Intra-subject sample size effects in plantar pressure analyses.

BACKGROUND: Recent work using large datasets (>500 records per subject) has demonstrated seemingly high levels of step-to-step variation in peak plantar pressure within human individuals during walking. One intuitive consequence of this variation is that smaller sample sizes (e.g., 10 steps per subject) may be quantitatively and qualitatively inaccurate and fail to capture the variance in plantar pressure of individuals seen in larger data sets. However, this remains quantitatively unexplored reflecting a lack of detailed investigation of intra-subject sample size effects in plantar pressure analysis. METHODS: Here we explore the sensitivity of various plantar pressure metrics to intra-subject sample size (number of steps per subject) using a random subsampling analysis. We randomly and incrementally subsample large data sets (>500 steps per subject) to compare variability in three metric types at sample sizes of 5-400 records: (1) overall whole-record mean and maximum pressure; (2) single-pixel values from five locations across the foot; and (3) the sum of pixel-level variability (measured by mean square error, MSE) from the whole plantar surface. RESULTS: Our results indicate that the central tendency of whole-record mean and maximum pressure within and across subjects show only minor sensitivity to sample size >200 steps. However, <200 steps, and particularly <50 steps, the range of overall mean and maximum pressure values yielded by our subsampling analysis increased considerably resulting in potential qualitative error in analyses of pressure changes with speed within-subjects and in comparisons of relative pressure magnitudes across subjects at a given speed. Our analysis revealed considerable variability in the absolute and relative response of the single pixel centroids of five regions to random subsampling. As the number of steps analysed decreased, the absolute value ranges were highest in the areas of highest pressure (medial forefoot and hallux), while the largest relative changes were seen in areas of lower pressure (the midfoot). Our pixel-level measure of variability by MSE across the whole-foot was highly sensitive to our manipulation of sample size, such that the range in MSE was exponentially larger in smaller subsamples. Random subsampling showed that the range in pixel-level MSE only came within 5% of the overall sample size in subsamples of >400 steps. The range in pixel-level MSE at low subsamples (<50) was 25-75% higher than that of the full datasets of >500 pressure records per subject. Overall, therefore, we demonstrate a high probability that the very small sample sizes (n < 20 records), which are routinely used in human and animal studies, capture a relatively low proportion of variance evident in larger plantar pressure data set, and thus may not accurately reflect the true population mean.

The nature of functional variability in plantar pressure during a range of controlled walking speeds.

During walking, variability in step parameters allows the body to adapt to changes in substrate or unexpected perturbations that may occur as the feet interface with the environment. Despite a rich literature describing biomechanical variability in step parameters, there are as yet no studies that consider variability at the body-environment interface. Here, we used pedobarographic statistical parametric mapping (pSPM) and two standard measures of variability, mean square error (m.s.e.) and the coefficient of variation (CV), to assess the magnitude and spatial variability in plantar pressure across a range of controlled walking speeds. Results by reduced major axis, and pSPM regression, revealed no consistent linear relationship between m.s.e. and speed or m.s.e. and Froude number. A positive linear relationship, however, was found between CV and walking speed and CV and Froude number. The spatial distribution of variability was highly disparate when assessed by m.s.e. and CV: relatively high variability was consistently confined to the medial and lateral forefoot when measured by m.s.e., while the forefoot and heel show high variability when measured by CV. In absolute terms, variability by CV was universally low (less than 2.5%). From these results, we determined that variability as assessed by m.s.e. is independent of speed, but dependent on speed when assessed by CV.

Vector field statistics for objective center-of-pressure trajectory analysis during gait, with evidence of scalar sensitivity to small coordinate system rotations.

