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    ABSTRACT: Suppose that U = (U(1), … , U(d)) has a Uniform ([0, 1](d)) distribution, that Y = (Y(1), … , Y(d)) has the distribution G on [Formula: see text], and let X = (X(1), … , X(d)) = (U(1)Y(1), … , U(d)Y(d)). The resulting class of distributions of X (as G varies over all distributions on [Formula: see text]) is called the Scale Mixture of Uniforms class of distributions, and the corresponding class of densities on [Formula: see text] is denoted by [Formula: see text]. We study maximum likelihood estimation in the family [Formula: see text]. We prove existence of the MLE, establish Fenchel characterizations, and prove strong consistency of the almost surely unique maximum likelihood estimator (MLE) in [Formula: see text]. We also provide an asymptotic minimax lower bound for estimating the functional f ↦ f(x) under reasonable differentiability assumptions on f ∈ [Formula: see text] in a neighborhood of x. We conclude the paper with discussion, conjectures and open problems pertaining to global and local rates of convergence of the MLE.
    Journal of Multivariate Analysis 05/2012; 107:71-89. DOI:10.1016/j.jmva.2012.01.001
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    ABSTRACT: Neuropeptide Y (NPY) coordinates inflammation and bone metabolism which are central to the pathogenesis of periodontitis. The present study was designed to determine whether NPY was quantifiable in human gingival crevicular fluid (GCF) and to test the null hypothesis that GCF levels of NPY were the same in periodontal health and disease. A subsidiary aim was to determine the potential functionality of released NPY by detecting the presence of NPY Y1 receptors in gingival tissue. The periodontitis group consisted of 20 subjects (10 females and 10 males) mean age 41.4 (S.D. 9.6 years). The control group comprised 20 subjects (10 females and 10 males) mean age 37.4 (S.D. 11.7 years). NPY levels in GCF were measured in periodontal health and disease by radioimmunoassay. NPY Y1 receptor expression in gingival tissue was determined by Western blotting of membrane protein extracts from healthy and inflamed gum. Healthy sites from control subjects had significantly higher levels of NPY than diseased sites from periodontitis subjects. NPY Y1 receptor protein was detected in both healthy and inflamed gingival tissue by Western blotting. The significantly elevated levels of NPY in GCF from healthy compared with periodontitis sites suggests a tonic role for NPY, the functionality of which is indicated by the presence of NPY Y1 receptors in local gingival tissue.
    Archives of oral biology 12/2008; 54(3):258-62. DOI:10.1016/j.archoralbio.2008.10.002
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    ABSTRACT: To determine the distribution of the NPY Y1 receptor in carious and noncarious human dental pulp tissue using immunohistochemistry. A subsidiary aim was to confirm the presence of the NPY Y1 protein product in membrane fractions of dental pulp tissue from carious and noncarious teeth using western blotting. Twenty two dental pulp samples were collected from carious and noncarious extracted teeth. Ten samples were processed for immunohistochemistry using a specific antibody to the NPY Y1 receptor. Twelve samples were used to obtain membrane extracts which were electrophoresed, blotted onto nitrocellulose and probed with NPY Y1 receptor antibody. Kruskal-Wallis one-way analysis of variance was employed to test for overall statistical differences between NPY Y1 levels in noncarious, moderately carious and grossly carious teeth. Neuropeptide Y Y1 receptor immunoreactivity was detected on the walls of blood vessels in pulp tissue from noncarious teeth. In carious teeth NPY Y1 immunoreactivity was observed on nerve fibres, blood vessels and inflammatory cells. Western blotting indicated the presence and confirmed the variability of NPY Y1 receptor protein expression in solubilised membrane preparations of human dental pulp tissue from carious and noncarious teeth. Neuropeptide Y Y1 is expressed in human dental pulp tissue with evidence of increased expression in carious compared with noncarious teeth, suggesting a role for NPY Y1 in modulation of caries induced pulpal inflammation.
