Nemours Biomedical Research

Wilmington, DE, United States

Nemours Biomedical Research

Wilmington, DE, United States
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Brescia A.C.,Thomas Jefferson University | Simonds M.M.,Nemours Biomedical Research | Sullivan K.E.,University of Pennsylvania | Rose C.D.,Thomas Jefferson University
Proteomics - Clinical Applications | Year: 2017

Purpose: The goal is to investigate the specific contribution of fibroblast-like synoviocytes (FLS) to the inflammatory milieu of the synovium in juvenile idiopathic arthritis (JIA) through detection of secreted proteins. Experimental design: Expression of 89 cytokines and chemokines is determined on unprocessed synovial fluid from controls and JIA patients using antibody arrays. Supernatants from pure cell cultures of FLS grown from synovial fluids or tissues from JIA and controls are also examined for protein expression. Ingenuity Pathway Analysis (IPA) is revealed top pathways and upstream regulators of significant proteins. Results: Protein studies is revealed that JIA FLS release pro-inflammatory cytokines and chemokines, including IL-4, IL-6, IL-17, CXCL1, and CXCL6, and lose expression of important regulator signals, such as IL-10 and TIMP2. Of the 84 proteins differentially expressed between controls and JIA in the synovial fluid, 1/3 (29 proteins) are differentially expressed in the cell culture supernatants of JIA and control FLS. ELISA of cell culture supernatants and synovial fluid confirmed seven key proteins. Conclusion and clinical relevance: JIA FLS are central to perpetuation of inflammation in JIA, including trafficking of inflammatory cells and effects on the extracellular matrix. These cells express key disease-specific chemokines that, with further refinement, may allow us to tailor therapy appropriately. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


Spinu L.,University of Western Ontario | Lilley J.,Nemours Biomedical Research
Journal of Phonetics | Year: 2016

In this paper we explore two methods for the classification of fricatives. First, for the coding of the speech, we compared two sets of acoustic measures obtained from a corpus of Romanian fricatives: (a) spectral moments and (b) cepstral coefficients. Second, we compared two methods of determining the regions of the segments from which the measures would be extracted. In the first method, the phonetic segments were divided into three regions of approximately equal duration. In the second method, Hidden Markov Models (HMMs) were used to divide each segment into three regions such that the variances of the measures within each region were minimized. The corpus we analyzed consists of 3674 plain and palatalized word-final fricatives from four places of articulation, produced by 31 native speakers of Romanian (20 females). We used logistic regression to classify fricatives by place, voicing, palatalization status, and gender. We found that cepstral coefficients reliably outperformed spectral moments in all classification tasks, and that using regions determined by HMM yielded slightly higher correct classification rates than using regions of equal duration. © 2016 Elsevier Ltd


Ketterer T.,Nemours Biomedical Research | West D.W.,Nemours Health Informatics | Sanders V.P.,NHI Business and Ancillary Support | Hossain J.,Nemours Biomedical Research | And 3 more authors.
Academic Pediatrics | Year: 2013

Objective: To identify the demographic, practice site, and clinical predictors of patient portal enrollment and activation among a pediatric primary care population. Methods: We conducted a cross-sectional analysis of the primary care database of an academic children's hospital that introduced a patient portal in December 2007. Results: We analyzed data for 84,015 children. Over a 4-year period, 38% enrolled in the portal; of these, 26% activated the account. The adjusted odds of portal enrollment was lower for adolescents, Medicaid recipients, low-income families, Asian or other race, and Hispanic ethnicity, and higher for patients with more office encounters, and presence of autism on the problem list. Once enrolled, the odds of portal activation [adjusted odds ratio (95% confidence interval)] was decreased for: Medicaid [0.55 (0.50-0.61)] and uninsured [0.79 (0.64-0.97)] (vs private insurance), black [0.53 (0.49-0.57)] and other [0.80 (0.71-0.91)] (vs white race), Hispanic ethnicity [0.77 (0.62-0.97)], and increased for: infant age [1.26 (1.15-1.37)] (vs school age), attendance at a resident continuity practice site [1.91 (1.23-2.97)], living further away from the practice (vs under 2 miles)[4.5-8.8 miles: 1.14 (1.02-1.29); more than 8.8 miles: 1.19 (1.07-1.33)], having more office encounters (vs 1-3) [4-7 encounters: 1.40 (1.24-1.59); 8-12 encounters: 1.58 (1.38-1.81); 13+ encounters: 2.09 (1.72-2.55)], and having 3 or more items on the problem list (vs 0) [1.19 (1.07-1.33)]. Conclusions: Sociodemographic disparities exist in patient portal enrollment/activation in primary care pediatrics. Attendance at a resident continuity practice site, living farther away from the practice, having more office encounters, and having more problem list items increased the odds of portal activation. Copyright © 2013 by Academic Pediatric Association.


