Patient-reported mobility function and engagement in young adults with cerebral palsy: a cross-sectional sample.

PURPOSE: To describe self-reported life satisfaction and motor function of young adults with cerebral palsy (CP). METHODS: A total of 57 young adults with spastic CP classified as levels I (seven), II (25), III (16), IV (nine) by the Gross Motor Function Classification System, followed from childhood by our CP clinic, returned at a mean age of 27 years two months (SD 3 years 4 months). Self-reported life satisfaction and mobility status were measured by the Pediatric Outcomes Data Collection Instrument (PODCI), Patient-Reported Outcomes Measurement Information System (PROMIS), Functional Mobility Scale (FMS) and a project questionnaire. Surgical history and childhood mobility were confirmed from medical records. RESULTS: The Functional Mobility Scale demonstrated limited but stable mobility function from childhood to adulthood. The PROMIS and PODCI revealed limited motor function compared with a non-disabled normative reference (p < 0.05). Descriptive results showed high dependence on transportation, housing and income; although PROMIS subscales revealed satisfaction with social activities. Self-recall of childhood mobility function using the FMS correlated highly (r = 0.8; p < 0.0001) with historical records. CONCLUSION: Although functional mobility is limited and community independence is not fully achieved in young adults with CP, these participants maintained childhood levels of mobility function into young adulthood, were satisfied with social roles and had minimal reports of pain.

Flexed-knee gait in children with cerebral palsy: a long-term follow-up study.

Aims: The purpose of this study was to evaluate the long-term outcome of adolescents with cerebral palsy who have undergone single-event multilevel surgery for a flexed-knee gait, followed into young adulthood using 3D motion analysis. Patients and Methods: A total of 59 young adults with spastic cerebral palsy, with a mean age of 26 years (sd 3), were enrolled into the study in which their gait was compared with an evaluation that had taken place a mean of 12 years (sd 2) previously. At their visits during adolescence, the children walked with excessive flexion of the knee at initial contact and surgical or therapeutic interventions were not controlled between visits. Results: Based on the change in flexed-knee gait over approximately ten years, improvements were seen in increased Gait Deviation Index (p < 0.001) and decreased flexion of the knee at initial contact (p < 0.001). Greater popliteal angle (p < 0.001), reduced Gross Motor Function Measure section D (p = 0.006), and reduced speed of gait (p = 0.007) suggested a mild decline in function. Quality-of-life measures showed that these patients fell within normal limits compared with typical young adults in areas other than physical function. Conclusion: While some small significant changes were noted, little clinically significant change was seen in function and gait, with gross motor function maintained between adolescence and young adulthood. Cite this article: Bone Joint J 2018;100-B:549-56.

Longitudinal change in foot posture in children with cerebral palsy.

PURPOSE: Foot deformities are common in children with cerebral palsy (CP), yet the evolution of such deformities is not well documented. We aimed to observe and analyse changes in foot posture during growth in children with CP. Methods We followed 51 children (16 unilateral, 35 bilateral; 37 Gross Motor Function Classification Scale (GMFCS) I/II, 14 III/IV) aged two to 12 years in this level II, IRB-approved prospective longitudinal study. Data after bony foot corrections were excluded. Outcome measures included coronal plane pressure index (CPPI) and pressure impulses from the heel, medial midfoot and medial forefoot. Data were LOESS smoothed and resulting models were compared for significant differences across time using a derived FANOVA method. RESULTS: The GMFCS I/II group had more foot valgus than typically developing (TD) children until seven years which normalised thereafter. From two to 12 years, GMFCS III/IV children had more foot valgus than TD children. Heel impulse was significantly reduced in both GMFCS groups compared with TD children, and the III/IV group had less heel contact than the I/II group. CONCLUSIONS: Due to early variability and the tendency for resolving valgus foot posture in children with CP, conservative management of coronal plane foot deformity is suggested in early childhood, especially for children classified as GMFCS I and II.

Fractionated radiation exposure amplifies the radioresistant nature of prostate cancer cells.

