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Reconstruction of porous material geometry by stochastic optimization based on bulk NMR measurements of the dipolar field.

The dependence of the bulk signal intensity from a CRAZED NMR pulse sequence on magnetic field gradient strength and direction as a method to probe the geometry of porous materials is investigated. In this article, we report on the reconstruction of three-dimensional media consisting of a void phase and an NMR-observable liquid phase using the bulk intensity of the distant dipolar field. The correlation gradient strength and direction provide the spatial encoding of the material geometry. An integral equation for the total signal intensity is then solved numerically by a simulated annealing algorithm to recover the indicator function of the fluid phase. Results show that cylindrical and spherical structures smaller than the volume contributing to the NMR signal can be resolved using three values of the correlation distance and three orthogonal gradient directions. This is done by minimizing a cost function which measures the distance between the bulk signal dependence on gradient parameters for the simulated configuration and the signal dependence for the target configuration. The algorithm can reconstruct and differentiate their spherical and cylindrical phase-inverted equivalents. It can also differentiate horizontal from vertical cylinders, demonstrating the potential for assessing structural anisotropy and other coarse geometric quantifiers in a porous material.

Algorithms↗

Total joint replacement of hip or knee as an outcome measure for structure modifying trials in osteoarthritis.

OBJECTIVE: The Group for the Respect of Ethics and Excellence in Science (GREES) organized a working group to assess the value of time to joint surgery as a potential therapeutic failure outcome criterion for osteoarthritis (OA) of the hip or knee in the assessment of potential structure modifying agents. METHODS: PubMed was searched for manuscripts from 1976 to 2004. Relevant studies were discussed at a 1-day meeting. RESULTS: There are no accepted guidelines for 'time to' and 'indications for' joint replacement surgery. A limited number of trials have examined joint replacement surgery within the study population. Several parameters, particularly joint space narrowing (interbone distance), correlate with surgical intervention. However, at the level of the knee, none of the parameters have positive predictive value for joint replacement surgery better than 30%. In contrast, lack of significant joint space narrowing has a strong negative predictive value for joint replacement surgery (>90%), that remains after controlling for OA pain severity. CONCLUSION: At this time, GREES cannot recommend time to joint surgery as a primary endpoint of failure for structure modifying trials of hip or knee OA-as the parameter has sensitivity but lacks specificity. In contrast, in existing trials, a lack of progression of joint space narrowing has predictive value of >90% for not having surgery. GREES suggests utilizing joint space narrowing (e.g., >0.3-0.7 mm) combined with a lack of clinically relevant improvement in symptoms (e.g., >/=20-25%) for 'failure' of a secondary outcome in structure modifying trials of the hip and knee.

Antirheumatic Agents↗

Chaos game representation of protein sequences based on the detailed HP model and their multifractal and correlation analyses.

Similar to the chaos game representation (CGR) of DNA sequences proposed by Jeffrey (Nucleic Acid Res. 18 (1990) 2163), a new CGR of protein sequences based on the detailed HP model is proposed. Multifractal and correlation analyses of the measures based on the CGR of protein sequences from complete genomes are performed. The Dq spectra of all organisms studied are multifractal-like and sufficiently smooth for the Cq curves to be meaningful. The Cq curves of bacteria resemble a classical phase transition at a critical point. The correlation distance of the difference between the measure based on the CGR of protein sequences and its fractal background is also proposed to construct a more precise phylogenetic tree of bacteria.

Bacterial Proteins↗

Imaging fluorescence correlation spectroscopy: nonuniform IgE distributions on planar membranes.

Fluorescence correlation spectroscopy is useful for detecting and characterizing molecular clusters that are smaller than or approximately equal to optical resolution in size. Here, we report the development of an approach in which the pixel-to-pixel fluorescence fluctuations from a single fluorescence image are spatially autocorrelated. In these measurements, tetramethylrhodamine-labeled, anti-trinitrophenyl IgE antibodies were specifically bound to substrate-supported planar membranes composed of trinitrophenyl-aminocaproyldipalmitoylphosphatidylethanolamine and dipalmitoylphosphatidylcholine. The antibody-coated membranes were illuminated with the evanescent field from a totally internally reflected laser beam, and the fluorescence arising from the IgE-coated membranes was recorded with a cooled CCD camera. The image was corrected for the elliptical Gaussian shape of the evanescent illumination after background subtraction. The spatial autocorrelation functions of the resulting images generated two useful parameters: the extrapolated initial values, which were related to the average cluster intensity and density; and the correlation distances, which were related to the average cluster size. These parameters varied with the IgE density, and unlabeled polyclonal anti-IgE enhanced the nonuniform IgE distributions. The autocorrelation functions calculated from images of planar membranes containing fluorescently labeled lipids rather than bound, labeled IgE demonstrated that the spatial nonuniformities were prominent only in the presence of IgE. Fluorescent beads were used to demonstrate the principles and the methods.