PubMed | Thomas Jefferson University, University of Pennsylvania and Nemours Biomedical Research
Type: | Journal: Proteomics. Clinical applications | Year: 2016

The goal was to investigate the specific contribution of fibroblast-like synoviocytes (FLS) to the inflammatory milieu of the synovium in juvenile idiopathic arthritis (JIA) through detection of secreted proteins.Expression of 89 cytokines and chemokines was determined on unprocessed synovial fluid from controls and JIA patients using antibody arrays. Supernatants from pure cell cultures of FLS grown from synovial fluids or tissues from JIA and controls were also examined for protein expression. Ingenuity Pathway Analysis (IPA) revealed top pathways and upstream regulators of significant proteins.Protein studies revealed that JIA FLS release pro-inflammatory cytokines and chemokines, including IL-4, IL-6, IL-17, CXCL1, and CXCL6, and lose expression of important regulator signals, such as IL-10 and TIMP2. Of the 84 proteins differentially expressed between controls and JIA in the synovial fluid, 1/3 (29 proteins) were differentially expressed in the cell culture supernatants of JIA and control FLS. ELISA of cell culture supernatants and synovial fluid confirmed seven key proteins.JIA FLS are central to perpetuation of inflammation in JIA, including trafficking of inflammatory cells and effects on the extracellular matrix. These cells express key disease-specific chemokines that, with further refinement, may allow us to tailor therapy appropriately. This article is protected by copyright. All rights reserved.


Objective This study was designed to investigate the pathogenic contributions of fibroblast-like synoviocytes (FLS) to juvenile idiopathic arthritis (JIA) by identifying pathways with dysregulated gene expression in FLS from patients with oligoarticular JIA. Methods FLS were derived from synovial fluid obtained by arthrocentesis from patients with JIA undergoing intraarticular steroid injections and from orthopedic control patients. Gene expression profiles of the JIA and control FLS were obtained using the Affymetrix platform, with application of Ingenuity Pathway Analysis and Gene Set Enrichment Analysis software to define gene sets in dysregulated pathways and networks of potential pathologic relevance in this disease. Biologically relevant differentially expressed genes were confirmed by RNA and protein analysis. Results Exploration of global gene expression profiles of the JIA FLS revealed important dysregulated pathways, including the transforming growth factor β (TGFβ) signaling, as well as endochondral bone formation, cartilage formation, and β-catenin networks. Importantly, bone morphogenetic protein 4 (BMP-4) was significantly overexpressed in the JIA FLS. FLS from patients with oligoarticular JIA exhibit a chondrocyte phenotype, as evidenced by expression of type II collagen and aggrecan. Conclusion Dysregulation of the pathways involved in the pathogenesis of oligoarticular JIA were revealed through gene expression profiling. JIA FLS displayed dysregulated TGFβ signaling and exhibited a hypertrophic chondrocyte phenotype. These characteristics, along with contributions from the β-catenin network may have implications for endochondral bone formation and local growth disturbances in oligoarticular JIA. Overexpression of BMP-4 in FLS from patients with oligoarticular JIA in particular may play an important role in disease pathogenesis, with a direct effect on functional outcome and with implications for future treatment. © 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.


Rose L.,Western New England University | Coulter M.M.,Thomas Jefferson University | Chan S.,DuPont Company | Hossain J.,Nemours Biomedical Research | And 2 more authors.
Pediatric Infectious Disease Journal | Year: 2014

We evaluated the correlation between fluoroquinolone use, measured by doses administered and days of therapy, with the emergence of ciprofloxacin and levofloxacin resistance among Gram-negative bacilli infections in children hospitalized at one pediatric center between April 2001 and March 2009. Both metrics and drug resistance were highly correlated. © 2013 by Lippincott Williams & Wilkins.


Mills T.,Northeastern University | Mills T.,University of Alberta | Bunnell H.T.,Nemours Biomedical Research | Patel R.,Northeastern University
AAC: Augmentative and Alternative Communication | Year: 2014

Text-to-speech options on augmentative and alternative communication (AAC) devices are limited. Often, several individuals in a group setting use the same synthetic voice. This lack of customization may limit technology adoption and social integration. This paper describes our efforts to generate personalized synthesis for users with profoundly limited speech motor control. Existing voice banking and voice conversion techniques rely on recordings of clearly articulated speech from the target talker, which cannot be obtained from this population. Our VocaliD approach extracts prosodic properties from the target talker's source function and applies these features to a surrogate talker's database, generating a synthetic voice with the vocal identity of the target talker and the clarity of the surrogate talker. Promising intelligibility results suggest areas of further development for improved personalization. © 2014 International Society for Augmentative and Alternative Communication.


