Quantification and stability of everolimus (SDZ RAD) in human blood by high-performance liquid chromatography-electrospray tandem mass spectrometry

We report here a validated method for the quantification of a new immunosuppressant drug, everolimus (SDZ RAD), using HPLC-tandem mass spectrometry. Whole blood samples (500 mul) were prepared by protein precipitation, followed by C-18 solid-phase extraction. Mass spectrometric detection was by selected reaction monitoring with an electrospray interface operating in positive ionization mode. The assay was linear from 0.5 to 100 mug/l (r(2) > 0.996, n = 9). The analytical recovery and inter-day imprecision, determined using whole blood quality control samples (n = 5) at 0.5, 1.2, 20.0, and 75.0 mug/l, was 100.3-105.4% and less than or equal to7.6%, respectively. The assay had a mean relative recovery of 94.8 +/- 3.8%. Extracted samples were stable for up to 24 h. Fortified everolimus blood samples were stable at -80 degreesC for at least 8 months and everolimus was found to be stable in blood when taken through at least three freeze-thaw cycles. The reported method provides accurate, precise and specific measurement of everolimus in blood over a wide analytical range and is currently supporting phase 11 and III clinical trials. (C) 2002 Elsevier Science B.V. All rights reserved.

Design of microchannel free-space optical interconnects based on vertical-cavity surface-emitting laser arrays

We investigate the design of free-space optical interconnects (FSOIs) based on arrays of vertical-cavity surface-emitting lasers (VCSELs), microlenses, and photodetectors. We explain the effect of the modal structure of a multimodeVCSEL beam on the performance of a FSOI with microchannel architecture. A Gaussian-beam diffraction model is used in combination with the experimentally obtained spectrally resolved VCSEL beam profiles to determine the optical channel crosstalk and the signal-to-noise ratio (SNR) in the system. The dependence of the SNR on the feature parameters of a FSOI is investigated. We found that the presence of higher-order modes reduces the SNR and the maximum feasible interconnect distance. We also found that the positioning of a VCSEL array relative to the transmitter microlens has a significant impact on the SNR and the maximum feasible interconnect distance. Our analysis shows that the departure from the traditional confocal system yields several advantages including the extended interconnect distance and/or improved SNR. The results show that FSOIs based on multimode VCSELs can be efficiently utilized in both chip-level and board-level interconnects. (C) 2002 Optical Society of America.

Enhanced optical properties of the GaAsN/GaAs quantum-well structure by the insertion of InAs monolayers

Microstructural and optical properties of InAs-inserted and reference single GaAsN/GaAs quantum-well (QW) structures grown by metalorganic chemical vapor deposition were investigated using cross-sectional transmission electron microscopy and photoluminescence (PL). Significant enhancement of PL intensity and a blueshift of PL emission were observed from the InAs-inserted GaAsN/GaAs QW structure, compared with the single GaAsN/GaAs QW structure. Strain compensation and In-induced reduction of N incorporation are suggested to be two major factors affecting the optical properties. (C) 2004 American Institute of Physics.

Accuracy of SRM and power tap power monitoring systems for bicycling

Purpose: Although manufacturers of bicycle power monitoring devices SRM and Power Tap (PT) claim accuracy to within 2.5%, there are limited scientific data available in support. The purpose of this investigation was to assess the accuracy of SRM and PT under different conditions. Methods: First, 19 SRM were calibrated, raced for 11 months, and retested using a dynamic CALRIG (50-1000 W at 100 rpm). Second, using the same procedure, five PT were repeat tested on alternate days. Third, the most accurate SRM and PT were tested for the influence of cadence (60, 80, 100, 120 rpm), temperature (8 and 21degreesC) and time (1 h at similar to300 W) on accuracy. Finally, the same SRM and PT were downloaded and compared after random cadence and gear surges using the CALRIG and on a training ride. Results: The mean error scores for SRM and PT factory calibration over a range of 50-1000 W were 2.3 +/- 4.9% and -2.5 +/- 0.5%, respectively. A second set of trials provided stable results for 15 calibrated SRM after 11 months (-0.8 +/- 1.7%), and follow-up testing of all PT units confirmed these findings (-2.7 +/- 0.1%). Accuracy for SRM and PT was not largely influenced by time and cadence; however. power output readings were noticeably influenced by temperature (5.2% for SRM and 8.4% for PT). During field trials, SRM average and max power were 4.8% and 7.3% lower, respectively, compared with PT. Conclusions: When operated according to manufacturers instructions, both SRM and PT offer the coach, athlete, and sport scientist the ability to accurately monitor power output in the lab and the field. Calibration procedures matching performance tests (duration, power, cadence, and temperature) are, however, advised as the error associated with each unit may vary.