Animals↗

A neural network-based similarity index for clustering DNA microarray data.

A common approach to the analysis of gene expression data is to define clusters of genes that have similar expression. A critical step in cluster analysis is the determination of similarity between the expression levels of two genes. We introduce a neural network-based similarity index as a non-linear similarity index and compare the results with other proximity measures for Saccharomyces cerevisiae gene expression data. We show that the clusters obtained using Euclidean distance, correlation coefficients, and mutual information were not significantly different. The clusters formed with the neural network-based index were more in agreement with those defined by functional categories and common regulatory motifs.

Algorithms↗

Lysozyme viscoelastic matrices in tetramethylurea/water media: a small angle X-ray scattering study.

Semi-solid viscoelastic matrices produced out of lysozyme in organic/aqueous media [tetramethylurea (TMU)/water] were characterized by small angle X-ray scattering (SAXS). The scattering curves were modeled in their form and interference factors. Radii of gyration of scattering particles were found to undergo a dramatic increase from 14 A in water to approximately 44 A in the matrices. Average correlation distances d=155 A were consistently verified for the scattering particles in the matrices, irrespective of solvent composition (in the 0.6<or=w(TMU)<or=0.8 range), in contrast to what is observed in water (d=62 A). At w(TMU)=0.9, however, a slight increase in R(g) (to R(g)=49 A) leads to interdigitation with the apolar prevailing medium of the matrix leading to the loss of the interference effect. Low dimensionality derived from the modeling procedure could be taken to indicate mass fractal character of the unfolded species, although polydispersion of samples could also have some contribution to that result. Despite the very significant shape distortion of the unfolded protein forms in the matrices, they still retain considerable globular character, as indicated by the Kratky plots obtained. The morphological results obtained in this work are compatible with the dynamical behavior displayed by the systems.

Animals↗

Assessment of stereopsis in college baseball pitchers and batters.

BACKGROUND/PURPOSE: In baseball pitching is a much less visually demanding task than hitting is. We sought to find a stronger relationship between visual function (as measured by stereopsis) and hitting a baseball than between stereopsis and pitching skill. METHODS: Multiple parameters including near and distance stereopsis (as a measure of visual function) were measured in 23 returning college baseball players (with a prior year's record). Their level of stereopsis (measured at distance with use of the B-VAT II BVS Binocular Vision Testing System) was compared with their batting statistics (in the case of the 14 position players) or their pitching statistics (for the 9 pitchers). Batting average and slugging percentage were used as measures of hitting skill, and earned run average, "out percentage" (1.000--Opposing players' batting average) and "strike-out percentage" (frequency of batters struck out) were used as pitching parameters. RESULTS: As a group, visual parameters were excellent in these college athletes. Although the newer test of distance stereopsis correlated with the standard near stereo test (Spearman coefficients), there was no correlation between distance stereopsis and any of the pitching or hitting performance parameters. CONCLUSIONS: The nature of the visual demands required of successful baseball hitters may have yet to be determined or are difficult to identify among a population homogeneous for excellent visual function, true for most groups of competitive athletes. In addition, simpler parameters such as plain visual acuity may be the most important factor(s).

Baseball↗

Intramolecular electron transfer in trimethylamine dehydrogenase: a thermodynamic analysis.

Within the enzyme trimethylamine dehydrogenase [TMADH], intramolecular electron transfer occurs between a fully reduced covalently bound 6-S-cysteinylflavin [FMN] cofactor, and an oxidized iron-sulfur [4Fe-4S]2+ center. When the enzyme is reduced by substrate trimethylamine, the kinetics of this intramolecular electron transfer [ET] reaction are biphasic, suggesting that ET occurs via two alternative processes [Falzon, L., & Davidson, V.L. (1996) Biochemistry 35, 2445-2452]. The formation of the FMN semiquinone was monitored by stopped-flow spectroscopy, and the two rate constants for the biphasic reaction were determined at temperatures ranging from 12 to 37 degrees C. Analysis of these rate constants by ET theory yielded values of 2.2 eV for the reorganizational energy [lambda] associated with each reaction and electronic coupling [H(AB)] of 5.9 and 47 cm-1 for the slower and faster ET reactions, respectively. The analysis also predicted average theoretical distance between the two redox centers of 12.3 A for the slower reaction and 8.1 A for the faster reaction. These predicted distances correlate well with the known crystal structure of TMADH and the most efficient pathways for ET that were predicted from the known structure using the Greenpath program. This analysis suggests that for each reaction the ET event is rate-limiting, but coupled to a highly unfavorable non-ET process, and that binding of a second molecule of substrate to reduced TMADH decreases the efficiency of the intramolecular ET.

Binding Sites↗

Metal-metal interactions in mixed-valence [M2Cl9]2- species: electronic structure of d1d2 (V, Nb, Ta) and d4d5 (Fe, Ru, Os) face-shared systems.

The molecular and electronic structures of mixed-valence d1d2 (V, Nb, Ta) and d4d5 (Fe, Ru, Os) face-shared [M2Cl(9)]2- dimers have been calculated by density functional methods in order to investigate metal-metal bonding in this series. General similarities are observed between d1d2 and d4d5 systems and can be considered to reflect the electron-hole equivalence of the individual d1-d5 and d2-d4 configurations. The electronic structures of the dimers have been analyzed using potential energy curves for the broken-symmetry and other spin states resulting from the d1d2 and d4d5 coupling modes. In general, a spin-doublet (S = 1/2) state, characterized by delocalization of the metal-based electrons in a metal-metal bond with a formal order of 1.5, is favored in the systems containing 4d and 5d metals, namely, the Nb, Ta, Ru, and Os dimers. In contrast, the calculated ground structures for [V2Cl9]2- and [Fe2Cl9]2- correspond to a spin-quartet (S = 3/2) state involving weaker coupling between the metal centers and electron localization. In the case of [Ru2Cl9]2-, both the spin-doublet and spin-quartet states are predicted to be energetically favored suggesting that this species may exhibit double-minima behavior. A comparison of computational results across the (d1d1, d1d2, d2d2) [Nb2Cl9]z- and [Ta2Cl9]z- and (d4d4, d4d5, d5d5) [Ru2Cl9]z- and [Os2Cl9]z- series has revealed that, in all four cases, the shortening of the metal-metal distances correlates with an increase in formal metal-metal bond order.

Journal Article↗

Rational Design of a Novel Intercalation System. Layer-Gap Control of Crystalline Coordination Polymers, {[Cu(CA)(H(2)O)(m)()](G)}(n)() (m = 2, G = 2,5-Dimethylpyrazine and Phenazine; m = 1, G = 1,2,3,4,6,7,8,9-Octahydrophenazine).

