Model-based control of neuromuscular block using mivacurium: design and clinical verification

BACKGROUND: Short-acting agents for neuromuscular block (NMB) require frequent dosing adjustments for individual patient's needs. In this study, we verified a new closed-loop controller for mivacurium dosing in clinical trials. METHODS: Fifteen patients were studied. T1% measured with electromyography was used as input signal for the model-based controller. After induction of propofol/opiate anaesthesia, stabilization of baseline electromyography signal was awaited and a bolus of 0.3 mg kg-1 mivacurium was then administered to facilitate endotracheal intubation. Closed-loop infusion was started thereafter, targeting a neuromuscular block of 90%. Setpoint deviation, the number of manual interventions and surgeon's complaints were recorded. Drug use and its variability between and within patients were evaluated. RESULTS: Median time of closed-loop control for the 11 patients included in the data processing was 135 [89-336] min (median [range]). Four patients had to be excluded because of sensor problems. Mean absolute deviation from setpoint was 1.8 +/- 0.9 T1%. Neither manual interventions nor complaints from the surgeons were recorded. Mean necessary mivacurium infusion rate was 7.0 +/- 2.2 microg kg-1 min-1. Intrapatient variability of mean infusion rates over 30-min interval showed high differences up to a factor of 1.8 between highest and lowest requirement in the same patient. CONCLUSIONS: Neuromuscular block can precisely be controlled with mivacurium using our model-based controller. The amount of mivacurium needed to maintain T1% at defined constant levels differed largely between and within patients. Closed-loop control seems therefore advantageous to automatically maintain neuromuscular block at constant levels.

Portfolio-optimization models for small investors

Since 2010, the client base of online-trading service providers has grown significantly. Such companies enable small investors to access the stock market at advantageous rates. Because small investors buy and sell stocks in moderate amounts, they should consider fixed transaction costs, integral transaction units, and dividends when selecting their portfolio. In this paper, we consider the small investor’s problem of investing capital in stocks in a way that maximizes the expected portfolio return and guarantees that the portfolio risk does not exceed a prescribed risk level. Portfolio-optimization models known from the literature are in general designed for institutional investors and do not consider the specific constraints of small investors. We therefore extend four well-known portfolio-optimization models to make them applicable for small investors. We consider one nonlinear model that uses variance as a risk measure and three linear models that use the mean absolute deviation from the portfolio return, the maximum loss, and the conditional value-at-risk as risk measures. We extend all models to consider piecewise-constant transaction costs, integral transaction units, and dividends. In an out-of-sample experiment based on Swiss stock-market data and the cost structure of the online-trading service provider Swissquote, we apply both the basic models and the extended models; the former represent the perspective of an institutional investor, and the latter the perspective of a small investor. The basic models compute portfolios that yield on average a slightly higher return than the portfolios computed with the extended models. However, all generated portfolios yield on average a higher return than the Swiss performance index. There are considerable differences between the four risk measures with respect to the mean realized portfolio return and the standard deviation of the realized portfolio return.

Portfolio-optimization models for small investors

Since 2010, the client base of online-trading service providers has grown significantly. Such companies enable small investors to access the stock market at advantageous rates. Because small investors buy and sell stocks in moderate amounts, they should consider fixed transaction costs, integral transaction units, and dividends when selecting their portfolio. In this paper, we consider the small investor’s problem of investing capital in stocks in a way that maximizes the expected portfolio return and guarantees that the portfolio risk does not exceed a prescribed risk level. Portfolio-optimization models known from the literature are in general designed for institutional investors and do not consider the specific constraints of small investors. We therefore extend four well-known portfolio-optimization models to make them applicable for small investors. We consider one nonlinear model that uses variance as a risk measure and three linear models that use the mean absolute deviation from the portfolio return, the maximum loss, and the conditional value-at-risk as risk measures. We extend all models to consider piecewise-constant transaction costs, integral transaction units, and dividends. In an out-of-sample experiment based on Swiss stock-market data and the cost structure of the online-trading service provider Swissquote, we apply both the basic models and the extended models; the former represent the perspective of an institutional investor, and the latter the perspective of a small investor. The basic models compute portfolios that yield on average a slightly higher return than the portfolios computed with the extended models. However, all generated portfolios yield on average a higher return than the Swiss performance index. There are considerable differences between the four risk measures with respect to the mean realized portfolio return and the standard deviation of the realized portfolio return.

Wavelet-denoising of electroencephalogram and the absolute slope method: a new tool to improve electroencephalographic localization and lateralization

OBJECTIVE: In ictal scalp electroencephalogram (EEG) the presence of artefacts and the wide ranging patterns of discharges are hurdles to good diagnostic accuracy. Quantitative EEG aids the lateralization and/or localization process of epileptiform activity. METHODS: Twelve patients achieving Engel Class I/IIa outcome following temporal lobe surgery (1 year) were selected with approximately 1-3 ictal EEGs analyzed/patient. The EEG signals were denoised with discrete wavelet transform (DWT), followed by computing the normalized absolute slopes and spatial interpolation of scalp topography associated to detection of local maxima. For localization, the region with the highest normalized absolute slopes at the time when epileptiform activities were registered (>2.5 times standard deviation) was designated as the region of onset. For lateralization, the cerebral hemisphere registering the first appearance of normalized absolute slopes >2.5 times the standard deviation was designated as the side of onset. As comparison, all the EEG episodes were reviewed by two neurologists blinded to clinical information to determine the localization and lateralization of seizure onset by visual analysis. RESULTS: 16/25 seizures (64%) were correctly localized by the visual method and 21/25 seizures (84%) by the quantitative EEG method. 12/25 seizures (48%) were correctly lateralized by the visual method and 23/25 seizures (92%) by the quantitative EEG method. The McNemar test showed p=0.15 for localization and p=0.0026 for lateralization when comparing the two methods. CONCLUSIONS: The quantitative EEG method yielded significantly more seizure episodes that were correctly lateralized and there was a trend towards more correctly localized seizures. SIGNIFICANCE: Coupling DWT with the absolute slope method helps clinicians achieve a better EEG diagnostic accuracy.

Right ventricular absolute myocardial blood flow in complex congenital heart disease

A consequence in patients with d-transposition of the great arteries (d-TGA) and tetralogy of Fallot (TOF) is right ventricular hypertrophy (RVH) and right ventricular failure. Myocardial contrast echocardiography (MCE) permits the determination of the myocardial microvascular density reflected by the relative myocardial blood volume (rBV; ml/ml). This study was conducted to elucidate the relationship between RVH and myocardial microvascular changes by quantitative MCE in patients with d-TGA and TOF.

Deviation from Murray's law is associated with a higher degree of calcification in coronary bifurcations

Murray's law describes the optimal branching anatomy of vascular bifurcations. If Murray's law is obeyed, shear stress is constant over the bifurcation. Associations between Murray's law and intravascular ultrasound (IVUS) assessed plaque composition near coronary bifurcations have not been investigated previously.

Absolute height-specific thresholds to identify elevated blood pressure in children

Identification of children with elevated blood pressure (BP) is difficult because of the multiple sex, age, and height-specific thresholds to define elevated BP. We propose a simple set of absolute height-specific BP thresholds and evaluate their performance to identify children with elevated BP in two different populations.