IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

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Effect of robotic gait training on cardiorespiratory system in incomplete spinal cord injury

The objectives in this study were to investigate the effect of robot-assisted gait training on cardiorespiratory fitness in subjects with motor incomplete spinal cord injury and document the exercise intensity of robotic walking in comparison with the recommended guidelines. Ten patients followed a 24-session training program with a robotic gait orthosis in addition to physiotherapy sessions completed within 10 to 16 wk. Cardiorespiratory fitness was determined in a graded arm crank exercise test before and after the training program. To assess the intensity of robot-assisted walking, oxygen consumption (V

Calibration and Validation of the Dutch-Flemish PROMIS Pain Interference Item Bank in Patients with Chronic Pain

The Dutch-Flemish PROMIS Group translated the adult PROMIS Pain Interference item bank into Dutch-Flemish. The aims of the current study were to calibrate the parameters of these items using an item response theory (IRT) model, to evaluate the cross-cultural validity of the Dutch-Flemish translations compared to the original English items, and to evaluate their reliability and construct validity. The 40 items in the bank were completed by 1085 Dutch chronic pain patients. Before calibrating the items, IRT model assumptions were evaluated using confirmatory factor analysis (CFA). Items were calibrated using the graded response model (GRM), an IRT model appropriate for items with more than two response options. To evaluate cross-cultural validity, differential item functioning (DIF) for language (Dutch vs. English) was examined. Reliability was evaluated based on standard errors and Cronbach's alpha. To evaluate construct validity correlations with scores on legacy instruments (e.g., the Disabilities of the Arm, Shoulder and Hand Questionnaire) were calculated. Unidimensionality of the Dutch-Flemish PROMIS Pain Interference item bank was supported by CFA tests of model fit (CFI = 0.986, TLI = 0.986). Furthermore, the data fit the GRM and showed good coverage across the pain interference continuum (threshold-parameters range: -3.04 to 3.44). The Dutch-Flemish PROMIS Pain Interference item bank has good cross-cultural validity (only two out of 40 items showing DIF), good reliability (Cronbach's alpha = 0.98), and good construct validity (Pearson correlations between 0.62 and 0.75). A computer adaptive test (CAT) and Dutch-Flemish PROMIS short forms of the Dutch-Flemish PROMIS Pain Interference item bank can now be developed.status: publishe

Standard errors across the range of the Dutch-Flemish PROMIS Pain Interference T-scores.

<p>Upper plot shows the standard errors of the Dutch-Flemish PROMIS Pain Interference 4-item short form (v1.0.4a), the 8-item short form (v1.0.8a), the 8-item simulated CAT, and the total item bank. Lower plot shows the distribution of the Dutch AMS-PAIN (Dutch clinical) sample, the US ACPA (US clinical) sample and the US Wave1 sample (US general population) along the T-score scale.</p