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Reports of joint instability in knee osteoarthritis: its prevalence and relationship to physical function.

OBJECTIVE: To report the prevalence and relationship of self-reported knee instability to physical function in a sample of subjects with knee osteoarthritis (OA), and to discuss the implications of these observations for rehabilitation. METHODS: Subjects were 105 individuals (80 females) with knee OA who rated their knee instability severity on a 6-point numeric scale in response to the query "To what degree does giving way, buckling, or shifting of the knee affect your level of daily activity?" A principal component analysis was used to combine The Western Ontario and McMaster Universities pain, stiffness, and physical function subscale scores, and the Timed Get Up and Go Test score into a principal component score for physical function (PCPF). Other variables that could affect the PCPF such as age, sex, years with knee OA, radiographic severity of knee OA, knee pain, knee motion, and quadriceps strength were also recorded. The prevalence of self-reported knee instability was determined by calculating the proportion of subjects who reported each severity level of knee instability. Hierarchical regression analysis was performed to determine if the level of self-reported knee instability could predict the PCPF, even after accounting for the effects of the other variables. RESULTS: Sixty-three percent of the subjects reported knee instability during activities of daily living, and 44% reported that instability affects their ability to function. The severity of self-reported knee instability was associated with the PCPF (eta2=0.40, P <0.001), and after controlling for all other independent variables, significantly increased the prediction of the PCPF (r2=0.56, r2 change=0.05; P <0.001). CONCLUSION: The results indicate that a substantial proportion of individuals with knee OA report episodes of knee instability during activities of daily living, and instability affects physical function beyond that which can be explained by contributions from other impairments such as knee pain, range of motion, and quadriceps strength. Knee instability is a problem that should be specifically addressed in rehabilitation programs and may require interventions beyond those that address pain, joint motion, and muscular strength, to maximize the effectiveness of rehabilitation for individuals with knee OA.

Activities of Daily Living↗

Inhibitors of glutamate transport modulate distinct patterns in brain metabolism.

High affinity uptake of glutamate plays a major role in the termination of excitatory neurotransmission. Identification of the ramifications of transporter function is essential to understand the diseases in which defective excitatory amino acid transporters (EAAT) have been implicated. In this work we incubated Guinea pig cortical tissue slices with [3-(13)C]pyruvate and major currently available glutamate uptake inhibitors and studied the resultant metabolic sequelae by (13)C and (1)H NMR spectroscopy using a multivariate statistical approach. Perturbation of glutamate uptake produced significant effects on metabolic flux through the Krebs cycle, and on glutamate/glutamine cycling rates, with this effect accounting for 76% of the variation in the total data set. The effects of all inhibitors were separable from each other along three major principal components. The competitive inhibitor L-CCG III ((2S,1'S,2'R)-2-carboxycyclopropyl)glycine) differed most from the other inhibitors, showing negative weightings on both the first and second principal components, whereas the EAAT2-specific inhibitor dihydrokainate (DHK) showed metabolic patterns similar to that of anti-endo-3,4-methanopyrolidine dicarboxylate but separate from those of DL-threo-beta-benzyloxyaspartate (TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (L-tPDC). This indicates that different inhibition mechanisms or different colocalisation of the separate transporter subtypes with glutamate receptors can produce significantly different metabolic and functional outcomes for the brain.

Animals↗

Local-structural diversity and protein folding: application to all-beta off-lattice protein models.

Global measures of structural diversity within a distribution of biopolymers, such as the radius of gyration and percent native contacts, have proven useful in the analysis of simulation data for protein folding. In this paper we describe a statistical-based methodology to quantify the local structural variability of a distribution of biopolymers, applied to 46- and 69-"residue" off-lattice, three-color model proteins. Each folds into beta-barrel structures. First we perform a principal component analysis of all interbead distance variables for a large number of independent, converged Boltzmann-distributed samples of conformations collected at each of a wide range of temperatures. Next, the principal component vectors are subjected to orthogonal (varimax) rotation. The results are displayed on so-called "squared-loading" plots. These provide a quantitative measure of the contribution to the sample variance of the position of each residue relative to the others. Dominant structural elements, those having the largest structural diversity within the sampled distribution, are responsible for peaks and shoulders observed in the specific heat versus temperature curves, generated using the weighted histogram analysis method. The loading plots indicate that the local-structural diversity of these systems changes gradually with temperature through the folding transition but radically changes near the collapse transition temperature. The analysis of the structural overlap order statistic suggests that the 46-mer thermodynamic folding transition involves the native state and at least three other nearly native intermediates. In the case of the 46-mer protein model, data are generated at sufficiently low temperatures that squared-loading plots, coupled with cluster analysis, provide a local and energetic description of its glassy state.

