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Sample records for auc

  1. AUC Optimisation and Collaborative Filtering

    OpenAIRE

    Dhanjal, Charanpal; Gaudel, Romaric; Clemencon, Stephan

    2015-01-01

    In recommendation systems, one is interested in the ranking of the predicted items as opposed to other losses such as the mean squared error. Although a variety of ways to evaluate rankings exist in the literature, here we focus on the Area Under the ROC Curve (AUC) as it widely used and has a strong theoretical underpinning. In practical recommendation, only items at the top of the ranked list are presented to the users. With this in mind, we propose a class of objective functions over matri...

  2. Development of MWL-AUC / CCD-C-AUC / SLS-AUC detectors for the analytical ultracentrifuge

    OpenAIRE

    Karabudak, Engin

    2009-01-01

    Analytical ultracentrifugation (AUC) has made an important contribution to polymer and particle characterization since its invention by Svedberg (Svedberg and Nichols 1923; Svedberg and Pederson 1940) in 1923. In 1926, Svedberg won the Nobel price for his scientific work on disperse systems including work with AUC. The first important discovery performed with AUC was to show the existence of macromolecules. Since that time AUC has become an important tool to study polymers in biophysics and b...

  3. AUC-Maximizing Ensembles through Metalearning.

    Science.gov (United States)

    LeDell, Erin; van der Laan, Mark J; Peterson, Maya

    2016-05-01

    Area Under the ROC Curve (AUC) is often used to measure the performance of an estimator in binary classification problems. An AUC-maximizing classifier can have significant advantages in cases where ranking correctness is valued or if the outcome is rare. In a Super Learner ensemble, maximization of the AUC can be achieved by the use of an AUC-maximining metalearning algorithm. We discuss an implementation of an AUC-maximization technique that is formulated as a nonlinear optimization problem. We also evaluate the effectiveness of a large number of different nonlinear optimization algorithms to maximize the cross-validated AUC of the ensemble fit. The results provide evidence that AUC-maximizing metalearners can, and often do, out-perform non-AUC-maximizing metalearning methods, with respect to ensemble AUC. The results also demonstrate that as the level of imbalance in the training data increases, the Super Learner ensemble outperforms the top base algorithm by a larger degree. PMID:27227721

  4. AUK: a simple alternative to the AUC

    NARCIS (Netherlands)

    U. Kaymak (Uzay); A. Ben-David (Arie); R. Potharst (Rob)

    2010-01-01

    textabstractThe area under Receiver Operating Characteristic (ROC) curve, also known as the AUC-index, is commonly used for ranking the performance of data mining models. The AUC has many merits, such as objectivity and ease of interpretation. However, since it is class indifferent, its usefulness w

  5. The purification capability analysis of AUC process

    International Nuclear Information System (INIS)

    Through calculation,the purification capability of four kinds of impurities in AUC(ammonium uranyl tricarbonate) process was discussed. The minimum level of some impurities which can produce slightly soluble carbonates or hydroxides was calculated and their minimum values in AUC crystal were below 1 μg/g U. Some impurities which can produce partly soluble carbonates,for example, the Li concentration reached to 2.09 x 104 μg/L in solution containing [(NH4)2CO3] of 2.8 mol/L, cannot come into AUC crystal. The impurities which compound solubility is higher than the solubility of AUC can be removed by means of the separation of solid and liquid and washing the AUC crystal. (authors)

  6. Purification of ADU and high-molybdenum AUC by recrystallization

    International Nuclear Information System (INIS)

    The ADU was converted to AUC by preparing pulp with (NH4)2CO3 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 (NH4)2CO3 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

  7. Study of stripping cristallization processus of AUC with ammonium carbonate

    International Nuclear Information System (INIS)

    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 (NH4)2CO3. The effects of operating conditions ((NH4)2CO3 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 (NH4)2CO3 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 (NH4)2CO3 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

  8. Sintering of uranium dioxide obtained by continuous precipitation of AUC

    International Nuclear Information System (INIS)

    The Nuclear Materials Division in Bariloche Atomic Center evaluates the ceramic behaviour of UO2 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 UO2 during sintering (compaction, sintering, pore and grain microstructure, etc.). 1 ref

  9. CREDIT SCORING MODELS WITH AUC MAXIMIZATION BASED ON WEIGHTED SVM

    OpenAIRE

    LIGANG ZHOU; KIN KEUNG LAI; JEROME YEN

    2009-01-01

    Credit scoring models are very important tools for financial institutions to make credit granting decisions. In the last few decades, many quantitative methods have been used for the development of credit scoring models with focus on maximizing classification accuracy. This paper proposes the credit scoring models with the area under receiver operating characteristics curve (AUC) maximization based on the new emerged support vector machines (SVM) techniques. Three main SVM models with differe...

  10. The handling of UF6 and preparation of AUC

    International Nuclear Information System (INIS)

    Ammonium uranyl carbonate, (NH4)4UO2(CO3)3 has been synthesized, starting with uranium hexafluoride by continuously introducting uranium hexafluoride, ammonia and carbon dioxide gases into the saturated ammonium carbonate solution in the fluidized precipitator. These were subjected to hydrolysis of uranium hexafluoride and subsequent reaction with ammonia and carbon dioxide gases to give the granular type of ammomium uranyl carbonate. All of the properties of AUC obtained from UF6 are suitable for the preparation of sinterable uranium dioxide powder. The transfer of UF6 from a large cylinder ( 2 ton) to a small cylinder (4 l) has sucessfully been done as gaseous phase via evaporation and condensation. The complete hydrolysis of UF6 especially a large amount of UF6 being used, are to be examined in the future. (Author)

  11. A limited sampling strategy for the estimation of Neoral AUCs in pediatric patients.

    Science.gov (United States)

    Meier-Kriesche, H U; Bonilla-Felix, M A; Ferris, M E; Swinford, R; Kahan, B D; Brannan, P; Portman, R J

    1999-11-01

    The improved pharmacokinetics of Neoral allows the development of an accurate estimate of the full area under the concentration time curve (AUC) from a limited sampling strategy. As no such strategy has been derived from pharmacokinetic data obtained from children on 12-hourly dosing, and as patient convenience demands shorter sampling times, we derived a limited sampling strategy from 45 AUCs obtained from 19 pediatric renal transplant patients by stepwise forward multiple regression, and prospectively tested them on a separate group of 49 AUCs obtained from 18 pediatric renal transplant patients. Full cyclosporine (CsA) AUCs were obtained from samples drawn pre dose (C0) and at 2, 4, 6, 8 and 12 h post dose (C2, C4, C6, C8, and C12). High-precision predictions of full AUC were obtained based on the formula: AUC = 444 + 3.69 x C0 + 1.77 x C2 + 4. 1 x C4 (mean prediction error +/- SD = 0.3 +/- 6.4%, 95% confidence interval=-1.7% to 1.9%.) In conclusion, CsA exposure in pediatric renal transplant patients on 12-hourly Neoral dosing can be reliably predicted by an early time point-based limited sampling strategy in children. This formula has the advantage of obtaining trough as well as AUC from one brief, convenient sampling period. PMID:10603112

  12. Preliminary Study On The Precipitation Of Ammonium Carbonate (AUC) From Uranylfluoride (UO2F2) Solution

    International Nuclear Information System (INIS)

    The preliminary studies on the precipitation process of ammonium uranyl carbonate (AUC)-(NH4)4UO2(CO3)3 from the UO2F2-HF solution system by using precipitation agent of ammonium carbonate (AC)-(NH4)2CO3 and on preparation ability of UO2 powder via AUC route are shown in this report. Our analysis results suggested that a product, identified as ammonium uranyl fluoride (AUF), was found along with the AUC precipitate. In order to prevent the formation of the undesirable AUF precipitate, the AUC precipitation process was carried out in the stable pH media ∼ 9, uranium concentration of 100 g/L and molar ratio of C to U ≥ 7.5. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-09-01

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

  14. Optimization of Cyclosporine Therapy with Predicted AUC in Renal Transplant Patients

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Background: Pre-dose concentration measurement is the most practical method to evaluate cyclosporine(CsA) therapy in renal transplant patients. But it gives no information about the total drug exposure,which relate to graft survival. A number of different new concepts of CsA monitoring,including approaches such as single,double,triple time-point and abbreviated area under curve(AUC) determinaiton,have been introduced. The full CsA AUC value is the most sensitive indicator of clinical outcome. However,its higher analytical costs and time-consuming sampling compromise the benefit of full AUC. Alternative method of predicted AUC by using 2 concentration-time points have been established and used for routine practice in our hospital. [Objectives] The purpose of this study is to determine more sensitive and more predictive markers for CsA dosage adjustment in renal transplant patients. [Methods] Total 44 patients completed the 12-hours CsA pharmacokinetic studies. They had stable renal function. None of them had history of gastrectomy,small bowel resection,cholecystectomy,cholestasis,or had use of medications that might cause an interaction with CsA before the study. Pharmacokinetic parameters were evaluated by use of noncompartmental methods. The correlation equations between drug concentration-time points and AUC were determined by simple and multiple linear regression models using one,two,or three concentration time points as independent variable. [Results] Most of Cmax achieved at about 1~2 hours after dosing,but some delayed absorption was observed at abour 3~5 hours after dosing. C0 and C1 are poorly correlated with AUC of CsA,two of three point have better correlation than single point. Depending on clinical outcomes,predicted AUC goes more reliable than single concentration-time point monitoring for consideration of total exposure amount of CsA. If Tmax of CsA concentration-time curve shifted(delayed) out of population range,the AUC prediction error will be

  15. Studies on the preparation and characterisation of ammonium uranyl carbonate (AUC)

    International Nuclear Information System (INIS)

    Studies have been carried out in the laboratory on the preparation of ammonium uranyl carbonate (AUC), using concentrated solution of uranyl nitrate. The precipitation of AUC has been done by addition of (NH4)2CO3 solution and injecting gaseous ammonia and carbon dioxide. The precipitates obtained under varying parameter have been characterised by chemical and XRD analysis and the precipitate obtained under ideal conditions have been found to have the formula [(NH4)4UO2(CO3)3]. Though the studies were mainly aimed at standardising the procedures for the identification of precipitates, some of the AUC samples have been tested to see their suitability for conversion to ceramic grade UO2 powder and its pelletisation and sintering properties of the pellets. The data collected during these studies is presented. (author). 15 refs., 3 figs., 2 tabs

  16. A study on the dissolution of uranium compounds(UO2, AUC) in nitric acid solutions

    International Nuclear Information System (INIS)

    The dissolution behavior of UO2 and AUC powder in nitric acid solutions was investigated to evaluate the performance of chemical decontamination process applicable to and internal surface of metallic system components such as tanks and piping in the uranium conversion plant. It was revealed that the dissolution of UO2 in nitric acid solutions containing low concentration of H2O2 was more effective than that in nitric acid solution without H2O2 as one of the conventional inorganic acid decontamination processes. AUC powder dissolved easily and continuously in nitric acid solutions before the solution pH attains about 3, but above that solution pH uranium concentration in the solution was lowered drastically by recrystallization. It was convinced that pH range of 2.5 ∼ 3 is desired in the decontamination of surface contaminated with AUC

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

    Science.gov (United States)

    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.

  18. 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.

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

    International Nuclear Information System (INIS)

    UO2 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/cm2. 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 UO2 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 UO2 powder ex-ADU is more or less agglomerated and contains very fine particles causing the difficulty in pressing. Therefore the green density resulted from UO2 ex-AUC (6.415 g/cm3) is higher than UO2 powder of UO2 ex-ADU (6.117 g/cm3. UO2 at lower pressure (4 tons/cm3) the compression strength ex-AUC green pellet (47.144 kgf) is lower than UO2 ex-ADU (63,364 kgf), and at higher temperature the compression strength of ex-AUC (92.86 kgf) is higher than UO2 ex-ADU (82.664 kgf). It is suggested that UO2 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)

  20. Estimation of AUC from 0 to Infinity in Serial Sacrifice Designs.

    OpenAIRE

    Wolfsegger, Martin J.; Jaki, Thomas

    2005-01-01

    Nonclinical in vivo animal studies have to be completed before starting clinical studies of the pharmacokinetic behavior of a drug in humans. The drug exposure in animal studies is often measured by the area under the concentration time curve (AUC). The classical complete data design where each animal is sampled for analysis once per time point is usually only applicable for large animals. In the case of rats and mice, where blood sampling is restricted, the batch design or the serial sacrifi...

  1. [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

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

    International Nuclear Information System (INIS)

    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 (UO2). 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

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

    DEFF Research Database (Denmark)

    Hälldahl, L.; Sørensen, Ole Toft

    1979-01-01

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

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

    International Nuclear Information System (INIS)

    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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Seenae Eum

    2016-09-01

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

  7. 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.

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

    NARCIS (Netherlands)

    Proost, J. H.

    2007-01-01

    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 us

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

    International Nuclear Information System (INIS)

    Ammonium uranium carbonate (AUC) process has been developed and industrially used in Germany for preparation of free-flowing and sinterable UO2 powder for fabrication of UO2 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 UO2 powder suitable for direct pelletisation and sintering to very high density (> 96% T.D.) UO2 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 UO2 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 UO2 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 UO2 pellets has been in the range of 95.5-96% T.D. (author). 11 refs

  10. First spectroscopic observation of gold(i) butadiynylide: Photodetachment velocity map imaging of the AuC4H anion.

    Science.gov (United States)

    Visser, Bradley R; Addicoat, Matthew A; Gascooke, Jason R; Lawrance, Warren D; Metha, Gregory F

    2016-07-28

    The velocity map imaging technique was used in the investigation of gold(i) butadiynylide, AuC4H(-), with images recorded at two excitation wavelengths. The resultant photodetachment spectra show a well defined vibrational progression in the neutral with an energy spacing of 343 ± 3 cm(-1). The adiabatic electron affinity was determined to be 1.775 ± 0.005 eV and assigned to the X(1)Σ(+)←X(2)Σ(+) transition between the anionic and neutral ground states. Franck-Condon simulations performed on density functional theory optimized geometries assisted the assignment of linear geometries to the neutral and anion and the observed vibrational progression to that of the Au-C4H stretch. PMID:27475374

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-06-15

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

  12. 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, 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 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. PMID:24825728

  13. 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.

  14. Au-C allotrope nano-composite films at extreme conditions generated by intense ultra-short laser

    Science.gov (United States)

    Khan, Saif A.; Saravanan, K.; Tayyab, M.; Bagchi, S.; Avasthi, D. K.

    2016-07-01

    Structural evolution of gold-carbon allotrope nano-composite films under relativistically intense, ultra-short laser pulse irradiation is studied in this work. Au-C nano-composite films, having 4 and 10 at.% of Au, were deposited by co-sputtering technique on silicon substrates. Au-C60 NC films with 2.5 at.% Au were deposited on 12 μm thick Al foil using co-evaporation technique. These samples were radiated with single pulse from 45 fs, 10 TW Ti:Sapphire Laser at RRCAT at an intensity of 3 × 1018 W cm-2. The morphological and compositional changes were investigated using scanning electron microscopy (SEM) and Rutherford back-scattering spectrometry (RBS) techniques. Laser pulse created three morphologically distinct zones around the point of impact on samples with silicon substrates. The gold content in 600 μm circular region around a point of impact is found to reduce by a factor of five. Annular rings of ∼70 nm in diameter were observed in case of Au-C NC film after irradiation. Laser pulse created a hole of about 400 μm in the sample with Al foil as substrate and wavy structures of 6 μm wavelength are found to be created around this hole. The study shows radial variation in nano-structure formation with varying local intensity of laser pulse.

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Peng Men

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

  18. 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)

    In the INB nuclear fuel cycle, the pellets production is based on UO2 powder made by AUC (Ammonium-Uranyl-Carbonate) route. AUC formation occurs by fluidising of UF6, NH3 and CO2 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 UO2 powder. At this point, the dried AUC decompounds to UO3, NH3 and C02, these 2 gases are absorbed at the gases washer, formin go the carbonated water (CW), whit is basically a (NH4)2CO3 solution. The UO2+x is reduced and stabilized to UO2 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 UO2 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)

  19. 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)

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

    Science.gov (United States)

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

    2011-08-01

    The ratio of AUC to the dose (AUC/dose) was previously found as a parameter that predicts a risk of bioinequivalence of oral drug products. On the basis of the combination of this parameter and the biopharmaceutics classification system (BCS), a perspective for biowaivers of human bioequivalence studies is discussed. Databases of bioequivalence studies using immediate-release solid oral dosage forms were disclosed by 6 Japanese generic pharmaceutical companies, and the number of subjects required for demonstrating bioequivalence between generic and reference products was plotted as a function of AUC/dose for each BCS category. A small variation in the number of subjects was constantly observed in bioequivalence studies using dosage forms containing an identical BCS class 1 or class 3 drug, even though formulations of the generic product differ between companies. The variation was extremely enlarged when the drugs were substituted with BCS class 2 drugs. Rate-determining steps in oral absorption of highly water-soluble BCS class 1 and class 3 drugs are independent of formulations when there is no significant difference in the in vitro dissolution profiles between formulations. The small variation observed for both BCS categories indicates that the number of subjects converges into one value for each drug. Our analysis indicates the appropriateness of biowaiver of bioequivalence studies for immediate-release solid oral dosage forms containing not only BCS class 1 drugs but also class 3 drugs. PMID:21630662

  1. Results of a planned interim toxicity analysis with trimodality therapy, including carboplatin AUC = 4, paclitaxel, 5-fluorouracil, amifostine, and radiation for locally advanced esophageal cancer: preliminary analyses and treatment recommendations from the North Central Cancer Treatment Group

    OpenAIRE

    Jatoi, Aminah; Martenson, James; Mahoney, Michelle R; Lair, Bradley S; Brindle, Jeffrey S; Nichols, Frank; Caron, Normand; Rowland, Kendrith; Tschetter, Loren; Alberts, Steven

    2004-01-01

    Purpose An aggressive trimodality approach from the Minnie Pearl Cancer Research Network [carboplatin AUC = 6, days 1 and 22; 5-fluorouracil 225 mg/m2 continuous infusion, days 1–42, paclitaxel 200 mg/m2, days 1 and 22; 45 Gy] has resulted in remarkable pathologic response rates but notable toxicity. This trial was designed to mitigate this toxicity by starting with a lower carboplatin dose, AUC = 4, and by adding subcutaneous amifostine. Methods This phase II trial included patients with loc...

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

    Directory of Open Access Journals (Sweden)

    Lorena H. Suárez

    2004-12-01

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

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

    KAUST Repository

    Kerdi, Fatmé

    2011-04-01

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

  4. An element through the looking glass: Exploring the Au-C, Au-H and Au-O energy landscape

    OpenAIRE

    Rosca, Dragos-Adrian; Wright, Joseph; Bochmann, Manfred

    2015-01-01

    Gold, the archetypal “noble metal”, used to be considered of little interest in catalysis. It is now clear that this was a misconception, and a multitude of gold-catalysed transformations has been reported. However, one consequence of the long-held view of gold as inert metal is that its organometallic chemistry contains many “unknowns”, and catalytic cycles devised to explain gold's reactivity draw largely on analogies with other transition metals. How realistic are such mechanistic assumpti...

  5. Derecho interno, derechos humanos y desmovilización de las AUC en Colombia 2002-2007

    OpenAIRE

    Pineda Bermúdez, Judith Esther; Sosa Posada, Juan Esteban Sosa Posada

    2007-01-01

    En el presente trabajo se hace un análisis del Proceso de desmovilización de los Paramilitares en Colombia, y para tal efecto se realiza un breve estudio del Derecho Internacional Público y de los Derechos Humanos. Sobre la Ley de Justicia y Paz se realiza un análisis a partir de los conceptos de Derecho Internacional y Derecho Interno, lo cual nos permitió llegar a las conclusiones contenidas en este trabajo.

  6. 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.;

    The present report suggests a revised Programme of Studies at the Faculty of Engineering at Ondo State University. The proposal is based on the present undergraduate teaching programme at the Faculty but at the same time it introduces the pedagogical approach in use at Aalborg University as a met......The present report suggests a revised Programme of Studies at the Faculty of Engineering at Ondo State University. The proposal is based on the present undergraduate teaching programme at the Faculty but at the same time it introduces the pedagogical approach in use at Aalborg University...... as a method of training engineers. The content of the proposed undergraduate teaching programme will to a great extent remain the same as at present and it therefore reflects the objectives of OSUA and the Faculty. At the same time it reflects the ideas regarding the pedagogical approach brought forward....... It is to be hoped that it will form the basis for fruitful discussions among all parties involved and that it will result in an agreed programme to be implemented at the Faculty of Engineering in a foreseeable future....

  7. 碱性溶液中铂、钯和金析氧性能比较%Performance comparison of oxygen evolution reaction for Pt/C,Pd/C and Au/C in alkaline medium

    Institute of Scientific and Technical Information of China (English)

    徐常威; 梁杰聪; 王静

    2015-01-01

    Activity and stability of oxygen evolution reaction (OER)for Pt/C,Pd /C and Au /C have been com-pared in 0.1 mol·L -1 KOH solution.The activity order of OER is Pd /C >Pt/C >Au /C and the stability order of OER is Pd /C >Au /C >Pt/C.The Pd /C gives the best OER stability,which is in agreement with that the Pd /C gives the best OER activity.Au /C gives a better stability than Pt/C,although it gives a worse activity than Pt/C.%比较研究了 Pt/C、Pd /C 和 Au/C 在0.1 mol·L -1 KOH 水溶液中的析氧催化活性和稳定性.3种催化剂的析氧催化活性的顺序:Pd /C >Pt/C >Au/C,析氧催化稳定性的顺序:Pd/C >Au/C >Pt/C.Pd/C 析氧稳定性最好,这和其最高的析氧催化活性一致.Au/C 虽然析氧催化活性比 Pt/C 低,但其析氧催化稳定性比 Pt/C 高.

  8. Proposal for a Revised Programme of Studies at the Faculty of Engineering, Ondo State University Using the Pedagogical Model at AUC as Reference:Ondo State/ Aalborg Universities Linkage

    OpenAIRE

    Jørgensen, Mogens B.; Borch, Ole; Esan, A. A.; Dalgaard-Jensen, Knud; Isager, P.; Kloch, Søren; Ritchie, Ewen; Müller, Jan; Mortensen, Lambert N.

    1992-01-01

    The present report suggests a revised Programme of Studies at the Faculty of Engineering at Ondo State University. The proposal is based on the present undergraduate teaching programme at the Faculty but at the same time it introduces the pedagogical approach in use at Aalborg University as a method of training engineers. The content of the proposed undergraduate teaching programme will to a great extent remain the same as at present and it therefore reflects the objectives of OSUA and the Fa...

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

    Science.gov (United States)

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

    2016-08-01

    We report a joint photoelectron spectroscopy and theoretical study on AuC4-, AuC6-, and AuCnH- (n = 2, 4, and 6) using high-resolution photoelectron imaging and ab initio calculations. The ground state of AuC2H-, AuC4H-, and AuC6H- is found to be linear, while that of AuC4- and AuC6- 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 AuC4 and AuC6, respectively. Both bending and stretching frequencies are resolved in the spectra of AuC4- and AuC6-. High-resolution data of AuCnH- reveal major vibrational progressions in the Au—C stretching and bending modes. AuC2H- has a ground state stretching frequency of 445(10) cm-1 and a bending frequency of 260(10) cm-1; AuC4H- has a ground state stretching frequency of 340(10) cm-1; AuC6H- 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 AuC2H, AuC4H, and AuC6H, 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 AuC4-, AuC6-, and AuCnH- (n = 2, 4, and 6) and their corresponding neutrals.

  10. Comparison of Stress-Hemoconcentration Correction Techniques for Stress-Induced Coagulation

    Directory of Open Access Journals (Sweden)

    Anthony W. Austin

    2013-01-01

    Full Text Available When examining stress effects on coagulation, arithmetic correction is typically used to adjust for concomitant hemoconcentration but may be inappropriate for coagulation activity assays. We examined a new physiologically relevant method of correcting for stress-hemoconcentration. Blood was drawn from healthy men (N=40 during baseline, mental stress, and recovery, and factor VII activity (FVII:C, factor VIII activity (FVIII:C, activated partial thromboplastin time (APTT, prothrombin time (PT%, fibrinogen, D-dimer, and plasma volume were determined. Three hemoconcentration correction techniques were assessed: arithmetic correction and two reconstitution techniques using baseline plasma or physiological saline. Area-under-the-curve (AUC was computed for each technique. For FVII:C, uncorrected AUC was significantly greater than AUC corrected arithmetically. For PT%, uncorrected AUC was significantly greater than AUC corrected with saline or arithmetically. For APTT, uncorrected AUC was significantly less than AUC corrected with saline and greater than AUC corrected arithmetically. For fibrinogen, uncorrected AUC was significantly greater than AUC corrected with saline or arithmetically. For D-dimer, uncorrected AUC was significantly greater than AUC corrected arithmetically. No differences in AUC were observed for FVIII:C. Saline reconstitution seems most appropriate when adjusting for hemoconcentration effects on clotting time and activity. Stress-hemoconcentration accounted for the majority of coagulation changes.

  11. BACKGROUND: Asthma and Allergic Rhinitis (AR) are two chronic inflammatory diseases that are often concomitant. The Control of Allergic Rhinitis and Asthma Test (CARAT) was developed to evaluate the control of these diseases from the patients' perspective. Its performance in asthma patients without AR has not been previously studied. AIM: To test the hypothesis that CARAT can be used to assess asthma control in patients with asthma and without AR. METHODS: A cross-sectional study was conducted in 3 primary healthcare centres in Northern Portugal. Adult patients identified in the Electronic Patient Record with a diagnosis of asthma were invited to participate. CARAT was used to assess asthma control and Asthma Control Test (ACT) as a comparator. The associations between asthma patients without AR (AsAR) and with AR (AwAR) were analyzed with Spearman correlation. Additionally, Receiver Operating Characteristic (ROC) curve analysis, summarized by Area Under the Curve (AUC), was used to assess performance of CARAT for screening asthma that was not well-controlled. RESULTS: A total of 103 asthma patients completed the study, 64 (62%) had AwAR and in 87 (85%) asthma was not well-controlled. We observed a strong correlation between CARAT and ACT scores (r=0.734) in all asthma patients and in both groups: AsAR (r=0.737) and AwAR (r=0.843). ROC curve demonstrated CARAT as having a good discriminative power for both AsAR and AwAR groups (AUC=0.894 and 0.946, respectively). CONCLUSION: These initial results suggest that CARAT has a good discriminative performance, similar to other asthma control assessment tools, for asthma patients with and without AR.

    OpenAIRE

    Riaz, M.; Certal, V; Nigam, G; Abdullatif, J; Zaghi, S; Kushida, CA; Camacho, M

    2015-01-01

    Objective. To quantify the effectiveness of nasal expiratory positive airway pressure (nasal EPAP) devices or Provent as treatment for obstructive sleep apnea (OSA). Methods. PubMed and six other databases were searched through November 15, 2015, without language limitations. Results. Eighteen studies (920 patients) were included. Pre- and post-nasal EPAP means ± standard deviations (M ± SD) for apnea-hypopnea index (AHI) in 345 patients decreased from 27.32 ± 22.24 to 12.78 ± 16.89 events/hr...

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

    International Nuclear Information System (INIS)

    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 m3/h) of design airflow capacity(31,500 m3/h) for AUC-556 and was 97%(22,800 m3/h) of design airflow capacity(22,800 m3/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%)

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

    Directory of Open Access Journals (Sweden)

    "Rouini MR

    2002-08-01

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

  14. β-adrenoceptor blocker pharmacokinetics and the oral contraceptive pill

    OpenAIRE

    Kendall, M. J.; Jack, D B; Quarterman, C P; Smith, S.R.; Zaman, R

    1984-01-01

    Higher AUC and Cmax values were obtained for metoprolol, oxprenolol and propranolol in groups receiving the low-dose oestrogen-ethinyl oestradiol oral contraceptive, but statistical significance was reached only with metoprolol AUC. The oral contraceptive had the opposite effect on acebutolol AUC and Cmax but this was not significant. The oral contraceptive had no detectable effects on the tmax and t½ values of any of the β-adrenoceptor blockers.

  15. Manufacture of uranium dioxide powder

    International Nuclear Information System (INIS)

    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 NH4OH 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

  16. Cerebrospinal fluid P-tau181P: biomarker for improved differential dementia diagnosis

    Directory of Open Access Journals (Sweden)

    Hanne eStruyfs

    2015-06-01

    Full Text Available The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau181P in the Alzheimer’s disease (AD cerebrospinal fluid (CSF biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients.The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of Aβ1-42, T-tau, and P-tau181P were determined with single analyte ELISA-kits (INNOTEST®, Fujirebio, Ghent, Belgium. Diagnostic accuracy was assessed through receiver operating characteristic (ROC curve analyses to obtain area under the curve (AUC values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUC values was performed by means of DeLong tests.The Aβ1-42/P-tau181P ratio (AUC=0.770 performed significantly better than Aβ1-42 (AUC=0.677, P=0.004, T-tau (AUC=0.592, P<0.001, and Aβ1-42/T-tau (AUC=0.678, P=0.001, while P-tau181P (AUC=0.720 performed significantly better than T-tau (AUC=0.592, P<0.001 to discriminate between AD and the pooled non-AD group. When comparing AD and the individual non-AD diagnoses, Aβ1-42/P-tau181P (AUC=0.894 discriminated AD from frontotemporal dementia significantly better than Aβ1-42 (AUC=0.776, P=0.020 and T-tau (AUC=0.746, P=0.004, while P-tau181P/T-tau (AUC=0.958 significantly improved the differentiation between AD and Creutzfeldt-Jakob disease as compared to Aβ1-42 (AUC=0.688, P=0.004, T-tau (AUC=0.874, P=0.040, and Aβ1-42/P-tau181P (AUC=0.760, P=0.003.In conclusion, this study demonstrates P-tau181P is an essential component of the AD CSF biomarker panel and combined assessment of Aβ1-42, T-tau, and P-tau181P renders, to present date, the highest diagnostic power to discriminate between AD and non-AD dementias.

  17. Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia.

    Science.gov (United States)

    Britt, Nicholas S; Patel, Nimish; Horvat, Rebecca T; Steed, Molly E

    2016-05-01

    While previous studies have examined the association between vancomycin (VAN) exposure and MIC with regard to outcomes in methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B), none have explored if a relationship exists with the VAN minimum bactericidal concentration (MBC). The objective of this study was to evaluate the VAN 24-h area under the curve (AUC24)/MBC ratio as a pharmacodynamic predictor of mortality. This retrospective cohort study included patients treated with VAN for MRSA-B with the primary outcome of 30-day all-cause mortality. Data collected included patient demographics, comorbidities, antimicrobial treatment data, therapeutic drug levels, and laboratory and microbiological data. Vancomycin MICs and MBCs were determined by Etest (MIC only) and broth microdilution (BMD). The vancomycin AUC24 was determined by pharmacokinetic maximum a posteriori probability Bayesian (MAP-Bayesian) analysis. The most significant breakpoint for 30-day mortality was determined by classification and regression tree (CART) analysis. The association between pharmacodynamic parameters (VAN AUC24/MICBMD, VAN AUC24/MICEtest, and AUC24/MBCBMD) and mortality were determined by χ(2) and multivariable Poisson regression. Overall mortality in this cohort (n = 53) was 20.8% (n = 11/53), and all corresponding MRSA blood isolates were VAN susceptible (MIC range, 0.5 to 2 μg/ml; MIC50, 1 μg/ml; MIC90, 1 μg/ml). The CART-derived breakpoints for mortality were 176 (VAN AUC24/MBC) and 334 (VAN AUC24/MICBMD). In multivariable analysis, the association between a VAN AUC24/MBC of ≥176 and survival persisted, but VAN AUC24/MICBMD values (≥334 or ≥400) were not associated with improved mortality. In conclusion, VAN AUC24/MBC was a more important predictor of 30-day mortality than VAN AUC24/MIC for MRSA-B. PMID:26953202

  18. 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.

  19. Biomarkers for predicting complete debulking in ovarian cancer

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent; Christensen, Ib Jarle;

    2014-01-01

    cohort of patients. RESULTS: Part I: The area under the receiver operating characteristic curve (AUC) was 0.82 for both indices. Part II: Linear regression analysis gave an R(2) value of 0.52 and 0.63 for transferrin and β2-microglobulin, respectively. Part III: The AUC of the two indices decreased to 0...

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

    NARCIS (Netherlands)

    Wende, van der 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 programm

  1. 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.

    2014-01-01

    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 al

  2. 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

    atropine 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...

  3. Determining the arterial stiffness through contour analysis of a PPG and its association with HbA1c among diabetic patients in Malaysia - doi: 10.4025/actascitechnol.v36i1.17096

    Directory of Open Access Journals (Sweden)

    Sahnius Usman

    2014-01-01

    Full Text Available Diabetes mellitus accelerates atherosclerosis. Monitoring arterial condition promises to be an advantage in the detection of any abnormalities. In this study, the characteristics of analysis by photoplethysmogram (PPG were investigated non-invasively among diabetic patients. An area under the curve (auc-PPG was compared for two levels of HbA1c, namely HbA1c 10% (Group 2. Auc-PPG was found to be significantly higher among diabetic subjects with HbA1c 10%. Further analysis was performed to investigate the effect of age on auc-PPG. The mean values of auc-PPG were still significantly higher among diabetic patients with HbA1c 10%. These results show that the auc-PPG method could be a parameter in determining the arterial stiffness in relation to the level of HbA1c.

  4. Application of appropriate use criteria for percutaneous coronary intervention in Japan

    Science.gov (United States)

    Inohara, Taku; Kohsaka, Shun; Ueda, Ikuko; Yagi, Takashi; Numasawa, Yohei; Suzuki, Masahiro; Maekawa, Yuichiro; Fukuda, Keiichi

    2016-01-01

    The aim of this review was to summarize the concept of appropriate use criteria (AUC) regarding percutaneous coronary intervention (PCI) and document AUC use and impact on clinical practice in Japan, in comparison with its application in the United States. AUC were originally developed to subjectively evaluate the indications and performance of various diagnostic and therapeutic modalities, including revascularization techniques. Over the years, application of AUC has significantly impacted patient selection for PCI in the United States, particularly in non-acute settings. After the broad implementation of AUC in 2009, the rate of inappropriate PCI decreased by half by 2014. The effect was further accentuated by incorporation of financial incentives (e.g., restriction of reimbursement for inappropriate procedures). On the other hand, when the United States-derived AUC were applied to Japanese patients undergoing elective PCI from 2008 to 2013, about one-third were classified as inappropriate, largely due to the perception gap between American and Japanese experts. For example, PCI for low-risk non-left atrial ascending artery lesion was more likely to be classified as appropriate by Japanese standards, and anatomical imaging with coronary computed tomography angiography was used relatively frequently in Japan, but no scenario within the current AUC includes this modality. To extrapolate the current AUC to Japan or any other region outside of the United States, these local discrepancies must be taken into consideration, and scenarios should be revised to reflect contemporary practice. Understanding the concept of AUC as well as its perception gap between different counties will result in the broader implementation of AUC, and lead to the quality improvement of patients’ care in the field of coronary intervention. PMID:27621773

  5. Application of appropriate use criteria for percutaneous coronary intervention in Japan

    Science.gov (United States)

    Inohara, Taku; Kohsaka, Shun; Ueda, Ikuko; Yagi, Takashi; Numasawa, Yohei; Suzuki, Masahiro; Maekawa, Yuichiro; Fukuda, Keiichi

    2016-01-01

    The aim of this review was to summarize the concept of appropriate use criteria (AUC) regarding percutaneous coronary intervention (PCI) and document AUC use and impact on clinical practice in Japan, in comparison with its application in the United States. AUC were originally developed to subjectively evaluate the indications and performance of various diagnostic and therapeutic modalities, including revascularization techniques. Over the years, application of AUC has significantly impacted patient selection for PCI in the United States, particularly in non-acute settings. After the broad implementation of AUC in 2009, the rate of inappropriate PCI decreased by half by 2014. The effect was further accentuated by incorporation of financial incentives (e.g., restriction of reimbursement for inappropriate procedures). On the other hand, when the United States-derived AUC were applied to Japanese patients undergoing elective PCI from 2008 to 2013, about one-third were classified as inappropriate, largely due to the perception gap between American and Japanese experts. For example, PCI for low-risk non-left atrial ascending artery lesion was more likely to be classified as appropriate by Japanese standards, and anatomical imaging with coronary computed tomography angiography was used relatively frequently in Japan, but no scenario within the current AUC includes this modality. To extrapolate the current AUC to Japan or any other region outside of the United States, these local discrepancies must be taken into consideration, and scenarios should be revised to reflect contemporary practice. Understanding the concept of AUC as well as its perception gap between different counties will result in the broader implementation of AUC, and lead to the quality improvement of patients’ care in the field of coronary intervention.

  6. 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

  7. The Evolution of Coronary Revascularization Appropriateness Use Criteria: From Mandatory to Forgotten.

    Science.gov (United States)

    Sattur, Sudhakar; Brener, Sorin J

    2015-01-01

    The appropriateness use criteria (AUC) for coronary revascularization have been formulated through the joint efforts of several professional societies. The goals of AUC were to aid in physician decision making and to objectively define the need and context for revascularization. These criteria, developed using a standardized approach, were widely promoted and adopted in many practices. Rigorous use in daily practice and public reporting of adherence to these criteria has exposed some of their deficiencies. Revisions to the original version were made to accommodate public and physician sentiments. Not surprisingly, the recent percutaneous coronary intervention performance measures developed by the same professional societies that have proposed AUC, have suggested that AUC should be used for internal quality improvement only at this time. Therefore, the present role and future application of AUC to cardiology practice is uncertain. The goals of this review are to describe methodology and development of the coronary revascularization AUC, to focus on the strengths and limitations of AUC, and to identify challenges related to application of these criteria in daily practice. PMID:26827745

  8. 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

    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...... 2 diabetes (n=363) exhibited no significant differences (P=not significant) in peak plasma GIP, total area under the curve (tAUC), time-corrected tAUC (tAUC×min(-1)), and time-corrected incremental area under the curve (iAUC×min(-1)) in comparison with nondiabetic control subjects (n=325) but had...... 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-01

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

  10. 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)

    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.)

  11. Investigation of the spatiotemporal responses of nanoparticles in tumor tissues with a small-scale mathematical model.

    Directory of Open Access Journals (Sweden)

    Cheng-Ying Chou

    Full Text Available The transport and accumulation of anticancer nanodrugs in tumor tissues are affected by many factors including particle properties, vascular density and leakiness, and interstitial diffusivity. It is important to understand the effects of these factors on the detailed drug distribution in the entire tumor for an effective treatment. In this study, we developed a small-scale mathematical model to systematically study the spatiotemporal responses and accumulative exposures of macromolecular carriers in localized tumor tissues. We chose various dextrans as model carriers and studied the effects of vascular density, permeability, diffusivity, and half-life of dextrans on their spatiotemporal concentration responses and accumulative exposure distribution to tumor cells. The relevant biological parameters were obtained from experimental results previously reported by the Dreher group. The area under concentration-time response curve (AUC quantified the extent of tissue exposure to a drug and therefore was considered more reliable in assessing the extent of the overall drug exposure than individual concentrations. The results showed that 1 a small macromolecule can penetrate deep into the tumor interstitium and produce a uniform but low spatial distribution of AUC; 2 large macromolecules produce high AUC in the perivascular region, but low AUC in the distal region away from vessels; 3 medium-sized macromolecules produce a relatively uniform and high AUC in the tumor interstitium between two vessels; 4 enhancement of permeability can elevate the level of AUC, but have little effect on its uniformity while enhancement of diffusivity is able to raise the level of AUC and improve its uniformity; 5 a longer half-life can produce a deeper penetration and a higher level of AUC distribution. The numerical results indicate that a long half-life carrier in plasma and a high interstitial diffusivity are the key factors to produce a high and relatively uniform

  12. Investigation of the spatiotemporal responses of nanoparticles in tumor tissues with a small-scale mathematical model.

    Science.gov (United States)

    Chou, Cheng-Ying; Huang, Chih-Kang; Lu, Kuo-Wei; Horng, Tzyy-Leng; Lin, Win-Li

    2013-01-01

    The transport and accumulation of anticancer nanodrugs in tumor tissues are affected by many factors including particle properties, vascular density and leakiness, and interstitial diffusivity. It is important to understand the effects of these factors on the detailed drug distribution in the entire tumor for an effective treatment. In this study, we developed a small-scale mathematical model to systematically study the spatiotemporal responses and accumulative exposures of macromolecular carriers in localized tumor tissues. We chose various dextrans as model carriers and studied the effects of vascular density, permeability, diffusivity, and half-life of dextrans on their spatiotemporal concentration responses and accumulative exposure distribution to tumor cells. The relevant biological parameters were obtained from experimental results previously reported by the Dreher group. The area under concentration-time response curve (AUC) quantified the extent of tissue exposure to a drug and therefore was considered more reliable in assessing the extent of the overall drug exposure than individual concentrations. The results showed that 1) a small macromolecule can penetrate deep into the tumor interstitium and produce a uniform but low spatial distribution of AUC; 2) large macromolecules produce high AUC in the perivascular region, but low AUC in the distal region away from vessels; 3) medium-sized macromolecules produce a relatively uniform and high AUC in the tumor interstitium between two vessels; 4) enhancement of permeability can elevate the level of AUC, but have little effect on its uniformity while enhancement of diffusivity is able to raise the level of AUC and improve its uniformity; 5) a longer half-life can produce a deeper penetration and a higher level of AUC distribution. The numerical results indicate that a long half-life carrier in plasma and a high interstitial diffusivity are the key factors to produce a high and relatively uniform spatial AUC

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

    International Nuclear Information System (INIS)

    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.

  14. Machine learning-based receiver operating characteristic (ROC) curves for crisp and fuzzy classification of DNA microarrays in cancer research.

    Science.gov (United States)

    Peterson, Leif E; Coleman, Matthew A

    2008-01-01

    Receiver operating characteristic (ROC) curves were generated to obtain classification area under the curve (AUC) as a function of feature standardization, fuzzification, and sample size from nine large sets of cancer-related DNA microarrays. Classifiers used included k nearest neighbor (kNN), näive Bayes classifier (NBC), linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), learning vector quantization (LVQ1), logistic regression (LOG), polytomous logistic regression (PLOG), artificial neural networks (ANN), particle swarm optimization (PSO), constricted particle swarm optimization (CPSO), kernel regression (RBF), radial basis function networks (RBFN), gradient descent support vector machines (SVMGD), and least squares support vector machines (SVMLS). For each data set, AUC was determined for a number of combinations of sample size, total sum[-log(p)] of feature t-tests, with and without feature standardization and with (fuzzy) and without (crisp) fuzzification of features. Altogether, a total of 2,123,530 classification runs were made. At the greatest level of sample size, ANN resulted in a fitted AUC of 90%, while PSO resulted in the lowest fitted AUC of 72.1%. AUC values derived from 4NN were the most dependent on sample size, while PSO was the least. ANN depended the most on total statistical significance of features used based on sum[-log(p)], whereas PSO was the least dependent. Standardization of features increased AUC by 8.1% for PSO and -0.2% for QDA, while fuzzification increased AUC by 9.4% for PSO and reduced AUC by 3.8% for QDA. AUC determination in planned microarray experiments without standardization and fuzzification of features will benefit the most if CPSO is used for lower levels of feature significance (i.e., sum[-log(p)] ~ 50) and ANN is used for greater levels of significance (i.e., sum[-log(p)] ~ 500). When only standardization of features is performed, studies are likely to benefit most by using CPSO for low levels

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

    International Nuclear Information System (INIS)

    At present the ammonium uranyl carbonate (AUC) route is developed at a scale of 10 kg/day of UO2. This UO2 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 U3O8. 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)

  16. In Vivo Doses of Acrylamide and Glycidamide in Humans after Intake of Acrylamide-Rich Food

    OpenAIRE

    Vikström, Anna C.; Abramsson-Zetterberg, Lilianne; Naruszewicz, Marek; Athanassiadis, Ioannis; Granath, Fredrik N.; Törnqvist, Margareta A.

    2011-01-01

    For assessment of cancer risk from acrylamide (AA) exposure through food, the relation between intake from food in humans and the in vivo doses (area under the concentration-time curve, AUC) of AA (AUC-AA) and of its genotoxic metabolite glycidamide (GA) (AUC-GA) is used as a basis for extrapolation between exposure levels and between species. In this study, AA-rich foods were given to nonsmokers: a high intake of 11 mu g AA/kg body weight (bw) and day for 4 days or an extra (medium) intake o...

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

    Science.gov (United States)

    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 < 0.05). Following the meal, BG was lower after lentils and chickpeas at 150 and 165 min, and AUC was lower after lentils compared with white bread (p < 0.05). PMID:24797207

  18. Pharmacokinetics and bioavailability of single dose ibuprofen and pseudoephedrine alone or in combination: a randomized three-period, cross-over trial in healthy Indian volunteers

    Directory of Open Access Journals (Sweden)

    Prashant eKale

    2014-05-01

    Full Text Available Objective To compare the bioavailability of single dose ibuprofen 200 mg and pseudoephedrine hydrochloride 30 mg administered alone or in combination as an oral suspension. Methods This was a single-center, randomized, single-dose, open-label, 3-period, crossover study. After an overnight fast (≥10 hours, 18 healthy male subjects received either ibuprofen 200 mg (reference-A, pseudoephedrine 30 mg (reference-B or the combination (test-C as a suspension, on 3 separate visits, with blood sampling up to 36-hours post-dose. The primary pharmacokinetic parameters, maximum plasma concentration (Cmax and area under the plasma concentration–time curve (AUC from time zero to last measurable concentration (AUC0-t and extrapolated to infinity (AUC0- were compared by an analysis of variance using log-transformed data. Bioequivalence was concluded if the 90% confidence intervals (CIs of the adjusted geometric mean (gMean ratios for Cmax and AUC were within the predetermined range of 80%-125%, in accordance with regulatory requirements. Results For the test formulation, the ibuprofen gMean Cmax was 17.0 µg/mL (vs. 18.1 µg/mL for reference-A, AUC0-t was 57.1 (vs. 60.0 µg•h/mL and AUC0- was 59.9 µg•h/mL (vs. 63.1 µg•h/mL. The 90% CIs for the ratio (test/reference-A were 81.0-108.1% for Cmax, 91.5-98.4% for AUC0-t and 91.6-97.9% for AUC0-. For pseudoephedrine, the gMean Cmax for the test formulation was 97.2 ng/mL (vs. 98.5 ng/mL for reference-B, AUC0-t was 878.4 (vs. 842.8 ng•h/mL and AUC0- was 907.8 ng•h/mL (vs. 868.3 ng•h/mL. The 90% CIs for the ratio (test/reference-B were 92.4-106.9% for Cmax, 97.7-111.0% for AUC0-t and 97.9-111.3% for AUC0-. All treatments were well tolerated. Conclusion This oral suspension containing ibuprofen and pseudoephedrine combined in a new formulation met the regulatory criterion for bioequivalence compared with oral suspensions containing the individual components.

  19. Sinemet-ferrous sulphate interaction in patients with Parkinson's disease.

    OpenAIRE

    Campbell, N R; Rankine, D; Goodridge, A E; Hasinoff, B B; Kara, M

    1990-01-01

    1. This study examined the effects of administering ferrous sulphate 325 mg with Sinemet (100/25 tablet) on levodopa and carbidopa bioavailability and on signs of Parkinson's disease in nine patients. 2. Ferrous sulphate ingestion with Sinemet resulted in a decrease in levodopa area under the curve (AUC) of 30% (P less than 0.01) and a greater than 75% decrease in carbidopa AUC. Despite a strong relationship between reductions in levodopa AUC and reductions in Sinemet efficacy (r = 0.83, P le...

  20. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Contact us Support AAD Media AAD store Advertise Employment Website feedback AAD American Academy of Dermatology Excellence ... Dialogues in Dermatology JAAD Mohs AUC Psoriasis Patient education resources Practice tools Coding Ask a coding expert ...

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

    Medline Plus

    Full Text Available ... Contact us Support AAD Media AAD store Advertise Employment Website feedback AAD American Academy of Dermatology Excellence ... Dialogues in Dermatology JAAD Mohs AUC Psoriasis Patient education resources Practice tools Coding Ask a coding expert ...

  2. Seborrheic Dermatitis

    Science.gov (United States)

    ... urticaria—for public Dialogues in Dermatology JAAD Mohs AUC Psoriasis Patient education resources Practice tools Coding Ask ... the following to remove scale from your skin: Wash your skin daily, as follows: Wet your skin ...

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

    Medline Plus

    Full Text Available ... Dialogues in Dermatology JAAD Mohs AUC Psoriasis Patient education resources Practice tools Coding Ask a coding expert ... measures Outcomes in Dermatology Pilot Affinity partner programs Education Online Learning Center MOC MOC overview Component parts ...

  4. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Dialogues in Dermatology JAAD Mohs AUC Psoriasis Patient education resources Practice tools Coding Ask a coding expert ... measures Outcomes in Dermatology Pilot Affinity partner programs Education Online Learning Center MOC MOC overview Component parts ...

  5. Aspirin metabolism and efficacy in postoperative dental pain.

    Science.gov (United States)

    Seymour, R A; Williams, F M; Ward, A; Rawlins, M D

    1984-01-01

    Aspirin 1200 mg was compared with placebo in a randomised, double-blind, crossover study in 15 patients with postoperative pain after removal of impacted lower third molars. Over a 5 h investigation period, patients reported significantly less pain (P less than 0.01) after treatment with aspirin, than after treatment with placebo. Peak concentrations of aspirin occurred at 15 min after dosage. Significant negative correlations were observed between plasma aspirin esterase activity and both AUC aspirin (r = -0.904, P less than 0.001) and AUC analgesia (r = -0.91, P less than 0.001). Similarly, a significant correlation was observed between AUC aspirin and AUC analgesia (r = 0.96, P less than 0.001). Evidence from this study would suggest that an individual's pain relief in postoperative dental pain is determined by the rate of aspirin hydrolysis to salicylate. PMID:6378231

  6. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... AAD CME Award AAD Cochrane Scholarship AAD Quality Improvement Activity Award Advocate of the Year Award Arnold ... Dialogues in Dermatology JAAD Mohs AUC Psoriasis Patient education resources Practice tools Coding Ask a coding expert ...

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

    Medline Plus

    Full Text Available ... AAD CME Award AAD Cochrane Scholarship AAD Quality Improvement Activity Award Advocate of the Year Award Arnold ... Dialogues in Dermatology JAAD Mohs AUC Psoriasis Patient education resources Practice tools Coding Ask a coding expert ...

  8. 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

  9. Evaluation of Once-Daily Vancomycin against Methicillin-Resistant Staphylococcus aureus in a Hollow-Fiber Infection Model

    OpenAIRE

    Nicasio, Anthony M.; Bulitta, Jürgen B.; Lodise, Thomas P.; D'Hondt, Rebecca E.; Kulawy, Robert; Louie, Arnold; Drusano, George L.

    2012-01-01

    For methicillin-resistant Staphylococcus aureus (MRSA) infections, data suggest that the clinical response is significantly better if the total vancomycin area under the concentration-time curve (AUC)/MIC ratio is ≥400. While the AUC/MIC ratio is the accepted pharmacokinetic/pharmacodynamic (PK/PD) index for vancomycin, this target has been achieved using multiple daily doses. We are unaware of a systematically designed dose fractionation study to compare the bactericidal activity of once-dai...

  10. Fluoroquinolone Resistance in Anaerobic Bacteria following Exposure to Levofloxacin, Trovafloxacin, and Sparfloxacin in an In Vitro Pharmacodynamic Model

    OpenAIRE

    Ross, Gigi H.; Wright, David H.; Hovde, Laurie Baeker; Peterson, Marnie L.; Rotschafer, John C.

    2001-01-01

    This investigation explored pharmacodynamic characteristics of fluoroquinolones against Bacteroides thetaiotamicron and the potential for development of resistance. An in vitro model was used to generate kill curves with three fluoroquinolones at various area under the concentration-time curve (AUC)/MIC ratios. Concentration-independent killing was observed. Increases in MICs were noted following exposure to fluoroquinolones at AUC/MIC ratios of 6 to 14.

  11. A relative bioavailability study of 500 mg calcium p-aminosalicylate film coating tablet in healthy individuals

    Directory of Open Access Journals (Sweden)

    Chinhwa Cheng

    2014-06-01

    Full Text Available The purpose of this study is to evaluate the only available calcium p-aminosalicylate (Ca PAS commercial product, which is one of the most commonly prescribed non-surveillance products from the Bureau of National Health Insurance (BNHI database in Taiwan. An open-randomized, balanced, two-way crossover study was designed to evaluate the relative bioavailability (F of a 500 mg Ca PAS F.C. tablet with a 500 mg Ca PAS suspension in 13 healthy individuals. Blood samples were collected according to a planned time schedule. The plasma concentrations of PAS were measured by a validated liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS method. Pharmacokinetic parameters of area under the plasma concentration-time curve from the time zero to the time of last quantifiable concentration (AUC0–t, area under the plasma concentration-time curve from time zero to infinity (AUC0–∞, maximum plasma concentration (Cmax, time to reach measured maximum plasma concentration (Tmax, elimination half-life (T1/2, and mean residence time (MRT were determined by non-compartment methods. F was calculated by [AUC0–∞] of the test drug divided by [AUC0–∞] of the reference drug. The mean geometric ratios of pharmacokinetic parameters, including AUC0–t, AUC0–∞, and Cmax obtained were 0.873, 0.874, and 0.569, respectively. The 90% confidence intervals of ln (AUC0–t, ln (AUC0–∞, and ln (Cmax after being back natural log-transformed were (74.0–103.0%, (74.1–103.0%, and (38.4–84.3%, respectively. The relative bioavailability of the Ca PAS tablet was 87.4%.

  12. 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

    .9%) and glibenclamide (1.0%, 2.2 mmol/L, 2.5 mmol/L, 17.5%). Repaglinide was also associated with an increase in the AUC60 and AUC120 for insulin (+56%, +61%) and C-peptide (+41%, +36%). GLP-1, GIP, IL-6, ICAM-1 and E-selectin levels did not change in either group. No association was observed between GLP-1, GIP-1...

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

    Directory of Open Access Journals (Sweden)

    Kaan Sözmen

    2016-03-01

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

  14. Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes

    OpenAIRE

    Akintola, Abimbola A.; VAN DEN BERG, Annette; Altmann-Schneider, Irmhild; Jansen, Steffy W.; van Buchem, Mark A.; Slagboom, P. Eline; Westendorp, Rudi G.; van Heemst, Diana; van der Grond, Jeroen

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic mo...

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

    Directory of Open Access Journals (Sweden)

    D. Hamish Wright, PhD

    2015-12-01

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

  16. The predictive validity of common risk assessment tools in men with intellectual disabilities and problematic sexual behaviors.

    Science.gov (United States)

    Fedoroff, J Paul; Richards, Deborah; Ranger, Rebekah; Curry, Susan

    2016-10-01

    This CIHR-funded study examined whether certain current risk assessment tools were effective in appraising risk of recidivism in a sample of sex offenders with intellectual disabilities (ID). Fifty men with ID who had engaged in problematic sexual behavior (PSB) were followed for an average of 2.5 years. Recidivism was defined and measured as any illegal or problematic behavior, as well as any problematic but not necessarily illegal behavior. At the beginning of the study, each participant was rated on two risk assessment tools: the Violence Risk Appraisal Guide (VRAG) and the Sex Offender Risk Appraisal Guide (SORAG). During each month of follow-up, participants were also rated on the Short-Dynamic Risk Scale (SDRS), an assessment tool intended to measure the risk of future problematic behaviors. Data was analyzed using t-tests, Cohen's d and area under the curve (AUC) to test predictive validity of the assessment tools. Using the AUC, results showed that the VRAG was predictive of sexual (AUC=0.74), sexual and/or violent (AUC=0.71) and of any criminally chargeable event (AUC=0.69). The SORAG was only significantly predictive of sexual events (AUC=0.70) and the SDRS was predictive of violent events (AUC=0.71). The t-test and Cohen's d analyses, which are less robust to deviations from the assumptions of normal and continuous distribution than AUC, did not yield significant results in each category, and therefore, while the results of this study suggest that the VRAG and the SORAG may be effective tools in measuring the short term risk of sexual recidivism; and the VRAG and SDRS may be effective tools in appraising long term risk of sexual and/or violent recidivism in this population, it should be used with caution. Regardless of the assessment tool used, risk assessments should take into account the differences between sex offenders with and without ID to ensure effective measurement. PMID:27372881

  17. In Vivo Pharmacokinetics and Pharmacodynamics of a New Triazole, Voriconazole, in a Murine Candidiasis Model

    OpenAIRE

    Andes, D.; Marchillo, K.; Stamstad, T.; Conklin, R.

    2003-01-01

    In vivo studies have described the pharmacodynamic (PD) characteristics of several triazoles. These investigations have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic (PK)-PD parameter associated with treatment efficacy. Further analyses from these in vivo studies have demonstrated that a triazole free drug 24-h AUC/MIC of 20 to 25 is predictive of treatment success. We used a neutropenic murine model of disseminated Candida ...

  18. Transdermal fentanyl matrix patches Matrifen and Durogesic DTrans are bioequivalent

    DEFF Research Database (Denmark)

    Kress, Hans G; Boss, Hildegard; Delvin, Thomas;

    2010-01-01

    least square means of the Test/Reference ratio (90% confidence intervals [CI]) were within the range of 80-125%, demonstrating bioequivalence of Matrifen and Durogesic DTrans: AUC(0-tlast) 92.5 (CI 88.7-96.4), AUC(0-inf) 91.7 (CI 88.0-95.7), and C(max) 98.3 (CI 92.9-104.1). After 72 h application...

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

    Science.gov (United States)

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

    2016-11-01

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

  20. Sex and Food Influence on Intestinal Absorption of Ketoprofen Gastroresistant Formulation.

    Science.gov (United States)

    Magallanes, Laura; Lorier, Marianela; Ibarra, Manuel; Guevara, Natalia; Vázquez, Marta; Fagiolino, Pietro

    2016-05-01

    Sixteen healthy volunteers (8 women and 8 men) participated in a 2-period, 2-treatment crossover study. A delayed-release gastroresistant formulation of ketoprofen was administered under fasting and fed conditions. Cmax , AUC, Cmax /AUC, and kel obtained after food coadministration did not differ from those calculated under fasting administration. Ninety-five percent confidence intervals for fed/fasting geometric mean ratio of Cmax /AUC and AUC were 0.80-1.14 and 0.80-1.23, respectively. A significant difference (P food intake (5.5 vs 2.5 hours). Also, a significant difference between the medians of Tmax was found (P food coadministration and 4.0 hours under fasting administration, but this difference disappeared once T0 was subtracted from Tmax . Cmax /AUC, which is related to drug absorption rate, showed significant differences between sexes. Men showed higher (P =.006) Cmax /AUC means (0.468 ± 0.094 vs 0.361 ± 0.087 h(-1) . Tmax was also significantly different (P Food coadministration extended the gastric residence time of formulation but exerted no effect on its intestinal absorption pattern. PMID:27163498

  1. Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

    Science.gov (United States)

    Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

    2016-01-01

    A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts. PMID:26589820

  2. 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 ( < 0.01) rapidly from fasted levels after both oral and i.v. 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. PMID:27065127

  3. Imaging-based differential diagnosis between multiple system atrophy and Parkinson's disease.

    Science.gov (United States)

    Sako, Wataru; Abe, Takashi; Murakami, Nagahisa; Miyazaki, Yoshimichi; Izumi, Yuishin; Harada, Masafumi; Kaji, Ryuji

    2016-09-15

    There are many tools for differentiating between multiple system atrophy with predominant parkinsonian features (MSA-P) and Parkinson's disease (PD). These include middle cerebellar peduncle (MCP) width, apparent diffusion coefficient (ADC) value of the putamen and cerebellum, and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy images. We aimed to directly compare the above-mentioned methods, and to determine the optimal tool for differential diagnosis. Eleven patients with MSA-P and 36 patients with PD were enrolled. Of these, 7 patients with MSA-P and 14 patients with PD were chosen as background-matched subjects. We measured MCP width, ADC value of the putamen and cerebellum, and MIBG myocardial scintigraphy images. Area under curve (AUC) of receiver operating characteristic (ROC) was assessed to compare the above-mentioned methods. MCP width and ADC value of the putamen may be helpful for differentiating between MSA-P and PD relative to other methods in background-matched patients (MCP, AUC=0.95; putamen ADC, AUC=0.88; cerebellar ADC, AUC=0.70; MIBG, AUC=0.78). Similar AUCs were seen in all patients with different backgrounds. Our findings suggested that MCP width and ADC value of the putamen could be superior to ADC value of the cerebellum and MIBG uptake for differentiating between MSA-P and PD. PMID:27538610

  4. Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis

    DEFF Research Database (Denmark)

    Mortensen, Joachim Høg; Godskesen, Line Elbjerg; Jensen, Michael Dam;

    2015-01-01

    BACKGROUND AND AIMS: A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC......-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling....... Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively...

  5. 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.

  6. Impact of area under the concentration-time curve to minimum inhibitory concentration ratio on vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus bacteraemia.

    Science.gov (United States)

    Song, Kyoung-Ho; Kim, Hong Bin; Kim, Hyung-sook; Lee, Myung Jin; Jung, Younghee; Kim, Gayeon; Hwang, Jeong-Hwan; Kim, Nak-Hyun; Kim, Moonsuk; Kim, Chung-Jong; Choe, Pyoeng Gyun; Chung, Jae-Yong; Park, Wan Beom; Kim, Eu Suk; Park, Kyoung Un; Kim, Nam Joong; Kim, Eui-Chong; Oh, Myoung-don

    2015-12-01

    There have been few clinical studies on the association between the vancomycin 24-h area under the concentration-time curve (AUC24) to minimum inhibitory concentration (MIC) ratio and vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infections. To examine this association and to establish a suitable cut-off value for AUC24/MIC, a multicentre prospective observational study was conducted in patients with MRSA bacteraemia. Data were collected on all patients aged ≥18 years with MRSA bacteraemia treated with vancomycin for ≥72 h without dialysis. The MIC was determined by broth microdilution (BMD) and Etest. Treatment failure was defined as (i) 30-day mortality, (ii) persistent bacteraemia (≥7 days) and (iii) recurrence (≤30 days after completion of therapy). AUC24 was estimated by a Bayesian approach based on individual vancomycin concentrations. The AUC24/MIC cut-off value for differentiating treatment success and failure was calculated by Classification and Regression Tree (CART) analysis. In total, 117 patients were enrolled, among which vancomycin treatment failure occurred in 38 (32.5%). In univariate analysis, high vancomycin MIC and low trough levels were unrelated to treatment outcomes. In the CART analysis, low vancomycin AUC24/MIC [vancomycin treatment outcomes in MRSA bacteraemia, and seeking individualised AUC24/MIC ratios above target (>400) may improve treatment outcomes.