The risk of recurrence following radiation therapy remains high for a significant number of prostate cancer patients. The development of in vitro isogenic models of radioresistance through exposure to fractionated radiation is an increasingly used approach to investigate the mechanisms of radioresistance in cancer cells and help guide improvements in radiotherapy standards. We treated 22Rv1 prostate cancer cells with fractionated 2 Gy radiation to a cumulative total dose of 60 Gy. This process selected for 22Rv1-cells with increased clonogenic survival following subsequent radiation exposure but increased sensitivity to Docetaxel. This RR-22Rv1 cell line was enriched in S-phase cells, less susceptible to DNA damage, radiation-induced apoptosis and acquired enhanced migration potential, when compared to wild type and aged matched control 22Rv1 cells. The selection of radioresistant cancer cells during fractionated radiation therapy may have implications in the development and administration of future targeted therapy in conjunction with radiation therapy.

Changes in mitochondrial stability during the progression of the Barrett's esophagus disease sequence.

BACKGROUND: Barrett's esophagus follows the classic step-wise progression of metaplasia-dysplasia-adenocarcinoma. While Barrett's esophagus is a leading known risk factor for esophageal adenocarcinoma, the pathogenesis of this disease sequence is poorly understood. Mitochondria are highly susceptible to mutations due to high levels of reactive oxygen species (ROS) coupled with low levels of DNA repair. The timing and levels of mitochondria instability and dysfunction across the Barrett's disease progression is under studied. METHODS: Using an in-vitro model representing the Barrett's esophagus disease sequence of normal squamous epithelium (HET1A), metaplasia (QH), dysplasia (Go), and esophageal adenocarcinoma (OE33), random mitochondrial mutations, deletions and surrogate markers of mitochondrial function were assessed. In-vivo and ex-vivo tissues were also assessed for instability profiles. RESULTS: Barrett's metaplastic cells demonstrated increased levels of ROS (p < 0.005) and increased levels of random mitochondrial mutations (p < 0.05) compared with all other stages of the Barrett's disease sequence in-vitro. Using patient in-vivo samples, Barrett's metaplasia tissue demonstrated significantly increased levels of random mitochondrial deletions (p = 0.043) compared with esophageal adenocarcinoma tissue, along with increased expression of cytoglobin (CYGB) (p < 0.05), a gene linked to oxidative stress, compared with all other points across the disease sequence. Using ex-vivo Barrett's metaplastic and matched normal patient tissue explants, higher levels of cytochrome c (p = 0.003), SMAC/Diablo (p = 0.008) and four inflammatory cytokines (all p values <0.05) were secreted from Barrett's metaplastic tissue compared with matched normal squamous epithelium. CONCLUSIONS: We have demonstrated that increased mitochondrial instability and markers of cellular and mitochondrial stress are early events in the Barrett's disease sequence.

Visceral obesity stimulates anaphase bridge formation and spindle assembly checkpoint dysregulation in radioresistant oesophageal adenocarcinoma

Purpose: Oesophageal adenocarcinoma is an exemplar model of obesity-associated cancer. Locally advanced disease is treated with neoadjuvant chemoradiotherapy, and survival rates are highest in patients demonstrating a pathological response following neoadjuvant therapy. Given that 55 % of oesophageal adenocarcinoma patients are obese, uncovering the effect of adipose tissue on radioresponse is clinically relevant. This study investigates if adipose tissue activates genomic instability events in radioresponsive (OE33P) and radioresistant (OE33R) oesophageal cancer cell lines and tumour samples. Methods: OE33R and OE33P were cultured with adiposeconditioned media derived from oesophageal adenocarcinoma patients (n = 10). Anaphase bridges, a marker of genomic instability, were enumerated in both cell lines following treatment with adipose media, and normalised to cell number. Genomic instability is regulated by the spindle assembly complex. Expression of two spindle assembly complex genes (MAD2L2, BUB1B) was assessed using qPCR, and validated in patient tumour specimens from viscerally obese (n = 46) and nonobese patients (n = 41). Results: Adipose-conditioned media increased anaphase bridging in OE33R (p < 0.0001), with a threefold increase in OE33R compared to OE33P (p < 0.01). Levels of anaphase bridges in OE33R cells correlated with visceral obesity status as measured by waist circumference (R = 0.709, p = 0.03) and visceral fat area (R = 0.794, p = 0.006). Adipose tissue altered expression of MAD2L2 in vitro. In vivo, MAD2L2 expression was higher in viscerally obese oesophageal adenocarcinoma patients compared with nonobese patients (p < 0.05). Conclusions: Anaphase bridge levels are influenced by obesity and radiosensitivity status in oesophageal adenocarcinoma. Furthermore, visceral adipose-conditioned media stimulates dysregulation of the spindle assembly complex in oesophageal adenocarcinoma patients

