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Results for “nonlinear analyses”

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PubMed1992

Effect of hearing loss of cochlear origin on the auditory brain stem response.

Auditory brain stem response (ABR) testing is widely used to detect lesions of the auditory neural pathways. The ABR waves depend not only on the integrity of the neural pathways, but also on the condition of the cochlea. To properly interpret the ABR response, it is necessary to understand the effects of cochlear hearing loss on the ABR wave latencies. We studied two populations of subjects with cochlear hearing loss: one with varying degrees of high-frequency hearing loss and the other with varying degrees of flat configuration hearing loss. The degree of cochlear hearing loss was quantified in several different ways and subjected to one linear and three nonlinear regression analyses to test for accuracy in predicting ABR wave latencies and interpeak intervals (waves I, III, V, I-V, I-III, and III-V) for three click intensities. Hearing loss levels from 2 to 6 kHz, in particular 4 kHz, were superior to other audiometric test frequencies as predictors of ABR wave latencies for the group with the high-frequency losses. No particular characterization was found to be superior for the flat hearing loss configurations. From these results, modeled predictions of wave latencies as a function of degree and configuration of hearing loss were made. The modeled predictions are then used to suggest guidelines for interpretations of ABR results where hearing impaired patients are involved.

Adult↗

PubMed1992

Psychophysiological processes during insight-oriented therapy. Further investigations into nonlinear psychodynamics.

Experimental evidence shows that many physiological processes abide by nonlinear dynamics and evidence chaos. Novel conceptual models postulate chaotic phenomena in psychological processes as well. The challenge in empirically testing these models is to develop measures that are sufficiently precise to permit nonlinear dynamical analyses and that also say something meaningful about psychological phenomena. Toward this end, we examined the spontaneously occurring autonomic activity of a patient during psychotherapy. Phase portraits were constructed of the patient's heart rate data for each of several therapy sessions. The flows within these phase spaces were visually segmented and assigned to one of four previously defined trajectory classifications. These trajectories were quantitatively analyzed, and the corresponding clinical material was assessed qualitatively. The trajectories in the physiological phase space were recognizable, recurrent, and robust; they appeared coupled to ongoing psychological processes. Possible refinements in this typology are discussed and suggestions are made for potentially using such analyses to track and navigate among psychophysiological states.

Adult↗

PubMed2005

The association between eye color and corneal sensitivity measured using a Belmonte esthesiometer.

PURPOSE: The purpose of this study is to determine the association between corneal sensitivity measured using a pneumatic esthesiometer and eye color quantified objectively. METHODS: Twenty subjects had ocular surface sensitivity measured using a Belmonte esthesiometer. An ascending method of limits followed by the method of constant stimuli were used to estimate 1) cold detection thresholds, 2) discomfort detection thresholds (both using pneumatic stimuli at 20 degrees C, 3) mechanical detection thresholds using pneumatic stimuli at 50 degrees C (ocular surface temperature approximately 33 degrees C), and 4) percent CO2 chemical detection thresholds using 50 degrees C pneumatic stimuli at flow rates set at half of each subject's pneumatic detection threshold (therefore detected by the chemical content and not the mechanical content). Eye color was estimated 1) clinically by two observers ranking the color (light to dark) of digital images of each subject's iris, 2) photometrically by measuring iris luminance, and 3) using chromaticity obtained from a Photo Research 650 spectroradiometer with controlled illumination. Correlation and linear and nonlinear regression analyses were used to examine relationships between variables. RESULTS: There were no associations between eye color (determined clinically or objectively) for mechanical and chemical detection thresholds (best r = 0.15, all p > 0.05). There was a significant linear association between 20 degrees detection thresholds and eye color (r = 0.39), which was substantially improved with a two-line function (part level and part increasing linearly, r = 0.65). CONCLUSIONS: We were generally unable to demonstrate the relationship between eye color and sensitivity reported previously using a Cochet-Bonnet esthesiometer. However, for a subset of subjects with palest irises, there appears to be a linear association between eye color and sensitivity to cooling stimuli.

