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The role of cerebral cortex in the generation of voluntary saccades: a positron emission tomographic study.

The purpose of this study was to define the location and behavior of cerebral structures within the normal human brain that participate in the generation of voluntary saccadic eye movements. Changes in regional cerebral blood flow (rCBF) during task performance were assumed to reflect like changes in regional neuronal activity induced by the task. The locations of all rCBF changes were described in stereotaxic coordinates. Cerebral blood flow (CBF) was measured with positron emission tomography (PET) and bolus intravenous injection of H2(15)O. The use of H2(15)O with PET allowed six, seven-slice measurements of brain blood flow to be made in rapid sequence for each subject, without removing the subject from the tomograph between scans. Nine paid normal volunteers were studied. The paradigm included three saccadic eye-movement (SEM) conditions, one finger-movement condition and two control conditions (initial and final). The three SEM conditions allowed comparisons to be drawn between targeted versus untargeted SEMs, auditorily cued versus visually cued SEMs, and stochastic versus rhythmic SEMs. All tasks were simple and deterministic in that each movement exactly mirrored the preceding movement: finger flexion then extension, saccade-left then saccade-right. Saccadic eye movements were associated with rCBF increases within the frontal eye fields, the supplementary motor area, and the cerebellum. Finger movements were associated with rCBF changes within the sensorimotor hand areas, the supplementary motor area, and the cerebellum. The frontal eye fields were discrete cortical regions consistently active during the generation of voluntary SEMs and uninfluenced by target presence, type of cue, or task complexity, indicating a predominantly motor function. The supplementary motor area (SMA) was consistently active during all motor tasks and was uninfluenced by the degree of task complexity or stochasticity. A role for SMA in establishing "motor set" during both simple and complex motor tasks is suggested. An anterior-posterior somatotopy was found for SMA-eye (anterior) versus SMA-hand (posterior). Lateral occipital visual association cortex activation was present only during targeted saccadic conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Record linkage of healthcare insurance claims.

Limitations of current record linkage techniques include difficulty in handling large and heterogeneous data sets, low sensitivity in deterministic matching, the necessity to provide a priori weights for probabilistic matching, low computational efficiency, and complex software. This paper provides a detailed description of a method developed for purposes of linking records of individuals across time and geography. The procedure for record-linkage consists of three major components: data standardization, weight estimation, and matching. The proposed method was designed to incorporate a combination of exact and probabilistic matching techniques. The procedure was validated using convergent, divergent, and criterion- validity measures. The authors feel that the procedure outlined in this paper is a first step in addressing the current trend toward larger and more complex databases.

Health Services Research↗

Application of dimension estimation and surrogate data to the time evolution of EEG topographic variables.

Dimensional complexity (estimated correlation dimension) was measured for two topographic EEG time series: (a) the time evolution of global field power (GFP) and (b) the time evolution of sequential dissimilarity (SQD) for resting, eyes-closed and eyes-open data. Eyes-closed GFP and eyes-closed/open SQD all had an element of nonlinearity in their dynamics as evidenced by increased dimensional complexity associated with the phase-angle randomization, Gaussian surrogate-data procedure. However, none of the three gave any evidence of being deterministic chaotic processes. Eyes-open GFP dimensional complexity could not be distinguished from a linear-stochastic process.

Adult↗

Comparison of computer simulations of total lung deposition to human subject data in healthy test subjects.

A mathematical model was used to predict the deposition fractions (DF) of PM within human lungs. Simulations using this computer model were previously validated with human subject data and were used as a control case. Human intersubject variation was accounted for by scaling the base lung morphology dimensions based on measured functional residual capacity (FRC) values. Simulations were performed for both controlled breathing (tidal volumes [VT] of 500 and 1000 mL, respiratory times [T] from 2 to 8 sec) and spontaneous breathing conditions. Particle sizes ranged from 1 to 5 microns. The deposition predicted from the computer model compared favorably with the experimental data. For example, when VT = 1000 mL and T = 2 sec, the error was 1.5%. The errors were slightly higher for smaller tidal volumes. Because the computer model is deterministic (i.e., derived from first principles of physics), the model can be used to predict deposition fractions for a range of situations (i.e., for different ventilatory parameters and particle sizes) for which data are not available. Now that the model has been validated, it may be applied to risk assessment efforts to estimate the inhalation hazards of airborne pollutants.

Adult↗

Power-law behavior of power spectra in low Prandtl number Rayleigh-Bénard convection.

