Migraine, Fibromyalgia, and Depression among People with IBS: A Prevalence Study

BACKGROUND. Case descriptions suggest IBS patients are more likely to have other disorders, including migraine, fibromyalgia, and depression. We sought to examine the prevalence of these conditions in cohorts of people with and without IBS. METHODS. The source of data was a large U.S. health plan from January 1, 1996 though June 30, 2002. We identified all people with a medical claim associated with an ICD-9 code for IBS. A non-IBS cohort was a random sample of people with an ICD-9 code for routine medical care. In the cohorts, we identified all claims for migraine, depression, and fibromyalgia. We estimated the prevalence odds ratios (PORs) of each of the three conditions using the Mantel-Haenszel method. We conducted quantitative sensitivity analyses to quantify the impact of residual confounding and in differential outcome identification. RESULTS. We identified 97,593 people in the IBS cohort, and a random sample of 27,402 people to compose the non-IBS comparison cohort. With adjustment, there was a 60% higher odds in the IBS cohort of having any one of the three disorders relative to the comparison cohort (POR 1.6, 95% CI 1.5 – 1.7). There was a 40% higher odds of depression in the IBS cohort (POR 1.4, 95% CI 1.3 – 1.4). The PORs for fibromyalgia and migraine were similar (POR for fibromyalgia 1.8, 95% CI 1.7 – 1.9; POR for migraine 1.6, 95% CI 1.4 – 1.7). Differential prevalence of an unmeasured confounder, or imperfect sensitivity or specificity of outcome detection would have impacted the observed results. CONCLUSION. People in the IBS cohort had a 40% to 80% higher prevalence odds of migraine, fibromyalgia, and depression

Rational combinations of Betti diagrams of complete intersections

We investigate decompositions of Betti diagrams over a polynomial ring within the framework of Boij-S\"oderberg theory. That is, given a Betti diagram, we determine if it is possible to decompose it into the Betti diagrams of complete intersections. To do so, we determine the extremal rays of the cone generated by the diagrams of complete intersections and provide a rudimentary algorithm for decomposition.Comment: This research was conducted at the Willamette Mathematics Consortium RE

Interpreting flash flood palaeoflow parameters from antidunes and gravel lenses: An example from Montserrat, West Indies

The wavelength of stationary water–surface waves and their associated antidune bedforms are related to the mean velocity and depth of formative flow. In sand-bed flume experiments, Alexander et al. (2001) found that lens structures were preserved during antidune growth and change, and the dimension of the lenses were empirically related to antidune wavelength, and thus could be used to estimate flow velocity and depth. This study is the first to compare observations of formative flow conditions and resulting sedimentary structures in a natural setting, testing the Alexander et al. (2001) relationship at a field-scale. Trains of stationary and upstream migrating water–surface waves were prevalent during the flash flood in October 2012 in the Belham Valley, Montserrat, West Indies. Wave positions and wavelengths were assessed at 900 s intervals through the daylight hours of the event within a monitored reach. The wave data indicate flow depths up to 1.3 m and velocity up to 3.6 m s−1. Sedimentary structures formed by antidune growth and change were preserved in the event deposit. These structures include lenses of clast-supported gravel and massive sand, with varying internal architecture. The lenses and associated low angle strata are comparable to sand-bed structures formed from stationary and upstream migrating waves in flume experiments, confirming the diagnostic value of these structures. Using mean lens length in the event deposit underestimated peak flow conditions during the flood, and implied that the lenses were preserved during waning flow

Dark Matter Halo Profiles in Scale-Free Cosmologies

We explore the dependence of the central logarithmic slope of dark matter halo density profiles $\alpha$ on the spectral index $n$ of the linear matter power spectrum $P(k)$ using cosmological $N$-body simulations of scale-free models (i.e. $P(k) \propto k^n$). For each of our simulations we identify samples of well resolved haloes in dynamical equilibrium and we analyse their mass profiles. By parameterising the mass profile using a ``generalised'' Navarro, Frenk & White profile in which the central logarithmic slope $\alpha$ is allowed to vary while preserving the $r^{-3}$ asymptotic form at large radii, we obtain preferred central slopes for haloes in each of our models. There is a strong correlation between $\alpha$ and $n$, such that $\alpha$ becomes shallower as $n$ becomes steeper. However, if we normalise our mass profiles by $r_{-2}$, the radius at which the logarithmic slope of the density profile is -2, we find that these differences are no longer present. We conclude that there is no evidence for convergence to a unique central asymptotic slope, at least on the scales that we can resolve.Comment: 9 pages, 4 figures. Accepted for publication in MNRA

