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Surgical Site Infection Calculator in predicting 30-day postoperative infection? (2) How accurate is the calculator in predicting 90-day postoperative infection? We isolated 1536 patients who underwent 1620 primary THAs and TKAs at our institution during 2011 to 2013. Minimum followup was 90 days. The ACS NSQIP Surgical Risk Calculator was assessed in its ability to predict acute PJI within 30 and 90 days postoperatively. Patients who underwent a repeat surgical procedure within 90 days of the index arthroplasty and in whom at least one positive intraoperative culture was obtained at time of reoperation were considered to have PJI. A total of 19 cases of PJI were identified, including 11 at 30 days and an additional eight instances by 90 days postoperatively. Patient-specific risk probabilities for PJI based on demographics and comorbidities were recorded from the ACS NSQIP Surgical Risk Calculator website. The area under the curve (AUC) for receiver operating characteristic (ROC) curves was calculated to determine the predictability of the risk probability for PJI. The AUC is an effective method for quantifying the discriminatory capacity of a diagnostic test to correctly classify patients with and without infection in which it is defined as excellent (AUC 0.9-1), good (AUC 0.8-0.89), fair (AUC 0.7-0.79), poor (AUC 0.6-0.69), or fail/no discriminatory capacity (AUC 0.5-0.59). A p value of fair accuracy in predicting 30

Population pharmacokinetics and limited sampling strategy for first-line tuberculosis drugs and moxifloxacin

NARCIS (Netherlands)

Magis-Escurra, C.; Later-Nijland, H. M. J.; Alffenaar, J. W. C.; Broeders, J.; Burger, D. M.; van Crevel, R.; Boeree, M. J.; Donders, A. R. T.; van Altena, R.; van der Werf, T. S.; Aarnoutse, R. E.

Therapeutic drug monitoring (TDM) of tuberculosis (TB) drugs currently focuses on peak plasma concentrations, yet total exposure [area under the 24-h concentration-time curve (AUC(0-24))] is probably most relevant to the efficacy of these drugs. We therefore assessed population AUC(0-24) data for

Performances comparées du HDL-cholestérol et du ratio cholestérol ...

African Journals Online (AJOL)

Pour le dépistage du SMet, l'AUC du CT/HDL-C est de 0,69 (IC 95% 0,61-0,77) chez les ... high blood pressure (BP), high fasting glucose, low HDL-C and high triglycerides. Areas under the "Receiver operator characteristic" curves (AUC)

Comparative performance of different stochastic methods to simulate drug exposure and variability in a population.

Science.gov (United States)

Tam, Vincent H; Kabbara, Samer

2006-10-01

Monte Carlo simulations (MCSs) are increasingly being used to predict the pharmacokinetic variability of antimicrobials in a population. However, various MCS approaches may differ in the accuracy of the predictions. We compared the performance of 3 different MCS approaches using a data set with known parameter values and dispersion. Ten concentration-time profiles were randomly generated and used to determine the best-fit parameter estimates. Three MCS methods were subsequently used to simulate the AUC(0-infinity) of the population, using the central tendency and dispersion of the following in the subject sample: 1) K and V; 2) clearance and V; 3) AUC(0-infinity). In each scenario, 10000 subject simulations were performed. Compared to true AUC(0-infinity) of the population, mean biases by various methods were 1) 58.4, 2) 380.7, and 3) 12.5 mg h L(-1), respectively. Our results suggest that the most realistic MCS approach appeared to be based on the variability of AUC(0-infinity) in the subject sample.

C2 (2-h) levels are not superior to trough levels as estimates of the area under the curve in tacrolimus-treated renal-transplant patients

DEFF Research Database (Denmark)

Jørgensen, Kaj; Povlsen, Johan; Madsen, Søren

2002-01-01

and AUC by Pearson's correlation coefficient, and pairs of correlation coefficients were compared by an asymptotic Wald-type test. RESULTS: AUC varied five-fold despite near-equal dosing. Pearson's correlation coefficient for trough level, 1, 2, 3, 4, and 6 h were 0.84, 0.60, 0.81, 0.95, 0.95, and 0.......94 on day 3 and 0.94, 0.69, 0.92, 0.96, 0.94, 0.92 on day 14. Three-, 4- and 6-h levels had significantly higher correlation coefficients compared to trough, 1- and 2-h levels. One-hour samples had significantly lower correlation coefficients compared to all other sampling times on day 14. The patient...... with the highest AUC developed nephrotoxicity despite trough levels in the desired range. CONCLUSIONS: Two-hour levels are not superior to trough levels in tacrolimus-treated renal transplant patients. Despite good correlation between trough level and AUC, some patients may still receive nephrotoxic doses despite...

Minor Contribution of Endogenous GLP-1 and GLP-2 to Postprandial Lipemia in Obese Men

DEFF Research Database (Denmark)

Matikainen, Niina; Björnson, Elias; Söderlund, Sanni

2016-01-01

CONTEXT: Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified. OBJECTIVE: To explore the responses of GLP-1, GLP-2 and GIP after...... and after a fat-rich meal in 65 healthy obese (BMI 26.5-40.2 kg/m2) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2) were measured after the fat-rich meal. MAIN OUTCOME MEASURES: Postprandial responses (area under the curve, AUC) for glucose...... AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2...

Bilirubin exposure is associated with neonatal sepsis in the eight days preceding symptoms: a retrospective study.

Science.gov (United States)

Raimondi, Francesco; Borrelli, Angela Carla; Ferrara, Teresa; Giannattasio, Antonietta; Capasso, Letizia

2017-09-01

To compare levels of bilirubin (using the area under the curve, AUC) in preterm infants before the onset of sepsis with healthy matched-controls. Preterm infants born between January 2011 and December 2015 with late-onset sepsis were enrolled in our retrospective study and were matched with healthy controls (sex, birth weight and gestational age). Levels of bilirubin were registered in the eight days preceding the onset of sepsis and the AUC was calculated for both groups. Eighty-eight neonates (44 cases) were studied. GA and BW did not differ between cases and controls. In cases, we found a higher value of AUC (30.7 versus 22.5; p = 0.021). In our retrospective cohort, we found that the levels of bilirubin and the AUC in the first eight days before the onset of sepsis in preterm infants were significantly higher than the healthy controls. These data suggest that the prolonged exposition to high levels of bilirubin could increase the infection susceptibility in preterm infants.

Incretin responses to oral glucose and mixed meal tests and changes in fasting glucose levels during 7 years of follow-up

DEFF Research Database (Denmark)

Koopman, A D M; Rutters, F; Rauh, S P

2018-01-01

. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC). The association between incretin response at baseline...... and changes in fasting glucose levels was assessed using linear regression. The average change in glucose over 7 years was 0.43 ± 0.5 mmol/l. For GIP, no significant associations were observed with changes in fasting glucose levels. In contrast, participants within the middle and highest tertile of GLP-1 iAUC...... responses to OGTT had significantly smaller increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively, compared to those in the lowest tertile. The same trend was observed for tAUC GLP-1 following OGTT (highest...

Comparison of consumption behavior and appetite sensations among patients with type 2 diabetes mellitus after bariatric surgery.

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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 AUC (ΔAUC) 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.

The advantages of combination therapy on hypertension: development of immediate release perindopril-indapamide tablet and assessment of bioequivalence studies.

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Ölçer, A; Ölçer, M; İnce, I; Karasulu, E

2016-03-01

Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Convers Plus tablet including perindopril erbumine (PE), which is an angiotensin converting enzyme (ACE) inhibitor, and indapamide, which is diuretic, was designed as a combined tablet to succes in the treatment of hypertension. Physico-pharmaceutical properties and characterization studies were evaluated in vitro conditions. Later on in vivo study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study via peroral route in 24 healthy male subjects. In this study, bioequivalence with primary pharmacokinetical target parameters reference (Bipreterax 4/1.25 mg Tablet-S.A.Servier Benelux N.V.) and test (Convers Plus 4/1.25 mg Tablet-ARGESAN Pharmaceutical Company) tablets have been found bioequivalent. The results of pharmacokinetic parameters for perindopril, perindoprilat and indapamide were found as Cmax = 23.179 µg/mL, tmax = 0.729 h, t1/2 = 1.429 h; AUC0-t = 26.998 µgs/mL, AUC0-inf = 27.117 µgs/mL; Cmax = 1.834 µg/mL, tmax = 8.792 h, t1/2 = 40.699 h; AUC0-t = 54.828 µgs/mL, AUC0-inf = 77.113 µgs/mL; Cmax = 18.994 µg/mL, tmax = 3.417 h, t1/2 = 16.626 h and AUC0-t = 385.829 µgs/mL, AUC0-inf = 410.728 µgs/mL respectively. In conclusion, physico-pharmaceutical properties and results of clinical trials show that Convers Plus tablets have been found as bioequivalent for perindopril, perindoprilat and indapamide in terms of AUC and Cmax, in 90% confidence limits.

Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma, Epithelial Lining Fluid, and Alveolar Cells of Healthy Adult Subjects.

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Gotfried, Mark H; Horn, Karolyn; Garrity-Ryan, Lynne; Villano, Stephen; Tzanis, Evan; Chitra, Surya; Manley, Amy; Tanaka, S Ken; Rodvold, Keith A

2017-09-01

The steady-state concentrations of omadacycline and tigecycline in the plasma, epithelial lining fluid (ELF), and alveolar cells (AC) of 58 healthy adult subjects were obtained. Subjects were administered either omadacycline at 100 mg intravenously (i.v.) every 12 h for two doses followed by 100 mg i.v. every 24 h for three doses or tigecycline at an initial dose of 100 mg i.v. followed by 50 mg i.v. every 12 h for six doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject following the start of the fifth dose of omadacycline at 0.5, 1, 2, 4, 8, 12, or 24 h and after the start of the seventh dose of tigecycline at 2, 4, 6, or 12 h. The value of the area under the concentration-time curve (AUC) from time zero to 24 h postdosing (AUC 0-24 ) (based on mean concentrations) in ELF and the ratio of the ELF to total plasma omadacycline concentration based on AUC 0-24 values were 17.23 mg · h/liter and 1.47, respectively. The AUC 0-24 value in AC was 302.46 mg · h/liter, and the ratio of the AC to total plasma omadacycline concentration was 25.8. In comparison, the values of the AUC from time zero to 12 h postdosing (AUC 0-12 ) based on the mean concentrations of tigecycline in ELF and AC were 3.16 and 38.50 mg · h/liter, respectively. The ratio of the ELF and AC to total plasma concentrations of tigecycline based on AUC 0-12 values were 1.71 and 20.8, respectively. The pharmacokinetic advantages of higher and sustained concentrations of omadacycline compared to those of tigecycline in plasma, ELF, and AC suggest that omadacycline is a promising antibacterial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. Copyright © 2017 Gotfried et al.

Estimation of plasma area under the curve for etanidazole (SR 2508) in toxicity prediction and dose adjustment

International Nuclear Information System (INIS)

Workman, P.; Ward, R.; Maughan, T.S.; Newman, H.F.; Bleehen, N.M.

1989-01-01

The hydrophilic 2-nitroimidazole radiosensitizer etanidazole is currently undergoing clinical evaluation. Although considerably less neurotoxic than misonidazole because of its rapid renal clearance and partial exclusion from the nervous system, total dose is limited by peripheral neuropathy. Monitoring plasma etanidazole concentration in patients to determine the area under the curve (AUC0-infinity) has been proposed as a method of predicting patients at risk, and of providing a quantitative basis for dose reduction in such patients. Successful application of this policy requires accurate assessment of AUC0-infinity. We have analyzed plasma data for 18 patients receiving 2 g/m2 etanidazole to determine the errors introduced in the estimation of AUC0-infinity caused by omitting selected time points from the analysis. A 'baseline' AUC0-infinity value was calculated by integration of the rate equation for the 2-compartment model using data points at 0, 15, and 30 min and 1, 2, 4, 8, 12, and 24 hr after the end of infusion. The mean +/- SD area for AUC0-infinity was 502 +/- 152 micrograms ml-1 h (2.35 +/- 0.71 mM.h). Omitting the zero or the 24 hr time point, the average errors were quite small (2.5% in both cases), but errors of up to 16.4 and 7.3%, respectively, were seen for individual patients. Leaving out both the 8 hr and 12 hr points at the same time gave a similar low average error of 2.9%, with a highest error of 7.3%. Omitting all data points after 4 hr, the mean error was 24.7% and 15 of 18 patients had errors in excess of 10%. In addition, failure to correct for infusion time results in an underestimation of AUC0-infinity averaging 4.5% (range 1.9-8.7%). The choice of sampling times for toxicological monitoring will depend upon the accuracy with which the AUC0-infinity must be known. Including all data points between 0 and 24 hr will minimize errors

Prognostic Value of Non-Invasive Fibrosis and Steatosis Tools, Hepatic Venous Pressure Gradient (HVPG and Histology in Nonalcoholic Steatohepatitis.

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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.

Is waist circumference a better predictor of diabetes than body mass index or waist-to-height ratio in Iranian adults?

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Hajian-Tilaki, Karimollah; Heidari, Bezad

2015-01-01

Several measures of adiposity have been used for predicting diabetes. The results of studies regarding superiority of waist circumference (WC) to body mass index (BMI) are inconsistent. This study designed to compare the ability of different anthropometric measures in predicting diabetes and to determine their optimal cut-off values. A population-based cross-sectional study was conducted with 1,000 representative sample among adults aged 20-80 years in Babol, the Northern Iran. The demographic data were collected in a household survey, and the anthropometric measures of weight, height, waist, and hip circumference were measured with a standard method. Fasting blood sugar (FBS) ≥126 mg/dl was considered as diabetes. receiver operating characteristic analysis was used to estimate the predictive ability of different anthropometric indexes and their optimal cut-off values for high FBS. The overall prevalence rate of diabetes was 14.0% (14.4% in men vs. 13.5% in women, P = 0.65). The prevalence rate was significantly higher in older age (>60 years), low educated and obese (P = 0.001). The mean of BMI, WC, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were significantly higher among diabetic in both sexes (P = 0.001). Among men, WC (area under the ROC curve [AUC] =0.64) and WHtR (AUC = 0.63) have slightly higher accuracy index compared with BMI (AUC = 0.62) or WHR (AUC = 0.60). In contrast, among women, WHtR (AUC = 0.69) and WC (AUC = 0.68) yielded slightly better predictive than BMI (AUC = 0.67). The optimal cut-off values obtained for BMI and WHtR were similar between two sexes (BMI = 24.95 kg/m(2) for men and BMI = 25.2 kg/m(2) for women, WHtR = 0.51 for both sexes) whereas the optimal cut-off value for WC was higher in men than women (98.5 cm men vs. 89.5 cm women). Overall WC and WHtR exhibited a slightly better discriminate performance than BMI for diabetes in both sexes, particularly in women.

AVC: Selecting discriminative features on basis of AUC by maximizing variable complementarity.

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Sun, Lei; Wang, Jun; Wei, Jinmao

2017-03-14

The Receiver Operator Characteristic (ROC) curve is well-known in evaluating classification performance in biomedical field. Owing to its superiority in dealing with imbalanced and cost-sensitive data, the ROC curve has been exploited as a popular metric to evaluate and find out disease-related genes (features). The existing ROC-based feature selection approaches are simple and effective in evaluating individual features. However, these approaches may fail to find real target feature subset due to their lack of effective means to reduce the redundancy between features, which is essential in machine learning. In this paper, we propose to assess feature complementarity by a trick of measuring the distances between the misclassified instances and their nearest misses on the dimensions of pairwise features. If a misclassified instance and its nearest miss on one feature dimension are far apart on another feature dimension, the two features are regarded as complementary to each other. Subsequently, we propose a novel filter feature selection approach on the basis of the ROC analysis. The new approach employs an efficient heuristic search strategy to select optimal features with highest complementarities. The experimental results on a broad range of microarray data sets validate that the classifiers built on the feature subset selected by our approach can get the minimal balanced error rate with a small amount of significant features. Compared with other ROC-based feature selection approaches, our new approach can select fewer features and effectively improve the classification performance.

Early detection of Alzheimer's disease using MRI hippocampal texture

DEFF Research Database (Denmark)

Sørensen, Lauge; Igel, Christian; Hansen, Naja Liv

2016-01-01

the receiver operating characteristic curve [AUC] 0.74 vs 0.67; DeLong test, p = 0.005), and provided even better prognostic results in AIBL (AUC 0.83). Hippocampal texture, but not volume, correlated with Addenbrooke's cognitive examination score (Pearson correlation, r = −0.25, p ...

Correlation of six-minute walking performance with quality of life is domain- and gender-specific in healthy older adults.

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Andrey Jorge Serra

Full Text Available We analyzed the relationship between performance on the 6-min walk test (6MWT and health-related quality of life (HRQoL in older subjects. Our secondary aim was to determine the distance to be completed on the 6MWT for the subject to achieve a score of 50 on the Short Form (36 Health Survey (SF-36. Associations were tested using linear correlation and multivariate linear regression. Participants were 130 healthy older individuals. The predictive performance of the 6MWT based on an SF-36 score of 50 was assessed using a receiver operating characteristic curve and its area under curve (AUC. Associations were observed between physical functioning, role-emotional, social functioning, vitality, general health score, and 6MWT performance in women, after adjusting for confounding variables (coefficients: 0.57, 0.38, 0.40, and 0.46, respectively; p < 0.05. No association was found for men. The distance for the 6MWT to predict an SF-36 score of 50 was 481 m for men in the physical functioning (AUC: 0.79 and role-physical (AUC: 0.84 domains, and 420 m for women in role-emotional (AUC: 0.75, role-physical (AUC: 0.80, and general health (AUC: 0.80 domains. Our results indicate that superior 6MWT performance may be associated with better HRQoL in several domains in only healthy older women. No association between 6MWT performance and role-emotional, mental health, or vitality domains was found. We suggest that a score of 50 is represented by a 6MWT distance of 481 m for men and 420 m for women, at least in the role-physical domain.

Automatic Detection of Compensation During Robotic Stroke Rehabilitation Therapy.

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Zhi, Ying Xuan; Lukasik, Michelle; Li, Michael H; Dolatabadi, Elham; Wang, Rosalie H; Taati, Babak

2018-01-01

Robotic stroke rehabilitation therapy can greatly increase the efficiency of therapy delivery. However, when left unsupervised, users often compensate for limitations in affected muscles and joints by recruiting unaffected muscles and joints, leading to undesirable rehabilitation outcomes. This paper aims to develop a computer vision system that augments robotic stroke rehabilitation therapy by automatically detecting such compensatory motions. Nine stroke survivors and ten healthy adults participated in this study. All participants completed scripted motions using a table-top rehabilitation robot. The healthy participants also simulated three types of compensatory motions. The 3-D trajectories of upper body joint positions tracked over time were used for multiclass classification of postures. A support vector machine (SVM) classifier detected lean-forward compensation from healthy participants with excellent accuracy (AUC = 0.98, F1 = 0.82), followed by trunk-rotation compensation (AUC = 0.77, F1 = 0.57). Shoulder-elevation compensation was not well detected (AUC = 0.66, F1 = 0.07). A recurrent neural network (RNN) classifier, which encodes the temporal dependency of video frames, obtained similar results. In contrast, F1-scores in stroke survivors were low for all three compensations while using RNN: lean-forward compensation (AUC = 0.77, F1 = 0.17), trunk-rotation compensation (AUC = 0.81, F1 = 0.27), and shoulder-elevation compensation (AUC = 0.27, F1 = 0.07). The result was similar while using SVM. To improve detection accuracy for stroke survivors, future work should focus on predefining the range of motion, direct camera placement, delivering exercise intensity tantamount to that of real stroke therapies, adjusting seat height, and recording full therapy sessions.

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

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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.

Diagnostic performances of serum liver enzymes and cytokines in non-alcoholic fatty liver disease

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Hakan Turkon

2015-03-01

Full Text Available Objective:Non-alcoholic fatty liver disease (NAFLD is affecting people worldwide with increasing prevalence. Non-invasive tests are required for both diagnosis and staging of the disease. We aimed to evaluate diagnostic accuracy of routine liver enzymes and cytokines in NAFLD. Methods:A total of 88 cases, aged between 20 and 62 years, were included in the study. Serum ALT, AST, GGT, triglyceride, TNF-alpha, IL-6 and IL-8 were measured in 40 patients with NAFLD and in 48 healthy control patients with similar BMI and demographic characteristics. Diagnostic performances of serum biomarkers for diagnosis of NAFLD were evaluated with ROC analysis. Results:ALT and AST showed good diagnostic performance in predicting patients with NAFLD in the overall group (AUC=0.817; 95% CI[0.721-0.913], AUC=0.815;95% CI[0.718-0.911] respectively but in obese subjects ALT and AST showed poor performance (AUC=0.659;95% CI[0.478-0.841], AUC=0.680; 95% CI[0.498-0.861] respectively. Among cytokines TNF-alpha showed best performance in the diagnosis of NAFLD in both overall group and obese subjects (AUC=0.892; 95% CI[0.824- 0.959], AUC=0.858; 95% CI[0.739-0.977] respectively. The optimal cut off value for TNF-alpha was 10.65pg/ml with a sensitivity of 75% and a specificity of 93% in the overall group. IL-6 and IL-8 showed poor performance. Conclusion: TNF-alpha may be a good parameter for predicting patients with NAFLD. J Clin Exp Invest 2015;6 (1: 16-20

Evaluation of current prediction models for Lynch syndrome: updating the PREMM5 model to identify PMS2 mutation carriers.

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Goverde, A; Spaander, M C W; Nieboer, D; van den Ouweland, A M W; Dinjens, W N M; Dubbink, H J; Tops, C J; Ten Broeke, S W; Bruno, M J; Hofstra, R M W; Steyerberg, E W; Wagner, A

2018-07-01

Until recently, no prediction models for Lynch syndrome (LS) had been validated for PMS2 mutation carriers. We aimed to evaluate MMRpredict and PREMM5 in a clinical cohort and for PMS2 mutation carriers specifically. In a retrospective, clinic-based cohort we calculated predictions for LS according to MMRpredict and PREMM5. The area under the operator receiving characteristic curve (AUC) was compared between MMRpredict and PREMM5 for LS patients in general and for different LS genes specifically. Of 734 index patients, 83 (11%) were diagnosed with LS; 23 MLH1, 17 MSH2, 31 MSH6 and 12 PMS2 mutation carriers. Both prediction models performed well for MLH1 and MSH2 (AUC 0.80 and 0.83 for PREMM5 and 0.79 for MMRpredict) and fair for MSH6 mutation carriers (0.69 for PREMM5 and 0.66 for MMRpredict). MMRpredict performed fair for PMS2 mutation carriers (AUC 0.72), while PREMM5 failed to discriminate PMS2 mutation carriers from non-mutation carriers (AUC 0.51). The only statistically significant difference between PMS2 mutation carriers and non-mutation carriers was proximal location of colorectal cancer (77 vs. 28%, p PMS2 mutation carriers (AUC 0.77) and overall (AUC 0.81 vs. 0.72). We validated these results in an external cohort of 376 colorectal cancer patients, including 158 LS patients. MMRpredict and PREMM5 cannot adequately identify PMS2 mutation carriers. Adding location of colorectal cancer to PREMM5 may improve the performance of this model, which should be validated in larger cohorts.

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.

Detection of small pulmonary nodules on chest radiographs: efficacy of dual-energy subtraction technique using flat-panel detector chest radiography

International Nuclear Information System (INIS)

Oda, S.; Awai, K.; Funama, Y.; Utsunomiya, D.; Yanaga, Y.; Kawanaka, K.; Nakaura, T.; Hirai, T.; Murakami, R.; Nomori, H.; Yamashita, Y.

2010-01-01

Aim: To investigate the effect of a double-exposure dual-energy subtraction (DES) technique on the diagnostic performance of radiologists detecting small pulmonary nodules on flat-panel detector (FPD) chest radiographs. Materials and methods: Using FPD radiography 41 sets of chest radiographs were obtained from 26 patients with pulmonary nodules measuring ≤20 mm and from 15 normal participants. Each dataset included standard and corresponding DES images. There were six non-solid, 10 part-solid, and 10 solid nodules. The mean size of the 26 nodules was 15 ± 4.8 mm. Receiver operating characteristic (ROC) analysis was performed to compare the performance of the eight board-certified radiologists. Results: For the eight radiologists, the mean value of the area under the ROC curve (AUC) without and with DES images was 0.62 ± 0.05 and 0.68 ± 0.05, respectively; the difference was statistically significant (p = 0.02). For part-solid nodules, the difference of the mean AUC value was statistically significant (AUC = 0.61 ± 0.07 versus 0.69 ± 0.05; p < 0.01); for non-solid nodules it was not (AUC = 0.62 ± 0.1 versus 0.61 ± 0.09; p = 0.73), and for solid nodules it was not (AUC = 0.75 ± 0.1 versus 0.78 ± 0.08; p = 0.23). For nodules with overlapping bone shadows, the difference of the mean AUC value was statistically significant (p = 0.03), for nodules without overlapping, it was not (p = 0.26). Conclusion: Use of a double-exposure DES technique at FPD chest radiography significantly improved the diagnostic performance of radiologists to detect small pulmonary nodules.

Volumetric quantitative characterization of human patellar cartilage with topological and geometrical features on phase-contrast X-ray computed tomography.

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Nagarajan, Mahesh B; Coan, Paola; Huber, Markus B; Diemoz, Paul C; Wismüller, Axel

2015-11-01

Phase-contrast X-ray computed tomography (PCI-CT) has attracted significant interest in recent years for its ability to provide significantly improved image contrast in low absorbing materials such as soft biological tissue. In the research context of cartilage imaging, previous studies have demonstrated the ability of PCI-CT to visualize structural details of human patellar cartilage matrix and capture changes to chondrocyte organization induced by osteoarthritis. This study evaluates the use of geometrical and topological features for volumetric characterization of such chondrocyte patterns in the presence (or absence) of osteoarthritic damage. Geometrical features derived from the scaling index method (SIM) and topological features derived from Minkowski Functionals were extracted from 1392 volumes of interest (VOI) annotated on PCI-CT images of ex vivo human patellar cartilage specimens. These features were subsequently used in a machine learning task with support vector regression to classify VOIs as healthy or osteoarthritic; classification performance was evaluated using the area under the receiver operating characteristic curve (AUC). Our results show that the classification performance of SIM-derived geometrical features (AUC: 0.90 ± 0.09) is significantly better than Minkowski Functionals volume (AUC: 0.54 ± 0.02), surface (AUC: 0.72 ± 0.06), mean breadth (AUC: 0.74 ± 0.06) and Euler characteristic (AUC: 0.78 ± 0.04) (p < 10(-4)). These results suggest that such geometrical features can provide a detailed characterization of the chondrocyte organization in the cartilage matrix in an automated manner, while also enabling classification of cartilage as healthy or osteoarthritic with high accuracy. Such features could potentially serve as diagnostic imaging markers for evaluating osteoarthritis progression and its response to different therapeutic intervention strategies.