The origin of the power-law decay measured in the power spectra of low Prandtl number Rayleigh-Bénard convection near the onset of chaos is addressed using long time numerical simulations of the three-dimensional Boussinesq equations in cylindrical domains. The power law is found to arise from quasidiscontinuous changes in the slope of the time series of the heat transport associated with the nucleation of dislocation pairs and roll pinch-off events. For larger frequencies, the power spectra decay exponentially as expected for time continuous deterministic dynamics.

Journal Article↗

Genetic and economic evaluation of Japanese Black (Wagyu) cattle breeding schemes.

Deterministic simulation was used to evaluate 10 breeding schemes for genetic gain and profitability and in the context of maximizing returns from investment in Japanese Black cattle breeding. A breeding objective that integrated the cow-calf and feedlot segments was considered. Ten breeding schemes that differed in the records available for use as selection criteria were defined. The schemes ranged from one that used carcass traits currently available to Japanese Black cattle breeders (Scheme 1) to one that also included linear measurements and male and female reproduction traits (Scheme 10). The latter scheme represented the highest level of performance recording. In all breeding schemes, sires were chosen from the proportion selected during the first selection stage (performance testing), modeling a two-stage selection process. The effect on genetic gain and profitability of varying test capacity and number of progeny per sire and of ultrasound scanning of live animals was examined for all breeding schemes. Breeding schemes that selected young bulls during performance testing based on additional individual traits and information on carcass traits from their relatives generated additional genetic gain and profitability. Increasing test capacity resulted in an increase in genetic gain in all schemes. Profitability was optimal in Scheme 2 (a scheme similar to Scheme 1, but selection of young bulls also was based on information on carcass traits from their relatives) to 10 when 900 to 1,000 places were available for performance testing. Similarly, as the number of progeny used in the selection of sires increased, genetic gain first increased sharply and then gradually in all schemes. Profit was optimal across all breeding schemes when sires were selected based on information from 150 to 200 progeny. Additional genetic gain and profitability were generated in each breeding scheme with ultrasound scanning of live animals for carcass traits. Ultrasound scanning of live animals was more important than the addition of any other traits in the selection criteria. These results may be used to provide guidance to Japanese Black cattle breeders.

Animals↗

Effects of age-related gait changes on the biomechanics of slips and falls.

A laboratory study was conducted to examine gait changes associated with aging and the effect of these changes on initiation of slips and frequency of falls utilizing newly defined biomechanical parameters of slips and falls. Twenty-eight participants from two age groups (young and old) walked around a circular track at a comfortable pace wearing a safety harness. A slippery floor surface was placed on the walking track over the force plate at random time intervals without the participants' awareness. Synchronized kinetic and kinematic measurements were obtained on both slippery and non-slippery walking surfaces. The results indicated that older participants' horizontal heel contact velocity was significantly faster, step length was significantly shorter, and transitional acceleration of the whole body centre-of-mass (COM) was significantly slower than younger participants. Older participants' initial friction demand, as measured by required coefficient of friction (RCOF), was not significantly different than their younger counterparts. Additionally, older participants slipped longer and faster, and fell more often than younger participants. A comparison of horizontal heel contact velocity for participants who fell with participants who did not fall indicated that, in general, fallers' horizontal heel contact velocity was faster than non-fallers. However, a comparison of RCOF for participants who fell with participants who did not fall suggested that RCOF was not a totally deterministic factor influencing actual fall events. These findings suggest that gait changes associated with aging (especially higher horizontal heel contact velocity and slower transition of the whole body COM) affect initiation of slip-induced falls.

Accidental Falls↗

[Statistics as support tool and not as a decision tool].

The use of statistics in medical articles has risen a lot during the last decades, however it is used in a thoughtless manner in many instances. Today, Statistics is the only tool that allows the medical researcher to obtain results and benefits from those studies the relationships of which can not be interpreted from a determinist perspective, because it is a branch of applied mathematics objective of which is to manage and quantify the uncertainty of the available information, to support decision taking. The objective of this article is to review the basic statistical concepts that every doctor should know to be able to perform and/or detect quality research, as well as to underline the most frequent errors committed when interpreting statistical results. We review the general concepts about data synthesis and differentiation of the different types of measurements, hypothesis testing and errors that can be committed doing it, the real meaning of the "p" value, differentiation between statistically significant and clinically relevant results, the importance of confidence intervals as a measure of significance and clinical relevance, the confusion generated between two concepts that are different as standard deviation and standard error, and the criteria that govern the selection of the adequate statistical tests to evaluate relationships between variables.

Confidence Intervals↗

Factors influencing total dietary exposures of young children.

