Longitudinal Changes in Symptom Cluster Membership in Inflammatory Bowel Disease

Purpose: To describe changes in symptom cluster membership over 1 year and to examine which demographic and clinical factors predict changes in symptom cluster membership among adults with inflammatory bowel disease. Design: A retrospective longitudinal study of the Crohn's & Colitis Foundation of America Partners Cohort from 2012 to 2015. Methods: We measured symptoms of pain interference, fatigue, sleep disturbance, depression, and anxiety. We used latent transition analysis to describe changes in symptom cluster membership (baseline, 6 months, and 12 months) and multinomial regressions to examine factors associated with symptom cluster membership transition. Findings: Four groups were identified (N = 5,296): high symptom burden (32.3%–35.3%), low symptom burden (24.2%–27.1%), physical symptoms (19.0%–20.9%; pain, fatigue, sleep disturbance), and psychological symptoms (20.0%–21.5%; depression, anxiety). The probability of staying in the same group was.814 to.905. Moving from active disease into remission was associated with moving from the high burden to low burden and psychological symptom groups. Conclusions: Symptom cluster membership was quite stable over 1 year. Research is needed to understand the underlying etiology of symptom clusters better and to develop interventions to reduce symptom burden in this vulnerable population. Clinical Relevance: Careful consideration of symptom management options should be done with patients to select options that are effective and potentially target multiple symptoms

Current status of turbulent dynamo theory: From large-scale to small-scale dynamos

Several recent advances in turbulent dynamo theory are reviewed. High resolution simulations of small-scale and large-scale dynamo action in periodic domains are compared with each other and contrasted with similar results at low magnetic Prandtl numbers. It is argued that all the different cases show similarities at intermediate length scales. On the other hand, in the presence of helicity of the turbulence, power develops on large scales, which is not present in non-helical small-scale turbulent dynamos. At small length scales, differences occur in connection with the dissipation cutoff scales associated with the respective value of the magnetic Prandtl number. These differences are found to be independent of whether or not there is large-scale dynamo action. However, large-scale dynamos in homogeneous systems are shown to suffer from resistive slow-down even at intermediate length scales. The results from simulations are connected to mean field theory and its applications. Recent work on helicity fluxes to alleviate large-scale dynamo quenching, shear dynamos, nonlocal effects and magnetic structures from strong density stratification are highlighted. Several insights which arise from analytic considerations of small-scale dynamos are discussed.Comment: 36 pages, 11 figures, Spa. Sci. Rev., submitted to the special issue "Magnetism in the Universe" (ed. A. Balogh

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