New copper(II) intercalation compounds, {[Cu(CA)(H(2)O)(2)](G)}(n)() (H(2)CA = chloranilic acid; G = 2,5-dimethylpyrazine (dmpyz) (1a and 1b) and phenazine (phz) (2)) have been synthesized and characterized. 1acrystallizes in the triclinic space group P&onemacr;, with a = 8.028(2) Å, b = 10.269(1) Å, c = 4.780(2) Å, alpha = 93.85(3) degrees, beta = 101.01(2) degrees, gamma = 90.04(3) degrees, and Z = 1. 1b crystallizes in the triclinic space group P&onemacr;, with a = 8.010(1) Å, b = 10.117(1) Å, c = 5.162(1) Å, alpha = 94.40(1) degrees, beta = 97.49(1) degrees, gamma = 112.64(1) degrees, and Z = 1. 2crystallizes in the triclinic space group P&onemacr;, with a = 8.071(1) Å, b = 11.266(1) Å, c = 4.991(1) Å, alpha = 97.80(1) degrees, beta = 99.58(1) degrees, gamma = 83.02(1) degrees, and Z = 1. For all the compounds, the crystal structures consist of one dimensional [Cu(CA)(H(2)O)(2)](m)() chains and uncoordinated guest molecules (G). Each copper atom for 1a, 1b, and 2 displays a six-coordinate geometry with the two bis-chelating CA(2)(-) anions and water molecules, providing an infinite, nearly coplanar linear chains running along the a-direction. Theses chains are linked by hydrogen bonds between the coordinated water and the oxygen atoms of CA(2)(-) on the adjacent chain, forming extended layers, which spread out along the ac-plane. The guest molecules are intercalated in between the {[Cu(CA)(H(2)O)(2)](k)()}(l)() layers, just like pillars, which are supported with N.H(2)O hydrogen bonding. The guest molecules are stacked each other with an interplanar distance of ca. 3.2 Å along the c-axis perpendicular to the [Cu(CA)(H(2)O)(2)](m)() chain. The EHMO band calculations of intercalated dmpyz and phz columns show an appreciable band dispersion of phz pi (b(2g) and b(3g)) and dmpyz pi (b(g)), indicative of the importance of planar pi structure for the formation of the intercalated structure. The distances of O-H---N (guest molecules) fall within the range 2.74-2.80 Å, insensitive to the guest, whereas the interlayer distances increase in the order 9.25 Å (1b), 10.24 Å (1a), and 11.03 Å (2). The degree in lengthening the distance correlates well with the size of a molecule, indicative of the stability of the 2-D sheet structure and the flexibility of the sheet packing. The magnetic susceptibilities were measured from 2 to 300 K and analyzed by a one-dimensional Heisenberg-exchange model to yield J = -1.83 cm(-)(1), g = 2.18 (1a), J = -0.39 cm(-)(1), g = 2.14 (1b), and J = -1.84 cm(-)(1), g = 2.18 (2). The absolute value of J is smaller than that value for [Cu(CA)](n)(), which has a planar ribbon structure suggesting that the magnetic orbital d(x)()()2(-)(y)()()2 is not parallel to the chloranilate plane. For comparison with phz another type of copper(II) coordination compound, {[Cu(CA)(H(2)O)](ohphz)}(n)() (ohphz = 1,2,3,4,6,7,8,9-octahydrophenazine (7)) has also been obtained. 7 crystallizes in the orthorhombic space group Cmcm with a = 7.601(2) Å, b = 13.884(2) Å, c = 17.676(4) Å, and Z = 4. Nonplanar ohphz molecules are in between [Cu(CA)(H(2)O)(2)](m)() chains with the N.H(2)O hydrogen bonding in a fashion parallel to the chain direction. The copper atom shows a five-coordinate square-pyramidal configuration with two CA and one water molecule, thus affording no hydrogen bonding links between chains, dissimilar to 1a, 1b, and 2. The magnetic susceptibilities yield J = -10.93 cm(-)(1) and g = 2.00, comparable to that of the four-coordinate [Cu(CA)](n)(). On this basis both hydrogen bonding and stack capability of a guest molecule is responsible for building the unique intercalated structure such as is seen in 1a, 1b, and 2.

Journal Article↗

Role of framework sodium versus local framework structure in determining the hydrothermal stability of MCM-41 mesostructures.

Two mesostructured MCM-41 silicas that differ dramatically in hydrothermal stability have been examined by (29)Si MAS NMR spectroscopy and pair distribution function (PDF) analysis of synchrotron X-ray scattering data. The less stable mesostructure assembled from sodium silicate and the substantially more stable derivative made from fumed silica possess equivalent local framework wall structures, as judged by NMR and PDF methods. Approximately 80% of the SiO(4) tetrahedra are fully cross-linked as Q(4) (Si(OSi)(4)) units in both calcined samples. Additionally, the structural correlation distances for the two materials are nearly identical, having values of 1.62(1), approximately 2.60, and 3.09(1) A for the Si-O, O-O, and nearest neighbor Si-Si distances in the framework. Sodium ions in the framework play a crucial role in limiting the hydrothermal stability of the mesostructure. Residual sodium ( approximately 0.05-0.10% Na(2)O) is retained in the MCM-41 made from sodium silicate, even after two ion exchange reactions with ammonium ions in more than 300 - fold excess. The entrapped framework sodium ions catalyze the collapse of the mesopores upon exposure to 20% steam at 800 degrees C for 5 h. The sodium - free mesostructure assembled from fumed silica retains an open framework under the same hydrothermal conditions. The stability of the fumed silica derivative, however, is greatly compromised when doped with as little as 0.10% Na(2)O, thus confirming the deleterious effect of sodium on hydrothermal stability.