A deterministic model was developed to identify the critical input parameters needed to assess dietary intakes of young children. The model was used as a framework for understanding the important factors in data collection and data analysis. Factors incorporated into the model included transfer efficiencies of pesticide from surfaces to food, transfer efficiencies of pesticide from surfaces to hands to food, and more accurate microactivity data related to contact frequency for the three variables of interest--hands, surfaces, and food. Results from range-finding measurements of transfer efficiencies using an aqueous pesticide solution of a mixture of malathion, diazinon, and chlorpyrifos sprayed on the surfaces indicate that a higher pesticide transfer occurred from hard surfaces to food (hardwood, plastic), with low transfer from soft surfaces (carpet, cloth). Six children, all less than 4 years old, were videotaped to obtain realistic contact frequency and times for the interaction of hands, surfaces, and foods during eating meals and snacks while in their homes or day care centers. The time range of eating events varied from about 2 to 55 min, with an average of about 20 min. The average number of contact frequencies between food and hands was 19 times for each eating event, with a range of 10-40. Contacts between the surface and hand were about the same as the food and hands. Contacts between foods and surfaces ranged from 0 to 32, but only five or less of the contacts per eating event were associated with surfaces other than eating utensil. The children's microactivity data collected during the eating events, together with the laboratory results from the transfer studies, were provided as input into a Monte Carlo simulation of the dietary ingestion model. Simulation results indicate that children's handling of the food could contribute 20-80% of the total dietary intake of pesticides. Dietary exposure due to residues in the food before handling accounted for 16% and 47%, respectively, of the total mean intake from simulations for a child's consumption of an apple or banana. These results indicated that transfer efficiencies for foods on various surfaces typically found in homes as well as children's hand contacts with the food and surfaces are important as determinants of dietary exposure.

Child, Preschool↗

Salmonella enteritidis infections in France and the United States: characterization by a deterministic model.

OBJECTIVES: Epidemiological surveillance can be used to identify problems, suggest hypotheses, and assess the effectiveness of preventive actions. These objectives are pursued in the analysis of the dynamic evolution of Salmonella enteritidis infections. In this analysis, development of the epidemic in France and the United States is compared. METHODS: This analysis is based on the formulation of a simple deterministic compartmental model, in which human contact with contaminated food is expressed in terms of a baseline transmission rate. RESULTS: In France, the baseline transmission rate, stable up until 1986, is multiplied by 2.3 in 1987 and by 4.1 in 1988. There is no evidence of a slowdown of the linear rate of increase. In the Middle Atlantic region of the United States, the linear increase of the epidemic is similar to that observed in France. From 1990 a potential effect of the preventive measures is observed. CONCLUSIONS: The pattern of increase of the baseline transmission rate is similar in France and in the Middle Atlantic region of the United States. However, preventive measures, used in both areas, appeared more effective in the United States.

Disease Susceptibility↗

[Analysis of heart rhythm variability by linear and non-linear dynamics methods].

INTRODUCTION: Spectral analysis of heart rhythm variability is a noninvasive method to study cardiovascular autonomic control. Nonlinear methods of analysis of heart rhythm variability may provide an additional information on properties of RR interval dynamics, which cannot be revealed by linear methods. The aim of this study was to investigate and to compare some parameters of deterministic chaos, tractal and spectral properties of heart rhythm variability in healthy subjects. METHODS: Sixty healthy subjects, who participated in this study, were divided in four different age groups: children (< 15 years old), young (15-24 years), adults (25-39 years) and middle-aged (40-61 years). We analyzed the heart period variability extracted from a 5-minute electrocardiograms recordings in supine rest. Short-term fractal scaling exponent, sample entropy, minimum embedding dimension and the largest Lyapunov exponent along with the spectral measures (low-frequency and high-frequency power) were determined. RESULTS: Heart frequency, short-term fractal scaling exponent, and the largest Lyapunov exponent did not differ between the tested groups (p > 0.05). Middle-aged subjects had the lower low-frequency power as compared to the children (p < 0.001) and the young (p < 0.05), and the lower high-frequency power as compared to the other three groups (p < 0.001). Middle-aged also had a significantly lower power of high frequency and sample entropy as compared to the other three groups (p < 0.001). Children had lower values of minimum embedding dimension compared to the middle aged (p < 0.001). Significant negative correlation between the age of the tested subjects, and the low-and, high-frequency power and sample entropy was found. CONCLUSION: The obtained results suggested that healthy aging was associated with significant alteration in heart rhythm dynamics reflected on a higher regularity and lower variability of heart rhythm time-series. Significant decrease in a high-frequency power with aging suggested that reduction in parasympathetic activity was the basic cause of these changes.

Adult↗

Gene expression analysis with the parametric bootstrap.