Sedation and mechanical hypoalgesia after sublingual administration of detomidine hydrochloride gel to donkeys.

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Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Varner, Kelley M; Robinson, Lauren S

2016-07-01

OBJECTIVE To compare sedative and mechanical hypoalgesic effects of sublingual administration of 2 doses of detomidine gel to donkeys. DESIGN Randomized blinded controlled trial. ANIMALS 6 healthy castrated male donkeys. PROCEDURES In a crossover study design, donkeys received each of the following sublingual treatments 1 week apart in a randomly assigned order: 1 mL of molasses (D0) or detomidine hydrochloride gel at 20 μg/kg (9 μg/lb; D20) or 40 μg/kg (18 μg/lb; D40). Sedation score (SS), head height above the ground (HHAG), and mechanical nociceptive threshold (MNT) were assessed before and for 180 minutes after treatment. Areas under the effect change-versus-time curves (AUCs) from 0 to 30, 30 to 60, 60 to 120, and 120 to 180 minutes after administration were computed for SS, HHAG, and MNT and compared among treatments. RESULTS D20 and D40 resulted in greater SS AUCs from 60 to 120 minutes and smaller HHAG AUCs from 30 through 180 minutes than did D0. The D40 resulted in smaller HHAG AUCs from 60 to 120 minutes than did D20. Compared with D0 values, MNT AUCs from 60 to 120 minutes were higher for D20, whereas MNT AUCs from 30 through 180 minutes were higher for D40. CONCLUSIONS AND CLINICAL RELEVANCE D20 and D40 induced sedation and mechanical hypoalgesia in donkeys by > 30 minutes after administration, but only sedation was dose dependent. Sublingual administration of detomidine gel at 40 μg/kg may be useful for sedation of standing donkeys prior to potentially painful minor procedures.

Fe3O4@Au composite magnetic nanoparticles modified with cetuximab for targeted magneto-photothermal therapy of glioma cells.

Science.gov (United States)

Lu, Qianling; Dai, Xinyu; Zhang, Peng; Tan, Xiao; Zhong, Yuejiao; Yao, Cheng; Song, Mei; Song, Guili; Zhang, Zhenghai; Peng, Gang; Guo, Zhirui; Ge, Yaoqi; Zhang, Kangzhen; Li, Yuntao

2018-01-01

Thermoresponsive nanoparticles have become an attractive candidate for designing combined multimodal therapy strategies because of the onset of hyperthermia and their advantages in synergistic cancer treatment. In this paper, novel cetuximab (C225)-encapsulated core-shell Fe 3 O 4 @Au magnetic nanoparticles (Fe 3 O 4 @Au-C225 composite-targeted MNPs) were created and applied as a therapeutic nanocarrier to conduct targeted magneto-photothermal therapy against glioma cells. The core-shell Fe 3 O 4 @Au magnetic nanoparticles (MNPs) were prepared, and then C225 was further absorbed to synthesize Fe 3 O 4 @Au-C225 composite-targeted MNPs. Their morphology, mean particle size, zeta potential, optical property, magnetic property and thermal dynamic profiles were characterized. After that, the glioma-destructive effect of magnetic fluid hyperthermia (MFH) combined with near-infrared (NIR) hyperthermia mediated by Fe 3 O 4 @Au-C225 composite-targeted MNPs was evaluated through in vitro and in vivo experiments. The inhibitory and apoptotic rates of Fe 3 O 4 @Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group were significantly higher than other groups in vitro and the marked upregulation of caspase-3, caspase-8, and caspase-9 expression indicated excellent antitumor effect by inducing intrinsic apoptosis. Furthermore, Fe 3 O 4 @Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group exhibited significant tumor growth suppression compared with other groups in vivo. Our studies illustrated that Fe 3 O 4 @Au-C225 composite-targeted MNPs have great potential as a promising nanoplatform for human glioma therapy and could be of great value in medical use in the future.

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

Change in end-tidal carbon dioxide outperforms other surrogates for change in cardiac output during fluid challenge.

Science.gov (United States)

Lakhal, K; Nay, M A; Kamel, T; Lortat-Jacob, B; Ehrmann, S; Rozec, B; Boulain, T

2017-03-01

During fluid challenge, volume expansion (VE)-induced increase in cardiac output (Δ VE CO) is seldom measured. In patients with shock undergoing strictly controlled mechanical ventilation and receiving VE, we assessed minimally invasive surrogates for Δ VE CO (by transthoracic echocardiography): fluid-induced increases in end-tidal carbon dioxide (Δ VE E'CO2 ); pulse (Δ VE PP), systolic (Δ VE SBP), and mean systemic blood pressure (Δ VE MBP); and femoral artery Doppler flow (Δ VE FemFlow). In the absence of arrhythmia, fluid-induced decrease in heart rate (Δ VE HR) and in pulse pressure respiratory variation (Δ VE PPV) were also evaluated. Areas under the receiver operating characteristic curves (AUC ROC s) reflect the ability to identify a response to VE (Δ VE CO ≥15%). In 86 patients, Δ VE E'CO2 had an AUC ROC =0.82 [interquartile range 0.73-0.90], significantly higher than the AUC ROC for Δ VE PP, Δ VE SBP, Δ VE MBP, and Δ VE FemFlow (AUC ROC =0.61-0.65, all P  1 mm Hg (>0.13 kPa) had good positive (5.0 [2.6-9.8]) and fair negative (0.29 [0.2-0.5]) likelihood ratios. The 16 patients with arrhythmia had similar relationships between Δ VE E'CO2 and Δ VE CO to patients with regular rhythm ( r 2 =0.23 in both subgroups). In 60 patients with no arrhythmia, Δ VE E'CO2 (AUC ROC =0.84 [0.72-0.92]) outperformed Δ VE HR (AUC ROC =0.52 [0.39-0.66], P AUC ROC =0.73 [0.60-0.84], P =0.21). In the 45 patients with no arrhythmia and receiving ventilation with tidal volume AUC ROC =0.86 [0.72-0.95] vs 0.66 [0.49-0.80], P =0.02. Δ VE E'CO2 outperformed Δ VE PP, Δ VE SBP, Δ VE MBP, Δ VE FemFlow, and Δ VE HR and, during protective ventilation, arrhythmia, or both, it also outperformed Δ VE PPV. A value of Δ VE E'CO2 >1 mm Hg (>0.13 kPa) indicated a likely response to VE. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

[Study on correlation of glucagons, type 2 diabetes and impaired glucose regulation].

Science.gov (United States)

Xu, Tao; Shi, Me; Qiu, Yun-Xia; Wang, Yan-Gang

2014-06-01

To analyze the changes of patients with type 2 diabetes in different stages in glucagon (GC) and free fatty acid (FFA) in fasting, OGT and L-Arg experiments, and discusses the role of pancreatic alphabeta cells in diabetes pathogenesis by studying the relations among indexes such as glucagon (GC), free fatty acid (FFA) and blood glucose (BG), insulin, insulin homeostasis model (HOMA) and glucose metabolism hormone secretion curve, in order to provide theoretical basis for the treatment of diabetes. Study objects were divided into the T2DM group (45 cases), the IGT group (28 cases) and the NGT group (30 cases) for an OGTT experiment and then an L-Arg experiment on the next day. Under the fasting state, their blood glucose (FBG), insulin (F), glucagon (FGC), free fatty acid (FFA) were detected to calculate HOMA-beta, insulin sensitivity index (ISI) and HOMA-IR of different groups. Meanwhile, efforts were made to calculate different time quantum detected in OGTT and L-Arg experiments and area under the curve AUC(BG), AUC(INS) and AUC(GC). Obvious overall differences were observed in FFA and FGC of the three groups. FGC of each group was negatively correlated with HOMA-beta and ISI. Among all of the 103 study objects, FGC was positively correlated with FBG and HOMA-IR and negatively correlated with HOMA-beta and ISI, with no correlation with FINS; FFA was positively correlated with FBG, HOMA-IR and negatively correlated with FINS, HOMA-beta, ISI. FGC and FFA were positively correlated in the T2DM group and the IGT group, but with no statistical correlation in the NGT group. The sequence of the three study objects was T2DM > IGR > NGT in AUC(GC) in the OGTT experiment and T2DM > IGR > NGT in in AUC(GC) in the L-Arg experiment, with the significant positive correlation between AUC(GC) and AUC(BG) and significant negative correlation with AUC(INS). Glucagon and free fatty acid of T2DM and IGT patients increased, which was positively correlated with blood glucose and HOMA

Textural features of "1"8F-fluorodeoxyglucose positron emission tomography scanning in diagnosing aortic prosthetic graft infection

International Nuclear Information System (INIS)

Saleem, Ben R.; Zeebregts, Clark J.; Beukinga, Roelof J.; Slart, Riemer H.J.A.; Boellaard, Ronald; Glaudemans, Andor W.J.M.; Reijnen, Michel M.P.J.

2017-01-01

The clinical problem in suspected aortoiliac graft infection (AGI) is to obtain proof of infection. Although "1"8F-fluorodeoxyglucose ("1"8F-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 "1"8F-FDG uptake heterogeneity characterized by textural features to diagnose AGI. Thirty patients with a history of aortic graft reconstruction who underwent "1"8F-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 "1"8F-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 "1"8F-FDG PET based textural features were applied to characterize "1"8F-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. SUVmax was found predictive

Contrast-enhanced transrectal ultrasound for prediction of prostate cancer aggressiveness: The role of normal peripheral zone time-intensity curves.

Science.gov (United States)

Huang, Hui; Zhu, Zheng-Qiu; Zhou, Zheng-Guo; Chen, Ling-Shan; Zhao, Ming; Zhang, Yang; Li, Hong-Bo; Yin, Li-Ping

2016-12-08

To assess the role of time-intensity curves (TICs) of the normal peripheral zone (PZ) in the identification of biopsy-proven prostate nodules using contrast-enhanced transrectal ultrasound (CETRUS). This study included 132 patients with 134 prostate PZ nodules. Arrival time (AT), peak intensity (PI), mean transit time (MTT), area under the curve (AUC), time from peak to one half (TPH), wash in slope (WIS) and time to peak (TTP) were analyzed using multivariate linear logistic regression and receiver operating characteristic (ROC) curves to assess whether combining nodule TICs with normal PZ TICs improved the prediction of prostate cancer (PCa) aggressiveness. The PI, AUC (p < 0.001 for both), MTT and TPH (p = 0.011 and 0.040 respectively) values of the malignant nodules were significantly higher than those of the benign nodules. Incorporating the PI and AUC values (both, p < 0.001) of the normal PZ TIC, but not the MTT and TPH values (p = 0.076 and 0.159 respectively), significantly improved the AUC for prediction of malignancy (PI: 0.784-0.923; AUC: 0.758-0.891) and assessment of cancer aggressiveness (p < 0.001). Thus, all these findings indicate that incorporating normal PZ TICs with nodule TICs in CETRUS readings can improve the diagnostic accuracy for PCa and cancer aggressiveness assessment.

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.)

Measures of total stress-induced blood pressure responses are associated with vascular damage.

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Nazzaro, Pietro; Seccia, Teresa; Vulpis, Vito; Schirosi, Gabriella; Serio, Gabriella; Battista, Loredana; Pirrelli, Anna

2005-09-01

The role of cardiovascular reactivity to study hypertension, and the assessment methods, are still controversial. We aimed to verify the association of hypertension and vascular damage with several measures of cardiovascular response. We studied 40 patients with normal-high (132 +/- 1/87 +/- 1 mm Hg) blood pressure (Group 1) and 80 untreated hypertensive subjects. Postischemic forearm vascular resistance (mFVR) served to differentiate hypertensive subjects (142 +/- 2/92 +/- 1 mm Hg v 143 +/- 2/94 +/- 2 mm Hg, P = NS) with a lower (Group 2) and higher (Group 3) hemodynamic index of vascular damage (4.8 +/- .05 v 6.3 +/- .09, P blood pressure, heart rate, forearm blood flow, and vascular resistance. Reactivity measures included: a) change from baseline, b) residualized score, c) cumulative change from baseline and residualized score, and d) total reactivity as area-under-the-curve (AUC), including changes occurring during baseline and recovery phases. The AUC of systolic blood pressure, diastolic blood pressure, and mFVR progressively increased in the groups (P AUC of SBP, DBP, and forearm blood flow and resistance demonstrated the highest (P AUC of SBP (beta = 0.634) and forearm blood flow (beta = -0.337) were predictive (P blood pressure stress response, as AUC, including baseline and recovery phases, was significantly better associated with hypertension and vascular damage than the other reactivity measures studied.

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.

Portal hypertension in patients with cirrhosis: indirect assessment of hepatic venous pressure gradient by measuring azygos flow with 2D-cine phase-contrast magnetic resonance imaging

International Nuclear Information System (INIS)

Gouya, Herve; Vignaux, Olivier; Saade, Anastasia; Legmann, Paul; Grabar, Sophie; Pol, Stanislas; Sogni, Philippe

2016-01-01

To measure azygos, portal and aortic flow by two-dimensional cine phase-contrast magnetic resonance imaging (2D-cine PC MRI), and to compare the MRI values to hepatic venous pressure gradient (HVPG) measurements, in patients with cirrhosis. Sixty-nine patients with cirrhosis were prospectively included. All patients underwent HVPG measurements, upper gastrointestinal endoscopy and 2D-cine PC MRI measurements of azygos, portal and aortic blood flow. Univariate and multivariate regression analyses were used to evaluate the correlation between the blood flow and HVPG. The performance of 2D-cine PC MRI to diagnose severe portal hypertension (HVPG ≥ 16 mmHg) was determined by receiver operating characteristic curve (ROC) analysis, and area under the curves (AUC) were compared. Azygos and aortic flow values were associated with HVPG in univariate linear regression model. Azygos flow (p < 10 -3 ), aortic flow (p = 0.001), age (p = 0.001) and presence of varices (p < 10 -3 ) were independently associated with HVPG. Azygos flow (AUC = 0.96 (95 % CI) [0.91-1.00]) had significantly higher AUC than aortic (AUC = 0.64 (95 % CI) [0.51-0.77]) or portal blood flow (AUC = 0.40 (95 % CI) [0.25-0.54]). 2D-cine PC MRI is a promising technique to evaluate significant portal hypertension in patients with cirrhosis. (orig.)

Diagnostic capability of Pulsar perimetry in pre-perimetric and early glaucoma.

Science.gov (United States)

Hirasawa, Kazunori; Takahashi, Natsumi; Matsumura, Kazuhiro; Kasahara, Masayuki; Shoji, Nobuyuki

2017-06-12

This study aimed to compare the diagnostic capability of Pulsar perimetry (Pulsar) in pre-perimetric glaucoma (PPG) and early glaucoma (EG) with that of Flicker perimetry (Flicker) and spectral-domain optical conference tomography (SD-OCT). This prospective cross-sectional study included 25 eyes of 25 PPG patients, 35 eyes of 35 EG patients, and 42 eyes of 42 healthy participants. The diagnostic capability using the area under the curve (AUC) of the best parameter and agreement of detectability between structural and functional measurements were compared. For PPG patients, the AUC of Pulsar, Flicker, OCT-disc, and OCT-macular was 0.733, 0.663, 0.842, and 0.780, respectively. The AUC of Flicker was significantly lower than that of OCT-disc (p = 0.016). For EG patients, the AUC of Pulsar, Flicker, OCT-disc, and OCT-macular were 0.851, 0.869, 0.907, and 0.861, respectively. There was no significant difference in AUC among these methods. The agreement between structural and functional measurements expressed by kappa value ranged from -0.16 to 0.07 for PPG and from 0.01 to 0.25 for EG. Although the diagnostic capability of Pulsar in the PPG and EG groups was equal to that of Flicker and SD-OCT, the agreements between structural and functional measurements for both PPG and EG were poor.

Pharmacokinetic equivalence study of two formulations of the anticonvulsant pregabalin

Directory of Open Access Journals (Sweden)

Tjandrawinata RR

2015-04-01

Full Text Available Raymond R Tjandrawinata,1 Effi Setiawati,2 Ratih Sofia Ika Putri,2 Vincent Angga Gunawan,2 Fenny Ong,1 Liana W Susanto,1 Dwi Nofiarny11Dexa Laboratories of Biomolecular Sciences, Cikarang, West Java, Indonesia; 2PT Equilab International Bioavailability and Bioequivalence Laboratory, Jakarta, IndonesiaPurpose: The present study was conducted to evaluate whether the bioavailability of pregabalin capsules 150 mg manufactured by PT Dexa Medica was equivalent to the reference formulation.Methods: This was a randomized, open-label, two-period, two-sequence, and crossover study under fasting condition, with a 1-week washout period. Plasma concentrations of pregabalin from 20 subjects were determined by using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS detection method. Pharmacokinetic parameters assessed in this study were: area under the plasma concentration–time curve from time zero to last observed quantifiable concentration (AUC0–t, area under the plasma concentration–time curve from time zero to infinity (AUC0–∞, maximum plasma concentration (Cmax, time to maximum plasma concentration (tmax, and terminal half-life (t1/2. The 90% confidence intervals (CIs for the geometric mean ratios of test formulation/reference formulation were calculated for the AUC and Cmax parameters; while tmax difference was analyzed nonparametrically on the original data using the Wilcoxon matched-pairs test, and t1/2 difference was analyzed using Student's paired t-test.Results: The mean (standard deviation [SD] AUC0–t, AUC0–∞, Cmax, and t1/2 of pregabalin from the test formulation were 27,845.86 (4,508.27 ng·h/mL, 28,311.70 (4,790.55 ng·h/mL, 3,999.71 (801.52 ng/mL, and 5.66 (1.20 hours, respectively; while the mean (SD AUC0–t, AUC0–∞, Cmax, and t1/2 of pregabalin from the reference formulation were 27,398.12 (4,266.28 ng·h/mL, 27,904.24 (4,507.31 ng·h/mL, 3,849.50 (814.50 ng/mL, and 5.87 (1.25 hours, respectively

Prostacyclin (epoprostenol) induces headache in healthy subjects

DEFF Research Database (Denmark)

Wienecke, Troels; Olesen, Jes; Oturai, Peter S

2008-01-01

on the placebo day (p=0.002). During epoprostenol (0-30 min) and in the post-infusion phase (30-90 min), the area under the curve (AUC) for headache score was significantly larger than during and after placebo (p=0.005). PGI(2) caused headache associated with the dilatation of STA (AUC, p

Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

Science.gov (United States)

Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

2015-02-01

Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.

Science.gov (United States)

Nardo, Luciano G; Gelbaya, Tarek A; Wilkinson, Hannah; Roberts, Stephen A; Yates, Allen; Pemberton, Phil; Laing, Ian

2009-11-01

To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

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

Linezolid for Infants and Toddlers With Disseminated Tuberculosis: First Steps.

Science.gov (United States)

Deshpande, Devyani; Srivastava, Shashikant; Pasipanodya, Jotam G; Bush, Stephen J; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda

2016-11-01

 Infants and toddlers often present with disseminated and lymph node tuberculosis, in which Mycobacterium tuberculosis (Mtb) is predominantly intracellular. Linezolid, used to treat tuberculosis in adults, has not been formally studied in infants. Infants clear linezolid 5 times faster than adults and achieve lower 0- to 24-hour area under the concentration-time curves (AUC 0-24 ).  To mimic intracellular disease, we infected human-derived THP-1 macrophages with Mtb and inoculated hollow fiber systems. We performed dose-effect and dose-scheduling studies in which we recapitulated the linezolid half-life of 3 hours encountered in infants. Repetitive sampling for linezolid pharmacokinetics, Mtb intracellular burden, viable monocyte count, and RNA sequencing reads were performed up to 28 days.  The linezolid extracellular half-life was 2.64 ± 0.38 hours, whereas intracellular half-life was 8.93 ± 1.30 hours (r 2 = 0.89). Linezolid efficacy was linked to the AUC 0-24 to minimum inhibitory concentration (MIC) ratio (r 2 = 0.98). The exposure associated with maximal Mtb kill was an AUC 0-24 /MIC of 23.37 ± 1.16. We identified a 414-gene transcript on exposure to toxic linezolid doses. The largest number of genes mapped to ribosomal proteins, a signature hitherto not associated with linezolid toxicity. The second-largest number of differentially expressed genes mapped to mitochondrial enzyme inhibition. Linezolid AUC 0-24 best explained the mitochondrial gene inhibition, with 50% inhibition at 94 mg × hour/L (highest r 2 = 0.98).  We identified the linezolid AUC 0-24 /MIC target for optimal efficacy against pediatric intracellular tuberculosis, and an AUC 0-24 threshold associated with mitochondrial inhibition. These constitute a therapeutic window to be targeted for optimal linezolid doses in children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Variable Linezolid Exposure in Intensive Care Unit Patients-Possible Role of Drug-Drug Interactions.

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Töpper, Christoph; Steinbach, Cathérine L; Dorn, Christoph; Kratzer, Alexander; Wicha, Sebastian G; Schleibinger, Michael; Liebchen, Uwe; Kees, Frieder; Salzberger, Bernd; Kees, Martin G

2016-10-01

Standard doses of linezolid may not be suitable for all patient groups. Intensive care unit (ICU) patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population. Plasma concentrations of linezolid were determined by high-performance liquid chromatography in a convenience sample of 20 ICU patients treated with intravenous linezolid 600 mg twice daily. Ultrafiltration applying physiological conditions (pH 7.4/37°C) was used to determine the unbound fraction. Individual pharmacokinetic (PK) parameters were estimated by population PK modeling. As measures of exposure to linezolid, area under the concentration-time curve (AUC) and trough concentrations (Cmin) were calculated and compared with published therapeutic ranges (AUC 200-400 mg*h/L, Cmin 2-10 mg/L). Coadministered inhibitors or inducers of cytochrome P450 and/or P-glycoprotein were noted. Data from 18 patients were included into the PK evaluation. Drug exposure was highly variable (median, range: AUC 185, 48-618 mg*h/L, calculated Cmin 2.92, 0.0062-18.9 mg/L), and only a minority of patients had values within the target ranges (6 and 7, respectively). AUC and Cmin were linearly correlated (R = 0.98), and classification of patients (underexposed/within therapeutic range/overexposed) according to AUC or Cmin was concordant in 15 cases. Coadministration of inhibitors was associated with a trend to higher drug exposure, whereas 3 patients treated with levothyroxine showed exceedingly low drug exposure (AUC ∼60 mg*h/L, Cmin linezolid is highly variable and difficult to predict in ICU patients, and therapeutic drug monitoring seems advisable. PK drug-drug interactions might partly be responsible and should be further investigated; protein binding appears to be stable and irrelevant.

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

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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.

Examination of some factors responsible for a food-induced increase in absorption of atovaquone.

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Rolan, P E; Mercer, A J; Weatherley, B C; Holdich, T; Meire, H; Peck, R W; Ridout, G; Posner, J

1994-01-01

1. Atovaquone is a potent antiprotozoal slowly and irregularly absorbed after administration as tablets to fasting volunteers. A series of studies was performed to investigate the effects of food, bile and formulation on atovaquone absorption. 2. In 18 healthy male volunteers, a high-fat breakfast administered 45 min before 500 mg atovaquone as tablets increased AUC by 3.3-fold (95% CI 2.8-4.0) and Cmax 5.3-fold (4.3-6.6) compared with fasting. 3. The absorption of atovaquone from tablets was examined in 12 healthy male volunteers after an overnight fast, following toast alone, toast with 28 g butter (LOFAT), or toast with 56 g butter (HIFAT). Compared with absorption when fasted, toast had no significant effect but LOFAT increased AUC 3.0-fold (2.1-4.2) and Cmax 3.9-fold (2.6-5.8). HIFAT increased AUC 3.9-fold (2.7-5.5) and Cmax 5.6-fold (3.8-8.4). 4. The absorption of atovaquone was examined in nine healthy fasting male volunteers from tablets, an aqueous suspension, and an oily solution/suspension in miglyol (fractionated coconut oil). Compared with tablets, AUC following the aqueous suspension was increased 1.7-fold (1.0-2.7) and Cmax 2.4-fold (1.7-3.5). Following miglyol, AUC was increased to the same extent but Cmax was only increased 1.8-fold (1.2-2.6). 5. Atovaquone absorption was examined in eight healthy fasting male volunteers following an i.v. infusion of cholecystokinin octapeptide (CCK-OP) which decreased gallbladder volume by 82% (73%-90%) on occasion 1 or saline on occasion 2. AUC(0,12) was increased following CCK-OP by 1.6-fold (1.1-2.4) and Cmax by 1.5-fold (0.98-2.4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8148213

A comparison of confidence/credible interval methods for the area under the ROC curve for continuous diagnostic tests with small sample size.

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Feng, Dai; Cortese, Giuliana; Baumgartner, Richard

2017-12-01

The receiver operating characteristic (ROC) curve is frequently used as a measure of accuracy of continuous markers in diagnostic tests. The area under the ROC curve (AUC) is arguably the most widely used summary index for the ROC curve. Although the small sample size scenario is common in medical tests, a comprehensive study of small sample size properties of various methods for the construction of the confidence/credible interval (CI) for the AUC has been by and large missing in the literature. In this paper, we describe and compare 29 non-parametric and parametric methods for the construction of the CI for the AUC when the number of available observations is small. The methods considered include not only those that have been widely adopted, but also those that have been less frequently mentioned or, to our knowledge, never applied to the AUC context. To compare different methods, we carried out a simulation study with data generated from binormal models with equal and unequal variances and from exponential models with various parameters and with equal and unequal small sample sizes. We found that the larger the true AUC value and the smaller the sample size, the larger the discrepancy among the results of different approaches. When the model is correctly specified, the parametric approaches tend to outperform the non-parametric ones. Moreover, in the non-parametric domain, we found that a method based on the Mann-Whitney statistic is in general superior to the others. We further elucidate potential issues and provide possible solutions to along with general guidance on the CI construction for the AUC when the sample size is small. Finally, we illustrate the utility of different methods through real life examples.