    International Endodontic Journal 09/2008; 41(10):850-5. DOI:10.1111/j.1365-2591.2008.01436.x
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    ABSTRACT: Many neuropeptides are similar in size, amino acid composition and charge to antimicrobial peptides. This study aimed to determine whether the neuropeptides substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), displayed antimicrobial activity against Streptococcus mutans, Lactobacillus acidophilus, Enterococcus faecalis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. SP, NPY, VIP and CGRP displayed variable degrees of antimicrobial activity against all the pathogens tested with the exception of S. aureus. These antimicrobial activities add a further dimension to the immunomodulatory roles for neuropeptides in the inflammatory and immune responses.
    Journal of Neuroimmunology 08/2008; 200(1-2):11-6. DOI:10.1016/j.jneuroim.2008.05.014
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    ABSTRACT: The aim of this paper is to use Markov modelling to investigate survival for particular types of kidney patients in relation to their exposure to anti-hypertensive treatment drugs. In order to monitor kidney function an intuitive three point assessment is proposed through the collection of blood samples in relation to chronic kidney disease for Northern Ireland patients. A five state Markov model was devised using specific transition probabilities for males and females over all age groups. These transition probabilities were then adjusted appropriately using relative risk scores for the event death for different subgroups of patients. The model was built using TreeAge software package in order to explore the effects of anti-hypertensive drugs on patients.
    Computer-Based Medical Systems, 2008. CBMS '08. 21st IEEE International Symposium on; 07/2008
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    ABSTRACT: To determine the diagnostic accuracy of advanced medical priority dispatch system (AMPDS) software used to dispatch public access defibrillation first responders to out-of-hospital cardiac arrests (OHCA). All true OHCA events in North and West Belfast in 2004 were prospectively collated. This was achieved by a comprehensive search of all manually completed Patient Report Forms compiled by paramedics, together with autopsy reports, death certificates and medical records. The dispatch coding of all emergency calls by AMPDS software was also obtained for the same time period and region, and a comparison was made between these two datasets. A single urban ambulance control centre in Northern Ireland. All 238 individuals with a presumed or actual OHCA in the North and West Belfast Health and Social Services Trust population of 138 591 (2001 Census), as defined by the Utstein Criteria. The accurate dispatch of an emergency ambulance to a true OHCA. The sensitivity of the dispatch mechanism for detecting OHCA was 68.9% (115/167, 95% confidence interval (CI) 61.3% to 75.8%). However, the sensitivity for arrests with ventricular fibrillation (VF) was 44.4% (12/27) with sensitivity for witnessed VF of 47.1% (8/17). The positive predictive value was 63.5% (115/181, 95% CI 56.1% to 70.6%). The sensitivity of this dispatch process for cardiac arrest is moderate and will constrain the effectiveness of Public Access Defibrillation (PAD) schemes which utilise it. controlled-trials.com ISRCTN07286796.
    Heart (British Cardiac Society) 04/2008; 94(3):349-53. DOI:10.1136/hrt.2006.109785
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    ABSTRACT: Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease (CKD) guidelines have focused on the utility of using the modified four-variable MDRD equation (now traceable by isotope dilution mass spectrometry IDMS) in calculating estimated glomerular filtration rates (eGFRs). This study assesses the practical implications of eGFR correction equations on the range of creatinine assays currently used in the UK and further investigates the effect of these equations on the calculated prevalence of CKD in one UK region Using simulation, a range of creatinine data (30-300 micromol/l) was generated for male and female patients aged 20-100 years. The maximum differences between the IDMS and MDRD equations for all 14 UK laboratory techniques for serum creatinine measurement were explored with an average of individual eGFRs calculated according to MDRD and IDMS < 60 ml/min/1.73 m(2) and 30 ml/min/1.73 m(2). Similar procedures were applied to 712,540 samples from patients > or = 18 years (reflecting the five methods for serum creatinine measurement utilized in Northern Ireland) to explore, graphically, maximum differences in assays. CKD prevalence using both estimation equations was compared using an existing cohort of observed data. Simulated data indicates that the majority of laboratories in the UK have small differences between the IDMS and MDRD methods of eGFR measurement for stages 4 and 5 CKD (where the averaged maximum difference for all laboratory methods was 1.27 ml/min/1.73 m(2) for females and 1.59 ml/min/1.73 m(2) for males). MDRD deviated furthest from the IDMS results for the Endpoint Jaffe method: the maximum difference of 9.93 ml/min/1.73 m(2) for females and 5.42 ml/min/1.73 m(2) for males occurred at extreme ages and in those with eGFR > 30 ml/min/1.73 m(2). Observed data for 93,870 patients yielded a first MDRD eGFR < 60 ml/min/1.73 m(2) in 2001. 