Recent developments in microarray technology make it possible to capture the gene expression profiles for thousands of genes at once. With this data researchers are tackling problems ranging from the identification of 'cancer genes' to the formidable task of adding functional annotations to our rapidly growing gene databases. Specific research questions suggest patterns of gene expression that are interesting and informative: for instance, genes with large variance or groups of genes that are highly correlated. Cluster analysis and related techniques are proving to be very useful. However, such exploratory methods alone do not provide the opportunity to engage in statistical inference. Given the high dimensionality (thousands of genes) and small sample sizes (often <30) encountered in these datasets, an honest assessment of sampling variability is crucial and can prevent the over-interpretation of spurious results. We describe a statistical framework that encompasses many of the analytical goals in gene expression analysis; our framework is completely compatible with many of the current approaches and, in fact, can increase their utility. We propose the use of a deterministic rule, applied to the parameters of the gene expression distribution, to select a target subset of genes that are of biological interest. In addition to subset membership, the target subset can include information about relationships between genes, such as clustering. This target subset presents an interesting parameter that we can estimate by applying the rule to the sample statistics of microarray data. The parametric bootstrap, based on a multivariate normal model, is used to estimate the distribution of these estimated subsets and relevant summary measures of this sampling distribution are proposed. We focus on rules that operate on the mean and covariance. Using Bernstein's Inequality, we obtain consistency of the subset estimates, under the assumption that the sample size converges faster to infinity than the logarithm of the number of genes. We also provide a conservative sample size formula guaranteeing that the sample mean and sample covariance matrix are uniformly within a distance epsilon > 0 of the population mean and covariance. The practical performance of the method using a cluster-based subset rule is illustrated with a simulation study. The method is illustrated with an analysis of a publicly available leukemia data set.

Journal Article↗

Secondary-task effects on sequence learning.

With a repeated sequence of stimuli, performance in a serial reaction-time task improves more than with a random sequence. The difference has been taken as a measure of implicit sequence learning. Implicit sequence learning is impaired when a secondary task is added to the serial RT task. In the first experiment, secondary-task effects on different types of sequences were studied to test the hypothesis that the learning of unique sequences (where each sequence element has a unique relation to the following one) is not impaired by the secondary task, while the learning of ambiguous sequences is. The sequences were random up to a certain order of sequential dependencies, where they became deterministic. Contrary to the hypothesis, secondary-task effects on the learning of unique sequences were as strong or stronger than such effects on the learning of ambiguous sequences. In the second experiment a hybrid sequence (with unique as well as ambiguous transitions) was used with different secondary tasks. A visuo-spatial and a verbal memory task did not interfere with the learning of the sequence, but interference was observed with an auditory go/no-go task in which high- and low-pitched tones were presented after each manual response and a foot pedal had to be pressed in response to high-pitched tones. Thus, interference seems to be specific to certain secondary tasks and may be related to memory processes (but most likely not to visuo-spatial and verbal memory) or to the organizations of sequences, consistent with previous suggestions.

Adolescent↗

Mechanisms of stochastic phase locking.

Periodically driven nonlinear oscillators can exhibit a form of phase locking in which a well-defined feature of the motion occurs near a preferred phase of the stimulus, but a random number of stimulus cycles are skipped between its occurrences. This feature may be an action potential, or another crossing by a state variable of some specific value. This behavior can also occur when no apparent external periodic forcing is present. The phase preference is then measured with respect to a time scale internal to the system. Models of these behaviors are briefly reviewed, and new mechanisms are presented that involve the coupling of noise to the equations of motion. Our study investigates such stochastic phase locking near bifurcations commonly present in models of biological oscillators: (1) a supercritical and (2) a subcritical Hopf bifurcation, and, under autonomous conditions, near (3) a saddle-node bifurcation, and (4) chaotic behavior. Our results complement previous studies of aperiodic phase locking in which noise perturbs deterministic phase-locked motion. In our study however, we emphasize how noise can induce a stochastic phase-locked motion that does not have a similar deterministic counterpart. Although our study focuses on models of excitable and bursting neurons, our results are applicable to other oscillators, such as those discussed in the respiratory and cardiac literatures. (c) 1995 American Institute of Physics.

Journal Article↗

Darwinian natural selection for orange bioluminescent color in a Jamaican click beetle.