Journal Article↗

Synthesis of mesoporous aluminophosphate (AlPO) and investigation of zirconium incorporation into mesoporous AlPOs.

Mesoporous aluminophosphate materials with variable amounts of zirconium have been synthesized at room temperature using a nonionic surfactant tri-block copolymer (PEO(20)PPO(70)PEO(20)) as the structure-directing agent. Powder X-ray diffraction of as-synthesized and calcined AlPO and ZrAlPO mesoporous materials shows a single broad peak near 2theta = 2.5 degrees, indicative of the average pore-pore correlation distance. Electron probe microanalysis shows that the ratio of P/Al in the powders is approximately 0.5, far lower than 1.0 for an ideal aluminophosphate framework. XRD, TEM, and N2 adsorption data indicate that the calcined samples consist of wormlike tubular materials having surface areas >350 m2/g and pores in the mesopore range. Electron spin resonance (ESR) studies of the gamma-irradiated and evacuated ZrAlPO samples show signals due to Zr3+ that increase with Zr content in addition to signals due to framework defects (i.e., V centers) and H atoms. The line shape and g values observed for Zr3+ are best explained as arising from a trivalent zirconium ion situated at the framework tetrahedral sites.

Journal Article↗

The development of adaptive head movements following enucleation.

Recent work in our laboratory has revealed that enucleated patients produce large lateral and vertical head movements during visually guided grasping. These movements may allow them to maximise the use of retinal motion cues in planning and controlling their grasp. The aim of the present study was to determine whether the tendency to produce these adaptive head movements increases as a function of time since enucleation. We tested a group of 12 enucleated patients in whom the time between surgery and testing varied from 2 weeks to 35 years (mean = 11.2 years). These patients were required to reach out and grasp oblong blocks of different sizes at different distances. Correlational tests revealed an increase in the proportion of self-generated lateral and vertical head movements versus forward head movements as a function of post-enucleation time (r(s)(12) = 0.68, p < 0.025 and r(s)(12) = 0.65, p < 0.025, respectively). This suggests that enucleated patients may be adapting to living with one eye by learning to increase the proportion of their lateral and vertical head movements during the performance of skilled motor acts.

Adaptation, Physiological↗

Structure of a protein determined by solid-state magic-angle-spinning NMR spectroscopy.

The determination of a representative set of protein structures is a chief aim in structural genomics. Solid-state NMR may have a crucial role in structural investigations of those proteins that do not easily form crystals or are not accessible to solution NMR, such as amyloid systems or membrane proteins. Here we present a protein structure determined by solid-state magic-angle-spinning (MAS) NMR. Almost complete (13)C and (15)N resonance assignments for a micro-crystalline preparation of the alpha-spectrin Src-homology 3 (SH3) domain formed the basis for the extraction of a set of distance restraints. These restraints were derived from proton-driven spin diffusion (PDSD) spectra of biosynthetically site-directed, labelled samples obtained from bacteria grown using [1,3-(13)C]glycerol or [2-(13)C]glycerol as carbon sources. This allowed the observation of long-range distance correlations up to approximately 7 A. The calculated global fold of the alpha-spectrin SH3 domain is based on 286 inter-residue (13)C-(13)C and six (15)N-(15)N restraints, all self-consistently obtained by solid-state MAS NMR. This MAS NMR procedure should be widely applicable to small membrane proteins that can be expressed in bacteria.

Animals↗

Gaining confidence in high-throughput protein interaction networks.

Although genome-scale technologies have benefited from statistical measures of data quality, extracting biologically relevant pathways from high-throughput proteomics data remains a challenge. Here we develop a quantitative method for evaluating proteomics data. We present a logistic regression approach that uses statistical and topological descriptors to predict the biological relevance of protein-protein interactions obtained from high-throughput screens for yeast. Other sources of information, including mRNA expression, genetic interactions and database annotations, are subsequently used to validate the model predictions without bias or cross-pollution. Novel topological statistics show hierarchical organization of the network of high-confidence interactions: protein complex interactions extend one to two links, and genetic interactions represent an even finer scale of organization. Knowledge of the maximum number of links that indicates a significant correlation between protein pairs (correlation distance) enables the integrated analysis of proteomics data with data from genetics and gene expression. The type of analysis presented will be essential for analyzing the growing amount of genomic and proteomics data in model organisms and humans.