Rose L.,Western New England University | Chan S.,DuPont Company | Hossain J.,Nemours Biomedical Research | Hossain J.,University of Delaware | Di Pentima M.C.,Vanderbilt University
Journal of Clinical Microbiology | Year: 2013

We evaluated the evolution of vancomycin MICs for Staphylococcus aureus and their relationship with vancomycin use among hospitalized children. S. aureus isolates recovered from sterile sites were prospectively tested for vancomycin susceptibility using the Etest between 1 April 2000 and 31 March 2008. Vancomycin MICs were grouped into three categories:≤1, 1.5, and 2 μg/ ml. The association between vancomycin MICs and aggregate vancomycin use and individual patient vancomycin exposure 6 months prior to the documented infection was assessed. The geometric mean values for vancomycin MICs for S. aureus fluctuated over time without a significant trend (P=0.146). Of the 436 patients included in the study, 363 (83%) had methicillin-susceptible S. aureus (MSSA) and 73 (17%) had methicillin-resistant S. aureus (MRSA) infections. The rate of isolates with a vancomycin MIC of 2 μg/ml increased from 4% (2 of 46) in 2000 to 2001 to 24% (11 of 46) in 2007 to 2008, despite a decrease in vancomycin use (r=-0.11; P=0.825). The percentage of isolates with a vancomycin MIC of 2 μg/ml was higher for MRSA (15%; 11 of 73) than for MSSA strains (5.2%; 19 of 363) (χ2=9.2; P=0.01). Individual patient vancomycin exposure was not associated with a higher vancomycin MIC. In the unadjusted model, in which we compared patients with S. aureus infections with MICs of≤1 μg/ml, the odds ratios of exposure rates for patients with isolates with MICs of 1.5 μg/ml and 2 μg/ml were 1.02 (P==0.929) and 1.13 (P=0.767), respectively. In our experience, the geometric means of vancomycin MICs from S. aureus isolates recovered from hospitalized children oscillated over time and were not associated with previous individual patient vancomycin exposure or aggregate vancomycin use. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Di Pentima M.C.,Vanderbilt University | Chan S.,DuPont Company | Briody C.,Christiana Health Care System | Power M.,Christiana Health Care System | And 2 more authors.
Antimicrobial Resistance and Infection Control | Year: 2014

Background: Rates of invasive vancomycin-resistant Enterococcus (VRE) in the USA remains on the rise. Efforts to control vancomycin use and nosocomial transmission have had limited success in halting the spread of this pathogen. The role of antibiotic exposure remains a topic of controversy. We evaluated the association between emergence of VRE-blood-stream infections (BSI), aggregate and individual-patient vancomycin- exposure, and clonal transmission of VRE at an academic pediatric tertiary care hospital. Methods: E. faecium and E. faecalis isolates recovered from blood specimens from hospitalized children from 2003-2010 were retrieved from the microbiology database. Aggregate vancomycin use and individual-patient vancomycin exposure 6 months preceding each event of bacteremia were recorded. Pulse-field electrophoresis was performed on selected VRE isolates. Results: Of 151 episodes of E. faecium and E. faecalis BSI among hospitalized children <18 years of age, 9% (14) were due to VRE. Of these, 5 (36%) were due to nosocomial transmission. Aggregate (r .19, P = 0.3) and individual-patient vancomycin-exposure (X2 = .26; P = .87) were not associated with VRE-BSI. On bivariate analysis, OR for developing VRE-BSI among patients infected with clonal isolates was 36 (P < .0001). Infection control interventions, rather than antimicrobial stewardship interventions to decrease vancomycin use, proved to be effective in reducing the rates of VRE-BSI. Conclusions: In our experience, VRE-BSI was associated with nosocomial transmission and was independent of aggregate and individual-patient vancomycin-exposure. Molecular epidemiology is a crucial tool to differentiate the role of nosocomial transmission and antibiotic exposure in the emergence of invasive VRE infections among hospitalized children. © 2014 Di Pentima et al.


Muthukumar P.K.,Carnegie Mellon University | Black A.W.,Carnegie Mellon University | Bunnell H.T.,Nemours Biomedical Research
Proceedings of the Annual Conference of the International Speech Communication Association, INTERSPEECH | Year: 2013

Every parametric speech synthesizer requires a good excitation model to produce speech that sounds natural. In this paper, we describe efforts toward building one such model using the Liljencrants-Fant (LF) model. We used the Iterative Adaptive Inverse Filtering technique to derive an initial estimate of the glottal flow derivative (GFD). Candidate pitch periods in the estimated GFD were then located and LF model parameters estimated using a gradient descent optimization algorithm. Residual energy in the GFD, after subtracting the fitted LF signal, was then modeled by a 4-term LPC model plus energy term to extend the excitation model and account for source information not captured by the LF model. The ClusterGen speech synthesizer was then trained to predict these excitation parameters from text so that the excitation model could be used for speech synthesis. ClusterGen excitation predictions were further used to reinitialize the excitation fitting process and iteratively improve the fit by including modeled voicing and segmental influences on the LF parameters. The results of all of these methods have been confirmed both using listening tests and objective metrics. Copyright © 2013 ISCA.

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