The measurement of nicotine in human plasma by high-performance liquid chromatography-electrospray-tandem mass spectrometry

The authors describe a reverse-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry method for the measurement of nicotine in human plasma. Samples (500 muL) with added deuterium-labeled d(3)-nicotine as an internal standard (IS) were treated with a 2-step process of ether extraction (6 mL) followed by back-extraction into 0.1% formic acid (50 muL). Chromatography was performed on a phenyl Novapak column with a mobile phase consisting of 50% 10 mM ammonium fortriate (pH 3.3) and acetonitrile (50:50, vol/vol). A flow rate of 0.2 mL/min resulted in a total analysis time of 5 minutes per sample. Mass spectrometric detection was by selected reactant monitoring (nicotine m/z 163.2 --> 130.2; IS m/z 166.2 --> 87.2). The assay was linear from 0.5 to 100 mug/L (r > 0.993, n = 9). The accuracy and imprecision of the method for quality control sampleswere 87.5% to 113% and < 10.2%, respectively. Interday accuracy and imprecision at the limit of quantification (0.5 mug/L) was 113% and 7.2% (n = 4). The process efficiency for nicotine in plasma was > 75%. The method described has good process efficiency, stabilized nicotine, avoided concentration steps, and most importantly minimized potential contamination. Further, we have established that water-based standards and controls are interchangeable with plasma-based samples. This method was used successfully to measure the pharmacokinetic profiles of subjects involved in the development of an aerosol inhalation drug delivery system.

Sampling times for monitoring tacrolimus in stable adult liver transplant recipients

The aim of this study was to determine the most informative sampling time(s) providing a precise prediction of tacrolimus area under the concentration-time curve (AUC). Fifty-four concentration-time profiles of tacrolimus from 31 adult liver transplant recipients were analyzed. Each profile contained 5 tacrolimus whole-blood concentrations (predose and 1, 2, 4, and 6 or 8 hours postdose), measured using liquid chromatography-tandem mass spectrometry. The concentration at 6 hours was interpolated for each profile, and 54 values of AUC(0-6) were calculated using the trapezoidal rule. The best sampling times were then determined using limited sampling strategies and sensitivity analysis. Linear mixed-effects modeling was performed to estimate regression coefficients of equations incorporating each concentration-time point (C0, C1, C2, C4, interpolated C5, and interpolated C6) as a predictor of AUC(0-6). Predictive performance was evaluated by assessment of the mean error (ME) and root mean square error (RMSE). Limited sampling strategy (LSS) equations with C2, C4, and C5 provided similar results for prediction of AUC(0-6) (R-2 = 0.869, 0.844, and 0.832, respectively). These 3 time points were superior to C0 in the prediction of AUC. The ME was similar for all time points; the RMSE was smallest for C2, C4, and C5. The highest sensitivity index was determined to be 4.9 hours postdose at steady state, suggesting that this time point provides the most information about the AUC(0-12). The results from limited sampling strategies and sensitivity analysis supported the use of a single blood sample at 5 hours postdose as a predictor of both AUC(0-6) and AUC(0-12). A jackknife procedure was used to evaluate the predictive performance of the model, and this demonstrated that collecting a sample at 5 hours after dosing could be considered as the optimal sampling time for predicting AUC(0-6).

Water quality monitoring: A combined approach to investigate gradients of change in the Great Barrier Reef, Australia

For the managers of a region as large as the Great Barrier Reef, it is a challenge to develop a cost effective monitoring program, with appropriate temporal and spatial resolution to detect changes in water quality. The current study compares water quality data (phytoplankton abundance and water clarity) from remote sensing with field sampling (continuous underway profiles of water quality and fixed site sampling) at different spatial scales in the Great Barrier Reef north of Mackay (20 degrees S). Five transects (20-30 km long) were conducted from clean oceanic water to the turbid waters adjacent to the mainland. The different data sources demonstrated high correlations when compared on a similar spatial scale (18 fixed sites). However, each data source also contributed unique information that could not be obtained by the other techniques. A combination of remote sensing, underway sampling and fixed stations will deliver the best spatial and temporal monitoring of water quality in the Great Barrier Reef. (c) 2004 Elsevier Ltd. All rights reserved.

A rapid HPLC-mass spectrometry cyclosporin method suitable for current monitoring practices

Objectives: Cyclosporin is an immunosuppressant drug with a narrow therapeutic window. Trough and 2-h post-dose blood samples are currently used for therapeutic drug monitoring in solid organ transplant recipients. The aim of the current study was to develop a rapid HPLC-tandem mass spectrometry (HPLC-MS) method for the measurement of cyclosporin in whole blood that was not only suitable for the clinical setting but also considered a reference method. Methods: Blood samples (50 mu L) were prepared by protein precipitation followed by C-18 solid-phase extraction while using d(12) cyclosporin as the internal standard. Mass spectrometric detection was by selected reaction monitoring with an electrospray interface in positive ionization mode. Results: The assay was linear from 10 to 2000 mu g/L (r(2) > 0.996, n = 9). Inter-day,analytical recovery and imprecision using whole blood quality control samples at 10, 30, 400, 1500, and 2000 mu g/L were 94.9-103.5% and