Center of pressure (COP) trajectories summarize the complex mechanical interaction between the foot and a contacted surface. Each trajectory itself is also complex, comprising hundreds of instantaneous vectors over the duration of stance phase. To simplify statistical analysis often a small number of scalars are extracted from each COP trajectory. The purpose of this paper was to demonstrate how a more objective approach to COP analysis can avoid particular sensitivities of scalar extraction analysis. A previously published dataset describing the effects of walking speed on plantar pressure (PP) distributions was re-analyzed. After spatially and temporally normalizing the data, speed effects were assessed using a vector-field paired Hotelling's T2 test. Results showed that, as walking speed increased, the COP moved increasingly posterior at heel contact, and increasingly laterally and anteriorly between ∼60 and 85% stance, in agreement with previous independent studies. Nevertheless, two extracted scalars disagreed with these results. Furthermore, sensitivity analysis found that a relatively small coordinate system rotation of 5.5° reversed the mediolateral null hypothesis rejection decision. Considering that the foot may adopt arbitrary postures in the horizontal plane, these sensitivity results suggest that non-negligible uncertainty may exist in mediolateral COP effects. As compared with COP scalar extraction, two key advantages of the vector-field approach are: (i) coordinate system independence, (ii) continuous statistical data reflecting the temporal extents of COP trajectory changes.

The evolution of compliance in the human lateral mid-foot.

Fossil evidence for longitudinal arches in the foot is frequently used to constrain the origins of terrestrial bipedality in human ancestors. This approach rests on the prevailing concept that human feet are unique in functioning with a relatively stiff lateral mid-foot, lacking the significant flexion and high plantar pressures present in non-human apes. This paradigm has stood for more than 70 years but has yet to be tested objectively with quantitative data. Herein, we show that plantar pressure records with elevated lateral mid-foot pressures occur frequently in healthy, habitually shod humans, with magnitudes in some individuals approaching absolute maxima across the foot. Furthermore, the same astonishing pressure range is present in bonobos and the orangutan (the most arboreal great ape), yielding overlap with human pressures. Thus, while the mean tendency of habitual mechanics of the mid-foot in healthy humans is indeed consistent with the traditional concept of the lateral mid-foot as a relatively rigid or stabilized structure, it is clear that lateral arch stabilization in humans is not obligate and is often transient. These findings suggest a level of detachment between foot stiffness during gait and osteological structure, hence fossilized bone morphology by itself may only provide a crude indication of mid-foot function in extinct hominins. Evidence for thick plantar tissues in Ardipithecus ramidus suggests that a human-like combination of active and passive modulation of foot compliance by soft tissues extends back into an arboreal context, supporting an arboreal origin of hominin bipedalism in compressive orthogrady. We propose that the musculoskeletal conformation of the modern human mid-foot evolved under selection for a functionally tuneable, rather than obligatory stiff structure.

Holocene footprints in Namibia: the influence of substrate on footprint variability.

We report a Holocene human and animal footprint site from the Namib Sand Sea, south of Walvis Bay, Namibia. Using these data, we explore intratrail footprint variability associated with small variations in substrate properties using a "whole foot" analytical technique developed for the studies in human ichnology. We demonstrate high levels of intratrail variability as a result of variations in grain size, depositional moisture content, and the degree of sediment disturbance, all of which determine the bearing capacity of the substrate. The two principal trails were examined, which had consistent stride and step lengths, and as such variations in print typology were primarily controlled by substrate rather than locomotor mechanics. Footprint typology varies with bearing capacity such that firm substrates show limited impressions associated with areas of peak plantar pressure, whereas softer substrates are associated with deep prints with narrow heels and reduced medial longitudinal arches. Substrates of medium bearing capacity give displacement rims and proximal movement of sediment, which obscures the true form of the medial longitudinal arch. A simple conceptual model is offered which summarizes these conclusions and is presented as a basis for further investigation into the control of substrate on footprint typology. The method, model, and results presented here are essential in the interpretation of any sites of greater paleoanthropological significance, such as recently reported from Ileret (1.5 Ma, Kenya; Bennett et al.: Science 323 (2009) 1197-1201).

Short-term step-to-step correlation in plantar pressure distributions during treadmill walking, and implications for footprint trail analysis.

