Defining the appropriate waiting time between multiple-breath nitrogen washout measurements

Research lette

Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene.

BackgroundPreserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.MethodsData from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.ResultsThe prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter's syndrome (47XXY) was observed (p-value < 0.001). Subgroups identified through k-means clustering include a putative "COPD-subtype", "Restrictive-subtype", and a highly symptomatic "Metabolic-subtype".ConclusionsPRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.Trial registrationClinicaltrials.gov Identifier: NCT000608764

The orbit rigidity matrix of a symmetric framework

A number of recent papers have studied when symmetry causes frameworks on a graph to become infinitesimally flexible, or stressed, and when it has no impact. A number of other recent papers have studied special classes of frameworks on generically rigid graphs which are finite mechanisms. Here we introduce a new tool, the orbit matrix, which connects these two areas and provides a matrix representation for fully symmetric infinitesimal flexes, and fully symmetric stresses of symmetric frameworks. The orbit matrix is a true analog of the standard rigidity matrix for general frameworks, and its analysis gives important insights into questions about the flexibility and rigidity of classes of symmetric frameworks, in all dimensions. With this narrower focus on fully symmetric infinitesimal motions, comes the power to predict symmetry-preserving finite mechanisms - giving a simplified analysis which covers a wide range of the known mechanisms, and generalizes the classes of known mechanisms. This initial exploration of the properties of the orbit matrix also opens up a number of new questions and possible extensions of the previous results, including transfer of symmetry based results from Euclidean space to spherical, hyperbolic, and some other metrics with shared symmetry groups and underlying projective geometry.Comment: 41 pages, 12 figure

Topological Graph Polynomials in Colored Group Field Theory

In this paper we analyze the open Feynman graphs of the Colored Group Field Theory introduced in [arXiv:0907.2582]. We define the boundary graph \cG_{\partial} of an open graph \cG and prove it is a cellular complex. Using this structure we generalize the topological (Bollobas-Riordan) Tutte polynomials associated to (ribbon) graphs to topological polynomials adapted to Colored Group Field Theory graphs in arbitrary dimension