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PubMed1997

Inter-individual variability of benzene metabolism to trans,trans-muconic acid and its implications in the biological monitoring of occupational exposure.

Unmodified benzene (UBz) and trans,trans-muconic acid (t,t-MA) were measured in urine samples collected at the end of the first half-shift in 80 bus drivers from a large city in Northern Italy. Mean UBz was 1155 ng/l (S.D. = 494), range 85-1980 ng/l; these values roughly correspond to 10-1000 micrograms/m3 of benzene in air. Mean t,t-MA was 297 micrograms/g creatinine; the range was large (20-1295 micrograms/g creatinine), and the distribution of values was bimodal. At further analysis of t,t-MA data, two subgroups of 59 and 18 subjects were identified (3 outliers were excluded): mean values of the index were 108 (S.D. = 65) and 916 (S.D. = 264) micrograms/g creatinine respectively, and the values within each subgroup were normally distributed. The mean ratio between t,t-MA and UBz in the subgroups were 0.15 and 0.85, respectively; the difference was significant. The first subgroup was defined as 'poor t,t-MA metabolizers', the other as 'efficient t,t-MA metabolizers'. No inter-subgroup differences were observed regarding the main characteristics (age, dietary and smoking habits, etc.). As the parent compound of t,t-MA, trans,trans-muconaldehyde is myelotoxic, and its production has been implicated in benzene-induced leukemia. 'efficient' t,t-MA metabolizers may be at higher risk of developing benzene toxicity. If confirmed in further studies, the inter-individual variability rate of metabolizing benzene to t,t-MA may introduce some limitations in the application of this metabolite as an exposure index of low benzene exposure. Nevertheless, the t,t-MA/UBz ratio may be an important index of susceptibility to benzene toxicity.

Adult↗
PubMed2001

The anatomy of auditory word processing: individual variability.

This study used functional magnetic resonance imaging (fMRI) to investigate the neural substrate underlying the processing of single words, comparing activation patterns across subjects and within individuals. In a word repetition task, subjects repeated single words aloud with instructions not to move their jaws. In a control condition involving reverse speech, subjects heard a digitally reversed speech token and said aloud the word "crime." The averaged fMRI results showed activation in the left posterior temporal and inferior frontal regions and in the supplementary motor area, similar to previous PET studies. However, the individual subject data revealed variability in the location of the temporal and frontal activation. Although these results support previous imaging studies, demonstrating an averaged localization of auditory word processing in the posterior superior temporal gyrus (STG), they are more consistent with traditional neuropsychological data, which suggest both a typical posterior STG localization and substantial individual variability. By using careful head restraint and movement analysis and correction methods, the present study further demonstrates the feasibility of using overt articulation in fMRI experiments.

Adult↗
PubMed1991

Individual variability in self-reported improvement for depressed psychiatric inpatients on the MCMI-II.

This study evaluated self-reported symptom improvement on the MCM-II Dysthymia (D) scale for 109 depressed psychiatric inpatients. Rather than presenting the findings in traditional "group mean" format, data were analyzed to highlight the variability of clinical improvement for individual patients. Two criteria for judging clinically significant improvement (Jacobson, Follette, & Revenstorf, 1984) were employed, namely, that the client move from the dysfunctional to functional range during treatment and that the change between pretest and posttest be statistically reliable. Results indicated that 39 (35.8%) of the 109 patients met these criteria.

Adult↗
PubMed1982

A method for estimating within-individual variability in clearance and in volume of distribution from standard bioavailability studies.

Bioavailability studies are commonly undertaken, and most, because they involve subjects taking repeated doses of a drug, contain information on intraindividual variability in pharmacokinetics. However, because in such studies bioavailability itself is unknown, it is difficult to resolve which pharmacokinetic parameters vary within individuals. A mathematical model is presented which permits estimation of variability in clearance and in volume of distribution. When applied to pooled data arising from five theophylline bioavailability studies, this model has given statistical evidence that clearance of theophylline is inherently more variable within individuals (coefficient of variation, 13%) than volume of distribution (8%). As a result, use of the measurement AUC-beta rather than AUC as a more precise index of bioavailability is justified in studies where beta is measured with reasonable precision. The model could be applied to estimation of within-batch within-person variability in bioavailability.

Biological Availability↗
PubMed2006

The generalization of perceptual-motor intra-individual variability in young and old adults.

We examined the generalizability of intra-individual perceptual-motor variability in young and old adults. Participants completed four motor tasks that all required the maintenance of a steady state: finger tremor, and single-digit, two-digit, and three-digit isometric force production. Older adults had a greater amount of variability and an increased time and frequency structure of variability, except in the tremor task. There was a moderate association between the magnitudes of variability across tasks in the oldest age group, but the structural measures of variability were more highly related across tasks and the strength of this relationship increased with age. These findings support the hypothesis that older adults are less able than younger adults to adapt the structure of their perceptual-motor variability to task demands.

