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A population genetics model of marker-assisted selection.

A deterministic two-loci model was developed to predict genetic response to marker-assisted selection (MAS) in one generation and in multiple generations. Formulas were derived to relate linkage disequilibrium in a population to the proportion of additive genetic variance used by MAS, and in turn to an extra improvement in genetic response over phenotypic selection. Predictions of the response were compared to those predicted by using an infinite-loci model and the factors affecting efficiency of MAS were examined. Theoretical analyses of the present study revealed the nonlinearity between the selection intensity and genetic response in MAS. In addition to the heritability of the trait and the proportion of the marker-associated genetic variance, the frequencies of the selectively favorable alleles at the two loci, one marker and one quantitative trait locus, were found to play an important role in determining both the short- and long-term efficiencies of MAS. The evolution of linkage disequilibrium and thus the genetic response over several generations were predicted theoretically and examined by simulation. MAS dissipated the disequilibrium more quickly than drift alone. In some cases studied, the rate of dissipation was as large as that to be expected in the circumstance where the true recombination fraction was increased by three times and selection was absent.

Computer Simulation↗

Raloxifene pharmacokinetics in males with normal and impaired renal function.

AIMS: To compare raloxifene pharmacokinetics between renally impaired and healthy subjects. METHODS: Raloxifene 120 mg was administered to 10 males with renal impairment (creatinine 2-4 mg dl(-1)) and to 10 healthy males. Data were analysed by two noncompartmental and one compartmental nonlinear regression methods. RESULTS: The medians (95% confidence interval) of the area under the curves (AUC) were 35.1 (25.8, 74) and 20.5 (16.8, 28.0) h ng ml(-1) per mg kg(-1), P < 0.01, and of the clearances (CL/F) were 28.5 (13.5, 38.8) and 48.8 (35.8, 59.4) l h(-1) kg(-1), P < 0.01, in renally impaired and healthy subjects, respectively. 95% Confidence intervals on the differences for AUC and CL/F were 6.5-44.1 and -35.1 to -7.9, respectively. CONCLUSION: Exposure to raloxifene was twice as high in males with renal impairment compared with healthy subjects.

Adult↗

Prevalence of sleep problems and their association with inattention/hyperactivity among children aged 6-15 in Taiwan.

This study investigated the 6-month prevalence rates of sleep-related problems and their association with daytime inadvertent napping, inattention, hyperactivity/impulsivity, and oppositional symptoms in children and adolescents. A representative school-based sample of 2463 first to ninth graders was recruited using a multistage sampling method. The instruments included the Sleep Habits Questionnaire (including dyssomnia, parasomnia, sleep schedules, and sleep-disordered breathing), the Chinese Health Questionnaire, and the Chinese versions of the Conners' Parent and Teacher Rating Scales-Revised: Short forms. The informants were mothers and teachers. The linear and nonlinear mixed models were used for statistical analyses and sex and age were controlled in the model. Results showed that the rates of middle insomnia, disturbed circadian rhythm, mouth breathing, and daytime inadvertent napping increased with age; whereas those of bedwetting, bruxism, sleep terrors decreased with age. Dyssomnia, sleep-disordered breathing problems, daytime inadvertent napping, and sleep schedules were related to attention-deficit/hyperactivity disorder (ADHD)-related symptoms as assessed by mothers' and teachers' ratings. Parasomnia was associated with ADHD-related symptoms as assessed by mothers' ratings. Our findings suggest an age trend of sleep problems similar to those found in the literature and the association of daytime inadvertent napping, inattention, hyperactivity/impulsivity, and oppositional symptoms with sleep-related problems.

Adolescent↗

Pharmacokinetics of diminazene in female Boran (Bos indicus) cattle.