An Inversion Method for Measuring Beta in Large Redshift Surveys

A precision method for determining the value of Beta= Omega_m^{0.6}/b, where b is the galaxy bias parameter, is presented. In contrast to other existing techniques that focus on estimating this quantity by measuring distortions in the redshift space galaxy-galaxy correlation function or power spectrum, this method removes the distortions by reconstructing the real space density field and determining the value of Beta that results in a symmetric signal. To remove the distortions, the method modifies the amplitudes of a Fourier plane-wave expansion of the survey data parameterized by Beta. This technique is not dependent on the small-angle/plane-parallel approximation and can make full use of large redshift survey data. It has been tested using simulations with four different cosmologies and returns the value of Beta to +/- 0.031, over a factor of two improvement over existing techniques.Comment: 16 pages including 6 figures Submitted to The Astrophysical Journa

Filaggrin-stratified transcriptomic analysis of pediatric skin identifies mechanistic pathways in patients with atopic dermatitis

BackgroundAtopic dermatitis (AD; eczema) is characterized by a widespread abnormality in cutaneous barrier function and propensity to inflammation. Filaggrin is a multifunctional protein and plays a key role in skin barrier formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a highly significant risk factor for atopic disease, but the molecular mechanisms leading to dermatitis remain unclear.ObjectiveWe sought to interrogate tissue-specific variations in the expressed genome in the skin of children with AD and to investigate underlying pathomechanisms in atopic skin.MethodsWe applied single-molecule direct RNA sequencing to analyze the whole transcriptome using minimal tissue samples. Uninvolved skin biopsy specimens from 26 pediatric patients with AD were compared with site-matched samples from 10 nonatopic teenage control subjects. Cases and control subjects were screened for FLG genotype to stratify the data set.ResultsTwo thousand four hundred thirty differentially expressed genes (false discovery rate, P < .05) were identified, of which 211 were significantly upregulated and 490 downregulated by greater than 2-fold. Gene ontology terms for “extracellular space” and “defense response” were enriched, whereas “lipid metabolic processes” were downregulated. The subset of FLG wild-type cases showed dysregulation of genes involved with lipid metabolism, whereas filaggrin haploinsufficiency affected global gene expression and was characterized by a type 1 interferon–mediated stress response.ConclusionThese analyses demonstrate the importance of extracellular space and lipid metabolism in atopic skin pathology independent of FLG genotype, whereas an aberrant defense response is seen in subjects with FLG mutations. Genotype stratification of the large data set has facilitated functional interpretation and might guide future therapy development

Residue Geometry Networks: A Rigidity-Based Approach to the Amino Acid Network and Evolutionary Rate Analysis.

Amino acid networks (AANs) abstract the protein structure by recording the amino acid contacts and can provide insight into protein function. Herein, we describe a novel AAN construction technique that employs the rigidity analysis tool, FIRST, to build the AAN, which we refer to as the residue geometry network (RGN). We show that this new construction can be combined with network theory methods to include the effects of allowed conformal motions and local chemical environments. Importantly, this is done without costly molecular dynamics simulations required by other AAN-related methods, which allows us to analyse large proteins and/or data sets. We have calculated the centrality of the residues belonging to 795 proteins. The results display a strong, negative correlation between residue centrality and the evolutionary rate. Furthermore, among residues with high closeness, those with low degree were particularly strongly conserved. Random walk simulations using the RGN were also successful in identifying allosteric residues in proteins involved in GPCR signalling. The dynamic function of these residues largely remain hidden in the traditional distance-cutoff construction technique. Despite being constructed from only the crystal structure, the results in this paper suggests that the RGN can identify residues that fulfil a dynamical function.A.S.F. is supported by a Doctoral Research Award from Microsoft Research. S.E.A. is supported by The Royal Society (UK). D.J.C. is supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme. A.W.C. is supported by the Winton Programme for the Physics of Sustainability.This is the final version of the article. It first appeared from Nature Publishing Group at http://dx.doi.org/10.1038/srep33213

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al