Drift Compensation of the Electronic Nose in the Development of Instruments for Out-of-Laboratory Analysis

A technique was developed to evaluate and compensate for the drift of eight mass-sensitive sensors in an open detection cell in order to estimate the influence of external factors (temperature, changes in the chemical composition of the background) on the out-of-laboratory analysis of biosamples. The daily internal standardization of the system is an effective way to compensate for the sensor signal drift when the sorption properties of sensitive coatings change during their long-term, intensive operation. In this study, distilled water was proposed as a standard for water matrix-based biosamples (blood, exhaled breath condensate, urine, etc.). Further, internal standardization was based on daily calculation of the specific sensor signals by dividing the sensor signals for the biosample according to the corresponding averaged values obtained from three to five standard measurements. The stability of the sensor array operation was estimated using the theory of statistical process control (exponentially weighted moving average control charts) based on the specific signal of the sensor array. The control limits for the statistical quantity of the central tendency for each sensor and the whole array, as well as the variations of the sensor signals, were determined. The average times required for signal and run lengths, for the purpose of statistically substantiated monitoring of the electronic nose’s stability, were calculated. Based on an analysis of the tendency and variations in sensor signals during 3 months of operation, a technique was formulated to control the stability of the sensor array for the out-of-laboratory analysis of the biosamples. This approach was successfully verified by classifying the results of the analysis of the blood and water samples obtained for this period. The proposed technique can be introduced into the software algorithm of the electronic nose, which will improve decision-making during the long-term monitoring of health conditions in humans and animals.

Validated Simple HPLC-UV Method for Mycophenolic Acid (MPA) Monitoring in Human Plasma. Internal Standardization: Is It Necessary?

The aim of the work was to prepare a simple but reliable HPLC-UV method for the routine monitoring of mycophenolic acid (MPA). Sample preparation was based on plasma protein precipitation with acetonitrile. The isocratic separation of MPA and internal standard (IS) fenbufen was made on Supelcosil LC-CN column (150 × 4.6 mm, 5 µm) using a mobile phase: CH3CN:H2O:0.5M KH2PO4:H3PO4 (260:700:40:0.4, v/v). UV detection was set at 305 nm. The calibration covered the MPA concentration range: 0.1–40 µg/mL. The precision was satisfactory with RSD of 0.97–7.06% for intra-assay and of 1.92–5.15% for inter-assay. The inaccuracy was found between −5.72% and +2.96% (+15.40% at LLOQ) and between −8.82% and +5.31% (+19.00% at LLOQ) for intra- and inter-assay, respectively, fulfilling acceptance criteria. After a two-year period of successful application, the presented method has been retrospectively calibrated using the raw data disregarding the IS in the calculations. The validation and stability parameters were similar for both calculation methods. MPA concentrations were recalculated and compared in 1187 consecutive routine therapeutic drug monitoring (TDM) trough plasma samples from mycophenolate-treated patients. A high agreement (r2 = 0.9931, p < 0.0001) of the results was found. A Bland–Altman test revealed a mean bias of −0.011 μg/mL (95% CI: −0.017; −0.005) comprising −0.14% (95% Cl: −0.39; +0.11), whereas the Passing–Bablok regression was y = 0.986x + 0.014. The presented method can be recommended as an attractive analytical tool for medical (hospital) laboratories equipped with solely basic HPLC apparatus. The procedure can be further simplified by disapplying an internal standard while maintaining appropriate precision and accuracy of measurements.

