Can HRCT be used as a marker of airway remodelling in children with difficult asthma?

BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with D

Illinois Waterfowl Surveys and Investigations W-43-R-63 Annual Progress Report FY2016 Period: 1 July 2015 – 30 June 2016

Objectives 1) Inventory abundance and distribution of waterfowl and other waterbirds (a minimum of 10 species and guilds) during autumn migration at a minimum of 30 sites along the Illinois and central Mississippi rivers of Illinois, 2) Estimate waterfowl and other waterbird population sizes (a minimum of 10 species and guilds) during autumn migration using an aerial quadrat survey along the central Illinois River for comparison with aerial inventories (Objective 1), 3) Investigate the ecology of up to 50 gadwall and 50 American green-winged teal during spring migration in and near the central Illinois River valley of Illinois, 4) Determine breeding bird use of and nest density in a minimum of 10 moist-soil wetlands managed for waterfowl during summer in central Illinois, 5) Investigate the breeding ecology of a minimum of 50 sandhill cranes during spring and summer in northeastern Illinois consistent with an ongoing research project, 6) Investigate movements and home range size of a minimum of 10 Canada geese during winter in and near the Greater Chicago Metropolitan Area of Illinois, and 7) Determine habitat quality of a minimum of 100 wetlands and deepwater habitats during spring, summer, and early autumn for migrating dabbling ducks, breeding wetland birds, and migrating shorebirds in Illinois.Illinois Department of Natural Resources, Division of Wildlife & U.S. Fish and Wildlife Service Contract Number: RC09-13FWUIUCunpublishednot peer reviewedOpe

Allergic rhinitis and asthma: inflammation in a one-airway condition

BACKGROUND: Allergic rhinitis and asthma are conditions of airway inflammation that often coexist. DISCUSSION: In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria). Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli). Structural alterations (that is, remodeling) of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened. CONCLUSION: Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

An Integrated Modeling Approach for Predicting Process Maps of Residual Stress and Distortion in a Laser Weld: A Combined CFD–FE Methodology

Laser welding has become an important joining methodology within a number of industries for the structural joining of metallic parts. It offers a high power density welding capability which is desirable for deep weld sections, but is equally suited to performing thinner welded joints with sensible amendments to key process variables. However, as with any welding process, the introduction of severe thermal gradients at the weld line will inevitably lead to process-induced residual stress formation and distortions. Finite element (FE) predictions for weld simulation have been made within academia and industrial research for a number of years, although given the fluid nature of the molten weld pool, FE methodologies have limited capabilities. An improvement upon this established method would be to incorporate a computational fluid dynamics (CFD) model formulation prior to the FE model, to predict the weld pool shape and fluid flow, such that details can be fed into FE from CFD as a starting condition. The key outputs of residual stress and distortions predicted by the FE model can then be monitored against the process variables input to the model. Further, a link between the thermal results and the microstructural properties is of interest. Therefore, an empirical relationship between lamellar spacing and the cooling rate was developed and used to make predictions about the lamellar spacing for welds of different process parameters. Processing parameter combinations that lead to regions of high residual stress formation and high distortion have been determined, and the impact of processing parameters upon the predicted lamellar spacing has been presented

Measurement of the Inclusive Semi-electronic D0D^0 Branching Fraction

Using the angular correlation between the $\pi^+$ emitted in a $D^{*+} \rightarrow D^0 \pi^+$ decay and the $e^+$ emitted in the subsequent $D^0 \rightarrow Xe^+\nu$ decay, we have measured the branching fraction for the inclusive semi-electronic decay of the $D^0$ meson to be: {\cal B}(D^0 \rightarrow X e^+ \nu) = [6.64 \pm 0.18 (stat.) \pm 0.29 (syst.)] \%. The result is based on 1.7 fb$^{-1}$ of $e^+e^-$ collisions recorded by the CLEO II detector located at the Cornell Electron Storage Ring (CESR). Combining the analysis presented in this paper with previous CLEO results we find, \frac{{\cal B} (D^0 \rightarrow X e^+ \nu)} {{\cal B} (D^0 \rightarrow K^- \pi^+)} = 1.684 \pm 0.056 (stat.) \pm 0.093(syst.) and \frac{{\cal B}(D\rightarrow K^-e^+\nu)} {{\cal B}(D\rightarrow Xe^+\nu)} = 0.581 \pm 0.023 (stat.) \pm 0.028(syst.). The difference between the inclusive rate and the sum of the measured exclusive branching fractions (measured at CLEO and other experiments) is $(3.3 \pm 7.2) \%$ of the inclusive rate.Comment: Latex file, 33pages, 4 figures Submitted to PR