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Comparison of decomposition rates between autopsied and non-autopsied human remains.

Penetrating trauma has been cited as a significant factor in the rate of decomposition. Therefore, penetrating trauma may have an effect on estimations of time-since-death in medicolegal investigations and on research examining decomposition rates and processes when autopsied human bodies are used. The goal of this study was to determine if there are differences in the rate of decomposition between autopsied and non-autopsied human remains in the same environment. The purpose is to shed light on how large incisions, such as those from a thorocoabdominal autopsy, effect time-since-death estimations and research on the rate of decomposition that use both autopsied and non-autopsied human remains. In this study, 59 non-autopsied and 24 autopsied bodies were studied. The number of accumulated degree days required to reach each decomposition stage was then compared between autopsied and non-autopsied remains. Additionally, both types of bodies were examined for seasonal differences in decomposition rates. As temperature affects the rate of decomposition, this study also compared the internal body temperatures of autopsied and non-autopsied remains to see if differences between the two may be leading to differential decomposition. For this portion of this study, eight non-autopsied and five autopsied bodies were investigated. Internal temperature was collected once a day for two weeks. The results showed that differences in the decomposition rate between autopsied and non-autopsied remains was not statistically significant, though the average ADD needed to reach each stage of decomposition was slightly lower for autopsied bodies than non-autopsied bodies. There was also no significant difference between autopsied and non-autopsied bodies in the rate of decomposition by season or in internal temperature. Therefore, this study suggests that it is unnecessary to separate autopsied and non-autopsied remains when studying gross stages of human decomposition in Central Texas and that penetrating trauma may not be a significant factor in the overall rate of decomposition.

Visceral obesity stimulates anaphase bridge formation and spindle assembly checkpoint dysregulation in radioresistant oesophageal adenocarcinoma.

PURPOSE: Oesophageal adenocarcinoma is an exemplar model of obesity-associated cancer. Locally advanced disease is treated with neoadjuvant chemoradiotherapy, and survival rates are highest in patients demonstrating a pathological response following neoadjuvant therapy. Given that 55 % of oesophageal adenocarcinoma patients are obese, uncovering the effect of adipose tissue on radioresponse is clinically relevant. This study investigates if adipose tissue activates genomic instability events in radioresponsive (OE33P) and radioresistant (OE33R) oesophageal cancer cell lines and tumour samples. METHODS: OE33R and OE33P were cultured with adipose-conditioned media derived from oesophageal adenocarcinoma patients (n = 10). Anaphase bridges, a marker of genomic instability, were enumerated in both cell lines following treatment with adipose media, and normalised to cell number. Genomic instability is regulated by the spindle assembly complex. Expression of two spindle assembly complex genes (MAD2L2, BUB1B) was assessed using qPCR, and validated in patient tumour specimens from viscerally obese (n = 46) and nonobese patients (n = 41). RESULTS: Adipose-conditioned media increased anaphase bridging in OE33R (p < 0.0001), with a threefold increase in OE33R compared to OE33P (p < 0.01). Levels of anaphase bridges in OE33R cells correlated with visceral obesity status as measured by waist circumference (R = 0.709, p = 0.03) and visceral fat area (R = 0.794, p = 0.006). Adipose tissue altered expression of MAD2L2 in vitro. In vivo, MAD2L2 expression was higher in viscerally obese oesophageal adenocarcinoma patients compared with nonobese patients (p < 0.05). CONCLUSIONS: Anaphase bridge levels are influenced by obesity and radiosensitivity status in oesophageal adenocarcinoma. Furthermore, visceral adipose-conditioned media stimulates dysregulation of the spindle assembly complex in oesophageal adenocarcinoma patients.

Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

Differential expression of mitochondrial energy metabolism profiles across the metaplasia-dysplasia-adenocarcinoma disease sequence in Barrett's oesophagus.

Contemporary clinical management of Barrett's oesophagus has highlighted the lack of accurate predictive markers of disease progression to oesophageal cancer. This study aims to examine alterations in mitochondrial energy metabolism profiles across the entire disease progression sequence in Barrett's oesophagus. An in-vitro model was used to screen 84 genes associated with mitochondrial energy metabolism. Three energy metabolism genes (ATP12A, COX4I2, COX8C) were significantly altered across the in-vitro Barrett's disease sequence. In-vivo validations across the Barrett's sequence demonstrated differential expression of these genes. Tissue microarrays demonstrated significant alterations in both epithelial and stromal oxidative phosphorylation (ATP5B and Hsp60) and glycolytic (PKM2 and GAPDH) protein markers across the in-vivo Barrett's sequence. Levels of ATP5B in sequential follow up surveillance biopsy material segregated Barrett's non progressors and progressors to HGD and cancer. Utilising the Seahorse XF24 flux analyser, in-vitro Barrett's and adenocarcinoma cells exhibited altered levels of various oxidative parameters. We show for the first time that mitochondrial energy metabolism is differentially altered across the metaplasia-dysplasia-adenocarcinoma sequence and that oxidative phosphorylation profiles have predictive value in segregating Barrett's non progressors and progressors to adenocarcinoma.

Energy cost of walking in children with spastic cerebral palsy: relationship with age, body composition and mobility capacity.

The energy cost (EC) of walking is different for typically developing (TD) and children with cerebral palsy (CP). The associated factors of EC are not fully understood in children with CP. We assessed the relationship between EC and age, body surface area (BSA), and gross motor function measure (GMFM). We retrospectively examined data collected between 2003 and 2011 on 276 children aged 4-18 years who were classified as Gross Motor Function Classification System level I, n=79; II, n=123; and III, n=74. Energy cost was assessed while children walked 6-8 min at a comfortable, self-selected speed using their typical walking aids and/or orthoses as part of a clinical gait analysis. During the test, participants wore a breath-by-breath portable gas analysis system, measuring oxygen consumption. To calculate EC (J/kg/m), oxygen consumption was converted to J/kg/min and divided by walking speed. Data were analyzed using linear regression model. Energy cost correlated inversely with age (ß=-0.16, R2=0.02, P=0.01), BSA (ß=-3.35, R2=0.11, P<0.0001), and GMFM (ß=-0.12, R2=0.42, P<0.0001). In the multiple linear regression model, GMFM was the most potent correlate of EC, BSA explained another 10% of the variance (R2=0.53), and age was a marginally significant correlate of EC (P=0.08). In summary, in children with CP in our study, EC decreased as GMFM and BSA increased, and GMFM was the most potent correlate of EC.

Rich and cold: diversity, distribution and drivers of fungal communities in patterned-ground ecosystems of the North American Arctic.