A simple isotope-labeled UHPLC–MS/MS assay for simultaneous quantification of methotrexate, imatinib and dasatinib

Aim: To assist therapeutic dose adjustment in clinic, a reliable concentration measurement is quite necessary for therapeutic drug monitoring. Results: A UHPLC–MS/MS bioassay for simultaneous determination of methotrexate, imatinib and dasatinib using isotope dilution internal standardization has been established and fully validated as per China Food and Drug Administration guideline. After a simple protein precipitation, the analytes were separated by a gradient elution within 3 min and mass detection was performed via ESI+ mode with SRM. The calibration curves were in the range of 5–100 ng/ml for methotrexate, 25–5000 ng/ml for imatinib and 1–250 ng/ml for dasatinib. Imprecision and inaccuracy values were ≤9.44% and ≤12.81% for all analytes, respectively. Conclusion: The developed method is appropriate for therapeutic drug monitoring, being applied to help individualized therapy in patients with acute lymphoblastic leukemia.

Can we trust the standardized mortality ratio? A formal analysis and evaluation based on axiomatic requirements

Background The standardized mortality ratio (SMR) is often used to assess and compare hospital performance. While it has been recognized that hospitals may differ in their SMRs due to differences in patient composition, there is a lack of rigorous analysis of this and other—largely unrecognized—properties of the SMR. Methods This paper proposes five axiomatic requirements for adequate standardized mortality measures: strict monotonicity (monotone relation to actual mortality rates), case-mix insensitivity (independence of patient composition), scale insensitivity (independence of hospital size), equivalence principle (equal rating of hospitals with equal actual mortality rates in all patient groups), and dominance principle (better rating of unambiguously better performing hospitals). Given these axiomatic requirements, effects of variations in patient composition, hospital size, and actual and expected mortality rates on the SMR were examined using basic algebra and calculus. In this regard, we distinguished between standardization using expected mortality rates derived from a different dataset (external standardization) and standardization based on a dataset including the considered hospitals (internal standardization). The results were illustrated by hypothetical examples. Results Under external standardization, the SMR fulfills the axiomatic requirements of strict monotonicity and scale insensitivity but violates the requirement of case-mix insensitivity, the equivalence principle, and the dominance principle. All axiomatic requirements not fulfilled under external standardization are also not fulfilled under internal standardization. In addition, the SMR under internal standardization is scale sensitive and violates the axiomatic requirement of strict monotonicity. Conclusions The SMR fulfills only two (none) out of the five proposed axiomatic requirements under external (internal) standardization. Generally, the SMRs of hospitals are differently affected by variations in case mix and actual and expected mortality rates unless the hospitals are identical in these characteristics. These properties hamper valid assessment and comparison of hospital performance based on the SMR.

Flow injection of slurries of a lithium borate fusion disc for multi-elemental analysis by mixed-gas inductively coupled plasma mass spectrometry

Slurry nebulization, a mixed-gas plasma and external calibration with internal standardization allow the accurate analysis of fused samples by ICPMS.

Meanders of the Polish Military Revolution — Standardization of Cavalry Units

The objective of the article is to show the phenomenon of the internal standardization of the units of the Polish cavalry in the 16th century. The references to this process, during which the diversisty of arms and equipment of soldiers was abandoned, are scarce in descriptive sources and are only reflected in normative acts. The only type of sources which enables to reconstruct the combat potential of units is inspection (rejestry popisowe). Consequently, the process of specialization of units and of formation of different types of cavalry was basically marginalized. In the Crown, as late as the 1530s, cavalry rotas were very diverse. They consisted of lancers, Polish winged hussars (later: hussars) and light cavalry combined in various proportions. This state of affairs is connected with three factors. Firstly, the units of Permanent Defense (obrona potoczna) in their structure referred to Mass Mobilization (pospolite ruszenie). Secondly, provisions of law were not used for standardizing the arms and armor; on the contrary, at least by the 1530s they stimulated the internal diversification. Thirdly, the Crown professional units were internally divided into towarzyszes and pocztowys, which prompted the diversification of armament inside a unit. The text shows the changes which occurred in the 1540s and 1550s, and brought about a situation in 1557, when the rate of standardization was as high as 82.93 %. The transformations were dynamic but were not top-down planned reforms, representing instead a bottom-up initiative of rotmistrzes.