Algorithms↗

Circadian rhythms of macrophages are altered by the acidic tumor microenvironment.

Tumor-associated macrophages (TAMs) are prime therapeutic targets due to their pro-tumorigenic functions, but varying efficacy of macrophage-targeting therapies highlights our incomplete understanding of how macrophages are regulated within the tumor microenvironment (TME). The circadian clock is a key regulator of macrophage function, but how circadian rhythms of macrophages are influenced by the TME remains unknown. Here, we show that conditions associated with the TME such as polarizing stimuli, acidic pH, and lactate can alter circadian rhythms in macrophages. While cyclic AMP (cAMP) has been reported to play a role in macrophage response to acidic pH, our results indicate pH-driven changes in circadian rhythms are not mediated solely by cAMP signaling. Remarkably, circadian disorder of TAMs was revealed by clock correlation distance analysis. Our data suggest that heterogeneity in circadian rhythms within the TAM population level may underlie this circadian disorder. Finally, we report that circadian regulation of macrophages suppresses tumor growth in a murine model of pancreatic cancer. Our work demonstrates a novel mechanism by which the TME influences macrophage biology through modulation of circadian rhythms.

Tumor Microenvironment↗

Evaluation of tuned aperture computed tomography (TACT) in the localization of simulated periodontal defects.

OBJECTIVES: To compare the diagnostic efficacy of tuned aperture computed tomography (TACT) with the application of the 'buccal object rule' (BOR) in the localization of simulated periodontal defects. METHODS: Thirty interproximal sites were selected in fifteen cadaver segments of maxillae and mandible. Artificial periodontal defects were created using round burs and 40% formic acid in the buccal, lingual or mid-buccolingual areas. Eight basis projections were obtained and TACT slices were reconstructed for each region of interest. Two of the basis images were used in application of BOR for localization of the defect. Eight observers scored the location of defects using TACT slices and the paired radiographs separately. Data were analysed using the kappa statistic and ANOVA. RESULTS: A mean weighted kappa of 0.14 for localization was obtained with both BOR and TACT. Using ANOVA, there was no significant difference between modality and observer. There was however, a significant difference (P=0.019) between different defect sizes. Both modalities performed better with larger defect sizes. TACT performed slightly better than BOR when the smaller lesions were included; however, with larger lesions, this trend was reversed. CONCLUSIONS: The results confirm the relationship between correlation distance (the resultant slice width) and object size in the application of TACT for localization. BOR remains a simple yet effective tool for localization. The clinical significance is not clear considering the low kappa scores obtained with both the modalities.

Algorithms↗

The relationship between self-reports and objective measures of disability in patients with late sequelae of poliomyelitis: a validation study.

OBJECTIVE: To establish the validity of 2 objective measures of disability based on 2 self-reports in individuals with the late sequelae of poliomyelitis (LSP). DESIGN: Nonexperimental research design. SETTING: Regional ambulatory clinic specializing in the management of patients with LSP. PARTICIPANTS: Seventeen community dwellers with LSP. INTERVENTION: Completion of 2 exercise tests: the 6-minute walk (6-MW) test and a steady-rate walking test to calculate the cardiorespiratory conditioning index (CRCI), and 2 health status questionnaires: the Sickness Impact Profile (SIP) and Medical Outcomes Study Short-Form 36 (SF-36). MAIN OUTCOME MEASURES: 6-MW distance and the CRCI, and scores from the physical dimensions of the SIP and the SF-36. RESULTS: The 6-MW distance correlated significantly with the physical dimension scores of both the SIP (r = -.57, p < .05) and the SF-36 (r = .67, p < .05). Significant correlations were also observed between the CRCI and the physical dimension scores of the SIP (r = -.51, p < .05) and the SF-36 (r = .70, p < .01). The 2 objective measures correlated significantly with each other (r = .51, p < .05) as did the 2 physical dimension scores of the SIP and the SF-36 (r = -.80, p < .01). CONCLUSIONS: Although objective measures of disability corroborated self-reports of patients with LSP and, thus, supported their validity, each measure has a distinct role in clinical decision making.

Analysis of Variance↗