The gait cycle is continuous, but for practical reasons one is often forced to analyze one or only a few adjacent cycles, for example in non-treadmill laboratory investigations and in fossilized footprint analysis. The nature of variability in long-term gait cycle dynamics has been well-investigated, but short-term variability, and specifically correlation, which are highly relevant to short gait bouts, have not. We presently tested for step-to-step autocorrelation in a total of 5243 plantar pressure (PP) distributions from ten subjects who walked at 1.1m/s on an instrumented treadmill. Following spatial foot alignment, data were analyzed both from three points of interest (POI): heel, central metatarsals, and hallux, and for the foot surface as a whole, in a mass-univariate manner. POI results revealed low average step-to-step autocorrelation coefficients (r=0.327±0.094; mean±st. dev.). Formal statistical testing of the whole-foot r distributions reached significance over an average of only 0.42±0.52% of the foot's surface, even for a highly conservative uncorrected threshold of p<0.05. The common assumption, that short gait bouts consist of independent cycles, is therefore not refuted by the present PP results.

Human-like external function of the foot, and fully upright gait, confirmed in the 3.66 million year old Laetoli hominin footprints by topographic statistics, experimental footprint-formation and computer simulation.

It is commonly held that the major functional features of the human foot (e.g. a functional longitudinal medial arch, lateral to medial force transfer and hallucal (big-toe) push-off) appear only in the last 2 Myr, but functional interpretations of footbones and footprints of early human ancestors (hominins) prior to 2 million years ago (Mya) remain contradictory. Pixel-wise topographical statistical analysis of Laetoli footprint morphology, compared with results from experimental studies of footprint formation; foot-pressure measurements in bipedalism of humans and non-human great apes; and computer simulation techniques, indicate that most of these functional features were already present, albeit less strongly expressed than in ourselves, in the maker of the Laetoli G-1 footprint trail, 3.66 Mya. This finding provides strong support to those previous studies which have interpreted the G-1 prints as generally modern in aspect.

Functional adaptations in the forelimb muscles of non-human great apes.

The maximum capability of a muscle can be estimated from simple measurements of muscle architecture such as muscle belly mass, fascicle length and physiological cross-sectional area. While the hindlimb anatomy of the non-human apes has been studied in some detail, a comparative study of the forelimb architecture across a number of species has never been undertaken. Here we present data from chimpanzees, bonobos, gorillas and an orangutan to ascertain if, and where, there are functional differences relating to their different locomotor repertoires and habitat usage. We employed a combination of analyses including allometric scaling and ancovas to explore the data, as the sample size was relatively small and heterogeneous (specimens of different sizes, ages and sex). Overall, subject to possible unidentified, confounding factors such as age effects, it appears that the non-human great apes in this sample (the largest assembled to date) do not vary greatly across different muscle architecture parameters, even though they perform different locomotor behaviours at different frequencies. Therefore, it currently appears that the time spent performing a particular behaviour does not necessarily impose a dominating selective influence on the soft-tissue portion of the musculoskeletal system; rather, the overall consistency of muscle architectural properties both between and within the Asian and African apes strengthens the case for the hypothesis of a possible ancient shared evolutionary origin for orthogrady under compressive and/or suspensory loading in the great apes.

Dynamics of longitudinal arch support in relation to walking speed: contribution of the plantar aponeurosis.

The plantar aponeurosis (PA), in spanning the whole length of the plantar aspect of the foot, is clearly identified as one of the key structures that is likely to affect compliance and stability of the longitudinal arch. A recent study performed in our laboratory showed that tension/elongation in the PA can be predicted from the kinematics of the segments to which the PA is attached. In the present investigation, stereophotogrammetry and inverse kinematics were employed to shed light on the mechanics of the longitudinal arch and its main passive stabilizer, the PA, in relation to walking speed. When compared with a neutral unloaded position, the medial longitudinal arch underwent greater collapse during the weight-acceptance phase of stance at higher walking speed (0.1 degrees +/-1.9 degrees in slow walking; 0.9 degrees +/-2.6 degrees in fast walking; P = 0.0368). During late stance the arch was higher (3.4 degrees +/-3.1 degrees in slow walking; 2.8 degrees +/-2.7 degrees in fast walking; P = 0.0227) and the metatarsophalangeal joints more dorsiflexed (e.g. at the first metatarsophalangeal joint, 52 degrees +/-5 degrees in slow walking; 64 degrees +/-4 degrees in fast walking; P < 0.001) during fast walking. Early-stance tension in the PA increased with speed, whereas maximum tension during late stance did not seem to be significantly affected by walking speed. Although, on the one hand, these results give evidence for the existence of a pre-heel-strike, speed-dependent, arch-stiffening mechanism, on the other hand they suggest that augmentation of arch height in late stance is enhanced by higher forces exerted by the intrinsic muscles on the plantar aspect of the foot when walking at faster speeds.