The disposition kinetics and bioavailability of diminazene in five healthy heifers were determined after single intravenous (i.v.) and intramuscular (i.m.) administration of the drug in sequence with a wash-out period between administrations of 6 weeks. Intact diminazene in plasma, whole blood and urine samples was analysed using high-performance liquid chromatography. Nonlinear regression analysis of the i.v. and i.m. data indicated that, for either route, the plasma disappearance curves of diminazene were best described by triexponential equations. The i.v. bolus was followed by rapid and biphasic distribution with half-life values of 0.04 h and 0.58 h, Vd(ss) was 1.91 +/- 0.42 l/kg, elimination half-life was 31.7 h while Cl averaged 1.74 +/- 0.40 ml/min/kg. Within 30 min of the i.v. dose, the erythrocyte/plasma partition ratio of diminazene was 0.30 +/- 0.15. Diminazene was rapidly absorbed following i.m. administration; t1/2ka was 0.60 h. Cmax, 4.68 +/- 1.12 micrograms/ml, was attained in 10-15 min and systemic availability was 102.42 +/- 7.25%. The half-life of the terminal disappearance phase was 145.48 h. About 8.26% of the i.m. dose was excreted intact in the urine within the first 24 h of treatment. In vitro, diminazene was bound to bovine plasma albumin to the extent of 38.01-91.10%.

Absorption↗

Effects of perfusate buffer capacity on capillary CO2-HCO3(-)-H+ reactions: theory.

The importance of perfusate nonbicarbonate buffer capacity (beta nonHCO3) to intracapillary CO2-HCO3(-)-H+ reactions was assessed by theoretical analysis of CO2 exchange in saline-perfused pulmonary capillaries. Time courses for perfusate PCO2, [HCO3-], and [H+] were computed for capillaries containing different activities of luminal vascular carbonic anhydrase and different amounts of perfusate nonbicarbonate buffers. Mobilization of perfusate HCO3- toward CO2 during capillary transit is determined by the availability of HCO3- and H+. A supply of protons from the nonbicarbonate buffer pool is necessary to maintain a high rate of HCO3- dehydration. The analyses indicate that beta nonHCO3 has marked nonlinear effects on transcapillary CO2 exchange and intravascular pH equilibration. These nonlinear effects differ from those previously computed for CO2 reactions in an open system because the present model system consists of a sequential combination of open (within capillary proper) and closed (within postcapillary vasculature) systems. The role of luminal vascular carbonic anhydrase in capillary CO2 reactions is strongly dependent on beta nonHCO3. Perfusate nonbicarbonate buffer capacity must be considered when the results of experimental studies of transcapillary CO2 exchange and/or intravascular pH equilibration are interpreted.

Bicarbonates↗

Population pharmacokinetics of ceftriaxone and pharmacodynamic considerations in haemodialysed patients.