Adaptation, Psychological↗
PubMed1990

Analysis of individual variability among older adults on the Stroop Color Word Interference Test.

The present study examines systematic variation in the pattern of response to the Stroop test among a sample of older adults (N = 41), as well as the extent to which various configural patterns of response are related to other individual difference factors. Pattern analysis identified four reasonably prototypic patterns of performance. Three significant discriminant functions, capable of differentiating the four response patterns, were significantly and uniquely related to age, level of cautiousness, and verbal intelligence, respectively. The analyses suggest that performance on the Stroop test is multidimensional with significant variation among older adults, and that different components of performance are differentially related to unique individual difference variables. The findings reinforce the importance of recognizing and understanding the nature of individual variation among elderly individuals in aging research.

Age Factors↗
PubMed1999

Inter- and intra-individual variability of ground reaction forces during sit-to-stand with principal component analysis.

Variable reduction is an important issue in biomechanics, because the definition of a non-redundant set of variables necessary for a complete description of a given motor act provides information about the motor strategy. A systematic tool for dealing with variable reduction problems is Principal Component Analysis. In this paper, as an example of an application of this technique, the set of Ground Reaction Forces (GRFs) provided by a six-component force plate, gained during standing up in a heterogeneous population of 82 normal individuals, was reduced to a set of fewer variables. Each subject was required to stand up from a chair five times at different, randomly self selected, speeds, obtaining a data set of 410 trials. Principal Components (PCs) of GRFs were computed for each trial. On average, over the ensemble of trials, first and second PCs (PC1 and PC2) explained together 90% of PCs. Inter- and intra-individual repeatability of the first two PCs was investigated by examining the correlation coefficient between PC waveforms obtained from the whole set of trials and within the set of trials performed by the same subject, respectively. While the PC1 exhibited repeatable patterns, the second one, although repeatable within the group of trials performed by the same subject, displayed marked inter-individual variability. Therefore, PC1 was related to intrinsic aspects of the motor task and PC2 to inter-subject features.

Adult↗
PubMed2000

Combining ecological and individual variables to reduce confounding by indication: case study--subarachnoid hemorrhage treatment.

Ecological studies may reduce the problem of confounding by indication; however, these studies introduce new biases not present in individual-level analyses. To study the potential for ecological variables to reduce confounding by indication, we used a large database of admissions for ruptured cerebral aneurysms to evaluate the association of in-hospital death with treatment type-surgery or endovascular therapy. We compared results of three multivariable models: individual-level, ecological, and a two-level model with an ecological treatment variable and individual-level covariates and outcome. Trends in the individual-level and ecological models were in opposite directions, suggesting confounding by indication in the individual-level analysis. The two-level analysis revealed a strong association between institutional utilization of endovascular therapy and reduced individual risk of in-hospital death. Using an ecological treatment variable in an individual analysis may combine reduced confounding by indication in ecological analyses with increased power and more precise specification of outcomes and covariates in individual-level analyses.

Bias↗
PubMed2003

Individual variability in Tityus serrulatus (Scorpiones, Buthidae) venom elicited by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Venom variability in specimens of Tityus serrulatus scorpion was assessed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) analyses. An expanded time lag venom extraction protocol was carried out using ten scorpions to study individual variations that might occur due to different rates in protein expression and/or processing. The first extraction of venom was made from the animals after 20 days of starvation, which allowed the venom gland to be filled up. The second extraction event was carried out 24 hours after the first one. The third was 8 days after the first extraction. By means of MALDI-TOF analyses, important variations were observed in venoms of a single specimen extracted at different times, especially in latter extraction events. These variations are most probably related to dynamics in cell gland production. Since T. serrulatus is a parthenogenetic species, sexual variations are naturally excluded and we did not expect intra-specific variations, which was confirmed. Knowledge of individual venom variability is extremely important to avoid misunderstandings in the use of venom proteomic analysis as a taxonomic tool.

Animals↗
PubMed1985

[Clinical pharmacokinetics of the antitumor antibiotic reumycin: an analysis of individual variability].

The pharmacokinetics of reumycin, an antitumor antibiotic, was studied with high performance liquid chromatography in patients with tumors of the brain and kidneys. The drug was injected intravenously in single doses of 30-300 mg. It was shown that the pharmacokinetics of reumycin was nonlinear and within every dose could be depicted by a three- or two-compartmental model. Its nonlinearity was due to saturation of the antibiotic binding to blood plasma proteins. 20-40 per cent of the intact antibiotic was excreted with the urine unchanged, which indicated a significant role of extrarenal excretion of the antibiotic. The dose dependence of the pharmacokinetic parameters and in the particular of the area under the reumycin blood concentration on the time curve and cumulative renal excretion varied with patients. Distribution of patients by these parameters was bimodal. This factor and the differences in renal excretion caused significant variability in the reumycin pharmacokinetics, which required individualization and control of the antibiotic use in patients. The reumycin half-life in man predicted with the use of the Dedrick pharmacokinetic time scale by the data of experiments on rats appeared close to that established in patients (41 and 33.5 hours, respectively).