Adult↗

PubMed2004

Quaternary diversification in European alpine plants: pattern and process.

Molecular clock approaches applied previously to European alpine plants suggest that Primula sect. Auricula, Gentiana sect. Ciminalis and Soldanella diversified at the beginning of the Quaternary or well within this period, whereas Globularia had already started diversifying in the (Late-)Tertiary. In the first part of this paper we present evidence that, in contrast to Globularia and Soldanella, the branching patterns of the molecular internal transcribed spacer phylogenies of both Primula and Gentiana are incompatible with a constant-rates birth-death model. In both of these last two taxa, speciation probably decreased through Quaternary times, perhaps because of some niche-filling process and/or a decrease in specific range size. In the second part, we apply nonlinear regression analyses to the lineage-through-time plots of P. sect. Auricula to test a range of capacity-dependent models of diversification, and the effect of Quaternary climatic oscillations on diversification and extinction. At least for one major clade of sect. Auricula there is firm evidence that both diversification and extinction are a function of temperature. Intriguingly, temperature appears to be correlated positively with extinction, but negatively with diversification. This suggests that diversification did not take place, as previously assumed, in geographical isolation in high-altitude interglacial refugia, but rather at low altitudes in geographically isolated glacial refugia.

Europe↗

PubMed2004

Optical patterns with different wavelengths.

The semiconductor resonator is an example of an optical system where two modulational instabilities with different wave numbers coexist. In the limit of nascent bistability, the dynamics is generically described by a nonvariational real order parameter equation, of which we give a detailed derivation. This considerably simplifies the linear and weakly nonlinear stability analyses. When the two instabilities are close together, we derive normal form equations and put special emphasis on "envelope" branches of solutions. These particular solutions may connect the two instability points or form an isola. On the basis of these rigorous results, we finally discuss the case of distant modulational instabilities, in both one and two transverse dimensions.

Journal Article↗

PubMed2001

Population pharmacokinetics of antifibroblast activation protein monoclonal antibody F19 in cancer patients.

AIMS: The population pharmacokinetics of 131I-mAbF19, a radiolabelled murine monoclonal antibody against fibroblast activation protein and a potential antitumour stroma agent, were investigated during two phase I studies in cancer patients. METHODS: 131I-mAbF19 serum concentration-time data were obtained in 16 patients from two studies involving imaging and dosimetry in colorectal carcinoma and soft tissue sarcoma. Doses of 0.2, 1 and 2 mg antibody were administered as 60 min intravenous infusions. The data were analysed by nonlinear mixed effect modelling. RESULTS: The data were described by a two-compartment model. Population mean values were 109 ml h(-1) for total serum clearance, 3.1 l for the volume of distribution of the central compartment, and 4.9 l for the volume of distribution at steady state. Mean terminal half-life was 38 h. Intersubject variability was high, but no patient covariates could be identified that further explained this variability. In particular, there was no influence of tumour type or mAbF19 dose. CONCLUSIONS: The pharmacokinetics of antistromal mAbF19 were well defined in these two studies with different solid tumour types, and were comparable with those of other murine monoclonal antibodies that do not bind to normal tissue antigens or blood cells.

Adult↗

PubMed2006

Population pharmacokinetics of darbepoetin alfa in haemodialysis and peritoneal dialysis patients after intravenous administration.

AIMS: To characterize the pharmacokinetics of darbepoetin alfa and covariate relationships in haemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Data were collected from 131 (63 HD and 68 PD) patients who received darbepoetin alfa intravenously. A total of 917 serum concentrations were available. The data were analysed by nonlinear mixed effect modelling using NONMEM with a model including endogenous erythropoietin production. In addition, the final model was evaluated using bootstrap resampling. RESULTS: The selected basic model was a two-compartment model with a combination of additive and the constant coefficient of variation error models. The significant covariates were weight (WT) for clearance (CL) and the volume of central compartment (V(1)), and the dialysis technique (DIA) for V(1). The typical values of CL and V(1) were 0.0807 l h(-1) and 2.51 l, respectively. V(1) in PD patients was 17% higher than in HD patients. With the introduction of WT in CL and WT and DIA in V(1), interindividual variability decreased from 27.1% to 20.6% in CL and from 29.1% to 21.8% in V(1). The mean parameter estimates from the bootstrap datasets were similar to those from the original dataset. Evaluation by bootstrapping showed that the final model was stable. CONCLUSIONS: The results of the present analysis suggest no dosage regimen change is warranted for darbepoetin alfa in HD and PD patients over the range of distribution of covariates included in this study.