OBJECTIVES: To determine the pharmacokinetic parameters of ceftriaxone following an infusion in haemodialysed outpatients and to use these parameters for an optimisation of dosing based on pharmacodynamic indices. METHODS: Fifty haemodialysed patients were enrolled in a single-centre, prospective, open-label study. They received short intravenous infusions of ceftriaxone 1 or 2 g every 48 hours for bronchopneumonia immediately after the dialysis session. Total plasma concentrations of ceftriaxone were analysed with a population pharmacokinetic approach using nonlinear mixed-effects modelling. Free drug concentrations were derived from published binding parameters in order to estimate the time when they exceed the minimum inhibitory concentration (MIC). RESULTS: The pharmacokinetics were best described by a two-compartment model. None of the covariates tested (age, bodyweight, height, sex, body mass index, albumin) influenced the pharmacokinetic parameters. The estimated population pharmacokinetic parameters (interindividual variability [percentage of coefficient of variation]) were clearance 0.36 L/h (48%), volume of distribution of the central compartment 4.53 L (47%), intercompartmental clearance 10.8 L/h and volume of distribution of the peripheral compartment 9.54 L (63%). The terminal elimination half-life (t(1/2)beta) from plasma was 27.5 hours. The mean (range) times when the free drug concentration exceeded the MIC (T>MIC) following ceftriaxone 1 g infusion were 60.3 (53.0-67.7) hours and 2.5 (1.0-3.9) hours for the breakpoints 1 and 8 mg/L (based on free drug concentration), respectively. After administration of ceftriaxone 2 g, the T>MIC was 88.5 (78.8-98.3) hours and 17.7 (13.3-22.0) hours for the breakpoints 1 and 8 mg/L, respectively. The simulated free drug concentrations (median, first and third quartile) for 48 and 72 hours following the first dose of ceftriaxone 1g were 1.11, 0.63 and 1.89 mg/L, and 0.63, 0.28 and 1.18 mg/L, respectively. For ceftriaxone 2g infusion, the simulated free concentrations (median, first and third quartile) at 48 and 72 hours were 2.50, 1.40 and 4.52 mg/L, and 1.37, 0.60 and 2.70 mg/L, respectively. CONCLUSIONS: On the basis of decreased clearance in haemodialysed patients, it can be argued that the dose of ceftriaxone should be decreased or the delay between doses should be increased. However, taking into account pharmacodynamic considerations, this study showed that following intravenous administration of ceftriaxone 1 g after each dialysis session, some patients were at risk of achieving a concentration below the MIC (1 mg/L), particularly if the second administration occurred 72 hours after the first dosing. Thus, a dose of ceftriaxone 2 g intravenously is recommended immediately following dialysis, particularly in patients with severe infections or when the dosing interval will be higher than 48 hours.

Adult↗

Feed intake pattern during lactation and subsequent reproductive performance of sows.

Daily feed intake during lactation was recorded for 20,296 lactating sows on 30 commercial farms in the United States. Each lactation feed record was categorized into one of six patterns: RAPID, rapid increase in feed intake; MAJOR, major drop; MINOR, minor drop; LLL, low feed intake throughout lactation; LHH, low intake during the 1st wk then an increase in feed intake for the remainder of lactation; and GRADUAL, gradual increase. A database containing 24,340 farrowing records and 19,015 subsequent litter records were abstracted from the PigCHAMP data files of the farms enrolled in the study. Multiple regression analyses revealed that ADFI during lactation had nonlinear or linear associations with weaning-to-first service interval (WSI), weaning-to-conception interval (WCI), litter weight at weaning (WWT), and subsequent litter size (SLS). Sows having LLL and LHH had longer (P < .01) WSI and WCI than the other patterns. Sows with MAJOR had a longer WCI (P < .05) than females with RAPID. Further, sows having MAJOR had lighter (P < .01) WWT than those with RAPID, MINOR, and GRADUAL. Sows having MAJOR had a higher (P < .01) proportion of females culled for anestrus relative to RAPID. Furthermore, sows exhibiting a drop in feed intake in either wk 1 or 2 were more likely to be culled for anestrus than sows having no drop. These results suggest that both the amount and pattern of feed intake during lactation influence subsequent reproductive performance.

Anestrus↗

[Can we use a Bayesian method to build a pharmacokinetic population in two steps?].

The aim of this study is to evaluate the use of a pharmacokinetic population model built by the two-stage method and individual parameters determined by a Bayesian estimation instead of nonlinear regression. We performed a retrospective analysis on 32 patient files (mean age: 82 years). First, we analysed prediction of amikacin serum levels for the Bayesian method (MAP) and nonlinear regression (MLS). Second, we compared pharmacokinetic parameter values for each patient with MAP and MLS methods for a one- or two-compartment model. For the one-compartment model, no difference in prediction performance was found (correlation coefficient: rMLS = 0.911, rMAP = 0.903, p > 0.05; precision: pMLS = 134.3, pMAP = 147, p > 0.05). A significant difference was observed only for systematic error (eMLS = -4.47, eMAP = -3.34, p < 0.05). For a two-compartment model, the Bayesian method was better for long-term prediction: 4-8 days (rMLS = 0.877, rMAP = 0.886, p > 0.05; eMLS = 5.26, eMAP = 0.04, p < 0.01; pMLS = 441.7, pMAP = 149, p < 0.05). The comparison of MAP and MLS estimated pharmacokinetic parameter values for a one-compartment model showed that the Bayesian method used to built a pharmacokinetic population in two stages does not influence pharmacokinetic parameter estimation (p > 0.05 for Vd, Kslope, Kel and t1/2). We conclude that we can use a Bayesian method to build a pharmacokinetic population in two steps in order to perform adaptative control of a drug-dosage regimen.