Comparison of Glasgow-Blatchford score and full Rockall score systems to predict clinical outcomes in patients with upper gastrointestinal bleeding

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Mokhtare M

2016-10-01

Full Text Available Marjan Mokhtare, Vida Bozorgi, Shahram Agah, Mehdi Nikkhah, Amirhossein Faghihi, Amirhossein Boghratian, Neda Shalbaf, Abbas Khanlari, Hamidreza Seifmanesh Colorectal Research Center, Rasoul Akram Hospital, Tehran, Iran Background: Various risk scoring systems have been recently developed to predict clinical outcomes in patients with upper gastrointestinal bleeding (UGIB. The two commonly used scoring systems include full Rockall score (RS and the Glasgow-Blatchford score (GBS. Bleeding scores were assessed in terms of prediction of clinical outcomes in patients with UGIB. Patients and methods: Two hundred patients (age >18 years with obvious symptoms of UGIB in the emergency department of Rasoul Akram Hospital were enrolled. Full RS and GBS were calculated. We followed the patients for records of rebleeding and 1-month mortality. A receiver operating characteristic curve by using areas under the curve (AUCs was used to statistically identify the best cutoff point. Results: Eighteen patients were excluded from the study due to failure to follow-up. Rebleeding and mortality rate were 9.34% (n=17 and 11.53% (n=21, respectively. Regarding 1-month mortality, full RS was better than GBS (AUC, 0.648 versus 0.582; P=0.021. GBS was more accurate in terms of detecting transfusion need (AUC, 0.757 versus 0.528; P=0.001, rebleeding rate (AUC, 0.722 versus 0.520; P=0.002, intensive care unit admission rate (AUC, 0.648 versus 0.582; P=0.021, and endoscopic intervention rate (AUC, 0.771 versus 0.650; P<0.001. Conclusion: We found the full RS system is better for 1-month mortality prediction while GBS system is better for prediction of other outcomes. Keywords: full Rockall score, Glasgow-Blatchford score, gastrointestinal bleeding, mortality, prognosis

Insulinaemic and glycaemic responses to three forages in ponies.

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Carslake, H B; Argo, C McG; Pinchbeck, G L; Dugdale, A H A; McGowan, C M

2018-05-01

Reduction of the hyperinsulinaemic response to feeding is central to the management of insulin dysregulation (ID). The aim of this study was to compare insulinaemic and glycaemic responses to soaked hay, dry hay and haylage in ponies. Twelve ponies of mixed breeds were maintained under identical management conditions. A randomised four-way crossover trial was conducted, in which fasted animals were fed a meal of 0.25% body weight as dry matter intake soaked hay, dry hay or haylage, or administered an oral glucose test (OGT). Blood glucose and serum insulin concentrations were measured before and at 2h following OGT, and regularly for 5h following forage meals. Median and interquartile range (IQR) area under the curve (AUC) for insulin (AUC i ) was greater for haylage (median 6495; IQR 17352) vs. dry hay (2932; IQR 5937; P=0.019) and soaked hay (1066; IQR 1753; P=0.002), and greater for dry hay vs. soaked hay (P=0.002). The AUC for glucose (AUC g ) was lower for soaked hay (1021; IQR 99) vs. dry hay (1075; IQR 105; P=0.002) and haylage (1107; IQR 221; P=0.003). Six ponies were classified as having ID based on the OGT. AUC i was greater in ID vs. non-ID ponies after all forages. In contrast, there was no detectable effect of ID status on AUC g . On an equivalent dry matter basis, soaked hay produced the lowest insulinaemic and glycaemic responses to feeding, while haylage produced the highest responses. The insulinaemic effects of all forages were greater in ponies with ID. These data support the practice of soaking hay with water to reduce postprandial insulinaemic responses in ponies. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Detection of lymph node metastases in head and neck cancer: A meta-analysis comparing US, USgFNAC, CT and MR imaging

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Bondt, R.B.J. de; Nelemans, P.J.; Hofman, P.A.M.; Casselman, J.W.; Kremer, B.; Engelshoven, J.M.A. van; Beets-Tan, R.G.H.

2007-01-01

Purpose: To perform a meta-analysis comparing ultrasonography (US), US guided fine needle aspiration cytology (USgFNAC), computed tomography (CT), and magnetic resonance imaging (MRI) in the detection of lymph node metastases in head and neck cancer. Methods: MEDLINE, EMBASE and Cochrane databases were searched (January 1990-January 2006) for studies reporting diagnostic performances of US, USgFNAC, CT, and MRI to detect cervical lymph node metastases. Two reviewers screened text and reference lists of potentially eligible articles. Criteria for study inclusion: (1) histopathology was the reference standard, (2) primary tumors and metastases were squamous cell carcinoma and (3) data were available to construct 2 x 2 contingency tables. Meta-analysis of pairs of sensitivity and specificity was performed using bivariate analysis. Summary estimates for diagnostic performance used were sensitivity, specificity, diagnostic odds ratios (DOR) (95% confidence intervals) and summary receiver operating characteristics (SROC) curves. Results: From seventeen articles, 25 data sets could be retrieved. Eleven articles studied one modality: US (n = 4); USgFNAC (n = 1); CT (n = 3); MRI (n = 3). Six articles studied two or more modalities: US and CT (n = 2); USgFNAC and CT (n = 1); CT and MRI (n = 1); MRI and MRI-USPIO (Sinerem) (n = 2); US, USgFNAC, CT and MRI (n = 1). USgFNAC (AUC = 0.98) and US (AUC = 0.95) showed the highest areas under the curve (AUC). MRI-USPIO (AUC = 0.89) and CT (AUC = 0.88) had similar results. MRI showed an AUC = 0.79. USgFNAC showed the highest DOR (DOR = 260) compared to US (DOR = 40), MRI-USPIO (DOR = 21), CT (DOR = 14) and MRI (DOR = 7). Conclusion USgFNAC showed to be the most accurate imaging modality to detect cervical lymph node metastases

A simplified score to quantify comorbidity in COPD.

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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.

The use of sonographic subjective tumor assessment, IOTA logistic regression model 1, IOTA Simple Rules and GI-RADS system in the preoperative prediction of malignancy in women with adnexal masses.

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Koneczny, Jarosław; Czekierdowski, Artur; Florczak, Marek; Poziemski, Paweł; Stachowicz, Norbert; Borowski, Dariusz

2017-01-01

Sonography based methods with various tumor markers are currently used to discriminate the type of adnexal masses. To compare the predictive value of selected sonography-based models along with subjective assessment in ovarian cancer prediction. We analyzed data of 271 women operated because of adnexal masses. All masses were verified by histological examination. Preoperative sonography was performed in all patients and various predictive models includ¬ing IOTA group logistic regression model LR1 (LR1), IOTA simple ultrasound-based rules by IOTA (SR), GI-RADS and risk of malignancy index (RMI3) were used. ROC curves were constructed and respective AUC's with 95% CI's were compared. Of 271 masses 78 proved to be malignant including 6 borderline tumors. LR1 had sensitivity of 91.0%, specificity of 91.2%, AUC = 0.95 (95% CI: 0.92-0.98). Sensitivity for GI-RADS for 271 patients was 88.5% with specificity of 85% and AUC = 0.91 (95% CI: 0.88-0.95). Subjective assessment yielded sensitivity and specificity of 85.9% and 96.9%, respectively with AUC = 0.97 (95% CI: 0.94-0.99). SR were applicable in 236 masses and had sensitivity of 90.6% with specificity of 95.3% and AUC = 0.93 (95% CI 0.89-0.97). RMI3 was calculated only in 104 women who had CA125 available and had sensitivity of 55.3%, specificity of 94% and AUC = 0.85 (95% CI: 0.77-0.93). Although subjective assessment by the ultrasound expert remains the best current method of adnexal tumors preoperative discrimination, the simplicity and high predictive value favor the IOTA SR method, and when not applicable, the IOTA LR1 or GI-RADS models to be primarily and effectively used.

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

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Kai, Joe; Garibaldi, Jonathan M.; Qureshi, Nadeem

2017-01-01

Background 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. Methods 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). Findings 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. Conclusions 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

Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study.

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Nivsarkar, Manish; Maroo, Sanjaykumar H; Patel, Ketan R; Patel, Dixit D

2015-12-01

Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS(®) with diclofenac emulgel. A 200 mg of diclofenac from either Dynapar QPS(®) (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Mean Cmax after administration of Dynapar QPS(®) and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0-t and AUC0-∞ after administration of Dynapar QPS(®) was higher as compared to diclofenac emulgel (AUC0-t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS(®) as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients.

The acute impact of the intake of four types of bread on satiety and blood concentrations of glucose, insulin, free fatty acids, triglyceride and acylated ghrelin. A randomized controlled cross-over trial.

Science.gov (United States)

Bo, S; Seletto, M; Choc, A; Ponzo, V; Lezo, A; Demagistris, A; Evangelista, A; Ciccone, G; Bertolino, M; Cassader, M; Gambino, R

2017-02-01

The purpose of the present study is to compare the effects of four different breads (one commercial par-baked wheat bread, three sourdough breads prepared with commercial wheat flour, organic wheat flour, organic einkorn flour) in 16 healthy subjects. The primary outcome of this randomized cross-over trial was evaluating intra-individual changes in glycemic areas-under-the-curve (AUCs) after 50g carbohydrate portions of each bread; secondary outcomes were changes in insulin, fatty free acids (FFA), triglyceride, acylated ghrelin and satiety AUCs. Blood samples and satiety ratings were collected every 30-min for 2-h after the consumption of each bread. The einkorn flour showed the lowest amylase activity, the commercial flour the highest; commercial bread had the highest carbohydrate content and the lowest dietary fiber content. Glucose AUCs were significantly lower after the consumption of sourdough breads made with organic (12,754±1433mg/dL×h) and einkorn flour (12,216±1210mg/dL×h), with respect to the commercial bread (13,849±2193mg/dL×h). Insulin AUCs decreased after the consumption of all sourdough breads when compared to commercial bread. FFA and triglyceride AUCs did not differ by kind of breads. Median ghrelin AUC was significantly lower and satiety higher after the einkorn bread (3710pg/mL×h; 3225±2414, respectively) than after commercial bread consumption (4140pg/mL×h; 1706±1766, respectively), but not with other sourdough breads. In conclusion, the use of sourdough may improve the nutritional features of breads; einkorn bread induced the least disturbance in carbohydrate homeostasis and the greater satiety. If confirmed by further research, these results might have implications in the approach towards chronic dysmetabolic diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

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 variability<30%) bioequivalence 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.

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

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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.

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

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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.

Bromocriptine and insulin sensitivity in lean and obese subjects

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L Bahler

2016-11-01

Full Text Available Bromocriptine is a glucose-lowering drug, which was shown to be effective in obese subjects with insulin resistance. It is usually administered in the morning. The exact working mechanism of bromocriptine still has to be elucidated. Therefore, in this open-label randomized prospective cross-over mechanistic study, we assessed whether the timing of bromocriptine administration (morning vs evening results in different effects and whether these effects differ between lean and obese subjects. We studied the effect of bromocriptine on insulin sensitivity in 8 lean and 8 overweight subjects using an oral glucose tolerance test. The subjects used bromocriptine in randomized cross-over order for 2 weeks in the morning and 2 weeks in the evening. We found that in lean subjects, bromocriptine administration in the evening resulted in a significantly higher post-prandial insulin sensitivity as compared with the pre-exposure visit (glucose area under the curve (AUC 742 mmol/L * 120 min (695–818 vs 641 (504–750, P = 0.036, AUC for insulin did not change, P = 0.575. In obese subjects, both morning and evening administration of bromocriptine resulted in a significantly higher insulin sensitivity: morning administration in obese: insulin AUC (55,900 mmol/L * 120 min (43,236–96,831 vs 36,448 (25,213–57,711, P = 0.012 and glucose AUC P = 0.069; evening administration in obese: glucose AUC (735 mmol/L * 120 min (614–988 vs 644 (568–829, P = 0.017 and insulin AUC, P = 0.208. In conclusion, bromocriptine increases insulin sensitivity in both lean and obese subjects. In lean subjects, this effect only occurred when bromocriptine was administrated in the evening, whereas in the obese, insulin sensitivity increased independent of the timing of bromocriptine administration.

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.)

Moxifloxacin pharmacokinetic profile and efficacy evaluation in empiric treatment of community-acquired pneumonia

DEFF Research Database (Denmark)

Öbrink-Hansen, Kristina; Hardlei, Tore Forsingdal; Brock, Birgitte

2015-01-01

for each patient were evaluated against epidemiological cutoff MIC values for Streptococcus pneumoniae, Haemophilus influenzae, and Legionella pneumophila. PK-PD targets adopted were a Cmax/MIC of ≥12.2 for all pathogens, an fAUC0-24/MIC of >34 for S. pneumoniae, and an fAUC0-24/MIC of >75 for H...

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...

Glaucoma Diagnostic Ability of the Optical Coherence Tomography Angiography Vessel Density Parameters.

Science.gov (United States)

Chung, Jae Keun; Hwang, Young Hoon; Wi, Jae Min; Kim, Mijin; Jung, Jong Jin

2017-11-01

To investigate the glaucoma diagnostic abilities of vessel density parameters as determined by optical coherence tomography (OCT) angiography in different stages of glaucoma. A total of 113 healthy eyes and 140 glaucomatous eyes were enrolled. Diagnostic abilities of the OCT vessel density parameters in the optic nerve head (ONH), peripapillary, and macular regions were evaluated by calculating the area under the receiver operation characteristic curves (AUCs). AUCs of the peripapillary vessel density parameters and circumpapillary retinal nerve fiber layer (RNFL) thickness were compared. OCT angiography vessel densities in the ONH, peripapillary, and macular regions in the glaucomatous eyes were significantly lower than those in the healthy eyes (P glaucoma detection. The peripapillary vessel density parameters showed similar AUCs with the corresponding sectoral RNFL thickness (P > 0.05). However, in the early stage of glaucoma, the AUCs of the inferotemporal and temporal peripapillary vessel densities were significantly lower than that of the RNFL thickness (P glaucoma diagnostic ability with circumpapillary RNFL thickness, in the early stage, the vessel density parameters showed limited clinical value.

A bioequivalence study of two tamsulosin sustained-release tablets in Indonesian healthy volunteers.

Science.gov (United States)

Prasaja, Budi; Harahap, Yahdiana; Lusthom, Windy; Setiawan, Evy C; Ginting, Mena B; Hardiyanti; Lipin

2011-06-01

The bioavailability of two 0.4 mg tamsulosin sustained-release film-coated tablet formulations was compared; using generic tablets (Prostam(®)) as test formulation and the originator product as reference formulation. Twenty-four subjects were included in this single-dose, open-label, randomized two-way crossover design following an overnight fasting. A one-week wash-out period was applied. Blood samples were drawn up to 72 h following drug administration. Plasma concentration of tamsulosin was determined by liquid chromatography-tandem mass spectrometry method with TurboIonSpray mode. Pharmacokinetic parameters AUC(0-t,) AUC(0-∞), C (max) and t (½) were determined and used for bioequivalence evaluation after log-transformation, whereas t (max) ratios were evaluated non-parametrically. The estimated point and 90% confidence intervals (CI) for AUC(0-t,) AUC(0-∞), C (max) and t (½) were 109.55% (96.41-124.49%), 109.94% (96.85-124.81%), 105.87% (92.88-120.67%) and 100.00% (90.56-110.43%), respectively. These results indicated that the two formulations of tamsulosin were bioequivalent; therefore they may be prescribed interchangeably.

Evidence of significant covalent bonding in Au(CN)(2)(-).

Science.gov (United States)

Wang, Xue-Bin; Wang, Yi-Lei; Yang, Jie; Xing, Xiao-Peng; Li, Jun; Wang, Lai-Sheng

2009-11-18

The Au(CN)(2)(-) ion is the most stable Au compound known for centuries, yet a detailed understanding of its chemical bonding is still lacking. Here we report direct experimental evidence of significant covalent bonding character in the Au-C bonds in Au(CN)(2)(-) using photoelectron spectroscopy and comparisons with its lighter congeners, Ag(CN)(2)(-) and Cu(CN)(2)(-). Vibrational progressions in the Au-C stretching mode were observed for all detachment transitions for Au(CN)(2)(-), in contrast to the atomic-like transitions for Cu(CN)(2)(-), revealing the Au-C covalent bonding character. In addition, rich electronic structural information was obtained for Au(CN)(2)(-) by employing 118 nm detachment photons. Density functional theory and high-level ab initio calculations were carried out to understand the photoelectron spectra and obtain insight into the nature of the chemical bonding in the M(CN)(2)(-) complexes. Significant covalent character in the Au-C bonding due to the strong relativistic effects was revealed in Au(CN)(2)(-), consistent with its high stability.

Cortisol and ghrelin concentrations following a cold pressor stress test in overweight individuals with and without night eating.

Science.gov (United States)

Geliebter, A; Carnell, S; Gluck, M E

2013-08-01

To explore appetite-related hormones following stress in overweight individuals, and their relationship with night eating (NE) status. We measured plasma cortisol and ghrelin concentrations, and recorded ratings of stress and hunger in response to a physiological laboratory stressor (cold pressor test, CPT), in overweight women with (n=11; NE) and without (n=17; non-NE) NE. Following the CPT, cortisol (Plevels increased, as did stress and hunger ratings (all Pcortisol (Plevels than non-NE. NE also had greater cortisol area under the curve (AUC) than non-NE (P=0.019), but not when controlling for baseline cortisol levels. Ghrelin baseline and AUC did not differ between groups. NE showed higher AUC stress (Pcortisol, ghrelin, stress and hunger following a laboratory stressor, and there was some evidence for greater increases in cortisol and subjective stress among NE. The greater AUC cortisol level in NE was due to higher baseline levels, but the group difference in stress was in direct response to the stressor. Our results support a role for cortisol and stress in NE.

Parasympathetic blockade attenuates augmented pancreatic polypeptide but not insulin secretion in Pima Indians

DEFF Research Database (Denmark)

de Courten, Barbora; Weyer, Christian; Stefan, Norbert

2004-01-01

was administered for 120 min at the following doses: 0, 2.5, 5, and 10 micro g. kg fat-free mass (FFM)(-1). h(-1). Areas under the curve for early (AUC(0-30 min)) and total (AUC(0-120 min)) postprandial insulin and PP secretory responses were calculated. Early postprandial insulin and PP secretory responses were...

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

Validation of the German Diabetes Risk Score among the general adult population: findings from the German Health Interview and Examination Surveys

Science.gov (United States)

Paprott, Rebecca; Mühlenbruch, Kristin; Mensink, Gert B M; Thiele, Silke; Schulze, Matthias B; Scheidt-Nave, Christa; Heidemann, Christin

2016-01-01

Objective To evaluate the German Diabetes Risk Score (GDRS) among the general adult German population for prediction of incident type 2 diabetes and detection of prevalent undiagnosed diabetes. Methods The longitudinal sample for prediction of incident diagnosed type 2 diabetes included 3625 persons who participated both in the examination survey in 1997–1999 and the examination survey in 2008–2011. Incident diagnosed type 2 diabetes was defined as first-time physician diagnosis or antidiabetic medication during 5 years of follow-up excluding potential incident type 1 and gestational diabetes. The cross-sectional sample for detection of prevalent undiagnosed diabetes included 6048 participants without diagnosed diabetes of the examination survey in 2008–2011. Prevalent undiagnosed diabetes was defined as glycated haemoglobin ≥6.5% (48 mmol/mol). We assessed discrimination as area under the receiver operating characteristic curve (ROC-AUC (95% CI)) and calibration through calibration plots. Results In longitudinal analyses, 82 subjects with incident diagnosed type 2 diabetes were identified after 5 years of follow-up. For prediction of incident diagnosed diabetes, the GDRS yielded an ROC-AUC of 0.87 (0.83 to 0.90). Calibration plots indicated excellent prediction for low diabetes risk and overestimation for intermediate and high diabetes risk. When considering the entire follow-up period of 11.9 years (ROC-AUC: 0.84 (0.82 to 0.86)) and including incident undiagnosed diabetes (ROC-AUC: 0.81 (0.78 to 0.84)), discrimination decreased somewhat. A previously simplified paper version of the GDRS yielded a similar predictive ability (ROC-AUC: 0.86 (0.82 to 0.89)). In cross-sectional analyses, 128 subjects with undiagnosed diabetes were identified. For detection of prevalent undiagnosed diabetes, the ROC-AUC was 0.84 (0.81 to 0.86). Again, the simplified version yielded a similar result (ROC-AUC: 0.83 (0.80 to 0.86)). Conclusions The GDRS might be applied

Comparison of Scheimpflug imaging and spectral domain anterior segment optical coherence tomography for detection of narrow anterior chamber angles.

Science.gov (United States)

Grewal, D S; Brar, G S; Jain, R; Grewal, S P S

2011-05-01

To compare the performance of anterior chamber volume (ACV) and anterior chamber depth (ACD) obtained using Scheimpflug imaging with angle opening distance (AOD500) and trabecular-iris space area (TISA500) obtained using spectral domain anterior segment optical coherence tomography (SD-ASOCT) in detecting narrow angles classified using gonioscopy. In this prospective, cross-sectional observational study, 265 eyes of 265 consecutive patients underwent sequential Scheimpflug imaging, SD-ASOCT imaging, and gonioscopy. Correlations between gonioscopy grading, ACV, ACD, AOD500, and TISA500 were evaluated. Area under receiver operating characteristic curve (AUC), sensitivity, specificity, and likelihood ratios (LRs) were calculated to assess the performance of ACV, ACD, AOD500, and TISA500 in detecting narrow angles (defined as Shaffer grade ≤1 in all quadrants). SD-ASOCT images were obtained at the nasal and temporal quadrants only. Twenty-eight eyes (10.6%) were classified as narrow angles on gonioscopy. ACV correlated with gonioscopy grading (P<0.001) for temporal (r=0.204), superior (r=0.251), nasal (r=0.213), and inferior (r=0.236) quadrants. ACV correlated with TISA500 for nasal (r=0.135, P=0.029) and temporal (P=0.160, P=0.009) quadrants and also with AOD500 for nasal (r=0.498, P<0.001) and temporal (r=0.517, P<0.001) quadrants. For detection of narrow angles, ACV (AUC=0.935; 95% confidence interval (CI) =0.898-0.961) performed similar to ACD (AUC=0.88, P=0.06) and significantly better than AOD500 nasal (AUC=0.761, P=0.001), AOD500 temporal (AUC=0.808, P<0.001), TISA500 nasal (AUC=0.756, P<0.001), and TISA500 temporal (AUC=0.738, P<0.001). Using a cutoff of 113 mm(3), ACV had 90% sensitivity and 88% specificity for detecting narrow angles. Positive and negative LRs for ACV were 8.63 (95% CI=7.4-10.0) and 0.11 (95% CI=0.03-0.4), respectively. ACV measurements using Scheimpflug imaging outperformed AOD500 and TISA500 using SD-ASOCT for detecting narrow angles.

Is waist circumference a better predictor of diabetes than body mass index or waist-to-height ratio in Iranian adults?

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Karimollah Hajian-Tilaki

2015-01-01

Full Text Available Background: Several measures of adiposity have been used for predicting diabetes. The results of studies regarding superiority of waist circumference (WC to body mass index (BMI are inconsistent. This study designed to compare the ability of different anthropometric measures in predicting diabetes and to determine their optimal cut-off values. Methods: A population-based cross-sectional study was conducted with 1,000 representative sample among adults aged 20-80 years in Babol, the Northern Iran. The demographic data were collected in a household survey, and the anthropometric measures of weight, height, waist, and hip circumference were measured with a standard method. Fasting blood sugar (FBS ≥126 mg/dl was considered as diabetes. receiver operating characteristic analysis was used to estimate the predictive ability of different anthropometric indexes and their optimal cut-off values for high FBS. Results: The overall prevalence rate of diabetes was 14.0% (14.4% in men vs. 13.5% in women, P = 0.65. The prevalence rate was significantly higher in older age (>60 years, low educated and obese (P = 0.001. The mean of BMI, WC, waist-to-hip ratio (WHR, and waist-to-height ratio (WHtR were significantly higher among diabetic in both sexes (P = 0.001. Among men, WC (area under the ROC curve [AUC] =0.64 and WHtR (AUC = 0.63 have slightly higher accuracy index compared with BMI (AUC = 0.62 or WHR (AUC = 0.60. In contrast, among women, WHtR (AUC = 0.69 and WC (AUC = 0.68 yielded slightly better predictive than BMI (AUC = 0.67. The optimal cut-off values obtained for BMI and WHtR were similar between two sexes (BMI = 24.95 kg/m 2 for men and BMI = 25.2 kg/m 2 for women, WHtR = 0.51 for both sexes whereas the optimal cut-off value for WC was higher in men than women (98.5 cm men vs. 89.5 cm women. Conclusions: Overall WC and WHtR exhibited a slightly better discriminate performance than BMI for diabetes in both sexes, particularly in women.

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

Reducing HAuCl4 by the C60 dianion: C60-directed self-assembly of gold nanoparticles into novel fullerene bound gold nanoassemblies

International Nuclear Information System (INIS)

Liu Wei; Gao Xiang

2008-01-01

The C 60 dianion is used to reduce tetrachloroauric acid (HAuCl 4 ) for the first time; three-dimensional C 60 bound gold (Au-C 60 ) nanoclusters are obtained from C 60 -directed self-assembly of gold nanoparticles due to the strong affinities of Au-C 60 and C 60 -C 60 . The process was monitored in situ by UV-vis-NIR spectroscopy. The resulting Au-C 60 nanoclusters were characterized using transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy-dispersive spectroscopy (EDS), x-ray powder diffraction (XRD), x-ray photoelectron spectroscopy (XPS), and FT-IR and Raman spectroscopies. TEM demonstrates the formation of 3D nanonetwork aggregates, which are composed of discrete gold nanocores covered with a C 60 monolayer. The SAED and XRD patterns indicate that the gold nanocores inside the capped C 60 molecules belong to the face-centred cubic crystal structure, while the C 60 molecules are amorphous. The EDS and XPS measurements validate that the Au-C 60 nanoclusters contain only Au and C elements and Au 3+ is reduced to Au 0 . FT-IR spectroscopy shows the chemiadsorption of C 60 to the gold nanocores, while Raman spectroscopy demonstrates the electron transfer from the gold nanocores to the chemiadsorbed C 60 molecules. Au-C 60 nanoclusters embedded in tetraoctyl-n-ammonium bromide (TOAB) on glassy carbon electrodes (GCEs) have been fabricated and have shown stable and well-defined electrochemical responses in aqueous solution

Comparative Pharmacodynamics and Antimutant Potentials of Doripenem and Imipenem with Ciprofloxacin-Resistant Pseudomonas aeruginosa in an In Vitro Model

Science.gov (United States)

Gilbert, Deborah; Greer, Kenneth; Portnoy, Yury A.; Zinner, Stephen H.