Algorithms↗

Fluorescence spectroscopy for cervical precancer detection: Is there variance across the menstrual cycle?

This study assesses one possible cause of inter-patient variation in fluorescence spectroscopy of the cervix: the menstrual cycle. Ten patients with no history of an abnormal Pap smear were seen daily throughout 30 consecutive days of their cycle. Fluorescence excitation-emission matrices were measured from three cervical sites on each patient. Principal component analysis was used to determine which spectral regions varied with the day of the cycle. Classification was performed to assess the influence of menstrual cycle on precancer diagnosis. Variations in the principal component scores and the redox ratio values show that the fluorescence emission spectra at 340-380 nm excitation appear to correlate with the cell metabolism of the cervical epithelium throughout the menstrual cycle; these changes do not affect diagnostic classification. The menstrual cycle affects intra-patient variation but does not appear to cause a significant level of inter-patient variation. It does not need to be controlled for in optical detection strategies based on fluorescence spectroscopy.

Female↗

Evaluating the correlation and prediction of trunk fat mass with five anthropometric indices in Chinese females aged 20-40 years.

BACKGROUND AND AIMS: Obesity is a worldwide problem, and excess trunk fat mass (FM(trunk)) has been associated with an increased risk of diseases. The early measurement of FM(trunk) has potential importance to evaluate trunk obesity. We sought to evaluate the correlation and predication of FM(trunk) with five anthropometric indices in Chinese females. METHODS AND RESULTS: A sample of 850 China females aged 20-40 years were recruited and divided into four age groups with a 5-year range in each group. Five anthropometric indices were measured or calculated. FM(trunk) in kg was measured using a dual-energy X-ray absorptiometry scanner. Principal component analysis (PCA) and multiple regression analysis were performed to develop prediction equations. There was an increasing trend of FM(trunk) and five anthropometric indices in successively older age groups. Four formed principal components (PCs) interpreted over 99% of the total variation of five relative anthropometric indices in all age groups. Regression analyses showed that four PCs combined explained a greater variance (R(2)=45.2-81.6%) in FM(trunk) than did each of the five indices alone (R(2)=2.4-72.2%). CONCLUSIONS: Our results suggested that there is an increasing trend of FM(trunk) and five anthropometric indices with aging; that age obviously influences the relationship of FM(trunk) and the anthropometric indices studied; and that the accuracy of predicting the FM(trunk) using five anthropometric indices combined is greater than using the five indices alone.

Absorptiometry, Photon↗

Characterization of aliphatic hydrocarbons in deep subsurface soils near the outskirts of Beijing, China.

Thirty-nine deep subsurface soils (150-180 cm depth) near the outskirts of Beijing were investagated. The concentrations including n-alkanes from C13 to C36, pristane and phytane were in the range of 0.60 to 170.10 microg/g, with a median value of 4.26. Carbon preference index values for n-alkanes ranged from 1.08 to 2.98, with a median value of 1.48. The percentage contribution of "wax" n-alkanes was in the range of 6.03%--46.22%. A predominance of odd/even carbon n-alkanes and unresolved complex mixtures with different shapes and ranges were frequently observed. Factor analysis reduced the data set into three principal components and confirming contributions from low (19.58%), medium (20.49%) molecular weight species and long-chain n-alkanes (43.41%), respectively. Molecular biomarkers such as pristane, phytane, hopanes and steranes were detected. Based on the principal component analysis, the concentration profiles and molecular markers, it was found that the aliphatic hydrocarbons were from both biogenic and anthropogenic sources.

Alkanes↗

Evidence for genetic factors underlying the insulin resistance syndrome in american indians.

Previous analyses of American Indians of the Strong Heart Study have demonstrated that various insulin-resistance variables cluster, although knowledge about the genetic determination of these clusters is unknown. In an effort to explore the influences on the aggregation of insulin-resistance phenotypes, we used principal component factor analysis to examine the clustering of these phenotypes in participants of the Strong Heart Family Study and evaluated the genetic and environmental contributions of such factors. Nine traits were chosen for principal component factor analysis: BMI, diastolic blood pressure, fasting glucose, high-density lipoprotein-cholesterol, natural log-transformed insulin, natural log-transformed triglycerides, percentage of body fat, systolic blood pressure, and waist-to-hip ratio. Analyses revealed three clusters: glucose/insulin/obesity, blood pressure, and dyslipidemia factors. Using a variance component approach and accounting for the effects of age, sex, center, and medication, we detected significant heritabilities (h2) for the three factors: h2 = 0.67, h2 = 0.33, and h2 = 0.61, respectively. In multivariate analysis, no significant genetic correlations among factors were found. These results suggest that heredity explains a substantial proportion of the variability of the factors that underlie the insulin resistance syndrome in American Indians and that these factors are genetically independent.

