Tactile Thresholds are Preserved yet Cortical Sensory Function is Impaired in Chronic Non-Specific Low Back Pain Patients

Introduction: A substantial amount of evidence points to an alteration in brain structure and function patients with chronic non-specific low back pain (CNSLBP) [1-6]. One interpretation of these findings is that the observed brain changes may represent a disruption of the brain’s representations of the body part and the resultant body perception disturbance may underpin this clinical problem. The current study aimed to investigate sensory dysfunction in CNSLBP. Specifically we aimed to distinguish cortically mediated sensory dysfunction from peripheral dysfunction by comparing simple tactile thresholds with more complex cortically mediated sensory tests Methods: We investigated tactile thresholds (TTH), two point discrimination (TPD) and graphaesthesia over the lumbar spine of 19 CLBP patients and 19 age and sex matched healthy controls as a way of investigating whether CLBP patients present with a perceptual disturbance of their lumbar spine. Differences in performance of the sensory tests was explored using the Mann Whitney U Test and one-way between groups multivariate analysis of variance. Results: We found no difference in tactile threshold between the two groups (P=.0.751). There was a statistically significant difference between controls and LBP for TPD: F(1,36)=10.15, p=.003 and letter error rate: F(1, 36)=6.54 p=0.015. The data indicate that LBP patients had a larger lumbar TPD distance and a greater letter recognition error rate. Discussion: Both TPD and graphaesthesia are dependant on the integrity of the primary sensory cortex [7]. These data support existing findings of perceptual abnormality in chronic back pain [8] and the preservation of tactile thresholds is suggestive of cortical rather than peripheral sensory dysfunction. Amelioration of these abnormalities may present a target for therapeutic intervention

Rethinking clinical trials of transcranial direct current stimulation: Participant and assessor blinding is inadequate at intensities of 2mA

Copyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.Background: Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding. Methods: A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation. Results: tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p = 0.005) and the second session (κ = 0.77, 95%CI 0.64 to 0.90), p = <0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ = 0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ = 0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding. Conclusions: Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution.GLM is supported by the National Health & Medical Research Council of Australia ID 571090

A multi-layer extension of the stochastic heat equation

Motivated by recent developments on solvable directed polymer models, we define a 'multi-layer' extension of the stochastic heat equation involving non-intersecting Brownian motions.Comment: v4: substantially extended and revised versio

Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients. A preliminary investigation

Objectives: To investigate impairments in sensory function in chronic non-specific low back pain patients and the relationship between any impairment and the clinical features of the condition. Design: A cross-sectional case-control study. Setting: Laboratory based study. Participants: Nineteen chronic non-specific low back pain patients and nineteen healthy controls. Main Outcome measures: Tactile threshold, two point discrimination distance and accuracy at a task involving recognizing letters drawn over the skin of the lower back (graphaesthesia) were assessed over the lumbar spine in both groups. Pain duration, pain intensity, physical function, anxiety and depression were assessed by questionnaire in the back pain group Results: We found no difference in tactile threshold between the two groups (median difference 0.00 95% CI -0.04 – 0.04). There was a significant difference between controls and back pain patients for two point discrimination (mean difference 17.85 95% CI 5.93 – 29.77) and graphaesthesia accuracy (mean difference 6.13 95% CI 1.27-10.99). Low back pain patients had a larger lumbar two point discrimination distance threshold and a greater letter recognition error rate. In the patient group, we found no relationship between clinical profile and sensory function and no relationship between the sensory tests. Conclusions: These data support existing findings of perceptual abnormalities in chronic non-specific low back pain patients and are suggestive of cortical rather than peripheral sensory dysfunction. Amelioration of these abnormalities may present a target for therapeutic intervention

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

The genome of the emerging barley pathogen Ramularia collo-cygni

Background Ramularia collo-cygni is a newly important, foliar fungal pathogen of barley that causes the disease Ramularia leaf spot. The fungus exhibits a prolonged endophytic growth stage before switching life habit to become an aggressive, necrotrophic pathogen that causes significant losses to green leaf area and hence grain yield and quality. Results The R. collo-cygni genome was sequenced using a combination of Illumina and Roche 454 technologies. The draft assembly of 30.3 Mb contained 11,617 predicted gene models. Our phylogenomic analysis confirmed the classification of this ascomycete fungus within the family Mycosphaerellaceae, order Capnodiales of the class Dothideomycetes. A predicted secretome comprising 1053 proteins included redox-related enzymes and carbohydrate-modifying enzymes and proteases. The relative paucity of plant cell wall degrading enzyme genes may be associated with the stealth pathogenesis characteristic of plant pathogens from the Mycosphaerellaceae. A large number of genes associated with secondary metabolite production, including homologs of toxin biosynthesis genes found in other Dothideomycete plant pathogens, were identified. Conclusions The genome sequence of R. collo-cygni provides a framework for understanding the genetic basis of pathogenesis in this important emerging pathogen. The reduced complement of carbohydrate-degrading enzyme genes is likely to reflect a strategy to avoid detection by host defences during its prolonged asymptomatic growth. Of particular interest will be the analysis of R. collo-cygni gene expression during interactions with the host barley, to understand what triggers this fungus to switch from being a benign endophyte to an aggressive necrotroph

The Eleventh and Twelfth Data Releases of the Sloan Digital Sky Survey: Final Data from SDSS-III

The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All of the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 deg2 of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include the measured abundances of 15 different elements for each star. In total, SDSS-III added 5200 deg2 of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 deg2; 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra. \ua9 2015. The American Astronomical Society

Effects of caffeine on reaction time are mediated by attentional rather than motor processes

Background Caffeine has a well-established effect on reaction times (RTs) but the neurocognitive mechanisms underlying this are unclear. Methods In the present study, 15 female participants performed an oddball task after ingesting caffeine or a placebo, and electroencephalographic data were obtained. Single-trial P3b latencies locked to the stimulus and to the response were extracted and mediation models were fitted to the data to test whether caffeine’s effect on RTs was mediated by its effect on either type of P3b latencies. Results Stimulus-locked latencies showed clear evidence of mediation, with approximately a third of the effect of caffeine on RTs running through the processes measured by stimulus-locked latencies. Caffeine did not affect response-locked latencies, so could not mediate the effect. Discussion These findings are consistent with caffeine’s effect on RTs being a result of its effect on perceptual-attentional processes, rather than motor processes. The study is the first to apply mediation analysis to single-trial P3b data and this technique holds promise for mental chronometric studies into the effects of psychopharmacological agents. The R code for performing the single trial analysis and mediation analysis are included as supplementary materials

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels