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PubMedDate not supplied

Evolution and analysis of model CPGs for walking: II. General principles and individual variability.

Are there general principles for pattern generation? We examined this question by analyzing the operation of large populations of evolved model central pattern generators (CPGs) for walking. Three populations of model CPGs were evolved, containing three, four, or five neurons. We identified six general principles. First, locomotion performance increased with the number of interneurons. Second, the top 10 three-, four-, and five-neuron CPGs could be decomposed into dynamical modules, an abstract description developed in a companion article. Third, these dynamical modules were multistable: they could be switched between multiple stable output configurations. Fourth, the rhythmic pattern generated by a CPG could be understood as a closed chain of successive destabilizations of one dynamical module by another. A combinatorial analysis enumerated the possible dynamical modular structures. Fifth, one-dimensional modules were frequently observed and, in some cases, could be assigned specific functional roles. Finally, dynamic dynamical modules, in which the modular structure itself changed over one cycle, were frequently observed. The existence of these general principles despite significant variability in both patterns of connectivity and neural parameters was explained by degeneracy in the maps from neural parameters to neural dynamics to behavior to fitness. An analysis of the biomechanical properties of the model body was essential for relating neural activity to behavior. Our studies of evolved model circuits suggest that, in the absence of other constraints, there is no compelling reason to expect neural circuits to be functionally decomposable as the number of interneurons increase. Analyzing idealized model pattern generators may be an effective methodology for gaining insights into the operation of biological pattern generators.

Algorithms↗
PubMed2003

Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver.

AIMS: To determine levels of microsomal protein (MPPGL) and hepatocellularity (HPGL) per gram of human liver and their interindividual variability. METHODS: Triplicate liver samples were used to determine values of MPPGL (n = 20) and HPGL (n = 7) after accounting for the fractional loss of microsomal protein or hepatocytes during processing. Repeated measurements from each liver sample allowed the estimation of true interindividual variability in MPPGL and HPGL using ANOVA. RESULTS: The value of MPPGL ranged from 26 to 54 mg g(-1) (mean(geo)= 33 mg g(-1)). The value of HPGL ranged from 65 to 185 x 10(6) cells g(-1) (mean(geo)= 10(7) x 10(6) cells g(-1)). CONCLUSIONS: There is significant interindividual variability in MPPGL, which has implications for the accurate extrapolation of in vitro data on drug metabolism to predict in vivo metabolic clearance.

Adult↗
PubMed1987

Intra-individual variability and measurement noise in estimates of energy expenditure by whole body indirect calorimetry.

1. Four men were each studied continuously over 12 d in a whole-body calorimeter. Dietary intake and daily activities were kept constant throughout the study. 2. Day-to-day coefficients of variation in energy expenditure within subjects were found to be 1.97% over 24 h, 5.93% during basal metabolic rate measurement, 2.40% overnight and 3.22% in exercise. 3. The contribution of measurement system noise to the observed variability was analysed and shown to be generally small. The source of this noise was considered. 4. The results reinforce and extend other comparable reports and show that within-subject variability forms a small part of reported observations of between-subject variability.

Adult↗
PubMed2004

The relationships between organizational and individual variables to on-the-job driver accidents and accident-free kilometres.

Highway fatalities are the leading cause of fatal work injuries in the US, accounting for approximately 1 in 4 of the 5900 job-related deaths during 2001. The present study focused on the contribution of organizational factors and driver behaviours to on-the-job driving accidents in a large Western Canadian corporation. A structural equation modelling (SEM) approach was used which allows researchers to test a complex set of relationships within a global theoretical framework. A number of scales were used to assess organizational support, driver errors, and driver behaviours. The sample of professional drivers that participated allowed the recording of on-the-job accidents and accident-free kilometres from their personnel files. The pattern of relationships in the fitted model, after controlling for exposure and social desirability, provides insight into the role of organizational support, planning, environment adaptations, fatigue, speed, errors and moving citations to on-the-job accidents and accident-free kilometres. For example, organizational support affected the capacity to plan. Time to plan work-related driving was found to predict accidents, fatigue and adaptations to the environment. Other interesting model paths, SEM limitations, future research and recommendations are elaborated.