  7. 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

  8. Analysis of Prognosis and Prognostic Factors of Cervical Adenocarcinoma and Adenosqumous Carcinoma of the Cervix

    Institute of Scientific and Technical Information of China (English)

    Guangwen Yuan; Lingying Wu; Xiaoguang Li; Manni Huang

    2009-01-01

    OBJECTIVE To analyze clinical characteristics and treatment methods of the patients with adenocarcinoma of the uterine cervix (AUC) and adenosquamous carcinoma of the cervix (ASCC). To compare the survival time of the patients in 2 groups and analyze the prognostic factors.METHODS Clinical data of both 123 patients with AUC and 32 patients with ASCC treated at the Cancer Hospital, Chinese Academy of Medical Science (CAMS) & Peking Union Medical College (PUMC), were retrospectively analyzed.RESULTS The median age of the AUC patients was 50 years, and that of the ASCC patients was 44, P = 0.019. Poorly-differentiated (grade 3) cases accounted for 59.5% of the total ASCC patients,while only 32.5% of the AUC patients were in grade 3, P = 0.002.In 123 AUC patients, relapse or failure of the treatment occurred in 63 of the patients (51.2%), and the median relapse time was 6 months (0-59 months). In 32 ASCC patients, relapse or failure of the treatment occurred in 8 of these patients (51.2%), with a median relapse time of 4.5 months (0-52 months). The overall 5-year survival rate of the AUC patients was 49.8%, which was significantly lower than that of the ASCC patients (74.1%), P =0.015. The 5-year survival rates of the ASCC patients in Stage Ⅰ-Ⅲ were higher than that of the AUC patients with the same stages.However, statistical significant difference could only be found among the patients in Stage Ⅱ, P = 0.006. The 5-year survival rates of the ASCC patients with various differential grade were higher than those of the AUC patients with the same differential grade,but statistical significant difference could only be found among the patients in the two groups with moderately differentiation,P = 0.039. It was found by Cox regression analysis that only clinical stage (P < 0.001) and histological type (P = 0.046) were the independent prognostic factors.CONCLUSION Clinical stage and histological type were the independent prognostic factors of the AUC and ASCC patients

  9. In vivo pharmacokinetics and pharmacodynamics of a new triazole, voriconazole, in a murine candidiasis model.

    Science.gov (United States)

    Andes, D; Marchillo, K; Stamstad, T; Conklin, R

    2003-10-01

    In vivo studies have described the pharmacodynamic (PD) characteristics of several triazoles. These investigations have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic (PK)-PD parameter associated with treatment efficacy. Further analyses from these in vivo studies have demonstrated that a triazole free drug 24-h AUC/MIC of 20 to 25 is predictive of treatment success. We used a neutropenic murine model of disseminated Candida albicans infection to similarly characterize the PK-PD of the new triazole voriconazole. PK and PD parameters (percentage of time that the concentration remains above the MIC [T > MIC], AUC/MIC ratio, and peak level in serum/MIC ratio) were correlated with in vivo efficacy, as measured by the organism number in kidney cultures after 24 h of therapy. Voriconazole kinetics and protein binding were studied in infected neutropenic mice. Peak level/dose and AUC/dose values ranged from 0.1 to 0.2 and 0.1 to 0.7, respectively. The serum elimination half-life ranged from 0.7 to 2.9 h. The level of protein binding in mouse serum was 78%. Treatment efficacy with the four dosing intervals studied was similar, supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (R(2) for AUC/MIC ratio = 82%, R(2) for peak level/MIC ratio = 63%, R(2) for T > MIC = 75%). Similar studies were conducted with nine additional C. albicans isolates with various voriconazole susceptibilities (MICs, 0.007 to 0.25 micro g/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The voriconazole free drug AUC/MIC ratios were similar for all of the organisms studied (range, 11 to 58; mean +/- standard deviation, 24 +/- 17 [P = 0.45]). These AUC/MIC ratios observed for free drug are similar to those observed for other triazoles in this model. PMID:14506026

  10. New red blood cell and reticulocyte parameters and reference values for healthy individuals and in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Patrícia S. Scherer

    2015-04-01

    Full Text Available Introduction: The importance of local references values has been well described in the literature; this is because the characteristics of the population may influence the laboratory tests. Objective: To establish the reference range for traditional and extended red blood cell parameters and reticulocyte indices in order to investigate its application in patients with chronic kidney disease (CKD. Materials and methods: 249 blood donors (125 males and 124 females were selected to establish the reference values. The hemodialysis sample consisted of 62 patients with terminal CKD (48 male and 14 female. All analyzes were performed using the Sysmex XE-5000 automated hematology analyzer. Results: Differences between reference values was observed in relation to gender: red blood cells (RBC, hemoglobin (HGB, hematocrit (HCT, mean corpuscular hemoglobin concentration (MCHC, percentage of hyperchromic red blood cells (%HYPER, percentage of microcytosis (%MICRO, percentage of macrocytosis (%MACRO, absolute reticulocyte count (RET, reticulocyte hemoglobin content (RET-He, immature reticulocyte fraction (IFR, low fluorescence reticulocytes (LFR, medium fluorescence reticulocytes (MFR, and high fluorescence reticulocytes (HFR. Individuals with CKD presented RBC, HGB, HCT, MCHC, red cell distribution width expressed as coefficient of variation (RDW-CV, percentage of hypochromic red blood cells (%HYPO, percentage of reticulocytes (RET%, RET (female group, IFR, LFR, MFR, and HFR results compatible with the anemic state, which can be observed in 91.8% of patients. All studied parameters were in the area under the curve (AUC > 0.4. In male group, %HYPO (AUC: 0.806 and IFR (AUC: 0.762 presented higher AUC values, while female group presented %HYPO (AUC: 0.806, %HYPER (AUC: 0.815, and IFR (AUC: 0.660. Conclusion: The medical advancement, the development of new techniques and hematological parameters have revealed important information about functional integrity of

  11. Pharmacokinetic evaluation of novel oral fluorouracil antitumor drug S-1 in Chinese cancer patients

    Institute of Scientific and Technical Information of China (English)

    Zhi-xiang ZHUANG; Hong ZHU; Ji WANG; Min-gao ZHU; Hui WANG; Wang-yang PU; Hua-hui BIAN

    2013-01-01

    Aim:S-1 is an oral anticancer fluoropyrimidine formulation consisting of tegafur,5-chloro-2,4-dihydroxypyridine and potassium oxonate.The aim of this study was to evaluate the pharmacokinetics and bioequivalence of a newly developed generic formulation of S-1 in Chinese cancer patients in comparison with the branded reference formulation of S-1.Methods:A single-dose,randomized-sequence,open-label,two-way self-crossover study was conducted in 30 Chinese cancer patients.The subjects alternatively received the two formulations (40 mg/m2,po) with a 7-d interval.Plasma concentrations of FT,CDHP,Oxo,and 5-Fu were determined using LC-MS/MS.Pharmacokinetic parameters,including C Tmax,t1/2,AUC0-t,and AUC0-∞ were determined using non-compartmental models with DAS2.0 software.Bioequivalence of the two formulations were to be evaluated according to 90% Cls for the log-transformed ratios of AUC and Cmax of S-1.Adverse events were evaluated through monitoring the symptom,physical and laboratory examinations,ECGs and subject interviews.Results:The mean values of Cmax,AUC0-t,and AUC0-∞ of FT,5-Fu,CDHP,and Oxo for the two formulations had no significant differences.The 90% Cls for natural log-transformed ratios of C AUC0-t,and AUC0-∞ were within the predetermined bioequivalence acceptance limits.A total of 11 mild adverse events,including fatigue,nausea and vomiting,anorexia,diarrhea and myelosuppression,were observed,and no serious and special adverse events were found.Conclusion:The newly developed generic formulation and reference formulation of S-1 have similar pharmacokinetics with one dose (40 mg/m2) in Chinese cancer patients.Both the formulations of S-1 are well tolerated.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-10-15

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

  13. Effect of intertrochanteric osteotomy on the proximal femur of rabbits: assessment with power Doppler sonography and scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Doria, Andrea S. [University of Toronto (Canada). Hospital for Sick Children. Dept. of Diagnostic Imaging; Cunha, Fabiano G.; Modena; Marcelo; Godoy Junior, Rui de; Bolliger Neto, Raul; Guarniero, Roberto [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. of Cirurgia Ortopedica]. E-mail: andrea.doria@sickkids.ca; Rodrigues, Consuelo Junqueira [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. de Patologia; Garcez, Alexandre Teles; Melo, Ivani Bortoleti; Buchpiguel, Carlos; Molnar, Laszlo J. [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. de Medicina Nuclear

    2007-07-01

    Objective: In bone injury, repair results in local increased vascularity and bone marrow remodeling. Characterizing the vascular and metabolic imaging patterns of the proximal femur following an intertrochanteric osteotomy may help clinicians decide proper management of the patient. Our objective was to measure Doppler sonography and scintigraphy interval changes in the proximal femur following intertrochanteric osteotomy and compare imaging and histomorphometric measurements in the late post-operative stage (6 weeks after surgery) in a rabbit model of bone injury. Materials and methods: Both hips of 12 adult rabbits were imaged with power Doppler sonography and scintigraphy prior to and after (7 days and 6 weeks) unilateral osteotomy. Accuracy of the imaging methods was evaluated using hip operative status and histomorphometric results (vascular fractional area and number of vessels per area unit) as reference standard measures. Results: A significant difference in the mean number of pixels was noted between operated and non-operated femura in late post-operative power Doppler examinations (P=0.049). Although without reaching statistical significance, the AUC of Doppler measurements (AUC=0.99) was numerically greater than the AUC of scintigraphy measurements (AUC=0.857{+-}0.099) (P=0.15) in differentiating proximal femura with regard to their fractional vascular areas in the late post-operative stage. In contrast, scintigraphy tended to perform better (AUC=0.984{+-}0.022) than Doppler ultrasound (AUC=0.746{+-}0.131) to demonstrate the vascularity intensity per area unit (P=0.07) in the late stage. Conclusion: Our results warrant further investigation to determine the value of different imaging modalities for assessment of pathologic changes following hip surgery. Power Doppler sonography demonstrated larger AUCs (representing higher accuracy) for the discrimination of vascular fractional areas and scintigraphy, for discrimination of the number of vessels per area

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

    Science.gov (United States)

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

    2011-01-01

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

  15. Pharmacokinetics and bioequivalence of ranitidine and bismuth derived from two compound preparations

    Institute of Scientific and Technical Information of China (English)

    Quan Zhou; Zou-Rong Ruan; Hong Yuan; Bo Jiang; Dong-Hang Xu

    2006-01-01

    AIM: To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations.METHODS: The bioavailability was measured in 20healthy male Chinese volunteers following a single oral dose (equivalent to 200 mg of ranitidine and 220 mg of bismuth) of the test or reference products in the fasting state. Then blood samples were collected for 24 h.Plasma concentrations of ranitidine and bismuth were analyzed by high-performance liquid chromatography and inductively coupled plasma-mass spectrometry (ICPMS), respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax,AUC(0-t) and AUC(0-∞) were tested for bioequivalence using ANOVA and Schuirmann two-one sided t-test. Tmax was analyzed by Wilcoxon's test.RESULTS: Various pharmacokinetic parameters of ranitidine derived from the two compound preparations,including Cmax, AUC(0-t), AUC(0-∞), Tmax and T1/2, were nearly consistent with previous observations. These parameters derived from test and reference drug were as follows: Cmax(0.67 ± 0.21 vs 0.68 ± 0.22mg/L), AUC(0-t)(3.1 ± 0.6 vs 3.0 ± 0.7 mg/L per hour),AUC(0-∞)(3.3 ± 0.6 vs 3.2 ± 0.8 mg/L per hour),Tmax (2.3 ± 0.9 vs 2.1 ± 0.9 h) and T1/2 (2.8 ± 0.3 vs 3.1± 0.4 h). In addition, double-peak absorption profiles of ranitidine were found in some Chinese volunteers.For bismuth, those parameters derived from test and reference drug were as follows: Cmax (11.80 ± 7.36 vs 11.40 ± 6.55 μg/L),AUC(0-t) (46.65 ± 16.97 vs 47.03 ±21.49 μg/L per hour), Tmax (0.50 ± 0.20 vs 0.50 ± 0.20 h)and T1/2 (10.2 ± 2.3 vs 13.0 ± 6.9 h). Ninety percent of confidence intervals for the test/reference ratio of Cmax,AUC(0-t) and AUC(0-∞) derived from both ranitidine and bismuth were found within the bioequivalence acceptable range of 80%-125%. No significant difference was found in Tmax derived from both ranitidine and bismuth.CONCLUSION: The two compound preparations are bioequivalent and may be prescribed

  16. Diagnosis of pulmonary embolism: ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography

    International Nuclear Information System (INIS)

    The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses. Copyright (2005) Blackwell Publishing Asia Pty Ltd

  17. Global and regional left ventricular strain indices in post-myocardial infarction patients with ventricular arrhythmias and moderately abnormal ejection fraction.

    Science.gov (United States)

    Nguyen, Bich Lien; Capotosto, Lidia; Persi, Alessandro; Placanica, Attilio; Rafique, Asim; Piccirillo, Gianfranco; Gaudio, Carlo; Gang, Eli S; Siegel, Robert J; Vitarelli, Antonio

    2015-02-01

    The aim of the study described here was to compare myocardial strains in ischemic heart patients with and without sustained ventricular tachycardia (VT) and moderately abnormal left ventricular ejection fraction (LVEF) to investigate which index could better predict VT on the basis of the analysis of global and regional left ventricular (LV) dysfunction. We studied 467 patients with previous myocardial infarction and LVEF >35%. Fifty-one patients had documented VT, and 416 patients presented with no VT. LV volumes and score index were obtained by 2-D echocardiography. Longitudinal, radial and circumferential strains were determined. Strains of the infarct, border and remote zones were also obtained. There were no differences in standard LV 2-D parameters between patients with and those without VT. Receiver operating characteristic values were -12.7% for global longitudinal strain (area under the curve [AUC] = 0.72), -4.8% for posterior-inferior wall circumferential strain (AUC = 0.80), 61 ms for LV mechanical dispersion (AUC = 0.84), -10.1% for longitudinal strain of the border zone (AUC = 0.86) and -9.2% for circumferential strain of the border zone (AUC = 0.89). In patients with previous myocardial infarction and moderately abnormal LVEF, peri-infarct circumferential strain was the strongest predictor of documented ventricular arrhythmias among all strain quantitative indices. Additionally, strain values from posterior-inferior wall infarctions had a higher association with arrhythmic events compared with global strain.

  18. Pharmacokinetics and target attainment of mycophenolate in pediatric renal transplant patients.

    Science.gov (United States)

    Martial, Lisa C; Jacobs, Bart A W; Cornelissen, Elisabeth A M; de Haan, Anton F J; Koch, Birgit C P; Burger, David M; Aarnoutse, Rob E; Schreuder, Michiel F; Brüggemann, Roger J M

    2016-06-01

    MPA is an immunosuppressive agent used to prevent graft rejection after renal transplantation. MPA shows considerable inter- and intraindividual variability in exposure in children and has a defined therapeutic window, and TDM is applied to individualize therapy. We aimed to study the exposure to MPA measured as the AUC in pediatric renal transplant patients, to identify factors influencing exposure and to assess target attainment. Children transplanted between 1998 and 2014 in a single center were included. Two groups were identified: Group 1 (AUC 18 months post-transplantation). Therapeutic targets were set at: AUC0-12h of 30-60 mg h/L. A total of 39 children were included in Group 1 (median age 13.3 yr) vs. 14 in Group 2 (median age 13.4 yr). AUC0-12h was 29.7 mg h/L in Group 1 and 56.6 mg h/L in Group 2, despite a lower dosage in Group 2 (584 and 426 mg/m(2) , respectively). About 46% of patients reached the target AUC0-12h in Group 1. Time since transplantation and serum creatinine were significantly associated with MPA exposure (p explaining 36% of the variability. Individualization of the mycophenolate dose by more intense and more early TDM could improve target attainment. PMID:26923724

  19. Predictors of ertapenem therapeutic efficacy in the treatment of urinary tract infections (UTIs) in hospitalized adults: the importance of renal insufficiency and urinary pH.

    Science.gov (United States)

    Cunha, B A; Giuga, J; Gerson, S

    2016-04-01

    In hospitalized adults acute uncomplicated cystitis (AUC) and catheter associated bacteriuria (CAB) may be treated with oral antibiotics. With AUC or CAB due to extended spectrum ß-lactamase (ESBL) + Gram negative bacilli (GNB) physicians often use intravenous therapy, e.g., ertapenem. We reviewed our recent experience in hospitalized adults with AUC and CAB treated with ertapenem. Therapeutic efficacy of ertapenem was assessed by decreased pyuria/bacteriuria, and elimination of the uropathogen. The effectiveness of ertapenem in the presence of renal insufficiency (CrCl ertapenem was highly effective in eliminating bacteriuria (TTNC 3 days) in patients with decreased renal function and alkaline urinary pH. We reviewed 45 hospitalized adults with AUC or CAB to determine if renal insufficiency and or alkaline urinary pH affected ertapenem efficacy. In the 33 adult hospitalized patients with AUC and 12 with CAB, we found that ertapenem was consistently effective in eliminating the GNB bacteriuria. In hospitalized adults, the presence of renal insufficiency and acid urine, bacteriuria was eliminated in  3 days which has not been previously reported. PMID:26873378

  20. Surface Decontamination of System Components in Uranium Conversion Plant at KAERI

    International Nuclear Information System (INIS)

    A chemical decontamination process using nitric acid solution was selected as in-situ technology for recycle or release with authorization of a large amount of metallic waste including process system components such as tanks, piping, etc., which is generated by dismantling a retired uranium conversion plant at Korea Atomic Energy Research Institute (KAERI). The applicability of nitric acid solution for surface decontamination of metallic wastes contaminated with uranium compounds was evaluated through the basic research on the dissolution of UO2 and ammonium uranyl carbonate (AUC) powder. Decontamination performance was verified by using the specimens contaminated with such uranium compounds as UO2 and AUC taken from the uranium conversion plant. Dissolution rate of UO2 powder is notably enhanced by the addition of H2O2 as an oxidant even in the condition of a low concentration of nitric acid and low temperature compared with those in a nitric acid solution without H2O2. AUC powders dissolve easily in nitric acid solutions until the solution pH attains about 2.5 ∼ 3. Above that solution pH, however, the uranium concentration in the solution is lowered drastically by precipitation as a form of U3(NH3)4O9 . 5H2O. Decontamination performance tests for the specimens contaminated with UO2 and AUC were quite successful with the application of decontamination conditions obtained through the basic studies on the dissolution of UO2 and AUC powders

  1. Multiple bonds to gold: a theoretical investigation of XAuC (X = F, Cl, Br, I) molecules

    International Nuclear Information System (INIS)

    Structures and spectroscopic properties are reported for the linear XAuC (X = F, Cl, Br, I) series of molecules and their related diatomic species at a high level of accuracy. The singles and doubles coupled cluster method including a perturbational correction for connected triple excitations, CCSD(T), with systematic sequences of new correlation consistent basis sets have been employed. Scalar relativistic effects have been accurately included by making use of relativistic effective core potentials. Extrapolation to the complete basis set limit has been used with accurate treatments of core-valence correlation and spin-orbit effects in order to accurately predict spectroscopic properties, as well as dissociation and atomization energies at 0 K of AuC, AuC+, AuF, AuCl, AuBr, AuI, and the XAuC molecules. The Au-C bond length in the FAuC molecule is predicted to be nearly identical to that calculated for AuC+, which makes it the shortest known for a neutral gold molecule. The Au-C and Au-F (0 K) bond dissociation energies in FAuC are predicted to be 92.5 and 93.1 kcal/mol, respectively, also making them some of the strongest known bonds to gold

  2. A Suite of Tools for ROC Analysis of Spatial Models

    Directory of Open Access Journals (Sweden)

    Hermann Rodrigues

    2013-09-01

    Full Text Available The Receiver Operating Characteristic (ROC is widely used for assessing the performance of classification algorithms. In GIScience, ROC has been applied to assess models aimed at predicting events, such as land use/cover change (LUCC, species distribution and disease risk. However, GIS software packages offer few statistical tests and guidance tools for ROC analysis and interpretation. This paper presents a suite of GIS tools designed to facilitate ROC curve analysis for GIS users by applying proper statistical tests and analysis procedures. The tools are freely available as models and submodels of Dinamica EGO freeware. The tools give the ROC curve, the area under the curve (AUC, partial AUC, lower and upper AUCs, the confidence interval of AUC, the density of event in probability bins and tests to evaluate the difference between the AUCs of two models. We present first the procedures and statistical tests implemented in Dinamica EGO, then the application of the tools to assess LUCC and species distribution models. Finally, we interpret and discuss the ROC-related statistics resulting from various case studies.

  3. Impact of disease states on the pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors.

    Science.gov (United States)

    LeBlanc, Jaclyn M; Dasta, Joseph F; Pruchnicki, Maria C; Schentag, Jerome J

    2006-09-01

    The pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors (ACE) in elderly patients and patients with renal and hepatic impairment were examined, and a role for an AUC/EC50 ratio to guide dosing was evaluated. A Medline and International Pharmaceutical Abstracts search was used to identify human studies and abstracts. Relevant data were evaluated and summarized. Dosing regimens were compared using an AUC/EC50 ratio. Most studies evaluating ACE inhibitors in renal impairment report a strong linear correlation between creatine clearance and drug elimination. AUC and EC50 values for these drugs in elderly subjects appear similar to younger and hypertensive patients. There is increased AUC in some patients with hepatic impairment. Pharmacodynamic data are conflicting. Prolonged ACE inhibition is evident in renal impairment but not necessarily other disease states. ACE inhibitor dosing for hypertension is reasonable based on pharmacokinetics and EC50 values. Further individualization of therapy may improve outcomes, and using the threshold AUC/EC50 ratio may help guide appropriate dosing. PMID:16920891

  4. Effect of the bile acid sequestrant colesevelam on the pharmacokinetics of pioglitazone, repaglinide, estrogen estradiol, norethindrone, levothyroxine, and glyburide.

    Science.gov (United States)

    Brown, Karen S; Armstrong, Ingrid C; Wang, Antonia; Walker, Joseph R; Noveck, Robert J; Swearingen, Dennis; Allison, Mark; Kissling, James C; Kisicki, James; Salazar, Daniel E

    2010-05-01

    The purpose of this study was to assess effects of colesevelam on the pharmacokinetics of glyburide, levothyroxine, estrogen estradiol (EE), norethindrone (NET), pioglitazone, and repaglinide in healthy volunteers. Six drugs with a potential to interact with colesevelam were studied in open-label, randomized clinical studies. The presence of a drug interaction was concluded if the 90% confidence intervals for the geometric least squares mean ratios of AUC(0-t) (AUC(0-48) for levothyroxine) and C(max) fell outside the no-effect limits of (80.0%, 125.0%). Concomitant administration of colesevelam had no effect on the AUC(0-t) or C(max) of pioglitazone but significantly decreased the AUC(0-t) and C(max) of glyburide, levothyroxine, and EE and the C(max) of repaglinide and NET. AUC(0-t) and C(max) of glyburide and EE, but not repaglinide or NET, were significantly decreased when the drug was given 1 hour before colesevelam. When glyburide, EE, or levothyroxine was given 4 hours before colesevelam, no drug interaction was observed. Although colesevelam has a cleaner drug interaction profile than other bile acid sequestrants, it does interfere with absorption of some drugs. A 4-hour window appears sufficient to eliminate these interactions.

  5. Nuclear Magnetic Resonance Solution Structures of Lacticin Q and Aureocin A53 Reveal a Structural Motif Conserved among Leaderless Bacteriocins with Broad-Spectrum Activity.

    Science.gov (United States)

    Acedo, Jeella Z; van Belkum, Marco J; Lohans, Christopher T; Towle, Kaitlyn M; Miskolzie, Mark; Vederas, John C

    2016-02-01

    Lacticin Q (LnqQ) and aureocin A53 (AucA) are leaderless bacteriocins from Lactococcus lactis QU5 and Staphylococcus aureus A53, respectively. These bacteriocins are characterized by the absence of an N-terminal leader sequence and are active against a broad range of Gram-positive bacteria. LnqQ and AucA consist of 53 and 51 amino acids, respectively, and have 47% identical sequences. In this study, their three-dimensional structures were elucidated using solution nuclear magnetic resonance and were shown to consist of four α-helices that assume a very similar compact, globular overall fold (root-mean-square deviation of 1.7 Å) with a highly cationic surface and a hydrophobic core. The structures of LnqQ and AucA resemble the shorter two-component leaderless bacteriocins, enterocins 7A and 7B, despite having low levels of sequence identity. Homology modeling revealed that the observed structural motif may be shared among leaderless bacteriocins with broad-spectrum activity against Gram-positive organisms. The elucidated structures of LnqQ and AucA also exhibit some resemblance to circular bacteriocins. Despite their similar overall fold, inhibition studies showed that LnqQ and AucA have different antimicrobial potency against the Gram-positive strains tested, suggesting that sequence disparities play a crucial role in their mechanisms of action.

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

    Directory of Open Access Journals (Sweden)

    Szu-Chia Chen

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

    The relative bioequivalence of crushed versus intact eslicarbazepine acetate (ESL) tablets (800 mg) administered orally in healthy adults was evaluated in an open-label, randomized, 2-period crossover study with a 5-day washout between treatments. Sample blood levels of eslicarbazepine and (R)-licarbazepine were determined; pharmacokinetic parameters were derived for eslicarbazepine. Bioequivalence was established if the 90% confidence intervals (CIs) for the geometric mean treatment ratios of eslicarbazepine AUC(0-∞) and Cmax were within the prespecified 80%-125% range. Twenty-seven subjects in the intent-to-treat population (n = 28) completed both treatment periods. Eslicarbazepine exposure measures were similar for crushed versus intact ESL tablets: average Cmax , 11 700 versus 11 500 ng/mL; AUC(0-∞) , 225 000 versus 234 000 ng·h/mL; AUC(0-last) , 222 000 versus 231 000 ng·h/mL, respectively. Geometric least squares mean ratios (90%CIs) comparing eslicarbazepine exposure measures were within the 80%-125% range (Cmax , 102.63% [97.07%-108.51%]; AUC(0-∞) , 96.72% [94.36%-99.13%]; AUC0-last , 96.69% [94.24%-99.21%]). In conclusion, ESL administered orally as a crushed tablet sprinkled on applesauce, or intact were bioequivalent in healthy subjects. Eslicarbazepine bioavailability was not significantly altered by crushing, indicating that ESL tablets can be administered intact or crushed. PMID:27249205

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. Influence of experimental diabetes and insulin treatment on the enantioselective pharmacokinetics of mexiletine and its metabolites.

    Science.gov (United States)

    Pardo Campos Godoy, Ana Leonor; Martinez, Edson Z; Marques, Maria Paula; de Carvalho Leone, Andréia; Barbosa Coelho, Eduardo; Lucia Lanchote, Vera

    2014-03-01

    This study evaluates the influence of streptozotocin-induced diabetes on the kinetic disposition and metabolism of mexiletine (MEX) enantiomers in rats. Animals in the control (n = 6 for each blood collection time), diabetic (single intravenous dosage of 45 mg·(kg body mass)(-1) of streptozotocin), and insulin-treated groups (diabetic rats treated daily with 2 IU insulin) received by gavage a single dose of 10 mg·(kg body mass)(-1) racemic MEX. MEX enantiomers and the metabolites hydroxymethylmexiletine (HMM) and p-hydroxymexiletine PHM) were analyzed by LC-MS/MS. Statistical analysis was based on a serial sacrifice design, and parameter estimation was performed using a Bayesian modeling procedure. Area under the curve (AUC) for the (-)-(R) enantiomers of MEX, HMM, and PHM did not differ between the control and diabetic groups. However, AUC for (+)-(S)-MEX and (+)-(S)-HMM were lower in the diabetic than in the control group. Insulin treatment recovered glucose levels to normal and the (+)-(S)-MEX AUC and (+)-(S)-HMM AUC became similar to the AUCs observed in the nondiabetic animals. PMID:24593792

  11. Predictors of ertapenem therapeutic efficacy in the treatment of urinary tract infections (UTIs) in hospitalized adults: the importance of renal insufficiency and urinary pH.

    Science.gov (United States)

    Cunha, B A; Giuga, J; Gerson, S

    2016-04-01

    In hospitalized adults acute uncomplicated cystitis (AUC) and catheter associated bacteriuria (CAB) may be treated with oral antibiotics. With AUC or CAB due to extended spectrum ß-lactamase (ESBL) + Gram negative bacilli (GNB) physicians often use intravenous therapy, e.g., ertapenem. We reviewed our recent experience in hospitalized adults with AUC and CAB treated with ertapenem. Therapeutic efficacy of ertapenem was assessed by decreased pyuria/bacteriuria, and elimination of the uropathogen. The effectiveness of ertapenem in the presence of renal insufficiency (CrCl 3 days) in patients with decreased renal function and alkaline urinary pH. We reviewed 45 hospitalized adults with AUC or CAB to determine if renal insufficiency and or alkaline urinary pH affected ertapenem efficacy. In the 33 adult hospitalized patients with AUC and 12 with CAB, we found that ertapenem was consistently effective in eliminating the GNB bacteriuria. In hospitalized adults, the presence of renal insufficiency and acid urine, bacteriuria was eliminated in i.e., time to negative cultures (TTNC) was prolonged, i.e., > 3 days which has not been previously reported.

  12. Multiple-dose acetaminophen pharmacokinetics.

    Science.gov (United States)

    Sahajwalla, C G; Ayres, J W

    1991-09-01

    Four different treatments of acetaminophen (Tylenol) were administered in multiple doses to eight healthy volunteers. Each treatment (325, 650, 825, and 1000 mg) was administered five times at 6-h intervals. Saliva acetaminophen concentration versus time profiles were determined. Noncompartmental pharmacokinetic parameters were calculated and compared to determine whether acetaminophen exhibited linear or dose-dependent pharmacokinetics. For doses less than or equal to 18 mg/kg, area under the curve (AUC), half-life (t1/2), mean residence time (MRT), and ratio of AUC to dose for the first dose were compared with the last dose. No statistically significant differences were observed in dose-corrected AUC for the first or last dose among subjects or treatments. Half-lives and MRT were not significantly different among treatments for the first or the last dose. Statistically significant differences in t1/2 and MRT were noted (p less than 0.05) among subjects for the last dose. A plot of AUC versus dose for the first and the last doses exhibited a linear relationship. Dose-corrected saliva concentration versus time curves for the treatments were superimposable. Thus, acetaminophen exhibits linear pharmacokinetics for doses of 18 mg/kg or less. Plots of AUC versus dose for one subject who received doses higher than 18 mg/kg were curved, suggesting nonlinear behavior of acetaminophen in this subject. PMID:1800709

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

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Muñoz-Ruiz

    2016-07-01

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

  14. Evaluation of Acid Tolerance of Drugs Using Rats and Dogs Controlled for Gastric Acid Secretion.

    Science.gov (United States)

    Kosugi, Yohei; Yamamoto, Syunsuke; Sano, Noriyasu; Furuta, Atsutoshi; Igari, Tomoko; Fujioka, Yasushi; Amano, Nobuyuki

    2015-09-01

    We attempted to establish animal models to evaluate the effects of drug degradation in the stomach on oral bioavailability. In addition, we assessed the utilization of animal studies in determining the need for enteric-coated formulations. In order to control the gastric pH in rats and dogs, appropriate dosing conditions were investigated using pentagastrin and rabeprazole, which stimulate and inhibit gastric acid secretion. Using animals controlled for gastric acid secretion, the area under curve (AUC) ratios (AUC with rabeprazole/AUC with pentagastrin) of all compounds unstable under acidic conditions were evaluated. The AUC ratios of omeprazole and erythromycin, which are administered orally to humans, as enteric-coated tablets, were greater than 1.9 in the rats and dogs controlled for gastric acid secretion. On the contrary, the AUC ratios of clarithromycin, azithromycin, and etoposide (commercially available as a standard immediate-release form) were less than 1.3 each. In conclusion, in vivo models using rats and dogs were optimized to evaluate the effects of gastric acid on the oral bioavailability of drugs, and demonstrated that in vivo models can lead to a better understanding of the oral bioavailability, with respect to the formulation development.

  15. 溃疡性结肠炎的微生态学改变及双歧杆菌的治疗作用研究%Micro-ecological Changes of Ulcerative Colitis and Effect of Bacillus Bifidus on It

    Institute of Scientific and Technical Information of China (English)

    邱春雷; 严红; 吴雄健; 刘洪荣

    2014-01-01

    目的:检测活动期溃疡性结肠炎( AUC)和缓解期溃疡性结肠炎( RUC)患者粪便菌群,观察其微生态学改变及双歧杆菌对溃疡性结肠炎( UC)的治疗作用,探讨UC的发病机制。方法选择2011年5月-2013年3月在井冈山大学附属医院门诊就诊或住院AUC患者64例( AUC组)和RUC患者71例( RUC组),另选择同期在本院体检健康者30例(对照组),收集其新鲜粪便,利用引物设计软件Primer Premier 5.0设计肠道菌群16SrDNA基因特异性PCR引物,分析肠道菌群变化。按照随机数字表法,将AUC组患者分为AUC1组32例和AUC2组32例,RUC组分为RUC1组36例和RUC2组35例;AUC1组和RUC1组患者口服诺氟沙星胶囊(氟哌酸胶囊),3粒/次,2次/d;AUC2组和RUC2组口服双歧杆菌活菌胶囊(丽珠肠乐胶囊),2粒/次,3次/d。4个亚组治疗疗程均为1个月,同时口服柳氮磺胺吡啶片,1.0 g/次,4次/d。检测各组受试者分泌型免疫球蛋白 A ( sIgA )含量和线粒体膜蛋白(Aoo-2.7)含量。结果与对照组相比,AUC组和RUC组双歧杆菌、乳酸杆菌、拟杆菌、球形梭菌、柔嫩梭菌、普拉梭菌及总细菌菌落数减少(P<0.05),大肠埃希菌、肠球菌菌落数增加(P<0.05);与RUC组相比,AUC组双歧杆菌、乳酸杆菌菌落数减少(P<0.05),大肠埃希菌菌落数增加(P<0.05)。4个亚组患者在治疗过程中均未出现明显不良反应。AUC2组、RUC2组临床疗效和组织学疗效分别优于AUC1组、RUC1组(P<0.05);且治疗后AUC2组、RUC2组双歧杆菌、乳酸杆菌菌落数分别较AUC1组、RUC1组增加,大肠埃希菌菌落数分别较AUC1组、RUC1组减少(P<0.05)。对照组与AUC1组、RUC1组sIgA、Aoo-2.7含量比较,差异均有统计学意义(P<0.05);AUC2组sIgA含量高于AUC1组,Aoo-2.7含量低于AUC1组(P<0.05);RUC2组sIgA含量高于RUC1组,Aoo-2.7

  16. High-frequency Electrocardiogram Analysis in the Ability to Predict Reversible Perfusion Defects during Adenosine Myocardial Perfusion Imaging

    Science.gov (United States)

    Tragardh, Elin; Schlegel, Todd T.; Carlsson, Marcus; Pettersson, Jonas; Nilsson, Klas; Pahlm, Olle

    2007-01-01

    Background: A previous study has shown that analysis of high-frequency QRS components (HF-QRS) is highly sensitive and reasonably specific for detecting reversible perfusion defects on myocardial perfusion imaging (MPI) scans during adenosine. The purpose of the present study was to try to reproduce those findings. Methods: 12-lead high-resolution electrocardiogram recordings were obtained from 100 patients before (baseline) and during adenosine Tc-99m-tetrofosmin MPI tests. HF-QRS were analyzed regarding morphology and changes in root mean square (RMS) voltages from before the adenosine infusion to peak infusion. Results: The best area under the curve (AUC) was found in supine patients (AUC=0.736) in a combination of morphology and RMS changes. None of the measurements, however, were statistically better than tossing a coin (AUC=0.5). Conclusion: Analysis of HF-QRS was not significantly better than tossing a coin for determining reversible perfusion defects on MPI scans.

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

    Science.gov (United States)

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

    2009-01-01

    There were authentic distinctions between the groups of healthy volunteers and patients with a peptic ulcer disease in Cmax, Tmax, AUC(0-t), AUC(0-infinity), CIt, Vd of omeprazole and Cmax of esomeprazole (Nexium, AstraZeneca). When the pharmacokinetics of omeprazole and ezomeprazole were compared in both groups, there were authentic distinctions in Cmax, AU(0-t), AUC(0-infinity), CIt, T1/2. The patients who had taken omeprazole the time of hypoacide condition was much shorter than in other groups. Disintegration test modeling pHmax for pH oscillation with large amplitude, that is typical for ulcer disease, demonstrated a possibility of early partial release of omeprazole, its acid-depended degradation and reduction of its bioavailability. PMID:19960999

  18. Power calculation for comparing diagnostic accuracies in a multi-reader, multi-test design.

    Science.gov (United States)

    Kim, Eunhee; Zhang, Zheng; Wang, Youdan; Zeng, Donglin

    2014-12-01

    Receiver operating characteristic (ROC) analysis is widely used to evaluate the performance of diagnostic tests with continuous or ordinal responses. A popular study design for assessing the accuracy of diagnostic tests involves multiple readers interpreting multiple diagnostic test results, called the multi-reader, multi-test design. Although several different approaches to analyzing data from this design exist, few methods have discussed the sample size and power issues. In this article, we develop a power formula to compare the correlated areas under the ROC curves (AUC) in a multi-reader, multi-test design. We present a nonparametric approach to estimate and compare the correlated AUCs by extending DeLong et al.'s (1988, Biometrics 44, 837-845) approach. A power formula is derived based on the asymptotic distribution of the nonparametric AUCs. Simulation studies are conducted to demonstrate the performance of the proposed power formula and an example is provided to illustrate the proposed procedure.

  19. Diagnostic Value of the Updated Diamond and Forrester Score to Predict Coronary Artery Disease in Patients with Acute-Onset Chest Pain

    DEFF Research Database (Denmark)

    Sørgaard, Mathias; Linde, Jesper James; Kofoed, Klaus Fuglsang;

    2016-01-01

    compared the diagnostic accuracy of PTP and stress testing assessed by the area under the receiver operating characteristic curve (AUC) to identify significant CAD, defined as at least 1 coronary artery branch with >70% diameter stenosis identified by CCTA. RESULTS: The diagnostic accuracy of PTP......OBJECTIVES: In the recently updated clinical guidelines from the European Society of Cardiology on the management of stable coronary artery disease (CAD), the updated Diamond Forrester score has been included as a pretest probability (PTP) score to select patients for further diagnostic testing. We...... was significantly higher than the stress test (AUC 0.80 vs. 0.69; p = 0.009), but the diagnostic accuracy of the combination of PTP and a stress test did not significantly increase when compared to PTP alone (AUC 0.86 vs. 0.80; p = 0.06). CONCLUSIONS: PTP using the updated Diamond and Forrester Score is a very...

  20. Systemic exposure to inhaled beclometasone/formoterol DPI is age and body size dependent

    DEFF Research Database (Denmark)

    Chawes, B L; Govoni, M; Kreiner-Møller, E;

    2014-01-01

    . RESULTS: The systemic exposure (AUC) for children versus adults was almost doubled for formoterol and similar for B17MP despite the halved BDP dose administered in children. In adolescents the AUC for formoterol and B17MP were approximately one third higher than in adults for both compounds. Upon...... normalization for the BDP/formoterol dose in the three populations the AUC and peak concentration (C(max)) correlated inversely with age and body surface area of the patients (r ≤ -0.53; p ... inversely with age and body size suggesting that dry powder dosage regimens should be adjusted for age and body size to avoid high systemic drug levels in children....

  1. Analytical Ultracentrifugation as a Tool to Study Nonspecific Protein–DNA Interactions

    Science.gov (United States)

    Yang, Teng-Chieh; Catalano, Carlos Enrique; Maluf, Nasib Karl

    2016-01-01

    Analytical ultracentrifugation (AUC) is a powerful tool that can provide thermodynamic information on associating systems. Here, we discuss how to use the two fundamental AUC applications, sedimentation velocity (SV), and sedimentation equilibrium (SE), to study nonspecific protein–nucleic acid interactions, with a special emphasis on how to analyze the experimental data to extract thermodynamic information. We discuss three specific applications of this approach: (i) determination of nonspecific binding stoichiometry of E. coli integration host factor protein to dsDNA, (ii) characterization of nonspecific binding properties of Adenoviral IVa2 protein to dsDNA using SE-AUC, and (iii) analysis of the competition between specific and nonspecific DNA-binding interactions observed for E. coli integration host factor protein assembly on dsDNA. These approaches provide powerful tools that allow thermodynamic interrogation and thus a mechanistic understanding of how proteins bind nucleic acids by both specific and nonspecific interactions. PMID:26412658

  2. 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

    BACKGROUND: Recently, 2-h samples (C2) have been found superior to trough levels for therapeutic monitoring of transplanted patients receiving cyclosporin. The present study was undertaken to see if the same was the case for tacrolimus. METHODS: Blood tacrolimus levels were determined in 21...... consecutive patients at 3 and 14 days after renal transplantation, and before and 1, 2, 3, 4, and 6 h after oral intake of 0.1 mg/kg tacrolimus. The area under the blood concentration/time curve (AUC) was determined by the trapezoidal method, association between blood concentration at each sampling time...... 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...

  3. Synthesis, Photochemical, and Redox Properties of Gold(I) and Gold(III) Pincer Complexes Incorporating a 2,2′:6′,2″-Terpyridine Ligand Framework

    OpenAIRE

    Gimeno, M. Concepción; López-de-Luzuriaga, José M.; Manso, Elena; Monge, Miguel; Olmos, M. Elena; Rodríguez-Castillo, Mariá; Tena, María-Teresa; Day, David P.; Lawrence, Elliot J.; Wildgoose, Gregory G

    2015-01-01

    Reaction of [Au(C6F5)(tht)] (tht = tetrahydrothiophene) with 2,2′:6′,2″-terpyridine (terpy) leads to complex [Au(C6F5)(η1-terpy)] (1). The chemical oxidation of complex (1) with 2 equiv of [N(C6H4Br-4)3](PF6) or using electrosynthetic techniques affords the Au(III) complex [Au(C6F5)(η3-terpy)](PF6)2 (2). The X-ray diffraction study of complex 2 reveals that the terpyridine acts as tridentate chelate ligand, which leads to a slightly distorted square-planar geometry. Complex 1 displays fluores...

  4. The combination of colesevelam with sitagliptin enhances glycemic control in diabetic ZDF rat model

    DEFF Research Database (Denmark)

    Shang, Quan; Liu, Matthew K; Saumoy, Monica;

    2012-01-01

    Bile acid sequestrants have been shown to reduce glucose levels in patients with type 2 diabetes. We previously reported that the bile acid sequestrant colesevelam HCl (Welchol) (COL) induced the release of glucagon-like peptide (GLP)-1 and improved glycemic control in insulin-resistant rats....... In the present study, we tested whether adding sitagliptin (Januvia) (SIT), which prolongs bioactive GLP-1 half life, to COL would further enhance glycemic control. Male Zucker diabetic fatty (ZDF) rats were assigned to four groups: diabetic model without treatment (the model), the model treated with 2% COL or 0.......4% (120 mg/day) SIT alone, or with the combination (COL+SIT). After 4 wk of treatment, the glucose area under the curve (AUC) was reduced more in the COL+SIT than the COL although both groups showed decreased glucose AUC with increased AUC of bioactive GLP-1 (GLP-1A) compared with the model group...

  5. Bioavailability of iron, zinc, folate, and vitamin C in the IRIS multi-micronutrient supplement: effect of combination with a milk-based cornstarch porridge.

    Science.gov (United States)

    Kamp, Fernanda; Jandel, Doris; Hoenicke, Imke; Pietrzk, Klaus; Gross, Rainer; Trugo, Nadia M; Donangelo, Carmen M

    2003-09-01

    The effect of combining a multi-micronutrient supplement with a milk-based cornstarch porridge on the bioavailability of iron, zinc, folate, and vitamin C was evaluated using the plasma curve response over time (8 hours) in healthy women. Three tests were carried out in a crossover design: S (multi-micronutrient supplement), MS (multi-micronutrient supplement plustest meal), and M (test meal). Relative bioavailability was determined as the percent ratio of the area under the curve (AUC) in MS corrected by M, and AUC in S. Compared to S, AUC in MS was smaller for iron (p porridge is small. Therefore, the tested meal is a suitable vehicle for the multi-micronutrient supplement.

  6. 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......-operating characteristic AUCs (areas under curves). Patients were classified by 2 sets of diagnostic criteria into: A) purulent meningitis, serous meningitis or non-meningitis, and B) systemic bacterial infection, local bacterial infection or non-bacterial disease. An elevated serum level of sCD163 was the most specific...... infection, the AUC of sCD163 (0.83) did not differ significantly from those of CRP or PCT. All markers had AUCs meningitis and other conditions. In conclusion, CRP and PCT had high diagnostic value and were superior as markers of bacterial infection compared to s...

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

    Science.gov (United States)

    Sclar, David Alexander

    2013-01-01

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

  8. Heritability of caffeine metabolism

    DEFF Research Database (Denmark)

    Matthaei, Johannes; Tzvetkov, Mladen V; Strube, Jakob;

    2016-01-01

    Heritability of caffeine pharmacokinetics and CYP1A2 activity is controversial. Here we analyzed the pharmacokinetics of caffeine, an in vivo probe drug for CYP1A2 and arylamine N-acetyltransferase 2 (NAT2) activity, in monozygotic and dizygotic twins. In the entire group, common and unique...... environmental effects explained most variation in caffeine AUC. Apparently, smoking and hormonal contraceptives masked the genetic effects on CYP1A2 activity. However, when excluding smokers and users of hormonal contraceptives, 89% of caffeine AUC variation was due to genetic effects and even in the entire...... group, 8% of caffeine AUC variation could be explained by a CYP1A1/1A2 promotor polymorphism (rs2470893). In contrast, nearly all of the variation (99%) of NAT2 activity was explained by genetic effects. This study illustrates two very different situations in pharmacogenetics, from an almost exclusively...

  9. 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....... influenzae and L. pneumophila. Individual predicted estimates for Cmax/MIC and fAUC0-24/MIC as well as simulated maximal MICs resulting in target attainment for oral and intravenous administration of the drug were suitable for S. pneumoniae and H. influenzae but not for L. pneumophila. These results indicate...

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Van Gorp Toon

    2012-06-01

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

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

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    Jing eJiang

    2013-08-01

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

  13. Pharmacokinetic Interactions Between Quinine and Lopinavir/Ritonavir in Healthy Thai Adults.

    Science.gov (United States)

    Rattanapunya, Siwalee; Cressey, Tim R; Rueangweerayut, Ronnatrai; Tawon, Yardpiroon; Kongjam, Panida; Na-Bangchang, Kesara

    2015-12-01

    This study aimed to investigate the pharmacokinetic interactions between quinine and lopinavir boosted with ritonavir (LPV/r) in healthy Thai adults (8 males and 12 females). Period 1 (day 1): subjects received a single oral dose of 600 mg quinine sulfate. Period 2: subjects received LPV/r (400/100 mg) twice daily. Period 3: subjects received a single quinine sulfate dose plus LPV/r twice a day. Intensive blood sampling was performed during each phase. Quinine AUC0-48h (area under the plasma concentration-time curve from time 0 to 48 hours), AUC0-∞ (area under the plasma concentration-time curve from time 0 to infinity), and Cmax (maximum concentration over the time-span specified), were 56%, 57%, and 47% lower, respectively, in the presence of LPV/r. 3-Hydroxyquinine AUC0-48h, AUC0-∞, and Cmax were significantly lower and the metabolite-to-parent ratio was significantly reduced. Lopinavir and ritonavir exposures were not significantly reduced with quinine coadministration, but Cmax of both drugs were significantly lower. The geometric mean ratio (GMR) and 90% CI of AUC0-48h, AUC0-∞, and Cmax for quinine, 3-hydroxyquinine, lopinavir, and ritonavir lay outside the bioequivalent range of 0.8-1.25. Drug treatments during all periods were generally well tolerated. The reduction in systemic exposure of quinine and 3-hydroxyquinine with concomitant LPV/r use raises concerns of suboptimal exposure. Studies in HIV/malaria coinfection patients are needed to determine the clinical impact to decide if any change to the quinine dose is warranted.

  14. 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.

  15. Actuarial Assessment of Sex Offender Recidivism Risk: A Validation of the German version of the Static-991

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    Martin Rettenberger

    2006-12-01

    Full Text Available The Static-99 and the RRASOR are actuarial risk assessment tools for evaluating the risk of sexual and violent recidivism in sexual offenders. The Static-99 was developed in 1999 by Karl R. Hanson (Canada and David Thornton (Great Britain and is in the mean time regularly used for risk assessment in North America and some countries in Europe. The RRASOR can be described as a predecessor of the Static-99 and was published by Hanson in 1997. At first we translated the revised version of the Static-99 (Harris, Phenix, Hanson & Thornton, 2003 and adapted the instrument and the manual to the forensic context in Germany and Austria (Rettenberger & Eher, 2006. In this retrospective study, interrater reliability and concurrent validity of the RRASOR and of the German adaption of the Static-99 is presented. Furthermore we evaluated the predictive accuracy of the Static-99 and the RRASOR and compared their results. The instruments were validated from file information of Austrian sexuel offenders, who were convicted between 1968 and 2002. Both the Static-99 and the RRASOR had good interrater reliability and concurrent validity. The Static-99 showed good predictive validity for general (r = .41, AUC = .74, sexual (r = .35, AUC = .74 and violent (r = .41, AUC = .76 recidivism, whereas the predictive accuracy of the RRASOR was moderate for general (r = .29, AUC = .66, sexual (r = .30, AUC = .68 and violent (r = .28, AUC = .67 recidivism. The Static-99 exhibited a higher accuracy for the prediction of sexual offender recidivism. Although further validation studies on German-speaking populations of sex offenders are necessary, these results support the utility of the German version of the revised version of the Static-99 in improving risk assessment of sexual offenders.

  16. The diagnostic performance of an antibody enzyme-linked immunosorbent assay using serum and colostrum to determine the disease status of a Jersey dairy herd infected with Mycobacterium avium subspecies paratuberculosis.

    Science.gov (United States)

    Jenvey, Caitlin J; Reichel, Michael P; Cockcroft, Peter D

    2016-01-01

    Colostrum may have the ability to improve the diagnostic accuracy of some tests when compared to serum for important livestock diseases because of the high concentrations of immunoglobulins present within this sample type. The ELISA for Johne's disease is one such test, as it suffers from low sensitivity when testing serum samples collected during the subclinical stage of infection. Blood and colostrum samples were collected from 34 Jersey dairy cows and tested for antibodies against Mycobacterium avium subspecies paratuberculosis (MAP) by ELISA. Fecal samples were also collected and tested by a high-throughput Johne's polymerase chain reaction (HT-J PCR) assay and fecal culture (FC), with the latter being used as the reference test. A receiver operating characteristic (ROC) analysis was performed, and the area under the curve (AUC) was calculated. The HT-J PCR and FC results were also compared. Of the 34 cows in this study, 4 had FC results consistent with MAP infection. The HT-J PCR did not identify any FC-positive cows. Using a 1:20 dilution and sample-to-positive (S/P) ratio cutoff threshold of 0.15, the relative sensitivity values of both serum (AUC 0. 56) and colostrum (AUC 0.63) were 0%. With lower sample dilutions, the relative sensitivity values of serum were 0% (1:2, AUC 0.62; 1:5, AUC 0.55); however, the relative sensitivity value of colostrum was 75% (95% confidence interval [CI]: 19-99%) at a dilution of 1:5, S/P ratio cutoff threshold of 0.15, and AUC of 0.73 (95% CI: 0.55-0.87). The testing of colostrum samples for MAP-specific antibodies by ELISA may provide improved identification of animals in the early stages of infection with MAP when compared with serum samples.

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

    Science.gov (United States)

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

    2009-04-01

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

  18. 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.

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

    Science.gov (United States)

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

    2016-09-01

    Biomarker measures of infarct size and myocardial salvage index (MSI) are important surrogate measures of clinical outcomes after a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post hoc analysis of Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE) ST-Segment Elevation Myocardial Infarction (STEMI) trial evaluates the association between left ventricular (LV) mass and infarct size as assessed by areas under the curve for creatine kinase-MB (CK-MB) and troponin I release over the first 72 hours (CK-MB area under the curve [AUC] and troponin I [TnI] AUC) and the MSI. Patients with first anterior STEMI, occluded left anterior descending artery, and available LV mass measurement in EMBRACE STEMI trial were included (n = 100) (ClinicalTrials.govNCT01572909). MSI, end-diastolic LV mass on day 4 cardiac magnetic resonance, and CK-MB and troponin I concentrations were evaluated by a core laboratory. After saturated multivariate analysis, dominance analysis was performed to estimate the contribution of each independent variable to the predicted variance of each outcome. In multivariate models that included age, gender, body surface area, lesion location, smoking, and ischemia time, LV mass remained independently associated with biomarker measures of infarct size (CK-MB AUC p = 0.02, TnI AUC p = 0.03) and MSI (p = 0.003). Dominance analysis demonstrated that LV mass accounted for 58%, 47%, and 60% of the predicted variances for CK-MB AUC, TnI AUC, and MSI, respectively. In conclusion, LV mass accounts for approximately half of the predicted variance in biomarker measures of infarct size. It should be considered as an adjustment variable in studies evaluating infarct size. PMID:27392509

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

    International Nuclear Information System (INIS)

    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

  1. 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.)

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

    Science.gov (United States)

    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. PMID:27308886

  3. 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.

  4. 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

  5. Emtricitabine seminal plasma and blood plasma population pharmacokinetics in HIV-infected men in the EVARIST ANRS-EP 49 study.

    Science.gov (United States)

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

    2015-11-01

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

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

    Directory of Open Access Journals (Sweden)

    AlJohara M AlQuaiz

    2015-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-06

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

  8. Determining the arterial stiffness through contour analysis of a PPG and its association with HbA1c among diabetic patients in Malaysia - doi: 10.4025/actascitechnol.v36i1.17096

    OpenAIRE

    Sahnius Usman; Mamun Bin Ibne Reaz; Mohd. Alauddin Mohd. Ali

    2014-01-01

    Diabetes mellitus accelerates atherosclerosis. Monitoring arterial condition promises to be an advantage in the detection of any abnormalities. In this study, the characteristics of analysis by photoplethysmogram (PPG) were investigated non-invasively among diabetic patients. An area under the curve (auc-PPG) was compared for two levels of HbA1c, namely HbA1c 10% (Group 2). Auc-PPG was found to be significantly higher among diabetic subjects with HbA1c 10%. Further ...

  9. Procedure for the obtainment of ammonium uranyl-tricarbonate suitable for the preparation of sinterable UO2

    International Nuclear Information System (INIS)

    Experiments carried out to obtain Ammonium Uranyl-Tricarbonate (AUC) of nuclear purity and with the appropriate physical characteristics to serve as an intermediate stage for the obtainment of sinterable Uranium Dioxide are described. AUC was obtained by precipitation with gaseous ammonium and carbon dioxide from aqueous solutions re-circulation, controlling, in both cases, the flow of the reactive gases, the pH and the temperature. The analyzed working conditions are described, giving also the results from the distribution of the particle size and morphology of the crystals. (M.E.L.)

  10. Bioequivalence study of two losartan formulations administered orally in healthy male volunteers.

    Science.gov (United States)

    Bienert, Agnieszka; Brzezińiski, Rafał; Szałek, Edyta; Dubai, Vitali; Grześkowiak, Edmund; Dyderski, Stanisław; Drobnik, Leon; Wolc, Anna; Olejniczak-Rabinek, Magdalena

    2006-01-01

    The bioavailability of a new losartan preparation (2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt, CAS 114798-26-4) was compared with the reference preparation of the drug in 24 healthy male volunteers, aged between 19 and 32. The open, randomized, single-blind two-sequence, two-period crossover study design was performed. Under fasting conditions, each subject received a single oral dose of 100 mg losartan as a test or reference formulation. The plasma concentrations of losartan and its active metabolite were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-36h, AUC0-infinity, Cmax, t1/2, and Ke. Values of AUC0-infinity demonstrate nearly identical bioavailability of losartan from the examined formulations. The AUC0-infinity of losartan was 2019.92+/-1002.90 and 2028.58+/-837.45 ng x h/ml for the test and reference formulation, respectively. The AUC0-infinity of the metabolite was 10851.52+/-4438.66 and 11041.18 +/-5015.81 ng x h/ml for test and reference formulation, respectively. The maximum plasma concentration (Cmax) of losartan was 745.94+/-419.75 ng/ml for the test and 745.74+/-329.99 ng/ml for the reference product and the Cmax of the metabolite was 1805.77+/-765.39 and 1606.22 +/-977.22 ng/ml for the test and reference product, respectively. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for both losartan and its active metabolite. 90 % confidence limits calculated for Cmax and AUC from zero to infinity (AUC0-infinity) of losartan and its metabolite were included in the bioequivalence range (0.8-1.25 for AUC). This study shows that the test formulation is bioequivalent to the reference formulation for losartan and its main active metabolite.

  11. LocARNA-P: Accurate boundary prediction and improved detection of structural RNAs

    DEFF Research Database (Denmark)

    Will, Sebastian; Joshi, Tejal; Hofacker, Ivo L.;

    2012-01-01

    from AUC 0.71 to AUC 0.87, significantly reduces the cost of successive analysis steps. The ready-to-use software tool LocARNA-P produces structure-based multiple RNA alignments with associated columnwise STARs and predicts ncRNA boundaries. We provide additional results, a web server for Loc...... on sequence and structure similarity; we refer to these structure-based alignment reliabilities as STARs. The columnwise STARs of alignments, or STAR profiles, provide a versatile tool for the manual and automatic analysis of ncRNAs. In particular, we improve the boundary prediction of the widely...

  12. Assessment of the accuracy of real-time continuous glucose monitoring system and its correlated factors

    Institute of Scientific and Technical Information of China (English)

    洛佩

    2014-01-01

    Objective To assess the factors that influence the accuracy of real-time continuous glucose monitoring system(RT-CGM).Methods A total of 79 diabetic patients wore RT-CGM for three days continuously while calibrating by interphalangeal glucose values 4-8 times a day.We counted matching rate of interphalangeal glucose values and RT-CGM probe value,and analyzed correlation of the matching rate with MAGE,SDBG,MBG,AUC10,AUC3.9,and NGE by Pearson correlation analysis and multiple linear

  13. 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

  14. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  15. Bioavalaibility and pharmacokinetic comparison of two formulations of metformin 850 mg tablets in healthy Colombian volunteers

    Directory of Open Access Journals (Sweden)

    Gloria Holguín

    2011-04-01

    Full Text Available urpose: The aim of this study was to compare the bioavailability of two formulations of metformin 850 mg tablets: Glucophage® from Merck Santè laboratories (reference product and Metformin from Winthrop Pharmaceuticals de Colombia SA (test product in healthy Colombian volunteers. Methods: A random, double blind, two-period, two-week wash out period, crossover study was performed in 24 healthy male and female volunteers for a single 850-mg dose of metformin tablets administrated with 240 ml of water after 12 hours of fasting. Once the drug was administrated, blood samples were collected before and within 24 hour, and plasma metformin concentration was determined by using a validated HPLC method. Pharmacokinetic parameters such as Cmax, AUC0-96h, AUC0-∞, and Tmax were determined. The formulations were considered bioequivalent if the logarithmic mean ratios of ln-transformed Cmax and AUC0-∞ values were within the equivalence range of 80%-125%. Results: ANOVA analysis of the ln-transformed Cmax and AUC0-∞ indicated that none of the effects examined (formulation, period, within and between-subjet variances and carry over was statistically significant. The mean (±SD of Cmax 1217.38 (± 251.72 ng/ml vs. 1305.25 (± 301.06 ng/ml, AUC0-96h 1363.49 (± 315.51 ng.h/ml vs. 1584.82 (± 368.75 ng.h/ml, AUC0-∞, 7155.75 (± 1440.74 ng.h/ml vs. 7777.08 (± 1896.49 ng.h/ml, and Tmax 2.57 (± 0.93 h vs. 2.22 (± 0.94 h were obtained with test and reference formulations, respectively. These pharmacokinetic parameters presented differences with the results from other published papers. The 90% confidence interval of the logarithmic ratio of AUC0-∞ and Cmax was within the range of 80-125%. Conclusions: In this study in healthy Colombian volunteers, a single 850-mg dose of metformin tablet test formulation met the criteria for bioequivalence to the reference formulation based on pharmacokinetic parameters AUC0-∞ and Cmax.

  16. Bioequivalence study of three ibuprofen formulations after single dose administration in healthy volunteers

    OpenAIRE

    Bramlage, Peter; Goldis, Adrian

    2008-01-01

    Background This phase I study was designed to determine the bioavailability and bioequivalence of 400 mg Eudorlin® extra* (Ibuprofen) in comparison to two reference formulations (400 mg Nurofen® forte and 400 mg Migränin® after single dose administration under fasting conditions in healthy subjects. Therefore the design of a randomized, open label, multiple sequence cross-over study with a wash-out period of 7–10 days was used. Results AUC0-t(last) and AUC0-∞ (90%CI) were within the 80 to 125...

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

    Directory of Open Access Journals (Sweden)

    PRASHANT eKALE

    2015-10-01

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

  18. PHARMACOKINETIC AND BIOEQUIVALENCE COMPARISON BETWEEN EXTENDED RELEASE CAPSULES OF VENLAFAXINE HYDROCHLORIDE 150MG: AN OPEN LABEL, BALANCED, RANDOMIZED-SEQUENCE, SINGLE-DOSE, TWO-PERIOD CROSSOVER STUDY IN HEALTHY INDIAN MALE VOLUNTEERS

    Directory of Open Access Journals (Sweden)

    I.Sarath chandiran

    2011-03-01

    Full Text Available This bioequivalence study was designed to determine the pharmacokinetic, bioavailability and bioequivalence of Venlafaxine HCl 150 mg Extended Release Capsules in comparison with Effexor®-XR 150mg Extended Release Capsules after single dose administration under fed conditions in 20 healthy adult male subjects. Therefore the design of an open label, balanced, randomized, two-sequence, single dose, two way crossover study with a washout period of at least 7 days was used.Each volunteer received a 150 mg capsule of the reference or test drug respectively. On the day of dosing, blood samples were collected before dosing and at various time points up to 72 hours after dosing. Analysis of venlafaxine and its metabolite O-Desmethylvenlafaxine concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS method. The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed.The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. The primary pharmacokinetic parameters (Cmax, AUC0-t and AUC0-inf 90%CI were within the 80 to 125% interval required for bioequivalence as stipulated in the current regulations of the USFDA acceptance criteria. The geometric mean ratios (Test/Reference between the two products of extended-release venlafaxine capsule under fed condition were 104.91% (92.86%-118.53% and 114.41% (103.43%-124.55% for Cmax ratios, 102.24% (95.95%-108.94% and 105.27% (96.76%-114.53% for AUC0-t ratios and 101.66% (95.73%-107.97% and 104.71% (96.13%-114.05% for AUC0-inf ratios of Venlafaxine and its metabolite O-Desmethylvenlafaxine (ODV respectively. 20 volunteers had completed both treatment periods. There was no significant difference of the Tmax parameter between the two

  19. 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

  20. Correlation between Fecal Concentrations of Ciprofloxacin and Fecal Counts of Resistant Enterobacteriaceae in Piglets Treated with Ciprofloxacin: toward New Means To Control the Spread of Resistance? : CIPROFLOXACIN LEVELS AND RESISTANT BACTERIA IN FECES

    OpenAIRE

    Nguyen, Thu Thuy; Chachaty, Elisabeth; Huy, Clarisse; Cambier, Carole; de Gunzburg, Jean; Mentré, France; Andremont, Antoine

    2012-01-01

    We assessed in a piglet model the relationship between fecal ciprofloxacin concentrations and ciprofloxacin-resistant Enterobacteriaceae counts. Twenty-nine piglets were orally treated with placebo or with 1.5 or 15 mg ciprofloxacin/kg of body weight/day from day 1 (D1) to D5. Areas under the curve (AUC) of concentrations increased sharply with dose and correlated positively with AUC of resistant bacteria log counts between D1 and D9. Removing residual colonic quinolones could help to control...