66,429 (71%) had a second test > 3 months later of which 47,093 (71%) continued to have an eGFR < 60 ml/min/1.73 m(2). Estimated crude prevalence was 3.97% for laboratory detected CKD in adults using the MDRD equation which fell to 3.69% when applying the IDMS equation. Over 95% of this difference in prevalence was explained by older females with stage 3 CKD (eGFR 30-59 ml/min/1.73 m(2)) close to the stage 2 CKD (eGFR 60-90 ml/min/1.73 m(2)) interface. Improved accuracy of eGFR is obtainable by using IDMS correction especially in the earlier stages of CKD 1-3. Our data indicates that this improved accuracy could lead to reduced prevalence estimates and potentially a decreased likelihood of onward referral to nephrology services particularly in older females.
    Nephrology Dialysis Transplantation 02/2008; 23(2):542-8. DOI:10.1093/ndt/gfm599
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    ABSTRACT: Previous research has introduced the conditional phase-type distribution as a model that can suitably represent a skewed survival distribution conditioned on a network of inter-related variables. The technique has successfully been applied to modeling the stay of elderly patients in hospital which typically includes extreme stays in hospital resulting in a highly skewed survival distribution. This paper uses the Conditional phase-type distribution in a different setting whereby the focus is on patients who are in hospital due to having suffered a hip fracture. The model represents the patient length of stay in hospital conditioned on a Bayesian network of inter-related patient variables. In particular, the network highlights the key factors influencing length of stay and identifies relationships between long stay patients, delays in surgery and the patients condition. The delays identified in the system, could therefore be addressed to hopefully reduce the length of stay in hospital and increase the flow of patients in the hospital system.
    Proceedings of the Twenty-First IEEE International Symposium on Computer-Based Medical Systems, June 17-19, 2008, Jyväskylä, Finland; 01/2008
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    ABSTRACT: The length of stay in hospital of geriatric patients may be modelled using the Coxian phase-type distribution. This paper examines previous methods which have been used to model health-care costs and presents a new methodology to estimate the costs for a cohort of patients for their duration of stay in hospital, assuming there are no further admissions. The model, applied to 1392 patients admitted into the geriatric ward of a local hospital in Northern Ireland, between 2002 and 2003, should be beneficial to hospital managers, as future decisions and policy changes could be tested on the model to investigate their influence on costs before the decisions were carried out on a real ward.
    Statistics in Medicine 06/2007; 26(13):2716-29. DOI:10.1002/sim.2728
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    ABSTRACT: While skin wounds heal by scarring, wounds of oral mucosa show privileged healing with minimal scar formation. Our hypothesis was that phenotypic differences between oral and skin fibroblasts underlie these differences in healing. The aims of this study were to compare MMP-3 expression by oral and skin fibroblasts and investigate a role for MMP-3 in mediating collagen gel contraction. Oral fibroblasts induced significantly greater gel contraction than did paired skin cells. Inhibition of MMP activity significantly inhibited gel contraction by both cell types. Specific inhibition of MMP-3 activity reduced gel contraction by oral, but not skin, fibroblasts. Oral fibroblasts produced significantly higher levels of MMP-3 than did skin fibroblasts at all levels studied. TGF-beta1 and -beta3 isoforms stimulated MMP-3 expression at mRNA, protein, and activity levels by both fibroblast populations. Results suggest that increased MMP-3 production by oral fibroblasts may underlie the differences in wound-healing outcome seen in skin and oral mucosa.
    Journal of Dental Research 06/2007; 86(5):457-62. DOI:10.1177/154405910708600513
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