Adult↗

PubMed1985

Androgen cytosol binding during compensatory overload-induced skeletal muscle hypertrophy.

This study was undertaken to evaluate whether the increased androgen cytosol binding is an early or later event in the sequence of skeletal muscle hypertrophy induced by surgical overload. Following removal of the synergistic gastrocnemius and soleus muscles, plantaris muscle weights of overloaded hypophysectomized made rats were heavier than those in the control by 29% at 2 days, 41% at 7 days, 38% at 14 days, and 47% at 35 days. Androgen cytosol receptor binding capacities (femtomoles per milligram protein), determined using a synthetic androgen, [3H]methyltrienolone (R1881), were higher than observed in muscles of controls at all points of muscle enlargement. At high concentrations of labeled ligand, Scatchard analyses became nonlinear and were resolved using a two-component binding model. Receptor capacity of the higher affinity "androgenic component" for methyltrienolone binding in plantaris muscles was lower at 2 days but 60-80% higher at 7, 14, and 35 days in the hypertrophied group than in the control group. The lower affinity "glucocorticoid component" was higher in the overloaded group at all points following surgery. Several glucocorticoids and estradiol-17 beta competed equally with androgens for methyltrienolone binding. However, when cytosols were incubated with triamcinolone acetonide to block methyltrienolone binding to glucocorticoid receptors, the androgenic component was highly specific for androgens. These results show that total [3H]methyltrienolone cytosol concentrations increased in parallel with the muscle hypertrophy, yet the individual components of methyltrienolone binding attained greater concentrations in overloaded muscles by an apparently different sequence of events.

Androgens↗

PubMed1985

Binding of phytohemagglutinin to porcine lymphocyte receptors. Time-course studies and comparative binding isotherms using whole cells or cellular receptors incorporated into phospholipid vesicles.

We have studied the binding of 125I-labeled phytohemagglutinin (PHA) to porcine splenic lymphocytes (10(7) cells . mL-1) at 37 degrees C. Our data show that PHA binding is dependent on the incubation period and that a maximum quantity of 4.53 +/- 0.13 micrograms is bound when 200 micrograms of PHA is added. The binding process is rapid and saturation can readily be achieved in less than 2 min. These observations suggest, in accordance with the mass-action principle, that the binding equilibrium can be rapidly displaced towards PHA-receptor complex formation when sufficient amounts of PHA are added. Our data further suggest that receptor sites are exposed at the cell surface and that putative cryptic receptor sites are unlikely to play a major role in the initial part of the binding process. We have studied this aspect by comparing Scatchard plots for PHA binding to receptors in intact lymphocytes and to lymphocyte-derived receptors incorporated into liposomes. In one case, partially purified plasma membranes were solubilized and incorporated into phosphatidylcholine-phosphatidylserine (PC-PS) vesicles prepared by detergent dialysis. In another case, PHA-receptor glycoproteins were purified by affinity chromatography and reassembled into PC-PS vesicles, using the same technique. Scatchard plot analyses showed nonlinear profiles with a concavity turned upward for PHA binding to receptors of intact cells or of PC-PS vesicles with plasma membranes, and a concavity turned downward for vesicles with purified glycoproteins. These observations suggest that PHA-receptor environment plays a determining role in the binding process of the lectin. Numerical data from binding experiments were obtained by computer-assisted nonlinear regression analysis, using a one ligand--two sites model. The (apparent) high-affinity constant (K1) for intact lymphocytes or partially purified plasma membrane components reassembled into liposomes was 4.6 X 10(7) M-1 and the (apparent) low-affinity constants (K2) were 4.4 X 10(6) +/- 1.5 X 10(6) M-1 (intact lymphocytes) and 1.7 X 10(6) +/- 0.6 X 10(6) M-1 (plasma membranes constituents reassembled into liposomes). The value obtained for reconstituted PHA-glycoprotein receptors (K) was 0.70 X 10(7) +/- 0.10 X 10(7) M-1. The apparent number of sites was n1 = 0.19 X 10(6) +/- 0.05 X 10(6) (high affinity) and n2 = 2.50 X 10(6) +/- 0.50 X 10(6) (low affinity) sites per intact lymphocyte cell.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2005

Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism.

Skeletal muscle contains two populations of mitochondria that appear to be differentially affected by disease and exercise training. It remains unclear how these mitochondrial subpopulations contribute to fiber type-related and/or training-induced changes in fatty acid oxidation and regulation of carnitine palmitoyltransferase-1beta (CPT1beta), the enzyme that controls mitochondrial fatty acid uptake in skeletal muscle. To this end, we found that fatty acid oxidation rates were 8.9-fold higher in subsarcolemmal mitochondria (SS) and 5.3-fold higher in intermyofibrillar mitochondria (IMF) that were isolated from red gastrocnemius (RG) compared with white gastrocnemius (WG) muscle, respectively. Malonyl-CoA (10 muM), a potent inhibitor of CPT1beta, completely abolished fatty acid oxidation in SS and IMF mitochondria from WG, whereas oxidation rates in the corresponding fractions from RG were inhibited only 89% and 60%, respectively. Endurance training also elicited mitochondrial adaptations that resulted in enhanced fatty acid oxidation capacity. Ten weeks of treadmill running differentially increased palmitate oxidation rates 100% and 46% in SS and IMF mitochondria, respectively. In SS mitochondria, elevated fatty acid oxidation rates were accompanied by a 48% increase in citrate synthase activity but no change in CPT1 activity. Nonlinear regression analyses of mitochondrial fatty acid oxidation rates in the presence of 0-100 muM malonyl-CoA indicated that IC(50) values were neither dependent on mitochondrial subpopulation nor affected by exercise training. However, in IMF mitochondria, training reduced the Hill coefficient (P < 0.05), suggesting altered CPT1beta kinetics. These results demonstrate that endurance exercise provokes subpopulation-specific changes in mitochondrial function that are characterized by enhanced fatty acid oxidation and modified CPT1beta-malonyl-CoA dynamics.

Animals↗

PubMed2004

Endogenous ACTH concentration-dependent drive of pulsatile cortisol secretion in the human.

According to current regulatory concepts, pulsatile ACTH concentrations (CON) stimulate time-lagged cortisol secretion rates (SEC) via an implicit CON-SEC dose-response relationship. The present analyses reconstruct nonlinear properties of this in vivo agonist-response interface noninvasively in order to investigate pulse-by-pulse coupling consistency and to obviate the need to infuse isotopes or exogenous effectors, which may disrupt pathway interactions. This approach required an ensemble strategy of 1) measuring ACTH and cortisol CON in plasma sampled every 10 min for 24 h in 32 healthy adults, and 2) estimating simultaneously a) variable-waveform ACTH and cortisol SEC bursts superimposed upon fixed basal SEC; b) biexponential kinetics of ACTH and cortisol disappearance; c) nonequilibrium exchange of cortisol among free and cortisol-binding globulin (CBG)- and albumin-bound moieties; d) two SEC-burst shapes demarcated by a statistically defined day/night boundary; e) feedforward efficacy, potency, and sensitivity; and f) stochastic variability in feedforward measures over time. Thereby, we estimate 1) ACTH SEC (microg.l(-1).day(-1)) of 0.27 +/- 0.04 basal and 0.87 +/- 0.07 pulsatile (means +/- SE); 2) cortisol SEC (micromol.l(-1).day(-1)) of 0.10 +/- 0.01 basal and 3.5 +/- 0.20 pulsatile; 3) free cortisol half-lives (min) of 1.8 +/- 0.20 (diffusion/advection) and 4.1 +/- 0.30 (elimination) and a half-life of total cortisol of 49 +/- 2.4 and of ACTH of 20 +/- 1.3; 4) ACTH potency (EC(50), ng/l) of 26 +/- 2.4, efficacy (nmol.l(-1).min(-1)) 10 +/- 1.8, and sensitivity (slope units) 0.65 +/- 0.09; 5) night/day augmentation of ACTH and cortisol SEC-burst mass by 2.1- and 1.7-fold (median); 6) abbreviation of the modal time to maximal ACTH and cortisol SEC rates by 4.4- and 4.3-fold, respectively, after a change point clock time of 0205 (median); 7) in vivo percentage distribution of cortisol as 6% free, 14% albumin bound, and 80% CBG bound with an absolute free cortisol CON (nmol/l) 11.5 +/- 0.54; and 8) significant (mean CV) stochastic variability in feedforward efficacy (140%), potency (38%), and sensitivity (56%) within the succession of paired ACTH/cortisol pulses of any given subject. In conclusion, the present composite formulation illustrates a platform for dissecting mechanisms of in vivo regulation of effector-response properties noninvasively in the corticotropic axis of the uninfused individual.

