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Identification of EEG patterns occurring in anesthesia by means of autoregressive parameters.

In EEG analysis an automatic pattern recognition is of interest. In this paper the usefulness of autoregressive parameters to classify EEG segments recorded during anesthesia is examined. Assuming that the AR parameters are multivariate normally distributed, parametric methods of discriminant analysis can be applied. The results show that AR parameters have high discriminating power and that the lowest error classification rate (smaller than 3%) is obtained by using quadratic discriminant functions. Consequently autoregressive parameters are efficient for classifying EEG segments into general stages of anesthesia.

Adult↗

Delay of intracortical bone remodelling following a stress change: a theoretical and experimental study.

BACKGROUND: A theoretical model and an experimental setup were specifically designed to identify and determine the delay of the cortical bone response (restricted to mineralization and demineralization) to a stress change. METHODS: The in vivo experiment considered two groups of rats: a running group and a control sedentary group. The running group rats were compelled to a running activity for 15 weeks, followed by a sedentary activity for 15 weeks. Bone density was derived from hardness measurements. The parameters of the remodelling theory, including the response delay and the remodelling rates, were determined from these experimental measurements. FINDINGS: Bone density increased significantly during the activity period, and decreased rapidly when rats returned to sedentary state. The identification of the model's parameters produced evolution curves that were within the limits of the standard deviation of the experimental data. The densification rate was lower than the resorption rate, and the densification delay was greater than bone resorption delay. INTERPRETATION: The delays determined with this macroscopic model are related to response delays due to biological internal processes in bone.

Adaptation, Physiological↗

Increased predictive value of parameters by fuzzy logic-based multiparameter analysis.

BACKGROUND: A recent study on postoperative effusions and edema was used to demonstrate the potential of fuzzy techniques in multiparameter data analysis. In this study, more than 50 parameters of 75 patients were collected and examined for correlations between some of the parameters and the later development of complications. METHODS: We employed a rule-based fuzzy-logic system in order to combine the diagnostic values of single parameters. The advantage of fuzzy sets is that they substitute sharp cut-off values with a smooth transition from one property to another. Therefore, there is no decision of "either-or" but rather a graded assessment of "more or less", which is often more suitable for a problem. RESULTS: The fuzzy combination of parameters led to a large increase of sensitivity and specificity when compared with the best single parameter. This increase was achieved by taking a close look at the parameters. A newly created parameter, relative weight, turned out to be very powerful. CONCLUSIONS: Fuzzy techniques can increase the discriminating power of classical statistical tools. In addition, results obtained by fuzzy analysis are highly interpretable. A combination of the CLASSIF1 algorithm for the identification of the most relevant parameters, followed by fuzzy analysis, represents a powerful tool for the handling of large amounts of multiparameter data.

Adolescent↗

Modeling aerobic carbon source degradation processes using titrimetric data and combined respirometric-titrimetric data: structural and practical identifiability.

The structural and practical identifiability of a model for description of respirometric-titrimetric data derived from aerobic batch substrate degradation experiments of a C(x)H(y)O(z) carbon source with activated sludge was evaluated. The model processes needed to describe titrimetric data included substrate uptake, CO(2) production, and NH(3) uptake for biomass growth. The structural identifiability was studied using the Taylor series method and a recently proposed generalization method. It showed that combining respirometric and titrimetric data allows structural identifiability of one extra parameter combination, the biomass yield, Y(H), compared to estimation on separate data sets, on condition that the nitrogen fraction in biomass (i(XB)) is known. However, data from short-term batch substrate degradation experiments were not sufficiently informative to allow practical identification of all structurally identifiable parameters. Combining respirometry and titrimetry resulted in improvements of parameter confidence intervals compared to estimation on separate respirometric or titrimetric data sets. However, the level of the improvement seems to be substrate dependent: parameter confidence intervals improved considerably more for dextrose than for acetate degradation models. Noteworthy is the finding that the half-saturation substrate concentrations can be different depending on whether they are estimated from respirometric or titrimetric data. Moreover, this difference appears to be dependent on the carbon source considered: for dextrose, titrimetry-based K(S) values are higher than respirometry-based values while for acetate the opposite was found. It was hypothesized that this can be explained by the different point in cell metabolism where the proton production or consumption takes place, leading to a corresponding difference in timing between pH effect and oxygen consumption. Finally, the biomass yield Y(H) and the nitrogen content of the biomass i(XB) could be estimated from combined respirometric-titrimetric data obtained with addition of a known amount of carbon source. Y(H) can also be estimated from r(O) data when the initial substrate concentration S(S)(0) is known. The values found correspond to values reported in literature, but, interestingly, also seem able to reflect the occurrence of storage processes when pulses of acetate and dextrose are added.