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

    DEFF Research Database (Denmark)

    Iversen, Martin; Nilsson, Folke; Sipponen, Jorma;

    2009-01-01

    BACKGROUND: Cyclosporine (CsA) absorption varies early after transplantation and can be accurately assessed by the area under the absorption curve (AUC). The 2-hour post-dose (C2) level of CsA in whole blood is reported to be a useful surrogate marker of CsA AUC in kidney and liver transplant...... monitoring, but should be further explored in thoracic organ recipients. METHODS: In a 12-month study we included de novo lung (n = 95) and heart (n = 96) recipients. All participants received cyclosporine (Sandimmun Neoral) monitored by C0 and blood was collected for analysis of C2 retrospectively...

  2. Lung deposition of inhaled drugs increases with age

    DEFF Research Database (Denmark)

    Onhøj, J; Thorsson, L; Bisgaard, H

    2000-01-01

    versus time (AUC). Terminal half-life (T(1/2)) was evaluated. Dose to patient, AUC, and T(1/2) were similar in the three age groups (p > 0.35). Nebuchamber delivers the same dose of budesonide to young children and adults. Yet the plasma concentration of budesonide was similar in young children...... and adults. Therefore, lung dose is increased with age. This suggests that from a safety perspective, the prescribed dose of budesonide inhaled from a pMDI with Nebuchamber spacer need not be adjusted for age or use of facemask. Children and adults can use the same nominal dose of budesonide via Nebuchamber...

  3. The inflammatory marker suPAR after cardiac arrest

    DEFF Research Database (Denmark)

    Rundgren, Malin; Lyngbaek, Stig; Fisker, Helle;

    2015-01-01

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

  4. 大鼠体内恩丹西酮与氯丙嗪的药动学相互作用研究%Study on Pharmacokinetic Interaction of ondansetron and Chlorpromazine in Rat

    Institute of Scientific and Technical Information of China (English)

    沈于兰; 冯芳

    2008-01-01

    目的 建立同时测定大鼠血浆中恩丹西酮、氯丙嗪的HPLC-UV分析方法,探索恩丹西酮与氯丙嗪在大鼠体内药动学的相互作用,并进行高蛋白食物对2种药物药动学影响的研究.方法 以替米沙坦为内标,乙酸乙酯提取,HPLC-UV分离、分析.色谱系统:C8柱(4.6 mm×250 mm,5 μm),甲醇-水(70:30)为流动相,流速1.0mL·min-1,柱温30℃.以大鼠为研究对象,分别在禁食和服用高蛋白食物状态下给以恩丹西酮、氯丙嗪或联合使用2种药物.用建立的血药浓度测定方法测定,计算其药动学参数并进行t检验.结果 联合用药后,恩丹西酮的pmax,tt/2,MRT,AUC0→t,AUC0→∞与单独用药时相比显著性增加.氯丙嗪单独用药和联合用药时的pmax,t1/2,MRT,AUC0→s,AUC0→∞无显著性差异.高蛋白食物能使恩丹西酮的pmax,AUC0→s,AUC0→∞明显增加,使氯丙嗪的tmax延长,pmax,AUC0→t,AUC0→∞降低.结论 恩丹西酮和氯丙嗪联合使用时,恩丹西酮的药动学过程会受到显著性影响;食用高蛋白食物后,恩丹西酮和氯丙嗪的药动学参数均会发生明显的改变,应在临床使用中注意这些问题,适当调整药物剂量.

  5. Immunity raised by recent European subtype 1 PRRSV strains allows better replication of East European subtype 3 PRRSV strain Lena than that raised by an older strain

    DEFF Research Database (Denmark)

    Trus, Ivan; Frydas, Ilias S.; Reddy, Vishwanatha R. A. P.;

    2016-01-01

    : 8.3). Reduction of respiratory disease, nasal shedding (mean AUC and mean peak values) and viremia (mean AUC and mean peak values) was more pronounced in 07V063-immune (p animals. Inoculation with subtype 1 PRRSV strains caused priming of the Lena......-specific virus neutralization antibody response. Upon challenge with Lena, we observed a very strong serological booster effect for neutralizing antibodies against strains used for the first inoculation. Our results indicate that inoculation with subtype 1 PRRSV strains can partially protect against...

  6. [Pharmacokinetics of cyclosporine and its metabolites in patients undergoing kidney transplantation].

    Science.gov (United States)

    Silva Junior, H T; Pereira, A B; Ajzen, H; Bueno, V; Pestana, J O

    1994-01-01

    Pharmacokinetics of cyclosporine shows high inter and intra-individual variability and changes in several parameters are often found after kidney transplantation. PURPOSE--Evaluate serial studies of the pharmacokinetics of cyclosporine and its metabolites in patients undergoing kidney transplantation. METHODS--The pharmacokinetics of cyclosporine and its metabolites were analyzed in 70 studies performed in 29 patients, 26 before and 44 after kidney transplantation. The blood cyclosporine concentration was determined in 17 samples obtained after is oral or intravenous administration, using radioimmunoassay with specific (RIE-MoSP) and nonspecific (RIE-MoNP) monoclonal antibodies. RESULTS--The values of area-under-the-time-concentration curve (AUC), bioavailability (F), peak concentration (Cmax) and the 12 and 24 trough levels (C12 and C24), determined with RIE-MoSP, were lower than that obtained with RIE-MoNP, and the clearance (CL) and the volume of distribution (Vd) were higher. The elimination half-lives (t1/2) for both methods were not different. The absorption followed a zero order kinetic, demonstrating an inverse correlation between cyclosporine dose (mg/kg) and AUC/dose (r = -0.55, RIE-MoSP and r = -0.42, RIE-MoNP). Bioavailability ranged between 18% and 68% (RIE-MoSP) and were overestimated when calculated using RIE-MoNP (38% to 100%) owing to extensive cyclosporine metabolization during the first passage through the intestine and the liver. The metabolic rate analyzed by the ratio of blood concentrations determined with RIE-MoNP and RIE-MoSP (NP/SP), increased during the first 12 hours after cyclosporine administration, and was higher after oral dosing. The hematocrit and the serum lipoproteins concentrations significantly correlated with several pharmacokinetics parameters, mainly when they were determined with RIE-MoSP. The correlation between one sample obtained at any time after cyclosporine administration and the AUC were unsatisfactory, even the

  7. Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India

    DEFF Research Database (Denmark)

    Dhanasekaran, S; Jenum, S; Stavrum, R;

    2013-01-01

    in discriminating between TB disease and controls (AUC 91.7%). A combination of 11 biomarkers predicted latent TB with moderate discriminatory power (AUC 72.2%). In conclusion, RAB33A is a potential biomarker for TB disease, whereas CD4, TGFβ-1 and IL-2, IL-13 may identify latent TB in children.......Pediatric tuberculosis (TB) often goes undiagnosed because of the lack of reliable diagnostic methods. With the aim of assessing biomarker(s) that can aid in the diagnosis of TB infection and disease, we investigated 746 Indian children with suspected TB. Whole-blood mRNA from 210 children...

  8. 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

  9. Evaluation of a pediatric liquid formulation to improve 6-mercaptopurine therapy in children

    DEFF Research Database (Denmark)

    Tiphaine, Adam de Beaumais; Hjalgrim, Lisa Lynqsie; Nersting, Jacob;

    2016-01-01

    and evaluated in the target population. Preclinical and clinical evaluations were performed according to a Pediatric Investigation Plan, in order to apply for a Pediatric Use Marketing Authorization. METHODS: The pre-clinical study assessed the maximum tolerated dosage-volume and evaluated local mucosal...... to 50mg registered tablets were evaluated in a random order on two consecutive days. Seven blood samples over 9h were obtained each day to determine 6-MP pharmacokinetic parameters, including Tmax, Cmax, AUC0-9 and AUC0-∞. A questionnaire adapted to children testing Loulla palatability and preference...

  10. 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)

    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

  11. 不同糖代谢水平人群胰岛素分泌和胰岛素敏感性的分析%Differences in insulin sensitivity and insulin secretion in subjects with impaired glucose regulation

    Institute of Scientific and Technical Information of China (English)

    李国春; 巫开文; 袁辉; 周莉

    2013-01-01

    Objective To explore the defects in insulin secretion and insulin sensitivity contributing to the development and progression of type 2 diabetes mellitus(T2DM).Methods Plasma insulin and glucose were measured after oral glucose tolerance test (OGTT) to calculate the insulinognic index(IGI) , AUC ins12/0AUC glu120,HOMA-IR and Matsuda index in 267 subjects with normal glucose tolerance(NGT) ,prediabetes(preDM) ,and T2DM patients with disease duration 5 years.Results The mean IGI and AUC ins120/AUC glu120 levels were similar in NGT and preDM subjects(P>0.05) ,ins120/AUC glu120 levels was significantly decreased with the duration of diabetes, but with no difference of IGI.The mean Matsuda index decreased relative to the deteroration of glucose tolerance in NGT and preDM subjects(P=0.004) , however differences in the Matsuda index was not related to disease duration in T2DM(P>0.05).There was no significant difference in HOMA-IR to the impaired glucose regulation(P>0.05).Conclusion Defects in both insulin sensitivity and insulin secretion could contribute to T2DM,but decreased total insulin secretion might be more important in the progression of T2DM.The total insulin secretion might be play a even more important role in the progression of T2DM than early insulin secretion.%目的 研究胰岛素分泌和胰岛素敏感性在2型糖尿病(T2DM)发展和进程中的作用.方法 267例研究对象做口服葡萄糖耐量试验(OGTT),分别在0、30、60、90、120 min测葡萄糖和胰岛素水平,计算胰岛素分泌指数(IGI)、胰岛素抵抗指数(HOMA-IR)、120分钟胰岛素分泌(AUC ins120/AUC glu120)及Matsuda指数;依据OGTT结果及临床资料将研究对象分为糖耐量正常组(NGT),糖尿病前期组(preDM),糖尿病病程(DM)5年组,比较5组胰岛素分泌及胰岛素敏感性差异.结果 IGI和AUC ins120/AUC glu120在NGT、preDM组均无统计学差异(P>0.05);DM 5年组间 AUC ins120/AUC glu120显著降

  12. Diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis by measurement of microRNA abundance in blood and tissue.

    Directory of Open Access Journals (Sweden)

    Andrea S Bauer

    Full Text Available A solid process for diagnosis could have a substantial impact on the successful treatment of pancreatic cancer, for which currently mortality is nearly identical to incidence. Variations in the abundance of all microRNA molecules from peripheral blood cells and pancreas tissues were analyzed on microarrays and in part validated by real-time PCR assays. In total, 245 samples from two clinical centers were studied that were obtained from patients with pancreatic ductal adenocarcinoma or chronic pancreatitis and from healthy donors. Utilizing the minimally invasive blood test, receiver operating characteristic (ROC curves and the corresponding area under the curve (AUC analysis demonstrated very high sensitivity and specificity of a distinction between healthy people and patients with either cancer or chronic pancreatitis; respective AUC values of 0.973 and 0.950 were obtained. Confirmative and partly even more discriminative diagnosis could be performed on tissue samples with AUC values of 1.0 and 0.937, respectively. In addition, discrimination between cancer and chronic pancreatitis was achieved (AUC = 0.875. Also, several miRNAs were identified that exhibited abundance variations in both tissue and blood samples. The results could have an immediate diagnostic value for the evaluation of tumor reoccurrence in patients, who have undergone curative surgical resection, and for people with a familial risk of pancreatic cancer.

  13. In vivo antimicrobial activity of marbofloxacin against Pasteurella multocida in a tissue cage model in calves

    Directory of Open Access Journals (Sweden)

    Changfu eCao

    2015-07-01

    Full Text Available Marbofloxacin is a fluoroquinolone specially developed for use in veterinary medicine with broad-spectrum antibacterial activity. The objective of our study was to re-evaluate in vivo antimicrobial activity of marbofloxacin against Pasteurella multocida using subcutaneously implanted tissue cages in calves. Calves were infected by direct injection into tissue cages with Pasteurella multocida(type B, serotype 2, then intramuscularly received a range of marbofloxacin doses 24h after inoculation. The ratio of 24h area under the concentration-time curve divided by the minimum inhibitory concentration or the mutant prevention concentration (AUC24h/MIC or AUC24h/MPC was the pharmacokinetic-pharmacodynamic (PK/PD index that best described the effectiveness of marbofloxacin against Pasteurella multocida (R2=0.8514 by nonlinear regression analysis. Marbofloxacin exhibited a good antimicrobial activity in vivo. The levels of AUC24h/MIC and AUC24h/MPC that produced 50% (1.5log10CFU/mL reduction and 90% (3log10CFU/mL reduction of maximum response were 18.60h and 50.65h, 4.67h and 12.89h by using sigmoid Emax model WINNONLIN software, respectively. The in vivo PK/PD integrated methods by tissue cage model display the advantage of the evaluation of antimicrobial activity and the optimization of the dosage regimen for antibiotics in the presence of the host defenses, especially in target animal of veterinary interest.

  14. In vivo antimicrobial activity of marbofloxacin against Pasteurella multocida in a tissue cage model in calves.

    Science.gov (United States)

    Cao, Changfu; Qu, Ying; Sun, Meizhen; Qiu, Zhenzhen; Huang, Xianhui; Huai, Binbin; Lu, Yan; Zeng, Zhenling

    2015-01-01

    Marbofloxacin is a fluoroquinolone specially developed for use in veterinary medicine with broad-spectrum antibacterial activity. The objective of our study was to re-evaluate in vivo antimicrobial activity of marbofloxacin against Pasteurella multocida using subcutaneously implanted tissue cages in calves. Calves were infected by direct injection into tissue cages with P. multocida(type B, serotype 2), then intramuscularly received a range of marbofloxacin doses 24 h after inoculation. The ratio of 24 h area under the concentration-time curve divided by the minimum inhibitory concentration or the mutant prevention concentration (AUC24 h/MIC or AUC24 h/MPC) was the pharmacokinetic-pharmacodynamic (PK/PD) index that best described the effectiveness of marbofloxacin against P. multocida (R (2) = 0.8514) by non-linear regression analysis. Marbofloxacin exhibited a good antimicrobial activity in vivo. The levels of AUC24 h/MIC and AUC24 h/MPC that produced 50% (1.5log10 CFU/mL reduction) and 90% (3log10 CFU/mL reduction) of maximum response were 18.60 and 50.65 h, 4.67 and 12.89 h by using sigmoid Emax model WINNONLIN software, respectively. The in vivo PK/PD integrated methods by tissue cage model display the advantage of the evaluation of antimicrobial activity and the optimization of the dosage regimen for antibiotics in the presence of the host defenses, especially in target animal of veterinary interest.

  15. Using quantitative image analysis to classify axillary lymph nodes on breast MRI: A new application for the Z 0011 Era

    Energy Technology Data Exchange (ETDEWEB)

    Schacht, David V., E-mail: dschacht@radiology.bsd.uchicago.edu; Drukker, Karen, E-mail: kdrukker@uchicago.edu; Pak, Iris, E-mail: irisgpak@gmail.com; Abe, Hiroyuki, E-mail: habe@radiology.bsd.uchicago.edu; Giger, Maryellen L., E-mail: m-giger@uchicago.edu

    2015-03-15

    Highlights: •Quantitative image analysis showed promise in evaluating axillary lymph nodes. •13 of 28 features performed better than guessing at metastatic status. •When all features were used in together, a considerably higher AUC was obtained. -- Abstract: Purpose: To assess the performance of computer extracted feature analysis of dynamic contrast enhanced (DCE) magnetic resonance images (MRI) of axillary lymph nodes. To determine which quantitative features best predict nodal metastasis. Methods: This institutional board-approved HIPAA compliant study, in which informed patient consent was waived, collected enhanced T1 images of the axilla from patients with breast cancer. Lesion segmentation and feature analysis were performed on 192 nodes using a laboratory-developed quantitative image analysis (QIA) workstation. The importance of 28 features were assessed. Classification used the features as input to a neural net classifier in a leave-one-case-out cross-validation and evaluated with receiver operating characteristic (ROC) analysis. Results: The area under the ROC curve (AUC) values for features in the task of distinguishing between positive and negative nodes ranged from just over 0.50 to 0.70. Five features yielded AUCs greater than 0.65: two morphological and three textural features. In cross-validation, the neural net classifier obtained an AUC of 0.88 (SE 0.03) for the task of distinguishing between positive and negative nodes. Conclusion: QIA of DCE MRI demonstrated promising performance in discriminating between positive and negative axillary nodes.

  16. Caffeine intake in pregnancy: Relationship between internal intake and effect on birth weight.

    Science.gov (United States)

    Partosch, F; Mielke, H; Stahlmann, R; Gundert-Remy, U

    2015-12-01

    We used a physiologically based kinetic model to simulate caffeine blood concentration-time profiles in non-pregnant and pregnant women. The model predicted concentration-time profile was in good accordance with experimental values. With 200 mg, the safe dose per occasion in non-pregnant women, AUC and peak concentration in pregnant women were nearly twice that of non-pregnant women. In order to derive a safe dose for the pregnant women we estimated the dose in the pregnant women model taken at once which would not exceed AUC and peak concentration in the non-pregnant women of 200 mg as single dose. The resulting dose is 100 mg caffeine per occasion which we recommend as safe. The caffeine dose of 200 mg per day is declared as safe for pregnant women with respect to the foetus by EFSA based on results on reduced birth weight in epidemiological studies. We modelled AUC and peak concentration for different caffeine doses to investigate the relationship between internal caffeine exposure and risk measures of reduced birth weight from epidemiological studies. The graphical analysis revealed that the reduction in birth weight was related to AUC and peak concentration up to a dose of 250 mg caffeine. PMID:26549379

  17. Procalcitonin Improves the Glasgow Prognostic Score for Outcome Prediction in Emergency Patients with Cancer: A Cohort Study

    Directory of Open Access Journals (Sweden)

    Anna Christina Rast

    2015-01-01

    Full Text Available The Glasgow Prognostic Score (GPS is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT, white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males, 81 (23.8% died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67 for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9, P<0.001, AUC 0.69 and significantly improved the GPS to a combined AUC of 0.74 (P=0.007. Considering all investigated biomarkers, the AUC increased to 0.76 (P<0.001. The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventional trials.

  18. Prognostic Aspects of DCE-MRI in Recurrent Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gollub, M.J.; Gultekin, D.H.; Sohn, M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Cao, K. [Peking University Cancer Hospital and Institute, Department of Radiology, Beijing (China); Kuk, D.; Gonen, M. [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Schwartz, L.H. [Columbia University Medical Center/New York Presbyterian Hospital, Department of Radiology, New York, NY (United States); Weiser, M.R.; Temple, L.K.; Nash, G.M.; Guillem, J.G.; Garcia-Aguilar, J.; Paty, P.B. [Memorial Sloan-Kettering Cancer Center, Department of Surgery, New York, NY (United States); Wang, M. [Fudan University Shanghai Cancer Center, Department of Colorectal Surgery, Shanghai (China); Goodman, K. [Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY (United States)

    2013-12-15

    To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K{sup trans}, K{sub ep}, V{sub e}, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K{sup trans} (0.55, P = 0.012) and K{sub ep} (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K{sup trans}, K{sub ep}, V{sub e}, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. K{sup trans} and K{sub ep} were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation. (orig.)

  19. CT colonography: effect of computer-aided detection of colonic polyps as a second and concurrent reader for general radiologists with moderate experience in CT colonography

    Energy Technology Data Exchange (ETDEWEB)

    Mang, Thomas; Ringel, Helmut; Weber, Michael [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Bogoni, Luca; Anand, Vikram X.; Hermosillo, Gerardo; Raykar, Vikas; Salganicoff, Marcos; Wolf, Matthias [H IM SY US, Siemens Medical Solutions, Malvern, PA (United States); Chandra, Dass [Temple University, Philadelphia, PA (United States); Curtin, Andrew J. [Tristate Imaging Consultants, Abington, PA (United States); Lev-Toaff, Anna S. [University of Pennsylvania, Philadelphia, PA (United States); Noah, Ralph [Diagnostic Imaging Associates, Wilmington, DE (United States); Shaw, Robert [The Chester County Hospital, West Chester, PA (United States); Summerton, Susan [Albert Einstein Medical Center, Philadelphia, PA (United States); Tappouni, Rafel F.R. [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Obuchowski, Nancy A. [Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio (United States)

    2014-07-15

    To assess the effectiveness of computer-aided detection (CAD) as a second reader or concurrent reader in helping radiologists who are moderately experienced in computed tomographic colonography (CTC) to detect colorectal polyps. Seventy CTC datasets (34 patients: 66 polyps ≥6 mm; 36 patients: no abnormalities) were retrospectively reviewed by seven radiologists with moderate CTC experience. After primary unassisted evaluation, a CAD second read and, after a time interval of ≥4 weeks, a CAD concurrent read were performed. Areas under the receiver operating characteristic (ROC) curve (AUC), along with per-segment, per-polyp and per-patient sensitivities, and also reading times, were calculated for each reader with and without CAD. Of seven readers, 86 % and 71 % achieved a higher accuracy (segment-level AUC) when using CAD as second and concurrent reader respectively. Average segment-level AUCs with second and concurrent CAD (0.853 and 0.864) were significantly greater (p < 0.0001) than average AUC in the unaided evaluation (0.781). Per-segment, per-polyp, and per-patient sensitivities for polyps ≥6 mm were significantly higher in both CAD reading paradigms compared with unaided evaluation. Second-read CAD reduced readers' average segment and patient specificity by 0.007 and 0.036 (p = 0.005 and 0.011), respectively. CAD significantly improves the sensitivities of radiologists moderately experienced in CTC for polyp detection, both as second reader and concurrent reader. (orig.)

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  1. Diagnosis of IPA in HIV: The role of the chest X-ray and radiologist

    Energy Technology Data Exchange (ETDEWEB)

    Zaspel, Uta [Charite - Universitaetsmedizin Berlin, Institut fuer Radiologie, Berlin (Germany); Denning, David W. [The University of Manchester, Education and Research Centre, Wythenshawe Hospital, Manchester (United Kingdom); Lemke, Arne J.; Roettgen, Rainer; Bittner, Roland; Oestmann, Joerg W. [Charite - Universitaetsmedizin Berlin, Klinik fuer Strahlenheilkunde, Berlin (Germany); Greene, Reginald [Massachusetts General Hospital, Department of Radiology, Harvard Medical School, Boston (United States); Schuermann, Dirk [Charite - Universitaetsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Infektiologie und Asthma-Poliklinik, Berlin (Germany); Maschmeyer, Georg [Charite - Universitaetsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Haematologie und Onkologie, Berlin (Germany); Ruhnke, Markus [Charite - Universitaetsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Onkologie und Haematologie, Berlin (Germany); Herbrecht, Raoul [Hopital de Hautepierre, Department d' Hematologie et d' Oncologie, Strasbourg (France); Ribaud, Patricia [Hopital Saint-Louis, Service d' Hematologie, Paris (France); Lortholary, Olivier [Universite Paris V, Centre National de Reference des Mycoses et des Antifongiques, Institut Pasteur, Service des Maladies Infectieuses et Tropicales, Hopital Necker, Paris (France); Zonderland, Harmien [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands); Rabe, Klaus F. [Leiden University Medical Centre, Department of Pulmology, Leiden (Netherlands); Neumann, Klaus [Krankenhaus und Herzzentrum Bernau, Bernau (Germany)

    2004-11-01

    The role of clinical information and chest film for the discrimination between invasive pulmonary aspergillosis (IPA) and its differential diagnoses in human immunodeficiency virus (HIV) infection was studied. The diagnostic performance of clinical information and chest film alone and in combination was studied for eight internists and eight radiologists with regular exposure to IPA patients. The multicenter case sample consisted of 25 patients with proven IPA and 25 with other pulmonary diseases typical for HIV. The cases were presented on a CD-ROM. Receiver operating characteristics (ROC) methodology was employed. With clinical information alone, internists achieved the highest diagnostic performance (area under curve/AUC=0.84). Viewing the chest films did not contribute to their performance (AUC=0.80, P=0.26). The radiologist's performance on the basis of viewing the chest film (AUC=0.75) increased significantly (P=0.012) when clinical information (AUC=0.83) was supplied. IPA cases with characteristic radiological appearance were correctly identified in 90% with chest film. For radiologists with regular exposure to HIV patients, chest films hold relevant information and contribute to the determination in cases with characteristic radiological appearance. Overall and especially in cases with less characteristic radiological appearance, they have significant profit from full access to the clinical data. For internists with regular exposure to HIV patients, chest films do not provide information essential for the verification or differentiation of potential IPA. (orig.)

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVES: Compare the area under the receiver operating characteristic curve (AUC) vs. the area under the precision-recall curve (AUPRC) in summarizing the performance of a diagnostic biomarker according to the disease prevalence. STUDY DESIGN AND SETTING: A simulation study was performed...

  3. Does image reduction affect the diagnostic accuracy of digital mammograms?

    Science.gov (United States)

    Takane, Yumi; Kawasumi, Yusuke; Horie, Tsunemitsu; Ishibashi, Tadashi

    2013-03-01

    We aimed to evaluate the influence of image reduction using a bi-cubic interpolation method on the accuracy of detection of clustered microcalcifications (MCLs) and masses on digital mammograms. Digital mammograms (n=194) of 97 subjects were selected retrospectively, comprising 47 patients with clustered MCLs or masses and 52 controls. Images were acquired in the craniocaudal view by phase-contrast mammography (PCM). Original PCM images comprised 25-μm pixels. The reduced images converted from the originals by bi-cubic interpolation were of 50-μm pixel size. Five observers independently interpreted all images, and rated their confidence concerning the presence of lesions on a continuous 0-100 scale. Receiver-operating characteristic (ROC) analysis was performed using the jackknife method and LABMRMC program. Differences in areas under the curve (AUC) values based on 95% confidence intervals were evaluated. The average AUC values for detection of masses were 0.8435 and 0.8646 for the original and reduced images, respectively. The difference between the average AUC values was not statistically significant (p=0.5855). Average AUC values for clustered MCLs detection were 0.9273 and 0.9574 for the original and reduced images, respectively. This difference was not statistically significant (p=0.1949). Detection of masses and clustered MCLs on digital mammograms was unaffected by bi-cubic interpolation image reduction.

  4. CT colonography: effect of computer-aided detection of colonic polyps as a second and concurrent reader for general radiologists with moderate experience in CT colonography

    International Nuclear Information System (INIS)

    To assess the effectiveness of computer-aided detection (CAD) as a second reader or concurrent reader in helping radiologists who are moderately experienced in computed tomographic colonography (CTC) to detect colorectal polyps. Seventy CTC datasets (34 patients: 66 polyps ≥6 mm; 36 patients: no abnormalities) were retrospectively reviewed by seven radiologists with moderate CTC experience. After primary unassisted evaluation, a CAD second read and, after a time interval of ≥4 weeks, a CAD concurrent read were performed. Areas under the receiver operating characteristic (ROC) curve (AUC), along with per-segment, per-polyp and per-patient sensitivities, and also reading times, were calculated for each reader with and without CAD. Of seven readers, 86 % and 71 % achieved a higher accuracy (segment-level AUC) when using CAD as second and concurrent reader respectively. Average segment-level AUCs with second and concurrent CAD (0.853 and 0.864) were significantly greater (p < 0.0001) than average AUC in the unaided evaluation (0.781). Per-segment, per-polyp, and per-patient sensitivities for polyps ≥6 mm were significantly higher in both CAD reading paradigms compared with unaided evaluation. Second-read CAD reduced readers' average segment and patient specificity by 0.007 and 0.036 (p = 0.005 and 0.011), respectively. CAD significantly improves the sensitivities of radiologists moderately experienced in CTC for polyp detection, both as second reader and concurrent reader. (orig.)

  5. Increased Systemic Exposure of Methotrexate by a Polyphenol-Rich Herb via Modulation on Efflux Transporters Multidrug Resistance-Associated Protein 2 and Breast Cancer Resistance Protein.

    Science.gov (United States)

    Yu, Chung-Ping; Hsieh, Yun-Chung; Shia, Chi-Sheng; Hsu, Pei-Wen; Chen, Jen-Yuan; Hou, Yu-Chi; Hsieh, Yo-Wen

    2016-01-01

    Scutellariae radix (SR, roots of Scutellaria baicalensis Georgi), a popular Chinese medicine, contains plenty of flavonoids such as baicalin, wogonoside, baicalein, and wogonin. Methotrexate (MTX), an important immunosuppressant with a narrow therapeutic index, is a substrate of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). This study investigated the effect of SR on MTX pharmacokinetics and the underlying mechanisms. Rats were orally administered MTX alone and with 1.0 or 2.0 g/kg of SR. The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. Cell models were used to explore the involvement of MRP2 and BCRP in the interaction. The results showed that 1.0 g/kg of SR significantly increased Cmax, AUC(0-30), AUC(0-2880), and mean residence time (MRT) of MTX by 50%, 45%, 501%, and 347%, respectively, and 2.0 g/kg of SR significantly enhanced the AUC(0-2880) and MRT by 242% and 293%, respectively, but decreased AUC(0-30) by 41%. Cell line studies indicated that SR activated the BCRP-mediated efflux transport, whereas the serum metabolites of SR inhibited both the BCRP- and MRP2-mediated efflux transports. In conclusion, SR ingestion increased the systemic exposure and MRT of MTX via modulation on MRP2 and BCRP.

  6. Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

    Directory of Open Access Journals (Sweden)

    Ryota Uchida

    2015-09-01

    Full Text Available α-Lipoic acid (LA is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA and S-α-lipoic acid (SLA mixed at the ratio of 50:50 to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C0, AUC, and half-life (T1/2 of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (FaFg and hepatic availability (Fh, and not from the total clearance.

  7. Development and validation of a nomogram for prediction of survival and local control in laryngeal carcinoma patients treated with radiotherapy alone: A cohort study based on 994 patients

    International Nuclear Information System (INIS)

    Introduction: To advise laryngeal carcinoma patients on the most appropriate form of treatment, a tool to predict survival and local control is needed. Materials and methods: We performed a population-based cohort study on 994 laryngeal carcinoma patients, treated with RT from 1977 until 2008. Two nomograms were developed and validated. Performance of the models is expressed as the Area Under the Curve (AUC). Results: Unfavorable prognostic factors for overall survival were low hemoglobin level, male sex, high T-status, nodal involvement, older age, lower EQD2T (total radiation dose corrected for fraction dose and overall treatment time), and non-glottic tumor. All factors except tumor location were prognostic for local control. The AUCs were 0.73 for overall survival and 0.67 for local control. External validation of the survival model yielded AUCs of 0.68, 0.74, 0.76 and 0.71 for the Leuven (n = 109), the VU Amsterdam (n = 178), the Manchester (n = 403) and the NKI cohort (n = 205), respectively, while the validation procedure for the local control model resulted in AUCs of 0.70, 0.71, 0.72 and 0.62. The resulting nomograms were made available on the website (www.predictcancer.org). Conclusions: For patients with a laryngeal carcinoma treated with RT alone, we have developed visual, easy-to-use nomograms for the prediction of overall survival and primary local control. These models have been successfully validated in four external centers.

  8. Reduced serum selenoprotein P concentrations in German prostate cancer patients.

    Science.gov (United States)

    Meyer, Hellmuth-Alexander; Hollenbach, Birgit; Stephan, Carsten; Endermann, Tobias; Morgenthaler, Nils G; Cammann, Henning; Köhrle, Josef; Jung, Klaus; Schomburg, Lutz

    2009-09-01

    Selenium (Se) is essentially needed for the biosynthesis of selenoproteins. Low Se intake causes reduced selenoprotein biosynthesis and constitutes a risk factor for tumorigenesis. Accordingly, some Se supplementation trials have proven effective to reduce prostate cancer risk, especially in poorly supplied individuals. Because Se metabolism is controlled by selenoprotein P (SEPP), we have tested whether circulating SEPP concentrations correlate to prostate cancer stage and grade. A total of 190 men with prostate cancer (n = 90) and "no evidence of malignancy" (NEM; n = 100) histologically confirmed by prostate biopsy were retrospectively analyzed for established tumor markers and for their Se and SEPP status. Prostate specific antigen (PSA), free PSA, total Se, and SEPP concentrations were determined from serum samples and compared with clinicopathologic parameters. The diagnostic performance was analyzed with receiver operating characteristic curves. Median Se and SEPP concentrations differed significantly (P curve (AUC) of a marker combination with age, PSA, and percent free PSA (%fPSA) in combination with the SEPP concentration, yielded the highest diagnostic value (AUC 0.80) compared with the marker combination without SEPP (AUC 0.77) or %fPSA (AUC 0.76). We conclude that decreased SEPP concentration in serum might represent an additional valuable marker for prostate cancer diagnostics. PMID:19690186

  9. Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I) to ADH 3 (Class III) in Mouse.

    Science.gov (United States)

    Haseba, Takeshi; Kameyama, Kouji; Mashimo, Keiko; Ohno, Youkichi

    2012-01-01

    ADH 1 and ADH 3 are major two ADH isozymes in the liver, which participate in systemic alcohol metabolism, mainly distributing in parenchymal and in sinusoidal endothelial cells of the liver, respectively. We investigated how these two ADHs contribute to the elimination kinetics of blood ethanol by administering ethanol to mice at various doses, and by measuring liver ADH activity and liver contents of both ADHs. The normalized AUC (AUC/dose) showed a concave increase with an increase in ethanol dose, inversely correlating with β. CL(T) (dose/AUC) linearly correlated with liver ADH activity and also with both the ADH-1 and -3 contents (mg/kg B.W.). When ADH-1 activity was calculated by multiplying ADH-1 content by its V(max⁡)/mg (4.0) and normalized by the ratio of liver ADH activity of each ethanol dose to that of the control, the theoretical ADH-1 activity decreased dose-dependently, correlating with β. On the other hand, the theoretical ADH-3 activity, which was calculated by subtracting ADH-1 activity from liver ADH activity and normalized, increased dose-dependently, correlating with the normalized AUC. These results suggested that the elimination kinetics of blood ethanol in mice was dose-dependently changed, accompanied by a shift of the dominant metabolizing enzyme from ADH 1 to ADH 3.

  10. Circadian variation in the pharmacokinetics of verapamil

    DEFF Research Database (Denmark)

    Jespersen, C M; Frederiksen, M; Hansen, J F;

    1989-01-01

    greater bioavailability (AUC) and a prolonged time to peak concentration was found. During the night (24.00 h-06.00 h) the half-life of verapamil was significantly longer than during the day (16.00 h-22.00 h). These differences in pharmacokinetics may be due to reduced hepatic blood flow at night...

  11. Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction

    Science.gov (United States)

    Brantley, S J; Gufford, B T; Dua, R; Fediuk, D J; Graf, T N; Scarlett, Y V; Frederick, K S; Fisher, M B; Oberlies, N H; Paine, M F

    2014-01-01

    Herb–drug interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential herb–drug interactions using the semipurified milk thistle preparation, silibinin, as an exemplar herbal product. Interactions between silibinin constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A) were simulated. A low silibinin dose (160 mg/day × 14 days) was predicted to increase midazolam area under the curve (AUC) by 1%, which was corroborated with external data; a higher dose (1,650 mg/day × 7 days) was predicted to increase midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept clinical study confirmed minimal interaction between high-dose silibinin and both midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively). Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be clinically important. Application of this PBPK modeling framework to other herb–drug interactions could facilitate development of guidelines for quantitative prediction of clinically relevant interactions. PMID:24670388

  12. 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. PMID:21432621

  13. Bioequivalence study of two oral tablet formulations containing tenofovir disoproxil fumarate in healthy volunteers.

    Science.gov (United States)

    Yerino, Gustavo A; Halabe, Emilia K; Zini, Elvira; Feleder, Ethel C

    2011-01-01

    Tenofovir disoproxil fumarate (TDF, CAS 147127-20-6) is a nucleotide reverse transcriptase inhibitor which is indicated in combination with other antiretroviral agents for the management of HIV-1 infection. The objective of this study was to compare the rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 300 mg of TDF and the innovator product. A randomized, single-center, open-label, single-dose, two-way crossover bioequivalence study in 40 healthy adult subjects was conducted. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 48 h and plasma levels of tenofovir (TFV) were determined by a validated HPLC assay. Rate and extent of absorption were similar between products. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence between the two formulations using the equivalence interval of 80 and 125%. In healthy subjects, the point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 0.99 (0.92-1.02), 0.99 (0.95-1.03) and 0.93 (0.85-1.02), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator. PMID:21355446

  14. Simulation study for the purification of depleted uranium product in FBTR fuel reprocessing

    International Nuclear Information System (INIS)

    A method is developed for the purification of depleted uranium product obtained after partitioning of uranium and plutonium in the third cycle of FBTR fuel reprocessing. Uranium and plutonium were partitioned and recovered by AUC method. It is observed from the study that plutonium recovery is quantitative (100%) if Pu concentration is 0.6 g/L. (author)

  15. Comparison of Simple Versus Performance-Based Fall Prediction Models

    Directory of Open Access Journals (Sweden)

    Shekhar K. Gadkaree BS

    2015-05-01

    Full Text Available Objective: To compare the predictive ability of standard falls prediction models based on physical performance assessments with more parsimonious prediction models based on self-reported data. Design: We developed a series of fall prediction models progressing in complexity and compared area under the receiver operating characteristic curve (AUC across models. Setting: National Health and Aging Trends Study (NHATS, which surveyed a nationally representative sample of Medicare enrollees (age ≥65 at baseline (Round 1: 2011-2012 and 1-year follow-up (Round 2: 2012-2013. Participants: In all, 6,056 community-dwelling individuals participated in Rounds 1 and 2 of NHATS. Measurements: Primary outcomes were 1-year incidence of “any fall” and “recurrent falls.” Prediction models were compared and validated in development and validation sets, respectively. Results: A prediction model that included demographic information, self-reported problems with balance and coordination, and previous fall history was the most parsimonious model that optimized AUC for both any fall (AUC = 0.69, 95% confidence interval [CI] = [0.67, 0.71] and recurrent falls (AUC = 0.77, 95% CI = [0.74, 0.79] in the development set. Physical performance testing provided a marginal additional predictive value. Conclusion: A simple clinical prediction model that does not include physical performance testing could facilitate routine, widespread falls risk screening in the ambulatory care setting.

  16. Paclitaxel and carboplatin concurrent with radiotherapy for primary cervical cancer

    NARCIS (Netherlands)

    De Vos, FYFL; Bos, AME; Gietema, JA; Pras, E; Van Der Zee, AGJ; De Vries, EGE; Willemse, PHB

    2004-01-01

    Background: Concurrent radiochemotherapy is currently considered the new standard treatment in locally advanced cervical cancer. Patients and Methods: Eight women with cervical cancer stage IB2-IVA were treated with standard radiation therapy in combination with standard carboplatin (AUC=2, once wee

  17. Preface and Program

    Directory of Open Access Journals (Sweden)

    Päivi Soppela

    2002-04-01

    Full Text Available A group of PhD students, post-doctoral scientists and senior scientists gathered together in Tromsø, August 1999 for the 1st CAES Workshop 'Reindeer 2000', in conjunction with the 10th Arctic Ungulate Conference (AUC. The purpose of the workshop was to stimulate the interdisciplinary approach and communication in studies relating to reindeer and reindeer husbandry.

  18. Interchangeability of two 500 mg amoxicillin capsules with one 1000 mg amoxicillin tablet after a single oral administration

    Directory of Open Access Journals (Sweden)

    Zaid A

    2010-01-01

    Full Text Available The aim of the study was to evaluate if two capsules (Amoxil® capsules, 500 mg/capsule and one tablet (Amoxicare® tablets, 1000 mg/tablet of amoxicillin have similar bioequivalence parameters. For this purpose a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers, divided into two groups of 12 subjects each. One group was treated with the reference standard (Amoxil® and the other one with the generic tablet Amoxicare® , with a crossover after a wash-out period of 7 days. Blood samples were collected at fixed time intervals and amoxicillin was determined by a validated HPLC method. The pharmacokinetic parameters AUC 0-8 , AUC 0-͵, C max , T max , K e and T 1/2 were determined for both formulations and statistically compared to evaluate the bioequivalence between the two brands of amoxicillin, using the statistical model recommended by the FDA. C max and AUC 0-͵ were statistically analyzed using analysis of variance (ANOVA; no statistically significant difference was observed between the two formulations. The 90% confidence intervals between the mean values of C max and AUC 0-͵ fall within the FDA specified bioequivalent limits (80-125% suggesting that the two products are bioequivalent and the two formulations are interchangeable. Based on these findings it was concluded that the practice of interchangeability between the above formulations to achieve better patient compliance could be followed without compromising the extent of amoxicillin absorption.

  19. Concentrations of gemifloxacin at the target site in healthy volunteers after a single oral dose.

    Science.gov (United States)

    Islinger, Florian; Bouw, Rene; Stahl, Mathias; Lackner, Edith; Zeleny, Petra; Brunner, Martin; Müller, Markus; Eichler, Hans Georg; Joukhadar, Christian

    2004-11-01

    Free gemifloxacin concentrations in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were measured by means of in vivo microdialysis to characterize the ability of gemifloxacin to penetrate human soft tissues. Twelve healthy volunteers received a single oral dose of 320 mg of gemifloxacin. The mean areas under the concentration-time curves from 0 to 10 h (AUC(0-10)) were significantly higher for soft tissue than for unbound gemifloxacin in plasma (P < 0.05). The ratios of the mean AUC(0-10) for tissue to the AUC(0-10) for free gemifloxacin in plasma were 1.7 +/- 0.7 (mean +/- standard deviation) for skeletal muscle and 2.4 +/- 1.0 for adipose tissue. The AUC(0-24) ratios for free gemifloxacin in tissues to the MIC at which 90% of frequently isolated bacteria are inhibited were close to or higher than 100 h. Therefore, based on pharmacokinetic and pharmacodynamic calculations, we conclude that gemifloxacin might be a useful therapeutic option for the treatment of soft tissue infections. PMID:15504848

  20. Influence of food on the oral bioavailability of deramciclane from film-coated tablet in healthy male volunteers.

    Science.gov (United States)

    Drabant, Sándor; Nemes, Katalin Balogh; Horváth, Viola; Tolokán, Antal; Grézal, Gyula; Anttila, Markku; Gachályi, Béla; Kanerva, Harri; Al-Behaisi, Samar; Horvai, George; Klebovich, Imre

    2004-11-01

    The effect of a high-fat meal on the oral bioavailability of deramciclane 30 mg tablet was evaluated in 18 healthy male volunteers in a randomised, single dose, two-way crossover study. The drug was administered following an overnight fast or a standardised high-fat breakfast. The plasma concentrations of deramciclane and N-desmethylderamciclane were determined by using a validated HPLC-MS -MS/MS method. An effect of food on the bioavailability was indicated if the 90% confidence interval (CI) for the ratio of geometric means of fed and fasted treatments was not contained in the equivalence limit of 0.8-1.25 for AUC and C(max). The ratios of the mean C(max) and AUC(0-infinity) values of deramciclane were 1.24 (90% CI 1.12-1.38) and 1.31 (90% CI 1.21-1.41) in fed versus fasted subjects, which overlapped but exceeded the equivalence limit. In contrast to the parent compound, the 90% CI of the mean ratios for AUC(0-infinity) and C(max) of N-desmethylderamciclane were within the predefined range. The 24 and 31% increase in C(max) and AUC(0-infinity) of deramciclane, respectively, under fed condition is modest and probably has no clinical significance since it is relatively small compared to the inter-individual variability of these parameters.

  1. Influence of Fructooligosaccharide on Pharmacokinetics of Isoflavones in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Supanimit Teekachunhatean

    2012-01-01

    Full Text Available The objective of the present paper was to determine the influence of fructooligosaccharide (FOS on the pharmacokinetics of isoflavones in healthy postmenopausal women. The study was a fixed-sequence, two-phase, crossover study. Twelve subjects received a single oral dose of 300 mL of a soy beverage. Blood samples were collected before the dose and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, and 32 h after the administration of the soy beverage. After a washout period of at least 1 week, subjects were assigned to receive oral doses of FOS, 5 g each time, twice a day (after breakfast and dinner for 14 days, followed by a single oral dose of the same soy beverage on the next day. Blood samples were then collected at the same time points mentioned previously. Plasma isoflavone concentrations were determined by HPLC. Continuous oral administrations of FOS followed by a single oral administration of soy beverage caused significant increases in Cmax, AUC0–32, and AUC0–∞ of genistein and AUC0–32 of daidzein, comparing to those obtained following a single oral dose of soy beverage alone. Other pharmacokinetic parameters (Tmax and t1/2 of both aglycones and AUC0–∞ of daidzein between both regimens were not significantly different.

  2. PLATELET INHIBITORY ACTIVITY AND PHARAMCOKINETCS OF PRASUGREL A NOVEL THIENOPYRIDINE P2Y12 INHIBITOR: A SINGLE DOSE CROSS OVER BIOEQUIVALENCE STUDY IN HEALTHY HUMAN VOLUNTEERS

    Directory of Open Access Journals (Sweden)

    Sahu Nimain Charan

    2013-08-01

    Full Text Available To compare the bioavailability and bioequivalence of two prasugrel formulations one as a test and the other was the standard. The study was performed according to a randomized, open label, balanced, two-treatment, two-period, two-sequence, single-dose, crossover under fasting period with minimum of seven days wash-out period and was evaluated in 20(+ 2 stand by subjects. To analyse pharmacokinetic properties, the blood samples were drawn taken up to 36 h after dosing. Plasma concentration of prasugrel was determined using liquid chromatography – tandem mass spectrometry method. Pharmacokinetic parameters tmax, Cmax, AUC0-t, AUC0-, t1/2 and λz (Kel were tested for bioequivalence after log-transformation of data and non-parametric evaluation was done for ratios of tmax. The point estimates and 90 % confidence intervals (CI for AUC0-t, AUC0-∞, and Cmax for active metabolite (R-138727 were 95.82-105.18, 96.00-104.69 and 90.80-103.20 respectively. These results indicated that the two formulations of Prasugrel were bioequivalent in case of active metabolite (R-138727, thus may be prescribed interchangeably.

  3. An automated method for nonparametric kinetic analysis of clinical DCE-MRI data: application to glioblastoma treated with bevacizumab.

    Science.gov (United States)

    Ferl, Gregory Z; Xu, Lu; Friesenhahn, Michel; Bernstein, Lisa J; Barboriak, Daniel P; Port, Ruediger E

    2010-05-01

    Here, we describe an automated nonparametric method for evaluating gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) kinetics, based on dynamic contrast-enhanced-MRI scans of glioblastoma patients taken before and after treatment with bevacizumab; no specific model or equation structure is assumed or used. Tumor and venous blood concentration-time profiles are smoothed, using a robust algorithm that removes artifacts due to patient motion, and then deconvolved, yielding an impulse response function. In addition to smoothing, robustness of the deconvolution operation is assured by excluding data that occur prior to the plasma peak; an exhaustive analysis was performed to demonstrate that exclusion of the prepeak plasma data does not significantly affect results. All analysis steps are executed by a single R script that requires blood and tumor curves as the sole input. Statistical moment analysis of the Impulse response function yields the area under the curve (AUC) and mean residence time (MRT). Comparison of deconvolution results to fitted Tofts model parameters suggests that AUCMRT and AUC of the Impulse response function closely approximate fractional clearance from plasma to tissue (K(trans)) and fractional interstitial volume (v(e)). Intervisit variability is shown to be comparable when using the deconvolution method (11% [AUCMRT] and 13%[AUC]) compared to the Tofts model (14%[K(trans)] and 24%[v(e)]). AUC and AUCMRT both exhibit a statistically significant decrease (P < 0.005) 1 day after administration of bevacizumab. PMID:20432307

  4. An Approach for Predicting Essential Genes Using Multiple Homology Mapping and Machine Learning Algorithms

    Science.gov (United States)

    Hua, Hong-Li; Zhang, Fa-Zhan; Labena, Abraham Alemayehu; Dong, Chuan; Jin, Yan-Ting

    2016-01-01

    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.

  5. Evaluation of the diagnostic value of tumor markers with ROC and logistic regression in gastrocolic tumors

    Institute of Scientific and Technical Information of China (English)

    Jinbo Liu; Mingsu Zhou; Yonglun Hang; Meizhu Cai; Min Song; Ting Ye; Kaizheng Wang

    2011-01-01

    Objective: The aim of the study was to evaluate the clinical significance of multiple tumor markers (CEA, AFP, CA72-4 and CA19-9) in patients with gastrocolic tumors by receiver operating characteristic (ROC) curve and stepwise lo-gistic regression (LR) analysis. Methods: The serum concentrations of CEA, AFP, CA72-4 and CA19-9 were measured with electrochemiluminescence immunoassay in 126 patients with gastrocolic tumors, 137 patients with benign gastrocolic disorders and 109 healthy controls. The area under the ROC curve (AUC) of CEA, AFP, CA72-4 and CA19-9 and stepwise LR results were compared by sensitivity, specificity, Youden's index and positive likelihood ratio/negative likelihood ratio. Results: The levels of four tested tumor markers in patients with gastrocolic tumors were significantly higher than those in benign gas-trocolic group and normal controls. In the benign gastrocolic group, the AUC from stepwise logistic regression was larger than the AUC of four tumor markers respectively. Sensitivity, Youden's index and positive likelihood ratio/negative likelihood ratio were the highest in the combination assay of CA72-4, CEA, and CA19-9, as compared with one of the tumor markers alone. Conclusion: The use of ROC established by LR analysis model improved the diagnostic accuracy of gastrocolic tumors. For the screening of gastrocolic tumors, the AUC value of the combination probability index (sensitivity and specificity) was significantly higher than the values of the different tumour markers.

  6. Methimazole increases the plasma concentrations of the albendazole metabolites of netobimin in sheep.

    Science.gov (United States)

    Lanusse, C E; Prichard, R K

    1992-03-01

    The influence of methimazole (MTZ) on the pharmacokinetics of netobimin (NTB) and its metabolites was investigated in adult sheep. NTB zwitterion suspension was administered at 20 mg kg-1 by intraruminal injection either alone or with simultaneous administration of MTZ intramuscularly at 1.5 mg kg-1. Blood samples were taken serially over a 120-h period and plasma was analysed by HPLC for NTB, albendazole (ABZ), albendazole sulphoxide (ABZSO), and albendazole sulphone (ABZSO2). NTB parent drug showed fast absorption, low area under the plasma concentration-time curve (AUC) and was rapidly removed from plasma after both treatments. The presence of MTZ did increase significantly the ABZ AUC (138 per cent) and mean residence time (MRT) (86 per cent). Concomitant treatment with MTZ resulted in a notably higher ABZSO plasma profile with significantly longer elimination half-life (t1/2 beta) (390 per cent) and MRT (252 per cent) and with significantly higher AUC (95 per cent). Also, MTZ induced significant increases in ABZSO2 t1/2 beta, AUC, and MRT. We have demonstrated a pharmacokinetic interaction between MTZ and NTB metabolites. MTZ may alter the liver biotransformation of ABZ metabolites which results in pronounced changes in the disposition kinetics of anthelmintically active metabolites. PMID:1550912

  7. Prediction models for platinum-based chemotherapy response and toxicity in advanced NSCLC patients.

    Science.gov (United States)

    Yin, Ji-Ye; Li, Xi; Li, Xiang-Ping; Xiao, Ling; Zheng, Wei; Chen, Juan; Mao, Chen-Xue; Fang, Chao; Cui, Jia-Jia; Guo, Cheng-Xian; Zhang, Wei; Gao, Yang; Zhang, Chun-Fang; Chen, Zi-Hua; Zhou, Hui; Zhou, Hong-Hao; Liu, Zhao-Qian

    2016-07-10

    In this study, we aimed to establish a platinum-based chemotherapy response and toxicity prediction model in advanced non-small cell lung cancer (NSCLC) patients. 416 single nucleotide polymorphisms (SNPs) in 185 genes were genotyped, and their association with drug response and toxicity were estimated using logistic regression. Nine data mining techniques were employed to establish the prediction model; the sensitivity, specificity, overall accuracy and receiver operating characteristic (ROC) curve were used to assess the models' performance. Finally, selected models were validated in an independent cohort. The models established by naïve Bayesian algorithm had the best performance. The response prediction model achieved a sensitivity of 0.90 and a specificity of 0.47 with the ROC area under curve (AUC) of 0.80. The overall toxicity prediction model achieved a sensitivity of 0.86 and a specificity of 0.46 with the ROC AUC of 0.73. The hematological toxicity prediction model achieved a sensitivity of 0.89 and a specificity of 0.39 with the ROC AUC of 0.76. The gastrointestinal toxicity prediction model achieved a sensitivity of 0.93 and a specificity of 0.35 with the ROC AUC of 0.80. In conclusion, we provided platinum-based chemotherapy response and toxicity prediction models for advanced NSCLC patients. PMID:27126360

  8. Association of neck circumference with general and abdominal obesity in children and adolescents: the weight disorders survey of the CASPIAN-IV study

    Science.gov (United States)

    Kelishadi, Roya; Djalalinia, Shirin; Motlagh, Mohammad Esmaiel; Rahimi, Ali; Bahreynian, Maryam; Arefirad, Tahereh; Ardalan, Gelayol; Safiri, Saeid; Hasani, Motahare; Asayesh, Hamid; Mansourian, Morteza; Qorbani, Mostafa

    2016-01-01

    Objectives This study aimed to evaluate the association of neck circumference (NC) with obesity to determine the sex-specific and age-specific optimal cut-off points of this measure in association with obesity in a national sample of the Iranian paediatric population. Methods This survey on weight disorders was conducted among a national sample of Iranian children and adolescents, aged 6–18 years. Using the area under the curve (AUC) of the receiver operator characteristic curves, we evaluated the association of NC with general and abdominal obesity. Results This national survey was conducted among 23 043 school students (50.8% boys) with a mean age (SD) of 12.55 (3.31) years. A significant association was documented between NC and other anthropometric measures in both sexes and in the whole population. In all age groups and genders, NC performed relatively well in classifying participants to overweight (AUC: 0.67 to 0.75, p<0.001), general obesity (AUC: 0.81 to 0.85, p<0.001) and abdominal obesity (AUC: 0.73 to 0.78, p<0.001). Conclusions NC can be considered as a simple time-saving clinical tool for obesity detection in large population-based studies in children and adolescents. It is significantly correlated with indices of adiposity and can reliably identify children with general and abdominal obesity in the Iranian paediatric population. PMID:27694487

  9. Role of leader peptide synthesis in tryptophanase operon expression in Escherichia coli K-12.

    OpenAIRE

    Stewart, V; Yanofsky, C

    1986-01-01

    We used site-directed mutagenesis to replace the Escherichia coli tryptophanase (tna) operon leader peptide start codon with AUC. This change greatly decreased the uninduced rate of tna operon expression, and it also lowered the response to inducer. We conclude that leader peptide synthesis plays an essential role in tna operon expression.

  10. The outcome of PIE *-ē̆i̯(C)# and *-ē̆u̯(C)# in Germanic

    DEFF Research Database (Denmark)

    Hansen, Bjarne Simmelkjær Sandgaard

    2014-01-01

    By suggesting an interconnected series of soundlaws for the outcome of Proto-Indo-European (PIE) falling e-vowel diphthongs in final syllables in Proto-Germanic (PG) and in the individual Germanic languages, viz. PIE *-ei̯(C)# > PG *-ai(C)#, PIE *-ēi̯(C)# > PG *-ei(C)#, PIE *-eu̯(C)# > PG *-au(C)...

  11. Variability of glycemic and insulin response to a standard meal, within and between healthy subjects

    Directory of Open Access Journals (Sweden)

    Sandra Hirsch

    2013-04-01

    Full Text Available Aim: To test the variability within and between subject of glycemic response test following the ingestion of a standard food. Material and methods: Glucose and insulin response of a standard meal (white bread was performed in ten healthy volunteers and repeated under identical conditions for 6 times. Blood glucose and insulin levels were measured in the fasted state and over the 180 min following commencement of consumption of the foods The Area Under the Curve (AUC for glucose and insulin was calculated for the values above baseline for the 3hour period following the standard meal. Within and between coefficient of variation was calculated. Results: The total intra-individual variation of the gAUC was 51.8% range 24.9 to 91.4%. The inter-individual variation of the gAUC in the complete study was 75.2% . The total intra-individual variation of the iAUC was 51.9%. ranged: 7.7 to 103%. The inter-individual variation in the complete study was 86%. Conclusion: Glucose and insulin response to a reference food has low reliability, therefore limits its clinical utility for individual dietary prescription.

  12. Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I to ADH 3 (Class III in Mouse

    Directory of Open Access Journals (Sweden)

    Takeshi Haseba

    2012-01-01

    Full Text Available ADH 1 and ADH 3 are major two ADH isozymes in the liver, which participate in systemic alcohol metabolism, mainly distributing in parenchymal and in sinusoidal endothelial cells of the liver, respectively. We investigated how these two ADHs contribute to the elimination kinetics of blood ethanol by administering ethanol to mice at various doses, and by measuring liver ADH activity and liver contents of both ADHs. The normalized AUC (AUC/dose showed a concave increase with an increase in ethanol dose, inversely correlating with β. CLT (dose/AUC linearly correlated with liver ADH activity and also with both the ADH-1 and -3 contents (mg/kg B.W.. When ADH-1 activity was calculated by multiplying ADH-1 content by its Vmax⁡/mg (4.0 and normalized by the ratio of liver ADH activity of each ethanol dose to that of the control, the theoretical ADH-1 activity decreased dose-dependently, correlating with β. On the other hand, the theoretical ADH-3 activity, which was calculated by subtracting ADH-1 activity from liver ADH activity and normalized, increased dose-dependently, correlating with the normalized AUC. These results suggested that the elimination kinetics of blood ethanol in mice was dose-dependently changed, accompanied by a shift of the dominant metabolizing enzyme from ADH 1 to ADH 3.

  13. Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.

    Science.gov (United States)

    Wang, Chang-Yu; Lee, Tsair-Fwu; Fang, Chun-Hsiung; Chou, Jyh-Horng

    2012-11-01

    Given the poor prognosis of esophageal cancer and the invasiveness of combined modality treatment, improved prognostic scoring systems are needed. We developed a fuzzy logic-based system to improve the predictive performance of a risk score based on the serum concentrations of C-reactive protein (CRP) and albumin in a cohort of 271 patients with esophageal cancer before radiotherapy. Univariate and multivariate survival analyses were employed to validate the independent prognostic value of the fuzzy risk score. To further compare the predictive performance of the fuzzy risk score with other prognostic scoring systems, time-dependent receiver operating characteristic curve (ROC) analysis was used. Application of fuzzy logic to the serum values of CRP and albumin increased predictive performance for 1-year overall survival (AUC=0.773) compared with that of a single marker (AUC=0.743 and 0.700 for CRP and albumin, respectively), where the AUC denotes the area under curve. This fuzzy logic-based approach also performed consistently better than the Glasgow Prognostic Score (GPS) (AUC=0.745). Thus, application of fuzzy logic to the analysis of serum markers can more accurately predict the outcome for patients with esophageal cancer.

  14. Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents

    Science.gov (United States)

    Schell, Ryan F.; Sidone, Brian J.; Caron, Whitney P.; Walsh, Mark D.; Zamboni, Beth A.; Ramanathan, Ramesh K.; Zamboni, William C.

    2013-01-01

    Purpose A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents. Methods Inter-patient PK variability of 9 liposomal and SM formulations of the same drug were evaluated. PK variability was measured as coefficient of variance (CV%) of area under the plasma concentration versus time curve (AUC) and the fold-difference between AUCmax and AUCmin (AUC range). Results CV% of AUC and AUC ranges were 2.7-fold (P<0.001) and 16.7-fold (P=0.13) greater, respectively, for liposomal compared with SM drugs. There was an inverse linear relationship between the clearance (CL) of liposomal agents and PK variability with a lower CL associated with greater PK variability (R2 = 0.39). PK variability of liposomal agents was greater when evaluated from 0–336 h compared with 0–24 h. Conclusion PK variability of liposomes is significantly greater than SM. The factors associated with the PK variability of liposomal agents needs to be evaluated. PMID:23891988

  15. Particle growth mechanisms in Ag-ZrO2 and Au-ZrO2 granular films obtained by pulsed laser deposition

    International Nuclear Information System (INIS)

    Thin films consisting of Ag and Au nanoparticles embedded in amorphous ZrO2 matrix were grown by pulsed laser deposition in a wide range of metal volume concentrations in the dielectric regime (0.08AgAuc(Ag)∼0.28 and xc(Au)∼0.52)

  16. Pharmacokinetics of azithromycin and the combination of ivermectin and albendazole when administered alone and concurrently in healthy volunteers.

    Science.gov (United States)

    Amsden, Guy W; Gregory, Thomas B; Michalak, Cheryl A; Glue, Paul; Knirsch, Charles A

    2007-06-01

    Azithromycin is a critical component of an integrated disease elimination program against trachoma. This study was conducted to evaluate whether azithromycin has a pharmacokinetic interaction with the combination of ivermectin and albendazole. Eighteen healthy volunteers were administered single doses of azithromycin, ivermectin/albendazole, and the combination of the three agents in random, crossover fashion. To assess the presence of interactions, test (combination) and reference (single dose) data were compared using an estimation approach. Compared with reference phases, the geometric mean values for the combination arm's azithromycin AUC(0-t) and C(max) were increased approximately 13% and 20%, respectively, albendazole AUC(0-t) decreased by approximately 3% and C(max) increased approximately 3%, and ivermectin AUC(0-t) and C(max) were increased 31% and 27%, respectively. Albendazole sulfoxide AUC(0-t) and C(max) were decreased approximately 16% and 14%, respectively. All treatments were well tolerated. The interactions for azithromycin and albendazole were minimal although the increase in ivermectin exposure requires further study. PMID:17556628

  17. Quercetin increases the bioavailability of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats

    NARCIS (Netherlands)

    Schutte, M.E.; Alink, G.M.; Freidig, A.P.; Spenkelink, A.; Vaessen, J.; Sandt, van de J.J.M.; Groten, J.P.; Rietjens, I.M.C.M.

    2008-01-01

    This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 micromol PhIP/kg bw and 30 micromol quercetin/kg bw significantly increased the blood AUC(0

  18. Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

    DEFF Research Database (Denmark)

    Nielsen, Mette J; Kazankov, Konstantin; Leeming, Diana J;

    2015-01-01

    .75 and AUC = 0.86. Combination of Pro-C3 and C4M with age, BMI and gender in a multiple ordered logistic regression model improved the diagnostic value for detecting ≥F2 and ≥F3 with AUC = 0.80 and AUC = 0.88. CONCLUSION: The Pro-C3 protein fragment provided clinically relevant diagnostic accuracy......BACKGROUND AND AIM: Detection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments...... the markers C3M, C4M, C6M and P4NP7S were significantly elevated in patients with advanced fibrosis (≥F3) compared to F0-F2 (pdetecting ≥F2 and ≥F3 was Pro-C3 with AUC = 0...