Aged↗

Propofol in rats: testing for nonlinear pharmacokinetics and modelling acute tolerance to EEG effects.

BACKGROUND AND OBJECTIVE: Pharmacokinetics of propofol in rats have usually been described using linear models. Furthermore, there are only a few investigations for a pharmacodynamic model of the electroencephalographic effects of propofol in rats. We investigated pharmacokinetics and pharmacodynamics of propofol in rats with special regard to linearity in pharmacokinetics and development of tolerance. METHODS: Twelve adult male Sprague-Dawley rats received propofol in three successive infusion periods of 30 min each with infusion rates of 0.5, 1 and 0.5 mg kg(-1) min(-1). Propofol plasma concentrations were determined from arterial blood samples. Pharmacokinetics were tested for linearity using the ratio of the concentrations at the end of the first and second infusion interval as a model independent criterion. Several linear and nonlinear models were investigated with population pharmacokinetic analysis. Pharmacodynamics were analysed using the median frequency of the electroencephalographic power spectrum as a quantitative measure of the hypnotic effect. RESULTS: Pharmacokinetics were found to be nonlinear and were best described by a two-compartment model with Michaelis-Menten elimination (Vm = 2.17 microg mL(-1) min(-1), Km = 2.65 microg mL(-1), k12 = 0.30 min(-1), k21 0.063 min(-1), Vc = 0.13 L). Acute tolerance to the electroencephalographic effect of propofol was observed. The hypnotic effect was best described by a sigmoid Emax model (E0 = 17.8 Hz, Emax = 17.7 Hz, EC50 = 4.1 microg mL(-1), gamma = 2.3, ke0 = 0.36 min(-1)) with competitive antagonism of propofol and a hypothetical drug in an additional tolerance compartment. CONCLUSIONS: For the applied infusion scheme, propofol pharmacokinetics in rats were nonlinear and a development of tolerance to the electroencephalographic effect of propofol was observed during an infusion time of 90 min.

Algorithms↗

Association of time-averaged systemic immune-inflammation indices with in-hospital mortality after intracerebral hemorrhage: a retrospective study.

BACKGROUND: Systemic inflammation plays a central role in secondary brain injury following intracerebral hemorrhage (ICH). Although inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) are linked to poor outcomes, their associations with mortality are commonly assumed to be linear, potentially overlooking nonlinear patterns where mortality risk rises steeply at higher levels. METHODS: We conducted a retrospective study using the MIMIC-IV database, including 440 patients with non-traumatic ICH who were alive and remained in the ICU for at least 72&#xa0;h after admission. Mean NLR, SII, and SIRI were calculated from measurements obtained during this period. Multivariable logistic regression and restricted cubic spline (RCS) analyses were applied to assess their independent and nonlinear associations with in-hospital mortality. Model discrimination and calibration were internally validated using 1,000 bootstrap resamples. RESULTS: The in-hospital mortality rate was 26.1%. After multivariable adjustment, NLR and SIRI remained independently associated with mortality. Patients in the highest SIRI quartile had the highest risk of death (aOR&#xa0;=&#xa0;5.12; 95% CI: 2.57-12.24; p&#xa0;<&#xa0;0.001). RCS analysis revealed a significant nonlinear association between SIRI and mortality (p-nonlinearity&#xa0;<&#xa0;0.05), showing a steep risk increase at higher SIRI levels. Adding SIRI to the base model provided a modest improvement in discrimination (AUC 0.762 to 0.785, p&#xa0;=&#xa0;0.045) and significantly improved risk reclassification (cNRI&#xa0;=&#xa0;0.4778, p&#xa0;<&#xa0;0.001; IDI&#xa0;=&#xa0;0.0240, p&#xa0;=&#xa0;0.0151). CONCLUSIONS: Among patients with ICH who met the 72-hour eligibility criterion, higher 72-hour average SIRI was independently associated with in-hospital mortality. As a time-averaged measure, SIRI should be interpreted as a dynamic marker integrating the initial inflammatory state and the early clinical course rather than as a purely baseline prognostic factor. Although adding SIRI to the base model modestly improved discrimination and risk reclassification, it should be considered a candidate prognostic marker requiring external validation before clinical application.