Acetates↗

On identification of Na(+) channel gating schemes using moving-average filtered hidden Markov models.

Transitions between distinct kinetic states of an ion channel are described by a Markov process. Hidden Markov models (HMM) have been successfully applied in the analysis of single ion channel recordings with a small signal-to-noise ratio. However, we have recently shown that the anti-aliasing low-pass filter misleads parameter estimation. Here, we show for the case of a Na(+) channel recording that the standard HMM do neither allow parameter estimation nor a correct identification of the gating scheme. In particular, the number of closed and open states is determined incorrectly, whereas a modified HMM considering the anti-aliasing filter (moving-average filtered HMM) is able to reproduce the characteristic properties of the time series and to perform gating scheme identification.

Cell Line↗

Optimal identification of biochemical reaction networks.

Advances in biotechnology and computer science are providing the possibility to construct mathematical models for complex biological networks and systematically understand their properties. Traditional network identification approaches, however, cannot accurately recover the model parameters from the noisy laboratory measurements. This article introduces the concept of optimal identification (OI), which utilizes a global inversion algorithm to extract the full distribution of parameters consistent with the laboratory data. In addition, OI integrates suitable computational algorithms with experimental capabilities in a closed loop fashion to maximally reduce the breadth of the extracted parameter distribution. The closed loop OI procedure seeks out the optimal set of control chemical fluxes and data observations that actively filter out experimental noise and enhance the sensitivity to the desired parameters. In this fashion, the highest quality network parameters can be attained from inverting the tailored laboratory data. The operation of OI is illustrated by identifying a simulated tRNA proofreading mechanism, in which OI provides superior solutions for all the rate constants compared with suboptimal and nonoptimal methods.

Algorithms↗

Recovery kinetics of oxygen uptake after cardiopulmonary exercise test and prognosis in patients with left ventricular dysfunction.

INTRODUCTION: The prognostic value of peak oxygen uptake (peak VO2) in patients with left ventricular systolic dysfunction is currently recognized and accepted. Some studies have shown that other cardiopulmonary exercise test (CPET) parameters have additional value. OBJECTIVES: To evaluate whether our population of patients with left ventricular dysfunction had similar results to those found by other investigators who showed that a slow normalization of oxygen uptake (VO2) during the recovery period of a CPET has prognostic value, and whether the recovery phase parameters have additional prognostic value to peak VO2 in these patients. METHODS: We studied 292 consecutive adult patients (81.5% male; mean age 52.4 +/- 10.6 years) with an ejection fraction below 40% (mean 23.6 +/- 8.8%) given their first symptom-limited CPET between 03/1993 and 08/2000. The etiology was ischemic heart disease in 154, idiopathic cardiomyopathy in 130 and other in 8 patients. NYHA class was I in 7%, II in 50.6% and III in 42.4% of the patients. Two years was defined as the maximum follow-up time; it was 551.5 +/- 242.2 days on average, and 62 events (death or cardiac transplantation) occurred. The following parameters were analyzed: peak VO2 (l/min and ml/kg/min), percent predicted peak VO2 (pred VO2) (l/min and ml/kg/min), VO2 every 15 seconds (sec) of the first 3 minutes of recovery (the difference between peak VO2/kg and VO2/kg every 15 sec in the recovery period (dif VO2), expressed in ml/kg/min, and also the time (sec) to reach 50% of peak VO2 (T1/2). It was considered that a combined end-point was reached if patients died or underwent cardiac transplantation. RESULTS: ROC curves of these parameters showed the following as cut-off values (area under the curve > 0.7) for the occurrence of events: peak VO2 < 60% of pred VO2, dif VO2 at 60 sec (< 3 ml/kg/min), 90 sec (< 5), 120 sec (< 8), 150 sec (< 8.6) and 180 sec (< 10.5) of the recovery and T1/2 > 115 sec. Survival analysis was performed considering pred VO2 < 60%, dif VO2 at 150 sec (the largest area under the curve) and T1/2 > 115 sec. In the survival analysis, when the decrease in VO2 at 150 sec was less than 8.6 ml/kg/min the number of patients with events increased from 9.2% to 43.5% (p < 0.001; log-rank), and when T1/2 was less than 115 sec the number of events increased from 12.3 to 34.2% (p < 0.001; log-rank). When the criteria of T1/2 and dif VO2 at 150 sec were considered together with pred VO2 < 60%, mortality increased from 31 to 54% and from 33 to 51%, respectively (p < 0.001, for both parameters; chi-square). CONCLUSIONS: A slow VO2 kinetics in the recovery period of the CPET by itself identified groups of patients with poor prognosis. The association of these parameters with peak VO2 enhanced the identification of groups at greater risk for events. A global evaluation of the CPET should be performed, considering other parameters besides peak VO2, particularly those related to VO2 kinetics in recovery (T1/2 and dif VO2 at 150 sec) as identified in this study.