Adrenal Cortex↗

PubMed2006

Left ventricular pressure-volume relationship in conscious mice.

With the availability of transgenic models, the mouse has become an increasingly important subject for genetic-hemodynamic studies. Recently, we developed a technique to measure left ventricular (LV) pressure in conscious mice with an implanted LV polyethylene tube. We extended our new method by evaluating the LV pressure-volume relationship and examined the feasibility of this method in this study. We studied 17 male mice (age, 11-20 wk) with a conductance catheter inserted into the LV through the polyethylene tube. Load-independent parameters of contractility derived from pressure-volume relationship [slope of the end-systolic pressure-volume relationship (E(es)), slope of the maximum first derivative of LV pressure (dP/dt(max))-end-diastolic volume (EDV) relation, and preload-recruitable stroke work (PRSW)] were evaluated by inferior vena caval occlusion with an implanted snare. LV function assessed by this technique on two different days showed that the parameters were very similar, indicating reproducibility. Both linear and nonlinear regression analyses were performed for E(es). Contractility was enhanced by isoproterenol (E(es), 13.1 +/- 6.6 to 20.8 +/- 8.7 mmHg/microl; dP/dt(max)-EDV, 496 +/- 139 to 825 +/- 178 mmHg.s(-1).microl(-1); and PRSW, 110 +/- 23 to 127 +/- 21 mmHg), depressed by atenolol (E(es), 14.5 +/- 6.1 to 4.6 +/- 2.0 mmHg/microl; dP/dt(max)-EDV, 543 +/- 188 to 185 +/- 94 mmHg.s(-1).microl(-1); and PRSW, 117 +/- 20 to 70 +/- 15 mmHg) and isoflurane (E(es), 12.3 +/- 6.0 to 5.7 +/- 2.1 mmHg/microl; dP/dt(max)-EDV, 528 +/- 172 to 164 +/- 68 mmHg/s.microl; and PRSW, 124 +/- 19 to 48 +/- 10 mmHg), significantly. In conclusion, this is the first description of the LV pressure-volume relationship in conscious mice. These findings suggest that this method is feasible to detect changes of contractility in the conscious state, allowing serial assessment of pressure-volume-derived cardiac function indexes over time without anesthesia or repeated surgery.