2012-01-01

To compare the antipseudomonal efficacy of doripenem and imipenem as well as their abilities to restrict the enrichment of resistant Pseudomonas aeruginosa, multiple-dosing regimens of each drug were simulated at comparable values of the cumulative percentages of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (T>MIC) and ratios of the 24-hour area under the curve (AUC24) to the MIC. Three clinical isolates of ciprofloxacin-resistant P. aeruginosa (MIC of doripenem, 1 μg/ml; MICs of imipenem, 1, 2, and 2 μg/ml) were exposed to thrice-daily doripenem or imipenem for 3 days at AUC24/MIC ratios of from 50 to 170 h (doripenem) and from 30 to 140 h (imipenem). The antimicrobial effects for susceptible and resistant subpopulations of bacteria were expressed by the areas between control growth and time-kill curves (IEs) and areas under the bacterial mutant concentration curves (AUBCMs), respectively. With each antibiotic, the IE and AUBCM versus log AUC24/MIC relationships were bacterial strain independent. At similar AUC24/MIC ratios, doripenem was slightly less efficient than imipenem against susceptible and resistant subpopulations of bacteria. However, doripenem appeared to be somewhat more efficient than imipenem at clinically achievable AUC24s related to the means of the MICs for the three studied strains and had higher antimutant potentials for two of the three strains. PMID:22203591

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.

Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.

Science.gov (United States)

Sahoo, Bijay Kumar; Das, Ayan; Agarwal, Sangita; Bhaumik, Uttam; Bose, Anirbandeep; Ghosh, Debotri; Roy, Bikash; Pal, Tapan Kumar

2009-01-01

The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. Rabeprazole and itopride plasma levels were determined by a validated HPLC method using UV detection. The formulations were compared using the pharmacokinetic parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma concentration (Cmax). General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.

Deep Convolutional Neural Networks for Endotracheal Tube Position and X-ray Image Classification: Challenges and Opportunities.

Science.gov (United States)

Lakhani, Paras

2017-08-01

The goal of this study is to evaluate the efficacy of deep convolutional neural networks (DCNNs) in differentiating subtle, intermediate, and more obvious image differences in radiography. Three different datasets were created, which included presence/absence of the endotracheal (ET) tube (n = 300), low/normal position of the ET tube (n = 300), and chest/abdominal radiographs (n = 120). The datasets were split into training, validation, and test. Both untrained and pre-trained deep neural networks were employed, including AlexNet and GoogLeNet classifiers, using the Caffe framework. Data augmentation was performed for the presence/absence and low/normal ET tube datasets. Receiver operating characteristic (ROC), area under the curves (AUC), and 95% confidence intervals were calculated. Statistical differences of the AUCs were determined using a non-parametric approach. The pre-trained AlexNet and GoogLeNet classifiers had perfect accuracy (AUC 1.00) in differentiating chest vs. abdominal radiographs, using only 45 training cases. For more difficult datasets, including the presence/absence and low/normal position endotracheal tubes, more training cases, pre-trained networks, and data-augmentation approaches were helpful to increase accuracy. The best-performing network for classifying presence vs. absence of an ET tube was still very accurate with an AUC of 0.99. However, for the most difficult dataset, such as low vs. normal position of the endotracheal tube, DCNNs did not perform as well, but achieved a reasonable AUC of 0.81.

Waist-to-Height Ratio Is a Better Anthropometric Index than Waist Circumference and BMI in Predicting Metabolic Syndrome among Obese Mexican Adolescents

Directory of Open Access Journals (Sweden)

Edel Rafael Rodea-Montero

2014-01-01

Full Text Available Objective. To identify the degree of association between anthropometric indices and components of metabolic syndrome (MS and to determine optimal cut-off points of these indices for predicting MS in obese adolescents. Methods. A cross-sectional study with a sample of (n=110 Mexican obese adolescents grouped by sex and the presence/absence of MS. BMI percentile, waist circumference (WC, and waist-to-height ratio (WHtR were tested. ROC curves of the anthropometric indices were created to identify whether an index was a significant predictor of MS. Results. BMI percentile, WC, and WHtR were significantly correlated with systolic and diastolic blood pressure. As predictors of MS overall patients, the BMI percentile generated an area under curve (AUC of 0.651 (P=0.008, cut-off point above the 99th percentile. WC generated an AUC of 0.704 (P<0.001, cut-off point of ≥90 cm. WHtR demonstrated an AUC of 0.652 (P=0.008, cut-off point of 0.60. WHtR ≥0.62 and WHtR ≥0.61 generate AUC of 0.737 (P=0.006 and AUC of 0.717 (P=0.014 for predicting hypertension and insulin resistance, respectively, in females. Conclusion. WHtR is a better tool than WC and BMI for identifying cardiometabolic risk. The overall criterion (WHtR ≥ 0.6 could be appropriate for predicting MS in obese Mexican adolescents.

Differential influence of distinct components of increased blood pressure on cardiovascular outcomes: from the atherosclerosis risk in communities study.

Science.gov (United States)

Cheng, Susan; Gupta, Deepak K; Claggett, Brian; Sharrett, A Richey; Shah, Amil M; Skali, Hicham; Takeuchi, Madoka; Ni, Hanyu; Solomon, Scott D

2013-09-01

Elevation in blood pressure (BP) increases risk for all cardiovascular events. Nevertheless, the extent to which different indices of BP elevation may be associated to varying degrees with different cardiovascular outcomes remains unclear. We studied 13340 participants (aged 54 ± 6 years, 56% women and 27% black) of the Atherosclerosis Risk in Communities Study who were free of baseline cardiovascular disease. We used Cox proportional hazards models to compare the relative contributions of systolic BP, diastolic BP, pulse pressure, and mean arterial pressure to risk for coronary heart disease, heart failure, stroke, and all-cause mortality. For each multivariable-adjusted model, the largest area under the receiver-operating curve (AUC) and smallest -2 log-likelihood values were used to identify BP measures with the greatest contribution to risk prediction for each outcome. A total of 2095 coronary heart disease events, 1669 heart failure events, 771 stroke events, and 3016 deaths occurred during 18 ± 5 years of follow-up. In multivariable analyses adjusting for traditional cardiovascular risk factors, the BP measures with the greatest risk contributions were the following: systolic BP for coronary heart disease (AUC=0.74); pulse pressure for heart failure (AUC=0.79); systolic BP for stroke (AUC=0.74); and pulse pressure for all-cause mortality (AUC=0.74). With few exceptions, results were similar in analyses stratified by age, sex, and race. Our data indicate that distinct BP components contribute variably to risk for different cardiovascular outcomes.

Differential Influence of Distinct Components of Increased Blood Pressure on Cardiovascular OutcomesR3

Science.gov (United States)

Cheng, Susan; Gupta, Deepak K.; Claggett, Brian; Sharrett, A. Richey; Shah, Amil M.; Skali, Hicham; Takeuchi, Madoka; Ni, Hanyu; Solomon, Scott D.

2013-01-01

Elevation in blood pressure (BP) increases risk for all cardiovascular events. Nevertheless, the extent to which different indices of BP elevation may be associated to varying degrees with different cardiovascular outcomes remains unclear. We studied 13,340 participants (aged 54±6 years, 56% women, 27% black) of the Atherosclerosis Risk in Communities Study who were free of baseline cardiovascular disease. We used Cox proportional hazards models to compare the relative contributions of systolic (SBP), diastolic (DBP), pulse pressure (PP), and mean arterial pressure (MAP) to risk for coronary heart disease (CHD), heart failure (HF), stroke, and all-cause mortality. For each multivariable-adjusted model, the largest area under the receiver-operating curve (AUC) and smallest -2 log likelihood values were used to identify BP measures with the greatest contribution to risk prediction for each outcome. A total of 2095 CHD events, 1669 HF events, 771 stroke events, and 3016 deaths occurred during up to 18±5 years of follow up. In multivariable analyses adjusting for traditional cardiovascular risk factors, the BP measures with the greatest risk contributions were: SBP for CHD (AUC=0.74); PP for HF (AUC=0.79), SBP for stroke (AUC=0.74), and PP for all-cause mortality (AUC=0.74). With few exceptions, results were similar in analyses stratified by age, sex, and race. Our data indicate that distinct BP components contribute variably to risk for different cardiovascular outcomes. PMID:23876475

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

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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.

Measurement of glucose area under the curve using minimally invasive interstitial fluid extraction technology: evaluation of glucose monitoring concepts without blood sampling.

Science.gov (United States)

Sato, Toshiyuki; Okada, Seiki; Hagino, Kei; Asakura, Yoshihiro; Kikkawa, Yasuo; Kojima, Junko; Watanabe, Toshihiro; Maekawa, Yasunori; Isobe, Kazuki; Koike, Reona; Nakajima, Hiromu; Asano, Kaoru

2011-12-01

Monitoring postprandial hyperglycemia is crucial in treating diabetes, although its dynamics make accurate monitoring difficult. We developed a new technology for monitoring postprandial hyperglycemia using interstitial fluid (ISF) extraction technology without blood sampling. The glucose area under the curve (AUC) using this system was measured as accumulated ISF glucose (IG) with simultaneous calibration with sodium ions. The objective of this study was to evaluate this technological concept in healthy individuals. Minimally invasive ISF extraction technology (MIET) comprises two steps: pretreatment with microneedles and ISF accumulation over a specific time by contact with a solvent. The correlation between glucose and sodium ion levels using MIET was evaluated in 12 subjects with stable blood glucose (BG) levels during fasting. BG and IG time courses were evaluated in three subjects to confirm their relationship while BG was fluctuating. Furthermore, the accuracy of glucose AUC measurements by MIET was evaluated several hours after a meal in 30 subjects. A high correlation was observed between glucose and sodium ion levels when BG levels were stable (R=0.87), indicating that sodium ion is a good internal standard for calibration. The variation in IG and BG with MIET was similar, indicating that IG is an adequate substitute for BG. Finally, we showed a strong correlation (R=0.92) between IG-AUC and BG-AUC after a meal. These findings validate the adequacy of glucose AUC measurements using MIET. Monitoring glucose using MIET without blood sampling may be beneficial to patients with diabetes.

Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis

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George G. Zhanel

2016-01-01

Full Text Available Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC in adult women infected with susceptible isolates of E. coli and Enterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared to β-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR E. coli. Resistance to fosfomycin in E. coli is rare (100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin’s in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC.

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

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

A comparative bioavailability study of two ibuprofen formulations after single-dose administration in healthy volunteers

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Metta S.S. Wiria

2007-09-01

Full Text Available This study was aimed to investigate the bioequivalence of ibuprofen 125 mg suppository formulation (Ibukal®, test formulation from PT. Kalbe Farma, Tbk., Jakarta and the ibuprofen suppository comparative formulation (Proris®, from PT. Pharos Indonesia, Jakarta in 12 healthy volunteers. The pharmacokinetic parameters used in this study were the area under the concentration-time curve from time zero to hour 10 (AUC0-t, the area under the concentration-time curve from time zero to infinite (AUC0-inf, the maximum concentration (Cmax, and the time needed to reach the maximum concentration (tmax. The study was designed as a random cross-over fashion, single-blinded which included 12 healthy adult volunteers. The volunteers were fasted overnight and in the morning they received a suppository of the test drug (Ibukal® or a suppository of the comparative drug (Proris®. Blood samples were withdrawn on hour 0 (control, 20 min; 40 min; 1; 1.5; 2; 2.5; 3; 4; 6; 8; and 10 time points after the administration of the drug. Following a wash-out period of 1 week, this procedure was repeated using the other drug. The serum concentration of the drug was determined by means of high-performance liquid chromatography with ultraviolet detection. The results of the study showed that, the mean (SD of AUC0-t, AUC0-inf, Cmax and tmax of the test drug were, respectively, 28.59(3.37 μg.h.mL-1, 30.47(3.56 μg.h.mL-1, 8.24(1.44 μg/mL, and 1.33(0.44 h. The mean (SD of AUC0-t, AUC0-inf, Cmax and tmax of the comparative drug were, respectively, 28.13(8.14 μg.h.mL-1, 30.56(8.05 μg.h.mL-1, 8.27(2.88 μg/mL, and 1.79(0.33 h. The geometric means ratio of the test to the comparative drug were 104.38% (CI 90%: 90.38-120.54% for AUC0-t, 101.97% (CI 90%: 89.51-116.16% for AUC0-inf, and 104.02% (CI 90%: 85.73-126.16% for Cmax. There was no side effect of the drug detected in this study. From the results we can conclude that the 125 mg of ibuprofen suppository of PT Kalbe Farma

PENERAPAN TEKNIK BAGGING PADA ALGORITMA KLASIFIKASI UNTUK MENGATASI KETIDAKSEIMBANGAN KELAS DATASET MEDIS

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Rizki Tri Prasetio

2016-03-01

Full Text Available ABSTRACT – The class imbalance problems have been reported to severely hinder classification performance of many standard learning algorithms, and have attracted a great deal of attention from researchers of different fields. Therefore, a number of methods, such as sampling methods, cost-sensitive learning methods, and bagging and boosting based ensemble methods, have been proposed to solve these problems. Some medical dataset has two classes has two classes or binominal experiencing an imbalance that causes lack of accuracy in classification. This research proposed a combination technique of bagging and algorithms of classification to improve the accuracy of medical datasets. Bagging technique used to solve the problem of imbalanced class. The proposed method is applied on three classifier algorithm i.e., naïve bayes, decision tree and k-nearest neighbor. This research uses five medical datasets obtained from UCI Machine Learning i.e.., breast-cancer, liver-disorder, heart-disease, pima-diabetes and vertebral column. Results of this research indicate that the proposed method makes a significant improvement on two algorithms of classification i.e. decision tree with p value of t-Test 0.0184 and k-nearest neighbor with p value of t-Test 0.0292, but not significant in naïve bayes with p value of t-Test 0.9236. After bagging technique applied at five medical datasets, naïve bayes has the highest accuracy for breast-cancer dataset of 96.14% with AUC of 0.984, heart-disease of 84.44% with AUC of 0.911 and pima-diabetes of 74.73% with AUC of 0.806. While the k-nearest neighbor has the best accuracy for dataset liver-disorder of 62.03% with AUC of 0.632 and vertebral-column of 82.26% with the AUC of 0.867. Keywords: ensemble technique, bagging, imbalanced class, medical dataset. ABSTRAKSI – Masalah ketidakseimbangan kelas telah dilaporkan sangat menghambat kinerja klasifikasi banyak algoritma klasifikasi dan telah menarik banyak perhatian dari

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

Conversion of ammonium uranyl carbonate to UO2 in a fluidized bed

International Nuclear Information System (INIS)

Zhao Jun; Qiu Lufu; Zhong Xing; Xu Heqing

1989-11-01

The conversion of AUC (Ammonium Uranyl Carbonate) to UO 2 was studied in a fluidized bed of 60 mm inner diameter based on the thermodynamics and kinetics data of decomposition-reduction of AUC. The influence of the reaction temperature, composition of fluidization gas and fluidization velocity on conversion were investigated by using N 2 , Ar and circulation gas (mixing gas of H 2 and CO obtained from the exhaust gas of the decomposition of AUC by catalyst crack-conversion) as the fluidization gas. The throughput is up to the high levels (3.32 kg(wet)/h·L) by using circulation gas or mixing of circulation gas and Ar (< 21%) as the fluidization gas when the reaction temperature exceeds 570 deg C

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

KAUST Repository

Kerdi, Fatmé ; Caps, Valerie; Tuel, Alain

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

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.

Femoral perfusion after pulsed electromagnetic field stimulation in a steroid-induced osteonecrosis model.

Science.gov (United States)

Ikegami, Akira; Ueshima, Keiichiro; Saito, Masazumi; Ikoma, Kazuya; Fujioka, Mikihiro; Hayashi, Shigeki; Ishida, Masashi; Fujiwara, Hiroyoshi; Mazda, Osam; Kubo, Toshikazu

2015-07-01

This study was designed to evaluate femoral perfusion after pulsed electromagnetic field (PEMF) stimulation in a steroid-induced osteonecrosis rabbit model by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Steroid-induced osteonecrosis was produced by single intramuscular injection of methylprednisolone in 15 rabbits. Eight rabbits underwent PEMF stimulation (PEMF group) and seven did not (control group). DCE-MRI was performed before PEMF stimulation, immediately before steroid administration, and 1, 5, 10, and 14 days after steroid administration. Regions of interest were set in the bilateral proximal femora. Enhancement ratio (ER), initial slope (IS), and area under the curve (AUC) were analyzed. ER, IS, and AUC in the control group significantly decreased after steroid administration compared with before administration (P<0.05). In PEMF group, IS significantly decreased; however, ER and AUC showed no significant differences after steroid administration compared with before. ER and IS in PEMF group were higher than in control group until 10th day, and AUC was higher until 5th day after steroid administration (P<0.05). PEMF stimulation restrains the decrease in blood flow after steroid administration. © 2015 Wiley Periodicals, Inc.

Computer-aided diagnosis in phase contrast imaging X-ray computed tomography for quantitative characterization of ex vivo human patellar cartilage.

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Nagarajan, Mahesh B; Coan, Paola; Huber, Markus B; Diemoz, Paul C; Glaser, Christian; Wismuller, Axel

2013-10-01

Visualization of ex vivo human patellar cartilage matrix through the phase contrast imaging X-ray computed tomography (PCI-CT) has been previously demonstrated. Such studies revealed osteoarthritis-induced changes to chondrocyte organization in the radial zone. This study investigates the application of texture analysis to characterizing such chondrocyte patterns in the presence and absence of osteoarthritic damage. Texture features derived from Minkowski functionals (MF) and gray-level co-occurrence matrices (GLCM) were extracted from 842 regions of interest (ROI) annotated on PCI-CT images of ex vivo human patellar cartilage specimens. These texture features were subsequently used in a machine learning task with support vector regression to classify ROIs as healthy or osteoarthritic; classification performance was evaluated using the area under the receiver operating characteristic curve (AUC). The best classification performance was observed with the MF features perimeter (AUC: 0.94 ±0.08 ) and "Euler characteristic" (AUC: 0.94 ±0.07 ), and GLCM-derived feature "Correlation" (AUC: 0.93 ±0.07). These results suggest that such texture features can provide a detailed characterization of the chondrocyte organization in the cartilage matrix, enabling classification of cartilage as healthy or osteoarthritic with high accuracy.

Comparing Postural Stability Entropy Analyses to Differentiate Fallers and Non-fallers.

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Fino, Peter C; Mojdehi, Ahmad R; Adjerid, Khaled; Habibi, Mohammad; Lockhart, Thurmon E; Ross, Shane D

2016-05-01

The health and financial cost of falls has spurred research to differentiate the characteristics of fallers and non-fallers. Postural stability has received much of the attention with recent studies exploring various measures of entropy. This study compared the discriminatory ability of several entropy methods at differentiating two paradigms in the center-of-pressure of elderly individuals: (1) eyes open (EO) vs. eyes closed (EC) and (2) fallers (F) vs. non-fallers (NF). Methods were compared using the area under the curve (AUC) of the receiver-operating characteristic curves developed from logistic regression models. Overall, multiscale entropy (MSE) and composite multiscale entropy (CompMSE) performed the best with AUCs of 0.71 for EO/EC and 0.77 for F/NF. When methods were combined together to maximize the AUC, the entropy classifier had an AUC of for 0.91 the F/NF comparison. These results suggest researchers and clinicians attempting to create clinical tests to identify fallers should consider a combination of every entropy method when creating a classifying test. Additionally, MSE and CompMSE classifiers using polar coordinate data outperformed rectangular coordinate data, encouraging more research into the most appropriate time series for postural stability entropy analysis.

Effects of genetic polymorphisms of CYP2C19*2/*3 and MDR1 C3435T on the pharmacokinetics of lansoprazole in healthy Chinese subjects.

Science.gov (United States)

Zhang, Yu-Xin; Wei, Shi-Jie; Yang, Xiao-Ying; Zhang, Wen-Ping; Wang, Xin-Yu; Dang, Hong-Wan

2014-10-01

To evaluate the influence of CYP2C19*2/*3 and MDR1 C3435T polymorphisms on the pharmacokinetics of lansoprazole (LPZ) in healthy Chinese subjects. All 24 subjects were from a study of bioequivalence. Plasma concentrations of LPZ were determined by liquid chromatography/mass spectrometry. Cytochrome P450 (CYP) 2C19*2/*3 and multidrug resistance transporter gene 1 (MDR1) C3435T of the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Significant differences were found in the area under the concentration-time curve from predose to T (AUC(0-T)), area under the concentration-time curve from predose to infinity (AUC(0-∞), t(1/2)), and apparent oral clearance (CL/F) of LPZ between CYP2C19 extensive metabolizers and intermediate metabolizers (p < 0.05). The AUC(0-T), AUC(0-∞), maximum plasma concentration, and CL/F of LPZ were significantly different between subjects with the MDR1 C3435T C/C, C/T, and T/T polymorphisms (p < 0.05). CYP2C19*2/*3 and MDR1 C3435T polymorphisms are important determinants of LPZ pharmacokinetics.

Relation of blood pressure and organ damage: comparison between feasible, noninvasive central hemodynamic measures and conventional brachial measures.

Science.gov (United States)

Lindroos, Annika S; Langén, Ville L; Kantola, Ilkka; Salomaa, Veikko; Juhanoja, Eeva P; Sivén, Sam S; Jousilahti, Pekka; Jula, Antti M; Niiranen, Teemu J

2018-06-01

The present cross-sectional study investigated whether central SBP and pulse pressure (PP) measured noninvasively with a novel cuff-based stand-alone monitor are more strongly associated with hypertensive end-organ damage than corresponding brachial measures. We investigated the cross-sectional association of central versus brachial SBP and PP with echocardiographic left ventricular mass index (LVMI), LV hypertrophy (LVH), carotid intima-media thickness (IMT), and increased IMT (IMT ≥ 75th percentile) among 246 participants drawn from the general population (mean age 57.2 years, 55.3% women). All blood pressure (BP) measures were positively correlated with LVMI and IMT (P area under curve (AUC) for SBP: 0.74 versus 0.76, P = 0.16; AUC for PP: 0.75 versus 0.73, P = 0.35] and IMT (AUC for SBP: 0.61 versus 0.61, P = 0.67; AUC for PP: 0.63 versus 0.61, P = 0.29). Our findings suggest that central SBP and PP measured with a stand-alone noninvasive BP monitor do not improve diagnostic accuracy for end-organ damage over corresponding brachial measures.

Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers.

Science.gov (United States)

Doshi, Maulik S; Naik, Anuja A; Mehta, Mohit R; Gogtay, Nithya J; Thatte, Urmila M; Menon, Mala D

2013-10-01

To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of Cmax, AUC0-t, and AUC0-∞ was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence. Twenty volunteers completed the study. It was seen that the log-transformed values of Cmax, AUC0-t, and AUC0-∞ of the test formulations were not within the specified limits. Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.

A Double-Blind, Randomized Pilot Trial of Chromium Picolinate for Overweight Individuals with Binge-Eating Disorder: Effects on Glucose Regulation.

Science.gov (United States)

Sala, Margarita; Breithaupt, Lauren; Bulik, Cynthia M; Hamer, Robert M; La Via, Maria C; Brownley, Kimberly A

2017-03-04

Chromium treatment has been shown to improve glucose regulation in some populations. The purpose of this study was to evaluate whether chromium picolinate (CrPic) supplementation improves glucose regulation in overweight individuals with binge-eating disorder (BED). In this double-blinded randomized pilot trial, participants (N = 24) were randomized to high (HIGH, 1000 mcg/day, n = 8) or moderate (MOD, 600 mcg/day, n = 9) dose of CrPic or placebo (PL, n = 7) for 6 months. Participants completed an oral glucose tolerance test (OGTT) at baseline, 3 months, and 6 months. Fixed effects models were used to estimate mean change in glucose area under the curve (AUC), insulin AUC , and insulin sensitivity index (ISI). Results revealed a significant group and time interaction (p < 0.04) for glucose AUC , with glucose AUC increasing significantly in the PL group (p < 0.02) but decreasing significantly in the MOD group (p < 0.03) at 6 months. Insulin AUC increased significantly over time (main effect, p < 0.02), whereas ISI decreased significantly over time (main effect, p < 0.03). As anticipated, a moderate dose of CrPic was associated with improved glycemic control, whereas PL was associated with decreased glycemic control. It was unexpected that the improved glycemic control seen in the MOD dose group was not seen in the HIGH dose group. However, although participants randomized to the HIGH dose group did not have improved glycemic control, they had better glycemic control than participants randomized to the PL group. These findings support the need for larger trials.

Application of Appropriate Use Criteria for Initial Transthoracic Echocardiography in an Academic Outpatient Pediatric Cardiology Program.

Science.gov (United States)

Safa, Raya; Aggarwal, Sanjeev; Misra, Amrit; Kobayashi, Daisuke

2017-08-01

Transthoracic echocardiography (TTE) is a non-invasive diagnostic modality for children with suspected heart disease. The American College of Cardiology published Appropriate Use Criteria (AUC) for an initial outpatient pediatric TTE in 2014 to promote effective care and improve resource utilization. The objective was to determine the appropriateness of TTE per the published AUC in a single academic pediatric cardiology clinic as a baseline performance quality measure. The echocardiography database was used to identify initial outpatient TTE in children during January-March 2014. TTE indications (appropriate [A], may be appropriate [M], or rarely appropriate [R]) and findings (normal, incidental, or abnormal) were recorded. The effect of AUC and age groups on yield of abnormal TTE findings was analyzed. Of the 2166 screened studies, our study cohort consisted of 247 TTEs. Indications rated A, M, and R were found in 129, 27, and 90, respectively, and 1 was unclassifiable. Majority of TTE (n = 183) were normal, although incidental findings were noted in 32 and abnormal findings in 32 cases. Abnormal findings were noted in 26/129 of A, 2/27 of M, and 4/90 of R. Indications rated A were significantly associated with yield of abnormal TTE findings, adjusted by age group. Infants and adolescents were more likely to have abnormal TTE findings compared to young children. Recently published AUC were validated for initial TTE in the outpatient pediatric cardiology clinic. Appropriateness rated by AUC was highly associated with yield of abnormal TTE findings and worked best in infants and adolescent.

Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.

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Sun Hee Ahn

Full Text Available Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection and was validated in outbred mice (AUC>0.97. A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI from healthy subjects (AUC 0.99 and E. coli BSI (AUC 0.84. Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84. Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively. The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.

Artificial neural network approach to predict surgical site infection after free-flap reconstruction in patients receiving surgery for head and neck cancer.