Adolescent↗

Can a pairwise contact potential stabilize native protein folds against decoys obtained by threading?

We present a method to derive contact energy parameters from large sets of proteins. The basic requirement on which our method is based is that for each protein in the database the native contact map has lower energy than all its decoy conformations that are obtained by threading. Only when this condition is satisfied one can use the proposed energy function for fold identification. Such a set of parameters can be found (by perceptron learning) if Mp, the number of proteins in the database, is not too large. Other aspects that influence the existence of such a solution are the exact definition of contact and the value of the critical distance Rc, below which two residues are considered to be in contact. Another important novel feature of our approach is its ability to determine whether an energy function of some suitable proposed form can or cannot be parameterized in a way that satisfies our basic requirement. As a demonstration of this, we determine the region in the (Rc, Mp) plane in which the problem is solvable, i.e., we can find a set of contact parameters that stabilize simultaneously all the native conformations. We show that for large enough databases the contact approximation to the energy cannot stabilize all the native folds even against the decoys obtained by gapless threading.

Algorithms↗

Objective identification of hyperactivated human spermatozoa by computerized sperm motion analysis with the Hamilton-Thorn sperm motility analyser.

Sperm from 10 fertile donors were incubated for 8 h in a capacitating medium (BWW 3.5% HSA) and treated with 1.25 microliters of 2 mM Ca-ionophore solution. Sperm motion was analysed using the Hamilton-Thorn system before and after incubation and treatment. The acrosome reaction was detected with PSA-FITC labelling of the acrosome. Critical values of sperm movement parameters were defined for objective identification of hyperactive movement by the Hamilton-Thorn system. The incidence of hyperactive movement in the sperm suspensions was approximately 2%. No significant changes of hyperactive movement could be observed after the incubation period or the ionophore treatment, in contrast to a significant rise in the percentage of acrosome-reacted cells after ionophore treatment. The implications of these findings for monitoring hyperactive cells to test sperm function are discussed.

Acrosome↗

Discrimination of anesthetic states using mid-latency auditory evoked potential and artificial neural networks.

This study was undertaken to determine whether artificial neural network (ANN) processing of mid-latency auditory evoked potentials (MLAEPs) can identify different anesthetic states during propofol anesthesia, and to determine those parameters that are most useful in the identification process. Twenty-one patients undergoing elective abdominal surgery were studied. To maintain general anesthesia, the patients received propofol (3-5 mgkg(-1) h(-1) intravenously). Epidural analgesia at the level of T4-5 blocked painful stimuli. MLAEP was recorded continuously with patients awake, during induction, during maintenance of general anesthesia, and during emergence until the patients were recovered from anesthesia. Latencies of the 5 MLAEP peaks and three peak to peak amplitudes were measured, along with hemodynamic parameters (heart rate, systolic, and diastolic arterial blood pressure). Four-layer ANNs were used to model the relationship between the parameters of the MLAEP and the four different states (awake, adequate anesthesia, during/before intraoperative movement, and emergence from anesthesia). The best identification accuracy was obtained using only the five latencies. The combination of five latencies and three amplitudes did not improve the identification accuracy. Use of the only the three hemodynamic parameters produced a much poorer identification. This study suggests that the MLAEP has useful information for identifying different anesthetic states, especially in its latencies. A nonlinear discrimination approach, such as the ANN, can effectively capture the relation between the MLAEP patterns and the different states of anesthesia.

Anesthesia↗

Vascular architecture and microenvironmental parameters in human squamous cell carcinoma xenografts: effects of carbogen and nicotinamide.