Humans↗

The effect of matrix tension-compression nonlinearity and fixed negative charges on chondrocyte responses in cartilage.

Thorough analyses of the mechano-electrochemical interaction between articular cartilage matrix and the chondrocytes are crucial to understanding of the signal transduction mechanisms that modulate the cell metabolic activities and biosynthesis. Attempts have been made to model the chondrocytes embedded in the collagen-proteoglycan extracellular matrix to determine the distribution of local stress-strain field, fluid pressure and the time-dependent deformation of the cell. To date, these models still have not taken into account a remarkable characteristic of the cartilage extracellular matrix given rise from organization of the collagen fiber architecture, now known as the tension-compression nonlinearity (TCN) of the tissue, as well as the effect of negative charges attached to the proteoglycan molecules, and the cell cytoskeleton that interacts with mobile ions in the interstitial fluid to create osmotic and electro-kinetic events in and around the cells. In this study, we proposed a triphasic, multi-scale, finite element model incorporating the Conewise Linear Elasticity that can describe the various known coupled mechanical, electrical and chemical events, while at the same time representing the TCN of the extracellular matrix. The model was employed to perform a detailed analysis of the chondrocytes' deformational and volume responses, and to quantitatively describe the mechano-electrochemical environment of these cells. Such a model describes contributions of the known detailed micro-structural and composition of articular cartilage. Expectedly, results from model simulations showed substantial effects of the matrix TCN on the cell deformational and volume change response. A low compressive Poisson's ratio of the cartilage matrix exhibiting TCN resulted in dramatic recoiling behavior of the tissue under unconfined compression and induced significant volume change in the cell. The fixed charge density of the chondrocyte and the pericellular matrix were also found to play an important role in both the time-dependent and equilibrium deformation of the cell. The pericellular matrix tended to create a uniform osmolarity around the cell and overall amplified the cell volume change. It is concluded that the proposed model can be a useful tool that allows detailed analysis of the mechano-electrochemical interactions between the chondrocytes and its surrounding extracellular matrix, which leads to more quantitative insights in the cell mechano-transduction.

Animals↗

Misuse of graphical analysis in nonlinear sugar transport kinetics by Eadie-Hofstee plots.

It has become common practice to analyse the sugar transport kinetics from initial uptake rates in Saccharomyces cerevisiae cells with Eadie-Hofstee plots. These plots often demonstrate a nonlinear behaviour. They have been resolved incorrectly into two quasilinear components indicating the presence of (at least) two uptake systems or components, with Km values differing by a factor of about 10. This graphical analysis neglects the obvious additivity of the two hypothetical systems and is therefore in error. A more efficient way to determine kinetic parameters from initial uptake experiments is to use computer-assisted nonlinear regression analysis.

Glucose↗

Influence of isometric loading on biceps EMG dynamics as assessed by linear and nonlinear tools.