Aged↗

Source apportionment of polycyclic aromatic hydrocarbons in surface soil in Tianjin, China.

Principal component analysis and multiple linear regression were applied to apportion sources of polycyclic aromatic hydrocarbons (PAHs) in surface soils of Tianjin, China based on the measured PAH concentrations of 188 surface soil samples. Four principal components were identified representing coal combustion, petroleum, coke oven plus biomass burning, and chemical industry discharge, respectively. The contributions of major sources were quantified as 41% from coal, 20% from petroleum, and 39% from coking and biomass, which are compatible with PAH emissions estimated based on fuel consumption and emission factors. When the study area was divided into three zones with distinctive differences in soil PAH concentration and profile, different source features were unveiled. For the industrialized Tanggu-Hangu zone, the major contributors were cooking (43%), coal (37%) and vehicle exhaust (20%). In rural area, however, in addition to the three main sources, biomass burning was also important (13%). In urban-suburban zone, incineration accounted for one fourth of the total.

Biomass↗

Genomic analysis of breed composition and population structure in Montana composite cattle.

The Montana composite was developed in Brazil from crosses between Bos indicus and Bos taurus and structured into four biological types: Zebu (N), adapted taurine (A), British taurine (B), and continental taurine (C). This study aimed to characterize the genetic diversity and population structure of the Montana composite using genomic data through principal component analysis (PCA), admixture analysis, and Wright's FST statistic. The PCA revealed a clear separation between Bos indicus and Bos taurus groups, with Montana animals distributed in an intermediate position. The first two principal components explained 69.48% and 3.45% of the total variation, respectively. Supervised admixture estimates indicated a predominance of taurine contribution, with type A accounting for 34.47%, 52.64%, and 51.71% at K&#x2009;=&#x2009;4, 9, and 11, respectively. Increasing the ancestry resolution refined the contribution of individual founder breeds without changing the overall predominance of taurine ancestry. Comparisons between breed proportions obtained from pedigree and genomic data revealed significant differences, for most biological types and ancestry models (P&#x2009;<&#x2009;0.001), indicating that realized breed composition deviates from theoretical expectations. Estimates of genetic differentiation confirmed greater divergence between Zebu and taurine groups, as well as reduced distances among populations sharing common ancestry. Specific relationships were identified between the composite and some of its founder breeds, particularly Belmont Red, Senepol, and Tuli. Overall, the results demonstrate that the Montana composite has a complex genomic structure, with genomic ancestry varying according to the resolution adopted and differing from pedigree-based expectations.

Animals↗

Fear of movement: factor structure of the tampa scale of kinesiophobia in patients with fibromyalgia syndrome.

UNLABELLED: Chronic pain patients often report fears that movement will exacerbate their symptoms. The Tampa Scale of Kinesiophobia (TSK) was designed to assess fear of movement. Previous findings with the TSK showed inconsistent factor structures and varied measurement properties. The TSK was completed by a sample of 233 patients with fibromyalgia syndrome who were being evaluated for participation in a rehabilitation program. A principal components analysis initially derived a 5-factor solution. However, the factor structure accounted for less than 50% of the variance, and the internal consistency of the factors was below conventional standards (<0.70). A series of principal components analyses "forcing" different factor structures revealed that the best solution was a single factor solution that contained 4 of the original 17 TSK items, accounting for more than 50% of the variance with adequate internal consistency (alpha =0.71). Inspection of the content of these 4 items, however, suggests that this factor more likely represents catastrophic thinking, rather than fear of movement. Nevertheless, for patients with fibromyalgia syndrome, a 4-item TSK appears to retain the most acceptable factor solution while also maintaining adequate internal consistency. PERSPECTIVE: Although the TSK is one of the most commonly used measures of fear of movement, the present study using the TSK with a sample of patients with fibromyalgia syndrome suggests that the measurement properties of the TSK are problematic. Recommendations for use of the TSK are provided.

Activities of Daily Living↗

The dimensions of responsiveness of a health system: a Taiwanese perspective.