BACKGROUND AND PURPOSE: A better understanding of the vascular architecture and the microenvironmental parameters (VAMP) will allow the identification of tumours that can be more effectively treated by intensified fractionated radiotherapy or modifiers of blood flow and oxygenation or combinations of these approaches. MATERIALS AND METHODS: Proliferation (BrdUrd), vascular architecture (endothelial marker), perfusion (Hoechst 33342) and oxygenation (NITP) were studied in two human laryngeal squamous cell carcinoma tumour lines grown as xenografts in nude mice. The effects of carbogen and nicotinamide on these parameters were evaluated. RESULTS: Carbogen treatment resulted in a decrease of the number of perfused blood vessels from 66% to 55% in one of the two tumour lines. In this tumour line nicotinamide prevented this reduction of tumour blood flow by carbogen. In both tumour lines the labelling index (LI) decreased after treatment with carbogen for 1 h, from 11-13% to 5-7%. Both tumour lines showed a drastic reduction of hypoxia by carbogen alone or by carbogen plus nicotinamide. CONCLUSIONS: In both laryngeal squamous cell carcinoma xenograft tumour lines carbogen was very effective in reducing diffusion limited hypoxia. Only in one of the two tested tumour lines carbogen also caused a reduction of tumour blood perfusion, which could be compensated for by nicotinamide. In addition, carbogen reduced tumour cell proliferation. The fact that differences in response to nicotinamide and carbogen were observed and that they can be studied in vivo provides a basis for further development of a 'predictive profile' which will guide the clinician to select the optimal treatment for individual patients or groups of patients.

Animals↗

High-performance liquid chromatography/continuous-flow liquid secondary ion mass spectrometry of flavonoid glycosides in leguminous plant extracts.

A method for the identification of flavonoid glycosides utilizing continuous-flow liquid secondary ion mass spectrometry (CF-LSIMS) is presented. Minimum detectable quantities (MDQs) were determined for three model flavonoid glycosides (rutin, naringin and esculin) by both positive ion direct insertion probe (DIP)-LSIMS (1.6 nmol, 1.7 nmol and 730 pmol, respectively) and positive ion CF-LSIMS (330 pmol, 340 pmol and 290 pmol, respectively). Optimization of CF-LSIMS instrumental parameters was performed using the model compound rutin. Parameters optimized included mobile phase composition, glycerol concentration, mobile phase flow rate, ion source temperature, acceleration lens potential (amplitude and polarity) and Cs+ primary ion energy. Final instrumental optimization yielded an MDQ of 1.0 ng (1.6 pmol) for rutin by flow-injection CF-LSIMS. The optimization parameters were utilized in the identification of flavonoid glucosides in alfalfa (Medicago sativa L) and chickpea (Cicer arietinum) extracts by high-performance liquid chromatogrphy/CF-LSIMS. The results support the controversial identification of a major extract component as formononetin-7-O-glucoside-6"-malonate as opposed to afrormosin-7-O-glucoside-6"-malonate.

Chromatography, High Pressure Liquid↗

Simple model for biaxial smectic-A liquid-crystal phases.

We have generalized the McMillan theory of liquid crystalline smectic order in uniaxial particle fluids to biaxial particles. Upon varying the control parameter, a uniaxial nematic phase may: (i) order biaxially first, then smectically; (ii) order smectically first, then biaxially; and (iii) simultaneously order biaxially and smectically. We investigate, in the limit of complete orientational order of the molecular major axes, which of these scenarios are realized for a simple model of particles with the symmetry of rectangular parallelepipeds. We also present a generic variational derivation of the theory based on the identification of the dominant order parameters for the most ordered phase.

Journal Article↗

The use of biologic response modifiers in human clinical trials.

To optimize regeneration of the periodontium, new cementum, periodontal ligament, and bone must be formed. Conventional periodontal surgery decreases the likelihood of continued progressive periodontal disease however, it does not lead to significant periodontal regeneration. In vitro studies have identified a class of biologic response modifiers loosely referred to as growth factors, which stimulate the cellular events of tissue regeneration. The most promising are mitogenic and differentiation factors. Based on promising results from animal studies, the application of growth factors to predictably stimulate periodontal regeneration is entering human clinical trials. This manuscript deals with several important considerations in testing biologic response modifiers in humans. Suggestions are made regarding the following parameters: 1) selection of the unit of measurement; 2) patient and lesion selection; 3) identification of controls; 4) selection of outcome parameters; 5) statistical approach; and 6) considerations in treatment regimens.

Animals↗

Multiple pregnancies conceived with intrauterine insemination during superovulation: an evaluation of clinical characteristics and monitored parameters of conception cycles.