  19. Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects.

    Science.gov (United States)

    Qayyum, Aisha; Najmi, Muzammil Hasan; Abbas, Mateen

    2013-11-01

    Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen (100mg) either generic or branded product according to randomization scheme on each of 2 periods. Blood samples were collected and plasma flurbiprofen concentration was determined by a validated HPLC method. Pharmacokinetic parameters like AUC(0-t), AUC(0-oo), Cmax, Tmax, t½, Vd and clearance were determined. The 90% CI for the ratio of geometric means of test to reference product's pharmacokinetic variables was calculated. Pharmacokinetic parameters for two formulations were comparable. Ratio of means of AUC(0-24), AUC(0-oo) and Cmax for test to reference products and 90% CI for these ratios were within the acceptable range. The p-values calculated by TOST were much less than the specified value (p-0.05). ANOVA gave p-values which were more than the specified value (p-0.05) for sequence, subject, period and formulation. Test formulation of flurbiprofen (tablet Flurso) was found to meet the criteria for bioequivalence to branded product (tablet Ansaid) based on pharmacokinetic parameters.

  20. Comparative bioavailability study of two brands of prazosin-containing tablets in healthy volunteers.

    Science.gov (United States)

    Guelen, P J; Janssen, T J; Lam, M H; Vree, T B; Exler, P S

    1990-10-19

    The bioavailability of two prazosin formulations was studied in 12 healthy volunteers. 1 Subject left the study. Based on the statistical tests of the pharmacokinetic parameters of prazosin in 11 volunteers, such as t 1/2, Cmax, tmax and AUC, it could be concluded that both preparations had comparable bioavailabilities. PMID:2255586

  1. Influence of fruit drinks with or without lactobacillus Lp299v on the gastrointestinal uptake of paracetamol in man

    DEFF Research Database (Denmark)

    Akerman, Ulrika; Edvinsson, Lars

    2009-01-01

    (a 95% confidence interval of 57,161). The corresponding 30 minutes values of paracetamol levels in the presence of rosehip with or without Lp299v were 0 mumol/l (95% confidence intervals contain only zero for both rosehip treatments). There were significant differences in AUC, maximal paracetamol...

  2. Bilateral Image Subtraction and Multivariate Models for the Automated Triaging of Screening Mammograms

    Directory of Open Access Journals (Sweden)

    José Celaya-Padilla

    2015-01-01

    Full Text Available Mammography is the most common and effective breast cancer screening test. However, the rate of positive findings is very low, making the radiologic interpretation monotonous and biased toward errors. This work presents a computer-aided diagnosis (CADx method aimed to automatically triage mammogram sets. The method coregisters the left and right mammograms, extracts image features, and classifies the subjects into risk of having malignant calcifications (CS, malignant masses (MS, and healthy subject (HS. In this study, 449 subjects (197 CS, 207 MS, and 45 HS from a public database were used to train and evaluate the CADx. Percentile-rank (p-rank and z-normalizations were used. For the p-rank, the CS versus HS model achieved a cross-validation accuracy of 0.797 with an area under the receiver operating characteristic curve (AUC of 0.882; the MS versus HS model obtained an accuracy of 0.772 and an AUC of 0.842. For the z-normalization, the CS versus HS model achieved an accuracy of 0.825 with an AUC of 0.882 and the MS versus HS model obtained an accuracy of 0.698 and an AUC of 0.807. The proposed method has the potential to rank cases with high probability of malignant findings aiding in the prioritization of radiologists work list.

  3. Pharmacokinetic parameters of nevirapine and efavirenz in relation to antiretroviral efficacy

    NARCIS (Netherlands)

    F. van Leth; B.S. Kappelhoff; D. Johnson; M.H. Losso; A. Boron-Kaczmarska; M.S. Saag; J.M. Livrozet; D.B. Hall; J. Leith; A.D.R. Huitema; F.W. Wit; J.H. Beijnen; J.M.A. Lange

    2006-01-01

    Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (C-min) and total drug exposure over 24 hr (AUC(24)) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the

  4. IL-18 Serum Level in Adult Onset Still’s Disease: A Marker of Disease Activity

    Directory of Open Access Journals (Sweden)

    Serena Colafrancesco

    2012-01-01

    Conclusions. Higher levels of IL-18 are detected in active AODS patients and correlate with disease activity and inflammatory laboratory features. ROC-AUC analysis of the serum concentration of IL-18 suggests that it can be considered a diagnostic marker of AOSD. This paper supports the targeting of this cytokine as a possible therapeutic option in AOSD.

  5. Intestinal first pass metabolism of midazolam in liver cirrhosis --effect of grapefruit juice

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Pedersen, Natalie; Larsen, Niels-Erik;

    2002-01-01

    subjects after ingestion of grapefruit juice. However, this interaction has not been studied in patients with impaired liver function. Accordingly, the effect of grapefruit juice on the AUC of midazolam and the metabolite alpha-hydroxymidazolam was studied in patients with cirrhosis of the liver....

  6. The Score Model Containing Chinese Medicine Syndrome Element of Blood Stasis Presented a Better Performance Compared to APRI and FIB-4 in Diagnosing Advanced Fibrosis in Patients with Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Xiao-Ling Chi

    2016-01-01

    Full Text Available This study aims to explore a useful noninvasive assessment containing TCM syndrome elements for liver fibrosis in CHB patients. The demographic, clinical, and pathological data were retrospectively collected from 709 CHB patients who had ALT less than 2 times the upper limit of normal from April 2009 to October 2012. Logistical regression and area under receiver-operator curve (AUROC were used to determine the diagnostic performances of simple tests for advanced fibrosis (Scheuer stage, F ≥ 3. Results showed that the most common TCM syndrome element observed in this CHB population was dampness and Qi stagnation, followed by blood stasis, by heat, and less by Qi deficiency and Yin deficiency. The logistical regression analysis identified AST ≥ 35 IU/L, PLT ≤ 161 × 109/L, and TCM syndrome element of blood stasis as the independent risk factors for advanced fibrosis. Therefore, a score model containing these three factors was established and tested. The score model containing blood stasis resulted in a higher AUC (AUC = 0.936 compared with APRI (AUC = 0.731 and FIB-4 (AUC = 0.709. The study suggested that the score model containing TCM syndrome element of blood stasis could be used as a useful diagnostic tool for advanced fibrosis in CHB patients and presented a better performance compared to APRI and FIB-4.

  7. The Score Model Containing Chinese Medicine Syndrome Element of Blood Stasis Presented a Better Performance Compared to APRI and FIB-4 in Diagnosing Advanced Fibrosis in Patients with Chronic Hepatitis B.

    Science.gov (United States)

    Chi, Xiao-Ling; Shi, Mei-Jie; Xiao, Huan-Ming; Xie, Yu-Bao; Cai, Gao-Shu

    2016-01-01

    This study aims to explore a useful noninvasive assessment containing TCM syndrome elements for liver fibrosis in CHB patients. The demographic, clinical, and pathological data were retrospectively collected from 709 CHB patients who had ALT less than 2 times the upper limit of normal from April 2009 to October 2012. Logistical regression and area under receiver-operator curve (AUROC) were used to determine the diagnostic performances of simple tests for advanced fibrosis (Scheuer stage, F ≥ 3). Results showed that the most common TCM syndrome element observed in this CHB population was dampness and Qi stagnation, followed by blood stasis, by heat, and less by Qi deficiency and Yin deficiency. The logistical regression analysis identified AST ≥ 35 IU/L, PLT ≤ 161 × 10(9)/L, and TCM syndrome element of blood stasis as the independent risk factors for advanced fibrosis. Therefore, a score model containing these three factors was established and tested. The score model containing blood stasis resulted in a higher AUC (AUC = 0.936) compared with APRI (AUC = 0.731) and FIB-4 (AUC = 0.709). The study suggested that the score model containing TCM syndrome element of blood stasis could be used as a useful diagnostic tool for advanced fibrosis in CHB patients and presented a better performance compared to APRI and FIB-4. PMID:26904141

  8. Development of an online, publicly accessible naive Bayesian decision support tool for mammographic mass lesions based on the American College of Radiology (ACR) BI-RADS lexicon

    International Nuclear Information System (INIS)

    To develop and validate a decision support tool for mammographic mass lesions based on a standardized descriptor terminology (BI-RADS lexicon) to reduce variability of practice. We used separate training data (1,276 lesions, 138 malignant) and validation data (1,177 lesions, 175 malignant). We created naive Bayes (NB) classifiers from the training data with tenfold cross-validation. Our ''inclusive model'' comprised BI-RADS categories, BI-RADS descriptors, and age as predictive variables; our ''descriptor model'' comprised BI-RADS descriptors and age. The resulting NB classifiers were applied to the validation data. We evaluated and compared classifier performance with ROC-analysis. In the training data, the inclusive model yields an AUC of 0.959; the descriptor model yields an AUC of 0.910 (P < 0.001). The inclusive model is superior to the clinical performance (BI-RADS categories alone, P < 0.001); the descriptor model performs similarly. When applied to the validation data, the inclusive model yields an AUC of 0.935; the descriptor model yields an AUC of 0.876 (P < 0.001). Again, the inclusive model is superior to the clinical performance (P < 0.001); the descriptor model performs similarly. We consider our classifier a step towards a more uniform interpretation of combinations of BI-RADS descriptors. We provide our classifier at www.ebm-radiology.com/nbmm/index.html. (orig.)

  9. Liberal Arts and Sciences Education for the 21st Century Knowledge Economy: A Case Study of Amsterdam University College, The Netherlands

    NARCIS (Netherlands)

    Klein Bog, Deirdre; Wende, van der Marijk; Jung, Insung; Nishimura, Mikiko; Sasao, Toshiaki

    2016-01-01

    This chapter describes how Amsterdam University College (AUC), a liberal arts and science honours college in The Netherlands, promotes internationalization and adopts a global approach in its curriculum and academic community. It shows how global learning outcomes and 21st century skills can be fost

  10. Insulin Resistance and Hypertension

    Institute of Scientific and Technical Information of China (English)

    张建华; 张春秀

    2002-01-01

    Summary: The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT),impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance(IR) under the disorder of glucose metabolism and hypertension were studied. By glucose toler-ance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucosetolerance curve (AUCG) to area under insulin release curve (AUC1) were calculated and analyzed.The results showed that ISI was decreased to varying degrees in the patients with hypertension,the mildest in the group of NGT with hypertension, followed by the group of IGT without hyper-tension, the group of IGT with hypertension and DM (P=0). There was very significant differ-ence in the ratio of AUCG/AUC1 between the hypertensive patients with NGT and controls (P=0). It was concluded that a significant IR existed during the development of IGT both in hyperten-sion and nonhypertension. The increase of total insulin secretion (AUC1) was associated with non-hypertension simultaneously. IR of the hypertensive patients even existed in NGT and was wors-ened with the deterioration of glucose metabolism disorder, but the AUC1 in the HT groupchanged slightly. A relative deficiency of insulin secretion or dysfunction of β-cell of islet existed inIGT and DM of the hypertensive patients.

  11. Shear-wave elastography for breast masses: local shear wave speed (m/sec versus Young modulus (kPa

    Directory of Open Access Journals (Sweden)

    Ji Hyun Youk

    2014-01-01

    Conclusion:

    The quantitative elasticity values measured in kPa and m/sec on SWE showed good diagnostic performance. The specificity of the SD and AUC of the wSD measured in kPa were significantly higher than those measured in m/sec.

  12. Toxicokinetics of 2-nitropropane in the rat

    NARCIS (Netherlands)

    Derks HJGM; Heinignen A van; Klaassen R; Olling M

    1989-01-01

    De toxicokinetiek van 2-nitropropaan na intraveneuze en orale toediening (in water en in olie) werd onderzocht. Uit de plasma-concentratie profielen werden farmacokinetische paramters berekend waarbij een open een-compartiment model werd gebruikt. Door AUC-waarden verkregen bij varierende intrav

  13. Caffeine intake in pregnancy: Relationship between internal intake and effect on birth weight.

    Science.gov (United States)

    Partosch, F; Mielke, H; Stahlmann, R; Gundert-Remy, U

    2015-12-01

    We used a physiologically based kinetic model to simulate caffeine blood concentration-time profiles in non-pregnant and pregnant women. The model predicted concentration-time profile was in good accordance with experimental values. With 200 mg, the safe dose per occasion in non-pregnant women, AUC and peak concentration in pregnant women were nearly twice that of non-pregnant women. In order to derive a safe dose for the pregnant women we estimated the dose in the pregnant women model taken at once which would not exceed AUC and peak concentration in the non-pregnant women of 200 mg as single dose. The resulting dose is 100 mg caffeine per occasion which we recommend as safe. The caffeine dose of 200 mg per day is declared as safe for pregnant women with respect to the foetus by EFSA based on results on reduced birth weight in epidemiological studies. We modelled AUC and peak concentration for different caffeine doses to investigate the relationship between internal caffeine exposure and risk measures of reduced birth weight from epidemiological studies. The graphical analysis revealed that the reduction in birth weight was related to AUC and peak concentration up to a dose of 250 mg caffeine.

  14. Development of an online, publicly accessible naive Bayesian decision support tool for mammographic mass lesions based on the American College of Radiology (ACR) BI-RADS lexicon

    Energy Technology Data Exchange (ETDEWEB)

    Benndorf, Matthias; Kotter, Elmar; Langer, Mathias [University Hospital Freiburg, Department of Radiology, Freiburg (Germany); Herda, Christoph [Kantonsspital Graubuenden, Chur (Switzerland); Wu, Yirong; Burnside, Elizabeth S. [University of Wisconsin-Madison School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

    2015-06-01

    To develop and validate a decision support tool for mammographic mass lesions based on a standardized descriptor terminology (BI-RADS lexicon) to reduce variability of practice. We used separate training data (1,276 lesions, 138 malignant) and validation data (1,177 lesions, 175 malignant). We created naive Bayes (NB) classifiers from the training data with tenfold cross-validation. Our ''inclusive model'' comprised BI-RADS categories, BI-RADS descriptors, and age as predictive variables; our ''descriptor model'' comprised BI-RADS descriptors and age. The resulting NB classifiers were applied to the validation data. We evaluated and compared classifier performance with ROC-analysis. In the training data, the inclusive model yields an AUC of 0.959; the descriptor model yields an AUC of 0.910 (P < 0.001). The inclusive model is superior to the clinical performance (BI-RADS categories alone, P < 0.001); the descriptor model performs similarly. When applied to the validation data, the inclusive model yields an AUC of 0.935; the descriptor model yields an AUC of 0.876 (P < 0.001). Again, the inclusive model is superior to the clinical performance (P < 0.001); the descriptor model performs similarly. We consider our classifier a step towards a more uniform interpretation of combinations of BI-RADS descriptors. We provide our classifier at www.ebm-radiology.com/nbmm/index.html. (orig.)

  15. Impact of Diabetes-Specific Nutritional Formulas versus Oatmeal on Postprandial Glucose, Insulin, GLP-1 and Postprandial Lipidemia

    Directory of Open Access Journals (Sweden)

    Adham Mottalib

    2016-07-01

    Full Text Available Diabetes-specific nutritional formulas (DSNFs are frequently used as part of medical nutrition therapy for patients with diabetes. This study aims to evaluate postprandial (PP effects of 2 DSNFs; Glucerna (GL and Ultra Glucose Control (UGC versus oatmeal (OM on glucose, insulin, glucagon-like peptide-1 (GLP-1, free fatty acids (FFA and triglycerides (TG. After an overnight fast, 22 overweight/obese patients with type 2 diabetes were given 200 kcal of each of the three meals on three separate days in random order. Blood samples were collected at baseline and at 30, 60, 90, 120, 180 and 240 min. Glucose area under the curve (AUC0–240 after GL and UGC was lower than OM (p < 0.001 for both. Insulin positive AUC0–120 after UGC was higher than after OM (p = 0.02. GLP-1 AUC0–120 and AUC0–240 after GL and UGC was higher than after OM (p < 0.001 for both. FFA and TG levels were not different between meals. Intake of DSNFs improves PP glucose for 4 h in comparison to oatmeal of similar caloric level. This is achieved by either direct stimulation of insulin secretion or indirectly by stimulating GLP-1 secretion. The difference between their effects is probably related to their unique blends of amino acids, carbohydrates and fat.

  16. In vivo evaluation of lipid-based formulations for oral delivery of apomorphine and its diester prodrugs

    DEFF Research Database (Denmark)

    Borkar, Nrupa Nitin; Holm, René; Yang, Mingshi;

    2016-01-01

    .05) than after DLA-w/o administration, indicating that triglycerides and surfactants improved the oral absorption of DLA. Similarly, Cmax and AUC after dosing apomorphine-o/w were significantly higher (p≤0.05) than that of aqueous suspension. This suggested that lipids and lipolysis products possibly aided...

  17. Faster Onset of Bronchodilation with Formoterol than with Salmeterol in Patients with Stable, Moderate-Severe Copd: Results of a Randomized, Double-Blind Clinical Study

    Directory of Open Access Journals (Sweden)

    John Kottakis

    2002-01-01

    Full Text Available OBJECTIVES: To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer versus salmeterol xinofoate (Serevent Diskus with respect to normalized (* forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1 AUC*0-1 h.

  18. Determination of Carboplatin Dose by Area Under the Curve in Combination Chemotherapy for Senile Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    YIN Tiejun; LIU Qingqing; HU Changyao; LIU Mengtao

    2007-01-01

    To preliminarily determine the appropriate dosage of carboplatin (CBP) at AUC of 5 mg·Ml-1·min-1 in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer (NSCLC). Thirty-five Chinese senile patients with NSCLC in advanced stage (Ⅲ/Ⅳ) were given 96 cycles of combination chemotherapy. Chemotherapy schedules included Taxol+CBE Gemzar+CBP and NVB+CBP. The dose of CBP was at 5 mg·mL-1·min-1 of area under the concen- tration-time curve (AUC). Side effects and quality of life were observed before and after the chemo- therapy. Myelosuppression was severe and commonly observed. Grade 3/4 of granuiocytopenia was found in 47.9% (46/96) of the patients and grade 3/4 of thrombocytopenia was noted in 28.1% (27/96) of the subjects. However, other side effects were slight. The mean score of quality of life (QOL), ac- cording to the criteria of QOL for Chinese cancer patients had reduced 6.8. At 5 mg·mL-1·min-1 by AUC, the hematological toxicity of CBP was severe and it had some negative effects on the QOL. The administration of CBP at 5 mg·mL-1·min-1 by AUC may be too high for Chinese senile patients with non-small cell lung cancer.

  19. Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; van Buchem, Mark A;

    2015-01-01

    [fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR...

  20. Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis

    DEFF Research Database (Denmark)

    Wuttge, D. M.; Carlsen, A. L.; Teku, G.;

    2015-01-01

    or more autoantibody groups, and five (miRNA-409, -184, -92a, -29a and -101) remained significant after correction for multiple comparisons. Multiple regression models accurately predicted ACA and anti-DNA topoisomerase I antibody positive patients (area under the curve (AUC) = 0.97 and 0.93, respectively...

  1. The Heathen Obama

    DEFF Research Database (Denmark)

    Christensen, Rune Reimer

    2008-01-01

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

  2. Therapeutic drug monitoring to individualize the dosing of pazopanib: a pharmacokinetic feasibility study

    NARCIS (Netherlands)

    Wit, D. de; Erp, N. van; Hartigh, J. den; Wolterbeek, R..; Hollander-van Deursen, M. den; Labots, M.; Guchelaar, H.J.; Verheul, H.M.; Gelderblom, H.

    2015-01-01

    BACKGROUND: Patients treated with the standard dose of pazopanib show a large interpatient variability in drug exposure defined as the area under the plasma concentration-time curve (AUC0-24h). The primary objective of this study was to evaluate the feasibility of pharmacokinetics (PK)-guided indivi

  3. Comparing five different iterative reconstruction algorithms for computed tomography in an ROC study

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Kristin; Martinsen, Anne Catrine T. [Rikshospitalet, The Intervention Centre, Postboks 4950, Oslo (Norway); University of Oslo, lnstitute of Physics, Oslo (Norway); Tingberg, Anders [Lund University, Skaane University Hospital, Department of Medical Radiation Physics, Malmoe (Sweden); Aaloekken, Trond Mogens [Rikshospitalet, Department of Radiology and Nuclear Medicine, Postboks 4950, Oslo (Norway); Fosse, Erik [Rikshospitalet, The Intervention Centre, Postboks 4950, Oslo (Norway); University of Oslo, lnstitute of Clinical Medicine, Oslo (Norway)

    2014-12-15

    The purpose of this study was to evaluate lesion conspicuity achieved with five different iterative reconstruction techniques from four CT vendors at three different dose levels. Comparisons were made of iterative algorithm and filtered back projection (FBP) among and within systems. An anthropomorphic liver phantom was examined with four CT systems, each from a different vendor. CTDI{sub vol} levels of 5 mGy, 10 mGy and 15 mGy were chosen. Images were reconstructed with FBP and the iterative algorithm on the system. Images were interpreted independently by four observers, and the areas under the ROC curve (AUCs) were calculated. Noise and contrast-to-noise ratios (CNR) were measured. One iterative algorithm increased AUC (0.79, 0.95, and 0.97) compared to FBP (0.70, 0.86, and 0.93) at all dose levels (p < 0.001 and p = 0.047). Another algorithm increased AUC from 0.78 with FBP to 0.84 (p = 0.007) at 5 mGy. Differences at 10 and 15 mGy were not significant (p-values: 0.084-0.883). Three algorithms showed no difference in AUC compared to FBP (p-values: 0.008-1.000). All of the algorithms decreased noise (10-71 %) and improved CNR. Only two algorithms improved lesion detection, even though noise reduction was shown with all algorithms. (orig.)

  4. Validation of LRG1 as a potential biomarker for detection of epithelial ovarian cancer by a blinded study.

    Directory of Open Access Journals (Sweden)

    Jing Wu

    Full Text Available Leucine-rich alpha-2-glycoprotein (LRG1 was found to be differentially expressed in sera from patients with Epithelial Ovarian Cancer (EOC. The aim of this study is to investigate the performance of LRG1 for detection of EOC, including early stage EOC, and to evaluate if LRG1 can complement CA125 in order to improve EOC detection using two independent blinded sample sets.Serum LRG1 and CA125 were measured by immunoassays. All assays were performed blinded to clinical data. Using the two independent sample sets (156 participants for sample set 1, and 233 for sample set 2, LRG1 was differentially expressed in EOC cases as compared to healthy, surgical, and benign controls, and its performance was not affected by the conditions of blood collection. The areas under the ROC curve (AUC for LRG1 in differentiating EOC cases from non-cases were 0.797 and 0.786 for sample set 1 and 2. For differentiating EOC cases from healthy controls, the AUC values for LRG1 were 0.792 and 0.794. At a fixed specificity of 95%, LRG1 detects 52%, and 53.5% of EOC cases from healthy controls for sample set 1 and 2. When combining LRG1 and CA125, the AUC value increased to 0.927, which was improved compared to CA125 (AUC=0.916 (p=0.008 alone in distinguishing EOC cases from non-cases. More importantly, LRG1 also showed potential performance in differentiating early stage EOC from non-cases with an AUC of 0.715 for sample set 1, and 0.690 for sample set 2. The combination of LRG1 and CA125 resulted in an AUC of 0.838, which outperforms CA125 (AUC=0.785 (p=0.018 in detecting early stage EOC cases from non-cases using the larger sample set.LRG1 could be a useful biomarker alone or in combination with CA125 for the diagnosis of ovarian cancer.

  5. 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

  6. Pharmacokinetic profile of defibrotide in patients with renal impairment.

    Science.gov (United States)

    Tocchetti, Paola; Tudone, Elena; Marier, Jean-Francois; Marbury, Thomas C; Zomorodi, Katie; Eller, Mark

    2016-01-01

    Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable, potentially life-threatening complication of hematopoietic stem cell transplant conditioning. Severe VOD/SOS, generally associated with multiorgan dysfunction (pulmonary or renal dysfunction), may be associated with >80% mortality. Defibrotide, recently approved in the US, has demonstrated efficacy treating hepatic VOD/SOS with multiorgan dysfunction. Because renal impairment is prevalent in patients with VOD/SOS, this Phase I, open-label, two-part study in adults examined the effects of hemodialysis and severe or end-stage renal disease (ESRD) on defibrotide pharmacokinetics (PK). Part 1 compared defibrotide PK during single 6.25 mg/kg doses infused with and without dialysis. Part 2 assessed defibrotide plasma PK after multiple 6.25 mg/kg doses in nondialysis-dependent subjects with severe/ESRD versus healthy matching subjects. Among six subjects enrolled in Part 1, percent ratios of least-squares mean and 90% confidence intervals (CIs) on dialysis and nondialysis days were 109.71 (CI: 97.23, 123.78) for maximum observed plasma concentration (Cmax); 108.39 (CI: 97.85, 120.07) for area under the concentration-time curve to the time of the last quantifiable plasma concentration (AUC0-t); and 109.98 (CI: 99.39, 121.70) for AUC extrapolated to infinity (AUC0-∞). These ranges were within 80%-125%, indicating no significant effect of dialysis on defibrotide exposure/clearance. In Part 2, defibrotide exposure parameters in six subjects with severe/ESRD after multiple doses (AUC0-t, 113 µg·h/mL; AUC over dosing interval, 113 µg·h/mL; Cmax, 53.8 µg/mL) were within 5%-8% of parameters after the first dose (AUC0-t, 117 µg·h/mL; AUC0-∞, 118 µg·h/mL; Cmax, 54.9 µg/mL), indicating no accumulation. Defibrotide peak and extent of exposures in those with severe/ESRD were ~35%-37% and 50%-60% higher, respectively, versus controls, following single and multiple

  7. Relative bioavailability of rifampicin in a three-drug fixed-dose combination formulation%三药固定剂量复方制剂的利福平相对生物利用度

    Institute of Scientific and Technical Information of China (English)

    R.C.Milán-Segovia; A.M.Domínguez-Ramírez; H.Jung-Cook; M.Maga(n)a-Aquino; M.C.Romero-Méndez; S.E.Medellíin-Garibay; M.Vigna-Pérez; S.Romano-Moreno; 金海霞

    2011-01-01

    背景:先前的一个利福平(RMP)监测性研究显示,结核病(TB)患者在使用常规的3药固定剂量复方制剂(3FDC)治疗时,RMP浓度很低.因此,我们对该制剂的生物利用度进行研究.目的:利用健康志愿者研究墨西哥卫生保健系统中常规使用的3FDC制剂相对于参比制剂的RMP相对生物利用度.设计:两周期、两序列的交叉研究.结果:受试制剂和参比制剂的药代动力学参数均值如下:达峰浓度(C_max)分别为3.13±2.01滩/而和9.95±2.66 μg/ml;对于血药浓度一时间曲线下面积(AUC),零到最后实测浓度的AUC(AUC_0-12h)分别为15.51±9.77 μg·h/ml和58.03±16.1 μg·h/ml,零到无限大时间的AUC(AUC_0-∞)分别为17.92±10.66 μg·h/ml和68.43±22.39 μg·h/ml.C_max的受试/参比均值比(90% CI)为25.36%(17.33~37.10);AUC0_12h为21.25%(14.61~30.89);AUC_0-∞为22.08% (15.44~31.56).这些结果不符合生物等效性标准.结论:受试制剂与参比制剂相比,显示吸收延迟和RMP生物利用度明显偏低.含RMP的常规制剂只有在其生物利用度评估后可确保与参比制剂互换,并确保在其使用过程中不出现RMP浓度明显偏低的危险时,才能应用.

  8. Cellulose nanofibrils improve the properties of all-cellulose composites by the nano-reinforcement mechanism and nanofibril-induced crystallization

    Science.gov (United States)

    Yang, Quanling; Saito, Tsuguyuki; Berglund, Lars A.; Isogai, Akira

    2015-10-01

    All-cellulose nanocomposite films containing crystalline TEMPO-oxidized cellulose nanofibrils (TOCNs) of 0-1 wt% were fabricated by mixing aqueous TOCN dispersions with alkali/urea/cellulose (AUC) solutions at room temperature. The mixtures were cast on glass plates, soaked in an acid solution, and the regenerated gel-like films were washed with water and then dried. The TOCN did not form agglomerates in the composites, and had the structure of TOCN-COOH, forming hydrogen bonds with the hydroxyl groups of the regenerated cellulose molecules. X-ray diffraction analysis revealed that the matrix cellulose molecules increased the cellulose II crystal size upon incorporation of TOCN. As a result, the TOCN/AUC composite films had high Young's modulus, tensile strength, thermal stability and oxygen-barrier properties. The TOCN/AUC composite films are promising all-cellulose nanocomposites for versatile applications as new bio-based materials.All-cellulose nanocomposite films containing crystalline TEMPO-oxidized cellulose nanofibrils (TOCNs) of 0-1 wt% were fabricated by mixing aqueous TOCN dispersions with alkali/urea/cellulose (AUC) solutions at room temperature. The mixtures were cast on glass plates, soaked in an acid solution, and the regenerated gel-like films were washed with water and then dried. The TOCN did not form agglomerates in the composites, and had the structure of TOCN-COOH, forming hydrogen bonds with the hydroxyl groups of the regenerated cellulose molecules. X-ray diffraction analysis revealed that the matrix cellulose molecules increased the cellulose II crystal size upon incorporation of TOCN. As a result, the TOCN/AUC composite films had high Young's modulus, tensile strength, thermal stability and oxygen-barrier properties. The TOCN/AUC composite films are promising all-cellulose nanocomposites for versatile applications as new bio-based materials. Electronic supplementary information (ESI) available: Fig. S1-S3 show an AFM image of TOCN, SEM

  9. Evaluation of the pharmacokinetic interaction between repeated doses of rifapentine or rifampin and a single dose of bedaquiline in healthy adult subjects.

    Science.gov (United States)

    Winter, Helen; Egizi, Erica; Murray, Stephen; Erondu, Ngozi; Ginsberg, Ann; Rouse, Doris J; Severynse-Stevens, Diana; Pauli, Elliott

    2015-02-01

    This study assessed the effects of rifapentine or rifampin on the pharmacokinetics of a single dose of bedaquiline and its M2 metabolite in healthy subjects using a two-period single-sequence design. In period 1, subjects received a single dose of bedaquiline (400 mg), followed by a 28-day washout. In period 2, subjects received either rifapentine (600 mg) or rifampin (600 mg) from day 20 to day 41, as well as a single bedaquiline dose (400 mg) on day 29. The pharmacokinetic profiles of bedaquiline and M2 were compared over 336 h after the administration of bedaquiline alone and in combination with steady-state rifapentine or rifampin. Coadministration of bedaquiline with rifapentine or rifampin resulted in lower bedaquiline exposures. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the maximum observed concentration (Cmax), area under the concentration-time curve to the last available concentration time point (AUC0-t), and AUC extrapolated to infinity (AUC0-inf) of bedaquiline were 62.19% (53.37 to 72.47), 42.79% (37.77 to 48.49), and 44.52% (40.12 to 49.39), respectively, when coadministered with rifapentine. Similarly, the GMRs and 90% CIs for the Cmax, AUC0-t, and AUC0-inf of bedaquiline were 60.24% (51.96 to 69.84), 41.36% (37.70 to 45.36), and 47.32% (41.49 to 53.97), respectively, when coadministered with rifampin. The Cmax, AUC0-t, and AUC0-inf of M2 were also altered when bedaquiline was coadministered with rifapentine or rifampin. Single doses of bedaquiline, administered alone or with multiple doses of rifapentine or rifampin, were well tolerated, with no safety concerns related to coadministration. Daily administration of rifapentine to patients with tuberculosis presents the same drug interaction challenges as rifampin and other rifamycins. Strong inducers of the cytochrome P450 isoenzyme CYP3A4 should be avoided when considering the use of bedaquiline. (This study is registered at clinicaltrials.gov under identifier NCT02216331

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

    Science.gov (United States)

    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. PMID:26794937

  11. Performance of Two Bioelectrical Impedance Analyses in the Diagnosis of Overweight and Obesity in Children and Adolescents: The FUPRECOL Study

    Directory of Open Access Journals (Sweden)

    Robinson Ramírez-Vélez

    2016-10-01

    Full Text Available This study aimed to determine thresholds for percentage of body fat (BF% corresponding to the cut-off values for overweight/obesity as recommended by the International Obesity Task Force (IOTF, using two bioelectrical impedance analyzers (BIA, and described the likelihood of increased cardiometabolic risk in our cohort defined by the IOTF and BF% status. Participants included 1165 children and adolescents (54.9% girls from Bogotá (Colombia. Body mass index (BMI was calculated from height and weight. BF% of each youth was assessed first using the Tanita BC-418® followed by a Tanita BF-689®. The sensitivity and specificity of both devices and their ability to correctly classify children as overweight/obesity (≥2 standard deviation, as defined by IOTF, was investigated using receiver operating characteristic (ROC by sex and age groups (9–11, 12–14, and 13–17 years old; Area under curve (AUC values were also reported. For girls, the optimal BF% threshold for classifying into overweight/obesity was found to be between 25.2 and 28.5 (AUC = 0.91–0.97 and 23.9 to 26.6 (AUC = 0.90–0.99 for Tanita BC-418® and Tanita BF-689®, respectively. For boys, the optimal threshold was between 16.5 and 21.1 (AUC = 0.93–0.96 and 15.8 to 20.6 (AUC = 0.92–0.94 by Tanita BC-418® and Tanita BF-689®, respectively. All AUC values for ROC curves were statistically significant and there were no differences between AUC values measured by both BIA devices. The BF% values associated with the IOTF-recommended BMI cut-off for overweight/obesity may require age- and sex-specific threshold values in Colombian children and adolescents aged 9–17 years and could be used as a surrogate method to identify individuals at risk of excess adiposity.

  12. Combined 3 Tesla MRI Biomarkers Improve the Differentiation between Benign vs Malignant Single Ring Enhancing Brain Masses

    Science.gov (United States)

    Salice, Simone; Esposito, Roberto; Ciavardelli, Domenico; delli Pizzi, Stefano; di Bastiano, Rossella; Tartaro, Armando

    2016-01-01

    Purpose 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. Materials and Methods 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. Results 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

  13. Multiparametric analysis of cell-free DNA in melanoma patients.

    Directory of Open Access Journals (Sweden)

    Francesca Salvianti

    Full Text Available Cell-free DNA in blood (cfDNA represents a promising biomarker for cancer diagnosis. Total cfDNA concentration showed a scarce discriminatory power between patients and controls. A higher specificity in cancer diagnosis can be achieved by detecting tumor specific alterations in cfDNA, such as DNA integrity, genetic and epigenetic modifications.The aim of the present study was to identify a sequential multi-marker panel in cfDNA able to increase the predictive capability in the diagnosis of cutaneous melanoma in comparison with each single marker alone. To this purpose, we tested total cfDNA concentration, cfDNA integrity, BRAF(V600E mutation and RASSF1A promoter methylation associated to cfDNA in a series of 76 melanoma patients and 63 healthy controls. The chosen biomarkers were assayed in cfDNA samples by qPCR. Comparison of biomarkers distribution in cases and controls was performed by a logistic regression model in both univariate and multivariate analysis. The predictive capability of each logistic model was investigated by means of the area under the ROC curve (AUC. To aid the reader to interpret the value of the AUC, values between 0.6 and 0.7, between 0.71 and 0.8 and greater than 0.8 were considered as indicating a weak predictive, satisfactory and good predictive capacity, respectively. The AUC value for each biomarker (univariate logistic model was weak/satisfactory ranging between 0.64 (BRAF(V600E to 0.85 (total cfDNA. A good overall predictive capability for the final logistic model was found with an AUC of 0.95. The highest predictive capability was given by total cfDNA (AUC:0.86 followed by integrity index 180/67 (AUC:0.90 and methylated RASSF1A (AUC:0.89.An approach based on the simultaneous determination of three biomarkers (total cfDNA, integrity index 180/67 and methylated RASSF1A could improve the diagnostic performance in melanoma.

  14. 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

  15. Performance of Two Bioelectrical Impedance Analyses in the Diagnosis of Overweight and Obesity in Children and Adolescents: The FUPRECOL Study

    Science.gov (United States)

    Ramírez-Vélez, Robinson; Correa-Bautista, Jorge Enrique; Martínez-Torres, Javier; González-Ruíz, Katherine; González-Jiménez, Emilio; Schmidt-RioValle, Jacqueline; Garcia-Hermoso, Antonio

    2016-01-01

    This study aimed to determine thresholds for percentage of body fat (BF%) corresponding to the cut-off values for overweight/obesity as recommended by the International Obesity Task Force (IOTF), using two bioelectrical impedance analyzers (BIA), and described the likelihood of increased cardiometabolic risk in our cohort defined by the IOTF and BF% status. Participants included 1165 children and adolescents (54.9% girls) from Bogotá (Colombia). Body mass index (BMI) was calculated from height and weight. BF% of each youth was assessed first using the Tanita BC-418® followed by a Tanita BF-689®. The sensitivity and specificity of both devices and their ability to correctly classify children as overweight/obesity (≥2 standard deviation), as defined by IOTF, was investigated using receiver operating characteristic (ROC) by sex and age groups (9–11, 12–14, and 13–17 years old); Area under curve (AUC) values were also reported. For girls, the optimal BF% threshold for classifying into overweight/obesity was found to be between 25.2 and 28.5 (AUC = 0.91–0.97) and 23.9 to 26.6 (AUC = 0.90–0.99) for Tanita BC-418® and Tanita BF-689®, respectively. For boys, the optimal threshold was between 16.5 and 21.1 (AUC = 0.93–0.96) and 15.8 to 20.6 (AUC = 0.92–0.94) by Tanita BC-418® and Tanita BF-689®, respectively. All AUC values for ROC curves were statistically significant and there were no differences between AUC values measured by both BIA devices. The BF% values associated with the IOTF-recommended BMI cut-off for overweight/obesity may require age- and sex-specific threshold values in Colombian children and adolescents aged 9–17 years and could be used as a surrogate method to identify individuals at risk of excess adiposity. PMID:27782039

  16. 泮托拉唑钠肠溶片的非临床生物等效性分析%Non clinical bioequivalence analysis Pantoprazole Sodium Enteric-coated Tablets

    Institute of Scientific and Technical Information of China (English)

    郭丽

    2013-01-01

    Objective The purpose of the use of non-clinical biological analysis of pantoprazole sodium enteric-coated tablets are bioequivalent. Methods 8 Beagle Harriers randomized crossover single dose administration of pantoprazole sodium enteric-coated tablets test preparation and reference preparation, using high-performance liquid chromatography - UV detection in plasma for different time pantoprazole concentrations were measured; using two one-sided t test, analysis of variance, etc. equivalence analysis. Results The data AUC0-12 is based on the relative bioavailability of the test formulation were calculated, the result is the average of 97.61 ± 1.77%. 90% confidence interval AUC0-12: The test preparation 96.5-100.8% for the reference formulation; AUC0-∞ and Cmax of 90% confidence interval: test preparation for the reference formulation of 91.2-107.2%. Two formulations similar factor of 99.98.Conclusion There was no significant difference between the two formulations, bio-equivalency testing eligibility in AUC0-12, AUC0-∞, Cmax, Tmax aspects.%目的:利用非临床生物,分析泮托拉唑钠肠溶片的生物等效性。方法对8条米格鲁猎兔犬随机交叉单剂量给予泮托拉唑钠肠溶片受试制剂及参比制剂,采用高效液相色谱-紫外线检测法对不同时刻的血浆中泮托拉唑浓度进行测定;采用双向单侧t 检验、方差分析等进行等效性分析。结果按照 AUC0-12的数据为基础对受试制剂的相对生物利用度进行计算,平均值结果为97.61±1.77%。AUC0-12的90%置信区间:受试制剂为参比制剂的96.5~100.8%;AUC0-∞及Cmax 的90%置信区间:受试制剂为参比制剂的91.2~107.2%。两种制剂的相似因子为99.98。结论两种制剂在 AUC0-12、AUC0-∞、Cmax、Tmax 方面没有显著差异,生物等效性检验合格。

  17. Mutant-prevention concentration and mechanism of resistance in clinical isolates and enrofloxacin/marbofloxacin-selected mutants of Escherichia coli of canine origin.

    Science.gov (United States)

    Gebru, Elias; Choi, Myung-Jin; Lee, Seung-Jin; Damte, Dereje; Park, Seung Chun

    2011-10-01

    The antibacterial activity and selection of resistant bacteria, along with mechanisms of fluoroquinolone resistance, were investigated by integrating the static [MIC or mutant-prevention concentration (MPC)] and in vitro dynamic model approaches using Escherichia coli isolates from diseased dogs. Using the dynamic models, selected E. coli strains and enrofloxacin and marbofloxacin at a range of simulated area under concentration-time curve over a 24 h interval (AUC(24 h))/MIC ratios were investigated. Our results indicated increasing losses in susceptibility of E. coli upon continuous exposure to enrofloxacin and marbofloxacin in vitro. This effect was transferable to other fluoroquinolones, as well as to structurally unrelated drugs. Our results also confirmed an AUC(24 h)/MIC (AUC(24 h)/MPC)-dependent antibacterial activity and selection of resistant E. coli mutants, in which maximum losses in fluoroquinolone susceptibility occurred at simulated AUC(24 h)/MIC ratios of 40-60. AUC(24 h)/MPC ratios of 39 (enrofloxacin) and 32 (marbofloxacin) were considered protective against the selection of resistant mutants of E. coli. Integrating our MIC and MPC data with published pharmacokinetic information in dogs revealed a better effect of the conventional dosing regimen of marbofloxacin than that of enrofloxacin in restricting the selection of resistant mutants of E. coli. Target mutations, especially at codon 83 (serine to leucine) of gyrA, and overexpression of efflux pumps contributed to resistance development in both clinically resistant and in vitro-selected mutants of E. coli. We also report here a previously undescribed mutation at codon 116 of parC in two laboratory-derived resistant mutants of E. coli. Additional studies would determine the exact role of this mutation in fluoroquinolone susceptibility, as well as establish the importance of our findings in the clinical setting.

  18. Exposure-Response Analyses for Tafenoquine after Administration to Patients with Plasmodium vivax Malaria.

    Science.gov (United States)

    Tenero, David; Green, Justin A; Goyal, Navin

    2015-10-01

    Tafenoquine (TQ), a new 8-aminoquinoline with activity against all stages of the Plasmodium vivax life cycle, is being developed for the radical cure of acute P. vivax malaria in combination with chloroquine. The efficacy and exposure data from a pivotal phase 2b dose-ranging study were used to conduct exposure-response analyses for TQ after administration to subjects with P. vivax malaria. TQ exposure (i.e., area under the concentration-time curve [AUC]) and region (Thailand compared to Peru and Brazil) were found to be statistically significant predictors of clinical response based on multivariate logistic regression analyses. After accounting for region/country, the odds of being relapse free at 6 months increased by approximately 51% (95% confidence intervals [CI], 25%, 82%) for each 25-U increase in AUC above the median value of 54.5 μg · h/ml. TQ exposure was also a significant predictor of the time to relapse of the infection. The final parametric, time-to-event model for the time to relapse, included a Weibull distribution hazard function, AUC, and country as covariates. Based on the model, the risk of relapse decreased by 30% (95% CI, 17% to 42%) for every 25-U increase in AUC. Monte Carlo simulations indicated that the 300-mg dose of TQ would provide an AUC greater than the clinically relevant breakpoint obtained in a classification and regression tree (CART) analysis (56.4 μg · h/ml) in more than 90% of subjects and consequently result in a high probability of being relapse free at 6 months. This model-based approach was critical in selecting an appropriate phase 3 dose. (This study has been registered at ClinicalTrials.gov under registration no. NCT01376167.).

  19. Environmental and socio-economic risk modelling for Chagas disease in Bolivia.

    Science.gov (United States)

    Mischler, Paula; Kearney, Michael; McCarroll, Jennifer C; Scholte, Ronaldo G C; Vounatsou, Penelope; Malone, John B

    2012-09-01

    Accurately defining disease distributions and calculating disease risk is an important step in the control and prevention of diseases. Geographical information systems (GIS) and remote sensing technologies, with maximum entropy (Maxent) ecological niche modelling computer software, were used to create predictive risk maps for Chagas disease in Bolivia. Prevalence rates were calculated from 2007 to 2009 household infection survey data for Bolivia, while environmental data were compiled from the Worldclim database and MODIS satellite imagery. Socio-economic data were obtained from the Bolivian National Institute of Statistics. Disease models identified altitudes at 500-3,500 m above the mean sea level (MSL), low annual precipitation (45-250 mm), and higher diurnal range of temperature (10-19 °C; peak 16 °C) as compatible with the biological requirements of the insect vectors. Socio-economic analyses demonstrated the importance of improved housing materials and water source. Home adobe wall materials and having to fetch drinking water from rivers or wells without pump were found to be highly related to distribution of the disease by the receiver operator characteristic (ROC) area under the curve (AUC) (0.69 AUC, 0.67 AUC and 0.62 AUC, respectively), while areas with hardwood floors demonstrated a direct negative relationship (-0.71 AUC). This study demonstrates that Maxent modelling can be used in disease prevalence and incidence studies to provide governmental agencies with an easily learned, understandable method to define areas as either high, moderate or low risk for the disease. This information may be used in resource planning, targeting and implementation. However, access to high-resolution, sub-municipality socio-economic data (e.g. census tracts) would facilitate elucidation of the relative influence of poverty-related factors on regional disease dynamics.

  20. Environmental and socio-economic risk modelling for Chagas disease in Bolivia

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    Paula Mischler

    2012-09-01

    Full Text Available Accurately defining disease distributions and calculating disease risk is an important step in the control and prevention of diseases. Geographical information systems (GIS and remote sensing technologies, with maximum entropy (Maxent ecological niche modelling computer software, were used to create predictive risk maps for Chagas disease in Bolivia. Prevalence rates were calculated from 2007 to 2009 household infection survey data for Bolivia, while environmental data were compiled from the Worldclim database and MODIS satellite imagery. Socio-economic data were obtained from the Bolivian National Institute of Statistics. Disease models identified altitudes at 500-3,500 m above the mean sea level (MSL, low annual precipitation (45-250 mm, and higher diurnal range of temperature (10-19 °C; peak 16 °C as compatible with the biological requirements of the insect vectors. Socio-economic analyses demonstrated the importance of improved housing materials and water source. Home adobe wall materials and having to fetch drinking water from rivers or wells without pump were found to be highly related to distribution of the disease by the receiver operator characteristic (ROC area under the curve (AUC (0.69 AUC, 0.67 AUC and 0.62 AUC, respectively, while areas with hardwood floors demonstrated a direct negative relationship (-0.71 AUC. This study demonstrates that Maxent modelling can be used in disease prevalence and incidence studies to provide governmental agencies with an easily learned, understandable method to define areas as either high, moderate or low risk for the disease. This information may be used in resource planning, targeting and implementation. However, access to high-resolution, sub-municipality socio-economic data (e.g. census tracts would facilitate elucidation of the relative influence of poverty-related factors on regional disease dynamics.

  1. [Endemic heteroresistant glycopeptide intermediate Staphylcoccus aureus (hGISA) comprising unrelated clonal types and not associated with vancomycin therapy].

    Science.gov (United States)

    Lecaillon, E; Gueudet, P; Wooton, M; Walsh, T R; Macgowan, A P; Jones, M E

    2002-11-01

    The detection of methicillin-resistant S. aureus (SA) (MRSA) refractory to glycopeptides is a serious clinical issue. The prevalence of hetero-resistant GISA (hGISA) strains at H. Maréchal Joffre, France is reported.858 non-repeat SA were isolated during 1999. 367 (43%) of these, from 257 patients, were MRSA (mean incidence 11.9/1000 admissions). All MSRA detected during 1999 were screened for vancomycin (VAN) resistance (BHI+4 mg/l VAN). Isolates recovered were retested using Etest strips (2 McFarland inoculum on BHI) and population analysis profile/area under the curve (PAP-AUC) analysis with hGISA SA Mu3 as a comparator. 58 selected strains were screened for teicoplanin resistance(TEI) using SFM recommended screen (2 McFarland inoculum on MH+5 mg/L TEI) and MIC (0.5 MF inoculum swabbed on MH agar) methods. 188 (51.3%) grew on VAN screen agar (6.1/1000 admissions). 58 strains (7.6%) possessed Etest VAN MIC > 8 mg/l all others being VAN 8 mg/l). PAP-AUC showed 12 strains to have PAP-AUC ratios > 0.95 but < 1.5 (ie. hGISA, not GISA). All 7 isolates defined as hGISA by both Etest and PAP-AUC comprised 1 PFGE clone (< 3 bands difference). Additionally 2 distinct PFGE types were detected among the other 5 hGISA identified PAP-AUC. The 12 hGISAs, were derived from 12 patients with severe underlying disease. None were on glycopeptide therapy prior to hGISA isolation. This is the first report of endemic hGISA, comprising 3 clonal types. The isolation of hVISA seems not to be associated with patient-specific glycopeptide therapies.

  2. 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.

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

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    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.

  4. Pathway analysis of GWAS provides new insights into genetic susceptibility to 3 inflammatory diseases.

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    Hariklia Eleftherohorinou

    Full Text Available Although the introduction of genome-wide association studies (GWAS have greatly increased the number of genes associated with common diseases, only a small proportion of the predicted genetic contribution has so far been elucidated. Studying the cumulative variation of polymorphisms in multiple genes acting in functional pathways may provide a complementary approach to the more common single SNP association approach in understanding genetic determinants of common disease. We developed a novel pathway-based method to assess the combined contribution of multiple genetic variants acting within canonical biological pathways and applied it to data from 14,000 UK individuals with 7 common diseases. We tested inflammatory pathways for association with Crohn's disease (CD, rheumatoid arthritis (RA and type 1 diabetes (T1D with 4 non-inflammatory diseases as controls. Using a variable selection algorithm, we identified variants responsible for the pathway association and evaluated their use for disease prediction using a 10 fold cross-validation framework in order to calculate out-of-sample area under the Receiver Operating Curve (AUC. The generalisability of these predictive models was tested on an independent birth cohort from Northern Finland. Multiple canonical inflammatory pathways showed highly significant associations (p 10(-3-10(-20 with CD, T1D and RA. Variable selection identified on average a set of 205 SNPs (149 genes for T1D, 350 SNPs (189 genes for RA and 493 SNPs (277 genes for CD. The pattern of polymorphisms at these SNPS were found to be highly predictive of T1D (91% AUC and RA (85% AUC, and weakly predictive of CD (60% AUC. The predictive ability of the T1D model (without any parameter refitting had good predictive ability (79% AUC in the Finnish cohort. Our analysis suggests that genetic contribution to common inflammatory diseases operates through multiple genes interacting in functional pathways.

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

    Science.gov (United States)

    Knopp, Matthias Manne; Chourak, Nabil; Khan, Fauzan; Wendelboe, Johan; Langguth, Peter; Rades, Thomas; Holm, René

    2016-08-01

    This study investigated the non-sink in vitro dissolution behavior and in vivo performance in rats of celecoxib (CCX) amorphous solid dispersions with polyvinyl acetate (PVA), polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) at different drug doses. Both in vitro and in vivo, the amorphous solid dispersions with the hydrophilic polymers PVP and HPMC led to higher areas under both, the in vitro dissolution and the plasma concentration-time curves (AUC) compared to crystalline and amorphous CCX for all doses. In contrast, the amorphous solid dispersion with the hydrophobic polymer PVA showed a lower AUC both in vitro and in vivo than crystalline CCX. For crystalline CCX and CCX:PVA, the in vitro AUC was limited by the low solubility of the drug and the slow release of the drug from the hydrophobic polymer, respectively. For the supersaturating formulations, amorphous CCX, CCX:PVP and CCX:HPMC, the in vitro performance was mainly dependent on the dissolution rate and precipitation/crystallization inhibition of the polymer. As expected, the crystallization tendency increased with increasing dose, and therefore the in vitro AUCs did not increase proportionally with dose. Even though the in vivo AUC for all formulations increased with increasing dose, the relative bioavailability decreased significantly, indicating that the supersaturating formulations also crystallized in vivo and that the absorption of CCX was solubility-limited. These findings underline the importance of evaluating relevant in vitro doses, in order to rationally assess the performance of amorphous solid dispersions and avoid confusion in early in vivo studies. PMID:27212472

  6. Measuring the Corticosteroid Responsiveness Endophenotype in Asthma

    Science.gov (United States)

    Clemmer, George L.; Wu, Ann Chen; Rosner, Bernard; McGeachie, Michael J.; Litonjua, Augusto A.; Tantisira, Kelan G.; Weiss, Scott T.

    2015-01-01

    Background Inhaled corticosteroids are the most commonly used controller therapies for asthma, producing treatment responses in six clinical phenotypes; lung function, bronchodilator response, airway responsiveness, symptoms, need for oral steroids and frequency of emergency department visits and hospitalizations. We hypothesize that treatment response in all of these phenotypes is modulated by a single, quantative corticosteroid responsiveness endophenotype. Objective To develop a composite phenotype that combines multiple clinical phenotypes to measure corticosteroid responsiveness with high accuracy, high stability across populations, and high robustness to missing data. Methods We employed principal component analysis (PCA) to determine a composite corticosteroid responsiveness phenotype that we tested in four replication populations. We evaluated the relative accuracy with which the composite and clinical phenotypes measure the endophenotype using treatment effect area under the receiver operating characteristic curve (AUC). Results In the study population, the composite phenotype measured the endophenotype with an AUC of 0.74, significantly exceeding the AUCs of the six individual clinical phenotypes, which ranged from 0.56 (p-value <.001) to 0.67 (p-value 0.015). In four replication populations with a total of 22 clinical phenotypes available, the composite phenotype AUC ranged from 0.69 to 0.73, significantly exceeded the AUCs of 14 phenotypes, and was not significantly exceeded by any single phenotype. Conclusion The composite phenotype measured the endophenotype with higher accuracy, higher stability across populations, and higher robustness to missing data than any clinical phenotype. This should provide the capability to model corticosteroid pharmacologic response and resistance with increased accuracy and reproducibility. PMID:25951964

  7. 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.

  8. Effects of DPP-4 inhibitors on the heart in a rat model of uremic cardiomyopathy.

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    Lyubov Chaykovska

    Full Text Available BACKGROUND: Uremic cardiomyopathy contributes substantially to mortality in chronic kidney disease (CKD patients. Glucagon-like peptide-1 (GLP-1 may improve cardiac function, but is mainly degraded by dipeptidyl peptidase-4 (DPP-4. METHODOLOGY/PRINCIPAL FINDINGS: In a rat model of chronic renal failure, 5/6-nephrectomized [5/6N] rats were treated orally with DPP-4 inhibitors (linagliptin, sitagliptin, alogliptin or placebo once daily for 4 days from 8 weeks after surgery, to identify the most appropriate treatment for cardiac dysfunction associated with CKD. Linagliptin showed no significant change in blood level AUC(0-∞ in 5/6N rats, but sitagliptin and alogliptin had significantly higher AUC(0-∞ values; 41% and 28% (p = 0.0001 and p = 0.0324, respectively. No correlation of markers of renal tubular and glomerular function with AUC was observed for linagliptin, which required no dose adjustment in uremic rats. Linagliptin 7 µmol/kg caused a 2-fold increase in GLP-1 (AUC 201.0 ng/l*h in 5/6N rats compared with sham-treated rats (AUC 108.6 ng/l*h (p = 0.01. The mRNA levels of heart tissue fibrosis markers were all significantly increased in 5/6N vs control rats and reduced/normalized by linagliptin. CONCLUSIONS/SIGNIFICANCE: DPP-4 inhibition increases plasma GLP-1 levels, particularly in uremia, and reduces expression of cardiac mRNA levels of matrix proteins and B-type natriuretic peptides (BNP. Linagliptin may offer a unique approach for treating uremic cardiomyopathy in CKD patients, with no need for dose-adjustment.

  9. Feed withdrawal abate regimens lipodystrophy and metabolic syndrome symptoms, such as glucose tolerance, are associated with the diameter of retroperitoneal adipocytes in rats.

    Science.gov (United States)

    He, Mao L; Sharma, Ranjana; Mir, Priya S; Okine, Erasmus; Dodson, Michael V

    2010-02-01

    Adipocyte numbers were increased by feed withdrawal (FW) regimens in cattle; thus, the effect of FW regimens was studied in male Wistar and fa/fa obese rats, as models for humans, in 2 completely randomized design experiments to abate lipodystrophy and progression of metabolic syndrome symptoms. The hypothesis was that application of FW regimens could alter adipose tissue cellularity, adipocyte size, and affect area under the curve (AUC) during glucose tolerance tests. Objectives were to determine associations among retroperitoneal and inguinal adipose tissue adipocyte number, diameter, and AUC, as affected by fortnightly or a single (at age 50 days) 24-hour FW regimen. Adipocyte marker peroxisome proliferator-activated receptor gamma expression was elevated (P = .054) in the retroperitoneal tissue of fa/fa obese rats in the fortnightly FW treatment because of a 13% increase in tissue cell density (cells per gram; P = .13). Average cell diameter in retroperitoneal adipose and AUC were negatively corelated. Regression analyses after including the square of average cell diameter indicated that average retroperitoneal adipocyte diameter (between 65 and 135 mum) and the AUC were related in a quadratic manner (R(2) = 0.14; n = 49; P = .03) for Wistar rats. Cell number of the inguinal and retroperitoneal adipocytes tended to be positively corelated (r = 0.24; P = .09 and r = 0.26; P = .07, n = 49, respectively) to the AUC and are indexes of adiposity. Results suggest that maintenance of retroperitoneal adipocytes at appropriate diameters may control progression of metabolic syndrome symptoms such as glucose tolerance. PMID:20226998

  10. 3D-Printing for Analytical Ultracentrifugation

    Science.gov (United States)

    Desai, Abhiksha; Krynitsky, Jonathan; Pohida, Thomas J.; Zhao, Huaying

    2016-01-01

    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. PMID:27525659

  11. Predicting hospital-acquired infections by scoring system with simple parameters.

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    Ying-Jui Chang

    Full Text Available BACKGROUND: Hospital-acquired infections (HAI are associated with increased attributable morbidity, mortality, prolonged hospitalization, and economic costs. A simple, reliable prediction model for HAI has great clinical relevance. The objective of this study is to develop a scoring system to predict HAI that was derived from Logistic Regression (LR and validated by Artificial Neural Networks (ANN simultaneously. METHODOLOGY/PRINCIPAL FINDINGS: A total of 476 patients from all the 806 HAI inpatients were included for the study between 2004 and 2005. A sample of 1,376 non-HAI inpatients was randomly drawn from all the admitted patients in the same period of time as the control group. External validation of 2,500 patients was abstracted from another academic teaching center. Sixteen variables were extracted from the Electronic Health Records (EHR and fed into ANN and LR models. With stepwise selection, the following seven variables were identified by LR models as statistically significant: Foley catheterization, central venous catheterization, arterial line, nasogastric tube, hemodialysis, stress ulcer prophylaxes and systemic glucocorticosteroids. Both ANN and LR models displayed excellent discrimination (area under the receiver operating characteristic curve [AUC]: 0.964 versus 0.969, p = 0.507 to identify infection in internal validation. During external validation, high AUC was obtained from both models (AUC: 0.850 versus 0.870, p = 0.447. The scoring system also performed extremely well in the internal (AUC: 0.965 and external (AUC: 0.871 validations. CONCLUSIONS: We developed a scoring system to predict HAI with simple parameters validated with ANN and LR models. Armed with this scoring system, infectious disease specialists can more efficiently identify patients at high risk for HAI during hospitalization. Further, using parameters either by observation of medical devices used or data obtained from EHR also provided good prediction

  12. Forced oscillation, integer and fractional-order modeling in asthma.

    Science.gov (United States)

    Faria, Alvaro C D; Veiga, Juliana; Lopes, Agnaldo J; Melo, Pedro L

    2016-05-01

    The purpose of this study was to evaluate the use of fractional-order (FrOr) modeling in asthma. To this end, three FrOr models were compared with traditional parameters and an integer-order model (InOr). We investigated which model would best fit the data, the correlation with traditional lung function tests and the contribution to the diagnostic of airway obstruction. The data consisted of forced oscillation (FO) measurements obtained from healthy (n=22) and asthmatic volunteers with mild (n=22), moderate (n=19) and severe (n=19) obstructions. The first part of this study showed that a FrOr was the model that best fit the data (relative distance: FrOr=4.3±2.4; InOr=5.1±2.6%). The correlation analysis resulted in reasonable (R=0.36) to very good (R=0.77) associations between FrOr parameters and spirometry. The closest associations were observed between parameters related to peripheral airway obstruction, showing a clear relationship between the FrOr models and lung mechanics. Receiver-operator analysis showed that FrOr parameters presented a high potential to contribute to the detection of the mild obstruction in a clinical setting. The accuracy [area under the Receiver Operating Characteristic curve (AUC)] observed in these parameters (AUC=0.954) was higher than that observed in traditional FO parameters (AUC=0.732) and that obtained from the InOr model (AUC=0.861). Patients with moderate and severe obstruction were identified with high accuracy (AUC=0.972 and 0.977, respectively). In conclusion, the results obtained are in close agreement with asthma pathology, and provide evidence that FO measurement associated with FrOr models is a non-invasive, simple and radiation-free method for the detection of biomechanical abnormalities in asthma. PMID:27040828

  13. Pharmacokinetic profiles of netobimin metabolites after oral administration of zwitterion and trisamine formulations of netobimin to cattle.