Fungi are abundant and functionally important in the Arctic, yet comprehensive studies of their diversity in relation to geography and environment are not available. We sampled soils in paired plots along the North American Arctic Transect (NAAT), which spans all five bioclimatic subzones of the Arctic. Each pair of plots contrasted relatively bare, cryoturbated patterned-ground features (PGFs) and adjacent vegetated between patterned-ground features (bPGFs). Fungal communities were analysed via sequencing of 7834 ITS-LSU clones. We recorded 1834 OTUs - nearly half the fungal richness previously reported for the entire Arctic. These OTUs spanned eight phyla, 24 classes, 75 orders and 120 families, but were dominated by Ascomycota, with one-fifth belonging to lichens. Species richness did not decline with increasing latitude, although there was a decline in mycorrhizal taxa that was offset by an increase in lichen taxa. The dominant OTUs were widespread even beyond the Arctic, demonstrating no dispersal limitation. Yet fungal communities were distinct in each subzone and were correlated with soil pH, climate and vegetation. Communities in subzone E were distinct from the other subzones, but similar to those of the boreal forest. Fungal communities on disturbed PGFs differed significantly from those of paired stable areas in bPGFs. Indicator species for PGFs included lichens and saprotrophic fungi, while bPGFs were characterized by ectomycorrhizal and pathogenic fungi. Our results suggest that the Arctic does not host a unique mycoflora, while Arctic fungi are highly sensitive to climate and vegetation, with potential to migrate rapidly as global change unfolds.

A phylogenetic analysis using full-length viral genomes of South American dengue serotype 3 in consecutive Venezuelan outbreaks reveals a novel NS5 mutation.

Dengue virus currently causes 50-100 million infections annually. Comprehensive knowledge about the evolution of Dengue in response to selection pressure is currently unavailable, but would greatly enhance vaccine design efforts. In the current study, we sequenced 187 new dengue virus serotype 3 (DENV-3) genotype III whole genomes isolated from Asia and the Americas. We analyzed them together with previously-sequenced isolates to gain a more detailed understanding of the evolutionary adaptations existing in this prevalent American serotype. In order to analyze the phylogenetic dynamics of DENV-3 during outbreak periods; we incorporated datasets of 48 and 11 sequences spanning two major outbreaks in Venezuela during 2001 and 2007-2008, respectively. Our phylogenetic analysis of newly sequenced viruses shows that subsets of genomes cluster primarily by geographic location, and secondarily by time of virus isolation. DENV-3 genotype III sequences from Asia are significantly divergent from those from the Americas due to their geographical separation and subsequent speciation. We measured amino acid variation for the E protein by calculating the Shannon entropy at each position between Asian and American genomes. We found a cluster of seven amino acid substitutions having high variability within E protein domain III, which has previously been implicated in serotype-specific neutralization escape mutants. No novel mutations were found in the E protein of sequences isolated during either Venezuelan outbreak. Shannon entropy analysis of the NS5 polymerase mature protein revealed that a G374E mutation, in a region that contributes to interferon resistance in other flaviviruses by interfering with JAK-STAT signaling was present in both the Asian and American sequences from the 2007-2008 Venezuelan outbreak, but was absent in the sequences from the 2001 Venezuelan outbreak. In addition to E, several NS5 amino acid changes were unique to the 2007-2008 epidemic in Venezuela and may give additional insight into the adaptive response of DENV-3 at the population level.

Impaired Ca2+-sequestration in dilated cardiomyopathy (review).

Excitation-contraction coupling is the process by which depolarisation of the myocardial surface membrane leads to the release of Ca2+-ions from the sarcoplasmic reticulum, inducing cardiac muscle contraction. This process is made possible by an elaborate system of ion-release, uptake and sequestration that controls the contraction and relaxation cycle of heart muscle fibres. The free intracellular Ca2+-concentration determines the contractile state of the myocardium, and the sequestration of Ca2+-ions into the lumen of the sarcoplasmic reticulum by the Ca2+-ATPase pump units represents a critical step towards the maintenance of normal Ca2+-cycling. The Ca2+-ATPase pump activity is regulated by phospholamban, a small 52-amino acid protein whose phosphorylation state dictates its inhibitory action on the pump. A large body of evidence points to the central role of abnormal Ca2+-ATPase-phospholamban interactions in pathophysiological heart conditions, thereby compromising the contractile state of the cardiac muscle cell. It has been shown that alterations in the oligomeric status of the Ca2+-ATPase and modified interactions between the Ca2+-pump and its regulatory subunit phospholamban underlie the contractile dysfunction that characterises certain forms of dilated cardiomyopathy. Hence, elucidation of interactions within physiological Ca2+-ATPase pump units in normal and diseased myocardium is a vital link in the development of improved diagnostic and therapeutic techniques for dealing with this elusive condition.