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Kuo, Pao-Jen; Wu, Shao-Chun; Chien, Peng-Chen; Chang, Shu-Shya; Rau, Cheng-Shyuan; Tai, Hsueh-Ling; Peng, Shu-Hui; Lin, Yi-Chun; Chen, Yi-Chun; Hsieh, Hsiao-Yun; Hsieh, Ching-Hua

2018-03-02

The aim of this study was to develop an effective surgical site infection (SSI) prediction model in patients receiving free-flap reconstruction after surgery for head and neck cancer using artificial neural network (ANN), and to compare its predictive power with that of conventional logistic regression (LR). There were 1,836 patients with 1,854 free-flap reconstructions and 438 postoperative SSIs in the dataset for analysis. They were randomly assigned tin ratio of 7:3 into a training set and a test set. Based on comprehensive characteristics of patients and diseases in the absence or presence of operative data, prediction of SSI was performed at two time points (pre-operatively and post-operatively) with a feed-forward ANN and the LR models. In addition to the calculated accuracy, sensitivity, and specificity, the predictive performance of ANN and LR were assessed based on area under the curve (AUC) measures of receiver operator characteristic curves and Brier score. ANN had a significantly higher AUC (0.892) of post-operative prediction and AUC (0.808) of pre-operative prediction than LR (both P <0.0001). In addition, there was significant higher AUC of post-operative prediction than pre-operative prediction by ANN (p<0.0001). With the highest AUC and the lowest Brier score (0.090), the post-operative prediction by ANN had the highest overall predictive performance. The post-operative prediction by ANN had the highest overall performance in predicting SSI after free-flap reconstruction in patients receiving surgery for head and neck cancer.

Understanding decision-making in cardiac imaging: determinants of appropriate use.

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Fonseca, Ricardo; Jose, Kim; Marwick, Thomas H

2018-03-01

Appropriate Use Criteria (AUC) for echocardiography were developed in 2007 to facilitate decision-making, reduce variability in test utilization, and encourage rational use of imaging. However, there is little evidence that the AUC have favourably influenced ordering behaviour. This study explores the factors that contribute to clinicians requesting echocardiograms with a focus on appropriate use. Semi-structured face-to-face interviews with cardiologists and non-cardiologists who had requested echocardiograms were conducted at an Australian tertiary hospital. The interview guide included hypothetical clinical scenarios to better understand decision-making in ordering echocardiograms and the actions they could take when receiving test reports. Interviews underwent thematic analysis. Seventeen clinicians were interviewed, ten of whom were cardiologists. All participants ordered echocardiograms to support their clinical decision-making. Awareness of the AUC was low. The categorization of tests as 'appropriate' or 'inappropriate' was considered ineffective as it failed to reflect the decision-making process. The decision to request echocardiograms was influenced by a number of personal and systemic factors as well as guidelines and protocols. Training and experience, patients' expectations, and management of uncertainty were key personal factors. Systemic factors involved the accessibility of services and health insurance status of the patient. Factors that influenced the ordering of echocardiograms by clinicians at a tertiary care hospital did not appear to be amenable to control with AUC. Alternative approaches may be more effective than the AUC in addressing the overuse of echocardiography. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Penentuan Efektifitas Oksitetrasiklin Melalui Parameter Farmakokinetik/farmakodinamik pada Plasma dan Jaringan Ayam Broiler

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Agustina Dwi Wijayanti

2010-06-01

Full Text Available A study was conducted to determine the effectiveness of oxytetracycline on the basis of itspharmacokinetic/pharmacodynamic (PK/PD parameters in the plasma and tissues of broiler following a50 mg/kg single dose of intravenous administration. The male broiler were injected with oxytetracycline attarsal medial venous. The blood, liver, kidney and abdominal muscle were collected at 14 points of timesamplings. Blood was centrifuged to obtain plasma and all tissues were extracted with Mc Ilvine buffer.Drug concentration in samples was determined by High Performance Liquid Chromatography (HPLCusing AOAC standard reference for tetracycline. The pharmacokinetic parameters of oxytetracycline werecalculated using non compartment method. The results were as follows. For plasma: the AUC was 790,615,5 ?g/mL minute , Clearance was 63,242 mL/min/kg bb, Tmax/Cmax was 1 minute/0,7 ?g/mL, T1/2elimination was 6,4, hours, Vd was 37 L/kg. For liver ; AUC was 36418,89, minute , Tmax/Cmax was 16hours/17,15 ?g/g, and T1/2 elimination was 24,5, hours. For kidney; AUC6808,41 ?g/g minute , Tmax/Cmax 1 minute/16,73 ?g/g, , T1/2 elimination was 11,55 hours. For muscle; AUC was 3502 ?g/g minute,Tmax/Cmax was 1 minute/2,58 ?g/g, T1/2 elimination was 167,39 hours. The ratio of AUC/MIC inplasma and tissues appeared to a good pharmacokinetic/pharmacodynamic parameter to determine theeffectiveness of oxytetracycline.

Effect of sucralfate on oral minocycline absorption in healthy dogs.

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KuKanich, K; KuKanich, B; Harris, A; Heinrich, E

2014-10-01

Sucralfate and minocycline may be administered concurrently to dogs. The relative bioavailability of tetracyclines may be reduced if administered with sucralfate, but studies confirming these interactions in dogs are not available. This study evaluated the pharmacokinetics of oral minocycline in dogs (M), determined the effects of concurrent administration of sucralfate and minocycline (MS) on minocycline pharmacokinetics, determined the effects of delaying sucralfate administration by 2 h (MS+2) on minocycline pharmacokinetics, and established dosing recommendations based on pharmacodynamic indices. Oral minocycline (300 mg) and sucralfate suspension (1 g) were administered to five greyhounds in a randomized crossover design. Minocycline plasma concentrations were evaluated using liquid chromatography with mass spectrometry. The maximum plasma concentration (CMAX ) and area under the curve (AUC) of minocycline were 1.15 μg/mL and 8.0 h* μg/mL, respectively. The CMAX and AUC were significantly lower (P < 0.05) in the MS group (CMAX  = 0.33 μg/mL, AUC 3.0 h*μg/mL) compared with M or MS+2 (CMAX = 0.97 μg/mL, AUC 10.3 h*μg/mL). Delaying sucralfate by 2 h did not decrease oral minocycline absorption, but concurrent administration significantly decreased minocycline absorption. A dose of 7.5 mg/kg p.o. q12 h achieves the pharmacodynamic index for a bacterial minimum inhibitory concentration (MIC) of 0.25 μg/mL (AUC:MIC≥33.9). © 2014 John Wiley & Sons Ltd.

Ultrasound contrast-enhanced study as an imaging biomarker for anti-cancer drug treatment: preliminary study with paclitaxel in a xenograft mouse tumor model (secondary publication)

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Lee, Hak Jong; Hwang, Sung Il; Jung, Hyun Sook; Kang, Mi Ra [Dept. of Radiology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Byun, Jong Hoe; Kong, Hoon Young [Dept. of Molecular Biology, Dankook University, Cheonan (Korea, Republic of)

2017-10-15

The purpose of this study was to assess tumor angiogenesis using contrast-enhanced ultrasonography (CEUS) of human prostate cancer cells (PC3) that were implanted in mice before and after paclitaxel injection. Twelve mice were injected with human PC3. The mice were grouped into two groups; one was the paclitaxel-treated group (n=6) and the other was the control group (n=6). Before administering paclitaxel into the peritoneal cavity, baseline CEUS was performed after the administration of 500 μL (1×108 microbubbles) of contrast agent. The area under the curve (AUC) up to 50 seconds after injection was derived from the time-intensity curves. After injection of paclitaxel or saline, CEUS studies were performed at the 1-week follow-up. Changes in tumor volume and the AUC in both two groups were evaluated. After CEUS, the microvessel density (MVD) was compared between the groups. In the paclitaxel-treated group, the AUC from CEUS showed a significant decrease 1-week after paclitaxel administration (P=0.030), even though the tumor volume showed no significant changes (P=0.116). In the control group, there was no significant decrease of the AUC (P=0.173). Pathologically, there was a significant difference in MVD between both groups (P=0.002). The AUC from the time intensity curve derived from CEUS showed an early change in response to the anti-cancer drug treatment that preceded the change in tumor size. The findings of CEUS could serve as an imaging biomarker for assessing tumor responses to anti-cancer drug treatment.

Fructose acute effects on glucose, insulin, and triglyceride after a solid meal compared with sucralose and sucrose in a randomized crossover study.

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Gallagher, Clare; Keogh, Jennifer B; Pedersen, Eva; Clifton, Peter M

2016-06-01

Fructose, which is a sweetener with a low glycemic index, has been shown to elevate postprandial triglyceride compared with glucose. There are limited data on the effect of fructose in a solid mixed meal containing starch and protein. We determined the effects of sucrose, fructose, and sucralose on triglyceride, glucose, and insulin in an acute study in healthy, overweight, and obese individuals. The study had a randomized crossover design. Twenty-seven participants with a mean age of 44 y and a mean body mass index (in kg/m(2)) of 26 completed the study. Fructose (52 g), sucrose (65 g), and sucralose (0.1 g) were delivered as sweet-taste-balanced muffins with a total fat load (66 g). Blood samples were taken at baseline and every 30 min for 4-h glucose, triglyceride, and insulin concentrations, and the area under the curve (AUC) and the incremental area under the curve (iAUC) were analyzed. No significant difference was shown between the 3 sweeteners for triglyceride and glucose concentrations and the AUC. The glucose iAUC was lower for fructose than for sucrose and sucralose (P triglyceride compared with sucrose or sucralose and lowered the glucose iAUC. These results indicate that these sweeteners, at an equivalent sweetness, can be used in normal solid meals. Fructose showed a lower insulin response, which may be beneficial in the long term in individuals at risk of type 2 diabetes. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12615000279527. © 2016 American Society for Nutrition.

Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes.

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Asmar, Meena; Højberg, Patricia V; Deacon, Carolyn F; Hare, Kristine; Holst, Jens J; Madsbad, Sten

2010-02-25

This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 8.0+/-0.4%) and after four weeks of near-normalization of blood glucose (BG) using insulin (mean diurnal BG: 6.4+/-0.3 mmol/l; HbA(1)c: 6.6+/-0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (PAUC amylin/C-peptide ratio was similar on both days, while AUC proinsulin/C-peptide ratio was higher with GLP-1 (P=0.02). In the patients, amylin, C-peptide and proinsulin AUCs were unaltered by near-normoglycaemia per se. Proinsulin responses to GLP-1 were unchanged, but amylin and C-peptide AUCs increased (PAUC amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P=0.04) with GLP-1, but still higher than with saline (P=0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks of near-normoglycaemia, whereas GLP-1 increased amylin and C-peptide secretion and amylin/C-peptide ratio. Near-normoglycaemia reduced proinsulin/C-peptide ratio during stimulation with GLP-1, suggesting that strict glycaemic control might ameliorate some of the disturbances in beta-cell function characterizing T2DM. Copyright 2010 Elsevier B.V. All rights reserved.

Fatty liver index vs waist circumference for predicting non-alcoholic fatty liver disease.

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Motamed, Nima; Sohrabi, Masoudreza; Ajdarkosh, Hossein; Hemmasi, Gholamreza; Maadi, Mansooreh; Sayeedian, Fatemeh Sima; Pirzad, Reza; Abedi, Khadijeh; Aghapour, Sivil; Fallahnezhad, Mojtaba; Zamani, Farhad

2016-03-14

To determine the discriminatory performance of fatty liver index (FLI) for non-alcoholic fatty liver disease (NAFLD). The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from body mass index, waist circumference (WC), triglyceride, and gamma glutamyl transferase data. Logistic regression analysis was conducted to determine the association between FLI and NAFLD. The discriminatory performance of FLI in the diagnosis of NAFLD was evaluated by receiver operating characteristic analysis. Area under the curves (AUCs) and related confidence intervals were estimated. Optimal cutoff points of FLI in the diagnosis of NAFLD were determined based on the maximum values of Youden's index. The mean age of men and women in the study population were 44.8 ± 16.8 and 43.78 ± 15.43, respectively (P = 0.0216). The prevalence of NAFLD was 40.1% in men and 44.2% in women (P < 0.0017). FLI was strongly associated with NAFLD, so that even a one unit increase in FLI increased the chance of developing NAFLD by 5.8% (OR = 1.058, 95%CI: 1.054-1.063, P < 0.0001). Although FLI showed good performance in the diagnosis of NAFLD (AUC = 0.8656 (95%CI: 0.8548-0.8764), there was no significant difference with regards to WC (AUC = 0.8533, 95%CI: 0.8419-0.8646). The performance of FLI was not significantly different between men (AUC = 0.8648, 95%CI: 0.8505-0.8791) and women (AUC = 0.8682, 95%CI: 0.8513-0.8851). The highest performance with regards to age was related to the 18-39 age group (AUC = 0.8930, 95%CI: 0.8766-0.9093). The optimal cutoff points of FLI were 46.9 in men (sensitivity = 0.8242, specificity = 0.7687, Youden's index = 0.5929) and 53.8 in women (sensitivity = 0.8233, specificity = 0.7655, Youden's index = 0.5888). Although FLI had acceptable discriminatory power in the diagnosis of NAFLD, WC was a simpler and more accessible index with a similar performance.

Morning and afternoon appetite and gut hormone responses to meal and stress challenges in obese individuals with and without binge eating disorder.

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Carnell, S; Grillot, C; Ungredda, T; Ellis, S; Mehta, N; Holst, J; Geliebter, A

2017-12-13

Eating late in the day is common, and stress can induce eating. Little is understood about how time of day and stress interact to affect appetite and thereby body weight. These may be particularly important influences in binge eaters, who tend to binge in the evening, and in response to stress. Obese participants with (n=16) and without (n=16) Binge Eating Disorder (BED) participated in two identical test protocols beginning either in the morning or the afternoon (AM condition/PM condition), each following an 8 h fast. For each protocol they first received a standardized liquid meal (9:00am/4:00pm), then a stress test (Socially-Evaluated Cold Pressor Test, 11:10am/6:1pm), then a multi-item ad libitum buffet meal (11:40am/6:40pm), while rating appetite and stress and having blood drawn for hormone measures. Appetite at baseline was greater in the PM than AM condition (higher hunger, lower fullness). Following the liquid meal, AUC values for hunger and ghrelin were greater, and AUC values for PYY lower, in the PM than AM condition. Only those with BED showed lower fullness AUC in the PM condition, as well as a pattern of higher initial PM and lower initial AM ghrelin. Following the stress test, cortisol and ghrelin increased in both the AM and PM conditions, but higher ghrelin AUC and lower cortisol AUC were observed in the PM condition. Again, only participants with BED showed lower fullness AUC in the PM condition. Buffet meal intake was similar across groups and conditions, but those with BED reported greater loss of control and binge resemblance than those without. Afternoon/evening may be a high-risk period for overeating, particularly when paired with stress exposure, and for those with binge eating.International Journal of Obesity accepted article preview online, 13 December 2017. doi:10.1038/ijo.2017.307.

Strategies to assess systemic exposure of chemicals in subchronic/chronic diet and drinking water studies

International Nuclear Information System (INIS)

Saghir, Shakil A.; Mendrala, Alan L.; Bartels, Michael J.; Day, Sue J.; Hansen, Steve C.; Sushynski, Jacob M.; Bus, James S.

2006-01-01

Strategies were developed for the estimation of systemically available daily doses of chemicals, diurnal variations in blood levels, and rough elimination rates in subchronic feeding/drinking water studies, utilizing a minimal number of blood samples. Systemic bioavailability of chemicals was determined by calculating area under the plasma concentration curve over 24 h (AUC-24 h) using complete sets of data (≥5 data points) and also three, two, and one selected time points. The best predictions of AUC-24 h were made when three time points were used, corresponding to C max , a mid-morning sample, and C min . These values were found to be 103 ± 10% of the original AUC-24 h, with 13 out of 17 values ranging between 96 and 105% of the original. Calculation of AUC-24 h from two samples (C max and C min ) or one mid-morning sample afforded slightly larger variations in the calculated AUC-24 h (69-136% of the actual). Following drinking water exposure, prediction of AUC-24 h using 3 time points (C max , mid-morning, and C min ) was very close to actual values (80-100%) among mice, while values for rats were only 63% of the original due to less frequent drinking behavior of rats during the light cycle. Collection and analysis of 1-3 blood samples per dose may provide insight into dose-proportional or non-dose-proportional differences in systemic bioavailability, pointing towards saturation of absorption or elimination or some other phenomenon warranting further investigation. In addition, collection of the terminal blood samples from rats, which is usually conducted after 18 h of fasting, will be helpful in rough estimation of blood/plasma half-life of the compound. The amount of chemical(s) and/or metabolite(s) in excreta and their possible use as biomarkers in predicting the daily systemic exposure levels are also discussed. Determining these parameters in the early stages of testing will provide critical information to improve the appropriate design of other longer

Salivary Cortisol and Cortisone do not Appear to be Useful Biomarkers for Monitoring Hydrocortisone Replacement in Addison's Disease.

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Ross, I L; Lacerda, M; Pillay, T S; Blom, D J; Johannsson, G; Dave, J A; Levitt, N S; Haarburger, D; van der Walt, J-S

2016-12-01

Salivary cortisol has been used to monitor hydrocortisone replacement in patients with Addison's disease (AD). Since salivary cortisol is metabolised to salivary cortisone, it may be an adjunctive analyte to assess adequacy of hydrocortisone replacement in patients with AD. We aimed to characterise the exposure of salivary cortisol and cortisone in patients and healthy controls. We measured salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry and constructed a day curve (08:00 until 24:00 h) with 16 time points in 25 AD patients taking their usual hydrocortisone dose and in 26 healthy controls. The median (interquartile range) area under the curve (AUC) for cortisol was not different for patients, compared with controls [55.63 (32.91-151.07) nmol*min*l -1 vs. 37.49 (27.41-52.00) nmol*min*l -1 ; p=0.098, respectively], whereas the peak cortisol C max was higher in patients [32.61 (5.75-146.19) nmol/l vs. 8.96 (6.96-12.23) nmol/l; p=0.013], compared with controls. The AUC for cortisone [23.65 (6.10-54.76) nmol*min*l -1 vs. 227.73 (200.10-280.52) nmol*min*l -1 ; p≤ 0.001, respectively], and peak cortisone C max was lower in patients than in controls [11.11 (2.91-35.85) nmol/l vs. 33.12 (25.97-39.95) nmol/l; p=0.002]. The AUC for salivary cortisol and salivary cortisone were not correlated with any measures of hydrocortisone dose. The time-course and AUC of salivary cortisol were similar between Addison's patients and healthy controls. Patients had substantially lower salivary cortisone AUC, compared to healthy controls. Salivary cortisol AUC and pharmacokinetics were not related to hydrocortisone dose and thus are not likely useful markers for the adequacy of hydrocortisone replacement. © Georg Thieme Verlag KG Stuttgart · New York.

Pharmacokinetics of neratinib during coadministration with lansoprazole in healthy subjects.

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Keyvanjah, Kiana; DiPrimeo, Daniel; Li, Ai; Obaidi, Mohammad; Swearingen, Dennis; Wong, Alvin

2017-03-01

To evaluate the effect of lansoprazole, a proton-pump inhibitor, on the absorption, pharmacokinetics, and safety of neratinib, a pan-HER tyrosine kinase inhibitor, in healthy subjects. This was an open-label, two-period, fixed-sequence study. Fifteen healthy adult subjects received a single oral dose of neratinib 240 mg (Period 1), followed by a washout period, then oral lansoprazole 30 mg once daily for 7 days and a single dose of neratinib 240 mg on Day 5 (Period 2). Pharmacokinetic sampling was performed for 72 h following each neratinib dose. Plasma neratinib concentration-time data were analysed using noncompartmental methods. Geometric mean ratios for AUC 0-t , AUC 0-inf , and peak plasma concentrations (C max ) for neratinib plus lansoprazole vs. neratinib were used to assess the magnitude of the drug-drug interaction if the 90% confidence intervals were outside 80.00-125.00%. Neratinib geometric least-squares mean (LSM) C max was reduced from 84.5 ng ml -1 with neratinib alone to 24.5 ng ml -1 with neratinib plus lansoprazole. The extent of exposure to neratinib was also decreased: geometric LSM AUC 0-t was 1478 ng ml -1  h with neratinib vs. 426 ng ml -1  h with neratinib plus lansoprazole, and geometric LSM AUC 0-inf was 1557 ng ml -1  h vs. 542 ng ml -1  h, respectively. Mean t ½ was similar with both treatments (approximately 14 h). Geometric mean ratios 90% confidence intervals for AUC 0-t , AUC 0-inf and C max fell outside the prespecified equivalence range (80.0-125.0%). Treatment-emergent adverse events, all mild, were reported by five (33%) subjects. Coadministration of lansoprazole with neratinib reduced the rate and extent of neratinib exposure in healthy subjects. © 2016 The British Pharmacological Society.

Discordance Between Appropriate Use Criteria for Nuclear Myocardial Perfusion Imaging From Different Specialty Societies: A Potential Concern for Health Policy.

Science.gov (United States)

Winchester, David E; Wolinsky, David; Beyth, Rebecca J; Shaw, Leslee J

2016-05-01

Appropriate use criteria (AUC) assist health care professionals in making decisions about procedures and diagnostic testing. In some cases, multiple AUC exist for a single procedure or test. To date, the extent of agreement between multiple AUC has not been evaluated. To measure discordance between the American College of Cardiology Foundation (ACCF) AUC and the American College of Radiology (ACR) Appropriateness Criteria for gauging the appropriateness of nuclear myocardial perfusion imaging. Retrospective cohort study at an academically affiliated Veterans Affairs medical center. Participants were Veteran patients who underwent nuclear myocardial perfusion imaging between December 2010 and July 2011 with rating of appropriateness by the ACCF and ACR criteria. Analysis was performed in March 2015. The primary outcome was the agreement of appropriateness category as measured by κ statistic. The secondary outcome was a comparison of nuclear myocardial perfusion imaging results and frequency of ischemia across appropriateness categories for the 2 rating methods. Of 67 indications in the ACCF AUC, 35 (52.2%) could not be matched to an ACR rating, 18 (26.9%) had the same appropriateness category, and 14 (20.9%) disagreed on appropriateness. The study cohort comprised 592 individuals. Their mean (SD) age was 62.6 (9.4) years, and 570 of 592 (96.2%) were male. When applied to the patient cohort, 111 patients (18.8%) could not be matched to an ACR rating, 349 patients (59.0%) had the same appropriateness category for the ACR and ACCF methods, and 132 patients (22.3%) were discordant. Overall, the agreement of appropriateness between the 2 methods was poor (κ = 0.34, P < .001). Ischemia was rare among patients rated as "inappropriate" by the ACCF AUC (1 of 39 patients [2.6%]), while ischemia was more common among patients rated as "usually not appropriate" by the ACR Appropriateness Criteria (14 of 80 patients [17.5%]). Substantial discordance may exist between

SU-F-T-107: Correlations Between Dosimetric Indices of Pharyngeal Constrictors and Proximal Esophagus with Associated Patient-Reported Outcomes Six Months After Radiation Therapy for Head and Neck Cancer

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Chera, B; Price, A; Kostich, M; Green, R; Das, S; Mavroidis, P [University of North Carolina, Chapel Hill, North Carolina (United States); Amdur, R; Mendenhall, W [University of Florida, Gainesville, FL (United States); Sheets, N [University of North Carolina, Raleigh, North Carolina (United States); Marks, L [UNC School of Medicine, Chapel Hill, NC (United States)

2016-06-15

Purpose: To compare the correlations between different dosimetric indices derived from the pharyngeal constrictor muscles and proximal esophagus with patient-reported difficulty in swallowing 6 months post radiotherapy using a novel patient reported outcome version of CTCAE (PRO-CTCAE). Methods: Forty-three patients with oropharyngeal squamous cell carcinoma were treated on a prospective multi-institutional study. All patients received de-intensified 60 Gy intensity modulated radiotherapy. We investigated correlations of individual patient dosimetric data of the superior (SPC), middle (MPC), inferior (IPC) pharyngeal constrictor muscles, the superior esophagus (SES), and the inferior esophagus (IES) to their self-reported 6 month post-treatment swallowing difficulty responses. Mild (≥ Grade 1) swallowing difficulty responses were used as the clinical endpoint indicating response. The predictive efficacy of Dmean and dose-volume (VD) points were assessed through the area under the Receiver Operating Characteristic curve (ROC) and Odds Ratio (OR). Results: The SES and SPC had more favorable area under the curves (AUC) for the Dmean (0.62 and 0.70) while the Dmean to the IPC, MPC, and IES produced suboptimal AUCs (0.42, 0.48, and 0.52). Additionally, over the range of VD, the V54 and V55 for the SES and SPC demonstrated the highest AUCs: AUC(SES) = 0.76–0.73 and AUC(SPC) = 0.72–0.69, respectively. The IES, IPC, and MPC had worse AUC results over the range of VD. An optimal OR can be found when V54 = 96% for the SPC, where OR = 3.96 (1.07–14.62). Conclusion: The V45 and V55 of the SES and SPC had the highest correlation to the clinical endpoint compared to the commonly used dosimetric index, Dmean for both the esophagus and constrictor muscles. The reported dosimetric data demonstrates that new dosimetric indices may need to be considered in the setting of dose de-escalation and self-reported outcomes.

Relationship between the temporal changes in positron-emission-tomography-imaging-based textural features and pathologic response and survival in esophageal cancer patients

Directory of Open Access Journals (Sweden)

Stephen ShingFan Yip

2016-03-01

Full Text Available Purpose: Although change in SUV measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer. Methods: Fifty-four esophageal cancer patients received PET/CT scans before and after chemo-radiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two co-occurrence matrix (Entropy and Homogeneity, two run-length-matrix (High-gray-run-emphasis and Short-run-high-gray-run-emphasis, and two size-zone-matrix (High-gray-zone-emphasis and Short-zone-high-gray-emphasis textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC and Kaplan-Meier statistics respectively. Results: All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC=0.79, p=1.7x10^-4 and partial (AUC=0.71, p=0.01 responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run length and size zone matrix textures (AUC=0.71‒0.76, p≤0.02. Homogeneity, SUVmax and SUVmean failed to differentiate between any of the responders (AUC=0.50‒0.57, p≥0.46. However, none of the measures were found to significantly distinguish between complete and partial responders with AUC0.25. Conclusions: For the patients studied, temporal change in Entropy and all Run length matrix were better correlated with pathological response and survival than the SUV

Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults.

Science.gov (United States)

Beyer, Peter L; Caviar, Elena M; McCallum, Richard W

2005-10-01

Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with

Local curvature analysis for classifying breast tumors: Preliminary analysis in dedicated breast CT

International Nuclear Information System (INIS)

Lee, Juhun; Nishikawa, Robert M.; Reiser, Ingrid; Boone, John M.; Lindfors, Karen K.