The effects of ambient music on simulated anaesthesia monitoring

We examined the effect of no music, classical music or rock music on simulated patient monitoring. Twenty-four non-anaesthetist participants with high or low levels of musical training were trained to monitor visual and auditory displays of patients' vital signs. In nine anaesthesia test scenarios, participants were asked every 50-70 s whether one of five vital signs was abnormal and the trend of its direction. Abnormality judgements were unaffected by music or musical training. Trend judgements were more accurate when music was playing (p = 0.0004). Musical participants reported trends more accurately (p = 0.004), and non-musical participants tended to benefit more from music than did the musical participants (p = 0.063). Music may provide a pitch and rhythm standard from which participants can judge changes in vital signs from auditory displays. Nonetheless, both groups reported that it was easier to monitor the patient with no music (p = 0.0001), and easier to rely upon the auditory displays with no music (p = 0.014).

Advanced patient monitoring displays: Tools or continuous informing

We reviewed the use of advanced display technologies for monitoring in anesthesia. Researchers are investigating displays that integrate information and that, in some cases, also deliver the results continuously to the anesthesiologist. Integrated visual displays reveal higher-order properties of patient state and speed in responding to events, but their benefits under an intensely timeshared load is unknown. Head-mounted displays seem to shorten the time to respond to changes, but their impact on peripheral awareness and attention is unknown. Continuous auditory displays extending pulse oximetry seem to shorten response times and improve the ability to time-share other tasks, but their integration into the already noisy operative environment still needs to be tested. We reviewed the advantages and disadvantages of the three approaches, drawing on findings from other fields, such as aviation, to suggest outcomes where there are still no results for the anesthesia context. Proving that advanced patient monitoring displays improve patient outcomes is difficult, and a more realistic goal is probably to prove that such displays lead to better situational awareness, earlier responding, and less workload, all of which keep anesthesia practice away from the outer boundaries of safe operation.

Image reconstruction in full-field Fourier-domain optical coherence tomography

Full-field Fourier-domain optical coherence tomography (3F-OCT) is a full-field version of spectral domain/swept source optical coherence tomography. A set of two-dimensional Fourier holograms is recorded at discrete wavenumbers spanning the swept source tuning range. The resultant three-dimensional data cube contains comprehensive information on the three-dimensional spatial properties of the sample, including its morphological layout and optical scatter. The morphological layout can be reconstructed in software via three-dimensional discrete Fourier transformation. The spatial resolution of the 3F-OCT reconstructed image, however, is degraded due to the presence of a phase cross-term, whose origin and effects are addressed in this paper. We present a theoretical and experimental study of the imaging performance of 3F-OCT, with particular emphasis on elimination of the deleterious effects of the phase cross-term.

Field evaluation of passive samplers: Monitoring polycyclic aromatic hydrocarbons (PAHs) in stormwater

The aim of this study was to evaluate the feasibility of using semipermeable membrane devices (SPMDs) and polyethylene-based passive sampler devices (PSDs) for monitoring PAHs in stormwater. Firstly, SPMDs were deployed at one site and SPMD-derived water concentrations were compared with water concentration measured from grab samples. In a subsequent deployment the performance of SPMDs and PSDs was compared. Finally PSDs of multiple surface area to volume ratios were used to compare PAH concentrations at the two sites. The results obtained in this study show that SPMDs can be used to measure the water concentration of PAHs with reasonable accuracy, when compared with grab samples collected at the same site. Importantly, several PAHs which could not be detected in a 10 L grab sample could be detected in the SPMDs. PSD and SPMD samplers produced similar results when deployed at the same site, with most estimated water concentrations within a factor of 1.5. The use of PSDs in multiple surface area to volume ratios proved to be an effective means of characterizing the uptake kinetics for PAHs in situ. Overall passive water samplers proved to be an efficient technique for monitoring PAHs in stormwater.

The multimodal world of medical monitoring displays

A vision of the future of intraoperative monitoring for anesthesia is presented-a multimodal world based on advanced sensing capabilities. I explore progress towards this vision, outlining the general nature of the anesthetist's monitoring task and the dangers of attentional capture. Research in attention indicates different kinds of attentional control, such as endogenous and exogenous orienting, which are critical to how awareness of patient state is maintained, but which may work differently across different modalities. Four kinds of medical monitoring displays are surveyed: (1) integrated visual displays, (2) head-mounted displays, (3) advanced auditory displays and (4) auditory alarms. Achievements and challenges in each area are outlined. In future research, we should focus more clearly on identifying anesthetists' information needs and we should develop models of attention in different modalities and across different modalities that are more capable of guiding design. (c) 2006 Elsevier Ltd. All rights reserved.