Accidents, Occupational↗
PubMed2006

Prediction of in vivo drug clearance from in vitro data. I: impact of inter-individual variability.

The Simcyp Population-Based ADME Simulator was used to predict median drug clearances and their associated variance from in vitro data. Fifteen drugs satisfied the entry criteria for the study and the relevant information (in vitro metabolism data and in vivo human clearance values) were collated from the literature. Predicted values of median clearances fell within 2-fold of observed values for 73% of the drugs (oral route) and 78% of the drugs (intravenous route) when microsomal binding was disregarded, and for 93% (oral) and 100% (intravenous) when it was considered. Irrespective of whether microsomal binding was considered, the predicted fold variability fell within 2-fold of the observed variability for 80% (oral) and 67% (intravenous) of the drugs.

Administration, Oral↗
PubMed1997

Individual variability in lipoprotein cholesterol response to National Cholesterol Education Program Step 2 diets.

The effects of National Cholesterol Education Program (NCEP) Step 2 diets on plasma lipoprotein profiles in 72 men [mean (+/- SD) age: 44 +/- 15 y, range: 19-81 y] and 48 women (mean age: 50 +/- 21 y, range: 21-78 y) participating in five previously published studies were examined. Subjects were placed on a baseline diet similar to an average American diet (35-41% total fat, 13-16% saturated fat, 31-45 mg cholesterol/MJ) and then on an NCEP Step 2 diet (18-29% total fat, 4-7% saturated fat, 11-20 mg cholesterol/MJ) under isoenergetic conditions. All food and drink were provided. Compared with the baseline diet, consumption of the NCEP Step 2 diets was associated with significant decreases in concentrations of low-density-lipoprotein (LDL) cholesterol (-18.9% and -15.6%, respectively) and high-density-lipoprotein (HDL) cholesterol (-17.0% and -11.2%, respectively) in both men and women. Men with the apolipoprotein (apo) E 3,4 phenotype had a significantly greater decrease in LDL cholesterol (-24.2%) with the NCEP Step 2 diets than men with the apo E 3,3 phenotype (-17.7%). Men with the apo A-IV 1,2 phenotype tended to have less LDL cholesterol lowering (-12.8%) than men with the apo A-IV 1,1 phenotype (-19.6%), but this difference was not significant. No differences were seen by apo E and A-IV phenotype in women. A large variability in lipid response to the diet was observed, with changes in LDL cholesterol ranging from +3% to -55% in men and and from +13% to -39% in women. Forty-eight percent of the variability in LDL-cholesterol response (in mmol/L) to the diet could be accounted for by baseline LDL concentrations and age in men, and 13% by age in women.

Adult↗
PubMed2003

Inter-individual variability in the morphological assessment of human sperm: effect of the level of experience and the use of standard methods.

BACKGROUND: The assessment of human sperm morphology is not devoid of methodological problems, making comparison among laboratories difficult. The main goal of this study was to assess how the experience and compliance to the recommended procedures can modulate it. METHODS: Sixty-two technicians and biologists of varying degrees of andrological experience classified the same 100 sperm in a blind study from images captured on a video microscope and projected onto a screen. David's morphology classification which distinguishes normal and abnormal sperm and calculates a Multiple Anomalies Index (MAI) was used. These sperm were also classified by two trained and experienced biologists using videotaped images to provide reference values. RESULTS: The inter-participant coefficient of variation was 40% for normal sperm, lower for five defects and, 12% for MAI. Experienced participants had the closest results to the reference values. Moreover, participants not routinely using the recommended methodologies, regardless of their experience level, consistently showed marked differences compared with the reference values. CONCLUSIONS: The present data confirm the wide variability in the assessment of normal sperm and show a lower variability for several anomalies and MAI. They underscore the role that experience plays and the importance of following the recommended methodologies for relevant and comparable results.

Clinical Competence↗