Intrasubject variability of selected force-platform parameters in the quantification of postural control

Platform stabilometry is increasingly applied to monitor or re-educate standing balance in clinical rehabilitation. Consequently, insight is needed into the validity, reliability, and sensitivity of different force-platform parameters. This study focuses on the intrasubject variability as the major source of variance (unreliability) in the study of human motor skills. The intrasubject variability of several, commonly applied force-platform parameters was determined across ten repeated tests of quiet two-legged standing in healthy subjects to identify the most consistent and stable parameters in the quantification of postural control. The variability of the root mean square (RMS) amplitude, peak-to-peak amplitude, mean frequency, and RMS velocity of the fore-aft and lateral components of the center-of-pressure fluctuations was investigated under varying (visual and cognitive) task conditions. The results indicate that all selected parameters show considerable intrasubject variability irrespective of the task context. Nonetheless, both the RMS amplitude and RMS velocity in either direction of sway do not demonstrate a significant trend across repeated tests. Among the selected parameters, the RMS velocity in the fore-aft direction shows the greatest intrasubject consistency, as well as a high sensitivity to, for example, visual deprivation. These findings support the reliability and validity of this parameter in the clinical quantification of postural control.     

A strategy to use soft data effectively in randomized controlled clinical trials.

Soft data are defined as measures having substantial intrasubject variability due to errors of measurement or to the inconsistency of subjects' responses. Such data are often important measures of response in randomized clinical trials. In this context, we show that using an intensive design and the slope of response on time as the outcome measure (a) maximizes sample retention and (b) decreases within-group variability, thus (c) maximizing the power of test procedures without requiring increased sample sizes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of stability of performance in patients with traumatic brain injury: Variability and consistency on reaction time tests.

The stability of performance of reaction times (RTs) on 3 visual discrimination tasks was assessed in patients with varying severity of traumatic brain injury (TBI) and in matched control Ss. Results were analyzed for group and individual variability and consistency of performance over time. There was significantly greater intersubject (group) variability in the TBI group. Individual patients (intrasubject) tended to be more variable in performance and less consistent over time than control Ss, but this occurred only with specific measures, which suggests that increased lack of stability in performance is not a general impairment after brain damage but requires specific analyses for identification of performance differences. This intrasubject variability was indepedent of test–retest and split-half test reliability. No obvious factors such as severity of brain injury were related to the variability and inconsistency of performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multidimensional analysis of reactive forces of the foot during normal walking]

The authors present the analysis of the three components of ground reaction forces on both left and right feet on 50 subjects. Fourier analysis shows that a 25-Hz sampling is sufficient to fully characterize the normal gait. The approach used in order to study the data tables built for each component consisted in principal component factor analysis. This multivariate method, which looses the least possible information in relation to raw data, has indicated a high variability between subjects. Concerning the intrasubject variability, great asymmetry occurred between the forward and back forces. With respect to the relationship, the three components, the medial-lateral force was very independent of the two others. Particular classes of normal gait have been proposed.     

Anxiety and the variability of word associates.

15 Ss who scored high on the Taylor MA scale and 15 Ss who scored low on the MA scale were given a word associate task. The highly anxious Ss tended to have sets of word associates lower in intersubject variability than the nonanxious Ss for stimulus words that elicited sets of word associates that are low in variability. Highly anxious Ss tended to give sets of word associates higher in intersubject variability than nonanxious Ss for stimulus words that elicited sets of word associates that are high in intersubject variability. A 2nd experiment reports data indicating a relationship between inter- and intrasubject variability of word associates. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Individual differences in intraperson variability in mood.

The experience sampling method and palm-top computers were used to obtain 75–200 randomly timed in situ assessments of 11 mood-related items from 54 Ss over 12–24 days. The variability in the distribution of an S's responses to each item was used as an estimate of intrasubject mood variability. Mood variability was stable across time and across situations. The intercorrelations among the individual item variabilities were also substantial; when the items were combined into a mood variability scale, the coefficient alpha was .84. The stability and internal consistency of mood variability could not be reasonably attributed to similarity in item valences, differences among the Ss in the situations they encountered, response biases, or response errors. It was concluded that mood variability is a stable personal characteristic, but additional analyses suggested that it may be independent from other kinds of intraperson variability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reproducibility of shear rate and shear stress assessment by means of ultrasound in the common carotid artery of young human males and females