    Science.gov (United States)

    Lanusse, C E; Trudeau, C; Ranjan, S; Prichard, R K

    1991-03-01

    Pharmacokinetic profiles of the major metabolites of netobimin were investigated in calves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and trisamine salt solution in a two-way cross-over design. Blood samples were taken serially over a 72-h period and plasma was analysed by HPLC for netobimin (NTB) and its metabolites, including albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). NTB was occasionally detected in plasma between 0.5 and 1.0 h post-treatment. ABZ was not detectable at any time. ABZSO was detected from 0.5-0.75 h up to 32 h post-administration, with a Cmax for the zwitterion suspension of 1.21 +/- 0.13 micrograms/ml and AUC of 18.55 +/- 1.45 micrograms.h/ml, respectively, which were significantly higher (P less than 0.01) than the Cmax (0.67 +/- 0.12 micrograms/ml) and AUC (8.57 +/- 0.91 micrograms.h/ml) for the trisamine solution. ABZSO2 was detected in plasma between 0.75 and 48 h post-administration. The zwitterion suspension resulted in a Cmax (2.91 +/- 0.10 micrograms/ml) and AUC (51.67 +/- 1.95 micrograms.h/ml) for ABZSO2, which were significantly higher (P less than 0.01) than those obtained for the trisamine solution (Cmax = 1.67 +/- 0.11 micrograms/ml and AUC = 22.77 +/- 1.09 micrograms.h/ml). The ratio of AUC for ABZSO2/ABZSO was 2.92 +/- 0.26 (zwitterion) and 2.80 +/- 0.20 (trisamine). The MRT for ABZSO2 was significantly longer (P less than 0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2038091

  14. Evaluation of a Scenario in Which Estimates of Bioequivalence Are Biased and a Proposed Solution: tlast (Common).

    Science.gov (United States)

    Fisher, Dennis; Kramer, William; Burmeister Getz, Elise

    2016-07-01

    In bioequivalence (BE) testing, it is the convention to identify tlast separately for each concentration-vs-time profile. Within-subject differences in tlast between treatments can arise when assay sensitivity is reached during washout, causing profiles to fall below the limit of quantitation (LOQ) at different sampling times. The resulting tlast difference may be systematic, due to true differences in exposure, and/or random, due to measurement noise. The conventional profile-specific tlast approach assumes that concentrations in the terminal phase are sufficiently low that use of different tlast values between treatments within a subject causes negligible bias in the AUC0-t geometric mean ratio (GMR). Here we investigate the validity of this assumption. Using concentration-vs-time data following oral inhalation of 50 μg salmeterol as an example data set, we conducted simulations to evaluate whether use of different test/reference AUC timeframes arising from a systematic difference in exposure causes sufficient AUC0-t GMR bias to influence the determination of BE. To ensure that results would be relevant to BE testing, we considered only test/reference relative systemic exposures within the BE window (80.00%-125.00%). We show that use of conventional profile-specific tlast exaggerates true differences in systemic exposure; the resulting AUC0-t ratios are biased from true relative exposure by an amount large enough to impact the conclusion of BE. Thus, drugs whose concentrations fall below LOQ during washout may fail BE inappropriately using conventional methods. AUC0-t calculated over a common timeframe within each subject (tlast [common]) minimizes this bias and harmonizes the statistical analysis of BE. PMID:26479406

  15. Effect of postprandial hyperglycaemia in non-invasive measurement of cerebral metabolic rate of glucose in non-diabetic subjects

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  16. Relationship between the level of fasting plasma glucose and beta cell functions in Chinese with or without diabetes

    Institute of Scientific and Technical Information of China (English)

    PANG Can; BAO Yu-qian; WANG Chen; LU Jun-xi; JIA Wei-ping; XIANG Kun-san

    2008-01-01

    Background Type 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions.However,the evaluation of beta cell functions is either expensive or inconvenient for clinical practice.We aimed to elucidate the association between the changes of insulin responsiveness and the fasting plasma glucose (FPG) during the development of diabetes.Methods A total of 1192 Chinese individuals with normal blood glucose or hyperglycemia were enrolled for the analysis.The early insulinogenic index (△I30/△G30),the area under the curve of insulin (AUC-I),and homeostasis model assessment were applied to evaluate the early phase secretion,total insulin secretion,and insulin resistance respectively.Polynomial regression analysis was performed to estimate the fluctuation of beta cell functions.Results The △I30/△G30 decreased much more rapidly than the AUC-I accompanying with the elevation of FPG.At the FPG of 110 mg/dl (a pre-diabetic stage),the △I30/△G30 lost 50% of its maximum while the AUC-I was still at a compensated normal level.The AUC-I exhibited abnormal and decreased gradually at the FPG of from 130 mg/dl to higher (overt diabetes),while the △I30/△G30 almost remained at 25% of its maximum value.When hyperglycemia continuously existed at >180 mg/dl,beth the △I30/△G30 and AUC-I were totally lost.Conclusion The increased fasting plasma glucose reflects progressive decompensation of beta cell functions,and could be used to guide the strategy of clinical treatments.

  17. Pharmacokinetics/pharmacodynamics of antofloxacin hydrochloride in a neutropenic murine thigh model of Staphylococcus aureus infection

    Institute of Scientific and Technical Information of China (English)

    Xiu-mei XIAO; Yong-hong XIAO

    2008-01-01

    Aim:Antofloxacin hydrochloride is a new fluoroquinolone antibiotic with broad-spectrum in vitro activity.Using the neutropenic murine thigh infection model,we defined the pharmacodynamic profile and property of antofloxacin hydroehloride against Staphylococcus aureus.Methods:Single-dose pharmacokinetic studies of antofloxacin hydrochloride were carried out in thigh infected mice.Therapy was initiated at 2 h postinoculation with 5-640 mg/kg per d fractionated for different dosing regimens.The thighs were removed for bacterial measurement after 24 h of therapy,the best pharmacokinetic/ pharmacodynamic (PK/PD) index correlated with the efficacy was determined by nonlinear regression analysis.A sigmoid Emax dose-response model was used to estimate the daily dose and AUC24 h/MIC (minimal inhibitory concentration) required to achieve a static effect.Results:The PK was linear with similar elimination half-life over the dose range studied.The AUC24 h/MIC ratio was the PK/PD parameter that best correlated with efficacy (R2=92.3%,90.8% for the two organisms,compared with Cmax/MIC and T>MIC [%],respectively).The 24 h static dose ranged from 34.3 to 153.7 mg/kg per d for all S aureus strains,the total AUC24h/MIC ratio to achieve bacteriostatic effect varied from 31.7 to 122.5 (mean,65.7±30.6).Conclusion:Antofloxacin hydrochloride showed powerful antibacterial activity against the S aureus isolates used in our neutropenic infected mice model.Our data suggested that the AUC/MIC ratio appeared to be most closely linked to the bacterial outcome (R290%),and a total AUC24/MIC ratio of 65.7 appears to be the target value to achieve a net bactericidal activity against S aureus,similar to the results of other fluoroquinolones.

  18. Population Pharmacokinetics of Isavuconazole from Phase 1 and Phase 3 (SECURE) Trials in Adults and Target Attainment in Patients with Invasive Infections Due to Aspergillus and Other Filamentous Fungi.

    Science.gov (United States)

    Desai, Amit; Kovanda, Laura; Kowalski, Donna; Lu, Qiaoyang; Townsend, Robert; Bonate, Peter L

    2016-09-01

    Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent used for the treatment of invasive fungal infections. The objective of this analysis was to develop a population pharmacokinetic (PPK) model to identify covariates that affect isavuconazole pharmacokinetics and to determine the probability of target attainment (PTA) for invasive aspergillosis patients. Data from nine phase 1 studies and one phase 3 clinical trial (SECURE) were pooled to develop the PPK model (NONMEM, version 7.2). Stepwise covariate modeling was performed in Perl-speaks-NONMEM, version 3.7.6. The area under the curve (AUC) at steady state was calculated for 5,000 patients by using Monte Carlo simulations. The PTA using the estimated pharmacodynamic (PD) target value (total AUC/MIC ratio) estimated from in vivo PD studies of invasive aspergillosis over a range of MIC values was calculated using simulated patient AUC values. A two-compartment model with a Weibull absorption function and a first-order elimination process adequately described plasma isavuconazole concentrations. The mean estimate for isavuconazole clearance was 2.360 liters/h (percent coefficient of variation [%CV], 34%), and the mean AUC from 0 to 24 h (AUC0-24) was ∼100 mg·h/liter. Clearance was approximately 36% lower in Asians than in Caucasians. The PTA calculated over a range of MIC values by use of the nonneutropenic murine efficacy index corresponding to 90% survival indicated that adequate isavuconazole exposures were achieved in >90% of simulated patients to treat infections with MICs up to and including 1 mg/liter according to European Committee on Antimicrobial Susceptibility Testing methodology and in >90% of simulated patients for infections with MICs up to and including 0.5 mg/liter according to Clinical and Laboratory Standards Institute methodology. The highest MIC result for PTA was the same for Caucasian and Asian patients. PMID:27381396

  19. 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.

  20. Cocoa extract intake for 4 weeks reduces postprandial systolic blood pressure response of obese subjects, even after following an energy-restricted diet

    Directory of Open Access Journals (Sweden)

    Idoia Ibero-Baraibar

    2016-03-01

    Full Text Available Background: Cardiometabolic profile is usually altered in obesity. Interestingly, the consumption of flavanol-rich foods might be protective against those metabolic alterations. Objective: To evaluate the postprandial cardiometabolic effects after the acute consumption of cocoa extract before and after 4 weeks of its daily intake. Furthermore, the bioavailability of cocoa extract was investigated. Design: Twenty-four overweight/obese middle-aged subjects participated in a 4-week intervention study. Half of the volunteers consumed a test meal enriched with 1.4 g of cocoa extract (415 mg flavanols, while the rest of the volunteers consumed the same meal without the cocoa extract (control group. Glucose and lipid profile, as well as blood pressure and cocoa metabolites in plasma, were assessed before and at 60, 120, and 180 min post-consumption, at the beginning of the study (Postprandial 1 and after following a 4-week 15% energy-restricted diet including meals containing or not containing the cocoa extract (Postprandial 2. Results: In the Postprandial 1 test, the area under the curve (AUC of systolic blood pressure (SBP was significantly higher in the cocoa group compared with the control group (p=0.007, showing significant differences after 120 min of intake. However, no differences between groups were observed at Postprandial 2. Interestingly, the reduction of postprandial AUC of SBP (AUC_Postprandial 2-AUC_Postprandial 1 was higher in the cocoa group (p=0.016. Furthermore, cocoa-derived metabolites were detected in plasma of the cocoa group, while the absence or significantly lower amounts of metabolites were found in the control group. Conclusions: The daily consumption of cocoa extract within an energy-restricted diet for 4 weeks resulted in a greater reduction of postprandial AUC of SBP compared with the effect of energy-restricted diet alone and independently of body weight loss. These results suggest the role of cocoa flavanols on

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

    Science.gov (United States)

    Zhanel, George G; Walkty, Andrew J; Karlowsky, James A

    2016-01-01

    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 (Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ~4000 µg/mL and remains at concentrations >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. PMID:27366158

  2. Single-Dose Pharmacokinetic Study of Tramadol Extended-Release Tablets in Children and Adolescents.

    Science.gov (United States)

    Vandenbossche, Joris; Van Peer, Achiel; Richards, Henry

    2016-09-01

    Combined analyses from 2 open-label, phase-1 studies-the pharmacokinetic profile of tramadol and its metabolite (M1) following a single oral dose of tramadol extended release (ER) (25 to 100 mg) in children (7 to 11 years old; study 1: n = 37) and adolescents (12 to 17 years old; study 2: n = 38) with painful conditions-were historically compared with that of healthy adults following similar dosing. The dose-normalized area under the curve (DN AUC0-24h ) and maximum concentration (DN Cmax ) of tramadol and of M1 in children and in adolescents were lower than those in adults (children vs adults: tramadol, DN AUC0-24h 82.19%; DN Cmax 80.38%, P = .0031; M1, DN AUC0-24h 51.19%, DN Cmax 52.68%, P < .0001; adolescents vs adults: tramadol, DN AUC0-24h 89.56%, DN Cmax 84.01%; M1, DN AUC0-24h 85.28%, DN Cmax 83.03%, P = .0004). The arithmetic mean terminal elimination t1/2 of tramadol in children and adolescents was comparable to that in adults (children 8.4 hours; adolescents 8.5 hours; adults 7.9 hours). The most frequently reported (≥5% of participants) treatment-emergent adverse events in children included headache, upper abdominal pain and constipation, and in adolescents were headache, nausea, dizziness, and stomach discomfort. Multiple factors may have contributed to these observations, including a higher proportion of children (56%) who may have a lower activity of CYP2D6, resulting in reduced clearance of tramadol.

  3. New serum biomarkers for prostate cancer diagnosis

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    Kailash C Chadha

    2014-01-01

    Full Text Available 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.

  4. New serum biomarkers for prostate cancer diagnosis

    Science.gov (United States)

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  5. Factor Structure and Clinical Utility of the Beck Depression Inventory in Patients with Binge Eating Disorder and Obesity

    Science.gov (United States)

    Udo, Tomoko; McKee, Sherry A.; Grilo, Carlos M.

    2015-01-01

    Objective The Beck Depression Inventory (BDI) is often used to assess depression symptoms, but its factor structure and clinical utility have not been evaluated in patients with binge eating disorder (BED) and obesity. Methods 882 treatment-seeking obese patients with BED were administered structured interviews (SCID-I/P) and completed self-report questionnaires. Results 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). 21-item BDI (cut-off score ≥16) showed higher negative predictive values (94.0% vs. 93.0% [MDD]; 92.4% vs. 88.3% [mood disorders]) than brief 16-item BDI (cut-off score ≥13). Conclusions 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. PMID:25537344

  6. Comparison of partial volume effects in arterial and venous contrast curves in CT brain perfusion imaging.

    Directory of Open Access Journals (Sweden)

    Alan J Riordan

    Full Text Available PURPOSE: In brain CT perfusion (CTP, the arterial contrast bolus is scaled to have the same area under the curve (AUC as the venous outflow to correct for partial volume effects (PVE. This scaling is based on the assumption that large veins are unaffected by PVE. Measurement of the internal carotid artery (ICA, usually unaffected by PVE due to its large diameter, may avoid the need for partial volume correction. The aims of this work are to examine i the assumptions behind PVE correction and ii the potential of selecting the ICA obviating correction for PVE. METHODS: The AUC of the ICA and sagittal sinus were measured in CTP datasets from 52 patients. The AUCs were determined by i using commercial CTP software based on a Gaussian curve-fitting to the time attenuation curve, and ii by simple integration of the time attenuation curve over a time interval. In addition, frames acquired up to 3 minutes after first bolus passage were used to examine the ratio of arterial and venous enhancement. The impact of selecting the ICA without PVE correction was illustrated by reporting cerebral blood volume (CBV measurements. RESULTS: In 49 of 52 patients, the AUC of the ICA was significantly larger than that of the sagittal sinus (p = 0.017. Measured after the first pass bolus, contrast enhancement remained 50% higher in the ICA just after the first pass bolus, and 30% higher 3 minutes later. CBV measurements were significantly lowered when the ICA was used without PVE correction. CONCLUSIONS: Contradicting the assumptions underlying PVE correction, contrast in the ICA was significantly higher than in the sagittal sinus, even 3 minutes after the first pass of the contrast bolus. PVE correction might lead to overestimation of CBV if the CBV is calculated using the AUC of the time attenuation curves.

  7. 3D-Printing for Analytical Ultracentrifugation.

    Science.gov (United States)

    Desai, Abhiksha; Krynitsky, Jonathan; Pohida, Thomas J; Zhao, Huaying; Schuck, Peter

    2016-01-01

    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.

  8. Evaluation of Respiratory Motion Effect on Defect Detection in Myocardial Perfusion SPECT: A Simulation Study.

    Science.gov (United States)

    Yang, Yu-Wen; Chen, Jyh-Cheng; He, Xin; Wang, Shyh-Jen; Tsui, Benjamin M W

    2009-06-01

    The objective of this study is to investigate the effects of respiratory motion (RM) on defect detection in Tc-99m sestamibi myocardial perfusion SPECT (MPS) using a phantom population that includes patient variability. Three RM patterns are included, namely breath-hold, slightly enhanced normal breathing, and deep breathing. For each RM pattern, six 4-D NCAT phantoms were generated, each with anatomical variations. Anterior, lateral and inferior myocardial defects with different sizes and contrasts were inserted. Noise-free SPECT projections were simulated using an analytical projector. Poisson noise was then added to generate noisy realizations. The projection data were reconstructed using the OS-EM algorithm with 1 and 4 subsets/iteration and at 1, 2, 3, 5, 7, and 10 iterations. Short-axis images centered at the centroid of the myocardial defect were extracted, and the channelized Hotelling observer (CHO) was applied for the detection of the defect. The CHO results show that the value of the area under the receiver operating characteristics (ROC) curve (AUC) is affected by the RM amplitude. For all the defect sizes and contrasts studied, the highest or optimal AUC values indicate maximum detectability decrease with the increase of the RM amplitude. With no respiration, the ranking of the optimal AUC value in decreasing order is anterior then lateral, and finally inferior defects. The AUC value of the lateral defect drops more severely as the RM amplitude increases compared to other defect locations. Furthermore, as the RM amplitude increases, the AUC values of the smaller defects drop more quickly than the larger ones. We demonstrated that RM affects defect detectability of MPS imaging. The results indicate that developments of optimal data acquisition methods and RM correction methods are needed to improve the defect detectability in MPS.

  9. A predictive model combining fecal calgranulin B and fecal occult blood tests can improve the diagnosis of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Byung Chang Kim

    Full Text Available AIM: Current fecal screening tools for colorectal cancer (CRC, such as fecal occult blood tests (FOBT, are limited by their low sensitivity. Calgranulin B (CALB was previously reported as a candidate fecal marker for CRC. This study investigated whether a combination of the FOBT and fecal CALB has increased sensitivity and specificity for a diagnosis of CRC. MATERIALS AND METHODS: Patients with CRC (n = 175, and healthy individuals (controls; n = 151 were enrolled into the development (81 cases and 51 controls and validation (94 cases and 100 controls sets. Stool samples were collected before bowel preparation. CALB levels were determined by western blotting. FOBT and fecal CALB results were used to develop a predictive model based on logistic regression analysis. The benefit of adding CALB to a model with only FOBT was evaluated as an increased area under the receiver operating curve (AUC, partial AUC, and reclassification improvement (RI in cases and controls, and net reclassification improvement (NRI. RESULTS: Mean CALB level was significantly higher in CRC patients than in controls (P<0.001. CALB was not associated with tumor stage or cancer site, but positivity on the FOBT was significantly higher in advanced than in earlier tumor stages. At a specificity of 90%, the cross-validated AUC and sensitivity were 89.81% and 82.72%, respectively, in the development set, and 92.74% and 79.79%, respectively, in the validation set. The incremental benefit of adding CALB to the model, as shown by the increase in AUC, had a p-value of 0.0499. RI in cases and controls and NRI all revealed that adding CALB significantly improved the prediction model. CONCLUSION: A predictive model using a combination of FOBT and CALB may have greater sensitivity and specificity and AUC for predicting CRC than models using a single marker.

  10. 3D-Printing for Analytical Ultracentrifugation.

    Science.gov (United States)

    Desai, Abhiksha; Krynitsky, Jonathan; Pohida, Thomas J; Zhao, Huaying; Schuck, Peter

    2016-01-01

    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. PMID:27525659

  11. Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects

    Directory of Open Access Journals (Sweden)

    Fang Tang

    2016-01-01

    Full Text Available The aim of this study was to apply the reference-scaled average bioequivalence (RSABE approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs for the log-transformed ratios and ratio of geometric means (GMR of AUC and Cmax of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and Cmax of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of Cmax, AUC0–t and AUC0–∞ of agomelatine (104.42–139.86, 101.33–123.83 and 97.90–117.94 were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55–123.03, 101.95–109.10 and 101.72–108.70 and 7-desmethyl-agomelatine (104.50–125.23, 102.36–111.50 and 101.62–110.64 were within the FDA bioequivalence definition intervals (0.80–1.25 for AUC and 0.75–1.33 for Cmax. The RSABE approach was successful in evaluating the bioequivalence of these two formulations.

  12. 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.

  13. Associations of cytological endometritis with energy metabolism and inflammation during the periparturient period and early lactation in dairy cows.

    Science.gov (United States)

    Yasui, T; McCann, K; Gilbert, R O; Nydam, D V; Overton, T R

    2014-05-01

    Multiparous Holstein cows (n=108) were used to determine the associations of cytological endometritis (CE) with plasma nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) as markers of energy metabolism, calculated energy balance (EB), and plasma haptoglobin (Hp) as a marker of inflammation during the periparturient period and early lactation. Evaluation of endometrial cytology by low-volume uterine lavage was conducted on 1d between 40 and 60 d postcalving. The incidence of CE among cows sampled was 40%. The area under the curve (AUC) was calculated for both NEFA and BHBA using data collected from 3 wk before to 3 wk after parturition. Data for NEFA and BHBA AUC were stratified into prepartum (wk -3 to parturition) and postpartum (parturition to wk +3) for statistical analysis. Prepartum AUC for neither NEFA nor BHBA was associated with subsequent CE; however, cows that subsequently developed CE tended to have higher postpartum AUC for NEFA and had higher postpartum AUC for BHBA. Consistent with the results for plasma NEFA and BHBA, calculated EB during the prepartum period was not different in cows that did or did not develop CE; however, cows with CE had lower EB during the 6-wk postpartum period compared with cows without CE. Analysis of EB by week (wk -3 to -1 before calving and wk +1 to +6 postcalving) indicated that EB in cows with CE was lower at wk +1, +2, and +3 and tended to be lower at wk +6 than cows without CE. Plasma Hp concentrations were analyzed from wk +1 to +8 of lactation; concentrations of Hp were not different during either wk +1 or the entire postpartum period between cows that did or did not develop CE. These results suggest that lower energy status during the first 3 wk postpartum, but not necessarily systemic inflammation, is associated with subsequent development of CE. PMID:24612816

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

    Science.gov (United States)

    Knopp, Matthias Manne; Chourak, Nabil; Khan, Fauzan; Wendelboe, Johan; Langguth, Peter; Rades, Thomas; Holm, René

    2016-08-01

    This study investigated the non-sink in vitro dissolution behavior and in vivo performance in rats of celecoxib (CCX) amorphous solid dispersions with polyvinyl acetate (PVA), polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) at different drug doses. Both in vitro and in vivo, the amorphous solid dispersions with the hydrophilic polymers PVP and HPMC led to higher areas under both, the in vitro dissolution and the plasma concentration-time curves (AUC) compared to crystalline and amorphous CCX for all doses. In contrast, the amorphous solid dispersion with the hydrophobic polymer PVA showed a lower AUC both in vitro and in vivo than crystalline CCX. For crystalline CCX and CCX:PVA, the in vitro AUC was limited by the low solubility of the drug and the slow release of the drug from the hydrophobic polymer, respectively. For the supersaturating formulations, amorphous CCX, CCX:PVP and CCX:HPMC, the in vitro performance was mainly dependent on the dissolution rate and precipitation/crystallization inhibition of the polymer. As expected, the crystallization tendency increased with increasing dose, and therefore the in vitro AUCs did not increase proportionally with dose. Even though the in vivo AUC for all formulations increased with increasing dose, the relative bioavailability decreased significantly, indicating that the supersaturating formulations also crystallized in vivo and that the absorption of CCX was solubility-limited. These findings underline the importance of evaluating relevant in vitro doses, in order to rationally assess the performance of amorphous solid dispersions and avoid confusion in early in vivo studies.

  15. Effect of breast cancer phenotype on diagnostic performance of MRI in the prediction to response to neoadjuvant treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bufi, Enida, E-mail: reagandus@alice.it [Department of Bioimaging and Radiological Sciences, Catholic University, Rome (Italy); Belli, Paolo; Di Matteo, Marialuisa [Department of Bioimaging and Radiological Sciences, Catholic University, Rome (Italy); Terribile, Daniela; Franceschini, Gianluca [Department of Surgery, Breast Unit, Catholic University, Rome (Italy); Nardone, Luigia [Department of Radiotherapy, Catholic University, Rome (Italy); Petrone, Gianluigi [Department of Pathology, Catholic University, Rome (Italy); Bonomo, Lorenzo [Department of Bioimaging and Radiological Sciences, Catholic University, Rome (Italy)

    2014-09-15

    Aim: The estimation of response to neoadjuvant chemotherapy (NAC) is useful in the surgical decision in breast cancer. We addressed the diagnostic reliability of conventional MRI, of diffusion weighted imaging (DWI) and of a merged criterion coupling morphological MRI and DWI. Diagnostic performance was analysed separately in different tumor subtypes, including HER2+ (human epidermal growth factor receptor 2)/HR+ (hormone receptor) (hybrid phenotype). Materials and methods: Two-hundred and twenty-five patients underwent MRI before and after NAC. The response to treatment was defined according to the RECIST classification and the evaluation of DWI with apparent diffusion coefficient (ADC). The complete pathological response – pCR was assessed (Mandard classification). Results: Tumor phenotypes were Luminal (63.6%), Triple Negative (16.4%), HER2+ (7.6%) or Hybrid (12.4%). After NAC, pCR was observed in 17.3% of cases. Average ADC was statistically higher after NAC (p < 0.001) among patients showing pCR vs. those who had not pCR. The RECIST classification showed adequate performance in predicting the pCR in Triple Negative (area under the receiver operating characteristic curve, ROC AUC = 0.9) and in the HER2+ subgroup (AUC = 0.826). Lower performance was found in the Luminal and Hybrid subgroups (AUC 0.693 and 0.611, respectively), where the ADC criterion yielded an improved performance (AUC = 0.787 and 0.722). The coupling of morphological and DWI criteria yielded maximally improved performance in the Luminal and Hybrid subgroups (AUC = 0.797 and 0.761). Conclusion: The diagnostic reliability of MRI in predicting the pCR to NAC depends on the tumor phenotype, particularly in the Luminal and Hybrid subgroups. In these cases, the coupling of morphological MRI evaluation and DWI assessment may facilitate the diagnosis.

  16. Criterion validity of the Short Mood and Feelings Questionnaire and one- and two-item depression screens in young adolescents

    Directory of Open Access Journals (Sweden)

    McCauley Elizabeth

    2010-02-01

    Full Text Available Abstract Background The use of short screening questionnaires may be a promising option for identifying children at risk for depression in a community setting. The objective of this study was to assess the validity of the Short Mood and Feelings Questionnaire (SMFQ and one- and two-item screening instruments for depressive disorders in a school-based sample of young adolescents. Methods Participants were 521 sixth-grade students attending public middle schools. Child and parent versions of the SMFQ were administered to evaluate the child's depressive symptoms. The presence of any depressive disorder during the previous month was assessed using the Diagnostic Interview Schedule for Children (DISC as the criterion standard. First, we assessed the diagnostic accuracy of child, parent, and combined scores of the full 13-item SMFQ by calculating the area under the receiver operating characteristic curve (AUC, sensitivity and specificity. The same approach was then used to evaluate the accuracy of a two-item scale consisting of only depressed mood and anhedonia items, and a single depressed mood item. Results The combined child + parent SMFQ score showed the highest accuracy (AUC = 0.86. Diagnostic accuracy was lower for child (AUC = 0.73 and parent (AUC = 0.74 SMFQ versions. Corresponding versions of one- and two-item screens had lower AUC estimates, but the combined versions of the brief screens each still showed moderate accuracy. Furthermore, child and combined versions of the two-item screen demonstrated higher sensitivity (although lower specificity than either the one-item screen or the full SMFQ. Conclusions Under conditions where parents accompany children to screening settings (e.g. primary care, use of a child + parent version of the SMFQ is recommended. However, when parents are not available, and the cost of a false positive result is minimal, then a one- or two-item screen may be useful for initial identification of at-risk youth.

  17. Timing of obstetrical assistance affects peripartal cardiac autonomic function and early maternal behavior of dairy cows.

    Science.gov (United States)

    Kovács, Levente; Kézér, Fruzsina Luca; Ruff, Ferenc; Szenci, Ottó

    2016-10-15

    Peripartal autonomic nervous system function and early maternal behavior were investigated in 79 multiparous Holstein-Friesian cows. Animals were allocated into four groups based on the technology of calving management: 1) unassisted calving in a group pen (UCG; N=19), 2) unassisted calving in an individual pen (UCI; N=21), 3) assisted calving with appropriately timed obstetrical assistance (ACA; N=20), and 4) assisted calving with premature obstetrical assistance (ACP; N=19). Heart rate, the high frequency (HF) component of heart rate variability (HRV) as a measure of vagal activity and the ratio between the low frequency (LF) and HF components (LF/HF ratio) as a parameter of sympathetic nervous system activity were calculated. Heart rate and HRV parameters were presented as areas under the curves (AUC) for the following periods: 1) prepartum period (between 96h before the onset of calving restlessness and the onset of restlessness), 2) parturition (between the onset calving restlessness and delivery), and 3) postpartum period (during a 48-h period after delivery). Pain-related behaviors were recorded during parturition (i.e., the occurrence of vocalization and stretching the neck towards the abdomen) and during a 2-h observation period after calving (i.e., the occurrence of vocalization, stretching the neck towards the abdomen and the duration of standing with an arched back). Early maternal behavior was observed during the first 2h following calving as follows: 1) latency and duration of sniffing calf's head/body, and 2) latency and duration of licking calf's head/body. No difference was found across groups in autonomic function before the onset of calving restlessness. Area under the heart rate curve was higher in ACP cows during parturition (39.6±2.5beats/min×h) compared to UCG, UCI and ACA animals (AUC=13.1±0.9beats/min×h, AUC=22.3±1.4beats/min×h and AUC=25.0±2.1beats/min×h, respectively). Area under the heart rate curve did not differ across the UCG

  18. Timing of obstetrical assistance affects peripartal cardiac autonomic function and early maternal behavior of dairy cows.

    Science.gov (United States)

    Kovács, Levente; Kézér, Fruzsina Luca; Ruff, Ferenc; Szenci, Ottó

    2016-10-15

    Peripartal autonomic nervous system function and early maternal behavior were investigated in 79 multiparous Holstein-Friesian cows. Animals were allocated into four groups based on the technology of calving management: 1) unassisted calving in a group pen (UCG; N=19), 2) unassisted calving in an individual pen (UCI; N=21), 3) assisted calving with appropriately timed obstetrical assistance (ACA; N=20), and 4) assisted calving with premature obstetrical assistance (ACP; N=19). Heart rate, the high frequency (HF) component of heart rate variability (HRV) as a measure of vagal activity and the ratio between the low frequency (LF) and HF components (LF/HF ratio) as a parameter of sympathetic nervous system activity were calculated. Heart rate and HRV parameters were presented as areas under the curves (AUC) for the following periods: 1) prepartum period (between 96h before the onset of calving restlessness and the onset of restlessness), 2) parturition (between the onset calving restlessness and delivery), and 3) postpartum period (during a 48-h period after delivery). Pain-related behaviors were recorded during parturition (i.e., the occurrence of vocalization and stretching the neck towards the abdomen) and during a 2-h observation period after calving (i.e., the occurrence of vocalization, stretching the neck towards the abdomen and the duration of standing with an arched back). Early maternal behavior was observed during the first 2h following calving as follows: 1) latency and duration of sniffing calf's head/body, and 2) latency and duration of licking calf's head/body. No difference was found across groups in autonomic function before the onset of calving restlessness. Area under the heart rate curve was higher in ACP cows during parturition (39.6±2.5beats/min×h) compared to UCG, UCI and ACA animals (AUC=13.1±0.9beats/min×h, AUC=22.3±1.4beats/min×h and AUC=25.0±2.1beats/min×h, respectively). Area under the heart rate curve did not differ across the UCG

  19. 多剂量口服硝苯地平控释片的人体药动学及生物等效性研究%Pharmacokinetics and Bioequivalence Study of Nifedipine Controlled-release Tablets after Multiple Doses Administration in Healthy Volunteers

    Institute of Scientific and Technical Information of China (English)

    周新腾; 魏敏吉; 石晓东; 张明; 张朴; 姜斯博

    2009-01-01

    OBJECTIVE Povidone/Copovidone were used as the main osmopolymers instead of Poly (ethylene oxide) (PEO) to prepare nifedipine controlled-release tablets of new osmotic pump type. The pharmacokinetic properties of nifedipine controlled-release tablets after multiple doses in healthy volunteers were studied, and the relative bioavailability of the test preparation was calculated and the bioequivalence was evaluated. METHODS Twenty four male healthy volunteers were enrolled in a randomized two-way crossover design. 30 mg nifedipine was administered per day during consecutive 7 d. The drug concentration in blood was determined with LC-MS/MS method. The pharmacokinetic parameters, relative bioavailability and the bioequivalence were calculated by DAS program. RESULTS The main pharmacokinetic parameters after multiple doses of test preparation and reference preparation were as follows: T_(1/2β) (9.0±2.2)h and (9.5±3.8)h; T_(max) (8.1±7.4)h and (6.7±4.1)h; C_(ssmax) (52.7±28.2)μg.L~(-1) and (44.5±22.6)μg·L~(-1); C_(ssmin) (29.4±22.2)μg·L~(-1) and (28.7 15.8)μg·L~(-1); AUC_(0-60) (1 087.4±671.6)μg·L~(-1)·h and (1 040.2±518.4)μg·L~(-1)·h; AUC_(0-∞) (1 113.1±677.2)μg·L~(-1)·h and (1 074.5±519.8)μg·L~(-1)·h, AUC_(ss) (809.1±454.0)μg·L~(-1)·h and (713.9±382.2)μg·L~(-1)·h. The average relative bioavailability of the test preparation versus the reference preparation was as follows: F_(AUC_(ss)) (115.2±29.2)%, F_(AUC_(0-40)) (103.4±30.2)% and F_(AUC_(0-)) (102.2±29.7)%. DF was (77.84±52.09)% and (55.48±30.54)%. The 90% confidence interval of C_(max), AUC_(0-60), AUC_(0-∞) and AUC_(ss) after longarithmic transform was (100.9-126.0)%, (87.5-111.8)%,(86.8-110.3)% and (98.8-124.4)% respectively. There was no significant difference in T_(max) after non-parameter rank sum test. No adverse reaction was observed during the trial. CONCLUSION The test preparation was bioequivalent to the reference preparation. Povidone/Copovidone could

  20. Effect of CYP2C19 genetic polymorphism on pharmacokinetic characterstics and 5-hydroxyl metabolic pathway of lansoprazole in Chinese volunteers%CYP2C19基因多态性对中国人体内兰索拉唑药代动力学及其5-羟基代谢通路的影响

    Institute of Scientific and Technical Information of China (English)

    严非; 夏春华; 熊玉卿

    2011-01-01

    AIM: To investigate the effect of CYP2C19 polymorphism on pharmacokinetic characteristics and 5-hydroxyl metabolic pathway of lansoprazole in Chinese subjects. METH-ODS: Twelve healthy subjects were typed by u-sing RFLP-PCR method. After intravenous drip 30 mg lansoprazole, the plasma concentrations of lansoprazole in subjects were determined byLC-MS method. The pharmacokinetic parameters of lansoprazole and AUClpz/AUC5-Ohlpz were calculated and compared between different groups. RESULTS-. After all the subjects were given 30 mg lansoprazole, it found that the AUCo-,, AUCo-(x), CLz, ( AUCLpz/ AUC5-oh)0-t, and (AUCLpZ/AUC5-oh)0-∞ of the mutant types were equivalent to 2.381, 2.572, 0. 428, 3. 602 and 4. 083-fold as those of the wild types, respectively. CONCLUSION: The CYP2C19 genetic polymorphism, which has significant influence on the pharmacokinetic characteristics of the lansoprazole in Chinese volun-teers (P<0. 05), has very significant influence on the 5-hydroxyl metabolic pathway of the lansoprazole (P<0. 01). The result suggests that CYP2C19 genetic polymorphism is one of the important factors leading to individual concentration differences of the lansoprazole and has a better relevance with the 5-hydroxyl metabolic pathway.%目的:研究CYP2C19基因多态性对中国人体内兰索拉唑药代动力学及其5-羟基代谢通路的影响.方法:采用RFLP-PCR方法对12名健康受试者进行CYP2C19基因多态性检测,并采用液相色谱-质谱法(LC-MS)检测兰索拉唑体内血药浓度并计算相关的药代动力学参数,比较不同基因型受试者之间主要药代动力学参数以及AUCLpz/AUC5-oH LPZ 比 值(AUGansoprazole/AUC5-hydroxylansoprazole,此参数用以评价5-羟基代谢的标准)的差异.结果:12名健康受试者在给予30 mg兰索拉唑后,发现突变型个体AUC0-t、AUC0-∞、CLz、(AUCLPZ/AUC5-OHLPZ)0-t、(AUCLPZ/AUC5-OH LPZ)0-.∞分别相当于野生型个体的2.381、2.572、0.428、3.602、4.083

  1. 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

  2. Petrogenesis of Late Triassic ultramafic rocks from the Andong Ultramafic Complex, South Korea

    Science.gov (United States)

    Kim, Nak Kyu; Choi, Sung Hi

    2016-11-01

    To constrain the source and tectonomagmatic processes that gave rise to the Andong Ultramafic Complex (AUC) in South Korea, we determined the clinopyroxene Sr-Nd-Hf-Pb isotope and trace element compositions as well as the whole-rock and mineral compositions for the Late Triassic (ca. 222 Ma) ultramafic rocks from the complex. They are composed of dunites, wehrlites, pyroxene/hornblende peridotites, and pyroxenites. The constituent minerals are olivines, diopsides/augites, bronzites, calcic-amphiboles, and spinels. Clinopyroxenes exhibit a convex-upward rare earth element (REE) pattern, with an apex at Sm. The whole-rock compositions plot away from the residual mantle peridotite trends, with variable but lower Al2O3 and SiO2 contents, and higher CaO, FeO*, and TiO2 contents at a given value of MgO. Estimated equilibrium temperatures for the AUC rocks range from 420 to 780 °C. These observations, together with the absence of reaction or melt impregnation textures, indicate that the AUC ultramafic rocks are magmatic cumulates emplaced within the crust rather than residual mantle or mantle-melt reaction products. The AUC clinopyroxenes have compositions intermediate between the oceanic island basalt- and arc basalt-related cumulate clinopyroxenes. The AUC spinels have lower Cr#s than the arc-related magmatic cumulate spinels. They plot within the field for spinels from mid-ocean ridge basalts (MORB) on a TiO2 vs. Cr# diagram. However, the AUC clinopyroxenes have much more radiogenic Sr ([87Sr/86Sr]i = 0.70554 to 0.70596), unradiogenic Nd ([εNd]i = - 1.0 to - 0.3), and Hf ([εHf]i = + 4.4 to + 6.6) isotopic compositions than those of the MORB or fore-arc basalts (FAB). In the Sr-Nd isotopic correlation diagram, the AUC clinopyroxenes plot in the enriched extension of the "mantle array". They also have more elevated 207Pb/204Pb ratios at a given 206Pb/204Pb than those of the MORB or FAB. In the Nd-Hf isotope space, the AUC clinopyroxenes have somewhat elevated 176Hf

  3. 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.

  4. Effects of contrast-enhancement, reconstruction slice thickness and convolution kernel on the diagnostic performance of radiomics signature in solitary pulmonary nodule

    Science.gov (United States)

    He, Lan; Huang, Yanqi; Ma, Zelan; Liang, Cuishan; Liang, Changhong; Liu, Zaiyi

    2016-01-01

    The Effects of contrast-enhancement, reconstruction slice thickness and convolution kernel on the diagnostic performance of radiomics signature in solitary pulmonary nodule (SPN) remains unclear. 240 patients with SPNs (malignant, n = 180; benign, n = 60) underwent non-contrast CT (NECT) and contrast-enhanced CT (CECT) which were reconstructed with different slice thickness and convolution kernel. 150 radiomics features were extracted separately from each set of CT and diagnostic performance of each feature were assessed. After feature selection and radiomics signature construction, diagnostic performance of radiomics signature for discriminating benign and malignant SPN was also assessed with respect to the discrimination and classification and compared with net reclassification improvement (NRI). Our results showed NECT-based radiomics signature demonstrated better discrimination and classification capability than CECT in both primary (AUC: 0.862 vs. 0.829, p = 0.032; NRI = 0.578) and validation cohort (AUC: 0.750 vs. 0.735, p = 0.014; NRI = 0.023). Thin-slice (1.25 mm) CT-based radiomics signature had better diagnostic performance than thick-slice CT (5 mm) in both primary (AUC: 0.862 vs. 0.785, p = 0.015; NRI = 0.867) and validation cohort (AUC: 0.750 vs. 0.725, p = 0.025; NRI = 0.467). Standard convolution kernel-based radiomics signature had better diagnostic performance than lung convolution kernel-based CT in both primary (AUC: 0.785 vs. 0.770, p = 0.015; NRI = 0.156) and validation cohort (AUC: 0.725 vs.0.686, p = 0.039; NRI = 0.467). Therefore, this study indicates that the contrast-enhancement, reconstruction slice thickness and convolution kernel can affect the diagnostic performance of radiomics signature in SPN, of which non-contrast, thin-slice and standard convolution kernel-based CT is more informative. PMID:27721474

  5. 超声造影对肝细胞癌与肝局灶性结节增生的定量对比分析%Quantification analysis of contrast enhanced ultrasonography on hepatocellular carcinoma and focal nodular hyperplasia

    Institute of Scientific and Technical Information of China (English)

    黄莺; 杜雅灵

    2012-01-01

    Objective To investigate the value of quantification analysis of contrast enhanced ultrasonography (CEUS)in differential diagnosis of hepatocellular carcinoma(HCC)and focal nodular hyperplasia(FNH). Methods 64 HCCs and 21 FNHs were off-line analyzed with dynamic images. Quantitative parameters such as derived peak intensity (DPI), time to peak(TTP), area under the curve(AUC), slop of rise, the absolute vslue for slop of down were acquired , and the standardized values (sDPI, sAUC) included the ratio of parameters from the focus to those from hepatic parenchyma. These quantitative parameters were analyzed by statistics. Results Quantitative parameters such as AUC, slop of rise, sDPI and sAUC in HCC group were smaller than those in FNH group(P0. 05). Conclusion TIC of contrast enhanced ultrasonography can provide quantitative analysis for HCC and FNH with preferable clinical application value.%目的 探讨超声造影(CEUS)对肝细胞癌(HCC)与肝局灶性结节增生(FNH)的声学定量对比价值.方法 回顾性分析64例HCC和21例FNH患者,对其CEUS检查结果进行定量分析,从时间-强度曲线(TIC)上得到下列定量参数:达峰绝对值(DPI)、达峰时间(TTP)、曲线下面积(AUC)、曲线上升支斜率、下降支斜率的绝对值以及病灶与肝实质相应参数相比所得的标化值sDPI、sAUC,进行统计学分析.结果 HCC组的AUC、曲线上升支斜率、sDPI及sAUC分别均小于FNH组(P<0.05),而TTP、曲线下降支斜率的绝对值大于FNH组(P<0.05),两组的DPI无显著差异(P>0.05).结论 超声造影技术结合时间-强度曲线定量分析对HCC和FNH的鉴别诊断有重要的临床应用价值.

  6. The Added Value of Medical Testing in Underwriting Life Insurance.

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    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

  7. Pharmacokinetics and bioavailability study of two ondansetron oral soluble film formulations in fasting healthy male Chinese volunteers

    Directory of Open Access Journals (Sweden)

    Zhu YB

    2015-08-01

    Full Text Available Yubing Zhu,1 Qian Zhang,1 Jianjun Zou,2 Meng Wan,1 Zheng Zhao,1 Junrong Zhu1 1Department of Pharmacy, 2Laboratory of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China Background: Ondansetron oral soluble film is designed to be applied on top of the tongue without requiring water to aid dissolution or swallowing, which is especially fitting for nausea and vomiting patients.Purpose: This study was conducted to compare the bioavailability of two 8 mg ondansetron oral soluble film formulations.Patients and methods: This randomized, open-label, two-period crossover study was performed under fasting conditions. A total of ten eligible subjects were randomly assigned at a 1:1 ratio to receive a single 8 mg dose of the test and reference ondansetron oral soluble film formulations, followed by a 1-week washout period and administration of the alternate formulation. The concentrations of ondansetron were assayed using an liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS method. For analysis of pharmacokinetic properties, including the peak concentration of Tmax (Cmax, AUC from time 0 (baseline to t hours (AUC0–t, and AUC from baseline to infinity (AUC0–∞, blood samples were obtained at intervals over the 24-hour period after studying drug administration. Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis and by questioning subjects about adverse events.Results: The mean (standard derivation [SD] relative bioavailability was 96.5 (23.7%. The 90% confidence intervals (CIs for the log-transformed ratios of Cmax and AUC0–t were 84.71%–103.28% and 91.38%–108.60%, respectively (P>0.05. Similar results were found for the data without log-transformation. No statistically significant differences were found based on analysis of variance. No significant adverse events occurred

  8. Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms

    Directory of Open Access Journals (Sweden)

    Hermann R

    2014-11-01

    Full Text Available Robert Hermann,1 Julius Mungo,2 Peter Jürgen Cnota,2 Dan Ziegler3 1Clinical Research Appliance (cr appliance, Gelnhausen, Germany; 2MEDA Pharma GmbH & Co KG, Bad Homburg, Germany; 3Institute for Clinical Diabetology, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany Abstract: The present study aimed to examine the enantiomer-selective pharmacokinetics (PK, relative bioavailability (Frel, and sex effects of various oral dosage forms of racemic alpha-lipoic acid (ALA. In an open-label, randomized, four-period, four-sequence crossover study, 24 healthy adult subjects (12 males and 12 females received single doses of 600 mg of ALA in fasted state at four different occasions as follows: three 200 mg tablets (T 200; two 300 mg tablets (T 300; one 600 mg tablet (T 600; and a racemic ALA solution (OS. All tablet formulations (Thioctacid HR were considered test treatments, while the OS (Thioctacid, 600 T served as the reference treatment. Serial blood samples were collected over 8 hours postdose to quantify R-(+- and S-(–-ALA enantiomer plasma concentrations for the PK evaluation. The maximum observed plasma concentration (Cmax and total exposure (area under the curve [AUC]0–t were compared between treatments by analysis of variance. Weight-normalized Cmax and the AUC data of male and female study subjects were applied to examine the presence of sex effects. All treatments displayed rapid absorption of both enantiomers with median time to maximum concentration (tmax values ranging from 0.33–0.5 hours. The Frel of all tablet formulations was comparable, with R-(+-enantiomer Cmax test/reference ratios ranging from 36% (T 600 to 43% (T 200, and R-(+-enantiomer AUC test/reference ratios ranging from 64% (T 600 to 79% (T 300, indicating a favorable Frel of all tablet formulations, especially in terms of the total extent of absorption (AUC. An examination of weight-normalized female/male Cmax and AUC sex ratios for both ALA

  9. A Phase 1, randomized, open-label crossover study to evaluate the safety and pharmacokinetics of 400 mg albaconazole administered to healthy participants as a tablet formulation versus a capsule formulation

    Directory of Open Access Journals (Sweden)

    van Rossem K

    2013-01-01

    Full Text Available Koen van Rossem,1 Jenny A Lowe21Stiefel, Research Triangle Park, NC, USA; 2Stiefel, Stockley Park West, Uxbridge, UKBackground: Albaconazole is a novel triazole being developed for the oral treatment of fungal diseases. Once-weekly oral dosing with 400 mg albaconazole for 24 or 36 weeks resulted in high rates of clinical and mycological resolution for distal subungual onychomycosis, as well as a favorable safety and tolerability profile.Purpose: To compare four 100-mg albaconazole capsules to one 400-mg albaconazole tablet for bioavailability, bioequivalence, tolerability, and safety.Patients and methods: Forty participants were enrolled in this Phase I, open-label, two-sequence crossover study. Twenty participants were exposed to a single 400-mg tablet dose of albaconazole before being crossed over to a single dose of four 100-mg albaconazole capsules. The second group of 20 participants received the study products in reverse order. Blood samples were taken over 15 days post-dose to assess the plasma concentrations and pharmacokinetic parameters of albaconazole and its primary metabolite, 6-hydroxyalbaconazole. Safety was assessed throughout the study.Results: The area under the curve (AUC and maximum measured plasma concentration (Cmax of the albaconazole tablet were approximately 10% and 22% lower, respectively, than for the albaconazole capsules. Statistical significance was reached for the Cmax but not for the AUC measurements (AUC0-t and AUC0-inf. Because the 90% confidence intervals based on the differences between the tablet and capsule were outside the 80%–125% range for both the Cmax and AUC, we concluded that the formulations were not bioequivalent with respect to the rate or extent of absorption. Both formulations were safe and well-tolerated in this study. All adverse events (AEs were generally mild and were mainly gastrointestinal- or nervous system-related (eg, dizziness, headache. No electrocardiogram findings were reported as

  10. In vivo pharmacokinetic comparisons of ferulic acid and puerarin after oral administration of monomer, medicinal substance aqueous extract and Nao-De-Sheng to rats

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    Zhen Ouyang

    2012-01-01

    Full Text Available Background: Nao-De-Sheng decoction (NDS, a traditional Chinese medicine (TCM prescription containing Radix puerariae lobatae, Floscarthami, Radix et Rhizoma Notoginseng, Rhizoma chuanxiong and Fructus crataegi, is effective in the treatment of cerebral arteriosclerosis, ischemic cerebral stroke and apoplexy linger effect. Ferulic acid and puerarin are the main absorbed effective ingredients of NDS. Objective: To assess the affection of other components in medical material and compound recipe compatibility on the pharmacokinetics of ferulaic acid and puerarin, of ferulic acid from the monomer Rhizoma chuanxiong aqueous extract and NDS were studied. And pharmacokinetics comparisons of puerarin from the monomer Radix puerariae extract and NDS decoction were investigated simultaneously. Materials and Methods: At respective different time points after oral administration of the monomer, medicinal substance aqueous extract and NDS at the same dose in rats, plasma concentrations of ferulic acid and puerarin in rats were determined by RP-HPLC, and the main pharmacokinetic parameters were estimated with 3P97 software. Results: The plasma concentration-time curves of ferulaic acid and puerarin were both best fitted with a two-compartment model. AUC 0−t, AUC 0→∞ , Tmax , and Cmax of ferulic acid in the monomer and NDS decoction were increased significantly (P < 0.05 compared with that in Rhizoma chuanxiong aqueous extract. And statistically significant increase (P < 0.05 in pharmacokinetic parameters of puerarin including AUC 0−t, AUC 0→∞ , CL, Tmax and Cmax were obtained after oral administration of puerarin monomer compared with Radix puerariae extract. Although the changes of AUC 0−t, AUC 0→∞ and CL had no statistically significant, Cmax of puerarin in NDS was increased remarkably (P < 0.05 compared with that in single puerarin. Conclusions: Some ingredients of Rhizoma chuanxiong and Radix puerariae may be suggested to remarkably

  11. 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

  12. The effect of weight, body mass index, age, sex, and race on plasma concentrations of subcutaneous sumatriptan: a pooled analysis

    Science.gov (United States)

    Munjal, Sagar; Gautam, Anirudh; Rapoport, Alan M; Fisher, Dennis M

    2016-01-01

    Objective/background Factors such as body size (weight and body mass index [BMI]), age, sex, and race might influence the clinical response to sumatriptan. We evaluated the impact of these covariates on the plasma concentration (Cp) profile of sumatriptan administered subcutaneously. Methods We conducted three pharmacokinetic studies of subcutaneous sumatriptan in 98 healthy adults. Sumatriptan was administered subcutaneously (236 administrations) as either DFN-11 3 mg, a novel 0.5 mL autoinjector being developed by Dr. Reddy’s Laboratories; Imitrex® (Sumatriptan) injection 3 mg or 6 mg (6 mg/0.5 mL); or Imitrex STATdose 4 mg or 6 mg (0.5 mL). Blood was sampled for 12 hours to determine sumatriptan Cp. Maximum Cp (Cmax), area under the curve during the first 2 hours (AUC0–2), and total area under the curve (AUC0–∞) were determined using noncompartmental methods. Post hoc analyses were conducted to determine the relationship between these exposure metrics and each of body weight, BMI, age, sex, and race (categorized as white, black, or others). Results Both weight and BMI correlated negatively with each exposure metric for each treatment group. Across all treatment groups, AUC0–2 for subjects with BMI less than or equal to median value was 1.03–1.12 times the value for subjects with BMI more than median value. For subjects with BMI less than or equal to median value receiving DFN-11, median AUC0–2 was slightly less than that for subjects with BMI more than median value receiving Imitrex 4 mg and larger than that for subjects with BMI more than median value receiving Imitrex 3 mg. Results were similar for the other exposure metrics and for weight. Exposure was higher in women than in men, which can be attributed in part to differences in weight. There was no relationship between exposure and age. For DFN-11, AUC0–2 and AUC0–∞ were lower in nonwhites compared with whites; the ratio of median values was 0.84 and 0.89, respectively. A similar

  13. Relationship between the temporal changes in positron-emission-tomography-imaging-based textural features and pathologic response and survival in esophageal cancer patients

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    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

  14. A virtual trial framework for quantifying the detectability of masses in breast tomosynthesis projection data

    Energy Technology Data Exchange (ETDEWEB)

    Young, Stefano [College of Optical Sciences, University of Arizona, Tucson, Arizona 85721 (United States); Bakic, Predrag R. [Radiology Department, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Myers, Kyle J.; Jennings, Robert J.; Park, Subok [Division of Imaging and Applied Mathematics, Center for Devices and Radiological Health, FDA, Silver Spring, Maryland 20993 (United States)

    2013-05-15

    Purpose: Digital breast tomosynthesis (DBT) is a promising breast cancer screening tool that has already begun making inroads into clinical practice. However, there is ongoing debate over how to quantitatively evaluate and optimize these systems, because different definitions of image quality can lead to different optimal design strategies. Powerful and accurate tools are desired to extend our understanding of DBT system optimization and validate published design principles. Methods: The authors developed a virtual trial framework for task-specific DBT assessment that uses digital phantoms, open-source x-ray transport codes, and a projection-space, spatial-domain observer model for quantitative system evaluation. The authors considered evaluation of reconstruction algorithms as a separate problem and focused on the information content in the raw, unfiltered projection images. Specifically, the authors investigated the effects of scan angle and number of angular projections on detectability of a small (3 mm diameter) signal embedded in randomly-varying anatomical backgrounds. Detectability was measured by the area under the receiver-operating characteristic curve (AUC). Experiments were repeated for three test cases where the detectability-limiting factor was anatomical variability, quantum noise, or electronic noise. The authors also juxtaposed the virtual trial framework with other published studies to illustrate its advantages and disadvantages. Results: The large number of variables in a virtual DBT study make it difficult to directly compare different authors' results, so each result must be interpreted within the context of the specific virtual trial framework. The following results apply to 25% density phantoms with 5.15 cm compressed thickness and 500 {mu}m{sup 3} voxels (larger 500 {mu}m{sup 2} detector pixels were used to avoid voxel-edge artifacts): 1. For raw, unfiltered projection images in the anatomical-variability-limited regime, AUC appeared to

  15. New Insights in Abdominal Pain in Paroxysmal Nocturnal Hemoglobinuria (PNH: A MRI Study.

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    Francesco De Cobelli

    Full Text Available Abdominal pain in PNH has never been investigated by in-vivo imaging studies. With MRI, we aimed to assess mesenteric vessels flow and small bowel wall perfusion to investigate the ischemic origin of abdominal pain.Six PNH patients with (AP and six without (NOP abdominal pain underwent MRI. In a blinded fashion, mean flow (MF, quantity of blood moving through a vessel within a second, in mL·s-1 and stroke volume (SV, volume of blood pumped out at each heart contraction, in mL of Superior Mesenteric Vein (SMV and Artery (SMA, areas under the curve at 60 (AUC60 and 90 seconds (AUC90 and Ktrans were assessed by two operators.Mean total perfusion and flow parameters were lower in AP than in NOP group. AUC60: 84.81 ± 11.75 vs. 131.73 ± 18.89 (P < 0.001; AUC90: 102.33 ± 14.16 vs. 152.58 ± 22.70 (P < 0.001; Ktrans: 0.0346 min-1 ± 0.0019 vs. 0.0521 ± 0.0015 (P = 0.093 duodenum, 0.009 jejunum/ileum. SMV: MF 4.67 ml/s ± 0.85 vs. 8.32 ± 2.14 (P = 0.002; SV 3.85 ml ± 0.76 vs. 6.55 ± 1.57 (P = 0.02. SMA: MF 6.95 ± 2.61 vs. 11.2 ± 2.32 (P = 0.07; SV 6.52 ± 2.19 vs. 8.78 ± 1.63 (P = 0.07. We found a significant correlation between MF and SV of SMV and AUC60 (MF:ρ = 0.88, P < 0.001; SV: ρ = 0.644, P = 0.024, AUC90 (MF: ρ = 0.874, P < 0.001; SV:ρ = 0.774, P = 0.003 and Ktrans (MF:ρ = 0.734, P = 0.007; SV:ρ = 0.581, P = 0.047.Perfusion and flow MRI findings suggest that the impairment of small bowel blood supply is significantly associated with abdominal pain in PNH.

  16. Pharmacokinetics on tramadol/acetaminophen combination tablets in Chinese healthy volunteers%曲马氨酚片的人体药物动力学研究

    Institute of Scientific and Technical Information of China (English)

    戴维; 梁建英

    2009-01-01

    To stury the pharmacokinetie of tramadol and aeetaminophen in healthy volunteers. Methods Totally 20 healthy adult male volunteers participated in the study were randomly assigned to 2 treatment groups and were given respectively the dose of one and two pills by oral administration. Serum was separated and the concentrations of tramadol and acetaminophen in human serum were determined by HPLC using fluorescence and UV detector. The values of concentration were directly detected, and AUC was calculated by linear trapezoid method. Results The main pharmacokinetie parameters of tramadol and acetaminophen of 2 dosages groups were as follow: Tramadol: AUC_(0-24h)(ng · h· mL~(-1)) were 2 724. 89 ± 1 016.54 and 1 361.61 + 441. 79; AUC_(0-∞)(ng·h·mL~(-1)) were3 065.49±1 190.66 and 1 555.04±582.51; t_(max)(h) were 1.8±0.75 and 1.9±0.57; t_(t/2)(h) were 7.34±1.39and7.63±2.02; Kel(h~(-1)) were 0. 098±0. 019 and 0. 097± 0.027; Cl_r(mL · min~(-1)) were 31.84±13.65 and 30.03 ± 9.20; MRT(h) were 7.62 ± 1.07 and 7.77 ± 0.75. Acetaminophen. AUC_(0-24h)(μg · h · mL~(-1)) were 40.28 ± 10.36 and 18.37 ± 3.84 ; AUC_(0-∞)(μg · h · mL~(-1)) were 41.63 ± 10. 96 and 18. 81 ± 4.06; t_(max)(h) were 0. 9 ± 0.46 and 0. 9 ± 0. 39; t_(t/2)(h) were5.39 ± 1. 16 and 4. 96 ± 1.03; Kel(h~(-1)) were 0. 13 ± 0. 03 and 0. 15 ± 0. 03; Clr (mL · min~(-1)) were 17.17 ± 4.57 and 18.42 ± 3.89; MRT(h) were 4.86 ± 0.48 and 4.50 ± 0.53. Conclusions No significant difference in pharmacokinetic parameters, such as t_(max), t_(t/2), Ke,Cl, MRT,AUC_(0-t)/dose, AUC_(0-∞)/dose and C_(max)/dose are shown between these two dose groups and a linear pharmacokinetic is featured.%目的 测定曲马氨酚片中曲马多和对乙酰氨基酚的药动学参数.方法 采用高效液相色谱法分别测定20名健康志愿者口服曲马氨酚片(2个剂量组:1片和2片,每组10名)后血清中的药物浓度,进行药动学分析.结果 2组健康志愿者口服曲马氨酚片

  17. Pharmacokinetics of amoxicillin administered in drinking water to recently weaned 3- to 4-week-old pigs with diarrhea experimentally induced by Escherichia coli O149 : F4

    DEFF Research Database (Denmark)

    Jensen, G.M.; Lykkesfeldt, J.; Frydendahl, K.;

    2006-01-01

    Objective-To measure effects of Escherichia coli 0149:F4-induced diarrhea on water consumption and pharmacokinetics of amoxicillin after administration in drinking water. Animals-24 recently weaned 24- to 28-day-old crossbred pigs. Procedure-10 pigs were inoculated with E coli O149:F4; all 10 pigs......%, respectively. The AUC of amoxicillin on the second day of medication for diarrheic pigs did not differ significantly from that of control pigs on the first day of medication. Conclusions and Clinical Relevance-E coli-induced diarrhea reduced the AUC of amoxicillin and time that plasma concentration...... of amoxicillin may be appropriate for administration in drinking water during a 4-hour period on the first day that pigs have diarrhea attributable to E coli 0149:F4....

  18. High resolution ECG-aided early prognostic model for comatose survivors of out of hospital cardiac arrest.

    Science.gov (United States)

    Rauber, Martin; Štajer, Dušan; Noč, Marko; Schlegel, Todd T; Starc, Vito

    2015-01-01

    Out of hospital cardiac arrest (OHCA) has a high mortality despite modern treatment. Reliable early prognosis in OHCA could significantly improve clinical decision making. We explored prognostic utility of advanced ECG parameters, obtained from high-resolution ECG, in combination with clinical and OHCA-related parameters during treatment with mild induced hypothermia (MIH) and after rewarming in unconscious survivors of OHCA. Ninety-two patients during MIH and 66 after rewarming were included. During MIH, a score based on initial rhythm, QRS-upslope and systolic pressure resulted in an area under curve (AUC) of 0.82 and accuracy of 80% for survival. After rewarming, a score based on admission rhythm, sum of 12 lead QRS voltages, and mean lateral ST segment level in leads I and V6 resulted in an AUC of 0.88 and accuracy of 85% for survival. ECG can assist with early prognostication in unconscious survivors of OHCA during MIH and after rewarming. PMID:25911585

  19. Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

    DEFF Research Database (Denmark)

    Duarte-Salles, Talita; Misra, Sandeep; Stepien, Magdalena;

    2016-01-01

    was conducted within the EPIC cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function and alpha-fetoprotein (AFP) tests were also conducted. Conditional...... subjects who developed HCC (AUC=0.86). For cases diagnosed within two years, the combination of OPN and AFP was best able to predict HCC risk (AUC=0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within two years of diagnosis, the...... combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis....

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

    Directory of Open Access Journals (Sweden)

    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

  1. Pharmacokinetics and metabolic effects of growth hormone injected subcutaneously in growth hormone deficient patients: thich versus abdomen

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Christiansen, Jens Sandahl

    1994-01-01

    Abstract OBJECTIVE: The absorption of insulin following subcutaneous (s.c.) injection is faster in the abdomen than the thigh. We therefore studied the effect of changing the site of injection on the absorption and metabolic effects of human growth hormone. DESIGN AND MEASUREMENTS: In a cross...... the s.c. tissue (mm) was higher on the abdominal site (9.35 +/- 1.38 (thigh), and 22.61 +/- 2.19 (abdomen), P < 0.001). Mean (+/- SEM) integrated levels (area under the curves (AUC) divided by time) of GH (mU/l) were identical: 5.54 +/- 0.70 (thigh) versus 5.48 +/- 0.64 (abdomen) (P = 0.91). AUC (m...

  2. Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Hansen, M; Stoltenberg, M;

    1999-01-01

    OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying a......OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease......-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P < 0.001), but not with baseline or AUC values of local or global clinical or biochemical parameters...

  3. Quantitative EEG Applying the Statistical Recognition Pattern Method

    DEFF Research Database (Denmark)

    Engedal, Knut; Snaedal, Jon; Hoegh, Peter;

    2015-01-01

    BACKGROUND/AIM: The aim of this study was to examine the discriminatory power of quantitative EEG (qEEG) applying the statistical pattern recognition (SPR) method to separate Alzheimer's disease (AD) patients from elderly individuals without dementia and from other dementia patients. METHODS...... accepted criteria by at least 2 clinicians. EEGs were recorded in a standardized way and analyzed independently of the clinical diagnoses, using the SPR method. RESULTS: In receiver operating characteristic curve analyses, the qEEGs separated AD patients from healthy elderly individuals with an area under...... the curve (AUC) of 0.90, representing a sensitivity of 84% and a specificity of 81%. The qEEGs further separated patients with Lewy body dementia or Parkinson's disease dementia from AD patients with an AUC of 0.9, a sensitivity of 85% and a specificity of 87%. CONCLUSION: qEEG using the SPR method could...

  4. Conversion of UF6 to UO2: A quasi-optimization of the ammonium uranyl carbonate process

    International Nuclear Information System (INIS)

    The ammonium uranyl carbonate (AUC) wet conversion process, one of the most important routes for preparation of uranium dioxide from UF6, was intensively investigated for process improvement and product identification. Both process variables and unit equipment were concerned. The target of this task was to prepare high quality UO2 ceramic powder and pellets. From the test results of UO2 pelletizing and sintering, the operation conditions were selected for process optimization. The criteria used in optimization condition determination were the reproducibility of the AUC product and the compressibility, the reactivity, as well as the sinterability of UO2 powder. Experimental results showed that UO2 pellets with sintered density higher than 98% TD were achieved. A set of quasi-optimum conditions for this process was also proposed. (orig.)

