Quantification of typical antipsychotics in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.

A selective and sensitive method was developed for the simultaneous quantification of seven typical antipsychotic drugs (cis-chlorprothixene, flupentixol, haloperidol, levomepromazine, pipamperone, promazine and zuclopenthixol) in human plasma. Ultra-high performance liquid chromatography (UHPLC) was used for complete separation of the compounds in less than 4.5min on an Acquity UPLC BEH C18 column (2.1mm×50mm; 1.7μm), with a gradient elution of ammonium formate buffer pH 4.0 and acetonitrile at a flow rate of 400μl/min. Detection was performed on a tandem quadrupole mass spectrometer (MS/MS) equipped with an electrospray ionization interface. A simple protein precipitation procedure with acetonitrile was used for sample preparation. Thanks to the use of stable isotope-labeled internal standards for all analytes, internal standard-normalized matrix effects were in the range of 92-108%. The method was fully validated to cover large concentration ranges of 0.2-90ng/ml for haloperidol, 0.5-90ng/ml for flupentixol, 1-450ng/ml for levomepromazine, promazine and zuclopenthixol and 2-900ng/ml for cis-chlorprothixene and pipamperone. Trueness (89.1-114.8%), repeatability (1.8-9.9%), intermediate precision (1.9-16.3%) and accuracy profiles (<30%) were in accordance with the latest international recommendations. The method was successfully used in our laboratory for routine quantification of more than 500 patient plasma samples for therapeutic drug monitoring. To the best of our knowledge, this is the first UHPLC-MS/MS method for the quantification of the studied drugs with a sample preparation based on protein precipitation.

Fast quantification of ten psychotropic drugs and metabolites in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.

A sensitive and selective ultra-high performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method was developed for the fast quantification of ten psychotropic drugs and metabolites in human plasma for the needs of our laboratory (amisulpride, asenapine, desmethyl-mirtazapine, iloperidone, mirtazapine, norquetiapine, olanzapine, paliperidone, quetiapine and risperidone). Stable isotope-labeled internal standards were used for all analytes, to compensate for the global method variability, including extraction and ionization variations. Sample preparation was performed by generic protein precipitation with acetonitrile. Chromatographic separation was achieved in less than 3.0min on an Acquity UPLC BEH Shield RP18 column (2.1mm×50mm; 1.7μm), using a gradient elution of 10mM ammonium formate buffer pH 3.0 and acetonitrile at a flow rate of 0.4ml/min. The compounds were quantified on a tandem quadrupole mass spectrometer operating in positive electrospray ionization mode, using multiple reaction monitoring. The method was fully validated according to the latest recommendations of international guidelines. Eight point calibration curves were used to cover a large concentration range 0.5-200ng/ml for asenapine, desmethyl-mirtazapine, iloperidone, mirtazapine, olanzapine, paliperidone and risperidone, and 1-1500ng/ml for amisulpride, norquetiapine and quetiapine. Good quantitative performances were achieved in terms of trueness (93.1-111.2%), repeatability (1.3-8.6%) and intermediate precision (1.8-11.5%). Internal standard-normalized matrix effects ranged between 95 and 105%, with a variability never exceeding 6%. The accuracy profiles (total error) were included in the acceptance limits of ±30% for biological samples. This method is therefore suitable for both therapeutic drug monitoring and pharmacokinetic studies.

Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods, [and] Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes

Rapport de synthèse1. Partie de laboratoireCette première étude décrit le développement et la validation, selon les standards internationaux, de deux techniques de mesure des concentrations sanguines de voriconazole, un nouvel agent antifongique à large spectre: 1) la chromatographic en phase liquide à haute pression et 2) le bio-essai utilisant une souche mutante de Candida hypersensible au voriconazole. Ce travail a aussi permis de mettre en évidence une importante et imprévisible variabilité inter- et intra-individuelle des concentrations sanguines de voriconazole malgré l'utilisation des doses recommandées par le fabriquant. Ce travail a été publié dans un journal avec "peer-review": "Variability of voriconazole plasma levels measured by new high- performance liquid chromatography and bioassay methods" by A. Pascual, V. Nieth, T. Calandra, J. Bille, S. Bolay, L.A. Decosterd, T. Buclin, P.A. Majcherczyk, D. Sanglard, 0. Marchetti. Antimicrobial Agents Chemotherapy, 2007; 51:137-432. Partie CliniqueCette deuxième étude a évalué de façon prospective l'impact clinique des concentrations sanguines de voriconazole sur l'efficacité et sécurité thérapeutique chez des patients atteints d'infections fongiques. Des concentrations sanguines élevées étaient significativement associés à la survenue d'une toxicité neurologique (encéphalopathie avec confusion, hallucinations et myoclonies) et des concentrations sanguines basses à une réponse insuffisante au traitement antifongique (persistance ou progression des signes cliniques et radiologiques de l'infection). Dans la majorité des cas, un ajustement de la dose de voriconazole, sur la base des concentrations mesurées, a abouti à une récupération neurologique complète ou à une résolution de l'infection, respectivement. Ce travail a été publié dans un journal avec "peer-review": " Voriconazole Therapeutic Drug Monitoring in Patients with Invasive Mycoses Improves Efficacy and Safety Outcomes" by A. Pascual, T. Calandra, S. Bolay, T. Buclin, J. Bille, and O. Marchetti. Clinical Infectious Diseases, 2008 January 15; 46(2): 201-11.Ces deux études, financées de façon conjointe par un "grant" international de la Société suisse d'infectiologie et la Société internationale de maladies infectieuses et par la Fondation pour le progrès en microbiologie médicale et maladies infectieuses (FAMMID, Lausanne), ont été réalisées au sein du Service des Maladies Infectieuses, Département de Médecine, au CHUV, en étroite collaboration avec la Division de Pharmacologie Clinique, Département de Médecine, au CHUV et l'Institut de Microbiologie du CHUV et de l'Université de Lausanne.

