148 research outputs found

    The Public Papers of Governor Brereton C. Jones, 1991-1995

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    In his inaugural address, Governor Brereton C. Jones proclaimed, This administration is committed to having the most positive, progressive, exciting four years in our state\u27s history. Through speeches and press releases, this volume reflects the principal concerns of Jones’s time in office. Thematically organized, the more than two hundred public statements included here present the public face of the Jones administration on such issues as health care, education, economic development, the environment, and governmental reform. Nowhere else has the full text of these speeches and press releases been printed. Governor Jones, born in 1939, was elected to the West Virginia legislature in 1964, where he served for four years before retiring from politics. After moving to Kentucky and switching allegiance from the Republican to the Democratic Party, he re-entered politics with a successful campaign to become lieutenant governor in 1987. He was elected the Commonwealth\u27s fifty-fourth governor in 1991 by a record margin of nearly two to one. Jones initiated a number of reforms once in office. He turned a 400millionbudgetdeficitintoa400 million budget deficit into a 300 million surplus in four years, and he passed dramatic ethics reform in both the executive and legislative branches. Health-care issues were also of great importance to Jones, who spent the years before his election working with the Kentucky Health Care Access Foundation in addition to farming. After surviving a helicopter crash in 1992, he turned the main focus of his administration toward health-care reform and initiatives. Though he met with legislative opposition when he proposed universal health care for all Kentuckians, he did help pass legislation in 1994 that would serve as a solid beginning on the issue for future governors. Penny M. Miller, a professor of political science at the University of Kentucky, is the author of Kentucky Politics and Government: Do We Stand United?, and the co-author of two other books, The Kentucky Legislature: Two Decades of Change and Political Parties and Primaries in Kentucky. Her articles have appeared in leading professional journals such as Journal of Politics, Western Politics Quarterly, Women & Politics, Kentucky Law Journal, and Political Science & Politics. She serves as a board member of the Kentucky Long-Term Policy Research Center and Kids Voting Kentucky. She also served as Chair of the Kentucky Commission on Women, and as a board member of the Kentucky Center for Public Issues and the White House Commission on Presidential Scholars. A good starting point for those interested in late-twentieth-century Kentucky politics. It deserves a place on every Kentucky bookshelf. —Filson History Quarterly Reflects the principal concerns of Jones’s administration through speeches and press releases. —Documentary Editing A useful resource for anyone interested in the main issues during his term as governor. . . . A valuable reference tool. —Northern Kentucky Heritage Contains the essence of the legacy of Brereton C. Jones. It is indispensable to research libraries and all who would know it, while understanding the art of politics and the power of the spoken word. —Register of the Kentucky Historical Societyhttps://uknowledge.uky.edu/upk_political_science_papers/1010/thumbnail.jp

    Topological Entanglement of Polymers and Chern-Simons Field Theory

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    In recent times some interesting field theoretical descriptions of the statistical mechanics of entangling polymers have been proposed by various authors. In these approaches, a single test polymer fluctuating in a background of static polymers or in a lattice of obstacles is considered. The extension to the case in which the configurations of two or more polymers become non-static is not straightforward unless their trajectories are severely constrained. In this paper we present another approach, based on Chern--Simons field theory, which is able to describe the topological entanglements of two fluctuating polymers in terms of gauge fields and second quantized replica fields.Comment: 16 pages, corrected some typos, added two new reference

    Somatostatin Secreted by Islet δ-Cells Fulfills Multiple Roles as a Paracrine Regulator of Islet Function

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    OBJECTIVE— Somatostatin (SST) is secreted by islet δ-cells and by extraislet neuroendocrine cells. SST receptors have been identified on α- and β-cells, and exogenous SST inhibits insulin and glucagon secretion, consistent with a role for SST in regulating α- and β-cell function. However, the specific intraislet function of δ-cell SST remains uncertain. We have used Sst−/− mice to investigate the role of δ-cell SST in the regulation of insulin and glucagon secretion in vitro and in vivo

    Autophagy inhibition-mediated epithelial–mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis

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    Idiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries to an ageing, susceptible alveolar epithelium. Ageing is a risk factor for IPF and incidence has been demonstrated to increase with age. Decreased (macro)autophagy with age has been reported extensively in a variety of systems and diseases, including IPF. However, it is undetermined whether the role of faulty autophagy is causal or coincidental in the context of IPF. Here, we report that in alveolar epithelial cells inhibition of autophagy promotes epithelial–mesenchymal transition (EMT), a process implicated in embryonic development, wound healing, cancer metastasis and fibrosis. We further demonstrate that this is attained, at least in part, by increased p62/SQSTM1 expression that promotes p65/RELA mediated-transactivation of an EMT transcription factor, Snail2 (SNAI2), which not only controls EMT but also regulates the production of locally acting profibrogenic mediators. Our data suggest that reduced autophagy induces EMT of alveolar epithelial cells and can contribute to fibrosis via aberrant epithelial–fibroblast crosstalk

    Serial CT analysis in idiopathic pulmonary fibrosis: comparison of visual features that determine patient outcome