A Bayesian network model for biomarker-based dose response.

A Bayesian network model was developed to integrate diverse types of data to conduct an exposure-dose-response assessment for benzene-induced acute myeloid leukemia (AML). The network approach was used to evaluate and compare individual biomarkers and quantitatively link the biomarkers along the exposure-disease continuum. The network was used to perform the biomarker-based dose-response analysis, and various other approaches to the dose-response analysis were conducted for comparison. The network-derived benchmark concentration was approximately an order of magnitude lower than that from the usual exposure concentration versus response approach, which suggests that the presence of more information in the low-dose region (where changes in biomarkers are detectable but effects on AML mortality are not) helps inform the description of the AML response at lower exposures. This work provides a quantitative approach for linking changes in biomarkers of effect both to exposure information and to changes in disease response. Such linkage can provide a scientifically valid point of departure that incorporates precursor dose-response information without being dependent on the difficult issue of a definition of adversity for precursors.

Regional peak plantar pressures are highly sensitive to region boundary definitions.

Traditional pedobarographic analyses subsample pressure data over a number of discrete anatomical regions of interest (ROIs). To our knowledge, the sensitivity of these data to ROI boundary definitions has not been previously addressed. Eight subjects each performed 20 trials of self-paced walking; commercial software was used to define 10 ROIs for each of the 160 total peak pressure images, and regional peak pressures (RPPs) were extracted for each image (total: 1600 values). We then asked three specific questions regarding RPP sensitivity to ROI boundary definition: (1) Is the ROI centroid representative of the RPP location? (2) How frequently do RPPs lie on the ROI boundary? and (3) By how much do RPP values change if the ROI boundary is changed by one pixel (resolution: 5.08 x 7.62 mm)? We found that the RPP locations differed from the ROI centroid in 80% of the cases and that the RPPs lay on the ROI boundary with a probability of 65%. We also found that a single-pixel change in the ROI boundary caused a mean RPP change of 10.8%. The most sensitive region was the midfoot for which a single-pixel ROI change yielded a median 29.4% change in RPP. These results indicate that RPP data are biased by regionalization schemes, which delineate pressure fields based on anatomy rather than on the field's geometric properties, and ultimately that regionalization may constitute a poor method of quantifying complex pressure fields. RPP sensitivity should be considered when making statistical inferences regarding foot function.

New insights into the plantar pressure correlates of walking speed using pedobarographic statistical parametric mapping (pSPM).

This study investigates the relation between walking speed and the distribution of peak plantar pressure and compares a traditional ten-region subsampling (10RS) technique with a new technique: pedobarographic statistical parametric mapping (pSPM). Adapted from cerebral fMRI methodology, pSPM is a digital image processing technique that registers foot pressure images such that homologous structures optimally overlap, thereby enabling statistical tests to be conducted at the pixel level. Following previous experimental protocols, we collected pedobarographic records from 10 subjects walking at three different speeds: slow, normal, and fast. Walking speed was recorded and correlated with the peak pressures extracted from the 10 regions, and subsequently with the peak pixel data extracted after pSPM preprocessing. Both methods revealed significant positive correlation between peak plantar pressure and walking speed over the rearfoot and distal forefoot after Bonferroni correction for multiple comparisons. The 10RS analysis found positive correlation in the midfoot and medial proximal forefoot, but the pixel data exhibited significant negative correlation throughout these regions (p<5x10(-5)). Comparing the statistical maps from the two approaches shows that subsampling may conflate pressure differences evident in pixel-level data, obscuring or even reversing statistical trends. The negative correlation observed in the midfoot implies reduced longitudinal arch collapse with higher walking speeds. We infer that this results from pre- or early-stance phase muscle activity and speculate that preferred walking speed reflects, in part, a balance between the energy required to tighten the longitudinal arch and the apparent propulsive benefits of the stiffened arch.

Methods and measurements for estimating human dermal uptake of volatile organic compounds and for deriving dermal permeability coefficients.