Monitoring bank performance in the presence of risk

This paper proposes a managerial control tool that integrates risk in efficiency scores. Building on existing efficiency specifications, our proposal reflects the real banking technology and accurately models the relationship between desirable and undesirable outputs. Specifically, the undesirable output is defined as non-performing loans to capture credit risk, and is linked only to the relevant dimension of the output set. We empirically illustrate how our efficiency measure functions for managerial control purposes. The application considers a unique dataset of Costa Rican banks during 1998-2012. Efficiency scores? implications are mostly discussed at bank-level, and their interpretations are enhanced by using accounting ratios. We also show the usefulness of our tool for corporate governance by examining performance changes around executive turnover. Results confirm that appointing CEOs from outside the bank significantly improves performance, thus suggesting the potential benefits of new organisational practices.

Practical Framework for Monitoring the Performance of Agile IT Projects in an Output-Based Outsourcing Context

Over the past decade, organizations worldwide have begun to widely adopt agile software development practices, which offer greater flexibility to frequently changing business requirements, better cost effectiveness due to minimization of waste, faster time-to-market, and closer collaboration between business and IT. At the same time, IT services are continuing to be increasingly outsourced to third parties providing the organizations with the ability to focus on their core capabilities as well as to take advantage of better demand scalability, access to specialized skills, and cost benefits. An output-based pricing model, where the customers pay directly for the functionality that was delivered rather than the effort spent, is quickly becoming a new trend in IT outsourcing allowing to transfer the risk away from the customer while at the same time offering much better incentives for the supplier to optimize processes and improve efficiency, and consequently producing a true win-win outcome. Despite the widespread adoption of both agile practices and output-based outsourcing, there is little formal research available on how the two can be effectively combined in practice. Moreover, little practical guidance exists on how companies can measure the performance of their agile projects, which are being delivered in an output-based outsourced environment. This research attempted to shed light on this issue by developing a practical project monitoring framework which may be readily applied by organizations to monitor the performance of agile projects in an output-based outsourcing context, thus taking advantage of the combined benefits of such an arrangement Modified from action research approach, this research was divided into two cycles, each consisting of the Identification, Analysis, Verification, and Conclusion phases. During Cycle 1, a list of six Key Performance Indicators (KPIs) was proposed and accepted by the professionals in the studied multinational organization, which formed the core of the proposed framework and answered the first research sub-question of what needs to be measured. In Cycle 2, a more in-depth analysis was provided for each of the suggested Key Performance Indicators including the techniques for capturing, calculating, and evaluating the information provided by each KPI. In the course of Cycle 2, the second research sub-question was answered, clarifying how the data for each KPI needed to be measured, interpreted, and acted upon. Consequently, after two incremental research cycles, the primary research question was answered describing the practical framework that may be used for monitoring the performance of agile IT projects delivered in an output-based outsourcing context. This framework was evaluated by the professionals within the context of the studied organization and received positive feedback across all four evaluation criteria set forth in this research, including the low overhead of data collection, high value of provided information, ease of understandability of the metric dashboard, and high generalizability of the proposed framework.

Comparative performance of two air samplers for monitoring airborne fungal propagules

Many studies have attempted to evaluate the importance of airborne fungi in the development of invasive fungal infection, especially for immunocompromised hosts. Several kinds of instruments are available to quantitate fungal propagule levels in air. We compared the performance of the most frequently used air sampler, the Andersen sampler with six stages, with a portable one, the Reuter centrifugal sampler (RCS). A total of 84 samples were analyzed, 42 with each sampler. Twenty-eight different fungal genera were identified in samples analyzed with the Andersen instrument. In samples obtained with the RCS only seven different fungal genera were identified. The three most frequently isolated genera in samples analyzed with both devices were Penicillium, Aspergillus and Cladophialophora. In areas supplied with a high efficiency particulate air filter, fungal spore levels were usually lower when compared to areas without these filters. There was a significant correlation between total fungal propagule measurements taken with both devices on each sampling occasion (Pearson coefficient = 0.50). However, the Andersen device recovered a broader spectrum of fungi. We conclude that the RCS can be used for quantitative estimates of airborne microbiological concentrations. For qualitative studies, however, this device cannot be recommended.