2015-01-01

Purpose: The purpose of this study is to measure the effectiveness of local curvature measures as novel image features for classifying breast tumors. Methods: A total of 119 breast lesions from 104 noncontrast dedicated breast computed tomography images of women were used in this study. Volumetric segmentation was done using a seed-based segmentation algorithm and then a triangulated surface was extracted from the resulting segmentation. Total, mean, and Gaussian curvatures were then computed. Normalized curvatures were used as classification features. In addition, traditional image features were also extracted and a forward feature selection scheme was used to select the optimal feature set. Logistic regression was used as a classifier and leave-one-out cross-validation was utilized to evaluate the classification performances of the features. The area under the receiver operating characteristic curve (AUC, area under curve) was used as a figure of merit. Results: Among curvature measures, the normalized total curvature (C_T) showed the best classification performance (AUC of 0.74), while the others showed no classification power individually. Five traditional image features (two shape, two margin, and one texture descriptors) were selected via the feature selection scheme and its resulting classifier achieved an AUC of 0.83. Among those five features, the radial gradient index (RGI), which is a margin descriptor, showed the best classification performance (AUC of 0.73). A classifier combining RGI and C_T yielded an AUC of 0.81, which showed similar performance (i.e., no statistically significant difference) to the classifier with the above five traditional image features. Additional comparisons in AUC values between classifiers using different combinations of traditional image features and C_T were conducted. The results showed that C_T was able to replace the other four image features for the classification task. Conclusions: The normalized curvature measure

Resting sympathetic activity is associated with the sympathetically mediated component of energy expenditure following a meal.

Science.gov (United States)

Limberg, Jacqueline K; Malterer, Katherine R; Matzek, Luke J; Levine, James A; Charkoudian, Nisha; Miles, John M; Joyner, Michael J; Curry, Timothy B

2017-08-01

Individuals with high plasma norepinephrine (NE) levels at rest have a smaller reduction in resting energy expenditure (REE) following β -adrenergic blockade. If this finding extends to the response to a meal, it could have important implications for the role of the sympathetic nervous system in energy balance and weight gain. We hypothesized high muscle sympathetic nerve activity (MSNA) would be associated with a low sympathetically mediated component of energy expenditure following a meal. Fourteen young, healthy adults completed two visits randomized to continuous saline (control) or intravenous propranolol to achieve systemic β -adrenergic blockade. Muscle sympathetic nerve activity and REE were measured (indirect calorimetry) followed by a liquid mixed meal (Ensure). Measures of energy expenditure continued every 30 min for 5 h after the meal and are reported as an area under the curve (AUC). Sympathetic support of energy expenditure was calculated as the difference between the AUC during saline and β -blockade (AUC P ropranolol -AUC S aline , β -REE) and as a percent (%) of control (AUC P ropranolol ÷AUC S aline  × 100). β -REE was associated with baseline sympathetic activity, such that individuals with high resting MSNA (bursts/100 heart beats) and plasma NE had the greatest sympathetically mediated component of energy expenditure following a meal (MSNA: β -REE R  =   -0.58, P =  0.03; %REE R  = -0.56, P =  0.04; NE: β -REE R  = -0.55, P  = 0.0535; %REE R  = -0.54, P  = 0.0552). Contrary to our hypothesis, high resting sympathetic activity is associated with a greater sympathetically mediated component of energy expenditure following a liquid meal. These findings may have implications for weight maintenance in individuals with varying resting sympathetic activity. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Impulsivity and Fast-Food Consumption: A Cross-Sectional Study among Working Adults.

Science.gov (United States)

Garza, Kimberly B; Ding, Meng; Owensby, Justin K; Zizza, Claire A

2016-01-01

Little is known about the decision-making process of adults who choose to eat at fast-food restaurants. Impulsivity is the concept that individuals value immediate rewards and disregard future costs. To determine the association between impulsivity and consumption of fast food among employed adults and to explore their reasons for eating fast food. A cross-sectional, online survey was conducted; participants were recruited using a mass electronic mailing. Four hundred seventy-eight adults employed in a university setting completed the survey. The association between frequency of fast-food consumption and impulsivity was assessed. Impulsivity is assessed by the area under the delay discounting curve (AUC). The AUC is estimated by using a binary choice delay discounting task incorporating hypothetical monetary rewards. Greater AUC reflects lower impulsivity. Analysis of variance, Student's t tests, and Pearson correlation coefficients were used to measure unadjusted associations among demographic variables, fast-food consumption, and AUC. Linear regression was used to assess whether AUC was a significant predictor of having consumed fast food in the past 7 days, controlling for age, total household income, and education. The majority (67%) of the participants reported eating one or more meals from a fast-food restaurant or pizza place in the past 7 days. The mean number of meals was 2.8±2.5 per week among those who reported eating at a fast-food restaurant or pizza place. Both fast-food consumption and body mass index (BMI) were correlated with greater impulsivity. Controlling for age, total household income, and education level, fast-food consumption was negatively related to AUC (P=0.017). The most commonly reported reasons for consuming fast food were convenience and to socialize. These findings indicate that greater impulsivity was associated with greater fast-food consumption. Successful efforts to encourage healthful dietary behaviors might emphasize methods

An optimal method for generating stable vancomycin heteroresistance and intermediate susceptibility in methicillin-resistant Staphylococcus aureusblood isolates under in-vitro vancomycin pressure

Directory of Open Access Journals (Sweden)

Riad Khatib

2012-12-01

Full Text Available Objectives: The relevance of vancomycin intermediately-susceptible (VISA and hetero-resistant (hVISA methicillin-resistantStaphylococcus aureus (MRSA remains uncertain because of their low frequency. In vitro attempts to generate reducedsusceptibility have been inconsistent. We describe a simple method for generating VISA/hVISA.Materials and methods: Twenty-four SCCmec type II and IV MRSA blood isolates plus USA100 and USA300 controls werecultured (107 CFU/ml in BHI broth with 0, 2 and 3 mg/L vancomycin for 10 days followed by 10 days vancomycin-freepassage.We monitored vancomycin minimum inhibitory concentration (MIC; Etest and population analysis profile-areaunder the curve (PAP-AUC ratios of tested isolate-Mu3 during and after vancomycin pressure (VP. PAP-AUC ratios 1.3 were considered consistent with susceptible, hVISA and VISA, respectively.Results: VP at 2 mg/L (VP-2 increased MIC to 3 mg/L in 20 (83.3% isolates and raised PAP-AUC ratio to hVISA (n=18; 75.0%and VISA (six; 25.0% ranges. VP-3 increased MIC to 3 and 4 mg/L in 19 (79.2% and three (12.5% isolates, respectively andraised PAP-AUC ratio to hVISA (n=3; 12.5% and VISA (n=19; 79.2% ranges. SCCmec IV isolates had lower pre-exposurePAP-AUC ratios (0.48±0.14 vs. 0.69±0.10; p<0.001 and lower MIC (1.6±0.2 vs. 1.8±0.2 mg/L; p=0.1 but MIC rise and VISA/hVISA emergence was comparable. MIC and PAP-AUC ratio rises were stable in 20/22 isolates during drug-free passages.Conclusions: VISA/hVISA readily emerges among MRSA SCCmec type II and IV isolates under VP. VP at the MIC level generateshVISA while pressure at slightly higher level results in the VISA phenotype. J Microbiol Infect Dis 2012; 2(4: 129-134Key words: Staphylococcus aureus; heteroresistance; glycopeptides; resistance; bacteremia.

Texture analysis of high-resolution dedicated breast {sup 18}F-FDG PET images correlates with immunohistochemical factors and subtype of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Moscoso, Alexis; Dominguez-Prado, Ines; Herranz, Michel; Argibay, Sonia; Silva-Rodriguez, Jesus [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Nuclear Medicine Department and Molecular Imaging Group, Santiago de Compostela (Spain); Ruibal, Alvaro [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Nuclear Medicine Department and Molecular Imaging Group, Santiago de Compostela (Spain); University of Santiago de Compostela (USC), Molecular Imaging Group, Department of Radiology, Faculty of Medicine, Santiago de Compostela (Spain); Fundacion Tejerina, Madrid (Spain); Fernandez-Ferreiro, Anxo [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Pharmacy Department and Pharmacology Group, Santiago de Compostela (Spain); Albaina, Luis [University Hospital A Coruna (SERGAS), Department of General Surgery, A Coruna (Spain); Pardo-Montero, Juan [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Nuclear Medicine Department and Molecular Imaging Group, Santiago de Compostela (Spain); Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Medical Physics Department, Santiago de Compostela (Spain); Aguiar, Pablo [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Nuclear Medicine Department and Molecular Imaging Group, Santiago de Compostela (Spain); University of Santiago de Compostela (USC), Molecular Imaging Group, Department of Radiology, Faculty of Medicine, Santiago de Compostela (Spain)

2018-02-15

This study aims to determine whether PET textural features measured with a new dedicated breast PET scanner reflect biological characteristics of breast tumors. One hundred and thirty-nine breast tumors from 127 consecutive patients were included in this analysis. All of them underwent a {sup 18}F-FDG PET scan before treatment. Well-known PET quantitative parameters such as SUV{sub m} {sub a} {sub x}, SUV{sub m} {sub e} {sub a} {sub n}, metabolically active tumor volume (MATV) and total lesion glycolysis (TLG) were extracted. Together with these parameters, local, regional, and global heterogeneity descriptors, which included five textural features (TF), were computed. Immunohistochemical classification of breast cancer considered five subtypes: luminal A like (LA), luminal B like/HER2 - (LB -), luminal B like/HER2+ (LB+), HER2-positive-non-luminal (HER2pnl), and triple negative (TN). Associations between PET features and tumor characteristics were assessed using non-parametric hypothesis tests. Along with well-established associations, new correlations were found. HER2-positive tumors had significantly higher uptake (p < 0.001, AUCs > 0.70) and presented different global and regional heterogeneity (p = 0.002, p = 0.016, respectively, AUCs < 0.70). Nine out of ten analyzed features were significantly associated with immunohistochemical subtype. Uptake was lower for LA tumors (p < 0.001) with AUCs ranging from 0.71 to 0.88 for each subgroup comparison. Heterogeneity metrics were significantly associated when comparing LA and LB - (p < 0.01), being regional heterogeneity metrics more discriminative than any other parameter (AUC = 0.80 compared to AUC = 0.71 for SUV). LB+ and HER2pnl tumors also showed more regional heterogeneity than LA tumors (AUCs = 0.79 and 0.84, respectively). After comparison with whole-body PET studies, we observed an overall improvement in the classification ability of both non-heterogeneity metrics and textural features. PET parameters

The Added Value of Medical Testing in Underwriting Life Insurance.

Directory of Open Access Journals (Sweden)

Jan Bronsema

Full Text Available In present-day life-insurance medical underwriting practice the risk assessment starts with a standard health declaration (SHD. Indication for additional medical screening depends predominantly on age and amount of insured capital. From a medical perspective it is questionable whether there is an association between the level of insured capital and medical risk in terms of mortality. The aim of the study is to examine the prognostic value of parameters from the health declaration and application form on extra mortality based on results from additional medical testing.A history register-based cohort study was conducted including about 15.000 application files accepted between 2007 and 2010. Blood pressure, lipids, cotinine and glucose levels were used as dependent variables in logistic regression models. Resampling validation was applied using 250 bootstrap samples to calculate area under the curves (AUC's. The AUC was used to discriminate between persons with and without at least 25% extra mortality.BMI and the overall assessment of the health declaration by an insurance physician or medical underwriter showed the strongest discrimination in multivariable analysis. Including all variables at minimum cut-off levels resulted in an AUC of 0.710 while by using a model with BMI, the assessment of the health declaration and gender, the AUC was 0.708. Including all variables at maximum cut-off levels lead to an AUC of 0.743 while a model with BMI, the assessment of the health declaration and age resulted in an AUC of 0.741.The outcome of this study shows that BMI and the overall assessment of the health declaration were the dominant variables to discriminate between applicants for life-insurance with and without at least 25 percent extra mortality. The variable insured capital set by insurers as factor for additional medical testing could not be established in this study population. The indication for additional medical testing at underwriting life

Development and optimization of SPECT gated blood pool cluster analysis for the prediction of CRT outcome

Energy Technology Data Exchange (ETDEWEB)

Lalonde, Michel, E-mail: mlalonde15@rogers.com; Wassenaar, Richard [Department of Physics, Carleton University, Ottawa, Ontario K1S 5B6 (Canada); Wells, R. Glenn; Birnie, David; Ruddy, Terrence D. [Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7 (Canada)

2014-07-15

Purpose: Phase analysis of single photon emission computed tomography (SPECT) radionuclide angiography (RNA) has been investigated for its potential to predict the outcome of cardiac resynchronization therapy (CRT). However, phase analysis may be limited in its potential at predicting CRT outcome as valuable information may be lost by assuming that time-activity curves (TAC) follow a simple sinusoidal shape. A new method, cluster analysis, is proposed which directly evaluates the TACs and may lead to a better understanding of dyssynchrony patterns and CRT outcome. Cluster analysis algorithms were developed and optimized to maximize their ability to predict CRT response. Methods: About 49 patients (N = 27 ischemic etiology) received a SPECT RNA scan as well as positron emission tomography (PET) perfusion and viability scans prior to undergoing CRT. A semiautomated algorithm sampled the left ventricle wall to produce 568 TACs from SPECT RNA data. The TACs were then subjected to two different cluster analysis techniques, K-means, and normal average, where several input metrics were also varied to determine the optimal settings for the prediction of CRT outcome. Each TAC was assigned to a cluster group based on the comparison criteria and global and segmental cluster size and scores were used as measures of dyssynchrony and used to predict response to CRT. A repeated random twofold cross-validation technique was used to train and validate the cluster algorithm. Receiver operating characteristic (ROC) analysis was used to calculate the area under the curve (AUC) and compare results to those obtained for SPECT RNA phase analysis and PET scar size analysis methods. Results: Using the normal average cluster analysis approach, the septal wall produced statistically significant results for predicting CRT results in the ischemic population (ROC AUC = 0.73;p < 0.05 vs. equal chance ROC AUC = 0.50) with an optimal operating point of 71% sensitivity and 60% specificity. Cluster

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

Development and optimization of SPECT gated blood pool cluster analysis for the prediction of CRT outcome

International Nuclear Information System (INIS)

Lalonde, Michel; Wassenaar, Richard; Wells, R. Glenn; Birnie, David; Ruddy, Terrence D.

2014-01-01

Purpose: Phase analysis of single photon emission computed tomography (SPECT) radionuclide angiography (RNA) has been investigated for its potential to predict the outcome of cardiac resynchronization therapy (CRT). However, phase analysis may be limited in its potential at predicting CRT outcome as valuable information may be lost by assuming that time-activity curves (TAC) follow a simple sinusoidal shape. A new method, cluster analysis, is proposed which directly evaluates the TACs and may lead to a better understanding of dyssynchrony patterns and CRT outcome. Cluster analysis algorithms were developed and optimized to maximize their ability to predict CRT response. Methods: About 49 patients (N = 27 ischemic etiology) received a SPECT RNA scan as well as positron emission tomography (PET) perfusion and viability scans prior to undergoing CRT. A semiautomated algorithm sampled the left ventricle wall to produce 568 TACs from SPECT RNA data. The TACs were then subjected to two different cluster analysis techniques, K-means, and normal average, where several input metrics were also varied to determine the optimal settings for the prediction of CRT outcome. Each TAC was assigned to a cluster group based on the comparison criteria and global and segmental cluster size and scores were used as measures of dyssynchrony and used to predict response to CRT. A repeated random twofold cross-validation technique was used to train and validate the cluster algorithm. Receiver operating characteristic (ROC) analysis was used to calculate the area under the curve (AUC) and compare results to those obtained for SPECT RNA phase analysis and PET scar size analysis methods. Results: Using the normal average cluster analysis approach, the septal wall produced statistically significant results for predicting CRT results in the ischemic population (ROC AUC = 0.73;p < 0.05 vs. equal chance ROC AUC = 0.50) with an optimal operating point of 71% sensitivity and 60% specificity. Cluster

Gender differences in the accuracy of time-dependent blood pressure indices for predicting coronary heart disease: A random-effects modeling approach.

Science.gov (United States)

Brant, Larry J; Ferrucci, Luigi; Sheng, Shan L; Concin, Hans; Zonderman, Alan B; Kelleher, Cecily C; Longo, Dan L; Ulmer, Hanno; Strasak, Alexander M

2010-12-01

Previous studies on blood pressure (BP) indices as a predictor of coronary heart disease (CHD) have provided equivocal results and generally relied on Cox proportional hazards regression methodology, with age and sex accounting for most of the predictive capability of the model. The aim of the present study was to use serially collected BP measurements to examine age-and gender-related differences in BP indices for predicting CHD. The predictive accuracy of time-dependent BP indices for CHD was investigated using a method of risk prediction based on posterior probabilities calculated from mixed-effects regression to utilize intraindividual differences in serial BP measurements according to age changes within gender groups. Data were collected prospectively from 2 community-dwelling cohort studies in the United States (Baltimore Longitudinal Study of Aging [BLSA]) and Europe (Vorarlberg Health Monitoring and Promotion Program [VHM&PP]). The study comprised 152,633 participants (aged 30-74 years) and 610,061 BP measurements. During mean follow-up of 7.5 years, 2457 nonfatal and fatal CHD events were observed. In both study populations, pulse pressure (PP) and systolic blood pressure (SBP) performed best as individual predictors of CHD in women (area under the receiver operating characteristic curve [AUC(ROC)] was between 0.83 and 0.85 for PP, and between 0.77 and 0.81 for SBP). Mean arterial pressure (MAP) and diastolic blood pressure (DBP) performed better for men (AUC(ROC) = 0.67 and 0.65 for MAP and DBP, respectively, in the BLSA; AUC(ROC) = 0.77 and 0.75 in the VHM&PP) than for women (AUC(ROC) = 0.60 for both MAP and DBP in the BLSA; AUC(ROC) = 0.75 and 0.52, respectively, in the VHM&PP). The degree of discrimination in both populations was overall greater but more varied for all BP indices for women (AUC(ROC) estimates between 0.85 [PP in the VHM&PP] and 0.52 [DBP in the VHM&PP]) than for men (AUC(ROC) estimates between 0.78 [MAP + PP in the VHM&PP] and 0.63 [PP

Glucose Metabolism in High-Risk Subjects for Type 2 Diabetes Carrying the rs7903146 TCF7L2 Gene Variant.

Science.gov (United States)

Daniele, Giuseppe; Gaggini, Melania; Comassi, Mario; Bianchi, Cristina; Basta, Giuseppina; Dardano, Angela; Miccoli, Roberto; Mari, Andrea; Gastaldelli, Amalia; Del Prato, Stefano

2015-08-01

The mechanisms responsible for contribution of variants in the gene TFC7L2 to the risk for type 2 diabetes (T2DM) remains far from being completely understood, and available studies have generated nonunivocal results. We investigated the postprandial glucose metabolism in subjects at risk for T2DM carrying the TCF7L2 risk allele. Twenty-three subjects carrying the risk-conferring TCF7L2 genotypes (11 TT and 12 CT at rs7901346) and 13 subjects with wild-type genotype (CC) underwent a standard mixed-meal test (MMT) in combination with stable isotope tracers. We evaluated endogenous and exogenous glucose fluxes and hormonal responses. Fasting plasma glucose, insulin, C-peptide, glycated hemoglobin, endogenous glucose production, and plasma glucose clearance were similar in the three groups, whereas plasma glucagon levels were lower in both CT and TT than in CC (64 ± 20, 63 ± 18 and 90 ± 29 pg/mL, respectively; both P = .01). In response to the MMT, TT subjects had lower plasma glucose levels than CC subjects [mean area under the time-concentration curve (AUC) 6.1 ± 3.9 vs 7.1 ± 12.0 mmol/L, P = .04] and lower insulin secretion rate (mean AUC 385 ± 95 vs 530 ± 159 pmol/m(2) · min, P = .02). Initial (0-60 min) rate of appearance (Ra) of oral glucose was lower in TT compared with CT/CC (AUC 2.7 ± 1.1 vs 3.8 ± 1.2 μmol/kg · min, P = .02) with no difference among the three groups in endogenous glucose production. The AUC0-60min for Ra of exogenous glucose (Raex) was positively correlated with the plasma glucose AUC0-60min. Total Raex AUC0-120min was correlated with total AUC0-120min of plasma glucose (r = 0.45, P glucose-dependent insulinotropic peptide levels in response to the MMT were not affected by genotype. In subjects at risk for T2DM, the TCF7L2 polymorphisms were associated with reduced Raex into systemic circulation, causing reduced postprandial blood glucose increase and, in turn, lower insulin secretion rate with no impairment in β-cell function

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...

Apparent diffusion coefficient in the analysis of prostate cancer: determination of optimal b-value pair to differentiate normal from malignant tissue.

Science.gov (United States)

Adubeiro, Nuno; Nogueira, Maria Luísa; Nunes, Rita G; Ferreira, Hugo Alexandre; Ribeiro, Eduardo; La Fuente, José Maria Ferreira

Determining optimal b-value pair for differentiation between normal and prostate cancer (PCa) tissues. Forty-three patients with diagnosis or PCa symptoms were included. Apparent diffusion coefficient (ADC) was estimated using minimum and maximum b-values of 0, 50, 100, 150, 200, 500s/mm2 and 500, 800, 1100, 1400, 1700 and 2000s/mm2, respectively. Diagnostic performances were evaluated when Area-under-the-curve (AUC)>95%. 15 of the 35 b-values pair surpassed this AUC threshold. The pair (50, 2000s/mm2) provided the highest AUC (96%) with ADC cutoff 0.89×10- 3 mm 2 /s, sensitivity 95.5%, specificity 93.2% and accuracy 94.4%. The best b-value pair was b=50, 2000s/mm2. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative forecasting of PTSD from early trauma responses: A Machine Learning application

DEFF Research Database (Denmark)

Galatzer-Levy, I. R.; Karstoft, K. I.; Statnikov, A.

2014-01-01

-traumatic stress disorder (PTSD) is plausible given the disorder's salient onset and the abundance of putative biological and clinical risk indicators. This work evaluates the ability of Machine Learning (ML) forecasting approaches to identify and integrate a panel of unique predictive characteristics...... algorithm identified a set of predictors that rendered all others redundant. Support Vector Machines (SVMs) as well as other ML classification algorithms were used to evaluate the forecasting accuracy of i) ML selected features, ii) all available features without selection, and iii) Acute Stress Disorder......). The feature selection algorithm identified 16 predictors, present in >= 95% cross-validation trials. The accuracy of predicting non-remitting PTSD from that set (AUC = .77) did not differ from predicting from all available information (AUC = .78). Predicting from ASD symptoms was not better then chance (AUC...

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...

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

Background and Objectives: Linezolid, a oxazolidinone, was the first in class to be approved for the treatment of bacterial infections arising from both susceptible and resistant strains of Gram-positive bacteria. Since overt exposure of linezolid may precipitate serious toxicity issues......, therapeutic drug monitoring (TDM) may be required in certain situations, especially in patients who are prescribed other co-medications. Methods: Using appropriate oral pharmacokinetic data (single dose and steady state) for linezolid, both maximum plasma drug concentration (Cmax) versus area under the plasma...... concentration–time curve (AUC) and minimum plasma drug concentration (Cmin) versus AUC relationship was established by linear regression models. The predictions of the AUC values were performed using published mean/median Cmax or Cmin data and appropriate regression lines. The quotient of observed and predicted...

Effect of postprandial hyperglycaemia in non-invasive measurement of cerebral metabolic rate of glucose in non-diabetic subjects

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Tsuchida, Tatsuro; Itoh, Harumi [Department of Radiology, Fukui Medical University, Matsuoka (Japan); Sadato, Norihiro; Nishizawa, Sadahiko; Yonekura, Yoshiharu [Biomedical Imaging Research Center, Fukui Medical University (Japan)

2002-02-01

The aim of this study was to determine the effect of postprandial hyperglycaemia (HG) on the non-invasive measurement of cerebral metabolic rate of glucose (CMRGlc). Five patients who had a meal within an hour before a fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) examination were recruited in this study. They underwent intermittent arterial blood sampling (measured input function), and, based on this sampling, CMRGlc was calculated using an autoradiographic method (CMRGlc{sub real}). Simulated input functions were generated based on standardised input function, body surface area and net injected dose of FDG, and simulated CMRGlc (CMRGlc{sub sim}) was also calculated. Percent error of the area under the curve (AUC) between measured (AUC{sub real}) and simulated input function (AUC{sub IFsim}) and percent error between CMRGlc{sub real} and CMRGlc{sub sim} were calculated. These values were compared with those obtained from a previous study conducted under fasting conditions (F). The serum glucose level in the HG group was significantly higher than that in the F group (165{+-}69 vs 100{+-}9 mg/dl, P=0.0007). Percent errors of AUC and CMRGlc in grey matter and white matter in HG were significantly higher than those in F (12.9%{+-}1.3% vs 3.5%{+-}2.2% in AUC, P=0.0015; 18.2%{+-}2.2% vs 2.9%{+-}1.9% in CMRGlc in grey matter, P=0.0028; 24.0%{+-}4.6% vs 3.4%{+-}2.2% in CMRGlc in white matter, P=0.0028). It is concluded that a non-invasive method of measuring CMRGlc should be applied only in non-diabetic subjects under fasting conditions. (orig.)

Diagnostic significance of haematological testing in patients presenting at the Emergency Department

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Giuseppe Lippi

2012-03-01

Full Text Available The use of simple and economic tests to rule out diseases of sufficient clinical severity is appealing in emergency department (ED, since it would be effective for contrasting ED overcrowding and decreasing healthcare costs. The aim of this study was to assess the diagnostic performance of simple and economic haematological testing in a large sample of adult patients presenting at the ED of the Academic Hospital of Parma during the year 2010 with the five most frequent acute pathologies (i.e., acute myocardial infarction, renal colic, pneumonia, trauma and pancreatitis. Both leukocyte count and hemoglobin showed a good diagnostic performance (Area Under the Curve [AUC] of 0.85 for leukocyte count and 0.76 for hemoglobin; both p < 0.01. Although the platelet count was significantly increased in all patients groups except pancreatitis, the diagnostic performance did not achieve statistical significance (AUC 0.53; p = 0.07. We also observed an increased RDW in all groups, except in those with trauma and the diagnostic performance was acceptable (AUC 0.705; p < 0.01. The mean platelet volume (MPV was consistently lower in all patients groups and also characterized by an efficient diagnostic performance (AUC 0.76; p < 0.01. This evidence led us to design an arbitrary formula, whereby MPV and hemoglobin were multiplied, and further divided by the leukocyte count, obtaining a remarkable AUC (0.91; p < 0.01. We conclude that simple, rapid and cheap hematological tests might provide relevant clinical information for decision making to busy emergency physicians, and the their combination into an arbitrary formula might further increase the specific diagnostic potential of each of them.