ABSTRACT Water contamination of public drinking and recreational waters with volatile organic compounds (VOCs) is widespread, resulting in human exposure through multiple routes. Although dermal absorption is of considerable importance, there is great uncertainty in the dermal permeability coefficient (K(P)) for many VOCs due to the methods by which they are derived. We present a human in vivo experimental approach for the measurement of VOC dermal uptake from water contaminated at environmentally relevant concentrations and for determination of K(P). Dermal permeability was estimated from 11 adult subjects following immersion of their hand and forearm into a sealed 4.8-L Plexiglas cylinder containing 100 mug/L each of chloroform, 1,1,1-trichloroethane (111-TCA), and toluene and 400 mug/L of methyl tertiary butyl ether (MTBE) in water. Uptake was determined by measuring the decrease in VOC water concentration during the exposure. A control glass arm accounted for nondermal losses. The concentration of VOCs was determined by solid-phase microextraction (SPME) and analysis with gas chromatography/mass spectrometry. For the eight male and three female adult subjects, on average there was a dermal uptake-attributed 13.5%, 14.9%, 20.8%, and 7.3% decrease in the concentration after 1 h exposure for chloroform, 111-TCA, toluene, and MTBE, respectively. The resulting mean K(P) (standard deviation) was estimated to be 0.166 (0.108), 0.167 (0.107), 0.250 (0.064), and 0.109 (0.157) cm/h for the respective analytes. The experimental K(P) values presented here exceed the previously published model-estimated K(P) values by factors ranging from 6 to 57, suggesting that the published model-estimated K(P) values may underestimate actual VOC dermal absorption from water.

Inertial properties of hominoid limb segments.

Quantitative, accurate data regarding the inertial properties of body segments are of paramount importance when developing musculo-skeletal locomotor models of living animals and, by inference, their ancestors. The limited number of available primate cadavers, and the destructive nature of the post-mortem, result in such data being very rare for primates. This study builds on the work of Crompton et al. (Am. J. Phys. Anthropol. 1996, 99, 547-570) and reports inertial properties of the body segments of gorillas, chimpanzees, orangutans and gibbons. Segment mass, centre of mass and the radius of gyration of five ape cadavers were measured using a complex-pendulum technique and compared with the results derived from external measurements of segment lengths and diameters on the same animals. With additional data from external measurements of eight more hominoid cadavers, and published data, intergeneric differences between the inertial properties and the distribution of mass between limb segments are analysed and related to the locomotor habits of the species. We found that segment inertial properties show extensive overlap between ape genera as a result of large interindividual variation. Segment mass distribution also overlaps between apes and humans, with the exception of the shank segment. However, owing to a different distribution of mass between the limb segments, the centre of mass of both the arms and the legs is located more distally in apes than in humans, and the natural pendular period of ape forelimbs is larger than that of the hindlimbs. This suggests that, in contrast to the limbs of cursorial mammals and cercopithecoid primates, hominoid limbs are not optimized for efficiency in quadrupedal walking, but rather reflect a compromise between various locomotor modes. Common chimpanzees may have secondarily evolved a more efficient quadrupedal gait.

Comparison of inverse-dynamics musculo-skeletal models of AL 288-1 Australopithecus afarensis and KNM-WT 15000 Homo ergaster to modern humans, with implications for the evolution of bipedalism.

Size and proportions of the postcranial skeleton differ markedly between Australopithecus afarensis and Homo ergaster, and between the latter and modern Homo sapiens. This study uses computer simulations of gait in models derived from the best-known skeletons of these species (AL 288-1, Australopithecus afarensis, 3.18 million year ago) and KNM-WT 15000 (Homo ergaster, 1.5-1.8 million year ago) compared to models of adult human males and females, to estimate the required muscle power during bipedal walking, and to compare this with those in modern humans. Skeletal measurements were carried out on a cast of KNM-WT 15000, but for AL 288-1 were taken from the literature. Muscle attachments were applied to the models based on their position relative to the bone in modern humans. Joint motions and moments from experiments on human walking were input into the models to calculate muscle stress and power. The models were tested in erect walking and 'bent-hip bent-knee' gait. Calculated muscle forces were verified against EMG activity phases from experimental data, with reference to reasonable activation/force delays. Calculated muscle powers are reasonably comparable to experimentally derived metabolic values from the literature, given likely values for muscle efficiency. The results show that: 1) if evaluated by the power expenditure per unit of mass (W/kg) in walking, AL 288-1 and KNM-WT 15000 would need similar power to modern humans; however, 2) with distance-specific parameters as the criteria, AL 288-1 would require to expend relatively more muscle power (W/kg.m(-1)) in comparison to modern humans. The results imply that in the evolution of bipedalism, body proportions, for example those of KNM-WT 15000, may have evolved to obtain an effective application of muscle power to bipedal walking over a long distance, or at high speed.