Monitoring growth of hard corals as performance indicators for coral reefs

Digital videophotography, computer image analysis and physical measurements have been used to monitor sedimentation rates, coral cover, genera richness, rugosity and estimated recruitment dates of massive corals at three different sites in the Wakatobi Marine National Park, Indonesia, and on the reefs around Discovery Bay, Jamaica. Semi-structured interviews with key stakeholders in the Wakatobi Marine National Park indicated that coral mining was extensively practised, and is responsible for the absence of large non-branching corals on the Sampela reef Blast fishing is also practised in the Wakatobi Marine Park, and the authors, together with students, showed that blast fishing resulted in coral bleaching and not mortality of two Porites lutea colonies. In addition, we showed that monitoring of bleaching in Porites colonies induced by blast fishing could be a useful way of monitoring blast fishing practices in susceptible areas in the Indo-Pacific. The techniques used in this study are appropriate for use by volunteers with sufficient training, and provide excellent projects for dissertation students reading undergraduate degrees.

Statistical monitoring of student performance: an early warning system

Weekly monitoring of profiles of student performances on formative and summative coursework throughout the year can be used to quickly identify those who need additional help, possibly due to acute and sudden-onset problems. Such an early-warning system can help retention, but also assist students in overcoming problems early on, thus helping them fulfil their potential in the long run. We have developed a simple approach for the automatic monitoring of student mark profiles for individual modules, which we intend to trial in the near future. Its ease of implementation means that it can be used for very large cohorts with little additional effort when marks are already collected and recorded on a spreadsheet.

Monitoring chronic physical stress using biomarkers, performance protocols and mathematical functions to identify physiological adaptations in rats

This study was undertaken to characterize the effects of monotonous training at lactate minimum (LM) intensity on aerobic and anaerobic performances; glycogen concentrationsin the soleus muscle, the gastrocnemius muscle and the liver; and creatine kinase (CK), free fatty acids and glucose concentrations in rats. The rats were separated into trained (n =10), baseline (n = 10) and sedentary (n=10) groups. The trained group was submitted to the following: 60 min/day, 6 day/week and intensity equivalent to LM during the 12-week training period. The training volume was reduced after four weeks according to a sigmoid function. The total CK (U/L) increased in the trained group after 12 weeks (742.0±158.5) in comparison with the baseline (319.6±40.2) and the sedentary (261.6+42.2) groups. Free fatty acids and glycogen stores (liver, soleus muscle and gastrocnemius muscle) increased after 12 weeks of monotonous training but aerobic and anaerobic performances were unchanged in relation to the sedentary group. The monotonous training at LM increased the level of energy substrates, unchanged aerobic performance, reduced anaerobic capacity and increased the serum CK concentration; however, the rats did not achieve the predicted training volume.

Performance of an electronic tongue during monitoring 2-rnethylisoborneol and geosmin in water samples

2-Methylisoborneol (MIB) and geosmin (GSM) are sub products from algae decomposition and, depending on their concentration, can be toxic: otherwise, they give unpleasant taste and odor to water. For water treatment companies it is important to constantly monitor their presence in the distributed water and avoid further costumer complaints. Lower-cost and easy-to-read instrumentation would be very promising in this regard. In this study, we evaluate the potentiality of an electronic tongue (ET) system based on non-specific polymeric sensors and impedance measurements in monitoring MIB and GSM in water samples. Principal component analysis (PCA) applied to the generated data matrix indicated that this ET was capable to perform with remarkable reproducibility the discrimination of these two contaminants in either distilled or tap water, in concentrations as low as 25 ng L-1. Nonetheless, this analysis methodology was rather qualitative and laborious, and the outputs it provided were greatly subjective. Also, data analysis based on PCA severely restricts automation of the measuring system or its use by non-specialized operators. To circumvent these drawbacks, a fuzzy controller was designed to quantitatively perform sample classification while providing outputs in simpler data charts. For instance, the ET along with the referred fuzzy controller performed with a 100% hit rate the quantification of MIB and GSM samples in distilled and tap water. The hit rate could be read directly from the plot. The lower cost of these polymeric sensors allied to the especial features of the fuzzy controller (easiness on programming and numerical outputs) provided initial requirements for developing an automated ET system to monitor odorant species in water production and distribution. (C) 2012 Elsevier B.V. All rights reserved.