In the present study, the reliability of an ultrasonic shear rate estimating system, in terms of intrasubject intrasession, intersubject intrasession and intersubject intersession variability coefficients for the assessment of wall shear rate (WSR) in the common carotid artery (CCA) was determined in eight presumed healthy volunteers. Measurements were performed on consecutive days (day 1, day 2 and day 7). To investigate whether there were differences in WSR due to gender, dynamic WSR in the CCA was assessed in 11 presumed healthy males (mean age 24 y) and 11 presumed healthy females (mean age 25 y). Wall shear stress (WSS) was estimated from WSR and calculated whole blood viscosity. The average intrasubject intrasession variability was about 15% for peak WSR and about 12% for mean WSR. The intersubject intrasession variability for peak WSR decreased from 19% on day 1 to 16% on day 7 and for mean WSR from 17% on day 1 to 11% on day 7. The intersubject intersession variability is on the order of 5% for peak WSR and about 4% for mean WSR. No significant differences could be detected between peak and mean WSR values on day 1, day 2 and day 7, indicating good short- and medium-term intersubject intersession reproducibilities. No differences in peak and mean WSR were found between the left and the right CCA in the male group as well as in the female group. Mean WSS was similar in males (1.3 +/- 0.3 Pa) and in females (1.2 +/- 0.2 Pa), but peak WSS was slightly, but significantly, higher in males (4.3 +/- 1.3 Pa) than in females (3.3 +/- 0.7 Pa). It can be concluded that peak and mean WSR can be reliably determined noninvasively using ultrasound.     

Computer-assisted measurement of lumbar spine radiographs

RATIONALE AND OBJECTIVES: The authors evaluated a method for obtaining reproducible, reliable measurements from standard lumbar spine radiographs for determining the degree of spondylolisthesis, vertebral body height, intervertebral disk space height, disk space angle, and degree of vertebral body wedging. MATERIALS AND METHODS: Four to six easily defined points were identified on each vertebral body on anteroposterior and lateral plain radiographs of the lumbosacral spine of patients. From these points, the degree of spondylolisthesis, the vertebral body height, the intervertebral disk space height, the disk space angle, and the degree of vertebral body wedging were easily calculated by using well-known geometric relationships. This method requires the use of a personal computer and a standard spreadsheet program but does not require the use of any other specialized radiographic equipment, computer hardware, or custom software. RESULTS: Calculations of intra- and interobserver variability for the measurement of spondylolisthesis, disk space height, disk space angle, and vertebral body height measurement showed that the technique is extremely reproducible. CONCLUSION: This technique may prove useful in the prospective evaluation of potential candidates for lumbar spinal stenosis surgery.     

Use of the repeated cross-over designs in assessing bioequivalence

We consider applications of the repeated 2 x 2 cross-over design to evaluating bioequivalence between the two formulations. The repeated 2 x 2 cross-over design allows us not only to assess bioequivalence on average bioavailability and to examine the subject-by-formulation interaction but also to obtain independent unbiased estimates of intrasubject variability. One consequence of unequal intrasubject variabilities is that the sum of squares of intersubject residuals and the sum of squares of subject-by-formulation residuals are not independent. We also discuss the relative merits of this design as compared to the standard 2 x 2 cross-over design without repeated measurements in terms of precision and sample size with respect to the ratio of the number of subjects to the repeated measurements per subject. We investigate other uses of the 2 x 2 cross-over in examining the bioequivalence between the two different dosing regimens. Possible applications of other repeated cross-over designs to bioequivalence for more than two formulations are explored. A numerical example illustrates the proposed procedure.     

A macro-driven Excel template for determining the anaerobic capacity using an air-braked ergometer

This paper describes a microcomputer system for automating the process of data collection, calculation and display of anaerobic capacity tests on an air-braked ergometer. The use of the spreadsheet Excel and associated 'Dalog' program represents an advance on current software which estimates the anaerobic capacity from work performed alone. Numerous calculations are required when air-braked, rather than friction-braked erogometers are used. Each 1 s power output collected during an all-out sprint on the ergometer is corrected against the criterion of a dynamic calibration rig and adjusted for differences in barometric pressure, ambient temperature and humidity. The Excel template features a series of macros invoked by buttons imbedded in the spreadsheet. Their selection displays various dialogue boxes which request input related to the calculation of oxygen deficit and related variables. Selecting the final macro prints a summary table and charts which include: power output, fatigue index, mechanical work performed, % aerobic contribution to work, oxygen demand, oxygen consumption and anaerobic capacity as determined by the maximal accumulated oxygen deficit.     

Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide

The study was conducted to assess the bioavailability of avitriptan after a standard high fat meal, in relation to gastrointestinal transit. Six healthy male subjects were enrolled in a four-period study with a partial replicate design where each was administered 150-mg avitriptan capsule (i) after an overnight fast, (ii) 5 min after a standard high-fat breakfast, and (iii) 4 hr after a standard high fat breakfast. The treatment administered in Period 3 was repeated in Period 4 to assess intrasubject variations in pharmacokinetics and gastrointestinal (GI) transit. Avitriptan capsules were specially formulated with nonradioactive samarium chloride hexahydrate which was neutron-activated to gamma-emitting samarium before dosing. Serial blood samples were collected for analysis of avitriptan up to 24-hr postdose, and serial scintigraphic images were obtained to assess the plasma concentration-time profile in relation to the GI transit of the avitriptan capsule contents. Bioavailability of avitriptan was reduced when administered in the fed condition but only the decrease in AUC(INF) was statistically significant. Tmax was significantly delayed between the fed conditions and the fasted condition. Qualitative appearance of plasma concentration-time profiles for avitriptan could be related to the manner in which the drug emptied from the stomach. It was also apparent that avitriptan exerted a secondary pharmacologic effect that temporarily suspended gastric emptying in the fasted treatment. Thus, when gastric emptying was interrupted and then resumed, the net result was a double peak in some of the individual plasma concentration profiles. Scintigraphic analysis also demonstrated that upon emptying from the stomach, avitriptan was rapidly absorbed from the upper small intestine. In the fed state, gastric emptying was slow and continuous resulting in extended absorption and a lower occurrence of double peaks. Qualitatively, the intrasubject variability in Cmax and AUC could be explained by the intrasubject variability in gastric emptying in both fasted and fed conditions.     

Program Assessment and Evaluation Using Student Grades Obtained on Outcome-Related Course Learning Objectives

A methodology was developed for assessing student performance with respect to program outcomes and course objectives using available graded coursework. The methodology uses a matrix formulation to relate individual coursework problems to program outcomes and course objectives. Assessment data and required mapping matrices are collected in spreadsheet form and automatically transferred to a relational database. Student and class performance with respect to program objectives is calculated using Structured Query Language (SQL) queries and data fitting through least-squares. The methodology was used to collect data, assess student performance, and identify necessary program changes over a four-year period in an engineering program.     

Construction Management Control with Microcomputers

The development of microcomputers is changing the nature of common construction management functions. The estimating function can now be used with greater ease to simultaneously evaluate the time required to perform different project activities and keep cost data related to cost control. While this procedure was time consuming for manual computation, it could be done in a reasonable amount of time when using microcomputers. This paper discusses the formation of a microcomputer system which can perform the functions of estimating, cost control, and scheduling at the same time. The procedure makes use of productivity of a crew of particular size, the materials and the equipment needed, to generate time data related to scheduling and cost data related to estimating and cost control. The software needed for implementing the system is an electronic spreadsheet program, a data base management program and a time management program available for most microcomputers at a relatively inexpensive cost.     

Practical aspects of faculty practice. A model for excellence

The aim of the study was to determine the intrasubject variability of the pressure-transmission ratio (PTR) with various cough intensities in subjects with genuine stress incontinence. Thirty-six patients with genuine stress incontinence underwent multichannel urodynamics and had a series of pressure-transmission ratios (PTRs) determined with the urethral transducer placed at the point of the maximal closure pressure. Patients were asked to cough with increasing intensities and three to four different cough-induced PTRs were recorded for each subject. The data were analysed using regression analysis, repeated measures analysis of variance and comparison of variance. The PTRs showed a high degree of variability within subjects. The mean within subject standard deviation was 18.5%. The effect of parity, maximal urethral closure pressure and age were insignificant on the variability. Cough intensities of greater than 90 cmH2O have a lesser degree of variability. The mean PTR across all cough intensities was fairly constant in the 82%-87% range. It was concluded that the PTR in an individual has a high degree of variability independent of cough intensity, and cannot be relied upon as a diagnostic measure in subjects with genuine stress incontinence. However, the PTR for the population as a whole was consistent across all cough intensities.     

Are self-perceivable neuropsychological deficits in patients with neuroses or personality disorder diagnoses indicative of later schizophrenia?

We designed a spreadsheet package for the computation of plausibility of paternity, that can cope with highly polymorphic genetic markers and cases of deceased parties. The application program is Microsoft EXCEL, which is one of the best-selling spreadsheet software running on both Microsoft Windows and Macintosh OS. Komatsu's formula for paternity testing was mainly employed in the spreadsheet package. Probability of the mother-child-alleged father combination was calculated using "IF" function to compare the members' genotypes, whereas "VLOOKUP (or HLOOKUP)" function was employed to refer to a list of genes and their frequencies. In case of a phenotype consisting of several genotypes, the list of phenotypes versus genotypes was also given, to which the function referred. To extend these spreadsheets available for the test of deceased party, additional sheets were also created to estimate frequencies of alleged father's possible genotypes. These probabilities were calculated on the basis of types of his parents and siblings, those of his wife and their biological children, and those of both. This package would be cut out to compute the probability of paternity with extremely polymorphic loci with gentle user interface. Calculation time is satisfactorily short, although it requires considerably large disk space in some extremely complicated cases. Japanese version of this package is freely available at anonymous FTP site of the Department of Forensic Medicine, Tohoku University School of Medicine.     