The use of human menopausal gonadotropins to induce superovulation in conjunction with intrauterine insemination as treatment for infertility is associated with an increased incidence of multiple gestation. Identification of clinical characteristics and/or monitored parameters of the stimulation cycles highly associated with multiple gestation would enable cancellation of these cycles. We retrospectively evaluated the clinical profiles and conception cycle characteristics of 48 infertile women undergoing the induction of superovulation and intrauterine insemination. We compared 14 of these women who conceived multiple gestations (eight twins and six triplets) with 34 who conceived singleton gestations. We found no differences between the groups in age, parity, cause or duration of infertility, duration or amount of human menopausal gonadotropin administration, serum estradiol concentrations on the day of human chorionic gonadotropin injection, number of preovulatory-sized follicles, or number of motile sperm inseminated. We conclude that neither the patients' clinical characteristics nor the parameters evaluated in monitoring human menopausal gonadotropin cycles provide information helpful in predicting which superovulation cycles will result in multiple pregnancy.

Adult↗

Closed-loop multivariable system identification for the characterization of the dynamic arm compliance using continuous force disturbances: a model study.

This study presents a new multivariable closed-loop identification technique for estimating the dynamic compliance of the multijoint human arm during posture maintenance. The method is designed for the application of continuous force disturbances that facilitate interaction of the limb with the environment. The dynamic compliance of the arm arises from different physiological mechanisms and is important for maintaining stable postures and to suppress disturbances. Estimates can be useful to analyze the ability of the nervous system to adapt the arm compliance to different types of disturbances and environments. The technique is linear and requires no a priori knowledge of the system. Linear system behavior is justified for posture tasks where the hand position deviates slightly from a reference position. Interaction results in a closed-loop configuration of arm and environment. The problem with previous methods is the restriction to open-loop systems. With the current technique, the dynamic arm compliance is separately estimated from the closed-loop. The accuracy of the identification technique is tested by simulations for different values of the dynamic compliance of the arm and environment and for different methodological parameters. It is concluded that the identification technique is accurate, even for short observation periods and severe noise.

Arm↗

Generation of rye (Secale cereale L.) plants with low transgene copy number after biolistic gene transfer and production of instantly marker-free transgenic rye.

Rye is extremely recalcitrant to tissue culture and genetic transformation. We describe the efficient and reproducible production of stably expressing transgenic rye plants after biolistic gene transfer to callus tissue derived from immature embryos. Key factors in the production of transgenic rye plants include the identification of biolistic gene transfer parameters and a selection protocol, which does not affect its regeneration ability. The bar gene was used as a selectable marker and selection was performed by spraying the regenerated shoots with 0.05% Basta solution without any previous selection of tissue cultures. Based on Southern blot analysis, a total of 21 transgenic rye plants with independent transgene integration patterns were produced. A low transgene copy number was observed in most transgenic plants and 40% of the plants had a single transgene copy insert. The high frequency of single transgene copy inserts might be a consequence of the selection system, which is based on the identification of stably expressing transgenic plantlets rather than stably expressing tissue cultures. All transgenic rye lines with single transgene inserts showed stable transgene expression in sexual progenies, but indications of transcriptional and post-transcriptional gene silencing were observed in few transgenic lines with multiple transgene inserts. Tissue culture-based selection was not necessary for the generation of transgenic rye. The identification of 17 transgenic rye plants without using any selectable marker gene by PCR amplification of transgene sequences is also demonstrated. Instant generation of selectable marker-free transgenic rye avoids a negative impact of selective agents on the transgenic tissue cultures, responds to public concerns on the safety of selectable markers and will support multiple transformation cycles for transgene pyramiding.

Aminobutyrates↗

Induced histidine decarboxylase in endotoxic shock: identification of the enzyme in rat liver and influence of its inhibitors on survival parameters.

The hypothesis of a causal relationship between a progressive and unrestrained increase of tissue histamine formation by activation of an inducible histidine decarboxylase (HDC) and lethality in endotoxic shock (Schayer's 'induced histamine concept') was tested in a standardized rat endotoxic shock model. Initial enzyme identification studies in the rat shock liver (8 hrs after endotoxin challenge) clearly demonstrate that the 'induced' histidine decarboxylase is an acid (specific) HDC. The succeeding randomized, controlled study with appropriate inhibitors of the enzyme, alpha-methyl-histidine (competitive inhibitor) and alpha-fluoromethyl-histidine (irreversible inhibitor) using doses of 2, 20 or 100 mg/kg showed no significant effect on the survival rate of rats in endotoxin shock. The survival rate of the non-treated endotoxin control group (NaCl) was 25%; all methylprednisolone treated rats (50 mg/kg) survived. Thus, the 'induced' histamine is not a predominant factor (necessary or sufficient determinant) for the lethal outcome in rat endotoxic shock. The protective effect of MP is not predominantly due to the inhibition of the 'induced' histidine decarboxylase. The use of HDC-inhibitors as the appropriate instruments for evaluation of the significance of this mechanism is discussed.

Animals↗