BACKGROUND: Responsiveness is an indicator used to measure how well a health system performs relative to non-health aspects. This study assessed whether seven dimensions proposed by the World Health Organization (WHO) to measure responsiveness (dignity, autonomy, confidentiality, prompt attention, social support, basic amenities, and choices of providers) are applicable in evaluating the health system of Taiwan. METHODS: A key informant survey and focus group research were used in this study. The translated WHO proposed questionnaire was sent to 205 nominated key informants by mail, and 132 (64.4%) were returned. We used principal component analysis to extract factors. Linear regression analysis was used to assess the relationship between the total score and the extracted factors. A qualitative content analysis was also carried out in focus group research. RESULTS: Principal component analysis produced five factors (respect, access, confidentiality, basic amenities, and social support) that explained 63.5% of the total variances. These five factors demonstrated acceptable internal consistency and four of them (except social support) were significantly correlated with the total responsiveness score. The focus group interviews revealed health providers' communication ability and medical ethics were also highly appraised by Taiwanese. CONCLUSION: When the performance of a health system is to be evaluated, elements of responsiveness proposed by WHO may have to be tailored to fit different cultural backgrounds. Four key features illustrate the uniqueness of Taiwanese perspectives: the idea of autonomy may not be conceptualized, prompt attention and choice of providers are on the same track, social support during care is trivially correlated to the total responsiveness score, and accountability of health providers is deemed essential to a health system.

Adult↗

A direct measure of facial similarity and its relation to human similarity perceptions.

Research is reported on a measure of facial similarity in which the similarity of 2 faces is defined as the Euclidean distance between them in a principal-component space. Five studies were conducted in which participants rated sets of facial images, and in which the measure was applied to 2 problems in the eyewitness literature. Comparisons of ratings with distances derived from the principal-component analysis suggest that the measure corresponds reasonably well to perceptions of facial similarity. In addition, the measure correlates strongly with empirical measures of lineup fairness and is related to eyewitness identification performance. Further potential applications include a software tool for constructing arrays of faces of varying similarity, and a software tool for reconstructing facial images from memory.

Adolescent↗

Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions.

Multiple nanosecond duration molecular dynamics simulations were performed on the transmembrane region of the Torpedo nicotinic acetylcholine receptor embedded within a bilayer mimetic octane slab. The M2 helices and M2-M3 loop regions were free to move, whereas the outer (M1, M3, M4) helix bundle was backbone restrained. The M2 helices largely retain their hydrogen-bonding pattern throughout the simulation, with some distortions in the helical end and loop regions. All of the M2 helices exhibit bending motions, with the hinge point in the vicinity of the central hydrophobic gate region (corresponding to residues alphaL251 and alphaV255). The bending motions of the M2 helices lead to a degree of dynamic narrowing of the pore in the region of the proposed hydrophobic gate. Calculations of Born energy profiles for various structures along the simulation trajectory suggest that the conformations of the M2 bundle sampled correspond to a closed conformation of the channel. Principal components analyses of each of the M2 helices, and of the five-helix M2 bundle, reveal concerted motions that may be relevant to channel function. Normal mode analyses using the anisotropic network model reveal collective motions similar to those identified by principal components analyses.

Amino Acid Sequence↗

An empirical delineation of the heterogeneity of chronic unexplained fatigue in women.

OBJECTIVES: To test the hypothesis that medically unexplained chronic fatigue and chronic fatigue syndrome (CFS) are heterogeneous conditions, and to define the different conditions using both symptom and laboratory data. METHODS: We studied 159 women from KS, USA. A total of 51 of these suffered from fatigue consistent with established criteria for CFS, 55 had chronic fatigue of insufficient symptoms/severity for a CFS diagnosis and 53 were healthy controls matched by age and body mass index (BMI) against those with CFS. We used principal components analyses to define factors that best described the variable space and to reduce the number of variables. The 38 most explanatory variables were then used in latent class analyses to define discrete subject groups. RESULTS: Principal components analyses defined six discrete factors that explained 40% of the variance. Latent class analyses provided several interpretable solutions with four, five and six classes. The four-class solution was statistically most convincing, but the six-class solution was more interpretable. Class 1 defined 41 (26%) subjects with obesity and relative sleep hypnoea. Class 2 were 38 (24%) healthy subjects. Class 3 captured 24 (15%) obese relatively hypnoeic subjects, but with low heart rate variability and cortisol. Class 4 were 23 (14%) sleep-disturbed and myalgic subjects without obesity or significant depression. The two remaining classes with 22 (14%) and 11 (7%) subjects consisted of the most symptomatic and depressed, but without obesity or hypnoea. Class 5 had normal sleep indices. Class 6 was characterized by disturbed sleep, with low sleep heart rate variability, cortisol, and sex hormones. CONCLUSION: Chronic medically unexplained fatigue is heterogeneous. The putative syndromes were differentiated by obesity, sleep hypnoea, depression, physiological stress response, sleep disturbance, interoception and menopausal status. If these syndromes are externally validated and replicated, they may prove useful in determining the causes, pathophysiology and treatments of CFS.