  5. Pharmacokinetics and Bioequivalence of Two Formulations of Febuxostat 40-Mg and 80-Mg Tablets: A Randomized, Open-Label, 4-Way Crossover Study in Healthy Chinese Male Volunteers.

    Directory of Open Access Journals (Sweden)

    Zhu Luo

    Full Text Available The present study aimed to investigate the pharmacokinetic properties of febuxostat in healthy Chinese male volunteers and evaluate whether the two formulations of febuxostat 40-mg and 80-mg tablets are bioequivalent. A randomized, open-label, 4-way crossover study was conducted in healthy Chinese male volunteers under fasting conditions. 24 eligible subjects were randomized in a 1:1:1:1 ratio to receive a single dose of test or reference formulation of febuxostat 40-mg or 80-mg tablet. The washout period between each administration was 1 week. Plasma febuxostat was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests. After single-dosing of 1 tablet of 40-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.22±0.87 and 1.85±1.03 h, Cmax 1689.16±461.31 and 1613.80±608.43 ng·mL-1, AUC0-t 5139.87±1349.28 and 5517.91±2024.26 ng·mL-1·h, AUC0-∞ 5263.06±1339.16 and 5640.48±2040.22 ng·mL-1·h, t1/2 4.82±2.61 and 4.85±1.78 h, respectively. After single-dosing of 1 tablet of 80-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.71±1.21 and 2.23±1.55 h, Cmax 2744.47±1157.44 and 2998.17±1200.13 ng·mL-1, AUC0-t 9634.03±2768.25 and 10467.95±3501.65 ng·mL-1·h, AUC0-∞ 9834.32±2730.51 and 10626.63±3504.08 ng·mL-1·h, t1/2 6.25±2.44 and 5.46±1.65 h, respectively. For single-dosing of 1 tablet of 40-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 89.79 to 102.55, 90.14 to 102.56 and 93.99 to 129.63, respectively. For single-dosing of 1 tablet of 80-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 86.67 to 100.00, 87.50 to 100.51 and 79.48 to 105.99, respectively. This single dose study revealed similar pharmacokinetic

  6. Quantitative analysis of contrast-enhanced ultrasound in renal transplant glomerular disease%超声造影定量分析诊断移植肾肾小球性病变

    Institute of Scientific and Technical Information of China (English)

    彭川; 黄漾; 熊韫祎; 王长希; 谢晓燕; 徐作峰

    2015-01-01

    目的 探讨超声造影(CEUS)定量分析在诊断移植肾肾小球性病变中的意义.方法 回顾性分析44例移植肾患者的CEUS图像,用TCA定量分析软件拟合实质增强时的平均时间强度曲线(TIC),并输出定量参数.根据镜下是否存在移植肾小球性病变分为病变组及非病变组.比较校正后的峰值强度(PI)、曲线下面积(AUC)、上升段曲线下面积(AUC of wash-in)、下降段曲线下面积(AUC of wash-out)、相对AUC of wash-out及达峰时间(TTP)、平均通过时间(,MTT)等参数及病例资料.采用受试者工作曲线(ROC)评估各参数的诊断效能,并计算最佳临界值及该值的敏感性、特异性.结果 排除取材不足的2例,余42例病例根据病理是否存在移植肾小球性病变分为病变组(n=22)及非病变组(n=20).两组校正PI、校正AUC、校正AUC of wash-in及校正AUC of wash-out等参数之间的差异具有统计学意义(P<0.05).上述参数的ROC曲线下面积分别为0.902、0.843、0.714及0.791,其诊断移植肾肾小球性病变的最佳临界值分别为≤0.237(敏感性90.9%,特异性83.0%)、≤0.188(敏感性63.6%,特异性100%)、≤0.148(敏感性77.3%,特异性75.0%)、≤0.179(敏感性59.1%,特异性90.0%).结论 校正PI、校正AUC、校正AUC of wash-in及校正AUC of wash-out等参数具有较高的诊断效能,其数值减低可提示移植肾肾小球性病变.

  7. 尼美舒利颗粒在健康人体的生物等效性%Bioequivalence of Nimesulide Granules in Healthy Volunteers

    Institute of Scientific and Technical Information of China (English)

    曾东向; 李坤艳; 符一岚

    2014-01-01

    目的:评价2种国产尼美舒利颗粒在中国健康人体的生物等效性。方法:18名健康男性受试者随机交叉单剂量口服试验制药或参比制剂各200 mg。用高效液相色谱法测定血浆中尼美舒利的浓度;用DAS2.1软件计算主要药动学参数,并对2种药物进行生物等效性评价。结果:试验制药和参比制剂的主要药动学参数:Cmax分别为(9.28±2.05)和(9.41±2.31)μg·ml-1;Tmax分别为(3.50±1.86)和(3.56±1.65)h; T1/2分别为(3.43±0.85)和(3.38±0.68)h;AUC0-24分别为(77.78±18.42)和(81.69±23.50)μg·ml·h-1;AUC(0-∞)分别为(79.07±19.21)和(82.92±24.11)μg·ml·h-1。 ln(AUC0-24)、ln (AUC0-∞)、ln(Cmax)的90%可信区间分别为90.7%~107.9%、90.6%~111.2%和90.7%~103.0%。试验制药相对于参比制剂的生物利用度F为(96.7±37.6)%。结论:受试制剂和参比制剂生物等效。%Objective:To evaluate the bioequivalence of two kinds of domestic nimesulide granules in healthy volunteers. Meth-ods:In self-control and two-way crossover design, 18 healthy male volunteers were divided into two groups randomly. Each subject was given 100 mg test or reference nimesulide granules with single dose. The concentration of nimesulide in plasma was determined by HPLC. The concentration of nimesulide in plasma was calculated and compared statistically to evaluate the bioequivalence between the two kinds of granules by DAS 2. 1 software. Results:The main pharmacokinetic parameters of test and reference preparations were as follows:Cmax was(9. 28 ± 2. 05) and(9. 41 ± 2. 31)μg·ml-1;Tmax was(3. 50 ± 1. 86)and(3. 56 ± 1. 65)h;T1/2 was (3. 43 ± 0. 85) and(3.38 ±0.68)h;AUC0-24 was(77.78 ±18.42)and(81.69 ±23.50)μg·ml·h-1;AUC(0-∞) was (79.07 ±19.21)and(82.92 ± 24. 11)μg·ml·h-1, respectively. The 90% confidential interval of ln(AUC0-24), ln(AUC0-∞) and ln(Cmax) of the test preparation was 90. 7%-107. 9%,90. 6%-111. 2% and 90. 7%-103. 0%, respectively. The

  8. Bioequivalence of Amoxicillin Suspension Injection in Pigs%阿莫西林混悬注射液在猪体内的生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    潘娟; 严凤; 顾欣

    2015-01-01

    为了研究阿莫西林混悬注射液在猪体内的药代动力学和生物等效性,采用双处理、双周期随机交叉试验设计,将24头健康猪随机分成2组,按15 mg/kg体重肌肉分别单剂量注射受试制剂和参比制剂,采用高效液相色谱法测定血浆中阿莫西林的浓度,利用WinNonlin6.4软件计算主要药动学参数,并评价两种制剂的生物等效性。结果显示,受试制剂和参比制剂的 Tmax分别为(3.45±2.49) h,(1.34±1.74) h;Cmax分别为(6.94±4.73) mg/L,(4.39±2.87) mg/L;AUC0-t分别为(37.00±11.48) mg·h·L-1,(30.02±8.93) mg·h·L-1;AUC0-∞分别为(40.26±13.36) mg·h·L-1,(38.46±15.38) mg·h·L-1。阿莫西林混悬注射液受试制剂和参比制剂的AUC0-t、AUC0-∞、Cmax、Tmax均有显著性差异,双单侧t检验结果显示两种制剂生物不等效,试验为兽医临床给药方案的制定以及合理用药提供参考。%To evaluate the pharmacokinetics and bioequivalence of amoxicillin suspension injection in pigs. In a randomized two-way self-crossover study, 24 healthy pigs were randomly divided into two groups, and were given respectively a single dose of test or reference preparations by intramuscular injection ( 15 mg/kg ) . Plasma concentrations of amoxicillin were measured by HPLC. The pharmacokinetic parameters were calculated by WinNonlin6.4 software, and the bioequivalence were evaluated. The main pharmacokinetic parameters of the test and reference preparations were as follows: Tmax were ( 3. 45 ± 2. 49 ) h, ( 1. 34 ± 1. 74 ) h; Cmax were (6.94±4.73) mg/L, (4.39±2.87) mg/L; AUC0-t were (37.00±11.48) mg·h·L-1, (30.02±8.93) mg·h·L-1;AUC0-∞ were (40.26±13.36) mg·h·L-1, (38.46±15.38) mg·h·L-1. The pharmacokinetic parameters (AUC0-t、AUC0-∞, Cmax、Tmax) showed significant difference between test and reference preparations of

  9. Bioequivalence of Two Different Ivermectin Injections in Rabbits%两种伊维菌素注射液在家兔体内的生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    李朋朋; 张聪; 张晓会; 周德刚; 李召斌; 张晓东; 刘栓

    2016-01-01

    To evaluate the pharmacokinetics and bioequivalence of two kinds of ivermectin injections in rabbits,in a randomized two -way self -crossover study,16 healthy rabbits were randomly divided into two groups,and were given respectively a single dose of two kinds of ivermectin injection by subcutaneous injection (5 mg/kg).Plasma concentrations of ivermectin were measured by HPLC.The pharmacokinetic parameters were calculated by 3P97 pharmacokinetic software,and the bioequivalence were evaluated.The main pharmacokinetic parameters of the test and reference preparations were as follows:Tmax were (26.45 ±8.62)h,(22.33 ±11.72)h;Cmax were (182.73 ± 59.27)ng/mL,(166.77 ±65.25)ng/mL;AUC0 -t were (21122 ±9999)ng·h·L -1 ,(19475 ±7009)ng·h·L -1;AUC0 -∞were (27390 ±12197)ng·h·L -1 ,(31559 ±13412)ng·h·L -1 .The pharmacokinetic parameters (AUC0 -t、AUC0 -∞、Cmax、Tmax ) showed no significant difference between test and reference preparations of ivermectin injections.The test and reference formulations were bioequivalent after two one -side t -test.This study provided theoretical basis for making of veterinary clinical dosage regimen and clinical rational administration.%为评价两种伊维菌素注射液在家兔体内的生物等效性,采用双周期交叉给药方式,将16只健康家兔随机分成2组,按5 mg/kg 体重皮下单剂量注射两种伊维菌素注射液,使用 HPLC法测定血浆中的伊维菌素,利用3P97药动软件计算主要药动学参数。结果显示,受试制剂和参比制剂的 Tmax分别为(26.45±8.62)h,(22.33±11.72)h;Cmax 分别为(182.73±59.27)ng/mL,(166.77±65.25)ng/mL;AUC0-t 分别为(21122±9999)ng·h·L -1,(19475±7009)ng·h·L -1;AUC0-∞分别为(27390±12197)ng·h·L -1,(31559±13412)ng·h·L -1。伊维菌素注射液受试制剂与参比制剂的 AUC0-t、AUC0-∞、Cmax、Tmax均无显著性差异(P >0.05

  10. Determination of lisinopril in human plasma by HP LC-MS/MS and bioequivalence of lisinopril tablets%赖诺普利片人体生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    周焕; 陈余清; 马涛; 霍强; 孙思雨; 张俊东

    2012-01-01

    Objective :To evaluate the bioequivalence of lisinopril tablets in healthy volunteers. Methods: A single oral dose of 10 mg test or reference formulations were given to 20 male healthy volunteers in a randomized crossover design. Three ml of blood was drawn out from the ulnar vein of the volunteers at 1,2,3 ,4 ,6,8 ,10,12,16,24,36,48 and 60 h before and after the administration. The plasma concentration of lisinopril was determined by LC-MS/MS method. The pharmacokinetic parameters and relative bioavailability were calculated with DAS program to evaluate the bioequivalence of the two formulations. Results: The pharmacokinetic parameters of lisinopril test formulation were obtained as follows-tmax was(6. 1 ±1.0) h,Cmax(64. 24 ±25.2) μg/L, AUC0_60 (942. 0 ±330) (μg ? T-1 ? h-1 and AUC0-∞ (969.6 ±327) μg ? L-1 ? h-1 ;for reference formulation:tmas(6. 1 ± 1. 2) h,Cmax (68. 19 ±26. 5 ) μg/L, AUC0-144(980.1 ±340) μg ? L-1 ? h-1 and AUC0-∞ (1002.3 ±337) μg ? L-1 ? h-1. Calculated with AUC0-144 ,the bioavailability of the two formulations was(98. 8 ±27. 5) %. Conclusions:The lisinopril tablet test formulation and reference formulation are bioequivalent.%目的:评价两种赖诺普利片的人体生物等效性.方法:20名男性健康志愿者随机交叉口服赖诺普利片试验制剂和参比制剂各10 mg,于给药前及给药后1、2、3、4、6、8、10、12、16、24、36、48、60 h从受试者肘静脉采血3 ml,采用液相-串联质谱法(LC-MS/MS)测定血药浓度.以DAS2.0软件计算其药动学参数,考察其生物等效性.结果:赖诺普利片试验制剂和参比制剂的tmax、Cmax、AUC0~60、AUC0~∞分别为(6.1±1.0)h和(6.1±1.2)h、(64.24±25.2)μg/L和(68.19±26.5)μg/L、(942.0±330)μg·L-1·h-1和(980.1±340)μg·L-1·h-1、(969.6±327)μg·L-1·h-1和(1002.3±337)μg·L-1·h-1.以AUC0~144计算,赖诺普利片试验制剂和参比制剂比较的人体相对生物利用度为(98.8±27.5)%.结论:试验制剂赖诺

  11. Comparison of circulating MMP-9, TIMP-1 and CA19-9 in the detection of pancreatic cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Brünner, Nils; De Muckadell, Ove B Schaffalitzky

    2010-01-01

    adenocarcinoma. PATIENTS AND METHODS: The patients had symptoms of pancreatic cancer. The discriminative strength of MMP-9 and TIMP-1 were compared to that of CA19-9 using receiver operating characteristics curves, area under the curves (AUC), specificity and sensitivity. RESULTS: The sensitivities of MMP-9......Background/Aim: The performance of the circulating tumor markers carbohydrate antigen 19-9 (CA19-9), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were evaluated separately and in combination for their potential value in detecting pancreatic ductal......, TIMP-1 and CA19-9 in detecting pancreatic ductal adenocarcinoma were 58.82%, 47.1% and 86%, respectively, with specificities of 34.6%, 69.2% and 73%. The AUCs of MMP-9, TIMP-1 and CA19-9 were 0.50, 0.64 and 0.84, respectively. Combining the three markers did not significantly improve detection...

  12. Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration.

    Science.gov (United States)

    Rawlins, M D; Henderson, D B; Hijab, A R

    1977-04-20

    Plasma paracetamol concentrations were measured in 6 volunteers after single intravenous (1000 mg) and oral (500 mg, 1000 mg and 2000 mg) doses of the drug. Paracetamol levels declined multiphasically with a mean clearance after intravenous administration of 352 +/- 40 ml/min. A two-compartment open model appeared to describe the decline adequately. Comparison of the areas under the plasma concentration-time curves (AUC) indicated that oral bioavailability increased from 0.63 +/- 0.02 after 500 mg, to 0.89 +/- 0.04 and 0.87 +/- 0.08 after 1000 mg and 2000 mg, respectively. As a consequence of the incomplete bioavailability of paracetamol, as well as its multicompartmental distribution, accurate estimates of its distribution volume and clearance cannot be obtained if the drug is given orally. However, an estimate of its total plasma clearance may be derived from the AUC after a 500 mg oral dose. PMID:862649

  13. Acute effects of tibolone on cerebral vascular reactivity in vitro

    DEFF Research Database (Denmark)

    Lund, C O; Nilas, Lisbeth; Dalsgaard, T;

    2003-01-01

    alpha-OH-tibolone, 3beta-OH-tibolone, Delta(4) isomer and 17beta-estradiol were obtained before and after addition of the NO blocker N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/l) or the potassium-channel blocker tetraethylammonium chloride (TEA, 10(-2) mol/l). Additionally, the effects...... of the hormones on the concentration-response curves with calcium were examined. RESULTS: Tibolone and its metabolites induced a concentration-dependent relaxation comparable to that of 17beta-estradiol (area under the curve (AUC); tibolone vs. 17beta-estradiol: 242 vs. 251; p < 0.05, analysis of...... variance). L-NAME increased the AUC for all substances compared with controls (p < 0.05, Student's t test), except for 17beta-estradiol. Preincubation with TEA induced no changes. The concentration-dependent contraction curves with calcium were shifted rightward by all hormones. CONCLUSIONS: The study...

  14. Serum miR-1297: a promising diagnostic biomarker in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wang, Cong; Li, Qingbao; Liu, Fang; Chen, Xuan; Nesa, Effat Un; Guan, Shanghui; Liu, Bowen; Han, Lihui; Tan, Bingxu; Wang, Ding; Chen, Pengxiang; Liu, Xiaoyue; Zhang, Han; Sun, Ying; Cheng, Yufeng

    2016-09-01

    We aimed to value the diagnostic potential of serum miR-1297 in esophageal squamous cell cancer (ESCC). Its expression level was detected in 156 pairs of patients with ESCC and healthy volunteers using quantitative real-time polymerase chain reaction (qRT-PCR) method. It was statistically decreased in ESCC patients compared with healthy controls. AUC based on serum miR-1297 was 0.840 ± 0.035 in discovery group and 0.837 ± 0.034 in validation group. Further analysis on early-stage patients revealed that the AUC was 0.819 ± 0.053 in discovery group and 0.814 ± 0.044 in validation group. Its sensitivity and specificity were promising. In conclusion, serum miR-1297 can serve as an ideal indicator for the diagnosis of ESCC. PMID:27152453

  15. Dose-dependent adsorptive capacity of activated charcoal for gastrointestinal decontamination of a simulated paracetamol overdose in human volunteers

    DEFF Research Database (Denmark)

    Gude, Anne-Bolette Jill; Hoegberg, Lotte Christine Groth; Riis Angelo, Helle;

    2010-01-01

    The amount of activated charcoal needed to treat drug overdoses has arbitrarily been set at a charcoal-drug ratio of 10:1. Recent in vitro studies have shown a larger adsorptive capacity for activated charcoal when used in a model of paracetamol overdose. In the present study, we investigated...... to be of similar size compared to the control, although statistics were weak. The AUC of the 5-g dose was 59% larger than the AUC of the 50-g dose (p = 0.0003). The terminal elimination half-life (t(1/2)) of paracetamol was 1.6 (CI 1.4-2.0) and 1.9 (CI 1.5-2.4) hr for 50 and 25 g, respectively (NS), and 2.5 (CI 1...

  16. MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis

    DEFF Research Database (Denmark)

    Løvendorf, Marianne B; Zibert, John R; Gyldenløve, Mette;

    2014-01-01

    including miR-223 and miR-143 which were found to be significantly upregulated in the PBMCs from patients with psoriasis compared with healthy controls (FCH=1.63, PmiR-223 and miR-143 significantly correlated with the PASIscore (r=0.46, P...miR-223 and -143 have the potential to distinguish between psoriasis and healthy controls (miR-223: area under the curve (AUC)=0.80, miR-143: AUC=0.75). Interestingly, after 3-5 weeks of treatment with methotrexate...... following a significant decrease in psoriasis severity, miR-223 and miR-143 were significantly downregulated in the PBMCs from patients with psoriasis. CONCLUSION: We suggest that changes in the miR-223 and miR-143 expressions in PBMCs from patients with psoriasis may serve as novel biomarkers for disease...

  17. Pharmacokinetics of mycophenolic acid in Chinese kidney transplant patients

    Institute of Scientific and Technical Information of China (English)

    LU Xiao-yang; HUANG Hong-feng; SHENG-TU Jian-zhong; LIU Jian

    2005-01-01

    To assess the influence ofcyclosporin A (CsA) and tacrolimus (FK506) on mycophenolic acid (MPA) and correlation analysis of the pharmacokinetic parameters and patient characteristics, clinical outcome in Chinese kidney transplant recipients,the pharmacokinetics of 1000 mg mycophenolate mofetil (MMF) twice daily was measured by high-performance liquid chromatography (HPLC). PKS (Pharmaceutical Kinetics Software) 1.0.2 software package was used for the calculation of pharmarespectively. The level of AUC(0-12) in the FK506 group was significantly higher than that in the CsA group. MPA appeared not to be affected by renal function. MPA AUC(0-12) showed statistically significant difference according to the patient's gender.

  18. Phase III study by the Norwegian lung cancer study group

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Bremnes, Roy M; Fløtten, Oystein;

    2009-01-01

    area under the curve (AUC) = 5 (Calvert's formula) on day 1 or gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles. The primary end point was health-related quality of life (HRQoL) defined as global quality of life, nausea/vomiting, dyspnea......, and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the lung cancer-specific module LC13 during the first 20 weeks. Secondary end points were overall survival and toxicity. Results Four hundred thirty-six eligible patients were enrolled....../carboplatin, including leukopenia (46% v 23%, respectively; P platelets, whereas the frequencies of neutropenic infections...

  19. Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and relationships with triglycerides and ALT

    DEFF Research Database (Denmark)

    Alssema, Marjan; Rijkelijkhuizen, Josina M; Holst, Jens Juul;

    2013-01-01

    ) vs 18.0 (95% CI 16.9-19.1), Pafter the mixed meal. GIP secretion among diabetic patients was increased on both occasions (82.9 pmol/l (55.9-109.8) vs 47.1 (43.8-50.4) for oral glucose and 130.6 (92.5-168.7) vs 83.2 (77.5-88.9) for mixed meal, both PAfter oral glucose, GLP-1 (t......-dependent insulinotropic polypeptide (GIP) and glucagon profiles were analysed as total area under the curve (tAUC) and incremental area under the curve. RESULTS: In diabetic patients compared with persons with NGM, we found increased GLP-1 secretion (tAUC per hour) following oral glucose (23.2 pmol/l (95% CI 17.7-28.7...

  20. Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin concentrations in healthy subjects

    DEFF Research Database (Denmark)

    Hlebowicz, Joanna; Hlebowicz, Anna; Lindstedt, Sandra;

    2009-01-01

    BACKGROUND: A previous study of healthy subjects showed that intake of 6 g cinnamon with rice pudding reduced postprandial blood glucose and the gastric emptying rate (GER) without affecting satiety. OBJECTIVE: The objective was to study the effect of 1 and 3 g cinnamon on GER, postprandial blood...... and without 1 or 3 g cinnamon. Fifteen healthy subjects were assessed in a crossover trial. RESULTS: The addition of 1 or 3 g cinnamon had no significant effect on GER, satiety, glucose, GIP, or the ghrelin response. The insulin response at 60 min and the area under the curve (AUC) at 120 min were...... significantly lower after ingestion of rice pudding with 3 g cinnamon (P = 0.05 and P = 0.036, respectively, after Bonferroni correction). The change in GLP-1 response (DeltaAUC) and the change in the maximum concentration (DeltaC(max)) were both significantly higher after ingestion of rice pudding with 3 g...

  1. Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography

    DEFF Research Database (Denmark)

    Rochitte, Carlos E; George, Richard T; Chen, Marcus Y;

    2014-01-01

    AIMS: To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed...... tomography (SPECT). METHODS AND RESULTS: We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon...... myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative...

  2. Bioavailability of a new oral formulation of medroxyprogesterone acetate compared with the standard formulation: a single dose randomized study.

    Science.gov (United States)

    Kjaer, M; Brunsgaard, N; Jakobsen, P; Edwards, D M; Strolin-Benedetti, M

    1993-08-01

    Twenty-six female patients with breast cancer participated in an open, randomized, cross-over study comparing single dose bioavailability of a recently developed oral medroxyprogesterone acetate (MPA) formulation (200 mg sachet where MPA is loaded in a polyvinylpyrrolidone cross-linked polymer, MPA/PVP) with the standard formulation (500 mg tablet). Blood tests were performed under standardized conditions for 120 h in all patients and MPA plasma concentrations determined by means of HPLC. Dose-normalized AUC(0-tz), AUC (0-infinity) and Cmax were all significantly higher for the MPA/PVP formulation than for the standard formulation. The relative bioavailability of the MPA/PVP formulation was on average three times superior to that of the standard formulation. This new MPA formulation might have important clinical implications for the treatment of hormone-sensitive cancer. PMID:8400345

  3. Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Teruo Murakami

    2012-08-01

    Full Text Available Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.

  4. Procesos de desmovilización de las Autodefensas Unidas de Colombia y el Frente Farabundo Martí para la Liberación Nacional en el marco de la Ley de Justicia y Paz en Colombia y los Acuerdos de Paz de Chapultepec en El Salvador.

    Directory of Open Access Journals (Sweden)

    María Fernanda Molina Álvarez

    2016-01-01

    Full Text Available Este trabajo establece una comparación entre los procesos de reinserción de los desmovilizados de las Autodefensas Unidas de Colombia (AUC en Colombia durante el 2006 y el Frente Farabundo Martí para la Liberación Nacional (FMLN en El Salvador en 1992. Desde el enfoque histórico- hermenéutico, se realizó un análisis de las investigaciones empíricas y de los informes académicos, estatales y de organizaciones internacionales. Hay una concurrencia entre los artículos científicos y los informes hallados con respecto al gran alcance de la violencia política y la implementación de estrategias por parte de las AUC y el FMLN. Sin embargo, existen diferencias relevantes entre ambos procesos de cara al escenario del postconflicto.

  5. Gold Thione Complexes

    OpenAIRE

    Francesco Caddeo; Vanesa Fernández-Moreira; Massimiliano Arca; Antonio Laguna; Vito Lippolis; M. Concepción Gimeno

    2014-01-01

    The reaction of the ligand Et4todit (4,5,6,7-Tetrathiocino-[1,2-b:3,4-b']-diimidazolyl-1,3,8,10-tetraethyl-2,9-dithione) with gold complexes leads to the dinuclear gold(I) complexes [{Au(C6F5)}2(Et4todit)] and [Au(Et4todit)]2(OTf)2, which do not contain any gold-gold interactions, or to the gold(III) derivative [{Au(C6F5)3}2(Et4todit)]. The crystal structures have been established by X-ray diffraction studies and show that the gold centers coordinate to the sulfur atoms of the imidazoline-2-t...

  6. Bioequivalence of Enalapril Maleate Tablets in Healthy Volunteers%马来酸依那普利片的人体生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    梁宇光; 李海燕; 高洪志; 王晓芳; 郝光涛; 刘泽源

    2009-01-01

    -48h)平均值分别为(59.22±20.46)、(64.43±23.42)mg · h · L-1;AUC(0-∞)平均值分别为(60.01±20.39)、(65.09±23.43)mg · h · L-1;以AUC(0-48h)计算,受试制剂的相对生物利用度为(97.8±34.1)%.结论 受试制剂和参比制剂具有生物等效性.

  7. Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure: An Observational Cohort Study.

    Science.gov (United States)

    Naesens, Maarten; Lerut, Evelyne; Emonds, Marie-Paule; Herelixka, Albert; Evenepoel, Pieter; Claes, Kathleen; Bammens, Bert; Sprangers, Ben; Meijers, Björn; Jochmans, Ina; Monbaliu, Diethard; Pirenne, Jacques; Kuypers, Dirk R J

    2016-01-01

    Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria 3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P3 months after transplant (AUC 0.73, P1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis.

  8. Variance of the SGK1 gene is associated with insulin secretion in different European populations: results from the TUEF, EUGENE2, and METSIM studies

    DEFF Research Database (Denmark)

    Friedrich, Björn; Weyrich, Peter; Stancáková, Alena;

    2008-01-01

    HYPOTHESIS: Serum- and Glucocorticoid-inducible Kinase 1 (SGK1) is involved in the regulation of insulin secretion and may represent a candidate gene for the development of type 2 diabetes mellitus in humans. METHODS: Three independent European populations were analyzed for the association of SGK1...... gene (SGK) variations and insulin secretion traits. The German TUEF project provided the screening population (N = 725), and four tagging SNPs (rs1763527, rs1743966, rs1057293, rs9402571) were investigated. EUGENE2 (N = 827) served as a replication cohort for the detected associations. Finally...... secretion only remained significant in lean TUEF participants (BMIEUGENE2 rs9402571 minor allele carriers, who had a significantly higher AUC(Ins)/AUC(Glc) (TT: 226+/-7, XG: 246+/-9; p = 0.019). Accordingly, the METSIM trial revealed a lower prevalence of type...

  9. Optical tomographic detection of rheumatoid arthritis with computer-aided classification schemes

    Science.gov (United States)

    Klose, Christian D.; Klose, Alexander D.; Netz, Uwe; Beuthan, Jürgen; Hielscher, Andreas H.

    2009-02-01

    A recent research study has shown that combining multiple parameters, drawn from optical tomographic images, leads to better classification results to identifying human finger joints that are affected or not affected by rheumatic arthritis RA. Building up on the research findings of the previous study, this article presents an advanced computer-aided classification approach for interpreting optical image data to detect RA in finger joints. Additional data are used including, for example, maximum and minimum values of the absorption coefficient as well as their ratios and image variances. Classification performances obtained by the proposed method were evaluated in terms of sensitivity, specificity, Youden index and area under the curve AUC. Results were compared to different benchmarks ("gold standard"): magnet resonance, ultrasound and clinical evaluation. Maximum accuracies (AUC=0.88) were reached when combining minimum/maximum-ratios and image variances and using ultrasound as gold standard.

  10. Postprandial diabetic glucose tolerance is normalized by gastric bypass feeding as opposed to gastric feeding and is associated with exaggerated GLP-1 secretion: a case report

    DEFF Research Database (Denmark)

    Dirksen, Carsten; Hansen, Dorte L; Madsbad, Sten;

    2010-01-01

    OBJECTIVE: To examine after gastric bypass the effect of peroral versus gastroduodenal feeding on glucose metabolism. RESEARCH DESIGN AND METHODS: A type 2 diabetic patient was examined on 2 consecutive days 5 weeks after gastric bypass. A standard liquid meal was given on the first day...... into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C-peptide, glucagon, incretin hormones, peptide YY, and free fatty acids were measured. RESULTS: Peroral feeding reduced 2-h postprandial plasma glucose (7.8 vs. 11.1 mmol/l) and incremental area under the glucose curve (i......AUC) (0.33 vs. 0.49 mmol . l(-1) . min(-1)) compared with gastroduodenal feeding. beta-Cell function (iAUC(Cpeptide/Glu)) was more than twofold improved during peroral feeding, and the glucagon-like peptide (GLP)-1 response increased nearly fivefold. CONCLUSIONS: Improvement in postprandial glucose...

  11. High beta-Lactamase Levels Change the Pharmacodynamics of beta-Lactam Antibiotics in Pseudomonas aeruginosa Biofilms

    DEFF Research Database (Denmark)

    Wang, Hengzhuang; Ciofu, Oana; Yang, Liang;

    2013-01-01

    Resistance to beta-lactam antibiotics is a frequent problem in Pseudomonas aeruginosa lung infection of cystic fibrosis (CF) patients. This resistance is mainly due to the hyperproduction of chromosomally encoded beta-lactamase and biofilm formation. The purpose of this study was to investigate......, microtiter plates, and on alginate beads were treated with different concentrations of ceftazidime and imipenem. The kinetics of antibiotics on the biofilms was investigated in vitro by time-kill methods. Time-dependent killing of ceftazidime was observed in PAO1 biofilms, but concentration-dependent killing......-lactamase, which can hydrolyze the beta-lactam antibiotics. The PK/PD indices of the AUC/MBIC and C-max/MBIC (AUC is the area under concentration-time curve, MBIC is the minimal biofilm-inhibitory concentration, and C-max is the maximum concentration of drug in serum) are probably the best parameters to describe...

  12. Advanced Hepatocellular Carcinoma: Early evaluation of response to targeted therapy and prognostic value of Perfusion CT and Dynamic Contrast Enhanced-Ultrasound. Preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Frampas, Eric, E-mail: eric.frampas@chu-nantes.fr [Central Department of Radiology and Medical Imaging, Hôtel-Dieu, 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1 (France); Lassau, Nathalie, E-mail: Nathalie.LASSAU@igr.fr [IR4M UMR 8081, Université Paris Sud 11, Institut Gustave Roussy, 114 Av. Edouard Vaillant, 94805 Villejuif (France); Zappa, Magaly, E-mail: magaly.zappa@bjn.aphp.fr [Department of Radiology, APHP Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, 100 Bd du général Leclerc, 92110 Clichy (France); Vullierme, Marie-Pierre, E-mail: marie-pierre.vullierme@bjn.aphp.fr [Department of Radiology, APHP Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, 100 Bd du général Leclerc, 92110 Clichy (France); Koscielny, Serge, E-mail: serge.koscielny@igr.fr [Department of Biostatistics, Institut Gustave Roussy, 114 Av. Edouard Vaillant, 94805 Villejuif (France); Vilgrain, Valérie, E-mail: valerie.vilgrain@bjn.aphp.fr [Department of Radiology, APHP Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, 100 Bd du général Leclerc, 92110 Clichy (France); Université Paris Diderot, Sorbonne Paris Cité, INSERM CRB3 U773, 75018 Paris (France)

    2013-05-15

    Purpose: To investigate whether there is any correlation between standard endpoints and tumor perfusion measurements with Perfusion CT and Dynamic Contrast-Enhanced Ultrasonography (DCE-US) in patients with advanced Hepatocellular Carcinoma (HCC) treated with targeted therapy. Materials and methods: Nineteen patients were evaluated during targeted therapy (sorafenib n = 16, sunitinib n = 3). Changes in tumor perfusion measurements between baseline and month 1 were assessed and compared using RECIST progression criteria at month 2. Results: Median time to progression according to RECIST was 117 days and median time to death was 208 days. Perfusion CT values before treatment were significantly increased in HCC compared to the surrounding liver (n = 17, P < .02). Eleven patients received complete examinations with both techniques at baseline and month 1. A non-significant decrease was found in all Perfusion CT values between RECIST nonprogressors (n = 7) and progressors (n = 4): mean Blood Volume: −27.9 vs. −11.1% and mean Blood Flow: −25.0 vs. −11.7% respectively. With DCE-US, opposite changes were found (mean Area Under the Curve AUC: −38.3 vs. 436.3%). RECIST progression at month 2 was significantly correlated with a threshold 40% decrease in AUC (P = .015). None of the patients with a decrease in AUC ≥ 40% was a progressor at month 2. Conclusion: Despite perfusion changes with both Perfusion CT and DCE-US in patients receiving treatment, only DCE-US at month 1 (with a decrease in the AUC of more than 40%) predicted non-progression at month 2 and may be a potential surrogate marker of tumor response during targeted therapy.

  13. Increased Insulin following an Oral Glucose Load, Genetic Variation near the Melatonin Receptor MTNR1B, but No Biochemical Evidence of Endothelial Dysfunction in Young Asian Men and Women.

    Directory of Open Access Journals (Sweden)

    Maria A Matuszek

    Full Text Available To identify biochemical and genetic variation relating to increased risk of developing type 2 diabetes mellitus and cardiovascular disease in young, lean male and female adults of different ethnicities.Fasting blood and urine and non-fasting blood following oral glucose intake were analysed in 90 Caucasians, South Asians and South East/East Asians.There were no differences in age, birthweight, blood pressure, body mass index, percent body fat, total energy, percentage of macronutrient intake, microalbumin, leptin, cortisol, adrenocorticotropic hormone, nitric oxide metabolites, C-reactive protein, homocysteine, tumor necrosis factor-α, interleukin-6, von Willebrand factor, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and tissue plasminogen activator. Fasting total cholesterol (P = .000, triglycerides (P = .050, low density lipoprotein (P = .009 and non-fasting blood glucose (15 min (P = .024 were elevated in South Asians compared with Caucasians, but there was no significant difference in glucose area under curve (AUC. Non-fasting insulin in South Asians (15-120 min, in South East/East Asians (60-120 min, and insulin AUC in South Asians and South East/East Asians, were elevated compared with Caucasians (P≤0.006. The molar ratio of C-peptide AUC/Insulin AUC (P = .045 and adiponectin (P = .037 were lower in South Asians compared with Caucasians. A significant difference in allele frequency distributions in Caucasians and South Asians was found for rs2166706 (P = 0.022 and rs10830963 (P = 0.009, which are both near the melatonin receptor MTNR1B.Elevated non-fasting insulin exists in young South Asians of normal fasting glucose and insulin. Hepatic clearance of insulin may be reduced in South Asians. No current biochemical evidence exists of endothelial dysfunction at this stage of development. MTNR1B signalling may be a useful therapeutic target in Asian populations in the prevention of type 2 diabetes mellitus.

  14. Challenges of predicting the potential distribution of a slow-spreading invader: a habitat suitability map for an invasive riparian tree

    Science.gov (United States)

    Jarnevich, Catherine S.; Reynolds, Lindsay V.

    2011-01-01

    Understanding the potential spread of invasive species is essential for land managers to prevent their establishment and restore impacted habitat. Habitat suitability modeling provides a tool for researchers and managers to understand the potential extent of invasive species spread. Our goal was to use habitat suitability modeling to map potential habitat of the riparian plant invader, Russian olive (Elaeagnus angustifolia). Russian olive has invaded riparian habitat across North America and is continuing to expand its range. We compiled 11 disparate datasets for Russian olive presence locations (n = 1,051 points and 139 polygons) in the western US and used Maximum entropy (Maxent) modeling to develop two habitat suitability maps for Russian olive in the western United States: one with coarse-scale water data and one with fine-scale water data. Our models were able to accurately predict current suitable Russian olive habitat (Coarse model: training AUC = 0.938, test AUC = 0.907; Fine model: training AUC = 0.923, test AUC = 0.885). Distance to water was the most important predictor for Russian olive presence in our coarse-scale water model, but it was only the fifth most important variable in the fine-scale model, suggesting that when water bodies are considered on a fine scale, Russian olive does not necessarily rely on water. Our model predicted that Russian olive has suitable habitat further west from its current distribution, expanding into the west coast and central North America. Our methodology proves useful for identifying potential future areas of invasion. Model results may be influenced by locations of cultivated individuals and sampling bias. Further study is needed to examine the potential for Russian olive to invade beyond its current range. Habitat suitability modeling provides an essential tool for enhancing our understanding of invasive species spread.

  15. DIC score in pregnant women--a population based modification of the International Society on Thrombosis and Hemostasis score.

    Directory of Open Access Journals (Sweden)

    Offer Erez

    Full Text Available OBJECTIVES: The objectives of this study were: 1 To determine the component needed to generate a validated DIC score during pregnancy. 2 To validate such scoring system in the identification of patients with clinical diagnosis of DIC. MATERIAL AND METHODS: This is a population based retrospective study, including all women who gave birth at the 'Soroka University Medical Center' during the study period, and have had blood coagulation tests including complete blood cell count, prothrombin time (PT(seconds, partial thromboplastin time (aPTT, fibrinogen, and D-dimers. Nomograms for pregnancy were established, and DIC score was constructed based on ROC curve analyses. RESULTS: 1 maternal plasma fibrinogen concentrations increased during pregnancy; 2 maternal platelet count decreased gradually during gestation; 3 the PT and PTT values did not change with advancing gestation; 4 PT difference had an area under the curve (AUC of 0.96 (p<0.001, and a PT difference ≥1.55 had an 87% sensitivity and 90% specificity for the diagnosis of DIC; 5 the platelet count had an AUC of 0.87 (p<0.001, an 86% sensitivity and 71% specificity for the diagnosis of DIC; 6 fibrinogen concentrations had an AUC of 0.95 (p<0.001 and a cutoff point ≤3.9 g/L had a sensitivity of 87% and a specificity of 92% for the development of DIC; and 7 The pregnancy adjusted DIC score had an AUC of 0.975 (p<0.001 and at a cutoff point of ≥26 had a sensitivity of 88%, a specificity of 96%, a LR(+ of 22 and a LR(- of 0.125 for the diagnosis of DIC. CONCLUSION: We could establish a sensitive and specific pregnancy adjusted DIC score. The positive likelihood ratio of this score suggests that a patient with a score of ≥26 has a high probability to have DIC.

  16. Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

    Energy Technology Data Exchange (ETDEWEB)

    Cella, Laura, E-mail: laura.cella@cnr.it [Institute of Biostructures and Bioimaging, National Council of Research, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); Liuzzi, Raffaele; Conson, Manuel [Institute of Biostructures and Bioimaging, National Council of Research, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); D’Avino, Vittoria [Institute of Biostructures and Bioimaging, National Council of Research, Naples (Italy); Salvatore, Marco [Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); Pacelli, Roberto [Institute of Biostructures and Bioimaging, National Council of Research, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy)

    2013-10-01

    Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity.

  17. Incidence of dengue in a rural hospital, Chinakakani, Andhra Pradesh, South India and comparison of two commercially available enzyme linked immunosorbent assays with immunochromatographic rapid test

    Directory of Open Access Journals (Sweden)

    Sumana Prudhivi

    2014-08-01

    Results: Out of 1180 samples tested, Pan Bio has shown an incidence rate of 284 [24.06%] (NS1 156+IgM 128, J Mitra 280 [23.72%] (NS1 156 + IgM 124 and SDRT 292 [24.74%] (NS1 156+IgM 136. As far as NS1 is concerned the same 156 samples were positive in all the three tests giving the sensitivity, specificity, positive and negative predictive values 100%. Remaining 1024 samples were negative for NS1. But this was not the case with IgM. AUC of IgM Pan Bio is 0.944 with sensitivity 90.32% and specificity 98.48%. AUC of IgM J Mitra is 0.932 with sensitivity 81.62% and specificity 98.75%. AUC of IgM SD RT is 0.992 with sensitivity 99.2% and specificity 99.1%. and lsquo;Z' test revealed that there is statistically significant difference between AUC's of SD RT when compared to Pan Bio (p value: 0.05 and J Mitra (p value 0.0001 The p values explain that SD RT is superior to Pan Bio and J Mitra in classifying between diseased and non-diseased. Conclusion: High incidence rate was noticed in our region during monsoon and post-monsoon season which calls for timely preventive and control measures. SDRT is a valuable screening test in laboratories with minimal resources. [Int J Res Med Sci 2014; 2(4.000: 1534-1540

  18. Kooperation und Asymmetrie : das Entwicklungsprofil eines betrieblichen Ost-West-Projekts

    OpenAIRE

    Dörr, Gerlinde; Kessel, Tanja

    2001-01-01

    "Das vorliegende Papier befaßt sich mit einer transnationalen Unternehmenskooperation. Rekonstruiert wird das Entwicklungsprofil der Kooperation der beiden Automobilhersteller Skoda und Volkswagen, das durch das Ineinandergreifen der beiden aktuellen Tendenzen von Transformation und Globalisierung geprägt ist. Als für den Kooperationserfolg entscheidend zeigte sich nicht nur der von Volkswagen geleistete beträchtliche Know-how- und Managementtransfer an den tschechischen Standort, sondern auc...

  19. Development of Internationalization into Strategic Policy Area in Light of the Merger Process. A case study of Oslo and Akershus University College of Applied Sciences (HiOA)

    OpenAIRE

    Bogun, Evgenia

    2015-01-01

    This master thesis investigates the interaction between Oslo and Akershus University College of Applied Sciences (HiOA) environmental pressures coming from a number of constituents and organizational strategies with respect to internationalization as a strategic policy area. This study adopts a case study approach. Using document analysis and qualitative semi-structured interviews, it investigates the way merger between OUC and AUC (the two institutions that became HiOA in 2011) effect the in...

  20. Meta-analysis of data from human ex vivo placental perfusion studies on genotoxic and immunotoxic agents within the integrated European project NewGeneris

    DEFF Research Database (Denmark)

    Mose, T; Mathiesen, L; Karttunen, V;

    2012-01-01

    highly ranked no matter which parameter was used. Antipyrine normalization resulted in the following ranking order of compounds according to AUC(120NORM) values: NDMA = EtOH = BPA = IQ =AA = GA = PCB180 = PhIP = AFB1 > DON = BP = PCB52 = TCDD. As the variance in all parameters within a study decreased...

  1. Differentiation between focal malignant marrow-replacing lesions and benign red marrow deposition of the spine with T2{sup *}-corrected fat-signal fraction map using a three -echo volume interpolated breath-hold gradient echo dixon sequence

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Pyo; Kim, Sung Jun; Chung, Tae Sub; Yoo, Yeon Hwa; Yoon, Choon Sik [Dept. of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kanneengiesser, Stephan [MR Applications Development, Siemens AG, Healthcare Sector, Erlangen (Germany); Paek, Moon Young [Siemens Ltd., Seoul (Korea, Republic of); Song, Ho Taek; Lee, Young Han; Suh, Jin Suck [Dept. of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-12-15

    To assess the feasibility of T2{sup *}-corrected fat-signal fraction (FF) map by using the three-echo volume interpolated breath-hold gradient echo (VIBE) Dixon sequence to differentiate between malignant marrow-replacing lesions and benign red marrow deposition of vertebrae. We assessed 32 lesions from 32 patients who underwent magnetic resonance imaging after being referred for assessment of a known or possible vertebral marrow abnormality. The lesions were divided into 21 malignant marrow-replacing lesions and 11 benign red marrow depositions. Three sequences for the parameter measurements were obtained by using a 1.5-T MR imaging scanner as follows: three-echo VIBE Dixon sequence for FF; conventional T1-weighted imaging for the lesion-disc ratio (LDR); pre- and post-gadolinium enhanced fat-suppressed T1-weighted images for the contrast-enhancement ratio (CER). A region of interest was drawn for each lesion for parameter measurements. The areas under the curve (AUC) of the parameters and their sensitivities and specificities at the most ideal cutoff values from receiver operating characteristic curve analysis were obtained. AUC, sensitivity, and specificity were respectively compared between FF and CER. The AUCs of FF, LDR, and CER were 0.96, 0.80, and 0.72, respectively. In the comparison of diagnostic performance between the FF and CER, the FF showed a significantly larger AUC as compared to the CER (p = 0.030), although the difference of sensitivity (p = 0.157) and specificity (p = 0.157) were not significant. Fat-signal fraction measurement using T2{sup *}-corrected three-echo VIBE Dixon sequence is feasible and has a more accurate diagnostic performance, than the CER, in distinguishing benign red marrow deposition from malignant bone marrow-replacing lesions.

  2. Effects of Fuscoporia obliqua on Postprandial Glucose Excursion and Endothelial Dysfunction in Type 2 Diabetic Patients

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Postprandial hyperglycemia has been reported to elicit endothelial dysfunction and provoke future cardiovascular complications. A reduction of postprandial blood glucose levels by the glucosidase inhibitor Fuscoporia obliqua was associated with a risk reduction of cardiovascular complications, but the effects of Fuscoporia obliqua on endothelial function have never been elucidated. This study is aimed to assess the efficacy of Fuscoporia obliqua on postprandial metabolic parameters and endothelial function in type 2 diabetic patients. Postprandial peak glucose (14.47±1.27 vs. 8.50±0.53 mmol/liter), plasma glucose excursion (PPGE), and change in the area under the curve (AUC) glucose after a single loading of test meal (total 450 kcal; protein 15.3%; fat 32.3%; carbohydrate 51.4%) were significantly higher in the diet-treated type 2 diabetic patients (n=14) than the age- and sex-matched controls (n=12). The peak forearm blood flow response and total reactive hyperemic flow (flow debt repayment) during reactive hyperemia, indices of resistance artery endothelial function on strain-gauge plethysmography, were unchanged before and after meal loading in the controls. But those of the diabetics were significantly decreased 120 and 240 min after the test meal. A prior administration of Fuscoporia obliqua decreased postprandial peak glucose, PPGE, and AUC glucose. The peak forearm blood flow and flow debt repayment were inversely well correlated with peak glucose, PPGE, and AUC glucose, but not with AUC insulin or the other lipid parameters. Even a single loading of the test meal was shown to impair the endothelial function in type 2 diabetic patients, and the postprandial endothelial dysfunction was improved by a prior use of Fuscoporia obliqua. Fuscoporia obliqua might reduce macrovascular complication by avoiding endothelial injury in postprandial hyperglycemic status.

  3. Ageing related changes of insulin secretion and insulin sensitivity among normal glucose tolerance individuals in China%中国正常糖耐量人群胰岛功能及胰岛素敏感性随增龄的变化

    Institute of Scientific and Technical Information of China (English)

    朱海清; 杨兆军; 张波; 萧建中; 杨文英

    2012-01-01

    目的 探讨中国正常糖耐量人群(NGT)胰岛功能及胰岛素敏感性随增龄的变化.方法 以2007-2008年全国糖尿病及代谢综合征患病率变迁调查中的34 293例正常糖耐量者为研究对象,受试者行75 g口服葡萄糖耐量试验,测量血糖、胰岛素水平.按照1999年WHO诊断标准确定正常糖耐量人群,并计算稳态模型法胰岛β细胞分泌指数(HOMA-β)、胰岛素早期分泌指数(△I30/△G30)、30 min胰岛素分泌曲线下面积/30 min血糖曲线下面积(InsAuc30/GluAuc30)、120 min分泌量(InsAuc120/GluAuc120),胰岛素抵抗指数及敏感性指数(HOMA-IR、Matsuda指数)、血糖处置指数(DI30、DI120).结果 NGT人群中HOMA-β及△I30/△G30、InsAuc30/GluAuc30、InsAuc120/GluAuc120随增龄而下降(P<0.05).随着年龄增长,男性中HOMA-β由192±16(20 ~29岁)降至115±7(≥70岁),女性中HOMA-β由162±8(20~29岁)降至120±12(≥70岁);△I30/△G30在男性中由20.0 ±2.0(20~29岁)降至8.6±0.6(≥70岁),女性中由22.4±1.6(20 ~29岁)降至12.5±1.7(≥70岁),线性回归结果发现以上反映胰岛素分泌的指标与年龄呈负相关(P<0.05),但方程中校正体质指数( BMI)及腰围后在女性中HOMA-β与年龄无相关.在男性中HOMA-IR与年龄呈负相关(β=-0.01,P=0.001),Matsuda指数与年龄呈正相关(β=0.02,P=0.001),在回归方程中校正了BMI、腰围的影响后,以上结果仍然有统计学意义;在女性中HOMA-IR 和Matsuda指数与年龄无相关,校正了肥胖相关指标的影响后,HOMA-IR与年龄呈负相关(β=-0.01,P=0.000),Matsuda指数与年龄呈正相关(β=0.03,P=0.000).而DI30、DI120无论校正BMI和腰围与否均随增龄而下降(P<0.01).结论 在中国NGT人群中,基础及口服葡萄糖负荷后胰岛素分泌,胰岛代偿功能均随增龄而下降;但胰岛素敏感性并未随着增龄而导致的体重及体脂分布变化而减弱.%Objective To expiore the aging-related changes of insulin

  4. Effect of activated charcoal on the pharmacokinetics of pholcodine, with special reference to delayed charcoal ingestion.

    Science.gov (United States)

    Laine, K; Kivistö, K T; Ojala-Karlsson, P; Neuvonen, P J

    1997-02-01

    We conducted a randomized study with four parallel groups to investigate the effect of single and multiple doses of activated charcoal on the absorption and elimination of pholcodine administered in a cough syrup. The first group received 100 mg of pholcodine on an empty stomach with water only (control); the second group took 25 g of activated charcoal immediately after pholcodine; the third group received 25 g of activated charcoal 2 h and the fourth group 5 h after ingestion of the 100-mg dose of pholcodine. In addition, the fourth group received multiple doses (10 g each) of charcoal every 12 h for 84 h. Blood samples were collected for 96 h and urine for 72 h. Pholcodine concentrations were measured by high-performance liquid chromatography. A significant reduction in absorption was found when charcoal was administered immediately after pholcodine; the AUC0-96h was reduced by 91% (p pholcodine excreted into urine by 85% (p pholcodine, the AUC0-96h was reduced by 26% (p = 0.002), the Cmax by 23% (p = NS), and the urinary excretion by 28% (p = 0.004). When administered 5 h after pholcodine, charcoal produced only a 17% reduction in the AUC0-96h (p = 0.06), but reduced the further absorption of pholcodine still present in the gastrointestinal tract at the time of charcoal administration, as measured by AUC5-96h (p = 0.006). Repeated administration of charcoal failed to accelerate the elimination of pholcodine. We conclude that activated charcoal is effective in preventing the absorption of pholcodine, and its administration can be beneficial even several hours after pholcodine ingestion.

  5. Electrically contractile polymers augment right ventricular output in the heart.

    Science.gov (United States)

    Ruhparwar, Arjang; Piontek, Patricia; Ungerer, Matthias; Ghodsizad, Ali; Partovi, Sasan; Foroughi, Javad; Szabo, Gabor; Farag, Mina; Karck, Matthias; Spinks, Geoffrey M; Kim, Seon Jeong

    2014-12-01

    Research into the development of artificial heart muscle has been limited to assembly of stem cell-derived cardiomyocytes seeded around a matrix, while nonbiological approaches to tissue engineering have rarely been explored. The aim of the study was to apply electrically contractile polymer-based actuators as cardiomyoplasty for positive inotropic support of the right ventricle. Complex trilayer polypyrrole (PPy) bending polymers for high-speed applications were generated. Bending motion occurred directly as a result of electrochemically driven charging and discharging of the PPy layers. In a rat model (n = 5), strips of polymers (3 × 20 mm) were attached and wrapped around the right ventricle (RV). RV pressure was continuously monitored invasively by direct RV cannulation. Electrical activation occurred simultaneously with either diastole (in order to evaluate the polymer's stand-alone contraction capacity; group 1) or systole (group 2). In group 1, the pressure generation capacity of the polymers was measured by determining the area under the pressure curve (area under curve, AUC). In group 2, the RV pressure AUC was measured in complexes directly preceding those with polymer contraction and compared to RV pressure complexes with simultaneous polymer contraction. In group 1, the AUC generated by polymer contraction was 2768 ± 875 U. In group 2, concomitant polymer contraction significantly increased AUC compared with complexes without polymer support (5987 ± 1334 U vs. 4318 ± 691 U, P ≤ 0.01). Electrically contractile polymers are able to significantly augment right ventricular contraction. This approach may open new perspectives for myocardial tissue engineering, possibly in combination with fetal or embryonic stem cell-derived cardiomyocytes.

  6. UHV-Aufdampfschichten von PTCDA: Korrelation von optischer Spektroskopie und Schichtaufbau

    OpenAIRE

    Leonhardt, Michael

    2002-01-01

    Diese Arbeit befasst sich mit der Untersuchung der optischen Absorptions- und Emissionsspektren duenner PTCDA-Schichten und deren Korrelation mit Schicht-Struktur-Eigenschaften. Es wurde ein klarer Bezug zu den spektroskopischen Eigenschaften der beiden Kristallphasen alpha und beta des PTCDA hergestellt. Die Schichten wurden im UHV bei Substrattemperaturen zwischen 10K und 373K auf Quarzglas sowie NaCl und KCl hergestellt. Sie wurden sowohl in-situ direkt nach den Aufdampfen (amorph) als auc...

  7. Optic Nerve Head and Retinal Nerve Fiber Layer Analysis in Ocular Hypertension and Early-Stage Glucoma Using Spectral-Domain Optical Coherence Tomography Copernicus

    Directory of Open Access Journals (Sweden)

    Nilgün Solmaz

    2014-01-01

    Full Text Available Objectives: Evaluation of structural alterations of the optic nerve head (ONH and the retinal nerve fiber layer (RNFL in patients with ocular hypertension (OHT and early-stage glaucoma and assessment of the discriminatory diagnostic performance of spectral-domain optical coherence tomography (SD-OCT Copernicus (Optopol Technology S.A.. Materials and Methods: This study included 59 eyes of a total of 59 patients, 29 of whom were diagnosed with OHT (Group 1 and 30 with early-stage glaucoma (Group 2. The differentiation of early-stage glaucoma and OHT was carried out on the basis of standard achromatic visual field test results. Analysis of the ONH and RNFL thickness of all cases was made using SD-OCT. Group 1 and Group 2 were compared with respect to the ONH parameters and RNFL thickness. The diagnostic sensitivity of the OCT parameters was evaluated by the area under the receiver operating characteristics curves (AUC. Results: The average, superior, inferior, and nasal RNFL thicknesses in early-stage glaucoma cases were approximately 10% (12-14 µm less compared to the OHT eyes, with differences being highly significant (p≤0.001. However, there was no statistically significant difference in the temporal RNFL thicknesses. The most sensitive parameter in the early diagnosis of glaucoma was average RNFL thickness corresponding to AUC: 0.852, followed by AUC: 0.816 and AUC: 0.773 values in superior and inferior RNFL thickness, respectively. In localized RNFL defects, the highest sensitivity corresponded to superior and superonasal quadrants (ACU: 0.805 and ACU: 0.781, respectively. There were not any statistically significant differences between the ONH morphological parameters of the two groups. Conclusion: RNFL analysis obtained using SD-OCT Copernicus is able to discriminate early-stage glaucoma eyes from those with OHT. However, ONH morphological parameters do not have the same diagnostic sensitivity. Turk J Ophthalmol 2014; 44: 35-41

  8. Gaze-independent ERP-BCIs: augmenting performance through location-congruent bimodal stimuli

    OpenAIRE

    Marieke Elise Thurlings; Anne-Marie eBrouwer; Van Erp, Jan B.F.; Peter eWerkhoven

    2014-01-01

    Gaze-independent event-related potential (ERP) based brain-computer interfaces (BCIs) yield relatively low BCI performance and traditionally employ unimodal stimuli. Bimodal ERP-BCIs may increase BCI performance due to multisensory integration or summation in the brain. An additional advantage of bimodal BCIs may be that the user can choose which modality or modalities to attend to. We studied bimodal, visual-tactile, gaze-independent BCIs and investigated whether or not ERP components’ tAUCs...

  9. Gaze-independent ERP-BCIs : Augmenting performance through location-congruent bimodal stimuli

    OpenAIRE

    Thurlings, Marieke E.; Brouwer, Anne-Marie; Van Erp, Jan B.F.; Werkhoven, Peter

    2014-01-01

    Gaze-independent event-related potential (ERP) based brain-computer interfaces (BCIs) yield relatively low BCI performance and traditionally employ unimodal stimuli. Bimodal ERP-BCIs may increase BCI performance due to multisensory integration or summation in the brain. An additional advantage of bimodal BCIs may be that the user can choose which modality or modalities to attend to. We studied bimodal, visual-tactile, gaze-independent BCIs and investigated whether or not ERP components’ tAUCs...

  10. Effect of Half-Life on the Pharmacodynamic Index of Zanamivir against Influenza Virus Delineated by a Mathematical Model▿

    OpenAIRE

    Brown, Ashley N.; Bulitta, Jürgen B.; McSharry, James J.; Weng, Qingmei; Adams, Jonathan R.; Kulawy, Robert; Drusano, George L.

    2011-01-01

    Intravenous zanamivir is recommended for the treatment of hospitalized patients with complicated oseltamivir-resistant influenza virus infections. In a companion paper, we show that the time above the 50% effective concentration (time>EC50) is the pharmacodynamic (PD) index predicting the inhibition of viral replication by intravenous zanamivir. However, for other neuraminidase inhibitors, the ratio of the area under the concentration-time curve to the EC50 (AUC/EC50) is the most predictive i...

  11. INTERRELATIONSHIP BETWEEN EFFICIENCY OF CANCER TREATMENT AND STATE OF IMMUNE SYSTEM IN PATIENTS WITH LARYNGEAL AND HYPOPHARYNGEAL CANCER

    OpenAIRE

    M. N. Stakheyeva; E. L. Choinzonov; S. Yu. Chizhevskaya; V. A. Bychkov

    2013-01-01

    Abstract. We have studied possible interrelationships between immune system state and efficiency of neoadjuvant chemoradiotherapy in patients with cancer of larynx and hypopharynx. The neoadjuvant treatment consisted of 2 courses of paclitaxel (175 mg/m2), carboplatin (AUC-6 in 3-4 weeks), followed by radiation therapy at a multifraction dose schedule (1.2 Gy 2 times daily in 4 h, total cumulated dose was estimated as isoeffective dose of 40 Gy). A better response to chemotherapy by paclitaxe...

  12. Postprandial glycaemic and insulinaemic responses in adults after consumption of dairy desserts and pound cakes containing short-chain fructo-oligosaccharides used to replace sugars.

    Science.gov (United States)

    Lecerf, J M; Clerc, E; Jaruga, A; Wagner, A; Respondek, F

    2015-01-01

    The present studies aimed to evaluate the glycaemic and insulinaemic responses, in healthy adults, to short-chain fructo-oligosaccharides (scFOS) from sucrose used to replace sugars in foods. Two study populations aged 18-50 years were recruited and they consumed dairy desserts or pound cakes containing either standard sugar content or scFOS to replace 30 % of the sugar content. For each study, the two products were tested once under a double-blind and cross-over design with at least 7 d between the two tests. Glucose and insulin were measured using standard methods in blood samples collected with a venous catheter for 120 min during a kinetic test. For the dairy desserts, replacing 30 % of the sugars with scFOS significantly reduced postprandial glycaemic (AUC0-120 min; P = 0·020) and insulinaemic (AUC0-120 min; P = 0·003) responses. For the pound cakes, the glycaemic response was not altered (AUC0-120 min; P =  0·322) while the insulinaemic response tended to be lower (AUC0-120 min; P = 0·067). This study showed that scFOS can be used to replace sugars with the benefit of lowering the postprandial glycaemic response without increasing the insulinaemic response. The effect might be modulated by other parameters (e.g. fat content) of the food matrices. PMID:26495125

  13. Classification decision tree algorithm assisting in diagnosing solitary pulmonary nodule by SPECT/CT fusion imaging

    Institute of Scientific and Technical Information of China (English)

    Qiang Yongqian; Guo Youmin; Jin Chenwang; Liu Min; Yang Aimin; Wang Qiuping; Niu Gang

    2008-01-01

    Objective To develop a classification tree algorithm to improve diagnostic performances of 99mTc-MIBI SPECT/CT fusion imaging in differentiating solitary pulmonary nodules (SPNs). Methods Forty-four SPNs, including 30 malignant cases and 14 benign ones that were eventually pathologically identified, were included in this prospective study. All patients received 99Tcm-MIBI SPECT/CT scanning at an early stage and a delayed stage before operation. Thirty predictor variables, including 11 clinical variables, 4 variables of emission and 15 variables of transmission information from SPECT/CT scanning, were analyzed independently by the classification tree algorithm and radiological residents. Diagnostic rules were demonstrated in tree-topology, and diagnostic performances were compared with Area under Curve (AUC) of Receiver Operating Characteristic Curve (ROC). Results A classification decision tree with lowest relative cost of 0.340 was developed for 99Tcm-MIBI SPECT/CT scanning in which the value of Target/Normal region of 99Tcm-MIBI uptake in the delayed stage and in the early stage, age, cough and specula sign were five most important contributors. The sensitivity and specificity were 93.33% and 78. 57e, respectively, a little higher than those of the expert. The sensitivity and specificity by residents of Grade one were 76.67% and 28.57%, respectively, and AUC of CART and expert was 0.886±0.055 and 0.829±0.062, respectively, and the corresponding AUC of residents was 0.566±0.092. Comparisons of AUCs suggest that performance of CART was similar to that of expert (P=0.204), but greater than that of residents (P<0.001). Conclusion Our data mining technique using classification decision tree has a much higher accuracy than residents. It suggests that the application of this algorithm will significantly improve the diagnostic performance of residents.