Modeling thermal skin burns on a personal computer

Mathematic models have been used for several decades to predict the severity of burn injury that would result from application of a given thermal stress to the surface of the skin. Solution of the governing mathematic equations has been achieved either by analytic methods, with required simplifying assumptions that may compromise the rigor with which the results are applied, or by numeric methods, which require programming of finite element or finite difference codes in computer languages. In recent years microcomputer hardware and the associated software have become both powerful and relatively simple to use, and the price per unit of computing capability has dropped dramatically. Thus it is now possible to perform on a desktop machine with relative case calculations that previously might have been prohibitively complex or expensive. Modeling of burn injuries fits into this category. This article presents a straightforward method for implementing a finite difference solution to the burn process through the combination of a Macintosh personal computer and a widely used spreadsheet software program; this hardware and software combination has been used widely for a broad spectrum of general computing activities. This article presents a model for a surface thermal burn, as implemented for solution on a spreadsheet, with example runs to illustrate and verify the method.     

Asymmetry of the mean-variability tradeoff raises questions about the model in investigations of individual bioequivalence

Tradeoff between changes of intraindividual variations of 2 drug formulations and of the difference between their means is a characteristic of a procedure suggested for the determination of individual bioequivalence [Schall and Luus 1993] and to be proposed by the Food and Drug Administration for adoption. Hauck et al. [1996] investigated properties of the tradeoff. Their procedure was applied and extended in the present study. The tradeoff was shown to be asymmetric. Notably, a small change in intrasubject variations can elicit, under various conditions, a comparatively large change in the allowable difference between means which can still be compatible with the declaration of bioequivalence. For instance, when the intraindividual coefficients of variations are 40% and 38% for the reference and test formulations, respectively, the allowable difference between means may increase, as a benefit, by 12.3%. A penalty by 11.2% is elicited if the intrasubject variations of the reference and test products are 40 and 42%, respectively. In addition, 4-period crossover trials were simulated. Ratios of estimated variances of the 2 formulations followed an F-distribution. Distributions of changes in allowable deviations between means were calculated from the tradeoff relationships; generally substantial changes were noted with high probabilities. For example, with an intraindividual variation of 30% there is an estimated 37% probability that a benefit of 10% increase, or larger, is gained by chance in the allowable difference between means, and an additional 36% probability that a penalty of a 10%, or larger, decrease in the allowable difference is suffered. With an intrasubject variation of 40%, the estimated probabilities are 42% and an additional 42% for a 10% expansion and contraction, respectively, of the allowable difference between means. Consequently, the strong asymmetry of the tradeoff could result in very large probabilities for benefits and penalties. Therefore, the investigated model assessing individual bioequivalence does not appear to be suitable for implementation.     

Analysis of Laterally Loaded Piles in Soil with Stiffness Increasing with Depth

This article reports a variational solution and its spreadsheet calculation procedure for the analysis of laterally loaded piles in a soil with stiffness increasing with depth. The aim of the paper is to provide solutions that can be used simply with recourse only to spreadsheet calculation to solve the displacement and bending moment of laterally loaded piles, so that they can be easily applied in practice as an alternative approach to analyze the response of laterally loaded piles.     

An approach for widening the bioequivalence acceptance limits in the case of highly variable drugs

PURPOSE: Highly variable drugs pose a problem in bioequivalence assessment because they often fail to meet current regulatory acceptance criteria for average bioequivalence (80-125%). This paper examines alternative approaches to establishing bioequivalence. METHODS: Suggested solutions have included alternate study designs, e.g., replicate and multiple dose studies, reducing the level of the confidence interval, and widening the acceptance limits. We focus on the latter approach. RESULTS: A rationale is presented for defining wider acceptance limits for highly variable drugs. Two previously described methods are evaluated, and a new method having more desirable properties is proposed. CONCLUSIONS: We challenge the "one size fits all" current definition of bioequivalence acceptance limits for highly variable drugs, proposing alternative limits or "goal posts" which vary in accordance with the intrasubject variability of the reference product.     

Presentation of the intrasubject coefficient of variation for sample size planning in bioequivalence studies

Bioequivalence studies are generally performed as crossover studies and, therefore, information on the intrasubject coefficient of variation is needed for sample size planning. Unfortunately, this information is usually not presented in publications on bioequivalence studies, and only the pooled inter- and intrasubject coefficient of variation for either test or reference formulation is reported. Thus, the essential information for sample size planning of future studies is not made available to other researchers. In order to overcome such shortcomings, the presentation of results from bioequivalence studies should routinely include the intrasubject coefficient of variation. For the relevant coefficients of variation, theoretical background together with modes of calculation and presentation are given in this communication with particular emphasis on the multiplicative model.