The summed electrical discharges generated by a contracting skeletal muscle constitute a dynamic system conveying electromyographic (EMG) information indicative of muscle physiological status. "Steady states" of activity can be achieved with light loads, but with heavy loads the dynamic system experiences continuous status transitions that culminate in task failure. The present study was designed to assess the applicability of two mathematical tools, one linear and the other nonlinear, in addressing the time course of EMG alterations under different loading challenges. Surface EMGs of the biceps brachii muscle were recorded from 14 healthy human volunteers during light and heavy loadings, and task failure occurred at varying times among the subjects. Digitized EMG signals were analyzed by linear spectral analysis (fast Fourier transform) and nonlinear recurrence-plot analysis. With light loading, computed variables from both analyses gave "quasi-steady-state" values over time, with recurrence-plot analysis having the higher variance. With heavy loading, the nonlinear variable (%determinism) increased sooner and exhibited larger changes from control values than decreases in the linear variable (spectral center frequency). Experimental results support the conclusion that both analyses can be combined to give a fuller assessment of the biceps EMG during light or heavy loading. Implications for the detection of muscular fatigue are discussed.

Adult↗

MR-based neurological disease classification methodology: application to lateralization of seizure focus in temporal lobe epilepsy.

Classification approaches for neurological diseases tend to concentrate on specific structures such as the hippocampus (HC). The hypothesis for the novel methodology presented in this work is that pathologies will impact large tissue areas with detectable variations of T1-weighted MR signal intensity and registration metrics. The technique is applied to lateralization of seizure focus in 127 patients with intractable temporal lobe epilepsy (TLE), in which the site of seizure onset was determined by comprehensive evaluation (69 with left MTL seizure focus (SF) (group "L") and 58 with right SF (group "R")). The method analyses large, non-specific Volumes of Interest (VOI) centered on the left and right medial temporal lobes (MTL) (55 x 82 x 80 voxels) in pre-processed scans aligned in stereotaxic space. Extracted VOIs are linearly and nonlinearly registered to a reference target image. Principal Components Analyses of (i) the normalized intensity and (ii) the trace, a measure of local volume change, are used to generate a multidimensional reference space from a set of 152 neurologically healthy subjects. VOIs from TLE patients, processed in a similar fashion, are projected in this space, and leave-one-out, forward stepwise linear discriminant analysis of the eigencoordinate distributions is used for classification. Following manual MRI volumetric analysis, 80 patients had HC atrophy (group "HA") ipsilateral to the SF (42 with left SF or "LHA", and 38 with right or "RHA"), and the remaining 47 had normal HC volumes (group "HNV") (27 with left SF or "LNV", and 20 with right SF or "RNV"). The automated method was 100% accurate at separating "HA" vs. "HNV", "LHA" vs. "RHA", and "LNV" vs "RNV". It was also 96% accurate at separating "L" vs. "R". Our results indicate that MR data projected in multidimensional feature domains can lateralize SF in epilepsy patients with a high accuracy, irrespective of HC volumes. This single-scan, practical and objective method holds promise for the pre-surgical evaluation of TLE patients.

Adult↗

Genetical ESS-models. I. Concepts and basic model.

Evolutionarily Stable Strategies (ESS) in phenotypic models are used to explain the evolution of animal interactive behaviour. As the behavioural features under consideration are assumed to be genetically determined, the question arises how underlying a genetical system might affect the results of phenotypic ESS-models. This question can be fully treated in terms of ESS-theory. A method of designing Genetical ESS-Models is proposed, which transfers the question of evolutionary stability to a "lower" level, the genetical basis. Genetical ESS-models - although nonlinear even in the simplest cases - can be analysed in a way that is familiar to ESS-theorists and yield immediate results on gene pool ESSs, which then may or may not maintain ESSs on the phenotypic level. Moreover, general results can be obtained to characterize evolutionarily stable gene pool states and their interrelation with commonsense, phenotypic ESSs. This part of the article presents the basic concepts and an outline of the method of genetical ESS-models. It gives, as a demonstration, a complete analysis for phenotypic two-strategy models (linear or nonlinear) based on a diploid, diallelic single-locus system under random mating. The results in this case suggest that a phenotypic ESS should indeed be expected to evolve but, maybe, only after passing through a succession of temporarily stable states.