Cut-Offs and Response Criteria for the Hospital Universitario La Princesa Index (HUPI and Their Comparison to Widely-Used Indices of Disease Activity in Rheumatoid Arthritis.

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Isidoro González-Álvaro

Full Text Available To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI in patients with chronic polyarthritis.Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal [PEARL] study and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide [EMECAR] including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC analysis. The areas under ROC (AUC were compared to those of validated indexes (SDAI, CDAI, DAS28. ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI.The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if ≤2, low disease activity if >2 and ≤5, moderate if >5 and <9 and high if ≥9. HUPI's AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28's AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756 and CDAI (AUCs: 0.789 and 0.728. HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values.The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis.

Quantitative analysis of Miller mobility index for the diagnosis of moderate to severe periodontitis - A cross-sectional study

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Chung-Ping Wu

2018-03-01

Full Text Available Background/purpose: We assessed the mobility of single-root teeth by using Miller's mobility index (MMI and to analyze the validity of MMI for the diagnosis of periodontitis. Materials and methods: A total of 30 patients were included and the Spearman correlation coefficient was used to assess the correlation between MMI, clinical attachment level (CAL, and probing depth (PD. The validity of MMI for the diagnosis of the severity of periodontitis was evaluated using the receiver operating characteristic (ROC curve, area under curve (AUC value, positive predictive value (PPV. Results: Strong correlations were observed between MMI and CAL (r = 0.92 and between MMI and PD (r = 0.76. When the CAL = 3–4 mm and CAL ≥5 mm groups were pooled together, the AUC value was 0.81. The AUC was 0.86 for diagnosis with MMI in the CAL ≥5 mm group. A PPV of 100% was achieved for all grades when MMI >1. When the teeth with PD ≥ 5 to <7 mm and PD ≥ 7 mm groups were pooled together, the AUC value for MMI was 0.80. The PPV was 98.8%, 99%, and 100% for MMI Grade 1, Grade 2, and Grade 3, respectively. When PD ≥ 7 mm was defined as severe periodontitis, the AUC value for MMI was 0.72. Conclusion: MMI may provide valuable information for the diagnosis of moderate and severe periodontitis when CAL is not obtainable during routine practice. Keywords: Miller's mobility index, Negative predictive value, Nonsurgical periodontal therapy, Positive predictive value, Receiver operating characteristic curve, Tooth mobility

Psychological stress during exercise: immunoendocrine and oxidative responses.

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Huang, Chun-Jung; Webb, Heather E; Evans, Ronald K; McCleod, Kelly A; Tangsilsat, Supatchara E; Kamimori, Gary H; Acevedo, Edmund O

2010-12-01

The purpose of this study was to examine the changes in catecholamines (epinephrine [EPI] and norepinephrine [NE]), interleukin-2 (IL-2) and a biomarker of oxidative stress (8-isoprostane) in healthy individuals who were exposed to a dual challenge (physical and psychological stress). Furthermore, this study also examined the possible relationships between catecholamines (NE and EPI) and 8-isoprostane and between IL-2 and 8-isoprostane following a combined physical and psychological challenge. Seven healthy male subjects completed two experimental conditions. The exercise-alone condition (EAC) consisted of cycling at 60% VO(2max) for 37 min, while the dual-stress condition (DSC) included 20 min of a mental challenge while cycling. DSC showed greater EPI and 8-isoprostane levels (significant condition by time interaction). NE and IL-2 revealed significant change across time in both conditions. In addition, following dual stress, EPI area-under-the-curve (AUC) demonstrated a positive correlation with NE AUC and IL-2 AUC. NE AUC was positively correlated with IL-2 AUC and peak 8-isoprostane, and peak IL-2 was positively correlated with peak 8-isoprostane in response to a dual stress. The potential explanation for elevated oxidative stress during dual stress may be through the effects of the release of catecholamines and IL-2. These findings may further provide the potential explanation that dual stress alters physiological homeostasis in many occupations including firefighting, military operations and law enforcement. A greater understanding of these responses to stress can assist in finding strategies (e.g. exercise training) to overcome the inherent psychobiological challenges associated with physically and mentally demanding professions.

Validity of Chinese Version of the Composite International Diagnostic Interview-3.0 in Psychiatric Settings

Institute of Scientific and Technical Information of China (English)

Jin Lu; Yue-Qin Huang; Zhao-Rui Liu; Xiao-Lan Cao

2015-01-01

Background:The Composite International Diagnostic Interview-3.0 (CIDI-3.0) is a fully structured lay-administered diagnostic interview for the assessment of mental disorders according to ICD-10 and Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (DSM-Ⅳ) criteria.The aim of the study was to investigate the concurrent validity of the Chinese CIDI in diagnosing mental disorders in psychiatric settings.Methods:We recruited 208 participants,of whom 148 were patients from two psychiatric hospitals and 60 healthy people from communities.These participants were administered with CIDI by six trained lay interviewers and the Structured Clinical Interview for DSM-Ⅳ Axis I Disorders (SCID-I,gold standard) by two psychiatrists.Agreement between CIDI and SCID-I was assessed with sensitivity,specificity,positive predictive value and negative predictive value.Individual-level CIDI-SCID diagnostic concordance was evaluated using the area under the receiver operator characteristic curve and Cohen's K.Results:Substantial to excellent CIDI to SCID concordance was found for any substance use disorder (area under the receiver operator characteristic curve [AUC] =0.926),any anxiety disorder (AUC =0.807) and any mood disorder (AUC =0.806).The concordance between the CIDI and the SCID for psychotic and eating disorders is moderate.However,for individual mental disorders,the CIDI-SCID concordance for bipolar disorders (AUC =0.55) and anorexia nervosa (AUC =0.50) was insufficient.Conclusions:Overall,the Chinese version of CIDI-3.0 has acceptable validity in diagnosing the substance use disorder,anxiety disorder and mood disorder among Chinese adult population.However,we should be cautious when using it for bipolar disorders and anorexia nervosa.

Comparison of saline infusion sonohysterography and hysteroscopy in diagnosis of premenopausal women with abnormal uterine bleeding.

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Soguktas, Suna; Cogendez, Ebru; Kayatas, Semra Eser; Asoglu, Mehmet Resit; Selcuk, Selcuk; Ertekin, Aktug

2012-03-01

The aim of this study was to compare the diagnostic effectiveness of transvaginal sonography (TVS), saline infusion sonohysterography (SIS), and diagnostic hysteroscopy (HS), with the pathologic specimen as a gold standard diagnostic method, in detecting endometrial pathology in premenopausal women with abnormal uterine bleeding. This prospective cohort study was conducted at Zeynep Kamil Education and Training Hospital, Istanbul, Turkey, and included 89 premenopausal women. All participants were examined first by TVS, further investigated with SIS and HS, and finally dilatation and curettage was performed when needed. The results obtained from these three methods were compared with the pathologic diagnoses. The positive and negative likelihood ratios (LR+ and LR-) of TVS, SIS and HS were calculated by comparison with the final pathological diagnosis. In addition, area under the curve (AUC) values were also calculated. Polypoid lesion was the most common abnormal pathology. LR+ and LR- of TVS, SIS, and HS were 3.13 and 0.15, 9.83 and 0.07, 13.7 and 0.02 respectively in detection of any abnormal pathology, and the AUCs of TVS, SIS, and HS were 0.804, 0.920, and 0.954 respectively. When the three procedures were compared with each other separately, HS had the best diagnostic accuracy, and the diagnostic accuracy of HS and SIS was superior to TVS (p(1)=0.000, p(2)=0.000). For the detection of polypoid lesions, HS was the most accurate diagnostic procedure (AUC=0.947), followed by SIS (AUC=0.894) and TVS (AUC=0.778). HS provides the most accurate diagnosis and allows treatment in the same session in premenopausal women with abnormal uterine bleeding. Published by Elsevier Ireland Ltd.

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

International Nuclear Information System (INIS)

Gondo, Tatsuo; Hricak, Hedvig; Sala, Evis; Vargas, Hebert Alberto; Zheng, Junting; Moskowitz, Chaya S.; Bernstein, Melanie; Eastham, James A.

2014-01-01

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 0.99 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.)

Cut-Offs and Response Criteria for the Hospital Universitario La Princesa Index (HUPI) and Their Comparison to Widely-Used Indices of Disease Activity in Rheumatoid Arthritis.

Science.gov (United States)

González-Álvaro, Isidoro; Castrejón, Isabel; Ortiz, Ana M; Toledano, Esther; Castañeda, Santos; García-Vadillo, Alberto; Carmona, Loreto

2016-01-01

To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal [PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide [EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if ≤2, low disease activity if >2 and ≤5), moderate if >5 and <9 and high if ≥9. HUPI's AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28's AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis.

Validity of Chinese Version of the Composite International Diagnostic Interview-3.0 in Psychiatric Settings

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Jin Lu

2015-01-01

Full Text Available Background: The Composite International Diagnostic Interview-3.0 (CIDI-3.0 is a fully structured lay-administered diagnostic interview for the assessment of mental disorders according to ICD-10 and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV criteria. The aim of the study was to investigate the concurrent validity of the Chinese CIDI in diagnosing mental disorders in psychiatric settings. Methods: We recruited 208 participants, of whom 148 were patients from two psychiatric hospitals and 60 healthy people from communities. These participants were administered with CIDI by six trained lay interviewers and the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I, gold standard by two psychiatrists. Agreement between CIDI and SCID-I was assessed with sensitivity, specificity, positive predictive value and negative predictive value. Individual-level CIDI-SCID diagnostic concordance was evaluated using the area under the receiver operator characteristic curve and Cohen′s K. Results: Substantial to excellent CIDI to SCID concordance was found for any substance use disorder (area under the receiver operator characteristic curve [AUC] = 0.926, any anxiety disorder (AUC = 0.807 and any mood disorder (AUC = 0.806. The concordance between the CIDI and the SCID for psychotic and eating disorders is moderate. However, for individual mental disorders, the CIDI-SCID concordance for bipolar disorders (AUC = 0.55 and anorexia nervosa (AUC = 0.50 was insufficient. Conclusions: Overall, the Chinese version of CIDI-3.0 has acceptable validity in diagnosing the substance use disorder, anxiety disorder and mood disorder among Chinese adult population. However, we should be cautious when using it for bipolar disorders and anorexia nervosa.

Factor structure and clinical utility of the Beck depression inventory in patients with binge eating disorder and obesity.

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Udo, Tomoko; McKee, Sherry A; Grilo, Carlos M

2015-01-01

The Beck Depression Inventory (BDI) is often used to assess depression symptoms, but its factor structure and its clinical utility have not been evaluated in patients with binge eating disorder (BED) and obesity. A total of 882 treatment-seeking obese patients with BED were administered structured interviews (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders) and completed self-report questionnaires. Exploratory and confirmatory factor analyses supported a brief 16-item BDI version with a three-factor structure (affective, attitudinal and somatic). Both 21- and 16-item versions showed excellent internal consistency (both α=0.89) and had significant correlation patterns with different aspects of eating disorder psychopathology; three factors showed significant but variable associations with eating disorder psychopathology. Area under the curves (AUC) for both BDI versions were significant in predicting major depressive disorder (MDD; AUC=0.773 [16-item], 73.5% sensitivity/70.2% specificity, AUC=0.769 [21-item], 79.5% sensitivity/64.1% specificity) and mood disorders (AUC=0.763 [16-item], 67.1% sensitivity/71.5% specificity, AUC=0.769 [21-item], 84.2% sensitivity/55.7% specificity). The 21-item BDI (cutoff score ≥16) showed higher negative predictive values (94.0% vs. 93.0% [MDD]; 92.4% vs. 88.3% [mood disorders]) than the brief 16-item BDI (cutoff score ≥13). Both BDI versions demonstrated moderate performance as a screening instrument for MDD/mood disorders in obese patients with BED. Advantages and disadvantages for both versions are discussed. A three-factor structure has potential to inform the conceptualization of depression features. Copyright © 2015 Elsevier Inc. All rights reserved.

Is it possible to shorten ambulatory blood pressure monitoring?

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Wolak, Talya; Wilk, Lior; Paran, Esther; Wolak, Arik; Gutmacher, Bella; Shleyfer, Elena; Friger, Michael

2013-08-01

The aim of this investigation was to find a time segment in which average blood pressure (BP) has the best correlation with 24-hour BP control. A total of 240 patients with full ambulatory BP monitoring (ABPM) were included; 120 had controlled BP (systolic BP [SBP] ≤135 mm Hg and diastolic BP [DBP] ≤85 mm Hg) and 120 had uncontrolled BP (SBP >135 mm Hg and/or DBP >85 mm Hg). Each ABPM was divided into 6- and 8-hour segments. Evaluation for correlation between mean BP for each time segment and 24-hour BP control was performed using receiver operating characteristic curve analysis and Youden's index for threshold with the best sensitivity and specificity. The mean BP in the following segments showed the highest area under the curve (AUC) compared with average controlled 24-hour BP: SBP 2 am to 8 am (AUC, 0.918; threshold value of 133.5 mm Hg, sensitivity-0.752 and specificity-0.904); SBP 2 pm to 10 pm (AUC, 0.911; threshold value of 138.5 mm Hg, sensitivity-0.803 and specificity-0.878); and SBP 6 am to 2 pm (AUC, 0.903; threshold value of 140.5 mm Hg, sensitivity-0.778 and specificity-0.888). The time segment 2 pm to 10 pm was shown to have good correlation with 24-hour BP control (AUC >0.9; sensitivity and specificity >80%). This time segment might replace full ABPM as a screening measure for BP control or as abbreviated ABPM for patients with difficulty in performing full ABPM. © 2013 Wiley Periodicals, Inc.

External validation of the NOBLADS score, a risk scoring system for severe acute lower gastrointestinal bleeding.

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Tomonori Aoki

Full Text Available We aimed to evaluate the generalizability of NOBLADS, a severe lower gastrointestinal bleeding (LGIB prediction model which we had previously derived when working at a different institution, using an external validation cohort. NOBLADS comprises the following factors: non-steroidal anti-inflammatory drug use, no diarrhea, no abdominal tenderness, blood pressure ≤ 100 mmHg, antiplatelet drug use, albumin < 3.0 g/dL, disease score ≥ 2, and syncope.We retrospectively analyzed 511 patients emergently hospitalized for acute LGIB at the University of Tokyo Hospital, from January 2009 to August 2016. The areas under the receiver operating characteristic curves (ROCs-AUCs for severe bleeding (continuous and/or recurrent bleeding were compared between the original derivation cohort and the external validation cohort.Severe LGIB occurred in 44% of patients. Several clinical factors were significantly different between the external and derivation cohorts (p < 0.05, including background, laboratory data, NOBLADS scores, and diagnosis. The NOBLADS score predicted the severity of LGIB with an AUC value of 0.74 in the external validation cohort and one of 0.77 in the derivation cohort. In the external validation cohort, the score predicted the risk for blood transfusion need (AUC, 0.71, but was not adequate for predicting intervention need (AUC, 0.54. The in-hospital mortality rate was higher in patients with a score ≥ 5 than in those with a score < 5 (AUC, 0.83.Although the external validation cohort clinically differed from the derivation cohort in many ways, we confirmed the moderately high generalizability of NOBLADS, a clinical risk score for severe LGIB. Appropriate triage using this score may support early decision-making in various hospitals.

Metabolic Effects of a Commonly Used Combined Hormonal Oral Contraceptive in Women With and Without Polycystic Ovary Syndrome

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Adeniji, Adeola A.; Essah, Paulina A.; Nestler, John E.

2016-01-01

Abstract Background: Data on combined hormonal oral contraceptives' (OCs) effects on metabolic changes in women with polycystic ovary syndrome (PCOS) have been conflicting and were predominantly based on OCs with cyproterone acetate (unavailable in the United States) Most studies did not include normal women as controls. We compared metabolic changes before and after an OC commonly used in the United States between women with and without PCOS. Methods: Ten PCOS and 20 control women took ethinyl estradiol 35 μg and norgestimate 0.18/0.215/0.25 mg. Fasting glucose and insulin, area-under-the-curve (AUC) glucose and insulin, insulin sensitivity (homeostatic model assessment of insulin sensitivity index [HOMA-ISI] and Matsuda index), insulinogenic index (Δinsulin0–30 minutes/Δglucose0–30 minutes), blood pressure, and lipids were evaluated at baseline and after three cycles of OC. Results: At baseline, PCOS women had lower insulin sensitivity (Matsuda index p = 0.0093, HOMA-ISI p = 0.0397), higher fasting insulin (p = 0.0495), fasting glucose (p = 0.0393), AUC insulin (p = 0.0023), and triglycerides (p = 0.0044) versus controls. Baseline AUC glucose did not differ between PCOS women and controls. After 3 months of OC use, glucose tolerance worsened in PCOS women versus controls (p = 0.0468). Higher baseline androgens were predictive of worsened glucose tolerance, and a reduction of AUC insulin during OC use. The insulinogenic index significantly decreased in PCOS women (p glucose tolerance (demonstrated by AUC glucose) after 3 months of a commonly used OC compared with control women. Larger studies with longer follow-up should confirm these findings. PMID:26871978

Effect of postprandial hyperglycaemia in non-invasive measurement of cerebral metabolic rate of glucose in non-diabetic subjects

International Nuclear Information System (INIS)

Tsuchida, Tatsuro; Itoh, Harumi; Sadato, Norihiro; Nishizawa, Sadahiko; Yonekura, Yoshiharu

2002-01-01

The aim of this study was to determine the effect of postprandial hyperglycaemia (HG) on the non-invasive measurement of cerebral metabolic rate of glucose (CMRGlc). Five patients who had a meal within an hour before a fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) examination were recruited in this study. They underwent intermittent arterial blood sampling (measured input function), and, based on this sampling, CMRGlc was calculated using an autoradiographic method (CMRGlc real ). Simulated input functions were generated based on standardised input function, body surface area and net injected dose of FDG, and simulated CMRGlc (CMRGlc sim ) was also calculated. Percent error of the area under the curve (AUC) between measured (AUC real ) and simulated input function (AUC IFsim ) and percent error between CMRGlc real and CMRGlc sim were calculated. These values were compared with those obtained from a previous study conducted under fasting conditions (F). The serum glucose level in the HG group was significantly higher than that in the F group (165±69 vs 100±9 mg/dl, P=0.0007). Percent errors of AUC and CMRGlc in grey matter and white matter in HG were significantly higher than those in F (12.9%±1.3% vs 3.5%±2.2% in AUC, P=0.0015; 18.2%±2.2% vs 2.9%±1.9% in CMRGlc in grey matter, P=0.0028; 24.0%±4.6% vs 3.4%±2.2% in CMRGlc in white matter, P=0.0028). It is concluded that a non-invasive method of measuring CMRGlc should be applied only in non-diabetic subjects under fasting conditions. (orig.)

New serum biomarkers for prostate cancer diagnosis

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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

Diagnostic performance of qualitative shear-wave elastography according to different color map opacities for breast masses

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Kim, Hana; Youk, Ji Hyun, E-mail: jhyouk@yuhs.ac; Gweon, Hye Mi; Kim, Jeong-Ah; Son, Eun Ju

2013-08-15

Purpose: To compare the diagnostic performance of qualitative shear-wave elastography (SWE) according to three different color map opacities for breast masses Materials and methods: 101 patients aged 21–77 years with 113 breast masses underwent B-mode US and SWE under three different color map opacities (50%, 19% and 100%) before biopsy or surgery. Following SWE features were reviewed: visual pattern classification (pattern 1–4), color homogeneity (E{sub homo}) and six-point color score of maximum elasticity (E{sub col}). Combined with B-mode US and SWE, the likelihood of malignancy (LOM) was also scored. The area under the curve (AUC) was obtained by ROC curve analysis to assess the diagnostic performance under each color opacity. Results: A visual color pattern, E{sub homo}, E{sub col} and LOM scoring were significantly different between benign and malignant lesions under all color opacities (P < 0.001). For 50% opacity, AUCs of visual color pattern, E{sub col}, E{sub homo} and LOM scoring were 0.902, 0.951, 0.835 and 0.975. But, for each SWE feature, there was no significant difference in the AUC among three different color opacities. For all color opacities, visual color pattern and E{sub col} showed significantly higher AUC than E{sub homo}. In addition, a combined set of B-mode US and SWE showed significantly higher AUC than SWE alone for color patterns, E{sub homo}, but no significant difference was found in E{sub col}. Conclusion: Qualitative SWE was useful to differentiate benign from malignant breast lesion under all color opacities. The difference in color map opacity did not significantly influence diagnostic performance of SWE.

Diagnostic performance of qualitative shear-wave elastography according to different color map opacities for breast masses

International Nuclear Information System (INIS)

Kim, Hana; Youk, Ji Hyun; Gweon, Hye Mi; Kim, Jeong-Ah; Son, Eun Ju

2013-01-01

Purpose: To compare the diagnostic performance of qualitative shear-wave elastography (SWE) according to three different color map opacities for breast masses Materials and methods: 101 patients aged 21–77 years with 113 breast masses underwent B-mode US and SWE under three different color map opacities (50%, 19% and 100%) before biopsy or surgery. Following SWE features were reviewed: visual pattern classification (pattern 1–4), color homogeneity (E homo ) and six-point color score of maximum elasticity (E col ). Combined with B-mode US and SWE, the likelihood of malignancy (LOM) was also scored. The area under the curve (AUC) was obtained by ROC curve analysis to assess the diagnostic performance under each color opacity. Results: A visual color pattern, E homo , E col and LOM scoring were significantly different between benign and malignant lesions under all color opacities (P < 0.001). For 50% opacity, AUCs of visual color pattern, E col , E homo and LOM scoring were 0.902, 0.951, 0.835 and 0.975. But, for each SWE feature, there was no significant difference in the AUC among three different color opacities. For all color opacities, visual color pattern and E col showed significantly higher AUC than E homo . In addition, a combined set of B-mode US and SWE showed significantly higher AUC than SWE alone for color patterns, E homo , but no significant difference was found in E col . Conclusion: Qualitative SWE was useful to differentiate benign from malignant breast lesion under all color opacities. The difference in color map opacity did not significantly influence diagnostic performance of SWE

3D-Printing for Analytical Ultracentrifugation.

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Abhiksha Desai

Full Text Available Analytical ultracentrifugation (AUC is a classical technique of physical biochemistry providing information on size, shape, and interactions of macromolecules from the analysis of their migration in centrifugal fields while free in solution. A key mechanical element in AUC is the centerpiece, a component of the sample cell assembly that is mounted between the optical windows to allow imaging and to seal the sample solution column against high vacuum while exposed to gravitational forces in excess of 300,000 g. For sedimentation velocity it needs to be precisely sector-shaped to allow unimpeded radial macromolecular migration. During the history of AUC a great variety of centerpiece designs have been developed for different types of experiments. Here, we report that centerpieces can now be readily fabricated by 3D printing at low cost, from a variety of materials, and with customized designs. The new centerpieces can exhibit sufficient mechanical stability to withstand the gravitational forces at the highest rotor speeds and be sufficiently precise for sedimentation equilibrium and sedimentation velocity experiments. Sedimentation velocity experiments with bovine serum albumin as a reference molecule in 3D printed centerpieces with standard double-sector design result in sedimentation boundaries virtually indistinguishable from those in commercial double-sector epoxy centerpieces, with sedimentation coefficients well within the range of published values. The statistical error of the measurement is slightly above that obtained with commercial epoxy, but still below 1%. Facilitated by modern open-source design and fabrication paradigms, we believe 3D printed centerpieces and AUC accessories can spawn a variety of improvements in AUC experimental design, efficiency and resource allocation.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Gd-EOB-DTPA for the Evaluation of Liver Fibrosis Induced by Carbon Tetrachloride in Rats.

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Wei Zhang

Full Text Available To investigate the utility of dynamic contrast-enhanced MRI (DCE-MRI with Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA for detecting liver fibrosis induced by carbon tetrachloride (CCl4 in rats.This study was approved by the institutional animal care and use committee. Liver fibrosis in rats was induced by intraperitoneal injection of 1 mL/kg 50% CCl4 twice a week for 4-13 weeks. Control rats were injected with saline. Liver fibrosis was graded using the Metaviar score: no fibrosis (F0, mild fibrosis (F1-F2 and advanced fibrosis (F3-F4. DCE-MRI with Gd-EOB-DTPA was performed for all rats. Ktrans, Kep, Ve and iAUC of the liver parenchyma were measured. Relative enhancement (RE value of the liver was calculated on T1-weighted images at 15, 20 and 25 min after Gd-EOB-DTPA administration.Thirty-five rats were included: no fibrosis (n=13, mild fibrosis (n=11 and advanced fibrosis (n=11. Ktrans and iAUC values were highest in advanced fibrosis group and lowest in no fibrosis group (P＜0.05. The area under the receiver operating characteristic curve (AUROC for fibrosis (stages F1 and greater were 0.773 and 0.882 for Ktrans and iAUC, respectively. AUROC for advanced fibrosis were 0.835 and 0.867 for Ktrans and iAUC, respectively. Kep and RE values were not able to differentiate fibrosis stages (all P＞0.05.Ktrans and iAUC obtained from DCE-MRI with Gd-EOB-DTPA are useful for the detection and staging of rat liver fibrosis induced by CCl4.

Differences in the associations of anthropometric measures with insulin resistance and type 2 diabetes mellitus between Korean and US populations: Comparisons of representative nationwide sample data.

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Yoon, Yeong Sook; Choi, Han Seok; Kim, Jin Kuk; Kim, Yu Il; Oh, Sang Woo

Variation among ethnic groups in the association between obesity and insulin resistance (IR)/diabetes has been suggested, but studies reported inconsistent results. We evaluated ethnic differences in the association between obesity and insulin resistance (IR)/diabetes. We conducted a cross-sectional analysis using Korea (n=18,845) and the USA (n=4657) National Health and Nutrition Examination Survey(NHANES) 2007-2010. We performed statistical comparisons of AUC-ROC (area under the curve in a receiver operating characteristic curve) values for body mass index (BMI), waist circumference (WC) and homeostasis model assessment of insulin resistance (HOMA-IR) to predict IR or diabetes among different ethnic groups. AUC-ROC values for BMI and WC for predicting IR were highest in Whites (0.8324 and 0.8468) and lowest in Koreans (0.7422 and 0.7367). Whites showed the highest AUC-ROC values for BMI (0.6869) and WC (0.7421) for predicting diabetes, while the AUC-ROC for HOMA-IR was highest in Koreans (0.8861). Linear regression showed significant interactions between ethnicity and the main effects (all Pdiabetes was highest in Whites, while the ability of HOMA-IR to predict diabetes was highest in Koreans. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Bioequivalence Studies of a Reformulated Dutasteride and Tamsulosin Hydrochloride Combination Capsule and a Commercially Available Formulation.