Protein kinase A–induced myofilament desensitization to Ca2+ as a result of phosphorylation of cardiac myosin–binding protein C

In skinned myocardium, cyclic AMP–dependent protein kinase A (PKA)-catalyzed phosphorylation of cardiac myosin–binding protein C (cMyBP-C) and cardiac troponin I (cTnI) is associated with a reduction in the Ca2+ responsiveness of myofilaments and an acceleration in the kinetics of cross-bridge cycling, although the respective contribution of these two proteins remains controversial. To further examine the relative roles that cTnI and cMyBP-C phosphorylation play in altering myocardial function, we determined the Ca2+ sensitivity of force (pCa50) and the activation dependence of the rate of force redevelopment (ktr) in control and PKA-treated mouse myocardium (isolated in the presence of 2,3-butanedione monoxime) expressing: (a) phosphorylatable cTnI and cMyBP-C (wild type [WT]), (b) phosphorylatable cTnI on a cMyBP-C–null background (cMyBP-C−/−), (c) nonphosphorylatable cTnI with serines23/24/43/45 and threonine144 mutated to alanines (cTnIAla5), and (d) nonphosphorylatable cTnI on a cMyBP-C–null background (cTnIAla5/cMyBP-C−/−). Here, PKA treatment decreased pCa50 in WT, cTnIAla5, and cMyBP-C−/− myocardium by 0.13, 0.08, and 0.09 pCa units, respectively, but had no effect in cTnIAla5/cMyBP-C−/− myocardium. In WT and cTnIAla5 myocardium, PKA treatment also increased ktr at submaximal levels of activation; however, PKA treatment did not have an effect on ktr in cMyBP-C−/− or cTnIAla5/cMyBP-C−/− myocardium. In addition, reconstitution of cTnIAla5/cMyBP-C−/− myocardium with recombinant cMyBP-C restored the effects of PKA treatment on pCa50 and ktr reported in cTnIAla5 myocardium. Collectively, these results indicate that the attenuation in myofilament force response to PKA occurs as a result of both cTnI and cMyBP-C phosphorylation, and that the reduction in pCa50 mediated by cMyBP-C phosphorylation most likely arises from an accelerated cross-bridge cycling kinetics partly as a result of an increased rate constant of cross-bridge detachment

Follow-up after curative treatment for colorectal cancer: longitudinal evaluation of patient initiated follow-up in the first 12 months

Purpose: To compare patient-triggered follow-up (PTFU) for curatively treated colorectal cancer against traditional outpatient follow-up (OPFU). Methods: Questionnaires were mailed at four time points over one-year post-treatment to two prospectively-recruited cohorts: A, patients entering follow-up and receiving OPFU pre-implementation of PTFU; B, patients entering follow-up (FU) and receiving either OPFU (B1) or PTFU (B2) post-implementation of PTFU. Bi-variate tests were used to compare patient characteristics and outcomes eight months after entering follow-up (generic and cancer-specific quality of life (QoL), satisfaction). Regression analysis explored associations between follow-up model and outcomes. Resource implications and costs of models were compared. Results: Patients in Cohort B1 were significantly more likely to have received chemotherapy (p<0.001), radiotherapy (p<0.05), and reported poorer QoL (p=0.001). Having a longstanding co-morbid condition was the most important determinant of QoL (p<0.001); model of care was not significant. Patients were satisfied with their follow-up care regardless of model. Health service costs were higher in PTFU over the first year. Conclusions: PTFU is acceptable to patients with colorectal cancer and can be considered to be a realistic alternative to OPFU for clinically suitable patients. The initial costs are higher due to provision of a self-management (SM) programme and remote surveillance. Further research is needed to establish long-term outcomes and costs