Animals↗

PubMed2001

Effect of age on cerebral blood flow velocity and incidence of vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Current transcranial Doppler criteria for vasospasm after aneurysmal subarachnoid hemorrhage are not age specific. We analyzed the effect of age on cerebral blood flow velocity changes after subarachnoid hemorrhage and constructed an age-adjusted predictive model of cerebral blood flow velocity in subarachnoid hemorrhage patients. METHODS: We identified patients with aneurysmal subarachnoid hemorrhage admitted between 1991 and 1999 with a prospective transcranial Doppler database. Eighty-one patients, with complete medical records and transcranial Doppler examinations of the vessels of interest, were included. Patients were subdivided into 2 groups by age: younger, <68 years of age (n=47) and older, >/=68 years of age (n=34). Maximum mean flow velocity and incidence of symptomatic vasospasm were reported. Linear and nonlinear regression analyses were performed. RESULTS: Middle cerebral artery and internal carotid artery mean flow velocity were lower in older patients (median 76 versus 114 cm/s and 76 versus 126 cm/s, respectively; P<0.003). Incidence of symptomatic vasospasm was lower in older patients (44% versus 66%; P=0.05). Older patients developed symptomatic vasospasm at lower middle cerebral artery (median 57 versus 103 cm/s; P=0.04) and internal carotid artery (median 54 versus 81 cm/s, P=0.02) mean flow velocity. Relationship between middle cerebral artery and internal carotid artery mean flow velocity and age was quadratic (ANOVA, P<0.0001). CONCLUSIONS: Older patients have a lower incidence of symptomatic vasospasm, and such vasospasm develops at lower cerebral blood flow velocity than younger patients. A quadratic relationship was found between age and cerebral blood flow velocity. This model could be used to create an age-adjusted nomogram that might improve diagnostic capabilities of transcranial Doppler.

Adult↗

PubMed2003

Cross-national comparisons of seafood consumption and rates of bipolar disorders.

OBJECTIVE: The authors sought to determine if greater seafood consumption, a measure of omega-3 fatty acid intake, is associated with lower prevalence rates of bipolar disorder in community samples. METHOD: Lifetime prevalence rates in various countries for bipolar I disorder, bipolar II disorder, bipolar spectrum disorder, and schizophrenia were identified from population-based epidemiological studies that used similar methods. These epidemiological studies used structured diagnostic interviews with similar diagnostic criteria and were population based with large sample sizes. Simple linear and nonlinear regression analyses were used to compare these prevalence data to differences in apparent seafood consumption, an economic measure of disappearance of seafood from the economy. RESULTS: Simple exponential decay regressions showed that greater seafood consumption predicted lower lifetime prevalence rates of bipolar I disorder, bipolar II disorder, and bipolar spectrum disorder. Bipolar II disorder and bipolar spectrum disorder had an apparent vulnerability threshold below 50 lb of seafood/person/year. The absence of a correlation between lifetime prevalence rates of schizophrenia and seafood consumption suggests a specificity to affective disorders. CONCLUSIONS: These data describe a robust correlational relationship between greater seafood consumption and lower prevalence rates of bipolar disorders. These data provide a cross-national context for understanding ongoing clinical intervention trials of omega-3 fatty acids in bipolar disorders.

Adolescent↗

PubMed1998

The relationship between nursing staffing levels and nursing home outcomes.

This study examined the effects of selected Minnesota nursing home attributes (size, ownership, noncompliance with a state correction order, and licensed and nonlicensed nursing hours) on specific outcomes (functional ability, discharge home, and death) for residents ages 65 and older, controlling for residents' age and previous functional ability. The functional outcome was operationalized by calculating the resident's Total Dependence Score (TDS), the total score on the assessment of eight activities of daily living (score range: 0-33). Ordinary least squares regression analysis was used to estimate the effects of facility attributes, admission TDS, and age on resident outcomes, and nonlinear probability analyses were used to estimate the effects of facility attributes, admission TDS, and age on the probability of death or discharge home. In the year after admission, licensed (but not nonlicensed) nursing homes were significantly related to improved functional ability, increased probability of discharge home, and decreased probability of death, but when limited to chronic residents, the role of professional nursing hours virtually disappears. Overall, the findings support greater use of licensed nurses in the nursing home setting.

Activities of Daily Living↗

PubMed2005

Field metabolic rate and body size.