Antibiotics, Antineoplastic↗
PubMed2005

Relation of neonatal iron status to individual variability in neonatal temperament.

The relation between indices of neonatal iron status and individual differences in neonatal temperament were investigated in a sample of 148 low-income Peruvian women and their newborn infants. Using cord blood, at birth we obtained measures of neonatal ferritin, serum iron, and hemoglobin. While neonates were still in the hospital, their behavior during a structured anthropometry examination was videotaped and subsequently coded on four temperament dimensions: activity level, negative emotionality, alertness, and soothability. The same dimensions were coded using a videotape obtained during a subsequent visit to the neonates' homes. Results indicated that lower levels of neonatal hemoglobin and serum iron were related to higher levels of negative emotionality and to lower levels of alertness and soothability. A similar pattern was found for ferritin, but only for females. For the most part, relations between neonatal iron measures and neonatal temperament were linear, operating across the full range of iron values. Our pattern of iron-temperament results could not be attributed to variation in family demographics, low birth weight, gestational age, maternal dietary intake, or markers of neonatal illness and maternal diabetes. Our findings are consistent with prior research with older infants relating iron deficiency to temperament. These results support the importance of increased research on the early functional-behavioral consequences of individual differences in iron status as well as on the mechanisms that underlie such consequences.

Affect↗
PubMed1990

The Multiple Sleep Latency Test: individual variability and time of day effect in normal young adults.

The influence of individual characteristics on diurnal physiological sleep tendency was investigated in young good sleepers. Fifty-five subjects underwent a Multiple Sleep Latency Test (MSLT) procedure. Among them 11 also participated in Repeated Test Sustained Wakefulness (RTSW) procedure. The MSLT results were analyzed as a function of both the number of sleep onsets per day and the time of day. Diurnal sleepiness seemed to be better appreciated by sleep onset (SO) frequency than by the traditional criteria of sleep latency. SO frequency, unlike latency, was influenced by factors such as usual sleep duration, morning/evening score, and RTSW procedure. Time of day effect was characterized by a decrease in sleep tendency at the beginning and at the end of the day (decrease in SO frequency and increase in SO latencies); between these two points a peak of sleepiness around 1400 was observed. The morning and evening periods of high alertness could represent important anchor points for the coupling of the sleep/wake and temperature rhythms.

Adult↗
PubMed1987

Genetic architecture of inter-individual variability in apolipoprotein, lipoprotein and lipid phenotypes.

Phenotypes that predict coronary heart disease (CHD) are the consequence of interactions between many genetic and environmental factors. Quantitative measures of plasma apolipoproteins, lipoproteins and lipids are examples of phenotypes that link genetic and environmental factors to the CHD end-point. Population studies in Hawaii, Michigan and elsewhere have established that a significant fraction of variability in these phenotypes is attributable to genetic differences among individuals. Recent advances in molecular biology provide measures of the gene loci that code for the apolipoproteins, the cellular receptors for lipoprotein particles and the catalysts and cofactors in lipoprotein metabolism. By measuring polymorphic protein variability and restriction site variability in small regions of DNA known to contain genes that code for the proteins involved in these functions, it is possible to assign polygenetic effects to specific alleles or haplotypes. This 'measured genotype' approach may be used to study the genetic architecture (number of loci involved, the frequencies and effects of their alleles, and the type of loci, i.e., structural or regulatory) of quantitative variation in the plasma apolipoproteins, lipoproteins and lipids. This paper reviews statistical models, sampling designs and results of studies designed to estimate the genetic architecture of selected apolipoproteins, lipoproteins and lipids. The usefulness of these studies for answering questions about the prediction of CHD in the population, the family and the individual are discussed and the directions that human quantitative genetic studies will take in the future are considered.

Apolipoproteins↗
PubMed2005

A method for detection of differential gene expression in the presence of inter-individual variability in response.

MOTIVATION: Many stimuli to biological systems result in transcriptional responses that vary across the individual organism either in type or in timing. This creates substantial difficulties in detecting these responses. This is especially the case when the data for any one individual are limited and when the number of genes, probes or probe sets is large. RESULTS: We have developed a procedure that allows for sensitive detection of transcriptional responses that differ between individuals in type or in timing. This consists of four steps: one is to identify a group of genes, probes or probe sets that detect genes that belong to a molecular class or to a common pathway. The second is to conduct a statistical test of the hypothesis that the gene is differentially expressed for each individual and for each gene in the set. The third is to examine the collection of these statistics to see if there is a detectable signal in the aggregate of them. The final step is to assess the significance of this by resampling to avoid correlational bias. AVAILABILITY: Software in the form of R code to perform the required test is available from the first author or from his website http://www.idav.ucdavis.edu/~dmrocke/software; however the procedures are also easily performed using any standard statistical software.

Algorithms↗