Impaired Ca2+-ATPase oligomerization and increased phospholamban expression in dilated cardiomyopathy.

Although primary genetic defects have been identified for some forms of inherited cardiomyopathy, it is not well understood how secondary abnormalities actually lead to muscle cell destruction. Since cardiomyopathies significantly influence morbidity and mortality rates world-wide, it is important to improve the differential diagnosis of these disorders and develop potential treatments for inherited diseases of the heart. Elucidation of the secondary molecular mechanisms underlying cardiac cell necrosis might help linking a specific mutation in a cardiac gene to acute heart failure. As disturbed Ca2+-homeostasis may contribute to heart failure, we have investigated the relative abundance and oligomeric status of the sarcoplasmic reticulum Ca2+-ATPase and phospholamban in various cardiomyopathies. These two proteins represent important factors in cardiac relaxation. The SERCA2 isoform of the Ca2+-ATPase represents a major Ca2+-removal system in cardiac muscle fibres and phospholamban is a regulator of Ca2+-pump activity. Although Ca2+-ATPase expression did not seem to be markedly altered, the comparative immunoblot analysis presented here clearly shows that phospholamban expression is increased in dilated cardiomyopathy, possibly explaining the decreased Ca2+-uptake in the disease. In contrast to the normal enzyme, the Ca2+-pump was demonstrated to exhibit an impairment of crosslinker-stabilized oligomerization in dilated cardiomyopathy. Since Ca2+-ATPase oligomerization is important for co-operative kinetics and protection against proteolytic degradation, the monomeric Ca2+-ATPase may trigger an abnormal contraction-relaxation cycle in dilated cardiomyopathy leading to heart failure.

Oligomerization of the sarcoplasmic reticulum Ca2+-ATPase SERCA2 in cardiac muscle.

The slow/cardiac isoform of the sarcoplasmic reticulum Ca2+-ATPase plays an important role in cardiac muscle Ca2+-homeostasis. To determine the native configuration of the SERCA2 ion pump, a chemical cross-linking analysis of heart microsomes was performed. Using one- and two-dimensional immunoblotting following incubation with the hydrophilic probe bis-sulfosuccinimidyl suberate or the hydrophobic crosslinker dithiobis-succinimidyl-propionate, we demonstrate here that SERCA2 forms high-molecular-mass aggregates. In contrast to the Na+/Ca2+-exchanger, Ca2+-ATPase clusters can be stabilized by hydrophilic 1.2 nm crosslinkers and are sensitive to chemical reduction. Hence, the native form of this important Ca2+-regulatory membrane protein involved in cardiac muscle relaxation appears not to exist as a monomeric ion pump unit. Protein-protein interactions might play an important role in the physiological functioning of this Ca2+-ATPase isoform, as has previously been shown for skeletal muscle Ca2+-pumps, Ca2+-binding proteins and Ca2+-channels.

Variability of energy-consumption measures in children with cerebral palsy.

Oxygen consumption measurements made on five repeated tests from five children with cerebral palsy (CP) and five nondisabled children of similar age and size were collected using the Cosmed K2 (Cosmed, Rome, Italy) oxygen-analysis system at free-walking velocity. Oxygen cost, oxygen consumption, and physiological cost index (PCI) were measured. There were no statistically significant differences in the percentage of variability of oxygen cost, oxygen consumption, or PCI between the disabled and nondisabled populations. Oxygen cost was the most reliable oxygen-use measurement with an average percentage of variability of 13.2% for the CP population and 13.9% for the nondisabled population. Physiological cost index was found be the least reliable measurement with the average percentages of variabilities of the disabled and nondisabled populations of 20.3 and 20.5%, respectively. Thus because of oxygen cost's relatively low variability, it was the most sensitive measurement of change in gait efficiency.