Animals↗

Nonlinear pharmacokinetics and interconversion of prednisolone and prednisone in rats.

The pharmacokinetics of prednisolone and prednisone were examined in 32 rats at four intravenous doses (5, 10, 25, and 50 mg/kg). Each rat was given one dose of either intravenous prednisolone or prednisone, and plasma concentrations of both compounds were measured by HPLC. Mammillary moment analysis showed the apparent clearance and volume of distribution of prednisolone and the apparent clearance of prednisone to be dose-dependent. Further diagnostic analysis using a linear interconversion model revealed modest interconversion between the two steroids and at least two saturable clearance processes: the conversion of prednisolone to prednisone and the irreversible elimination of prednisone. A comprehensive model which incorporates the nonlinear clearances of prednisolone and prednisone plus the additional feature of nonlinear tissue distribution of prednisolone was then constructed. Four differential equations describing the rate of change of each steroid in each compartment were used to numerically fit by nonlinear least squares analysis all plasma concentration-time profiles simultaneously. The final estimates from the full model only partly agreed with the results from the two moment analyses but confirmed the general structure of the model. The nonlinear tissue distribution of prednisolone was reinforced by assay of muscle tissue. This study demonstrates the utility of the model-building process where simpler models yield insights into more elaborate schemes with complex nonlinear features.

Analysis of Variance↗

Functional signal- and paradigm-dependent linear relationships between synaptic activity and hemodynamic responses in rat somatosensory cortex.

Linear relationships between synaptic activity and hemodynamic responses are critically dependent on functional signal etiology and paradigm. To investigate these relationships, we simultaneously measured local field potentials (FPs) and optical intrinsic signals in rat somatosensory cortex while delivering a small number of electrical pulses to the hindpaw with varied stimulus intensity, number, and interstimulus interval. We used 570 and 610 nm optical signals to estimate cerebral blood volume (CBV) and oxygenation, respectively. The spatiotemporal evolution patterns and trial-by-trial correlation analyses revealed that CBV-related optical signals have higher fidelity to summed evoked FPs (SigmaFPs) than oxygenation-derived signals. CBV-related signals even correlated with minute SigmaFP fluctuations within trials of the same stimulus condition. Furthermore, hemodynamic signals (CBV and late oxygenation signals) increased linearly with SigmaFP while varying stimulus number, but they exhibited a threshold and steeper gradient while varying stimulus intensity, suggesting insufficiency of the homogeneity property of linear systems and the importance of spatiotemporal coherence of neuronal population activity in hemodynamic response formation. These stimulus paradigm-dependent linear and nonlinear relationships demonstrate that simple subtraction-based analyses of hemodynamic signals produced by complex stimulus paradigms may not reflect a difference in SigmaFPs between paradigms. Functional signal- and paradigm-dependent linearity have potentially profound implications for the interpretation of perfusion-based functional signals.

Animals↗

Method for ventricular fibrillation detection in the external electrocardiogram using nonlinear prediction.

The automatic external defibrillator is a lifesaving device which processes and analyses the electrocardiogram (ECG) and delivers defibrillation shock when necessary. The accuracy of the built-in algorithm for ECG analysis must be very high, with sensitivity and specificity aimed to approach the maximum values of 100%. An algorithm based on nonlinear prediction of the external ECG signal is proposed. It extracts seven parameters characterizing the prediction possibility of the assessed ECG signal. By means of the K-nearest neighbours rule the diagnostic accuracy of different combinations of these parameters was evaluated. Thus the accuracy obtained was higher than 95% with sensitivity and specificity values depending on the combination of parameters. The method was tested with ECG records from the widely recognized databases of the American Heart Association (AHA) and Massachusetts Institute of Technology (MIT).

Electrocardiography↗