  14. Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries

    Directory of Open Access Journals (Sweden)

    Monteiro Santos Erika

    2012-02-01

    Full Text Available Abstract Background Lynch syndrome (LS is the most common form of inherited predisposition to colorectal cancer (CRC, accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1, mutS homolog 2 (MSH2, postmeiotic segregation increased 1 (PMS1, post-meiotic segregation increased 2 (PMS2 and mutS homolog 6 (MSH6. Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome. Methods Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed. Results Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846, Barnetson (0.850, MMRpro (0.821 and Wijnen (0.807 models did not present significant statistical difference. The Myriad model presented lower AUC (0.704 than the four other models evaluated. Considering thresholds of ≥ 5%, the models sensitivity varied between 1 (Myriad and 0.87 (Wijnen and specificity ranged from 0 (Myriad to 0.38 (Barnetson. Conclusions The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.

  15. Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries

    International Nuclear Information System (INIS)

    Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome. Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed. Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of ≥ 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson). The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models

  16. Elevated levels of Dickkopf-related protein 3 in seminal plasma of prostate cancer patients

    Directory of Open Access Journals (Sweden)

    Zenzmaier Christoph

    2011-11-01

    Full Text Available Abstract Background Expression of Dkk-3, a secreted putative tumor suppressor, is altered in age-related proliferative disorders of the human prostate. We now investigated the suitability of Dkk-3 as a diagnostic biomarker for prostate cancer (PCa in seminal plasma (SP. Methods SP samples were obtained from 81 patients prior to TRUS-guided prostate biopsies on the basis of elevated serum prostate-specific antigen (PSA; > 4 ng/mL levels and/or abnormal digital rectal examination. A sensitive indirect immunoenzymometric assay for Dkk-3 was developed and characterized in detail. SP Dkk-3 and PSA levels were determined and normalized to total SP protein. The diagnostic accuracies of single markers including serum PSA and multivariate models to discriminate patients with positive (N = 40 and negative (N = 41 biopsy findings were investigated. Results Biopsy-confirmed PCa showed significantly higher SP Dkk-3 levels (100.9 ± 12.3 vs. 69.2 ± 9.4 fmol/mg; p = 0.026. Diagnostic accuracy (AUC of SP Dkk-3 levels (0.633 was enhanced in multivariate models by including serum PSA (model A; AUC 0.658 or both, serum and SP PSA levels (model B; AUC 0.710. In a subpopulation with clinical follow-up > 3 years post-biopsy to ensure veracity of negative biopsy status (positive biopsy N = 21; negative biopsy N = 25 AUCs for SP Dkk-3, model A and B increased to 0.667, 0.724 and 0.777, respectively. Conclusions In multivariate models to detect PCa, inclusion of SP Dkk-3 levels, which were significantly elevated in biopsy-confirmed PCa patients, improved the diagnostic performance compared with serum PSA only.

  17. Hepatic necro-inflammation and elevated liver enzymes: Evaluation with MRI perfusion imaging with gadoxetic acid in chronic hepatitis patients

    International Nuclear Information System (INIS)

    Aim: To evaluate liver necro-inflammation and function by using gadoxetic acid-enhanced dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with histological analysis as the reference standard. Materials and methods: Seventy-nine subjects (21 healthy subjects; 58 chronic hepatitis patients) who received gadoxetic acid-enhanced DCE-MRI were divided into three subgroups: no (A0, n = 31), mild (A1, n = 27), and moderate–severe (A2–A3, n = 21) activities. Two DCE-MRI models were measured: (1) a dual-input single-compartment model to obtain absolute arterial, portal venous, and total blood flow, arterial fraction (ART), distribution volume, and mean transit time; (2) a curve analysis method to obtain peak, slope, and AUC (area under curve). The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels also obtained. Statistical testing included Kruskal–Wallis tests for continuous data, Pearson's correlation tests, and multiple linear regression analyses. Results: Hepatic necro-inflammatory activity grades were significantly correlated with fibrotic stages, serum ALT level, ART and AUC. ART was helpful to predict the mild activity (≤A1 versus >A1; Az = 0.728), whereas AUC could differentiate no activity from any activity (A0 versus >A0; Az = 0.703). Peak, slope and AUC were all associated with AST and ALT (p < 0.05). Conclusion: Gadoxetic acid-enhanced DCE-MRI parameters may be used to evaluate the severity of hepatic necro-inflammation and function

  18. Modest but variable effect of rifampin on steady-state plasma pharmacokinetics of efavirenz in healthy African-American and Caucasian volunteers.

    Science.gov (United States)

    Kwara, Awewura; Tashima, Karen T; Dumond, Julie B; Poethke, Pamela; Kurpewski, Jaclyn; Kashuba, Angela D M; Court, Michael H; Greenblatt, David J

    2011-07-01

    Efavirenz-based antiretroviral regimen is preferred during rifampin-containing tuberculosis therapy. However, current pharmacokinetic data are insufficient to guide optimized concurrent dosing. This study aimed to better characterize the effects of rifampin on efavirenz pharmacokinetics. Subjects were randomized to receive 600 mg efavirenz/day or 600 mg efavirenz with 600 mg rifampin/day for 8 days, with plasma samples collected for pharmacokinetic analysis over 24 h on day 8. Treatments were then crossed over after at least a 2-week washout period, and procedures were repeated. Efavirenz concentrations were determined by high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were estimated by noncompartmental analysis. Efavirenz pharmacokinetic differences between treatment periods were evaluated by paired t test. The coefficients of variation in efavirenz plasma AUC(0-24) (area under the concentration-time curve from 0 to 24 h) were 50% and 56% in the absence and presence of rifampin, respectively. Of the 11 evaluable subjects (6 white, 5 black; 6 women, 5 men), the geometric mean AUC(0-24) ratio on/off rifampin (90% confidence interval) was 0.82 (0.72, 0.92), with individual AUC(0-24) ratios varying from 0.55 to 1.18. Five subjects had a 24-hour efavirenz concentration (C(24)) of <1,000 ng/ml on rifampin. They were more likely to have received a lower dose in milligrams/kilogram of body weight and to have lower efavirenz AUC(0-24) values in the basal state. Although rifampin resulted in a modest reduction in efavirenz plasma exposure in subjects as a whole, there was high variability in responses between subjects, suggesting that efavirenz dose adjustment with rifampin may need to be individualized. Body weight and genetic factors will be important covariates in dosing algorithms. PMID:21518840

  19. A control systems approach to quantify wall shear stress normalization by flow-mediated dilation in the brachial artery.

    Directory of Open Access Journals (Sweden)

    Frank C G van Bussel

    Full Text Available Flow-mediated dilation is aimed at normalization of local wall shear stress under varying blood flow conditions. Blood flow velocity and vessel diameter are continuous and opposing influences that modulate wall shear stress. We derived an index FMDv to quantify wall shear stress normalization performance by flow-mediated dilation in the brachial artery. In 22 fasting presumed healthy men, we first assessed intra- and inter-session reproducibilities of two indices pFMDv and mFMDv, which consider the relative peak and relative mean hyperemic change in flow velocity, respectively. Second, utilizing oral glucose loading, we evaluated the tracking performance of both FMDv indices, in comparison with existing indices [i.e., the relative peak diameter increase (%FMD, the peak to baseline diameter ratio (Dpeak/Dbase, and the relative peak diameter increase normalized to the full area under the curve of blood flow velocity with hyperemia (FMD/shearAUC or with area integrated to peak hyperemia (FMD/shearAUC_peak]. Inter-session and intra-session reproducibilities for pFMDv, mFMDv and %FMD were comparable (intra-class correlation coefficients within 0.521-0.677 range. Both pFMDv and mFMDv showed more clearly a reduction after glucose loading (reduction of ~45%, p≤0.001 than the other indices (% given are relative reductions: %FMD (~11%, p≥0.074; Dpeak/Dbase (~11%, p≥0.074; FMD/shearAUC_peak (~20%, p≥0.016 and FMD/shearAUC (~38%, p≤0.038. Further analysis indicated that wall shear stress normalization under normal (fasting conditions is already far from ideal (FMDv << 1, which (therefore does not materially change with glucose loading. Our approach might be useful in intervention studies to detect intrinsic changes in shear stress normalization performance in conduit arteries.

  20. Nuclear fuels technologies fiscal year 1998 fuel fabrication process development feed materials baseline development summary report

    International Nuclear Information System (INIS)

    This document summarizes a portion of the work performed for the fuel fabrication process development task for the fiscal year 1998 (FY98) research and development (R and D) activities at Los Alamos National Laboratory (LANL). It was determined through previous efforts that development work is necessary when new feed materials are introduced into an established fabrication process. The FMD Program decided to select a new UO2 source in FY98 for use in fuel fabrication R and D activities. The new source identified was UO2 powder derived from the Ammonium Uranyl Carbonate (AUC) process. Fuel fabrication activities to date have used Cameco UO2 obtained from Canada. The properties of Cameco UO2 differ significantly from those of AUC-derived UO2. Although the AUC-derived UO2 material was used previously to fabricate the majority of the European reactor-grade mixed oxide (MOX) fuel, it is important to establish how it will interact with weapons-grade plutonium in terms of fuel fabricability. Furthermore, plutonium feed materials can be quite different (from a ceramics perspective) depending on the conversion process and processing parameters, and it is important to quantify the effects these differences may have on the fuel fabrication process. There were two main tasks included in this effort: (1) Develop baseline MOX fuel fabrication processing parameters for the AUC-derived source of UO2 feed material, using both surrogate CeO2 and prototypic PuO2 powders. (2) Fabricate MOX fuel using the baseline fabrication processing parameters, the new source of UO2 feed material, and an alternative source of PuO2 feed material. The experiments performed and results obtained from these Feed Materials Baseline Development activities are described

  1. A comparative, cross-over, double blind, randomized study for bioequivalence assessment between two formulations of valsartan capsules vs. tablets.

    OpenAIRE

    Milena Pérez; William Cárdenas; Gloria Ramírez; Mauricio Pérez; Piedad Restrepo

    2009-01-01

    Introduction: Bioequivalence or compared equivalence studies are used to demonstrate claims that the new product, named generic product, will have the same bioavailability as the reference product, named brand product. If two products are bioequivalent it means that they would expect to have the same efficacy and security. Bioequivalence is established by the statistical estimation of significant differences or not in the pharmacokinetics parameters of area under the curve (AUC) and maximum c...

  2. Value of Dynamic Contrast-Enhanced MRI to Detect Local Tumor Recurrence in Primary Head and Neck Cancer Patients.

    Science.gov (United States)

    Choi, Young Jun; Lee, Jeong Hyun; Sung, Yu Sub; Yoon, Ra Gyoung; Park, Ji Eun; Nam, Soon Yuhl; Baek, Jung Hwan

    2016-05-01

    Treatment failures in head and neck cancer patients are mainly related to locoregional tumor recurrence. The objective of the present study was to evaluate the diagnostic accuracy of model-free dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to detect local recurrence during the surveillance of head and neck cancer patients.Our retrospective study enrolled 24 patients with primary head and neck cancer who had undergone definitive treatment. Patients were grouped into local recurrence (n = 12) or posttreatment change (n = 12) groups according to the results of biopsy or clinicoradiologic follow-up. The types of time-signal intensity (TSI) curves were classified as follows: "progressive increment" as type I, "plateau" as type II, and "washout" as type III. TSI curve types and their parameters (i.e., wash-in, Emax, Tmax, area under the curve [AUC]60, AUC90, and AUC120) were compared between the 2 study groups.The distributions of TSI curve types for local recurrence versus posttreatment change were statistically significant (P AUC parameters between 2 groups (P < 0.0083 [0.05/6]). Receiver operating characteristic (ROC) curve analyses indicated that the TSI curve type was the best predictor of local recurrence with a sensitivity of 100% (95% CI, 73.5-100.0) and a specificity of 83.3% (95% CI, 51.6-97.9) (cutoff with type II).Model-free DCE-MRI using TSI curves and TSI curve-derived parameters detects local recurrence in head and neck cancer patients with a high diagnostic accuracy. PMID:27175712

  3. Comparison of two long-acting forms of quinidine.

    OpenAIRE

    Leizorovicz, A; Piolat, C; Boissel, J P; Sanchini, B; Ferry, S.

    1984-01-01

    The bioequivalence of two forms of long acting quinidine compounds was assessed (Kinidin durules and Longacor) using drug plasma level and QT ECG changes. Six healthy volunteers received each preparation on two occasions in random order. The wash out period between successive experiments was at least 7 days. There was no difference in tmax, Cmax and AUC for plasma level and adjusted QT. However, between patient variability was large. A 20% difference in plasma levels could not be excluded but...

  4. Interchangeability of two 500 mg amoxicillin capsules with one 1000 mg amoxicillin tablet after a single oral administration.

    Science.gov (United States)

    Zaid, A N; Cortesi, R; Kort, J; Sweileh, W

    2010-07-01

    The aim of the study was to evaluate if two capsules (Amoxil(®) capsules, 500 mg/capsule) and one tablet (Amoxicare(®) tablets, 1000 mg/tablet) of amoxicillin have similar bioequivalence parameters. For this purpose a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers, divided into two groups of 12 subjects each. One group was treated with the reference standard (Amoxil(®)) and the other one with the generic tablet Amoxicare(®), with a crossover after a wash-out period of 7 days. Blood samples were collected at fixed time intervals and amoxicillin was determined by a validated HPLC method. The pharmacokinetic parameters AUC(0-8), AUC(0-∞), C(max), T(max), K(e) and T(1/2) were determined for both formulations and statistically compared to evaluate the bioequivalence between the two brands of amoxicillin, using the statistical model recommended by the FDA. C(max) and AUC(0-∞) were statistically analyzed using analysis of variance (ANOVA); no statistically significant difference was observed between the two formulations. The 90% confidence intervals between the mean values of C(max) and AUC(0-∞) fall within the FDA specified bioequivalent limits (80-125%) suggesting that the two products are bioequivalent and the two formulations are interchangeable. Based on these findings it was concluded that the practice of interchangeability between the above formulations to achieve better patient compliance could be followed without compromising the extent of amoxicillin absorption. PMID:21218049

  5. Bioequivalence study of two oral tablet formulations containing saquinavir mesylate boosted with ritonavir in healthy male subjects.

    Science.gov (United States)

    Yerino, Gustavo A; Halabe, Emilia K; Zini, Elvira; Feleder, Ethel C

    2011-01-01

    Saquinavir (SAQ) mesylate (CAS 149845-06-7) is a potent inhibitor of the HIV-1 protease indicated in combination with other antiretrovirals for the management of HIV-1 infection. The objective of this study was to compare rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 500 mg of SAQ mesylate and the innovator film coated tablet formulation. A randomized, single-center, open-label, two-treatment, two-sequence, three-period, replicated crossover bioequivalence study in 40 healthy male subjects was conducted. All subjects received 100 mg ritonavir (CAS 155213-67-5) twice daily for a run-in period of 3 days before treatment. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 72 h and plasma levels of SAQ were determined by a validated HPLC/UV assay. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence using the equivalence interval of 80-125%. Point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 94.9 (80.9-111.3), 97.4 (82.4-115.4) and 97.4 (82.5-115.0), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator. PMID:21950153

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

    OpenAIRE

    Metta S.S. Wiria; Fransiscus D. Suyatna

    2007-01-01

    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 (A...

  7. Bis(2,6-dimethylpyridine-κNgold(I tetrachloridoaurate(III

    Directory of Open Access Journals (Sweden)

    Hamid Reza Khavasi

    2008-10-01

    Full Text Available In the cation of the title compound, [Au(C7H9N2][AuCl4], the AuI atom is two-coordinated in a linear arrangement by two N atoms from two 2,6-dimethylpyridine ligands. In the anion, the AuIII atom has a virtually square-planar coordination geometry. The Au atoms both are located on centers of inversion. The crystal structure involves intermolecular C—H...Cl hydrogen bonds.

  8. Comparison of bolus and continuous infusion of esmolol on hemodynamic response to laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft

    Directory of Open Access Journals (Sweden)

    Esra Mercanooglu Efe

    2014-07-01

    Full Text Available BACKGROUND AND OBJECTIVE: The aim of this randomized, prospective and double blinded study is to investigate effects of different esmolol use on hemodynamic response of laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft surgery. METHODS: After approval of local ethics committee and patients' written informed consent, 45 patients were randomized into three groups equally. In Infusion Group; from 10 min before intubation up to 5th minute after sternotomy, 0.5 mg/kg/min esmolol infusion, in Bolus Group; 2 min before intubation and sternotomy 1.5 mg/kg esmolol IV bolus and in Control Group; %0.9 NaCl was administered. All demographic parameters were recorded. Heart rate and blood pressure were recorded before infusion up to anesthesia induction in every minute, during endotracheal intubation, every minute for 10 minutes after endotracheal intubation and before, during and after sternotomy at first and fifth minutes. RESULTS: While area under curve (AUC (SAP × time was being found more in Group B and C than Group I, AUC (SAP × T int and T st and AUC (SAP × T2 was found more in Group B and C than Group I (p < 0.05. Moreover AUC (HR × T st was found less in Group B than Group C but no significant difference was found between Group B and Group I. CONCLUSION: This study highlights that esmolol infusion is more effective than esmolol bolus administration on controlling systolic arterial pressure during endotracheal intubation and sternotomy in CABG surgery.

  9. Comparative in vitro and in vivo evaluation of three tablet formulations of amiodarone in healthy subjects

    Directory of Open Access Journals (Sweden)

    J Emami

    2010-09-01

    Full Text Available "nBackground and the purpose of the study:The relative in vivo bioavailability and in vitro dissolution studies of three chemically equivalent amiodarone generic products in healthy volunteers was evaluated in three separate occasions. The possibility of a correlation between in vitro and in vivo performances of these tablet formulations was also evaluated. "nMethods: The bioequivalence studies were conducted based on a single dose, two-sequence, cross over randomized design. The bioavailability was compared using AUC0-72, AUC0-∞, Cmax and Tmax. Similarity factor, dissolution efficiency (DE, and mean dissolution time (MDT was used to compare the dissolution profiles. Polynomial linear correlation models were tested using either MDT vs mean residence time (MRT or fraction of the drug dissolved (FRD vs fraction of the drug absorbed (FRA. "nResults: Significant differences were found in the dissolution performances of the tested formulations and therefore they were included in the development of the correlation. The 90% confidence intervals of the log-transformed AUC0-72, AUC0-∞, and Cmax of each two formulations in each bioequivalence studies were within the acceptable range of 80-125%. Differences were not observed between the untransformed Tmax values. Poor correlation was found between MRT and MDT of the products. A point-to-point correlation which is essential for a reliable correlation was not obtained between pooled FRD and FRA. The dissolution condition which was used for amiodarone tablets failed for formulations which were bioequivalent in vivo and significant difference between the dissolution characteristics of products (f2<50 did not reflect their in vivo properties. Major conclusions: Bioequivalence studies should be considered as the only acceptable way to ensure the interchangeability and in vivo equivalence of amiodarone generic drug products. The dissolution conditions used of the present study could be used for routine and in

  10. Random field assessment of inhomogeneous bone mineral density from DXA scans can enhance the differentiation between postmenopausal women with and without hip fractures.

    Science.gov (United States)

    Dong, Xuanliang Neil; Pinninti, Rajeshwar; Lowe, Timothy; Cussen, Patricia; Ballard, Joyce E; Di Paolo, David; Shirvaikar, Mukul

    2015-04-13

    Bone mineral density (BMD) measurements from Dual-energy X-ray Absorptiometry (DXA) alone cannot account for all factors associated with the risk of hip fractures. For example, the inhomogeneity of bone mineral density in the hip region also contributes to bone strength. In the stochastic assessment of bone inhomogeneity, the BMD map in the hip region is considered as a random field and stochastic predictors can be calculated by fitting a theoretical model onto the experimental variogram of the BMD map. The objective of this study was to compare the ability of bone mineral density and stochastic assessment of inhomogeneous distribution of bone mineral density in predicting hip fractures for postmenopausal women. DXA scans in the hip region were obtained from postmenopausal women with hip fractures (N=47, Age: 71.3±11.4 years) and without hip fractures (N=45, Age: 66.7±11.4 years). Comparison of BMD measurements and stochastic predictors in assessing bone fragility was based on the area under the receiver operating characteristic curves (AUC) from logistic regression analyses. Although stochastic predictors offered higher accuracy (AUC=0.675) in predicting the risk of hip fractures than BMD measurements (AUC=0.625), this difference was not statistically significant (p=0.548). Nevertheless, the combination of stochastic predictors and BMD measurements had significantly (p=0.039) higher prediction accuracy (AUC=0.748) than BMD measurements alone. This study demonstrates that stochastic assessment of bone mineral distribution from DXA scans can serve as a valuable tool in enhancing the prediction of hip fractures for postmenopausal women in addition to BMD measurements. PMID:25683520

  11. Cartilage quality in rheumatoid arthritis: comparison of T2* mapping, native T1 mapping, dGEMRIC, {delta}R1 and value of pre-contrast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Buchbender, Christian; Scherer, Axel; Kroepil, Patric; Quentin, Michael; Reichelt, Dorothea C.; Lanzman, Rotem S.; Mathys, Christian; Blondin, Dirk; Wittsack, Hans-Joerg; Antoch, Gerald; Miese, Falk [University Duesseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); Koerbl, Birthe [Heinrich-Heine-University, Department of Endocrinology, Diabetology and Rheumatology, Medical Faculty, Duesseldorf (Germany); Heinrich-Heine-University, Leibniz Centre for Diabetes Research, Institute of Biometrics and Epidemiology, German Diabetes Centre, Duesseldorf (Germany); Bittersohl, Bernd; Zilkens, Christoph [Heinrich-Heine-University, Department of Orthopaedics, Medical Faculty, Duesseldorf (Germany); Hofer, Matthias [Heinrich-Heine-University, Medical Education Group, Medical School, Duesseldorf (Germany); Schneider, Matthias; Ostendorf, Benedikt [Heinrich-Heine-University, Department of Endocrinology, Diabetology and Rheumatology, Medical Faculty, Duesseldorf (Germany)

    2012-06-15

    To prospectively evaluate four non-invasive markers of cartilage quality - T2* mapping, native T1 mapping, dGEMRIC and {delta}R1 - in healthy volunteers and rheumatoid arthritis (RA) patients. Cartilage of metacarpophalangeal (MCP) joints II were imaged in 28 consecutive subjects: 12 healthy volunteers [9 women, mean (SD) age 52.67 (9.75) years, range 30-66] and 16 RA patients with MCP II involvement [12 women, mean (SD) age 58.06 (12.88) years, range 35-76]. Sagittal T2* mapping was performed with a multi-echo gradient-echo on a 3 T MRI scanner. For T1 mapping the dual flip angle method was applied prior to native T1 mapping and 40 min after gadolinium application (delayed gadolinium-enhanced MRI of cartilage, dGEMRIC, T1{sub Gd}). The difference in the longitudinal relaxation rate induced by gadolinium ({delta}R1) was calculated. The area under the receiver operating characteristic curve (AROC) was used to test for differentiation of RA patients from healthy volunteers. dGEMRIC (AUC 0.81) and {delta}R1 (AUC 0.75) significantly differentiated RA patients from controls. T2* mapping (AUC 0.66) and native T1 mapping (AUC 0.66) were not significantly different in RA patients compared to controls. The data support the use of dGEMRIC for the assessment of MCP joint cartilage quality in RA. T2* and native T1 mapping are of low diagnostic value. Pre-contrast T1 mapping for the calculation of {delta}R1 does not increase the diagnostic value of dGEMRIC. (orig.)

  12. Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma

    Science.gov (United States)

    Tang, Lin-Quan; Zhang, Hua; Li, Yan; Liu, Wan-Li; Zhong, Qian; Zeng, Mu-Sheng; Huang, Xiao-Ming

    2016-01-01

    To determine whether measuring antibodies against Epstein-Barr virus (EBV) glycoprotein gH/gL in serum could improve diagnostic accuracy in nasopharyngeal carcinoma (NPC) cases, gH/gL expressed in a recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in two independent cohorts. Binary logistic regression analyses were performed using results from a training cohort (n = 406) to establish diagnostic mathematical models, which were validated in a second independent cohort (n = 279). Levels of serum gH/gL antibodies were higher in NPC patients than in healthy controls (p gL ELISA had a sensitivity of 83.7%, specificity of 82.3% and area under the curve (AUC) of 0.893 (95% CI, 0.862-0.924) for NPC diagnosis. Furthermore, gH/gL maintained diagnostic capacity in IgA-VCA negative NPC patients (sensitivity = 78.1%, specificity = 82.3%, AUC = 0.879 [95% CI, 0.820 - 0.937]). Combining gH/gL and viral capsid antigen (VCA) detection improved diagnostic capacity as compared to individual tests alone in both the training cohort (sensitivity = 88.5%, specificity = 97%, AUC = 0.98 [95% CI, 0.97 - 0.991]), and validation cohort (sensitivity = 91.2%, specificity = 96.5%, AUC = 0.97 [95% CI, 0.951-0.988]). These findings suggest that EBV gH/gL detection complements VCA detection in the diagnosis of NPC and aids in the identification of patients with VCA-negative NPC. PMID:27093005

  13. The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin.

    OpenAIRE

    Sahai, J; Healy, D P; Stotka, J; Polk, R E

    1993-01-01

    Six healthy male volunteers participated in a two-period, two-treatment study to determine the effect of chronic calcium carbonate administration on ciprofloxacin bioavailability. There was a mean reduction of 40% in Cmax and 43% in AUC when calcium carbonate was administered with ciprofloxacin, compared with ciprofloxacin alone (P < 0.05). There were no changes in either half-life or tmax. It is therefore recommended that patients being treated with ciprofloxacin for serious infections refra...

  14. Single vs double antiplatelet therapy in acute coronary syndrome: Predictors of bleeding after coronary artery bypass grafting

    Institute of Scientific and Technical Information of China (English)

    Vincenzo; Tarzia; Giacomo; Bortolussi; Edward; Buratto; Carla; Paolini; Carlo; Dal; Lin; Giulio; Rizzoli; Tomaso; Bottio; Gino; Gerosa

    2015-01-01

    AIM:To investigate the contribution of anti-platelet therapy and derangements of pre-operative classical coagulation and thromboelastometry parameters to major bleeding post-coronary artery bypass grafting(CABG).METHODS:Two groups of CABG patients were studied:Group A,treated with aspirin alone(n=50),and Group B treated with aspirin and clopidogrel(n=50).Both had similar preoperative,clinical,biologic characteristics and operative management.Classic coagulation parameters and rotational thromboelastometry(ROTEM)profiles were determined preoperatively for both groups and the same heparin treatment was administered.ROTEM profiles(INTEM and EXTEM assays)were analyzed,both for traditional parameters,and thrombin generation potential,expressed by area-under-curve(AUC).RESULTS:There was no significant difference betweenrates of major bleeding between patients treated with aspirin alone,compared with those treated with aspirin and clopidogrel(12%vs 16%,P=0.77).In the 14 cases of major bleeding,pre-operative classic coagulation and traditional ROTEM parameters were comparable.Conversely we observed that the AUC in the EXTEM test was significantly lower in bleeders(5030±1115 Ohm*min)than non-bleeders(6568±548Ohm*min)(P<0.0001).CONCLUSION:We observed that patients with a low AUC value were at a significantly higher risk of bleeding compared to patients with higher AUC,regardless of antiplatelet treatment.This suggests that thrombin generation potential,irrespective of the degree of platelet inhibition,correlates with surgical bleeding.

  15. Comparison of three dimensional isotropic and two dimensional conventional indirect MR arthrography for the diagnosis of rotator cuff tears

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hyun; Yoon, Young Cheol; Kwon, Jong Won; Yoo, Jae Chul [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Cha, Jang Kyu [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Jee, Suk Kyoung [Joeun Madi Hospital, Seoul (Korea, Republic of)

    2014-12-15

    To compare the accuracy between a three-dimensional (3D) indirect isotropic T1-weighted fast spin-echo (FSE) magnetic resonance (MR) arthrography and a conventional two-dimensional (2D) T1-weighted sequences of indirect MR arthrography for diagnosing rotator cuff tears. The study was approved by our Institutional Review Board. In total, 205 patients who had undergone indirect shoulder MR arthrography followed by arthroscopic surgery for 206 shoulders were included in this study. Both conventional 2D T1-weighted FSE sequences and 3D isotropic T1-weighted FSE sequence were performed in all patients. Two radiologists evaluated the images for the presence of full- or partial-thickness tears in the supraspinatus-infraspinatus (SSP-ISP) tendons and tears in the subscapularis (SSC) tendons. Using the arthroscopic findings as the reference standard, the diagnostic performances of both methods were analyzed by the area under the receiver operating characteristic curve (AUC). Arthroscopy confirmed 165 SSP-ISP tendon tears and 103 SSC tendon tears. For diagnosing SSP-ISP tendon tears, the AUC values were 0.964 and 0.989 for the 2D sequences and 3D T1-weighted FSE sequence, respectively, in reader I and 0.947 and 0.963, respectively, in reader II. The AUC values for diagnosing SSC tendon tears were 0.921 and 0.925, respectively, for reader I and 0.856 and 0.860, respectively, for reader II. There was no significant difference between the AUC values of the 2D and 3D sequences in either reader for either type of tear. 3D indirect isotropic MR arthrography with FSE sequence and the conventional 2D arthrography are not significantly different in terms of accuracy for diagnosing rotator cuff tears.

  16. Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

    Science.gov (United States)

    Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

    2015-10-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects.

  17. Accuracy and Calibration of Computational Approaches for Inpatient Mortality Predictive Modeling.

    Directory of Open Access Journals (Sweden)

    Christos T Nakas

    Full Text Available Electronic Health Record (EHR data can be a key resource for decision-making support in clinical practice in the "big data" era. The complete database from early 2012 to late 2015 involving hospital admissions to Inselspital Bern, the largest Swiss University Hospital, was used in this study, involving over 100,000 admissions. Age, sex, and initial laboratory test results were the features/variables of interest for each admission, the outcome being inpatient mortality. Computational decision support systems were utilized for the calculation of the risk of inpatient mortality. We assessed the recently proposed Acute Laboratory Risk of Mortality Score (ALaRMS model, and further built generalized linear models, generalized estimating equations, artificial neural networks, and decision tree systems for the predictive modeling of the risk of inpatient mortality. The Area Under the ROC Curve (AUC for ALaRMS marginally corresponded to the anticipated accuracy (AUC = 0.858. Penalized logistic regression methodology provided a better result (AUC = 0.872. Decision tree and neural network-based methodology provided even higher predictive performance (up to AUC = 0.912 and 0.906, respectively. Additionally, decision tree-based methods can efficiently handle Electronic Health Record (EHR data that have a significant amount of missing records (in up to >50% of the studied features eliminating the need for imputation in order to have complete data. In conclusion, we show that statistical learning methodology can provide superior predictive performance in comparison to existing methods and can also be production ready. Statistical modeling procedures provided unbiased, well-calibrated models that can be efficient decision support tools for predicting inpatient mortality and assigning preventive measures.

  18. A meta-analysis of the value of fluorodeoxyglucose-PET/PET-CT in the evaluation of fever of unknown origin

    International Nuclear Information System (INIS)

    Background and purpose: The diagnosis of patients with fever of unknown origin (FUO) remains a challenging medical problem for internal medicine. A reliable estimate of the diagnostic performance of FDG-PET and FDG-PET/CT in the assessment of FUO unidentified by conventional workup has never been systematically assessed, and present systematic review was aimed at this issue. Methods: A systematic search for relevant studies was performed of the PubMed, Embase, and Cochrane databases. Methodological quality of each study was assessed. Sensitivity, specificity and area under the curve (AUC) were meta-analyzed. Subgroup analyses were performed if results of individual studies were heterogeneous. Results: The inclusion criteria were met by nine studies. Overall, the studies had good methodological quality. Pooled sensitivity and specificity of FDG-PET for the detection of FUO were 0.826 (95% CI; 0.729–0.899) and 0.578 (95% CI; 0.488–0.665), respectively, and the AUC was 0.810. Heterogeneity among the results of FDG PET studies was present (QSE = 12.40, I2 = 67.7%; QSp = 35.98, I2 = 88.9%). Pooled sensitivity and specificity of FDG-PET/CT were 0.982 (95% CI; 0.936–0.998) and 0.859 (95% CI; 0.750–0.934), respectively, and the AUC was 0.947. We did not find any statistical differences in the AUC and Q* index between FDG-PET and FDG-PET/CT (Z = 0.566, p > 0.05). Conclusions: Although the FDG-PET studies that we examined were heterogeneous, FDG-PET appears to be a sensitive and promising diagnostic tool for the detection of the causes of FUO. FDG-PET/CT should be considered among the first diagnostic tools for patients with FUO in whom conventional diagnostics have been unsuccessful.

  19. Theorie und Praxis der Lerngruppensprache im Musikunterricht

    OpenAIRE

    Biegholdt, Georg

    2014-01-01

    Der Umgang mit der musikalischen Fachsprache wird in den meisten Lehrplänen für den Musikunterricht der Sekundarstufe I gefordert. Allerdings fehlt nicht nur in den Lehrplänen, sondern auch in der musikdidaktischen Literatur eine inhaltliche Ausgestaltung dieser Forderung. Über Inhalt, Umfang und Ziel der in der Schule anzuwendenden musikalischen Fachsprache herrscht daher keine Klarheit. Empirische Untersuchungen zu den sprachlichen Inhalten im Musikunterricht liegen ebenfalls nicht vor. Auc...

  20. A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

    Directory of Open Access Journals (Sweden)

    Huaying Zhao

    Full Text Available Analytical ultracentrifugation (AUC is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188 S (4.4%. After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%. In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.

  1. Deep Learning for Identifying Metastatic Breast Cancer

    OpenAIRE

    Wang, Dayong; Khosla, Aditya; Gargeya, Rishab; Irshad, Humayun; Beck, Andrew H

    2016-01-01

    The International Symposium on Biomedical Imaging (ISBI) held a grand challenge to evaluate computational systems for the automated detection of metastatic breast cancer in whole slide images of sentinel lymph node biopsies. Our team won both competitions in the grand challenge, obtaining an area under the receiver operating curve (AUC) of 0.925 for the task of whole slide image classification and a score of 0.7051 for the tumor localization task. A pathologist independently reviewed the same...

  2. Influence of Multiple Genetic Polymorphisms on Genitourinary Morbidity After Carbon Ion Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: To investigate the genetic risk of late urinary morbidity after carbon ion radiotherapy in prostate cancer patients. Methods and Materials: A total of 197 prostate cancer patients who had undergone carbon ion radiotherapy were evaluated for urinary morbidity. The distribution of patients with dysuria was as follows: Grade 0, 165; Grade 1, 28; and Grade 2, 4 patients. The patients were divided (2:1) consecutively into the training and test sets and then categorized into control (Grade 0) and case (Grade 1 or greater) groups. First, 450 single nucleotide polymorphisms (SNPs) in 118 candidate genes were genotyped in the training set. The associations between the SNP genotypes and urinary morbidity were assessed using Fisher's exact test. Then, various combinations of the markers were tested for their ability to maximize the area under the receiver operating characteristics (AUC-ROC) curve analysis results. Finally, the test set was validated for the selected markers. Results: When the SNP markers in the SART1, ID3, EPDR1, PAH, and XRCC6 genes in the training set were subjected to AUC-ROC curve analysis, the AUC-ROC curve reached a maximum of 0.86. The AUC-ROC curve of these markers in the test set was 0.77. The SNPs in these five genes were defined as 'risk genotypes.' Approximately 90% of patients in the case group (Grade 1 or greater) had three or more risk genotypes. Conclusions: Our results have shown that patients with late urinary morbidity after carbon ion radiotherapy can be stratified according to the total number of risk genotypes they harbor

  3. Prebiotic fibres dose-dependently increase satiety hormones and alter Bacteroidetes and Firmicutes in lean and obese JCR:LA-cp rats.

    Science.gov (United States)

    Parnell, Jill A; Reimer, Raylene A

    2012-02-01

    There is a growing interest in modulating gut microbiota with diet in the context of obesity. The purpose of the present study was to evaluate the dose-dependent effects of prebiotics (inulin and oligofructose) on gut satiety hormones, energy expenditure, gastric emptying and gut microbiota. Male lean and obese JCR:LA-cp rats were randomised to either of the following: lean 0 % fibre (LC), lean 10 % fibre (LF), lean 20 % fibre (LHF), obese 0 % fibre (OC), obese 10 % fibre (OF) or obese 20 % fibre (OHF). Body composition, gastric emptying, energy expenditure, plasma satiety hormone concentrations and gut microbiota (using quantitative PCR) were measured. Caecal proglucagon and peptide YY mRNA levels were up-regulated 2-fold in the LF, OF and OHF groups and 3-fold in the LHF group. Ghrelin O-acyltransferase mRNA levels were higher in obese v. lean rats and decreased in the OHF group. Plasma ghrelin response was attenuated in the LHF group. Microbial species measured in the Bacteroidetes division decreased, whereas those in the Firmicutes increased in obese v. lean rats and improved with prebiotic intake. Bifidobacterium and Lactobacillus increased in the OHF v. OC group. Bacteroides and total bacteria negatively correlated with percentage of body fat and body weight. Enterobacteriaceae increased in conjunction with glucose area under the curve (AUC) and glucagon-like peptide-1 AUC. Bacteroides and total bacteria correlated positively with ghrelin AUC yet negatively with insulin AUC and energy intake (P < 0·05). Several of the mechanisms through which prebiotics act (food intake, satiety hormones and alterations in gut microbiota) are regulated in a dose-dependent manner. The combined effects of prebiotics may have therapeutic potential for obesity.

  4. Assessing liver function in patients with HBV-related HCC: a comparison of T{sub 1} mapping on Gd-EOB-DTPA-enhanced MR imaging with DWI

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ying; Rao, Sheng-Xiang; Chen, Caizhong; Li, Renchen; Zeng, Meng-Su [Zhongshan Hospital of Fudan University, Department of Radiology, 180 Fenglin Road, Xuhui District, Shanghai (China)

    2015-05-01

    To compare the potential of T{sub 1} mapping on gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) for assessing liver function in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). One hundred consecutive patients with known HBV-related HCCs were included. T{sub 1} relaxation time and apparent diffusion coefficient (ADC) of the liver were measured, and the reduction rate of T{sub 1} relaxation time (∇%) was calculated. T{sub 1} relaxation time measurements were compared with ADC values according to the Model for End-Stage Liver Disease (MELD) score. Hepatobiliary phase (HBP) and ∇% of T{sub 1} relaxation time measurements showed significant correlations with MELD score (rho = 0.571, p < 0.0001; rho = -0.573, p < 0.0001, respectively). HBP and ∇% of T{sub 1} relaxation time were significantly different between good (MELD ≤8) and poor liver function (MELD ≥9) (p < 0.0001 for both). Areas under the receiver operating characteristic curves (AUCs) of T{sub 1} relaxation time for HBP (AUC 0.84) and ∇% (AUC 0.82) were significantly better than for ADC (AUC 0.53; p < 0.0001). T{sub 1} mapping on Gd-EOB-DTPA-enhanced MRI showed promise for evaluating liver function in patients with HBV-related HCC, while DWI was not reliable. HBP T{sub 1} relaxation time measurement was equally accurate as ∇% measurement. (orig.)

  5. Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant

    OpenAIRE

    Petri, Camille R.; O’Donnell, Peter H.; Cao, Hongyuan; Artz, Andrew S.; Stock, Wendy; Wickrema, Amittha; Hard, Marjie; van Besien, Koen

    2014-01-01

    We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I–II study of clofarabine–melphalan–alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration–time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) e...

  6. Comparison of severity of illness scoring systems in the prediction of hospital mortality in severe sepsis and septic shock

    Directory of Open Access Journals (Sweden)

    Crowe Colleen

    2010-01-01

    Full Text Available Background : New scoring systems, including the Rapid Emergency Medicine Score (REMS, the Mortality in Emergency Department Sepsis (MEDS score, and the confusion, urea nitrogen, respiratory rate, blood pressure, 65 years and older (CURB-65 score, have been developed for emergency department (ED use in various patient populations. Increasing use of early goal directed therapy (EGDT for the emergent treatment of sepsis introduces a growing population of patients in which the accuracy of these scoring systems has not been widely examined. Objectives : To evaluate the ability of the REMS, MEDS score, and CURB-65 score to predict mortality in septic patients treated with modified EGDT. Materials and Methods : Secondary analysis of data from prospectively identified patients treated with modified EGDT in a large tertiary care suburban community hospital with over 85,000 ED visits annually and 700 inpatient beds, from May 2007 through May 2008. We included all patients with severe sepsis or septic shock, who were treated with our modified EGDT protocol. Our major outcome was in-hospital mortality. The performance of the scores was compared by area under the ROC curves (AUCs. Results : A total of 216 patients with severe sepsis or septic shock were treated with modified EGDT during the study period. Overall mortality was 32.9%. Calculated AUCs were 0.74 [95% confidence interval (CI: 0.67-0.81] for the MEDS score, 0.62 (95% CI: 0.54-0.69 for the REMS, and 0.59 (95% CI: 0.51-0.67 for the CURB-65 score. Conclusion : We found that all three ED-based systems for scoring severity of illness had low to moderate predictive capability. The MEDS score demonstrated the largest AUC of the studied scoring systems for the outcome of mortality, although the CIs on point estimates of the AUC of the REMS and CURB-65 scores all overlap.

  7. Impairment of ciprofloxacin absorption by calcium polycarbophil.

    Science.gov (United States)

    Kato, Ryuji; Ueno, Kazuyuki; Imano, Hideki; Kawai, Masayuki; Kuwahara, Shiro; Tsuchishita, Yoshimasa; Yonezawa, Emi; Tanaka, Kazuhiko

    2002-07-01

    The effect of calcium polycarbophil on the absorption of ciprofloxacin, a broad-spectrum antibacterial agent, was evaluated in an in vitro and in vivo study. In the in vitro study, the release of ciprofloxacin from the cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, male ST Wistar rats and male volunteers were employed. First, 20 mg/kg of ciprofloxacin alone (Rat Study 1) or 20 mg/kg of ciprofloxacin in combination with 64 mg/kg of calcium chloride (Rat Study 2) was administered orally to 3 rats. Second, a volunteer study was employed and a randomized crossover design with twophases was used. In onephase, volunteers received 400 mg of ciprofloxacin alone (Study 1); in the other phase, they received 400 mg of ciprofloxacin and 1200 mg of fine calcium polycarbophil granules concomitantly (Study 2). The plasma and serum concentrations of ciprofloxacin were measured by high-performance liquid chromatography. The release of ciprofloxacin from the cellulose membrane in the presence of aluminum, calcium, or iron ions was slower than that in the absence of these metal ions. The AUC0-4 and Cmax in Rat Study 2 were lower than those respective values in Rat Study 1. AUC0-4 was approximately 60% lower in Rat Study 2 than Rat Study 1. In the volunteer study, the AUC0-12 and Cmax in Study 2 were lower than those respective values in Study 1. In particular, AUC0-12 was approximately 50% lowerin Study 2 than in Study 1. These findings suggest that when ciprofloxacin and calcium polycarbophil were coadministered concomitantly, a decrease of ciprofloxacin absorption was observed, and this action was caused by the formation of chelate complexes. Therefore, it seems clear that we should avoid the concomitant administration of ciprofloxacin and calcium polycarbophil.

  8. MDR1 C3435T基因多态性对环孢素体内代谢影响的荟萃分析%Meta-analysis of the effect of MDR1 C3435T polymorphism on cyclosporine pharmacokinetics

    Institute of Scientific and Technical Information of China (English)

    姜志平; 王一任; 徐萍; 刘荣荣; 赵谢兰; 陈方平

    2008-01-01

    目的 通过荟萃分析进一步观察MDR1 C3435T 基因多态性对于环孢素体内代谢的影响.方法 通过Pubmed搜索C3435T 基因多态性对于环孢素体内代谢影响的相关文献,提取AUC0-4, AUC0-12, AUC0-inf,Cmax, CL/F, 和C0等药物动力学参数,使用STATA 9.1软件进行荟萃分析.结果 共有14篇,包括1 036名受试者符合本次荟萃分析的入选条件,荟萃分析显示在C3435T野生型杂合子(CC)中,AUC0-12低于其他基因型的受试者.在白种人中,C3435T野生型杂合子(CC)携带者的C0低于其他基因型的白种受试者.其他药物动力学参数在C3435T各基因型之间未见显著差异.结论 本荟萃分析没有发现MDR1 C3435T 基因多态性对于环孢素体内代谢有较大的影响,但是观察指标的选择是观察结果差异的原因之一;MDR1 C3435T表型和基因型的相关性可能存在种族差异.

  9. Ketosis Onset Type 2 Diabetes Had Better Islet β-Cell Function and More Serious Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hongyun Lu

    2014-01-01

    Full Text Available Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM, but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases and nonketotic onset group (78 cases. After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β and insulin resistance (HOMA-IR. Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD than nonketotic group (P=0.04. Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC0–0.5, AUC0–1, AUC0–3 (P<0.05. Moreover, this group also had higher HOMA-β and HOMA-IR than nonketotic group (P<0.05. From these data, we concluded that ketosis onset T2DM had better islet β-cell function and more serious insulin resistance than nonketotic onset T2DM.

  10. The pharmacokinetics of perindopril in patients with liver cirrhosis.

    OpenAIRE

    Thiollet, M; Funck-Brentano, C.; Grangé, J D; Midavaine, M; Resplandy, G; Jaillon, P

    1992-01-01

    Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were dou...

  11. How Fast Is Recovery of Impaired Glucose Tolerance after 21-Day Bed Rest (NUC Study in Healthy Adults?

    Directory of Open Access Journals (Sweden)

    Martina Heer

    2014-01-01

    Full Text Available Aim. We hypothesized that 4 days of normal daily activity after 21 days of experimental bed rest (BR will not reverse BR induced impaired glucose tolerance. Design. Glucose tolerance of seven male, healthy, untrained test subjects (age: 27.6 (3.3 years (mean (SD; body mass: 78.6 (6.4 kg; height: 1.81 (0.04 m; VO2 max: 39.5 (5.4 ml/kg body mass/min was studied. They stayed twice in the metabolic ward (crossover design, 21 days in bed and 7 days before and after BR each. Oral glucose tolerance tests were applied before, on day 21 of BR, and 5 and 14 days after BR. Results. On day 21 of BR, AUC120 min of glucose concentration was increased by 28.8 (5.2% and AUC120 min of insulin by 35.9 (10.2% (glucose: P<0.001; insulin: P=0.02. Fourteen days after BR, AUC120 min of serum insulin concentrations returned to pre-bed-rest concentrations (P=0.352 and AUC120 min of glucose was still higher (P=0.038. Insulin resistance did not change, but sensitivity index was reduced during BR (P=0.005. Conclusion. Four days of light physical workload does not compensate inactivity induced impaired glucose tolerance. An individually tailored and intensified training regime is mandatory in patients being in bed rest to get back to normal glucose metabolism in a reasonable time frame.

  12. Accuracy and Calibration of Computational Approaches for Inpatient Mortality Predictive Modeling.

    Science.gov (United States)

    Nakas, Christos T; Schütz, Narayan; Werners, Marcus; Leichtle, Alexander B

    2016-01-01

    Electronic Health Record (EHR) data can be a key resource for decision-making support in clinical practice in the "big data" era. The complete database from early 2012 to late 2015 involving hospital admissions to Inselspital Bern, the largest Swiss University Hospital, was used in this study, involving over 100,000 admissions. Age, sex, and initial laboratory test results were the features/variables of interest for each admission, the outcome being inpatient mortality. Computational decision support systems were utilized for the calculation of the risk of inpatient mortality. We assessed the recently proposed Acute Laboratory Risk of Mortality Score (ALaRMS) model, and further built generalized linear models, generalized estimating equations, artificial neural networks, and decision tree systems for the predictive modeling of the risk of inpatient mortality. The Area Under the ROC Curve (AUC) for ALaRMS marginally corresponded to the anticipated accuracy (AUC = 0.858). Penalized logistic regression methodology provided a better result (AUC = 0.872). Decision tree and neural network-based methodology provided even higher predictive performance (up to AUC = 0.912 and 0.906, respectively). Additionally, decision tree-based methods can efficiently handle Electronic Health Record (EHR) data that have a significant amount of missing records (in up to >50% of the studied features) eliminating the need for imputation in order to have complete data. In conclusion, we show that statistical learning methodology can provide superior predictive performance in comparison to existing methods and can also be production ready. Statistical modeling procedures provided unbiased, well-calibrated models that can be efficient decision support tools for predicting inpatient mortality and assigning preventive measures. PMID:27414408

  13. Limited sampling pharmacokinetics of subcutaneous ondansetron in healthy geriatric cats, cats with chronic kidney disease, and cats with liver disease.

    Science.gov (United States)

    Fitzpatrick, R L; Wittenburg, L A; Hansen, R J; Gustafson, D L; Quimby, J M

    2016-08-01

    Ondansetron, a 5-HT3 receptor antagonist, is an effective anti-emetic in cats. The purpose of this study was to compare pharmacokinetics of subcutaneous (SQ) ondansetron in healthy geriatric cats to cats with chronic kidney disease (CKD) or liver disease using a limited sampling strategy. 60 cats participated; 20 per group. Blood was drawn 30 and 120 min following one 2 mg (mean 0.49 mg/kg, range 0.27-1.05 mg/kg) SQ dose of ondansetron. Ondansetron concentrations were measured by liquid chromatography coupled to tandem mass spectrometry. Drug exposure represented as area under the curve (AUC) was predicted using a limited sampling approach based on multiple linear regression analysis from previous full sampling studies, and clearance (CL/F) estimated using noncompartmental methods. Kruskal-Wallis anova was used to compare parameters between groups. Mean AUC (ng/mL·h) of subcutaneous ondansetron was 301.4 (geriatric), 415.2 (CKD), and 587.0 (liver). CL/F (L/h/kg) of SQ ondansetron was 1.157 (geriatric), 0.967 (CKD), and 0.795 (liver). AUC was significantly higher in liver and CKD cats when compared to geriatric cats (P < 0.05). CL/F in liver cats was significantly decreased (P < 0.05) compared to geriatric cats. In age-matched subset analysis, AUC and CL/F in liver cats remained significantly different from geriatric cats. PMID:26667224

  14. Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Giada Sebastiani; Alessandro Vario; Maria Guido; Alfredo Alberti

    2007-01-01

    AIM: To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis (F ≥ 2 by METAVIR) and cirrhosis (F4 by METAVIR) in chronic hepatitis B (CHB).METHODS: One hundred and ten consecutive patients (80 males, 30 females, mean age: 42.6 ± 11.3) with CHB undergoing diagnostic liver biopsy were included. ASTto-Platelet ratio (APRI), Forns' index, AST-to-ALT Ratio,Goteborg University Cirrhosis Index (GUCI), Hui's model and Fibrotest were measured on the day of liver biopsy.The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive (PPV) and negative (NPV) predictive values, accuracy and area under the curve (AUC).RESULTS: PPV for significant fibrosis was excellent (100%) with Forns and high (> 92%) with APRI, GUCI,Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker (NPV < 65%). Fibrotest had the best PPV and NPV for cirrhosis (87% and 90%, respectively). Fibrotest showed the best AUC for both significant fibrosis and cirrhosis (0.85 and 0.76,respectively). Stepwise combination algorithms of APRI,Fibrotest and biopsy showed excellent performance (0.96 AUC, 100% NPV) for significant fibrosis and 0.95 AUC,98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy.CONCLUSION: In CHB sequential combination of APRI,Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.

  15. Quercetin increases the bioavailability of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats

    NARCIS (Netherlands)

    Schutte, M.E.; Alink, G.M.; Freidig, A.P.; Spenkelink, B.; Vaessen, J.C.H.; Sandt, J.J.M. van de; Groten, J.P.; Rietjens, I.M.C.M.

    2008-01-01

    This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 μmol PhIP/kg bw and 30 μmol quercetin/kg bw significantly increased the blood AUC(0-8 h) of

  16. Using a consensus approach based on the conservation of inter-residue contacts to rank CAPRI models

    KAUST Repository

    Vangone, Anna

    2013-10-17

    Herein we propose the use of a consensus approach, CONSRANK, for ranking CAPRI models. CONSRANK relies on the conservation of inter-residue contacts in the analyzed decoys ensemble. Models are ranked according to their ability to match the most frequently observed contacts. We applied CONSRANK to 19 CAPRI protein-protein targets, covering a wide range of prediction difficulty and involved in a variety of biological functions. CONSRANK results are consistently good, both in terms of native-like (NL) solutions ranked in the top positions and of values of the Area Under the receiver operating characteristic Curve (AUC). For targets having a percentage of NL solutions above 3%, an excellent performance is found, with AUC values approaching 1. For the difficult target T46, having only 3.4% NL solutions, the number of NL solutions in the top 5 and 10 ranked positions is enriched by a factor 30, and the AUC value is as high as 0.997. AUC values below 0.8 are only found for targets featuring a percentage of NL solutions within 1.1%. Remarkably, a false consensus emerges only in one case, T42, which happens to be an artificial protein, whose assembly details remain uncertain, based on controversial experimental data. We also show that CONSRANK still performs very well on a limited number of models, provided that more than 1 NL solution is included in the ensemble, thus extending its applicability to cases where few dozens of models are available.© 2013 Wiley Periodicals, Inc.

  17. Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset

    Science.gov (United States)

    Chan, M K; Krebs, M-O; Cox, D; Guest, P C; Yolken, R H; Rahmoune, H; Rothermundt, M; Steiner, J; Leweke, F M; van Beveren, N J M; Niebuhr, D W; Weber, N S; Cowan, D N; Suarez-Pinilla, P; Crespo-Facorro, B; Mam-Lam-Fook, C; Bourgin, J; Wenstrup, R J; Kaldate, R R; Cooper, J D; Bahn, S

    2015-01-01

    Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples. First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls. Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95–1.00) for schizophrenia detection. Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals. The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86–0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71–0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82–0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset. PMID:26171982

  18. Churn analysis using deep convolutional neural networks and autoencoders

    OpenAIRE

    Wangperawong, Artit; Brun, Cyrille; Laudy, Olav; Pavasuthipaisit, Rujikorn

    2016-01-01

    Customer temporal behavioral data was represented as images in order to perform churn prediction by leveraging deep learning architectures prominent in image classification. Supervised learning was performed on labeled data of over 6 million customers using deep convolutional neural networks, which achieved an AUC of 0.743 on the test dataset using no more than 12 temporal features for each customer. Unsupervised learning was conducted using autoencoders to better understand the reasons for c...

  19. First-pass gastric mucosal metabolism of ethanol is negligible in the rat.

    OpenAIRE

    SMITH, T; DeMaster, E G; Furne, J K; Springfield, J; Levitt, M D

    1992-01-01

    Ethanol metabolism by gastric alcohol dehydrogenase (ADH) is thought to be an important determinant of peripheral ethanol time-concentration curves (AUCs) in rats and humans. We quantitated this metabolism in rats by measuring the gastric absorption of oral ethanol (0.25 g/kg) and the gastric venous-arterial (V-A) difference of ethanol versus ethanol metabolites (acetate, acetaldehyde, and bicarbonate). Over 1 h, approximately 20% of the ethanol was absorbed from the stomach and 70% was empti...

  20. The influence of non-steroidal anti-inflammatory drugs on the gut microbiome.

    Science.gov (United States)

    Rogers, M A M; Aronoff, D M

    2016-02-01

    The composition of the gut microbiome with the use of non-steroidal anti-inflammatory drugs (NSAIDs) has not been fully characterized. Drug use within the past 30 days was ascertained in 155 adults, and stool specimens were submitted for analysis. Area under the receiver operating characteristic curve (AUC) was calculated in logit models to distinguish the relative abundance of operational taxonomic units (OTUs) by medication class. The type of medication had a greater influence on the gut microbiome than the number of medications. NSAIDs were particularly associated with distinct microbial populations. Four OTUs (Prevotella species, Bacteroides species, family Ruminococcaceae, and Barnesiella species) discriminated aspirin users from those using no medication (AUC = 0.96; 95% CI 0.84-1.00). The microbiome profile of celecoxib users was similar to that of ibuprofen users, with both showing enrichment of Acidaminococcaceae and Enterobacteriaceae. Bacteria from families Propionibacteriaceae, Pseudomonadaceae, Puniceicoccaceae and Rikenellaceae were more abundant in ibuprofen users than in controls or naproxen users. Bacteroides species and Erysipelotrichaceae species discriminated individuals using NSAIDs plus proton-pump inhibitors from those using NSAIDs alone (AUC = 0.96; 95% CI 0.87-1.00). Bacteroides species and a bacterium of family Ruminococcaceae discriminated individuals using NSAIDs in combination with antidepressants and laxatives from those using NSAIDs alone (AUC = 0.98; 95% CI 0.93-1.00). In conclusion, bacteria in the gastrointestinal tract reflect the combinations of medications that people ingest. The bacterial composition of the gut varied with the type of NSAID ingested. PMID:26482265

  1. Dietary composition and its associations with insulin sensitivity and insulin secretion in youth.

    Science.gov (United States)

    Henderson, Mélanie; Benedetti, Andrea; Gray-Donald, Katherine

    2014-02-01

    The objectives of the present study were to examine the associations between macronutrient intake and insulin sensitivity (IS) and insulin secretion (ISct), taking into consideration moderate-to-vigorous physical activity (MVPA), fitness and sedentary behaviour. Caucasian youth (n 630) aged 8-10 years at recruitment, with at least one obese biological parent, were studied (QUebec Adipose and Lifestyle InvesTigation in Youth cohort). IS was measured using the homeostasis model assessment (HOMA) of insulin resistance and Matsuda IS index. ISct was measured using HOMA2%-β, the ratio of the AUC of insulin:glucose over the first 30 min (AUC I/G(t= 30 min)) of the oral glucose tolerance test and AUC I/G(t= 120 min) over 2 h. Fitness was measured using VO₂(peak), percentage of fat mass by dual-energy X-ray absorptiometry, and 7 d MVPA using accelerometry; screen time (ST) by average daily hours of self-reported television, video game or computer use. Dietary composition was measured using three non-consecutive dietary recalls. Non-parametric smoothing splines were used to model non-linear associations; all models were adjusted for age, sex, season, pubertal stage, MVPA, fitness, ST and adiposity. The percentage of total daily energy from dietary protein, fat, saturated fat and carbohydrate and the consumption of dietary vitamin D, sugar-sweetened beverages, fibre and portions of fruits and vegetables were taken into consideration. No dietary component was associated with any measure of IS after adjusting for MVPA, fitness, ST and adiposity. For every 1% increase in daily protein intake (%), AUC I/G(t= 30 min) decreased by 1·1% (P= 0·033). Otherwise, dietary composition was not associated with ISct. While long-term excess of energy intake has been shown to lead to overweight and obesity, dietary macronutrient composition is not independently correlated with IS or ISct in youth. PMID:24047611

  2. Efficacy of digital breast tomosynthesis for breast cancer diagnosis

    Science.gov (United States)

    Alakhras, M.; Mello-Thoms, C.; Rickard, M.; Bourne, R.; Brennan, P. C.

    2014-03-01

    Purpose: To compare the diagnostic performance of digital breast tomosynthesis (DBT) in combination with digital mammography (DM) with that of digital mammography alone. Materials and Methods: Twenty six experienced radiologists who specialized in breast imaging read 50 cases (27 cancers and 23 non-cancer cases) of patients who underwent DM and DBT. Both exams included the craniocaudal (CC) and mediolateral oblique (MLO) views. Histopathologic examination established truth in all lesions. Each case was interpreted in two modes, once with DM alone followed by DM+DBT, and the observers were asked to mark the location of any lesions, if present, and give it a score based on a five-category assessment by the Royal Australian and New Zealand College of Radiologists (RANZCR). The diagnostic performance of DM compared with that of DM+DBT was evaluated in terms of the difference between areas under receiver-operating characteristic curves (AUCs), Jackknife free-response receiver operator characteristics (JAFROC) figure-of-merit, sensitivity, location sensitivity and specificity. Results: Average AUC and JAFROC for DM versus DM+DBT was significantly different (AUCs 0.690 vs 0.781, p=< 0.0001), (JAFROC 0.618 vs. 0.732, p=< 0.0001) respectively. In addition, the use of DM+DBT resulted in an improvement in sensitivity (0.629 vs. 0.701, p=0.0011), location sensitivity (0.548 vs. 0.690, p=< 0.0001) and specificity (0.656 vs. 0.758, p=0.0015) when compared to DM alone. Conclusion: Adding DBT to the standard DM significantly improved radiologists' performance in terms of AUCs, JAFROC figure of merit, sensitivity, location sensitivity and specificity values.

  3. Similarities and differences among paramilitaries, severe aggressors and communal control, a case-control study in Medellín, Colombia

    OpenAIRE

    Luis F. Duque; Nilton Edu Montoya; Marcela Montoya

    2007-01-01

    A case-control study was performed in Medellín during 2003-2004 to compare characteristics of severe aggressors, members of Colombian United Selfdefense Forces members (AUC), otherwise named paramilitaries, and communal control. Severe aggressors and paramilitaries have lower educational level than communal control; their families were biparental in a lower proportion, and experienced drug and alcohol abuse in a higher proportion than in the case of families of communal control. Severe aggres...

  4. Computational pathology to discriminate benign from malignant intraductal proliferations of the breast.

    Directory of Open Access Journals (Sweden)

    Fei Dong

    Full Text Available The categorization of intraductal proliferative lesions of the breast based on routine light microscopic examination of histopathologic sections is in many cases challenging, even for experienced pathologists. The development of computational tools to aid pathologists in the characterization of these lesions would have great diagnostic and clinical value. As a first step to address this issue, we evaluated the ability of computational image analysis to accurately classify DCIS and UDH and to stratify nuclear grade within DCIS. Using 116 breast biopsies diagnosed as DCIS or UDH from the Massachusetts General Hospital (MGH, we developed a computational method to extract 392 features corresponding to the mean and standard deviation in nuclear size and shape, intensity, and texture across 8 color channels. We used L1-regularized logistic regression to build classification models to discriminate DCIS from UDH. The top-performing model contained 22 active features and achieved an AUC of 0.95 in cross-validation on the MGH data-set. We applied this model to an external validation set of 51 breast biopsies diagnosed as DCIS or UDH from the Beth Israel Deaconess Medical Center, and the model achieved an AUC of 0.86. The top-performing model contained active features from all color-spaces and from the three classes of features (morphology, intensity, and texture, suggesting the value of each for prediction. We built models to stratify grade within DCIS and obtained strong performance for stratifying low nuclear grade vs. high nuclear grade DCIS (AUC = 0.98 in cross-validation with only moderate performance for discriminating low nuclear grade vs. intermediate nuclear grade and intermediate nuclear grade vs. high nuclear grade DCIS (AUC = 0.83 and 0.69, respectively. These data show that computational pathology models can robustly discriminate benign from malignant intraductal proliferative lesions of the breast and may aid pathologists in the diagnosis

  5. Diagnostic accuracy of posterior pole asymmetry analysis parameters of spectralis optical coherence tomography in detecting early unilateral glaucoma

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    Paaraj Dave

    2015-01-01

    Full Text Available Purpose: To report the diagnostic ability of posterior pole asymmetry analysis (PPAA parameters of spectralis optical coherence tomography (OCT in detecting early unilateral glaucoma. Methods: A prospective, cross-sectional study which included 80 eyes of 80 normal subjects and 76 eyes of 76 patients with unilateral early primary open-angle glaucoma by Hodapp-Anderson-Parrish classification. All subjects were of age more than 18 years, best-corrected visual acuity 20/40 or better, and a refractive error within ± 5 diopter (D sphere and ± 3 D cylinder. Control subjects had a normal ocular examination, intraocular pressure (IOP <22 mmHg, no past history of high IOP, no family history of glaucoma, normal optic disc morphology, and visual field in both eyes. One eye of the control subject was randomly included. All eyes underwent OCT for retinal nerve fiber layer (RNFL analysis and PPAA. The number of continuous black squares was noted in the asymmetry analysis (right-left + hemisphere asymmetry. The area under curve (AUC was calculated for all OCT parameters. Results: The best value for AUC for RNFL analysis was 0.858 for the inferotemporal quadrant thickness. This was similar to the best value for AUC for PPAA which was 0.833 for the inferior macular thickness parameter (P = 0.5. The AUC for the right-left and the hemisphere asymmetry part of PPAA was 0.427 and 0.499, respectively. Conclusion: The macular thickness PPAA parameters were equally good as the RNFL parameters. However, the asymmetry analysis parameters performed poorly and need further refinement before its use in early unilateral glaucoma diagnosis.