The field metabolic rates (FMRs) of 229 species of terrestrial vertebrates, all measured using the doubly labeled water method in free-living individuals, were evaluated. Daily rates of energy expenditure were as low as 0.23 kJ per day in a small reptile (gecko), to as high as 52 500 kJ per day in a marine mammal (seal). This is a range of nearly six orders of magnitude. More than 70% of the variation in log-transformed data is due to variation in body size (expressed as body mass). Much of the remaining variation is accounted for by thermal physiology, with the endothermic mammals and birds having FMRs that are about 12 and 20 times higher, respectively, than FMRs of equivalent-sized, but ectothermic, reptiles. Variation in log(body mass) within each of these three taxonomic classes accounts for over 94% of the variation in log(FMR), and results from nonlinear regression analyses using untransformed data support this conclusion. However, the range of residual variation in mass-adjusted FMR within classes is still more than sixfold (ratio of highest over lowest). Some of this variation is associated with affiliations with lower taxonomic levels (Infraclass: eutherian vs metatherian mammals; Family: passerine, procellariform and galliform birds vs other birds), some is associated with habitat (especially desert vs nondesert), and some with differences in basic diet preference and foraging mode and season. The scaling slopes for FMR often differ from BMR slopes for the same Class of animals, and most differ from the theoretical slope of 0.75. Differences among slopes and intercepts that were detected using conventional regression analyses were largely confirmed upon reanalysis using Independent Contrasts Analysis to adjust for phylogenetic biases.

Animals↗

PubMed1990

Population pharmacokinetics of phenytoin from routine clinical data in Japan: an update.

Routine clinical pharmacokinetic data collected from outpatients receiving phenytoin (PHT) were reanalyzed to estimate population pharmacokinetic parameters. There were 756 steady-state PHT concentrations and associated dosage rates (mg/d) from 334 outpatients. The data were analysed using nonlinear mixed effects model (NONMEM), a computer program designed for population pharmacokinetic analysis that allows pooling of data from many individuals. The influence of weight, co-anticonvulsants on the maximum elimination rate (Vm) and age, co-anticonvulsants on the Michaelis-Menten constant (Km) and the influence of dosage form on the bioavailability (F) of PHT were investigated. The Vm and Km of a 60 kg adult outpatient treated with PHT alone were estimated to be 325 mg/d and 2.41 micrograms/ml, respectively, while for a same size individual taking PHT with co-anticonvulsants respective estimates were 351 mg/d and 3.18 micrograms/ml. The parameter of a power function of weight was estimated to adjust Vm for body size. The best function adjusts Vm in proportion to weight to the 0.737 power. The Km for patients less than 15 years old was 24.8% less than that of adults. Assuming the F of PHT to be 1 in patients prescribed a tablet, the F value in patients prescribed a powder was [1-exp(-9.92/Dij)]; Dij is the daily dose of PHT for the ith Cpss in the jth patients (mg/kg/d).

Adolescent↗

PubMed2001

Eye activity correlates of workload during a visuospatial memory task.

Changes in six measures of eye activity were assessed as a function of task workload in a target identification memory task. Eleven participants completed four 2-hr blocks of a mock anti-air-warfare task, in which they were required to examine and remember target classifications (friend/enemy) for subsequent prosecution (fire upon/allow to pass), while targets moved steadily toward two centrally located ship icons. Target density served as the task workload variable; between one and nine targets were simultaneously present on the display. For each participant, moving estimates of blink frequency and duration, fixation frequency and dwell time, saccadic extent, and mean pupil diameter, integrated over periods of 10 to 20 s, demonstrated systematic changes as a function of target density. Nonlinear regression analyses found blink frequency, fixation frequency, and pupil diameter to be the most predictive variables relating eye activity to target density. Participant-specific artificial neural network models, developed through training on two or three sessions and subsequently tested on a different session from the same participant, correlated well with actual target density levels (mean R = 0.66). Results indicate that moving mean estimation and artificial neural network techniques enable information from multiple eye measures to be combined to produce reliable near-real-time indicators of workload in some visuospatial tasks. Potential applications include the monitoring of visual activity of system opetators for indications of visual workload and scanning efficiency.

Adult↗