Adult↗

Molecular alterations in primary prostate cancer after androgen ablation therapy.

PURPOSE: After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen-independent cancer. The molecular mechanisms underlying progression are not well known in part due to the rarity of androgen-independent samples from primary and metastatic sites. EXPERIMENTAL DESIGN: We compared the gene expression profiles of 10 androgen-independent primary prostate tumor biopsies with 10 primary, untreated androgen-dependent tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A GeneChip. Differential expression was examined with principal component analysis, hierarchical clustering, and Student's t testing. Analysis of gene ontology was done with Expression Analysis Systematic Explorer and gene expression data were integrated with genomic alterations with Differential Gene Locus Mapping. RESULTS: Unsupervised principal component analysis showed that the androgen-dependent and androgen-independent tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between androgen-independent and androgen-dependent tumors: macromolecule biosynthesis was down-regulated and cell adhesion was up-regulated in androgen-independent tumors. Other differentially expressed genes were related to interleukin-6 signaling as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The Differential Gene Locus Mapping analysis identified nine regions of potential chromosomal deletion in the androgen-independent tumors, including 1p36, 3p21, 6p21, 8p21, 11p15, 11q12, 12q23, 16q12, and 16q21. CONCLUSIONS: Taken together, these data identify several unique characteristics of androgen-independent prostate cancer that may hold potential for the development of targeted therapeutic intervention.

Aged↗

The effect of size variation on univariate assessments of morphological difference in human crania.

The present research was undertaken to determine the contribution of general size to craniometric variation in two previously described Paleo-Amerindian series, and to evaluate the effect of size variation on univariate assessments of morphological difference between the two. The analysis was based upon 19 measurements of 81 crania representing the Iswanid and Fort Ancient Muskogid varieties. The results of principal components analysis indicate that the 19 measurements can be represented as five principal component variates. Inspection of component eigenvectors indicates that variation in body size accounts for 40% of the variation within the metric data. Analysis of covariance lends support to the hypothesis that this size variation contributes substantially to statistical tests of difference between the two groups based on Student's t.

Analysis of Variance↗

Relationships between growth at the sutures of the rabbit calvarium.

The present study was designed to elucidate the relationships between growth increments at the cranial vault sutures in rabbits. Thirteen male New Zealand white rabbits were followed regularly from age 31 to 142 days using a roentgen stereophotogrammetric system. Spherical tantalum markers were implanted into the nasal, frontal, and parietal bones, and implant stability was checked at each stereo examination. Problems with instability were encountered only in the nasal bones. Registered growth rates conformed to our previous investigations. High correlations were observed between the following areas; the coronal suture to the frontonasal suture, the first principal component of the neurocranial suture group to the frontonasal suture, and the principal component of the craniofacial suture group to the coronal suture. Remaining relationships demonstrated dispersion to various extents. The findings indicate that there seems to exist a basic mutual dependence between neural and facial skeletal growth, as well as complex covariations between the various sutures of the rabbit calvarium.

Animals↗

Synthetic cancer variables and the construction and testing of synthetic risk maps.

Cancer cluster investigations are usually univariate in nature; they focus on a particular cancer, such as leukaemia, and attempt to determine whether excess risk is associated with a suspected cancer-causing agent. Although several causes of death (such as leukaemia, lymphoma, Hodgkin's) may be considered, the approach is univariate because the causes of death are analysed sequentially and independently of one another. This approach is consistent with a one-cause one-effect model. Rarely, however, is the action of a carcinogen manifested at only one body site, and correlations among causes of death are the norm rather than the exception. A multiple effects model is therefore appropriate, and the multivariate nature of cancer mortality data should be exploited when exploring geographic pattern in cancer risks. This paper describes such an approach. We construct maps based on a principal components analysis of cancer mortality rates from different geographic areas. The resulting principal components are called synthetic cancer variables (SCVs), and maps of the SCV scores are synthetic risk maps (SRMs). These maps quantify geographic variation in cancer risk at several body sites simultaneously, and may be analysed for (1) spatial structure and (2) geographic association with potential risk factors. As an example, we use synthetic risk maps to determine whether high-risk counties in Illinois cluster near nuclear facilities. Much work remains to be done, but synthetic cancer risk maps appear to be a useful tool for quantifying geographic pattern and multivariate structure in cancer mortality.

Air Pollutants, Radioactive↗