Assessing biomarker use in risk assessment--a survey of practitioners.

Advances in molecular epidemiology and mechanistic toxicology have provided increased opportunities for incorporating biomarkers in the human health risk assessment process. For years, the published literature has lauded the concept of incorporating biomarkers into risk assessments as a means to reduce uncertainty in estimating health risk. For all the potential benefits, one would think that markers of effective dose, markers of early biological effects, and markers of human susceptibility are frequently selected as the basis for quantitative human health risk assessments. For this article, we sought to determine the degree to which this evolution in risk assessment has come to pass. The extent to which biomarkers are being used in current human health risk assessment was determined through an informal survey of leading risk assessment practitioners. Case studies highlighting the evolution of risk assessment methods to include biomarkers are also described. The goal of this review was to enhance the implementation of biomarker technology in risk assessment by (1) highlighting successes in biomarker implementation, (2) identifying key barriers to overcome, and (3) describing evolutions in risk assessment methods.

Applying new biotechnologies to the study of occupational cancer--a workshop summary.

As high-throughput technologies in genomics, transcriptomics, and proteomics evolve, questions arise about their use in the assessment of occupational cancers. To address these questions, the National Institute for Occupational Safety and Health, the National Cancer Institute, the National Institute of Environmental Health Sciences, and the American Chemistry Council sponsored a workshop 8-9 May 2002 in Washington, DC. The workshop brought together 80 international specialists whose objective was to identify the means for best exploiting new technologies to enhance methods for laboratory investigation, epidemiologic evaluation, risk assessment, and prevention of occupational cancer. The workshop focused on identifying and interpreting markers for early biologic effect and inherited modifiers of risk.

Two-dimensional electrophoretic protein profile analysis following exposure of human uroepithelial cells to occupational bladder carcinogens.

Protein biomarkers to occupational carcinogens were investigated using a transformable human uroepithelial cell system, SV-HUC.PC. SV-HUC.PC was treated with N-hydroxy-4,4'-methylene bis (2-chloroaniline) (N-OH-MOCA) or N-hydroxy-4 aminobiphenyl (N-OH-ABP). Two-dimensional gel electrophoresis of cell lysates compared protein changes across treatments. Increasing N-OH-MOCA resulted in a dose-related increase in protein spots altered. Comparing cell profiles treated with either carcinogen revealed alterations in the expression of nine proteins, identified using the TagIdent database. These demonstrated isoelectric point shift (1) or quantity change (8). Our investigation may be useful in identifying biomarkers of effects of exposure to bladder carcinogens.

Priorities for development of research methods in occupational cancer.

Occupational cancer research methods was identified in 1996 as 1 of 21 priority research areas in the National Occupational Research Agenda (NORA). To implement NORA, teams of experts from various sectors were formed and given the charge to further define research needs and develop strategies to enhance or augment research in each priority area. This article is a product of that process. Focus on occupational cancer research methods is important both because occupational factors play a significant role in a number of cancers, resulting in significant morbidity and mortality, and also because occupational cohorts (because of higher exposure levels) often provide unique opportunities to evaluate health effects of environmental toxicants and understand the carcinogenic process in humans. Despite an explosion of new methods for cancer research in general, these have not been widely applied to occupational cancer research. In this article we identify needs and gaps in occupational cancer research methods in four broad areas: identification of occupational carcinogens, design of epidemiologic studies, risk assessment, and primary and secondary prevention. Progress in occupational cancer will require interdisciplinary research involving epidemiologists, industrial hygienists, toxicologists, and molecular biologists.