The Jamaican click beetle Pyrophorus plagiophthalamus (Coleoptera: Elateridae) is unique among all bioluminescent organisms in displaying a striking light color polymorphism [Biggley, W. H., Lloyd, J. E. & Seliger, H. H. (1967) J. Gen. Physiol. 50, 1681-1692]. Beetles on the island vary in the color of their ventral light organs from yellow-green to orange and their dorsal organs from green to yellow-green. The genetic basis for the color variation involves specific amino acid substitutions in the enzyme luciferase. Here, we show that dorsal and ventral light color in P. plagiophthalamus are under separate genetic control, we resolve the allelic basis for color variation, and, through analyses of luciferase sequence variation, we demonstrate that natural selection has produced a long-term adaptive trend for longer wavelength (more orange) ventral light on Jamaica. Our results constitute a novel example connecting the selective fixation of specific nucleotides in nature to their precisely determined phenotypic effects. We also present evidence suggesting that a recently derived ventral orange luciferase allele on the island has deterministically increased in frequency. Thus, the current luciferase polymorphism for P. plagiophthalamus appears to be mirroring the long-term anagenic trend on Jamaica, revealing a possible ongoing adaptive color transition in progress.

Alleles↗

Dynamical mechanism for sharp orientation tuning in an integrate-and-fire model of a cortical hypercolumn.

Orientation tuning in a ring of pulse-coupled integrate-and-fire (IF) neurons is analyzed in terms of spontaneous pattern formation. It is shown how the ring bifurcates from a synchronous state to a non-phase-locked state whose spike trains are characterized by clustered but irregular fluctuations of the interspike intervals (ISIs). The separation of these clusters in phase space results in a localized peak of activity as measured by the time-averaged firing rate of the neurons. This generates a sharp orientation tuning curve that can lock to a slowly rotating, weakly tuned external stimulus. Under certain conditions, the peak can slowly rotate even to a fixed external stimulus. The ring also exhibits hysteresis due to the subcritical nature of the bifurcation to sharp orientation tuning. Such behavior is shown to be consistent with a corresponding analog version of the IF model in the limit of slow synaptic interactions. For fast synapses, the deterministic fluctuations of the ISIs associated with the tuning curve can support a coefficient of variation of order unity.

Action Potentials↗

PCB contamination from polysulphide sealants in residential areas-exposure and risk assessment.

From the late 1950s to the early 1970s elastic polysulphide sealants were used in outdoor seams between concrete blocks in prefabricated buildings. The sealants contained 5-30% polychlorinated biphenyls (PCBs). Due to the weathering of sealants in general and the replacement of seams with new PCB-free materials in the 1990s, PCBs have drifted to the soil adjacent to buildings. The objectives of this study were to survey PCB contamination in the surroundings of former PCB-containing buildings and to evaluate the risks to human health. Samples from soil, and also from blood serum of residents, were collected to obtain data for exposure assessment. The health risk assessment was based on deterministic and probabilistic calculations for cancer and non-cancer risks. Soil ingestion and dermal contact were considered the main routes of exposure and children the most important exposed group. The mean total PCB concentration was 6.83 mg/kg within 2m of the buildings and 0.52 mg/kg within 3-10 m from of the buildings. The deterministic risk assessment with conservative parameters resulted in lifetime cancer risk estimates on the order of 10(-6)-10(-7). The lifetime average daily dose (LADD) for PCBs was less than 10% of the reference dose (RfD) 0.02 microg/kg day, which is based on immunosupression in monkeys. The LADD corresponding to the total site attributable exposure was less than 10% of the estimated average dietary PCB intake in Finland. Children can, however, in worst cases be exposed to daily doses near the level of the RfD. Low cost measures are recommended to reduce possible exposure of children.

Construction Materials↗

Visual signal detectability with two noise components: anomalous masking effects.

We measured human observers' detectability of aperiodic signals in noise with two components (white and low-pass Gaussian). The white-noise component ensured that the signal detection task was always noise limited rather than contrast limited (i.e., image noise was always much larger than observer internal noise). The low-pass component can be considered to be a statistically defined background. Contrast threshold elevation was not linearly related to the rms background contrast. Our results gave power-law exponents near 0.6, similar to that found for deterministic masking. The Fisher-Hotelling linear discriminant model assessed by Rolland and Barrett [J. Opt. Soc. Am. A 9, 649 (1992)] and the modified nonprewhitening matched filter model suggested by Burgess [J. Opt. Soc. Am. A 11, 1237 (1994)] for describing signal detection in statistically defined backgrounds did not fit our more precise data. We show that it is not possible to find any nonprewhitening model that can fit our data. We investigated modified Fisher-Hotelling models by using spatial-frequency channels, as suggested by Myers and Barrett [J. Opt. Soc. Am. A 4, 2447 (1987)]. Two of these models did give good fits to our data, which suggests that we may be able to do partial prewhitening of image noise.

Contrast Sensitivity↗