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Kurczewski, Renee; Bowen, Chet; Collins, David; Zhu, John; Serbest, Gulyeter; Manyak, Michael

2017-09-01

A dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg combination (DTC) capsule (Duodart ® ) was reformulated to reduce the capsule size and enhance product stability. Bioequivalence of the reformulated DTC capsule with the commercial formulation was evaluated in 2 single-dose, open-label, randomized, 2-way crossover studies in healthy adult male volunteers. Subjects in a fasted or fed state received a single oral dose of either the reformulated DTC or the commercial formulation followed by a 28-day washout period between treatments. Blood samples were taken predose and up to 72 hours postdose for pharmacokinetic (PK) analysis of dutasteride and tamsulosin serum concentrations. From the serum concentration-vs-time data, a noncompartmental method was used to calculate the maximum observed serum concentration (C max ) and area under the serum concentration-time curve (AUC 0-t ) for dutasteride and tamsulosin, and AUC 0-∞ for tamsulosin. The 90% confidence intervals for the ratios of the C max and AUC 0-t (for dutasteride and tamsulosin) and for AUC 0-∞ (for tamsulosin) were all completely contained within the range of 80% to 125%; therefore, the reformulated DTC capsule is bioequivalent to the commercial formulation under both fed and fasted states. © 2017, The American College of Clinical Pharmacology.

Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats.

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Antunes, Luciana C; Elkfury, Jessica L; Jornada, Manoela N; Foletto, Kelly C; Bertoluci, Marcello C

2016-04-01

Objective The present study aimed to validate homeostasis model assessment of insulin resistance (HOMA-IR) in relation to the insulin tolerance test (ITT) in a model of insulin-resistance in Wistar rats induced by a 19-week high-fat diet. Materials and methods A total of 30 male Wistar rats weighing 200-300 g were allocated into a high-fat diet group (HFD) (55% fat-enriched chow, ad lib, n = 15) and a standard-diet group (CD) standard chow, ad lib, n = 15), for 19 weeks. ITT was determined at baseline and in the 19th week. HOMA-IR was determined between the 18-19th week in three different days and the mean was considered for analysis. Area under the curve (AUC-ITT) of the blood glucose excursion along 120 minutes after intra-peritoneal insulin injection was determined and correlated with the corresponding fasting values for HOMA-IR. Results AUC-ITT and HOMA-IR were significantly greater after 19th week in HFD compared to CD (p HOMA-IR was strongly correlated (Pearson's) with AUC-ITT r = 0.637; p HOMA-IR and AUC-ITT showed similar sensitivity and specificity. Conclusion HOMA-IR is a valid measure to determine insulin-resistance in Wistar rats. Arch Endocrinol Metab. 2016;60(2):138-42.

An Approach for Predicting Essential Genes Using Multiple Homology Mapping and Machine Learning Algorithms.

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Hua, Hong-Li; Zhang, Fa-Zhan; Labena, Abraham Alemayehu; Dong, Chuan; Jin, Yan-Ting; Guo, Feng-Biao

Investigation of essential genes is significant to comprehend the minimal gene sets of cell and discover potential drug targets. In this study, a novel approach based on multiple homology mapping and machine learning method was introduced to predict essential genes. We focused on 25 bacteria which have characterized essential genes. The predictions yielded the highest area under receiver operating characteristic (ROC) curve (AUC) of 0.9716 through tenfold cross-validation test. Proper features were utilized to construct models to make predictions in distantly related bacteria. The accuracy of predictions was evaluated via the consistency of predictions and known essential genes of target species. The highest AUC of 0.9552 and average AUC of 0.8314 were achieved when making predictions across organisms. An independent dataset from Synechococcus elongatus , which was released recently, was obtained for further assessment of the performance of our model. The AUC score of predictions is 0.7855, which is higher than other methods. This research presents that features obtained by homology mapping uniquely can achieve quite great or even better results than those integrated features. Meanwhile, the work indicates that machine learning-based method can assign more efficient weight coefficients than using empirical formula based on biological knowledge.

Procalcitonin Improves the Glasgow Prognostic Score for Outcome Prediction in Emergency Patients with Cancer: A Cohort Study

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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.

Effect of ezetimibe on lipid and glucose metabolism after a fat and glucose load.

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Hiramitsu, Shinya; Miyagishima, Kenji; Ishii, Junichi; Matsui, Shigeru; Naruse, Hiroyuki; Shiino, Kenji; Kitagawa, Fumihiko; Ozaki, Yukio

2012-11-01

The clinical benefit of ezetimibe, an intestinal cholesterol transporter inhibitor, for treatment of postprandial hyperlipidemia was assessed in subjects who ingested a high-fat and high-glucose test meal to mimic westernized diet. We enrolled 20 male volunteers who had at least one of the following: waist circumference ≥ 85 cm, body mass index ≥ 25 kg/m(2), or triglycerides (TG) from 150 to 400mg/dL. After 4 weeks of treatment with ezetimibe (10mg/day), the subjects ingested a high-fat and high-glucose meal. Then changes in serum lipid and glucose levels were monitored after 0, 2, 4, and 6h, and the area under the curve (AUC) was calculated for the change in each parameter. At 4 and 6h postprandially, TG levels were decreased (pAUC for TG was also decreased (pAUC for apo-B48 was also significantly decreased (pBlood glucose and insulin levels at 2h postprandially were significantly decreased by ezetimibe (pAUCs for blood glucose and insulin were also significantly decreased (pglucose metabolism, this drug is likely to be beneficial for dyslipidemia in patients with postprandial metabolic abnormalities. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Management of Carpal Tunnel Syndrome.

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Mooar, Pekka A; Doherty, William J; Murray, Jayson N; Pezold, Ryan; Sevarino, Kaitlyn S

2018-03-15

The American Academy of Orthopaedic Surgeons (AAOS) has developed Appropriate Use Criteria (AUC) for Management of Carpal Tunnel Syndrome. Evidence-based information, in conjunction with the clinical expertise of physicians, was used to develop the criteria to improve patient care and obtain best outcomes while considering the subtleties and distinctions necessary in making clinical decisions. To provide the evidence foundation for this AUC, the AAOS Evidence-Based Medicine Unit provided the writing panel and voting panel with the 2016 AAOS Clinical Practice Guideline titled Management of Carpal Tunnel Syndrome Evidence-Based Clinical Practice Guideline. The Management of Carpal Tunnel Syndrome AUC clinical patient scenarios were derived from indications typical of patients with suspected carpal tunnel syndrome in clinical practice, as well as from current evidence-based clinical practice guidelines and supporting literature to identify the appropriateness of treatments. The 135 patient scenarios and 6 treatments were developed by the writing panel, a group of clinicians who are specialists in this AUC topic. Next, a separate, multidisciplinary, voting panel (made up of specialists and nonspecialists) rated the appropriateness of treatment of each patient scenario using a 9-point scale to designate a treatment as Appropriate (median rating, 7 to 9), May Be Appropriate (median rating, 4 to 6), or Rarely Appropriate (median rating, 1 to 3).

High density UO2 powder preparation for HWR fuel

International Nuclear Information System (INIS)

Hwang, S. T.; Chang, I. S.; Choi, Y. D.; Cho, B. R.; Kwon, S. W.; Kim, B. H.; Moon, B. H.; Kim, S. D.; Phyu, K. M.; Lee, K. A.

1992-01-01

The objective of this project is to study on the preparation of method high density UO 2 powder for HWR Fuel. Accordingly, it is necessary to character ize the AUC processed UO 2 powder and to search method for the preparation of high density UO 2 powder for HWR Fuel. Therefore, it is expected that the results of this study can effect the producing of AUC processed UO 2 powder having sinterability. (Author)

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients

OpenAIRE

Uemura, Mei

2017-01-01

Background: Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting h...

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients

OpenAIRE

Mei Uemura; Yutaka Yano; Toshinari Suzuki; Taro Yasuma; Toshiyuki Sato; Aya Morimoto; Samiko Hosoya; Chihiro Suminaka; Hiromu Nakajima; Esteban C. Gabazza; Yoshiyuki Takei

2017-01-01

Background Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hy...

Progressive dysregulation of autonomic and HPA axis functions in HIV-1 clade C infection in South India.

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Chittiprol, Seetharamaiah; Kumar, Adarsh M; Satishchandra, P; Taranath Shetty, K; Bhimasena Rao, R S; Subbakrishna, D K; Philip, Mariyamma; Satish, K S; Ravi Kumar, H; Kumar, Mahendra

2008-01-01

Human immunodeficiency virus type 1 (HIV-1) infection causes a wide spectrum of abnormalities in neurological, neuropsychological, and neuroendocrinological functions. Several studies report disturbance in autonomic nervous system (ANS) and hypothalamic pituitary-adrenal (HPA) axis function in HIV-1B infected individuals. However, no such investigations on the effect of HIV-1 clade C infection, particularly during the initial phase of the disease progression, have been reported. The present investigations were carried out longitudinally over a 2-year period at 12 monthly intervals in clinically asymptomatic HIV-1 clade C seropositive patients (n=120) and seronegative control subjects (n=29). We determined both the basal levels and the dynamic changes in plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotrophic hormone (ACTH) and cortisol (CORT). Studies were also extended longitudinally (at three separate yearly visits of each participant), to evaluate the response of autonomic and HPA axis to mirror star tracing challenge test (MSTCT) and the values were determined as area under the curve (AUC, corrected for baseline levels of NE, E, ACTH, and CORT). The findings show that the values of basal plasma NE levels, as well as NE response to MSTCT (AUC) at the first visit of HIV-1 seropositive individuals did not differ from those found in the control subjects (NE, pg/ml, HIV-1C=313.5+/-12.7 vs. controls=353.0+/-21.3; p=NS; AUC, HIV-1C=225+/-14.75 vs. controls=232.7+/-19.34; p=NS, respectively). At the subsequent two visits of HIV-1 positive patients however, NE response to MSTCT challenge was progressively attenuated (AUC=235+/-19.5 and 162.7+/-13.6; p<0.01 and 0.05, respectively) compared to that found at the first visit. On the other hand, plasma levels of E as well as E response to MSTCT at the first visit were significantly lower in HIV-1C seropositive individuals compared to those in the control subjects (pg/ml, HIV-1C=77.30+/-5.7 vs. controls

Pharmacokinetic Properties of Three Forms of Vaginal Progesterone Administered in Either Single Or Multiple Dose Regimen in Healthy Post-menopausal Chinese Women

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Jianzhong Shentu

2017-04-01

Full Text Available Objective: A generic vaginal progesterone gel has recently been developed in China. Little is known about its pharmacokinetic properties in Chinese subjects. The purpose of our study was to investigate the pharmacokinetics of three forms of vaginal progesterone gel (test formulations at 4 and 8% strength vs. a reference formulation: Crinone 8% in Chinese healthy post-menopausal women.Methods: This study consisted of two parts study. The part 1 study was a single-center, open-label, 3-period study. Twelve healthy post-menopausal women were to evaluate the safety and pharmacokinetics of 45 mg vaginal progesterone gel (Test 4% following single dose and multiple doses administered once every other day (q.o.d. for six times or once daily (q.d. for 6 days. The part 2 study was a randomized, open-label, 3-stage crossover study. Twelve post-menopausal women received 90 mg vaginal progesterone gel (Test 8% or 90 mg Crinone (Reference 8% following single dose and multiple doses (q.o.d. or q.d.. Plasma concentrations of progesterone were measured up to 72 h by using a validated liquid chromatography tandem-mass spectrometry method. 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.Results: Totally 24 subjects were enrolled in and completed the study. Following single dose, The geometric mean Cmax values for Test 4%, Test 8%, and Crinone 8% were 6.35, 10.34, 10.45 ng/mL, and their geometric mean AUC0-t (AUC0-∞ were 113.73 (118.00, 169.39 (173.98, and 190.07 (201.13 ng⋅h/mL, respectively. The mean T1/2 values of progesterone were 11.00, 10.92, and 11.40 h, respectively. For 8% test formulation vs. reference, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞ were 78.32–124

A randomized two-way crossover comparative pharmacokinetic study of two different tablet formulations containing ilaprazole in healthy human Indian volunteers

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Shubhasis Dan

2014-01-01

Full Text Available Background: Proton Pump Inhibitors (PPI are observed to be great healer in gastroesophageal reflux disorder (GERD and duodenal ulcer. Quantification of the drugs in human plasma by validated bioanalytical method are very important to determine pharmacokinetic parameters for undergoing comparative study with standard available formulations to make the newer one commercially available. Objective: The objective of this study was to determine the relative bioavailability of Ilaprazole, a novel PPI comparing the test formulation to the reference one according to standard regulatory guidelines. Materials and Methods: The bioequivalence of two tablet formulations, one as reference and other as test containing 10 mg of ilaprazole [CAS No. 172152-36-2] was studied in 12 healthy Indian volunteers. This was a single dose, twoperiod and randomized crossover study separated with a washout period of one week. Plasma samples for pharmacokinetic analysis were collected before dosing and at pre-specified time points after dosing. The concentration of ilaprazole in plasma was determined by a validated HPLC-UV method using theophylline as internal standard. The formulations were compared using the parameters Area under the plasma concentration-time curve (AUC 0-t , Area under the plasma concentration-time curve from zero to infinity (AUC 0-͵, Peak plasma concentration (C max , and time to reach peak plasma concentration (t max . Results: Mean AUC 0-t of test and reference product were calculated to be 2627.793 ± 154.989 ng h ml−1 and 2555.905 ± 225.916 ng h ml−1 , with a C max of 347.459 ± 48.175 ng h ml−1 . While mean AUC 0-͵ of test and reference product were calculated to be 2733.334 ± 242.438 ng h ml−1 and 2728.716 ± 284.408 ng h ml−1 . Conclusion: The results of this investigation indicated no statistically significant differences between the logarithmic transformed AUC 0-͵ and C max values of the two preparations. The 90% confidence

Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

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Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

2013-10-01

To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP�

Comparison of quantification algorithms for circulating cell-free DNA methylation biomarkers in blood plasma from cancer patients.

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de Vos, Luka; Gevensleben, Heidrun; Schröck, Andreas; Franzen, Alina; Kristiansen, Glen; Bootz, Friedrich; Dietrich, Dimo

2017-01-01

SHOX2 and SEPT9 methylation in circulating cell-free DNA (ccfDNA) in blood are established powerful and clinically valuable biomarkers for diagnosis, staging, prognosis, and monitoring of cancer patients. The aim of the present study was to evaluate different quantification algorithms (relative quantification, absolute quantification, quasi-digital PCR) with regard to their clinical performance. Methylation analyses were performed in a training cohort (141 patients with head and neck squamous cell carcinoma [HNSCC], 170 control cases) and a testing cohort (137 HNSCC cases, 102 controls). DNA was extracted from plasma samples, bisulfite-converted, and analyzed via quantitative real-time PCR. SHOX2 and SEPT9 methylations were assessed separately and as panel [mean SEPT9 / SHOX2 ] using the ΔCT method for absolute quantification and the ΔΔCT-method for relative quantification. Quasi-digital PCR was defined as the number of amplification-positive PCR replicates. The diagnostic (sensitivity, specificity, area under the curve (AUC) of the receiver operating characteristic (ROC)) and prognostic accuracy (hazard ratio (HR) from Cox regression) were evaluated. Sporadic methylation in control samples necessitated the introduction of cutoffs resulting in 61-63% sensitivity/90-92% specificity ( SEPT9 /training), 53-57% sensitivity/87-90% specificity ( SHOX2 /training), and 64-65% sensitivity/90-91% specificity (mean SEPT9 / SHOX2 /training). Results were confirmed in a testing cohort with 54-56% sensitivity/88-90% specificity ( SEPT9 /testing), 43-48% sensitivity/93-95% specificity ( SHOX2 /testing), and 49-58% sensitivity/88-94% specificity (mean SEPT9 / SHOX2 /testing). All algorithms showed comparable cutoff-independent diagnostic accuracy with largely overlapping 95% confidence intervals ( SEPT9 : AUC training  = 0.79-0.80; AUC testing  = 0.74-0.75; SHOX2 : AUC training  = 0.78-0.81, AUC testing  = 0.77-0.79; mean SEPT9 / SHOX2 : AUC training  = 0

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

OCT angiography and Color Doppler Imaging in the study of hemoperfusion in the retina and optic nerve in POAG

Directory of Open Access Journals (Sweden)

N. I. Kurysheva

2016-01-01

Full Text Available Purpose: To evaluate the hemoperfusion of Optic Nerve Disk (OND, peripapillary and macular areas, and retrobulbar blood flow in patients with primary open-angle glaucoma using optical coherence tomography with angiography (OCT-A and Сolor Doppler Imaging (CDI.Patients and Methods: 65 eyes of patients with primary open angle glaucoma (POAG and 22 eyes of age-matched healthy subjects were examined using the SD-OCT-А (RtVue xR Avanti with the AngioVue software. Retinal Thickness and Angio Flow Density (AFD were measured. AFD Disc and Peripapillary Flow Density were measured in OND and in peripapillary area. AFD Retina were evaluated in Macula inсluding Fovea- and Parafovea regions (superficial and deep of the inner retinal layers. Ophthalmic Artery (OA, Central Retinal Artery (CRA, Posterior short Ciliary Arteries (PCA, Central Retinal Vein (CRV and Vortex Vein (VV were measured by CDI. Statistical analysis was performed using SPSS version 21 and MASS library of language R. The value of each diagnostic indicator (z-value was calculated with the Wilcoxon-Mann-Whitney test and the area under the receiver operating characteristic curve (AUC.Results: Both OCT-A and CDI indicators were reduced in glaucoma compared to healthy eyes. The following indicators had the largest AUC and diagnostic value (z-value to discriminate the early glaucoma from normal eyes: AFD Retina Superficial Whole En Face (z = 3,83, p<0,0001; AUC 0,8 (0,69‑0,90, AFD Retina Deep Whole En Face (z = 3,31, p = 0,0007; AUC 0,76 (0,64‑0,88, Peripapillary Vessel Density (z = 3,2, p = 0,001; AUC 0,75 (0,63‑0,87, end-diastolic flow velocity in AO (z = 3,03, p = 0,002; AUC 0,74 (0,61‑0,86 and in TPCA (z = 2,78, p = 0,005; AUC 0,72 (0,58‑0,86; and to discriminate the early glaucoma from the advanced and far advanced stages: AFD Disc Peripapillary Inferior Temporalis (z = 5,61, p<0,0001; AUC 0,94 (0,86‑1,0 and the mean flow velocity in the CRA (z = 4,16, p<0

Bioavailability of two single-dose oral formulations of omeprazole 20 mg: an open-label, randomized sequence, two-period crossover comparison in healthy Mexican adult volunteers.

Science.gov (United States)

Poo, Jorge Luis; Galán, Juan Francisco; Rosete, Alejandra; de Lago, Alberto; Oliva, Iván; González-de la Parra, Mario; Jiménez, Patricia; Burke-Fraga, Victoria; Namur, Salvador

2008-04-01

Omeprazole is a proton-pump inhibitor that acts to reduce acid secretion in the stomach and is used for treating various acid-related gastrointestinal disorders. There are several generic formulations of omeprazole available in Mexico; however, a literature search failed to identify published data concerning the bioavailability of these formulations in the Mexican population. The aim of this study was to compare the bioavailability of 2 oral formulations of omeprazole 20-mg capsules, marketed for use in Mexico, in healthy volunteers: Inhibitron (test formulation) and LosecA 20 mg (reference formulation). This study used a single-dose, open-label, randomized sequence, 2 x 2 crossover (2 administration periods x 2 treatments) design to compare the 2 formulations. Eligible subjects were healthy adult Mexican volunteers of both sexes. Subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test formulation followed by the reference formulation, or vice versa, with a 7-day washout period between administration periods. After a 12-hour (overnight) fast, subjects received a single, 20-mg dose of the corresponding formulation. Plasma samples were obtained over a 12-hour period after administration. Plasma omeprazole concentrations were analyzed by a nonstereospecific high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and 0.17, 0.33, 0.50, 0.75, 1, 1.25, 1.50, 1.75, 2, 2.50, 3, 4, 6, 8, and 12 hours after administration. The formulations were considered bioequivalent if the natural log (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125%, and if P disability, or required intervention to prevent permanent impairment or damage. Thirty-four subjects were enrolled and completed the study (25 men and 9

{sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Can Quantify and Predict Esophageal Injury During Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Niedzielski, Joshua S., E-mail: jsniedzielski@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States); Yang, Jinzhong [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States); Liao, Zhongxing; Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Stingo, Francesco [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe; Martel, Mary K.; Briere, Tina M.; Court, Laurence E. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States)

2016-11-01

Purpose: We sought to investigate the ability of mid-treatment {sup 18}F-fluorodeoxyglucose positron emission tomography (PET) studies to objectively and spatially quantify esophageal injury in vivo from radiation therapy for non-small cell lung cancer. Methods and Materials: This retrospective study was approved by the local institutional review board, with written informed consent obtained before enrollment. We normalized {sup 18}F-fluorodeoxyglucose PET uptake to each patient's low-irradiated region (<5 Gy) of the esophagus, as a radiation response measure. Spatially localized metrics of normalized uptake (normalized standard uptake value [nSUV]) were derived for 79 patients undergoing concurrent chemoradiation therapy for non-small cell lung cancer. We used nSUV metrics to classify esophagitis grade at the time of the PET study, as well as maximum severity by treatment completion, according to National Cancer Institute Common Terminology Criteria for Adverse Events, using multivariate least absolute shrinkage and selection operator (LASSO) logistic regression and repeated 3-fold cross validation (training, validation, and test folds). This 3-fold cross-validation LASSO model procedure was used to predict toxicity progression from 43 asymptomatic patients during the PET study. Dose-volume metrics were also tested in both the multivariate classification and the symptom progression prediction analyses. Classification performance was quantified with the area under the curve (AUC) from receiver operating characteristic analysis on the test set from the 3-fold analyses. Results: Statistical analysis showed increasing nSUV is related to esophagitis severity. Axial-averaged maximum nSUV for 1 esophageal slice and esophageal length with at least 40% of axial-averaged nSUV both had AUCs of 0.85 for classifying grade 2 or higher esophagitis at the time of the PET study and AUCs of 0.91 and 0.92, respectively, for maximum grade 2 or higher by treatment completion

Quantum dots-based quantitative and in situ multiple imaging on ki67 and cytokeratin to improve ki67 assessment in breast cancer.

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Jing Ping Yuan

Full Text Available As a marker for tumor cell proliferation, Ki67 has important impacts on breast cancer (BC prognosis. Although immunohistochemical staining is the current standard method, variations in analytical practice make it difficult for pathologists to manually measure Ki67 index. This study was to develop a fluorescent spectrum-based quantitative analysis of Ki67 expression by quantum-dots (QDs multiple imaging technique.A QDs-based in situ multiple fluorescent imaging method was developed, which stained nuclear Ki67 as red signal and cytoplasmic cytokeratin (CK as green signal. Both Ki67 and CK signals were automatically separated and quantified by professional spectrum analysis software. This technique was applied to tissue microarrays from 240 BC patients. Both Ki67 and CK values, and Ki67/CK ratio were obtained for each patient, and their prognostic value on 5-year disease free survival was assessed.This method simultaneously stains nuclear Ki67 and cytoplasmic CK with clear signal contrast, making it easy for signal separation and quantification. The total fluorescent signal intensities of both Ki67 sum and CK sum were obtained, and Ki67/CK ratio calculated. Ki67 sum and Ki67/CK ratio were each attributed into two grades by X-tile software based on the best P value principle. Multivariate analysis showed Ki67 grade (P = 0.047 and Ki67/CK grade (P = 0.004 were independent prognostic factors. Furthermore, area under curve (AUC of ROC analysis for Ki67/CK grade (AUC: 0.683, 95%CI: 0.613-0.752 was higher than Ki67 grade (AUC: 0.665, 95%CI: 0.596-0.734 and HER-2 gene (AUC: 0.586, 95%CI: 0.510-0.661, but lower than N stage (AUC: 0.760, 95%CI: 0.696-0.823 and histological grade (AUC: 0.756, 95%CI: 0.692-0.820 on predicting the risk for recurrence.A QDs-based quantitative and in situ multiple imaging on Ki67 and CK was developed to improve Ki67 assessment in BC, and Ki67/CK grade had better performance than Ki67 grade in predicting prognosis.

Short communication: concentrations of nonesterified fatty acids and β-hydroxybutyrate in dairy cows are not well correlated during the transition period.

Science.gov (United States)

McCarthy, M M; Mann, S; Nydam, D V; Overton, T R; McArt, J A A

2015-09-01

The objective was to use longitudinal data of blood nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) concentrations to describe the relationship between NEFA and BHBA in dairy cows during the periparturient period. Blood NEFA and BHBA concentration data collected from d 21 prepartum to 21 postpartum for 269 multiparous Holstein cows were selected from 4 different studies carried out within our research groups. Overall, NEFA concentrations were increased beginning near parturition with a relatively steady elevation of NEFA through d 9, after which concentrations gradually decreased. Prepartum BHBA concentrations began to increase beginning several days before parturition, continued to increase during the first week after parturition, and remained elevated through d 21 postpartum. Of the 269 cows included in the data set, 117 cows (43.5%) had at least one postpartum hyperketonemic event (BHBA ≥1.2mmol/L), and 202 cows (75.1%) had at least one event of elevated postpartum NEFA concentrations (≥0.70mmol/L) between 3 and 21 d in milk. Area under the curve (AUC) was used to investigate relationships between metabolites over time. Overall, the correlations between transition period NEFA and BHBA AUC were weak. We detected a negative correlation between prepartum BHBA AUC and postpartum NEFA AUC (r=-0.26). A positive correlation existed between postpartum NEFA AUC and postpartum BHBA AUC; however, the correlation coefficient was low (r=0.26). Large variation was found between the day of maximum NEFA concentration within the first 21 d in milk and day of maximum BHBA concentration for the same period. The mean and median times of maximum NEFA concentration were 6.8 and 6 d, respectively, whereas the mean and median times of maximum BHBA were 9.6 and 8 d, respectively; however, the range in days for both the mean and median day of maximum concentrations was very large. Overall, our data set indicates a weak relationship between blood concentrations of NEFA