Ability to discriminate between healthy and low back pain sufferers using ultrasound during maximum lumbar extension

Objective To analyze the ability to discriminate between healthy individuals and individuals with chronic nonspecific low back pain (CNLBP) by measuring the relation between patient-reported outcomes and objective clinical outcome measures of the erector spinae (ES) muscles using an ultrasound during maximal isometric lumbar extension. Design Cross-sectional study with screening and diagnostic tests with no blinded comparison. Setting University laboratory. Participants Healthy individuals (n=33) and individuals with CNLBP (n=33). Interventions Each subject performed an isometric lumbar extension. With the variables measured, a discriminate analysis was performed using a value ≥6 in the Roland and Morris disability questionnaire (RMDQ) as the grouping variable. Then, a logistic regression with the functional and architectural variables was performed. A new index was obtained from each subject value input in the discriminate multivariate analysis. Main Outcome Measures Morphologic muscle variables of the ES muscle were measured through ultrasound images. The reliability of the measures was calculated through intraclass correlation coefficients (ICCs). The relation between patient-reported outcomes and objective clinical outcome measures was analyzed using a discriminate function from standardized values of the variables and an analysis of the reliability of the ultrasound measurement. Results The reliability tests show an ICC value >.95 for morphologic and functional variables. The independent variables included in the analysis explained 42% (P=.003) of the dependent variable variance. Conclusions The relation between objective variables (electromyography, thickness, pennation angle) and a subjective variable (RMDQ ≥6) and the capacity of this relation to identify CNLBP within a group of healthy subjects is moderate. These results should be considered by clinicians when treating this type of patient in clinical practice.

Substrate effects in the supramolecular assembly of 1,3,5-benzene tricarboxylic acid on graphite and graphene

The behavior of small molecules on a surface depends critically on both molecule–substrate and intermolecular interactions. We present here a detailed comparative investigation of 1,3,5-benzene tricarboxylic acid (trimesic acid, TMA) on two different surfaces: highly oriented pyrolytic graphite (HOPG) and single-layer graphene (SLG) grown on a polycrystalline Cu foil. On the basis of high-resolution scanning tunnelling microscopy (STM) images, we show that the epitaxy matrix for the hexagonal TMA chicken wire phase is identical on these two surfaces, and, using density functional theory (DFT) with a non-local van der Waals correlation contribution, we identify the most energetically favorable adsorption geometries. Simulated STM images based on these calculations suggest that the TMA lattice can stably adsorb on sites other than those identified to maximize binding interactions with the substrate. This is consistent with our net energy calculations that suggest that intermolecular interactions (TMA–TMA dimer bonding) are dominant over TMA–substrate interactions in stabilizing the system. STM images demonstrate the robustness of the TMA films on SLG, where the molecular network extends across the variable topography of the SLG substrates and remains intact after rinsing and drying the films. These results help to elucidate molecular behavior on SLG and suggest significant similarities between adsorption on HOPG and SLG.

ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients

The association of endoplasmic reticulum aminopeptidase 2 (ERAP2) with ankylosing spondylitis (AS) was recently described in the large International Genetics of AS Consortium Immunochip study...

Spanish version of the screening Orebro Musculoskeletal Pain Questionnaire: A cross-cultural adaptation and validation

Background Spanish is one of the five most spoken languages in the world. There is currently no published Spanish version of the Örebro Musculoskeletal Pain Questionnaire (OMPQ). The aim of the present study is to describe the process of translating the OMPQ into Spanish and to perform an analysis of reliability, internal structure, internal consistency and concurrent criterion-related validity. Methods Design: Translation and psychometric testing. Procedure: Two independent translators translated the OMPQ into Spanish. From both translations a consensus version was achieved. A backward translation was made to verify and resolve any semantic or conceptual problems. A total of 104 patients (67 men/37 women) with a mean age of 53.48 (±11.63), suffering from chronic musculoskeletal disorders, twice completed a Spanish version of the OMPQ. Statistical analysis was performed to evaluate the reliability, the internal structure, internal consistency and concurrent criterion-related validity with reference to the gold standard questionnaire SF-12v2. Results All variables except “Coping” showed a rate above 0.85 on reliability. The internal structure calculation through exploratory factor analysis indicated that 75.2% of the variance can be explained with six components with an eigenvalue higher than 1 and 52.1% with only three components higher than 10% of variance explained. In the concurrent criterion-related validity, several significant correlations were seen close to 0.6, exceeding that value in the correlation between general health and total value of the OMPQ. Conclusions The Spanish version of the screening questionnaire OMPQ can be used to identify Spanish patients with musculoskeletal pain at risk of developing a chronic disability.

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.

Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

Using genome-Wwide complex trait analysis to quantify 'missing heritability' in Parkinson's disease

Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI 17-38, P = 8.08E - 08) phenotypic variance associated with all types of PD, 15% (95% CI -0.2 to 33, P = 0.09) phenotypic variance associated with early-onset PD and 31% (95% CI 17-44, P = 1.34E - 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5%) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered. © Published by Oxford University Press 2012.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Self-assembly of indole-2-carboxylic acid at graphite and gold surfaces

Model systems are critical to our understanding of self-assembly processes. As such, we have studied the surface self-assembly of a small and simple molecule, indole-2-carboxylic acid (I2CA). We combine density functional theory gas-phase (DFT) calculations with scanning tunneling microscopy to reveal details of I2CA assembly in two different solvents at the solution/solid interface, and on Au(111) in ultrahigh vacuum (UHV). In UHV and at the trichlorobenzene/highly oriented pyrolytic graphite (HOPG) interface, I2CA forms epitaxial lamellar structures based on cyclic OH⋯O carboxylic dimers. The structure formed at the heptanoic acid/HOPG interface is different and can be interpreted in a model where heptanoic acid molecules co-adsorb on the substrate with the I2CA, forming a bicomponent commensurate unit cell. DFT calculations of dimer energetics elucidate the basic building blocks of these structures, whereas calculations of periodic two-dimensional assemblies reveal the epitaxial effects introduced by the different substrates.

Crystal engineering in two dimensions: An approach to molecular nanopatterning

We describe a surprising cooperative adsorption process observed by scanning tunneling microscopy (STM) at the liquid−solid interface. The process involves the association of a threefold hydrogen-bonding unit, trimesic acid (TMA), with straight-chain aliphatic alcohols of varying length (from C7 to C30), which coadsorb on highly oriented pyrolytic graphite (HOPG) to form linear patterns. In certain cases, the known TMA “flower pattern” can coexist temporarily with the linear TMA−alcohol patterns, but it eventually disappears. Time-lapsed STM imaging shows that the evolution of the flower pattern is a classical ripening phenomenon. The periodicity of the linear TMA−alcohol patterns can be modulated by choosing alcohols with appropriate chain lengths, and the precise structure of the patterns depends on the parity of the carbon count in the alkyl chain. Interactions that lead to this odd−even effect are analyzed in detail. The molecular components of the patterns are achiral, yet their association by hydrogen bonding leads to the formation of enantiomeric domains on the surface. The interrelation of these domains and the observation of superperiodic structures (moiré patterns) are rationalized by considering interactions with the underlying graphite surface and within the two-dimensional crystal of the adsorbed molecules. Comparison of the observed two-dimensional structures with the three-dimensional crystal structures of TMA−alcohol complexes determined by X-ray crystallography helps reveal the mechanism of molecular association in these two-component systems.

Supramolecular ordering in oligothiophene−fullerene monolayers

Scanning tunneling microscopy (STM) of monolayers comprising oligothiophene and fullerene molecular semiconductors reveals details of their molecular-scale phase separation and ordering with potential implications for the design of organic electronic devices, in particular future bulk heterojunction solar cells. Prochiral terthienobenzenetricarboxylic acid (TTBTA) self-assembles at the solution/graphite interface into either a porous chicken wire network linked by dimeric hydrogen bonding associations of COOH groups (R22(8)) or a close-packed network linked in a novel hexameric hydrogen bonding motif (R66(24)). Analysis of high-resolution STM images shows that the chicken wire phase is racemically mixed, whereas the close-packed phase is enantiomerically pure. The cavities of the chicken wire structure can efficiently host C60 molecules, which form ordered domains with either one, two, or three fullerenes per cavity. The observed monodisperse filling and long-range co-alignment of fullerenes is described in terms of a combination of an electrostatic effect and the commensurability between the graphite and molecular network, which leads to differentiation of otherwise identical adsorption sites in the pores.

Supramolecular assembly of heterocirculenes in 2D and 3D

The results of a high-resolution ambient STM study of ‘sulflower’ (octathio[8]circulene) and ‘selenosulflower’ (sym-tetraselena-tetrathio[8]circulene) molecules, immobilized in a hydrogen-bonded matrix of trimesic acid (TMA) at the solid–liquid interface, are compared with the STM and X-ray structure of separate host and guest 2D and 3D crystals, respectively.

Inducing nonlocal reactions with a local probe

The scanning tunneling microscope (STM) has evolved continually since its invention, as scientists have expanded its use to encompass atomic-scale manipulation, momentum-resolved electronic characterization, localized chemical reactions (bond breaking and bond making) in adsorbed molecules, and even chain reactions at surfaces. This burgeoning field has recently expanded to include the use of the STM to inject hot electrons into substrate surface states; the injected electrons can travel laterally and induce changes in chemical structure in molecules located up to 100 nm from the STM tip. We describe several key demonstrations of this phenomenon, including one appearing in this issue of ACS Nano by Chen et al. Possible applications for this technique are also discussed, including characterizing the dispersion of molecule−substrate interface states and the controlled patterning of molecular overlayers.

The critical role of water in spider silk and its consequence for protein mechanics

Due to its remarkable mechanical and biological properties, there is considerable interest in understanding, and replicating, spider silk's stress-processing mechanisms and structure-function relationships. Here, we investigate the role of water in the nanoscale mechanics of the different regions in the spider silk fibre, and their relative contributions to stress processing. We propose that the inner core region, rich in spidroin II, retains water due to its inherent disorder, thereby providing a mechanism to dissipate energy as it breaks a sacrificial amide-water bond and gains order under strain, forming a stronger amide-amide bond. The spidroin I-rich outer core is more ordered under ambient conditions and is inherently stiffer and stronger, yet does not on its own provide high toughness. The markedly different interactions of the two proteins with water, and their distribution across the fibre, produce a stiffness differential and provide a balance between stiffness, strength and toughness under ambient conditions. Under wet conditions, this balance is destroyed as the stiff outer core material reverts to the behaviour of the inner core.