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    Aims: Patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotic medication and patients with non-IPF fibrosing lung disease often demonstrate rates of annualised forced vital capacity (FVC) decline within the range of measurement variation (5.0%–9.9%). We examined whether change in visual CT variables could help confirm whether marginal FVC declines represented genuine clinical deterioration rather than measurement noise. Methods: In two IPF cohorts (cohort 1: n=103, cohort 2: n=108), separate pairs of radiologists scored paired volumetric CTs (acquired between 6 and 24 months from baseline). Change in interstitial lung disease, honeycombing, reticulation, ground-glass opacity extents and traction bronchiectasis severity was evaluated using a 5-point scale, with mortality prediction analysed using univariable and multivariable Cox regression analyses. Both IPF populations were then combined to determine whether change in CT variables could predict mortality in patients with marginal FVC declines. Results: On univariate analysis, change in all CT variables except ground-glass opacity predicted mortality in both cohorts. On multivariate analysis adjusted for patient age, gender, antifibrotic use and baseline disease severity (diffusing capacity for carbon monoxide), change in traction bronchiectasis severity predicted mortality independent of FVC decline. Change in traction bronchiectasis severity demonstrated good interobserver agreement among both scorer pairs. Across all study patients with marginal FVC declines, change in traction bronchiectasis severity independently predicted mortality and identified more patients with deterioration than change in honeycombing extent. Conclusions: Change in traction bronchiectasis severity is a measure of disease progression that could be used to help resolve the clinical importance of marginal FVC declines

    Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis

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    BACKGROUND: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). METHODS: Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. RESULTS: Δ-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045). INTERPRETATION: Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression

    Cost effectiveness of ulcerative colitis treatment in Germany: a comparison of two oral formulations of mesalazine

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    <p>Abstract</p> <p>Background</p> <p>The treatment of ulcerative colitis (UC) can place a substantial financial burden on healthcare systems. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA; mesalazine) is the recommended first-line treatment for patients with UC. In this analysis, the incremental cost effectiveness ratio (ICER) of two oral formulations of 5-ASA (Mezavant<sup>® </sup>and Asacol<sup>®</sup>) is examined in the treatment of patients with mild-to-moderate, active UC in Germany.</p> <p>Methods</p> <p>A Markov cohort model was developed to assess the cost effectiveness of Mezavant compared with Asacol over a 5-year period in the German Statutory Health Insurance (SHI). Drug pricing details for 2009 were applied throughout the model, and overall resource use was determined and also fitted to 2009 from published results of a large cross sectional study of German SHI patients. Cost per quality adjusted life year (QALY) was the primary endpoint for this study. Remission rates were obtained using data from a randomised, phase III trial of Mezavant with an active Asacol reference arm and a long-term, open label, safety and tolerability trial of Mezavant. Uncertainty in the study model was assessed using one-way and probabilistic sensitivity analyses applying a Monte Carlo simulation.</p> <p>Results</p> <p>Over a 5-year period, healthcare costs for patients receiving Mezavant were 624 Euro lower than for patients receiving Asacol. Additionally, patients receiving Mezavant gained 0.011 QALYs or 18 more days in remission compared with Asacol. One-way sensitivity analyses suggest that these results are driven by both differences in the acquisition cost between mesalazine formulations and differences in treatment efficacy. Furthermore, sensitivity analyses suggest a probability of 76% for cost savings and higher QALYs with Mezavant compared with Asacol. If adherence and its influence on the remission rates and the risk of developing colorectal cancer were included in the model, the results might have even been more favorable to Mezavant due to its once daily dosing regimen.</p> <p>Conclusions</p> <p>This model suggests that patients treated with Mezavant may achieve increased time in remission and higher QALYs, with lower direct costs to the SHI when compared with Asacol. Mezavant may therefore be a suitable first-line option for the induction and maintenance of remission in UC.</p

    Developing a predictive modelling capacity for a climate change-vulnerable blanket bog habitat: Assessing 1961-1990 baseline relationships

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    Aim: Understanding the spatial distribution of high priority habitats and developing predictive models using climate and environmental variables to replicate these distributions are desirable conservation goals. The aim of this study was to model and elucidate the contributions of climate and topography to the distribution of a priority blanket bog habitat in Ireland, and to examine how this might inform the development of a climate change predictive capacity for peat-lands in Ireland. Methods: Ten climatic and two topographic variables were recorded for grid cells with a spatial resolution of 1010 km, covering 87% of the mainland land surface of Ireland. Presence-absence data were matched to these variables and generalised linear models (GLMs) fitted to identify the main climatic and terrain predictor variables for occurrence of the habitat. Candidate predictor variables were screened for collinearity, and the accuracy of the final fitted GLM was evaluated using fourfold cross-validation based on the area under the curve (AUC) derived from a receiver operating characteristic (ROC) plot. The GLM predicted habitat occurrence probability maps were mapped against the actual distributions using GIS techniques. Results: Despite the apparent parsimony of the initial GLM using only climatic variables, further testing indicated collinearity among temperature and precipitation variables for example. Subsequent elimination of the collinear variables and inclusion of elevation data produced an excellent performance based on the AUC scores of the final GLM. Mean annual temperature and total mean annual precipitation in combination with elevation range were the most powerful explanatory variable group among those explored for the presence of blanket bog habitat. Main conclusions: The results confirm that this habitat distribution in general can be modelled well using the non-collinear climatic and terrain variables tested at the grid resolution used. Mapping the GLM-predicted distribution to the observed distribution produced useful results in replicating the projected occurrence of the habitat distribution over an extensive area. The methods developed will usefully inform future climate change predictive modelling for Irelan
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