  6. Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base.

    Science.gov (United States)

    García-Arieta, Alfredo; Ferrero-Cafiero, Juan Manuel; Puntes, Montse; Gich, Ignasi; Morales-Alcelay, Susana; Tarré, Maite; Font, Xavier; Antonijoan, Rosa Maria

    2016-05-01

    The purpose was to assess the impact of the use of a chiral bioanalytical method on the conclusions of a bioequivalence study that compared two ibuprofen suspensions with different rates of absorption. A comparison of the conclusion of bioequivalence between a chiral method and an achiral approach was made. Plasma concentrations of R-ibuprofen and S-ibuprofen were determined using a chiral bioanalytical method; bioequivalence was tested for R-ibuprofen and for S-ibuprofen separately and for the sum of both enantiomers as an approach for an achiral bioanalytical method. The 90% confidence interval (90% CI) that would have been obtained with an achiral bioanalytical method (90% CI: Cmax: 117.69-134.46; AUC0 (t) : 104.75-114.45) would have precluded the conclusion of bioequivalence. This conclusion cannot be generalized to the active enantiomer (90% CI: Cmax : 103.36-118.38; AUC0 (t) : 96.52-103.12), for which bioequivalence can be concluded, and/or the distomer (90% CI: Cmax : 132.97-151.33; AUC0 (t) : 115.91-135.77) for which a larger difference was observed. Chiral bioanalytical methods should be required when 1) the enantiomers exhibit different pharmacodynamics and 2) the exposure (AUC or Cmax ) ratio of enantiomers is modified by a difference in the rate of absorption. Furthermore, the bioequivalence conclusion should be based on all enantiomers, since the distomer(s) might not be completely inert, in contrast to what is required in the current regulatory guidelines. In those cases where it is unknown if the ratio between enantiomers is modified by changing the rate of absorption, chiral bioanalytical methods should be employed unless enantiomers exhibit the same pharmacodynamics. Chirality 28:429-433, 2016. © 2016 Wiley Periodicals, Inc. PMID:27094918

  7. Islet Oxygen Consumption Rate (OCR Dose Predicts Insulin Independence in Clinical Islet Autotransplantation.

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    Klearchos K Papas

    Full Text Available Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR in predicting clinical islet autotransplant (IAT insulin independence (II. IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity.Membrane integrity staining (FDA/PI, OCR normalized to DNA (OCR/DNA, islet equivalent (IE and OCR (viable IE normalized to recipient body weight (IE dose and OCR dose, and OCR/DNA normalized to islet size index (ISI were used to characterize autoislet preparations (n = 35. Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis.Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001. These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC = 0.94 for IE dose and 0.96 for OCR dose. FDA/PI (AUC = 0.49 and OCR/DNA (AUC = 0.58 did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72.Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.

  8. Anthropometric surrogates to identify low birth weight Nepalese newborns: a hospital-based study

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    Singh Dela

    2008-04-01

    Full Text Available Abstract Background In Nepal, more than 90% of the deliveries take place at home where birth weight is often not recorded. In developing countries, low birth weight (LBW, Methods A cross-sectional study was carried out in Western Regional Hospital, Pokhara between April and June, 2006. All consecutive full-term, singleton, live born babies were included. To ensure reliability and avoid inter-observer bias one of the investigators weighed all the newborns and carried out anthropometric measurements within 24 hours after birth. Circumferences of head, chest, mid-upper arm, thigh and calf were measured according to standard techniques. Non-parametric receiver operating characteristic (ROC curve analyses were carried out using bootstrap to calculate 95% confidence intervals of areas under the curve (AUC. The cut-points with lowest total misclassification rate were chosen to identify LBW babies. Results Out of 400 newborns studied, 204 (51% were males and 196 (49% were females. The mean birth weight was 3029 ± 438 grams and 34 (8.5% newborns were LBW. By ROC-AUC analyses, head circumference (AUC = 0.89, 95% CI 0.85 to 0.93 and chest circumference (AUC = 0.86, 95% CI 0.80 to 0.91 were identified as the optimal surrogate indicators of LBW babies. The optimal cut-points for head circumference and chest circumference to identify LBW newborns were ≥ 33.5 cm and ≥ 30.8 cm respectively. Conclusion Head and chest circumferences were the best anthropometric surrogates of LBW among Nepalese newborns. Further studies are needed in the field to cross-validate our results.

  9. Non-sentinel lymph node metastasis prediction in breast cancer with metastatic sentinel lymph node: impact of molecular subtypes classification.

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    Fabien Reyal

    Full Text Available INTRODUCTION: To decipher the interaction between the molecular subtype classification and the probability of a non-sentinel node metastasis in breast cancer patients with a metastatic sentinel lymph-node, we applied two validated predictors (Tenon Score and MSKCC Nomogram on two large independent datasets. MATERIALS AND METHODS: Our datasets consisted of 656 and 574 early-stage breast cancer patients with a metastatic sentinel lymph-node biopsy treated at first by surgery. We applied both predictors on the whole dataset and on each molecular immune-phenotype subgroups. The performances of the two predictors were analyzed in terms of discrimination and calibration. Probability of non-sentinel lymph node metastasis was detailed for each molecular subtype. RESULTS: Similar results were obtained with both predictors. We showed that the performance in terms of discrimination was as expected in ER Positive HER2 negative subgroup in both datasets (MSKCC AUC Dataset 1 = 0.73 [0.69-0.78], MSKCC AUC Dataset 2 = 0.71 (0.65-0.76, Tenon Score AUC Dataset 1 = 0.7 (0.65-0.75, Tenon Score AUC Dataset 2 = 0.72 (0.66-0.76. Probability of non-sentinel node metastatic involvement was slightly under-estimated. Contradictory results were obtained in other subgroups (ER negative HER2 negative, HER2 positive subgroups in both datasets probably due to a small sample size issue. We showed that merging the two datasets shifted the performance close to the ER positive HER2 negative subgroup. DISCUSSION: We showed that validated predictors like the Tenon Score or the MSKCC nomogram built on heterogeneous population of breast cancer performed equally on the different subgroups analyzed. Our present study re-enforce the idea that performing subgroup analysis of such predictors within less than 200 samples subgroup is at major risk of misleading conclusions.

  10. Effect of activated charcoal on the pharmacokinetics of pholcodine, with special reference to delayed charcoal ingestion.

    Science.gov (United States)

    Laine, K; Kivistö, K T; Ojala-Karlsson, P; Neuvonen, P J

    1997-02-01

    We conducted a randomized study with four parallel groups to investigate the effect of single and multiple doses of activated charcoal on the absorption and elimination of pholcodine administered in a cough syrup. The first group received 100 mg of pholcodine on an empty stomach with water only (control); the second group took 25 g of activated charcoal immediately after pholcodine; the third group received 25 g of activated charcoal 2 h and the fourth group 5 h after ingestion of the 100-mg dose of pholcodine. In addition, the fourth group received multiple doses (10 g each) of charcoal every 12 h for 84 h. Blood samples were collected for 96 h and urine for 72 h. Pholcodine concentrations were measured by high-performance liquid chromatography. A significant reduction in absorption was found when charcoal was administered immediately after pholcodine; the AUC0-96h was reduced by 91% (p pholcodine excreted into urine by 85% (p pholcodine, the AUC0-96h was reduced by 26% (p = 0.002), the Cmax by 23% (p = NS), and the urinary excretion by 28% (p = 0.004). When administered 5 h after pholcodine, charcoal produced only a 17% reduction in the AUC0-96h (p = 0.06), but reduced the further absorption of pholcodine still present in the gastrointestinal tract at the time of charcoal administration, as measured by AUC5-96h (p = 0.006). Repeated administration of charcoal failed to accelerate the elimination of pholcodine. We conclude that activated charcoal is effective in preventing the absorption of pholcodine, and its administration can be beneficial even several hours after pholcodine ingestion. PMID:9029746

  11. Evaluation of Pulmonary Hypertension with CMR: Pulmonary Hypertension 
Patients and Healthy Volunteers Control Study

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    Meng WANG

    2016-05-01

    Full Text Available Background and objective The clinical course of pulmonary hypertension (PH is one of progressive deterioration interspersed with episodes of acute decompensation. It is difficult to predict when patients will die because death may come either suddenly or slowly due to progressive heart failure. The aim of this study is to investigate morphology, function and hemodynamics in PH, compared with healthy people, and to investigate the clinical value of detection of PH by use of cardiac magnetic resonance (CMR parameters. Methods CMR was performed in 56 PH patients collected from Tianjin Medical University General Hospital from January 2012 to December 2014 and 22 healthy controls. The following parameters were calculated: right ventricle (RV end-diastolic volume (EDV, end-systolic volume (ESV, ejection fraction (EF, myocardial mass (MM, RV fractional area change (RVFAC, interventricular septal curvature (CIVS, left ventricular free wall curvature (CFW, and CIVS/CFW, main pulmonary artery (MPA positive peak velocity, maximal area, minimal area and distensibility. Comparisons of CMR measurements between PH patients and controls were analyzed by using the student t-tests. Receiver operating characteristic (ROC curve analysis was used to compare the PH diagnostic abilities for four parameters (MPA positive peak velocity, distensibility, curvature ratio, and RVFAC and combined CMR parameter. P<0.05 was considered significant. Results Compared with healthy controls, RV morphology, function and hemodynamics of PH group declined and deteriorate obviously. The ROC curve analysis showed that among the four parameters distensibility of MPA had the highest AUC value (AUC=0.95. Additionally, combined CMR parameter (positive peak velocity+distensibility+curvature ratio+RVFAC had even higher AUC (AUC=0.988. Conclusion Comprehensive CMR parameters is conducive to accurately reflect the overall state RV-pulmonary circulation in patients with PH.

  12. Accuracy of GastroPanel for the diagnosis of atrophic gastritis

    Science.gov (United States)

    Forné, Montserrat; Barrio, Jesus; De la Coba, Cristobal; González, Begoña; Rivera, Robin; Esteve, Maria; Fernandez-Bañares, Fernando; Madrigal, Beatriz; Gras-Miralles, Beatriz; Perez-Aisa, Angeles; Viver-Pi-Sunyer, Jose M.; Bory, Felipe; Rosinach, Merce; Loras, Carmen; Esteban, Carlos; Santolaria, Santos; Gomollon, Fernando; Valle, Julio; Gisbert, Javier P.

    2014-01-01

    Background It has been suggested that GastroPanel might be a useful tool for the diagnosis of chronic atrophic gastritis (CAG) measuring four biomarkers in blood: basal gastrin-17 (G17), pepsinogen I and II (PGI and PGII), and Helicobacter pylori antibodies. Aim To determine the accuracy of GastroPanel for the diagnosis of CAG. Methods This was a prospective, blinded, multicenter study that included dyspeptic patients. G17, PGI, and PGII were determined by enzyme immunoassays. Three antrum and two corpus biopsies were obtained for standard histological analysis and rapid urease test. Biopsies were analyzed by a single blinded expert pathologist. Results Ninety-one patients were included (77% women, mean age 44 years, 51% H. pylori positive, 17% with CAG). G17 was reduced in patients with antrum CAG (5.4 vs. 13.4 pmol/l; P<0.01) and increased in patients with corpus CAG (11 vs. 24 pmol/l; P<0.05), but its accuracy was only acceptable in the case of corpus localization [area under the receiver operating characteristic curve (AUC), 74%]; PGII difference was almost statistically significant only when testing for corpus atrophy (33 vs. 21 μg/l; P=0.05; AUC=72%). The PGI and PGI/PGII ratio showed no significant differences (AUCs were all unacceptably low). Helicobacter pylori antibody levels were higher in H. pylori-infected patients (251 vs. 109 EIU, P=0.01; AUC=70). The accuracy of GastroPanel for the diagnosis of CAG was as follows: sensitivity 50%; specificity 80%; positive 25% and negative 92% predictive values; and positive 2.4 and negative 0.6 likelihood ratios. Conclusion GastroPanel is not accurate enough for the diagnosis of CAG; thus, its systematic use in clinical practice cannot be recommended. PMID:25014624

  13. Relationship of computed tomography perfusion and positron emission tomography to tumour progression in malignant glioma

    Energy Technology Data Exchange (ETDEWEB)

    Yeung, Timothy P C [London Regional Cancer Program, London Health Sciences Centre, Ontario, Canada, N6A 4L6 (Canada); Robarts Research Institute, The University of Western Ontario, Ontario, Canada, N6A 5B7 (Canada); Department of Medical Biophysics, The University of Western Ontario, Ontario, Canada, N6A 5C1 (Canada); Yartsev, Slav [London Regional Cancer Program, London Health Sciences Centre, Ontario, Canada, N6A 4L6 (Canada); Department of Medical Biophysics, The University of Western Ontario, Ontario, Canada, N6A 5C1 (Canada); Department of Oncology, The University of Western Ontario, London Health Sciences Centre, London Regional Cancer Program, Ontario, Canada, N6A 4L6 (Canada); Lee, Ting-Yim [Robarts Research Institute, The University of Western Ontario, Ontario, Canada, N6A 5B7 (Canada); Department of Medical Biophysics, The University of Western Ontario, Ontario, Canada, N6A 5C1 (Canada); Department of Oncology, The University of Western Ontario, London Health Sciences Centre, London Regional Cancer Program, Ontario, Canada, N6A 4L6 (Canada); Department of Medical Imaging, The University of Western Ontario, London Health Sciences Centre, Victoria Hospital, Ontario, Canada, N6A 5W9 (Australia); Lawson Health Research Institute, St. Joseph' s Health Care London, Ontario, Canada, N6A 4V2 (Canada); Wong, Eugene [London Regional Cancer Program, London Health Sciences Centre, Ontario, Canada, N6A 4L6 (Canada); Department of Oncology, The University of Western Ontario, London Health Sciences Centre, London Regional Cancer Program, Ontario, Canada, N6A 4L6 (Canada); Department of Physics and Astronomy, The University of Western Ontario, Ontario, Canada, N6A 3K7 (Canada); He, Wenqing [Department of Statistical and Actuarial Sciences, The University of Western Ontario, Ontario, Canada, N6A 5B7 (Canada); Fisher, Barbara; VanderSpek, Lauren L [London Regional Cancer Program, London Health Sciences Centre, Ontario, Canada, N6A 4L6 (Canada); Department of Oncology, The University of Western Ontario, London Health Sciences Centre, London Regional Cancer Program, Ontario, Canada, N6A 4L6 (Canada); Macdonald, David [London Regional Cancer Program, London Health Sciences Centre, Ontario, Canada, N6A 4L6 (Canada); Department of Oncology, The University of Western Ontario, London Health Sciences Centre, London Regional Cancer Program, Ontario, Canada, N6A 4L6 (Canada); Department of Clinical Neurological Sciences, The University of Western Ontario, London Health Sciences Centre, University Hospital, Ontario, Canada, N6A 5A5 (Canada); Bauman, Glenn, E-mail: glenn.bauman@lhsc.on.ca [London Regional Cancer Program, London Health Sciences Centre, Ontario, Canada, N6A 4L6 (Canada); Department of Medical Biophysics, The University of Western Ontario, Ontario, Canada, N6A 5C1 (Canada); Department of Oncology, The University of Western Ontario, London Health Sciences Centre, London Regional Cancer Program, Ontario, Canada, N6A 4L6 (Canada)

    2014-02-15

    Introduction: This study aimed to explore the potential for computed tomography (CT) perfusion and 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting sites of future progressive tumour on a voxel-by-voxel basis after radiotherapy and chemotherapy. Methods: Ten patients underwent pre-radiotherapy magnetic resonance (MR), FDG-PET and CT perfusion near the end of radiotherapy and repeated post-radiotherapy follow-up MR scans. The relationships between these images and tumour progression were assessed using logistic regression. Cross-validation with receiver operating characteristic (ROC) analysis was used to assess the value of these images in predicting sites of tumour progression. Results: Pre-radiotherapy MR-defined gross tumour; near-end-of-radiotherapy CT-defined enhancing lesion; CT perfusion blood flow (BF), blood volume (BV) and permeability-surface area (PS) product; FDG-PET standard uptake value (SUV); and SUV:BF showed significant associations with tumour progression on follow-up MR imaging (P < 0.0001). The mean sensitivity (±standard deviation), specificity and area under the ROC curve (AUC) of PS were 0.64 ± 0.15, 0.74 ± 0.07 and 0.72 ± 0.12 respectively. This mean AUC was higher than that of the pre-radiotherapy MR-defined gross tumour and near-end-of-radiotherapy CT-defined enhancing lesion (both AUCs = 0.6 ± 0.1, P ≤ 0.03). The multivariate model using BF, BV, PS and SUV had a mean AUC of 0.8 ± 0.1, but this was not significantly higher than the PS only model. Conclusion: PS is the single best predictor of tumour progression when compared to other parameters, but voxel-based prediction based on logistic regression had modest sensitivity and specificity.

  14. Glucoregulation in normal weight schizophrenia patients treated by first generation antipsychotics

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    Marić Nađa

    2008-01-01

    Full Text Available Introduction Schizophrenia patients are at greater risk of obesity, diabetes mellitus (DM, lipid abnormalities and cardiovascular disorders. The metabolic complications in patients are associated with several risk factors: family history of DM, lifestyle, smoking, dietary habits, physical inactivity, but also with antipsychotic medication. In literature, most publications have been focused on the effects of the second generation antipsychotics (SGA on glucose metabolism. However, less attention has been paid to abnormality in glucoregulation, patients with schizophrenia treated with the first generation antipsychotics (FGA. Objective The present study evaluated glucose metabolism in normal weight schizophrenia patients treated with FGA. METHOD The cross-sectional study included 18 patients (FGA treated and 20 healthy controls with neither group differences in sex distribution, age, nor in BMI. Inclusion criteria were normal BMI (20-25 kg/m2. The glucose levels, insulin levels and growth hormone levels during oral glucose tolerance test (OGTT were measured. Results Fasting glucose and insulin levels did not differ significantly between groups. Groups differed in OGTT glucose and insulin peak and area under curve (AUC, level of significance p<0.05 (patients vs. controls: glucose peak 8.3±0.4 vs.6.9±0.5 mmol/l, glucose AUC 758±28 vs. 640±36 mU/l/120 min; insulin peak in patients 92.7±15.6 mU/l; insulin AUC 6060±1016 mU/l/120 min, insulin peak in controls 47.9±6.5 mU/l; insulin AUC 2597±256 mU/l/120 min. Conclusion Patients with schizophrenia, although with normal body mass index, are at high risk of abnormal glucose regulation. Not only SGA increase the risk of impaired glucoregulation and metabolic syndrome, but this may also be due to FGA or schizophrenia per se. .

  15. Does diabetes mellitus influence the efficacy of FDG-PET in the diagnosis of cervical cancer?

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    Chang, Yu-Chen; Yen, Tzu-Chen [Chang Gung University, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan (Taiwan); Ng, Koon-Kwan [Chang Gung University, Department of Radiology, Chang Gung Memorial Hospital, Taoyuan (Taiwan); See, Lai-Chu [Chang Gung University, Biostatistics Consulting Center/Department of Public Health, Taoyuan (Taiwan); Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh [Chang Gung University, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan (Taiwan); Tsai, Chien-Sheng; Hong, Ji-Hong [Chang Gung University, Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan (Taiwan); Hsueh, Swei [Chang Gung University, Department of Pathology, Chang Gung Memorial Hospital, Taoyuan (Taiwan)

    2005-06-01

    Compared with computed tomography (CT) and magnetic resonance imaging (MRI), positron emission tomography (PET) may have additional value in the assessment of primary and recurrent cervical cancer. However, the degree of tumour uptake of {sup 18}F-2-fluoro-2-deoxy-d-glucose (FDG) uptake is sometimes influenced by diabetes mellitus (DM). Therefore, we conducted this prospective study to compare the diagnostic ability of FDG-PET in patients with cervical cancer complicated by DM and those without DM. Patients with untreated locally advanced primary or clinically curable recurrent cervical carcinoma were enrolled. Both FDG-PET and MRI/CT scans were performed within 2 weeks. Patients were categorised into the following groups: hyperglycaemic DM (fasting blood sugar >126 mg/dl), euglycaemic DM and non-DM. The lesions were confirmed histologically or by clinical follow-up. The receiver operating characteristic curve method, with calculation of the area under the curve (AUC), was used to evaluate the discriminative power. From February 2001 to January 2003, 219 patients (75 with primary and 144 with recurrent cervical cancer) were eligible for analysis. Sixteen had hyperglycaemic DM, 12 had euglycaemic DM and 191 were in the non-DM group. The diagnostic power of PET in the hyperglycaemic DM, euglycaemic DM and non-DM groups did not differ significantly with regard to the identification of either metastatic lesions (AUC, 0.967/0.947/0.925, P>0.05) or primary tumours/local recurrence (AUC, 0.950/0.938/0.979, P>0.05). Considering all DM patients, PET showed a significantly higher detection power than MRI/CT scans in respect of metastatic lesions (AUC=0.956 vs 0.824, P=0.012). In comparison with its accuracy in non-DM patients, the accuracy of PET in cervical cancer patients with mild to moderate DM was not significantly reduced. (orig.)

  16. Factor Analysis of Wildfire and Risk Area Estimation in Korean Peninsula Using Maximum Entropy

    Science.gov (United States)

    Kim, Teayeon; Lim, Chul-Hee; Lee, Woo-Kyun; Kim, YouSeung; Heo, Seongbong; Cha, Sung Eun; Kim, Seajin

    2016-04-01

    The number of wildfires and accompanying human injuries and physical damages has been increased by frequent drought. Especially, Korea experienced severe drought and numbers of wildfire took effect this year. We used MaxEnt model to figure out major environmental factors for wildfire and used RCP scenarios to predict future wildfire risk area. In this study, environmental variables including topographic, anthropogenic, meteorologic data was used to figure out contributing variables of wildfire in South and North Korea, and compared accordingly. As for occurrence data, we used MODIS fire data after verification. In North Korea, AUC(Area Under the ROC Curve) value was 0.890 which was high enough to explain the distribution of wildfires. South Korea had low AUC value than North Korea and high mean standard deviation which means there is low anticipation to predict fire with same environmental variables. It is expected to enhance AUC value in South Korea with environmental variables such as distance from trails, wildfire management systems. For instance, fire occurred within DMZ(demilitarized zone, 4kms boundary from 38th parallel) has decisive influence on fire risk area in South Korea, but not in North Korea. The contribution of each environmental variables was more distributed among variables in North Korea than in South Korea. This means South Korea is dependent on few certain variables, and North Korea can be explained as number of variables with evenly distributed portions. Although the AUC value and standard deviation of South Korea was not high enough to predict wildfire, the result carries an significant meaning to figure out scientific and social matters that certain environmental variables has great weight by understanding their response curves. We also made future wildfire risk area map in whole Korean peninsula using the same model. In four RCP scenarios, it was found that severe climate change would lead wildfire risk area move north. Especially North

  17. Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia

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    Nishihori Taiga

    2010-10-01

    Full Text Available Abstract Optimal conditioning therapy for hematopoietic cell transplantation (HCT in acute myelogenous leukemia (AML remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days and cyclophosphamide (60 mg/kg IV × 2 days - (Bu/Cy with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC

  18. Moxifloxacin Population Pharmacokinetics and Model-Based Comparison of Efficacy between Moxifloxacin and Ofloxacin in African Patients

    OpenAIRE

    Zvada, Simbarashe P.; Denti, Paolo; Sirgel, Frederick A.; Chigutsa, Emmanuel; Hatherill, Mark; Charalambous, Salome; Mungofa, Stanley; Wiesner, Lubbe; Simonsson, Ulrika S. H.; Jindani, Amina; Harrison, Thomas; McIlleron, Helen M.

    2014-01-01

    Pharmacokinetic exposure and the MIC of fluoroquinolones are important determinants of their efficacy against Mycobacterium tuberculosis. Population modeling was used to describe the steady-state plasma pharmacokinetics of moxifloxacin in 241 tuberculosis (TB) patients in southern Africa. Monte Carlo simulations were applied to obtain the area under the unbound concentration-time curve from 0 to 24 h (fAUC0–24) after daily doses of 400 mg or 800 mg moxifloxacin and 800 mg ofloxacin. The MIC d...

  19. Dose independent pharmacokinetics of mexiletine in healthy volunteers.

    OpenAIRE

    Pringle, T.; Fox, J.; McNeill, J A; Kinney, C D; Liddle, J.; Harron, D W; Shanks, R G

    1986-01-01

    In 12 healthy volunteers who received orally 100, 200, 300, 400 and 600 mg mexiletine at weekly intervals, the maximum plasma concentration of mexiletine and AUC increased linearly with the dose of mexiletine. Between doses there were no significant differences in the values for clearance and volume of distribution of mexiletine but there were for plasma elimination half-life. These results indicate that the kinetics of mexiletine are linear.

  20. P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Latha G.; Sannigrahi, Mousumi; Bogen, Stephane; Pinto, Patrick; Chen, Kevin X.; Prongay, Andrew; Tong, Xiao; Cheng, K.-C.; Girijavallabhann, Viyyoor; Njoroge, F. George (Merck)

    2010-09-03

    SAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described. Extensive SAR studies resulted in the identification of 36 bearing 4,4-dimethyl lactam as the new P4 cap unit with improved potency (K*{sub i}, EC 90 = 70 nM) and pharmacokinetic properties (Rat AUC (PO) = 3.52 {micro}M h) compared to 1.

  1. Evaluation of Major Online Diabetes Risk Calculators and Computerized Predictive Models.

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    Gregor Stiglic

    Full Text Available Classical paper-and-pencil based risk assessment questionnaires are often accompanied by the online versions of the questionnaire to reach a wider population. This study focuses on the loss, especially in risk estimation performance, that can be inflicted by direct transformation from the paper to online versions of risk estimation calculators by ignoring the possibilities of more complex and accurate calculations that can be performed using the online calculators. We empirically compare the risk estimation performance between four major diabetes risk calculators and two, more advanced, predictive models. National Health and Nutrition Examination Survey (NHANES data from 1999-2012 was used to evaluate the performance of detecting diabetes and pre-diabetes. American Diabetes Association risk test achieved the best predictive performance in category of classical paper-and-pencil based tests with an Area Under the ROC Curve (AUC of 0.699 for undiagnosed diabetes (0.662 for pre-diabetes and 47% (47% for pre-diabetes persons selected for screening. Our results demonstrate a significant difference in performance with additional benefits for a lower number of persons selected for screening when statistical methods are used. The best AUC overall was obtained in diabetes risk prediction using logistic regression with AUC of 0.775 (0.734 and an average 34% (48% persons selected for screening. However, generalized boosted regression models might be a better option from the economical point of view as the number of selected persons for screening of 30% (47% lies significantly lower for diabetes risk assessment in comparison to logistic regression (p < 0.001, with a significantly higher AUC (p < 0.001 of 0.774 (0.740 for the pre-diabetes group. Our results demonstrate a serious lack of predictive performance in four major online diabetes risk calculators. Therefore, one should take great care and consider optimizing the online versions of questionnaires that

  2. N-methyl-D-Aspartate Receptors Contribute to Complex Spike Signaling in Cerebellar Purkinje Cells: An In vivo Study in Mice.

    Science.gov (United States)

    Liu, Heng; Lan, Yan; Bing, Yan-Hua; Chu, Chun-Ping; Qiu, De-Lai

    2016-01-01

    N-methyl-D-aspartate receptors (NMDARs) are post-synaptically expressed at climbing fiber-Purkinje cell (CF-PC) synapses in cerebellar cortex in adult mice and contributed to CF-PC synaptic transmission under in vitro conditions. In this study, we investigated the role of NMDARs at CF-PC synapses during the spontaneous complex spike (CS) activity in cerebellar cortex in urethane-anesthetized mice, by in vivo whole-cell recording technique and pharmacological methods. Under current-clamp conditions, cerebellar surface application of NMDA (50 μM) induced an increase in the CS-evoked pause of simple spike (SS) firing accompanied with a decrease in the SS firing rate. Under voltage-clamp conditions, application of NMDA enhanced the waveform of CS-evoked inward currents, which expressed increases in the area under curve (AUC) and spikelet number of spontaneous CS. NMDA increased the AUC of spontaneous CS in a concentration-dependent manner. The EC50 of NMDA for increasing AUC of spontaneous CS was 33.4 μM. Moreover, NMDA significantly increased the amplitude, half-width and decay time of CS-evoked after-hyperpolarization (AHP) currents. Blockade of NMDARs with D-(-)-2-amino-5-phosphonopentanoic acid (D-APV, 250 μM) decreased the AUC, spikelet number, and amplitude of AHP currents. In addition, the NMDA-induced enhancement of CS activity could not be observed after α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors were blocked. The results indicated that NMDARs of CF-PC synapses contributed to the spontaneous CS activity by enhancing CS-evoked inward currents and AHP currents. PMID:27445699

  3. Cognitive impairment in ALS patients and validation of the Spanish version of the ALS-CBS test.

    Science.gov (United States)

    Turon-Sans, Janina; Gascon-Bayarri, Jordi; Reñé, Ramon; Rico, Imma; Gámez, Cristina; Paipa, Andres; Povedano, Monica

    2016-01-01

    Our aim was to develop and validate the Spanish version of the Amyotrophic Lateral Sclerosis Cognitive Behavioural Screen (ALS-CBS) and investigate behavioural/cognitive impairment in our ALS patients. We enrolled 50 patients with definite or probable ALS, evaluated by the Motor Neuron Disease Unit (using El Escorial criteria) and Dementia Unit, and assessed with the Spanish ALS-CBS. The patients' cognitive/behavioural status was classified according to current criteria. Patients were classified into each diagnostic category: ALS-no impairment, 36%; ALS-mild cognitive impairment, 34%; ALS-mild behavioural impairment, 6%; ALS-mild cognitive/behavioural impairment, 12%; ALS-frontotemporal dementia, 12%. Cognitive impairment was more common in bulbar (90.9%) than spinal (48.7%) forms (p impaired individuals was: 1) cognition (cut-off 15; AUC, 84.7%): sensitivity 86.2%, specificity 62%, positive predictive value 75.8%, negative predictive value 76.5%; 2) behaviour (cut-off 36; AUC, 83.3%): sensitivity 93.3%, specificity 74.3%, positive predictive value 61%, negative predictive value 96.3%. Performance to differentiate between patients with and without dementia: 1) cognition (cut-off 8; AUC, 87.3%): sensitivity 83.3%, specificity 75%, positive predictive value 31.3%, negative predictive value 97.1%; 2) behaviour (cut-off 35; AUC, 80.9%): sensitivity 83.3%, specificity 69%, positive predictive value 25%, negative predictive value 96.7%. In conclusion, cognitive impairment is common in ALS patients, particularly in bulbar forms. The Spanish version of the ALS-CBS is useful for screening cognitive/behavioural impairment in this population. PMID:26726932

  4. Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Ulla Knorr

    Full Text Available INTRODUCTION: The mechanisms by which selective serotonin re-uptake inhibitors (SSRI act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA system may interact. The aim of the AGENDA trial was to investigate whether long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH test in healthy first-degree relatives to patients with major depressive disorder (MDD. METHODS: Eighty healthy first-degree relatives to patients with MDD were randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUC(total for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention. RESULTS: Change in CorAUC(total showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in CorAUC(total, rho = -0.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUC(total. CONCLUSION: The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first-degree relatives to patients with MDD. Increasing levels of escitalopram tended to decrease the HPA-response in the DEX-CRH test and this effect increased with age. TRIAL REGISTRATION: ClinicalTrials.gov NCT00386841.

  5. Delayed postoperative gastric emptying following intrathecal morphine and intrathecal bupivacaine.

    LENUS (Irish Health Repository)

    Lydon, A M

    2012-02-03

    PURPOSE: A decrease in the rate of gastric emptying can delay resumption of enteral feeding, alter bioavailability of orally administered drugs, and result in larger residual gastric volumes, increasing the risk of nausea and vomiting. We compared the effects of 1) intrathecal bupivacaine (17.5 mg) and 2) the combination of intrathecal morphine (0.6 mg) and intrathecal bupivacaine (17.5 mg) on the rate of gastric emptying in patients undergoing elective hip arthroplasty. METHODS: Twenty four fasting ASA 1-3 patients were randomly assigned, in a double blind manner, to receive intrathecal hyperbaric bupivacaine (17.5 mg), either alone (group 1), or followed by intrathecal morphine (0.6 mg) (group 2). Gastric emptying was measured (using an acetaminophen absorption technique), twice in each patient; preoperatively, and approximately one hour postoperatively. Gastric emptying parameters are: AUC (area under the plasma acetaminophen concentration time curve), maximum plasma acetaminophen concentration (Cmax), and time to Cmax (tCmax), analyzed using paired Student\\'s t tests. RESULTS: Gastric emptying rates were reduced in both group 1 (AUC = 14.98 (3.8) and 11.05 (4.6) pre- and postoperatively, respectively) and group 2 (AUC = 13.93 (3.59) and 6.4 (3.42) pre- and postoperatively, respectively); the magnitude of the reduction was greater in group 2 [AUC (P = 0.04), Cmax (P = 0.05), tCmax (P = 0.13)]. CONCLUSION: The combination of intrathecal morphine (0.6 mg) and intrathecal bupivacaine (17.5 mg) delays gastric emptying postoperatively.

  6. Toxicokinetics of 2-nitropropane in the rat

    OpenAIRE

    Derks HJGM; Heinignen A van; Klaassen R; Olling M

    1989-01-01

    De toxicokinetiek van 2-nitropropaan na intraveneuze en orale toediening (in water en in olie) werd onderzocht. Uit de plasma-concentratie profielen werden farmacokinetische paramters berekend waarbij een open een-compartiment model werd gebruikt. Door AUC-waarden verkregen bij varierende intraveneuze doses te vergelijken werd vastgesteld dat de kinetiek lineair is in het bestudeerde dosis-interval (10-50 mg/kg). De plasma halfwaardetijd was 45 min. en het distributievolume 2 1/kg. De systemi...

  7. Age-correction of test scores reduces the validity of mild cognitive impairment in predicting progression to dementia.

    Directory of Open Access Journals (Sweden)

    Johannes Hessler

    Full Text Available A phase of mild cognitive impairment (MCI precedes most forms of neurodegenerative dementia. Many definitions of MCI recommend the use of test norms to diagnose cognitive impairment. It is, however, unclear whether the use of norms actually improves the detection of individuals at risk of dementia. Therefore, the effects of age- and education-norms on the validity of test scores in predicting progression to dementia were investigated.Baseline cognitive test scores (Syndrome Short Test of dementia-free participants aged ≥65 were used to predict progression to dementia within three years. Participants were comprehensively examined one, two, and three years after baseline. Test scores were calculated with correction for (1 age and education, (2 education only, (3 age only and (4 without correction. Predictive validity was estimated with Cox proportional hazard regressions. Areas under the curve (AUCs were calculated for the one-, two-, and three-year intervals.82 (15.3% of initially 537 participants, developed dementia. Model coefficients, hazard ratios, and AUCs of all scores were significant (p<0.001. Predictive validity was the lowest with age-corrected scores (-2 log likelihood  = 840.90, model fit χ2 (1  = 144.27, HR  = 1.33, AUCs between 0.73 and 0.87 and the highest with education-corrected scores (-2 log likelihood  = 815.80, model fit χ2 (1  = 171.16, HR  = 1.34, AUCs between 0.85 and 0.88.The predictive validity of test scores is markedly reduced by age-correction. Therefore, definitions of MCI should not recommend the use of age-norms in order to improve the detection of individuals at risk of dementia.

  8. Prebiotic fibres dose-dependently increase satiety hormones and alter Bacteroidetes and Firmicutes in lean and obese JCR:LA-cp rats.

    Science.gov (United States)

    Parnell, Jill A; Reimer, Raylene A

    2012-02-01

    There is a growing interest in modulating gut microbiota with diet in the context of obesity. The purpose of the present study was to evaluate the dose-dependent effects of prebiotics (inulin and oligofructose) on gut satiety hormones, energy expenditure, gastric emptying and gut microbiota. Male lean and obese JCR:LA-cp rats were randomised to either of the following: lean 0 % fibre (LC), lean 10 % fibre (LF), lean 20 % fibre (LHF), obese 0 % fibre (OC), obese 10 % fibre (OF) or obese 20 % fibre (OHF). Body composition, gastric emptying, energy expenditure, plasma satiety hormone concentrations and gut microbiota (using quantitative PCR) were measured. Caecal proglucagon and peptide YY mRNA levels were up-regulated 2-fold in the LF, OF and OHF groups and 3-fold in the LHF group. Ghrelin O-acyltransferase mRNA levels were higher in obese v. lean rats and decreased in the OHF group. Plasma ghrelin response was attenuated in the LHF group. Microbial species measured in the Bacteroidetes division decreased, whereas those in the Firmicutes increased in obese v. lean rats and improved with prebiotic intake. Bifidobacterium and Lactobacillus increased in the OHF v. OC group. Bacteroides and total bacteria negatively correlated with percentage of body fat and body weight. Enterobacteriaceae increased in conjunction with glucose area under the curve (AUC) and glucagon-like peptide-1 AUC. Bacteroides and total bacteria correlated positively with ghrelin AUC yet negatively with insulin AUC and energy intake (P alterations in gut microbiota) are regulated in a dose-dependent manner. The combined effects of prebiotics may have therapeutic potential for obesity. PMID:21767445

  9. Breast density and parenchymal texture measures as potential risk factors for estrogen-receptor positive breast cancer

    Science.gov (United States)

    Keller, Brad M.; Chen, Jinbo; Conant, Emily F.; Kontos, Despina

    2014-03-01

    Accurate assessment of a woman's risk to develop specific subtypes of breast cancer is critical for appropriate utilization of chemopreventative measures, such as with tamoxifen in preventing estrogen-receptor positive breast cancer. In this context, we investigate quantitative measures of breast density and parenchymal texture, measures of glandular tissue content and tissue structure, as risk factors for estrogen-receptor positive (ER+) breast cancer. Mediolateral oblique (MLO) view digital mammograms of the contralateral breast from 106 women with unilateral invasive breast cancer were retrospectively analyzed. Breast density and parenchymal texture were analyzed via fully-automated software. Logistic regression with feature selection and was performed to predict ER+ versus ER- cancer status. A combined model considering all imaging measures extracted was compared to baseline models consisting of density-alone and texture-alone features. Area under the curve (AUC) of the receiver operating characteristic (ROC) and Delong's test were used to compare the models' discriminatory capacity for receptor status. The density-alone model had a discriminatory capacity of 0.62 AUC (p=0.05). The texture-alone model had a higher discriminatory capacity of 0.70 AUC (p=0.001), which was not significantly different compared to the density-alone model (p=0.37). In contrast the combined density-texture logistic regression model had a discriminatory capacity of 0.82 AUC (pbreast density and texture measures may have the potential to identify women specifically at risk for estrogen-receptor positive breast cancer and could be useful in triaging women into appropriate risk-reduction strategies.

  10. Pharmacokinetics of a novel submicron budesonide dispersion for nebulized delivery in asthma.

    Science.gov (United States)

    Shrewsbury, Stephen B; Bosco, Andrew P; Uster, Paul S

    2009-01-01

    The objective of this study was to evaluate the safety and pharmacokinetics of unit dose budesonide (UDB), an aqueous dispersion of submicron-sized budesonide particles, and a commercially available budesonide suspension formulation. This was a randomized, double-blind, active-controlled, 4-period, 4-way crossover trial in 16 healthy, adult volunteers. Subjects received UDB 0.24, 0.12, and 0.06 mg or commercial budesonide 0.25 mg via a jet nebulizer. T(max) was significantly (p<0.05) earlier for UDB 0.06, 0.12, and 0.24 mg (4.5+/-3.3, 3.1+/-1.5, 3.7+/-1.5 min) vs. commercial budesonide (9.1+/-7.1 min). C(max) was significantly (p<0.05) higher for UDB 0.24 mg vs. commercial budesonide 0.25 mg (434.5+/-246.9 pg/mL vs. 303.5+/-177.4 pg/mL) but not between UDB 0.12 mg (239.9+/-140 pg/mL) and commercial budesonide 0.25 mg (p=0.448). AUC(0-infinity) was marginally, but significantly lower for UDB 0.24 mg than commercial budesonide 0.25 mg. AUCs for UDB 0.12 mg were lower than commercial budesonide 0.25 mg. UDB 0.24 mg was absorbed more rapidly and achieved higher peak concentrations than commercial budesonide 0.25 mg, but had a lower AUC(0-infinity). UDB 0.12 mg also was absorbed more rapidly but had lower C(max) and AUCs than commercial budesonide 0.25 mg.

  11. A Population-Based Clinical Trial of Irinotecan and Carboplatin

    Directory of Open Access Journals (Sweden)

    Derick Lau

    2009-01-01

    Full Text Available Purpose. Phase I trials of anticancer drugs are commonly conducted using the method of modified Fibonacci. We have developed a population-based design for phase I trials of combining anticancer drugs such as irinotecan and carboplatin. Patients and Methods. Intrapatient dose escalation of irinotecan and carboplatin was performed according to a predetermined schema to reach individual dose-limiting toxicity (DLT in 50 patients with solid tumors refractory to previous chemotherapy. The individual toxicity-limiting dose levels were analyzed for normal distribution using the method of Ryan-Joiner and subsequently used to determine a population-based maximum tolerated dose (pMTD. For comparison, a simulation study was performed using the method of modified Fibonacci. Results. The most common dose-limiting toxicities (DLTs included neutropenia (58%, thrombocytopenia (16%, and diarrhea (8%. The frequency of individual toxicity-limiting dose levels of 50 patients approximated a normal distribution. The dose levels associated with individual limiting toxicities ranged from level 1 (irinotecan 100 mg/m2 and carboplatin AUC = 4 mg/mL x min to level 8 (irinotecan 350 mg/m2 and carboplatin AUC = 6. The pMTD was determined to be dose level 3 (150 mg/m2 for irinotecan and AUC = 5 for carboplatin. In contrast, the MTD was determined to be dose level 4 (200 mg/m2 for irinotecan and AUC 5 for carboplatin by modified-Fibonacci simulation. Conclusions. The population-based design of phase I trial allows optimization of dose intensity and derivation of a pMTD. The pMTD has been applied in phase II trial of irinotecan and carboplatin in patients with small-cell lung cancer.

  12. Effect of different protein types on second meal postprandial glycaemia in normal weight and normoglycemic subjects

    Directory of Open Access Journals (Sweden)

    Winder Tadeu Silva Ton

    2014-03-01

    Full Text Available Background: Diabetes mellitus is a global epidemic affecting 346 million people in the world. The glycemic control is the key for diabetes prevention and management. Some proteins can stimulate insulin release and modulate glycemic response. Objectives: To assess the effect of the consumption of different types of protein (whey protein, soy protein and egg white on a second meal postprandial glycaemia in normal weight and normoglycemic subjects. Methodology: Randomized crossover clinical trial. After an overnight fast of 12-hours, ten subjects attended the laboratory to drink one of the protein shakes (whey, soy or egg white or the control drink. Thirty minutes later, the subjects consumed a glucose solution (25 g glucose. Glycemic response was monitored at times 0 (before glucose solution and 15, 30, 45, 60, 90 and 120 min (after glucose solution consumption. Incremental area under the glycemic curve (iAUC was calculated by the trapezoidal method. Furthermore, glycemic response was assessed by a new method using iG equation. Results: Compared with control, whey and soy protein drinks reduced postprandial iAUC in 56.5% (p = 0.004 and 44.4% (p = 0.029, respectively. Whey protein was the only protein capable of avoiding great fluctuations and a peak in postprandial glycemia. The assessment of glycemic response by iG equation showed positive correlation with iAUC (Pearson 0.985, p < 0.05. Conclusion: The consumption of whey and soy protein 30 minutes before a glucose load resulted in lower iAUC compared with control drink. Whey protein maintained postprandial glycemia more stable.

  13. Bakkesand, Lund nr. 0

    DEFF Research Database (Denmark)

    Sørensen, Carsten Steen

    Bakkesand, Lund nr. 0 er en sorteret sand fra Lund grusgrav, der ligger vest for Horsens. Denne sand er valgt som generel forsøgssand ved udførelse af modelforsøg på sand i Funderingslaboratoriet ved AUC. For at få et kendskab til denne sands styrkeegenskaber blev der i efteråret 1984 udført 30...

  14. Faster Onset of Bronchodilation with Formoterol than with Salmeterol in Patients with Stable, Moderate-Severe Copd: Results of a Randomized, Double-Blind Clinical Study

    OpenAIRE

    John Kottakis; Giovanni Della Cioppa; Jacques Creemers; Louis Greefhorst; Violette Leclerc; Riccardo Pistelli; Tim Overend; Denise Till; Günter Rapatz; Vincent LeGros; Demosthenes Bouros; Nikolaos Siafakas

    2002-01-01

    OBJECTIVES: To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1 AUC*0-1 h).DESIGN: A double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study.SETTING: Five centres in four countries -- one centre each in ...

  15. Nevirapine Significantly Reduces the Levels of Racemic Methadone and (R)-Methadone in Human Immunodeficiency Virus-Infected Patients

    OpenAIRE

    Stocker, Hartmut; Kruse, Guido; Kreckel, Peter; Herzmann, Christian; Arastéh, Keikawus; Claus, Jörg; Jessen, Heiko; Cordes, Christiane; Hintsche, Bettina; Schlote, Frank; Schneider, Lothar; Kurowski, Michael

    2004-01-01

    Methadone is metabolized by various isoforms of the cytochrome P450 family, which can be induced by many drugs, including nevirapine. The objective of the present study was to determine the effects of coadministration of nevirapine and methadone on the dose-adjusted areas under the concentration-time curves (AUCs) of racemic and (R)-methadone. Twenty-five human immunodeficiency virus-infected subjects taking stable single daily doses of racemic methadone or (R)-methadone were included in this...

  16. Relationship of computed tomography perfusion and positron emission tomography to tumour progression in malignant glioma

    International Nuclear Information System (INIS)

    Introduction: This study aimed to explore the potential for computed tomography (CT) perfusion and 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting sites of future progressive tumour on a voxel-by-voxel basis after radiotherapy and chemotherapy. Methods: Ten patients underwent pre-radiotherapy magnetic resonance (MR), FDG-PET and CT perfusion near the end of radiotherapy and repeated post-radiotherapy follow-up MR scans. The relationships between these images and tumour progression were assessed using logistic regression. Cross-validation with receiver operating characteristic (ROC) analysis was used to assess the value of these images in predicting sites of tumour progression. Results: Pre-radiotherapy MR-defined gross tumour; near-end-of-radiotherapy CT-defined enhancing lesion; CT perfusion blood flow (BF), blood volume (BV) and permeability-surface area (PS) product; FDG-PET standard uptake value (SUV); and SUV:BF showed significant associations with tumour progression on follow-up MR imaging (P < 0.0001). The mean sensitivity (±standard deviation), specificity and area under the ROC curve (AUC) of PS were 0.64 ± 0.15, 0.74 ± 0.07 and 0.72 ± 0.12 respectively. This mean AUC was higher than that of the pre-radiotherapy MR-defined gross tumour and near-end-of-radiotherapy CT-defined enhancing lesion (both AUCs = 0.6 ± 0.1, P ≤ 0.03). The multivariate model using BF, BV, PS and SUV had a mean AUC of 0.8 ± 0.1, but this was not significantly higher than the PS only model. Conclusion: PS is the single best predictor of tumour progression when compared to other parameters, but voxel-based prediction based on logistic regression had modest sensitivity and specificity

  17. A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

    Science.gov (United States)

    Zhao, Huaying; Ghirlando, Rodolfo; Alfonso, Carlos; Arisaka, Fumio; Attali, Ilan; Bain, David L.; Bakhtina, Marina M.; Becker, Donald F.; Bedwell, Gregory J.; Bekdemir, Ahmet; Besong, Tabot M. D.; Birck, Catherine; Brautigam, Chad A.; Brennerman, William; Byron, Olwyn; Bzowska, Agnieszka; Chaires, Jonathan B.; Chaton, Catherine T.; Cölfen, Helmut; Connaghan, Keith D.; Crowley, Kimberly A.; Curth, Ute; Daviter, Tina; Dean, William L.; Díez, Ana I.; Ebel, Christine; Eckert, Debra M.; Eisele, Leslie E.; Eisenstein, Edward; England, Patrick; Escalante, Carlos; Fagan, Jeffrey A.; Fairman, Robert; Finn, Ron M.; Fischle, Wolfgang; de la Torre, José García; Gor, Jayesh; Gustafsson, Henning; Hall, Damien; Harding, Stephen E.; Cifre, José G. Hernández; Herr, Andrew B.; Howell, Elizabeth E.; Isaac, Richard S.; Jao, Shu-Chuan; Jose, Davis; Kim, Soon-Jong; Kokona, Bashkim; Kornblatt, Jack A.; Kosek, Dalibor; Krayukhina, Elena; Krzizike, Daniel; Kusznir, Eric A.; Kwon, Hyewon; Larson, Adam; Laue, Thomas M.; Le Roy, Aline; Leech, Andrew P.; Lilie, Hauke; Luger, Karolin; Luque-Ortega, Juan R.; Ma, Jia; May, Carrie A.; Maynard, Ernest L.; Modrak-Wojcik, Anna; Mok, Yee-Foong; Mücke, Norbert; Nagel-Steger, Luitgard; Narlikar, Geeta J.; Noda, Masanori; Nourse, Amanda; Obsil, Tomas; Park, Chad K.; Park, Jin-Ku; Pawelek, Peter D.; Perdue, Erby E.; Perkins, Stephen J.; Perugini, Matthew A.; Peterson, Craig L.; Peverelli, Martin G.; Piszczek, Grzegorz; Prag, Gali; Prevelige, Peter E.; Raynal, Bertrand D. E.; Rezabkova, Lenka; Richter, Klaus; Ringel, Alison E.; Rosenberg, Rose; Rowe, Arthur J.; Rufer, Arne C.; Scott, David J.; Seravalli, Javier G.; Solovyova, Alexandra S.; Song, Renjie; Staunton, David; Stoddard, Caitlin; Stott, Katherine; Strauss, Holger M.; Streicher, Werner W.; Sumida, John P.; Swygert, Sarah G.; Szczepanowski, Roman H.; Tessmer, Ingrid; Toth, Ronald T.; Tripathy, Ashutosh; Uchiyama, Susumu; Uebel, Stephan F. W.; Unzai, Satoru; Gruber, Anna Vitlin; von Hippel, Peter H.; Wandrey, Christine; Wang, Szu-Huan; Weitzel, Steven E.; Wielgus-Kutrowska, Beata; Wolberger, Cynthia; Wolff, Martin; Wright, Edward; Wu, Yu-Sung; Wubben, Jacinta M.; Schuck, Peter

    2015-01-01

    Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies. PMID:25997164

  18. A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

    KAUST Repository

    Zhao, Huaying

    2015-05-21

    Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.

  19. Assessing ectasia susceptibility prior to LASIK: the role of age and residual stromal bed (RSB in conjunction to Belin-Ambrósio deviation index (BAD-D

    Directory of Open Access Journals (Sweden)

    Renato Ambrósio Jr

    2014-04-01

    Full Text Available Purpose: To compare the ability to detect preoperative ectasia risk among LASIK candidates using classic ERSS (Ectasia Risk Score System and Pentacam Belin-Ambrósio deviation index (BAD-D, and to test the benefit of a combined approach including BAD-D and clinical data. Methods: A retrospective nonrandomized study involved preoperative LASIK data from 23 post-LASIK ectasia cases and 266 stable-LASIK (follow up > 12 months. Preoperative clinical and Pentacam (Oculus; Wetzlar, Germany data were obtained from all cases. Mann-Whitney's test was performed to assess differences between groups. Stepwise logistic regression was used for combining parameters.The areas under the Receiver Operating Characteristic (ROC curves (AUC were calculated for all parameters and combinations, with pairwise comparisons of AUC (DeLong's method. Results: Statistically significant differences were found for age, residual stromal bed (RSB, central corneal thickness and BAD-D (p0.05. ERSS was 3 or more on 12/23 eyes from the ectasia group (sensitivity = 52.17% and 48/266 eyes from the stable LASIK group (18% false positive. BAD-D had AUC of 0.931 (95% CI: 0.895 to 0.957, with cut-off of 1.29 (sensitivity = 87%; specificity = 92.1%. Formula combining BAD-D, age and RSB provided 100% sensitivity and 94% specificity, with better AUC (0.989; 95% CI: 0.969 to 0.998 than all individual parameters (p>0.001. Conclusion: BAD-D is more accurate than ERSS. Combining clinical data and BAD-D improved ectasia susceptibility screening. Further validation is necessary. Novel combined functions using other topometric and tomographic parameters should be tested to further enhance accuracy.

  20. Comparison of the performance of two measures of central adiposity among apparently healthy Nigerians using the receiver operating characteristic analysis

    Directory of Open Access Journals (Sweden)

    Christian Ifedili Okafor

    2011-01-01

    Full Text Available Objective: To compare the performance of waist circumference (WC and waist-to-hip ratio (WHR in predicting the presence of cardiovascular risk factors (hypertension and generalized obesity in an apparently healthy population. Materials and Methods: We recruited 898 apparently healthy subjects (318 males and 580 females of the Igbo ethnic group resident in Enugu (urban, Southeast Nigeria. Data collection was done using the World Health Organization Stepwise approach to Surveillance of risk factors (STEPS instrument. Subjects had their weight, height, waist and hip circumferences, systolic and diastolic blood pressures measured according to the guidelines in the step 2 of STEPS instrument. Generalized obesity and hypertension were defined using body mass index (BMI and JNC 7 classifications, respectively. Quantitative and qualitative variables were analyzed using t-test and Chi-square analysis, respectively, while the performance of WC and WHR was compared using the Receiver Operating Characteristic (ROC analysis. P value was set at <0.05. Results: The mean age of the subjects was 48.7 (12.9 years. Central obesity was found in 76.9% and 66.5% of subjects using WHR and WC, respectively. WC had a significantly higher area under the curve (AUC than WHR in all the cardiovascular risk groups, namely, generalized obesity (AUC = 0.88 vs. 0.62, hypertension alone (AUC = 0.60 vs. 0.53, and both generalized obesity and hypertension (AUC = 0.86 vs. 0.57. Conclusion: WC performed better than WHR in predicting the presence of cardiovascular risk factors. Being a simple index, it can easily be measured in routine clinic settings without the need for calculations or use of cumbersome techniques.

  1. Impact of respiratory motion correction and spatial resolution on lesion detection in PET: a simulation study based on real MR dynamic data

    International Nuclear Information System (INIS)

    The aim of this study is to investigate the impact of respiratory motion correction and spatial resolution on lesion detectability in PET as a function of lesion size and tracer uptake. Real respiratory signals describing different breathing types are combined with a motion model formed from real dynamic MR data to simulate multiple dynamic PET datasets acquired from a continuously moving subject. Lung and liver lesions were simulated with diameters ranging from 6 to 12 mm and lesion to background ratio ranging from 3:1 to 6:1. Projection data for 6 and 3 mm PET scanner resolution were generated using analytic simulations and reconstructed without and with motion correction. Motion correction was achieved using motion compensated image reconstruction. The detectability performance was quantified by a receiver operating characteristic (ROC) analysis obtained using a channelized Hotelling observer and the area under the ROC curve (AUC) was calculated as the figure of merit. The results indicate that respiratory motion limits the detectability of lung and liver lesions, depending on the variation of the breathing cycle length and amplitude. Patients with large quiescent periods had a greater AUC than patients with regular breathing cycles and patients with long-term variability in respiratory cycle or higher motion amplitude. In addition, small (less than 10 mm diameter) or low contrast (3:1) lesions showed the greatest improvement in AUC as a result of applying motion correction. In particular, after applying motion correction the AUC is improved by up to 42% with current PET resolution (i.e. 6 mm) and up to 51% for higher PET resolution (i.e. 3 mm). Finally, the benefit of increasing the scanner resolution is small unless motion correction is applied. This investigation indicates high impact of respiratory motion correction on lesion detectability in PET and highlights the importance of motion correction in order to benefit from the increased resolution of future

  2. HCC-DETECT: a combination of nuclear, cytoplasmic, and oncofetal proteins as biomarkers for hepatocellular carcinoma.

    Science.gov (United States)

    Attallah, Abdelfattah M; El-Far, Mohamed; Malak, Camelia A Abdel; Omran, Mohamed M; Shiha, Gamal E; Farid, Khaled; Barakat, Lamiaa A; Albannan, Mohamed S; Attallah, Ahmed A; Abdelrazek, Mohamed A; Elbendary, Mohamed S; Sabry, Refaat; Hamoda, Gehan A; Elshemy, Mohamed M; Ragab, Abdallah A; Foda, Basma M; Abdallah, Sanaa O

    2015-09-01

    Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy. PMID:25929809

  3. Energy dense, protein restricted diet increases adiposity and perturbs metabolism in young, genetically lean pigs.

    Directory of Open Access Journals (Sweden)

    Kimberly D Fisher

    Full Text Available Animal models of obesity and metabolic dysregulation during growth (or childhood are lacking. Our objective was to increase adiposity and induce metabolic syndrome in young, genetically lean pigs. Pre-pubertal female pigs, age 35 d, were fed a high-energy diet (HED; n = 12, containing 15% tallow, 35% refined sugars and 9.1-12.9% crude protein, or a control corn-based diet (n = 11 with 12.2-19.2% crude protein for 16 wk. Initially, HED pigs self-regulated energy intake similar to controls, but by wk 5, consumed more (P<0.001 energy per kg body weight. At wk 15, pigs were subjected to an oral glucose tolerance test (OGTT; blood glucose increased (P<0.05 in control pigs and returned to baseline levels within 60 min. HED pigs were hyperglycemic at time 0, and blood glucose did not return to baseline (P = 0.01, even 4 h post-challenge. During OGTT, glucose area under the curve (AUC was higher and insulin AUC was lower in HED pigs compared to controls (P = 0.001. Chronic HED intake increased (P<0.05 subcutaneous, intramuscular, and perirenal fat deposition, and induced hyperglycemia, hypoinsulinemia, and low-density lipoprotein hypercholesterolemia. A subset of HED pigs (n = 7 was transitioned back to a control diet for an additional six weeks. These pigs were subjected to an additional OGTT at 22 wk. Glucose AUC and insulin AUC did not improve, supporting that dietary intervention was not sufficient to recover glucose tolerance or insulin production. These data suggest a HED may be used to increase adiposity and disrupt glucose homeostasis in young, growing pigs.

  4. Pharmacokinetics of chlorogenic acid and corydaline in DA-9701, a new botanical gastroprokinetic agent, in rats.

    Science.gov (United States)

    Jung, Ji Won; Kim, Ju Myung; Jeong, Jin Seok; Son, Miwon; Lee, Hye Suk; Lee, Myung Gull; Kang, Hee Eun

    2014-07-01

    1.Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been reported. The aim of the present study is to evaluate the pharmacokinetic properties CA and CRD following intravenous and oral administration of pure CA (1-8 mg/kg) or CRD (1.1-4.5 mg/kg) and their equivalent dose of DA-9701 to rats. 2.  Dose-proportional AUC and dose-independent clearance (10.3-12.1 ml/min/kg) of CA were observed following its administration. Oral administration of CA as DA-9701 did not influence the oral pharmacokinetic parameters of CA. Incomplete absorption of CA, its decomposition in the gastrointestinal tract, and/or pre-systemic metabolism resulted in extremely low oral bioavailability (F) of CA (0.478-0.899%). 3.  CRD showed greater dose-normalized AUC in the higher dose group than that in lower dose group(s) after its administration due to saturation of its metabolism via decreased non-renal clearance (by 51.3%) and first-pass extraction. As a result, the F of CRD following 4.5 mg/kg oral CRD (21.1%) was considerably greater than those of the lower dose groups (9.10 and 13.8%). However, oral administration of CRD as DA-9701 showed linear pharmacokinetics as a result of increased AUC and F in lower-dose groups (by 182% and 78.5%, respectively) compared to those of pure CRD. The greater oral AUC of CRD for DA-9701 than for pure CRD could be due to decreased hepatic and/or GI first-pass extraction of CRD by other components in DA-9701.

  5. Regularization in Retrieval-Driven Classification of Clustered Microcalcifications for Breast Cancer

    Directory of Open Access Journals (Sweden)

    Hao Jing

    2012-01-01

    Full Text Available We propose a regularization based approach for case-adaptive classification in computer-aided diagnosis (CAD of breast cancer. The goal is to improve the classification accuracy on a query case by making use of a set of similar cases retrieved from an existing library of known cases. In the proposed approach, a prior is first derived from a traditional CAD classifier (which is typically pre-trained offline on a set of training cases. It is then used together with the retrieved similar cases to obtain an adaptive classifier on the query case. We consider two different forms for the regularization prior: one is fixed for all query cases and the other is allowed to vary with different query cases. In the experiments the proposed approach is demonstrated on a dataset of 1,006 clinical cases. The results show that it could achieve significant improvement in numerical efficiency compared with a previously proposed case adaptive approach (by about an order of magnitude while maintaining similar (or better improvement in classification accuracy; it could also adapt faster in performance with a small number of retrieved cases. Measured by the area of under the ROC curve (AUC, the regularization based approach achieved AUC = 0.8215, compared with AUC = 0.7329 for the baseline classifier (-value=0.001.

  6. Regularization in Retrieval-Driven Classification of Clustered Microcalcifications for Breast Cancer

    Science.gov (United States)

    Jing, Hao; Yang, Yongyi; Nishikawa, Robert M.

    2012-01-01

    We propose a regularization based approach for case-adaptive classification in computer-aided diagnosis (CAD) of breast cancer. The goal is to improve the classification accuracy on a query case by making use of a set of similar cases retrieved from an existing library of known cases. In the proposed approach, a prior is first derived from a traditional CAD classifier (which is typically pre-trained offline on a set of training cases). It is then used togeth