Digital Commons Network^™

Quantitative Factors Proposed To Influence The Prevalence Of Canine Tick-Borne Disease Agents In The United States, Roger W. Stich, Byron L. Blagburn, Dwight D. Bowman, Christopher Carpenter, M. Roberto Cortinas, Sidney A. Ewing, Desmond Foley, Janet E. Foley, Holly Gaff, Graham J. Hickling, R. Ryan Lash, Susan E. Little, Catherine Lund, Robert Lund, Thomas N. Mather, Glen R. Needham, William L. Nicholson, Julia Sharp, Andrea Varela-Stokes, Dongmei Wang

Plant Sciences and Entomology Faculty Publications

The Companion Animal Parasite Council hosted a meeting to identify quantifiable factors that can influence the prevalence of tick-borne disease agents among dogs in North America. This report summarizes the approach used and the factors identified for further analysis with mathematical models of canine exposure to tick-borne pathogens.

The Multivariate Ewma Model And Health Care Monitoring, Xia Pan, Jeffrey E. Jarrett

College of Business Faculty Publications

We introduce the construction of MEWMA (Multivariate exponentially weighted movingaverage) process control in the field of bio surveillance. Such introduction will both improve the reliability of data collected in bio surveillance, better interpretation of the results,improvement in the quality of results and standardization of results when more than two variables are involved. We propose sensitivity ratios as a measure of the effects of the mean shift and dispersion shift in processes under study. Using these sensitivity measures, we designed the optimal exponential weighting factor, which is consistent to results reported in control chart applications. Although ARL (average run length) is …

Preliminary Evaluation Of Near Infrared Spectroscopy As A Method To Detect Plasma Leakage In Children With Dengue Hemorrhagic Fever, Babs Soller, Anon Srikiatkachorn, Fengmei Zou, Alan Rothman, In-Kyu Yoon, Robert V. Gibbons, Siripen Kalayanarooj, Stephen J. Thomas, Sharone Green

Institute for Immunology and Informatics Faculty Publications

Background: Dengue viral infections are prevalent in the tropical and sub-tropical regions of the world, resulting in substantial morbidity and mortality. Clinical manifestations range from a self-limited fever to a potential life-threatening plasma leakage syndrome (dengue hemorrhagic fever). The objective of this study was to assess the utility of near infrared spectroscopy (NIRS) measurements of muscle oxygen saturation (SmO2) as a possible continuous measure to detect plasma leakage in children with dengue.

Methods: Children ages 6 months to 15 years of age admitted with suspected dengue were enrolled from the dengue ward at Queen Sirikit National Institute for Child Health. …

Clinical Implication Of Changes In Serum Adiponectin In Patients With Hepatogenic Diabetes, Zhongying Bao, Xiaodong Yuan, Shuhong Duan, Xiaoqun Dong

Biomedical and Pharmaceutical Sciences Faculty Publications

Adiponectin is a protein hormone that modulates glucose metabolism and fatty acid oxidation. Weexplored the clinical implication of serum adiponectin in hepatogenic diabetes. Serum adiponectin levels were determined using enzyme–linked immunochemistry assay in 78 individuals including 19 hepatogenic diabetes, 20 type 2 diabetes (T2D), 20 chronic liver disease and 19 healthy controls. Cases and controls were matched by gender and body mass index (BMI). There is no difference in serum adiponectin levels among hepatogenic diabetic, T2D and healthy control groups. The levels of adiponectin are highest in chronic liver disease and lowest in T2D. Insulin levels are highest in hepatic …

Activity Of Daptomycin Or Linezolid In Combination With Rifampin Or Gentamicin Against Biofilm-Forming Enterococcus Faecalis Or E. Faecium In An In Vitro Pharmacodynamic Model Using Simulated Endocardial Vegetations And An In Vivo Survival Assay Using Galleria Mellonella Larvae, Megan K. Luther, Arvanitis, Eleftherios Mylonakis, Kerry L. Laplante

Pharmacy Practice and Clinical Research Faculty Publications

Enterococci are the third most frequent cause of infective endocarditis. A high-inoculum stationary-phase in vitro pharmacodynamic model with simulated endocardial vegetations was used to simulate the human pharmacokinetics of daptomycin at 6 or 10 mg/kg of body weight/day or linezolid at 600 mg every 12 h (q12h), alone or in combination with gentamicin at 1.3 mg/kg q12h or rifampin at 300 mg q8h or 900 mg q24h. Biofilm-forming, vancomycin-susceptible Enterococcus faecalis and vancomycin-resistant Enterococcus faecium (vancomycin-resistant enterococcus [VRE]) strains were tested. At 24, 48, and 72 h, all daptomycin-containing regimens demonstrated significantly more activity (decline in CFU/g) than any linezolid-containing …

Curricular Affairs Committee Report #515, University Of Rhode Island Faculty Senate

Faculty Senate Committee Reports and Appendices

No abstract provided.

Global Malnutrition: Challenges Associated With Current Intervention Strategies And Prevention Initiatives, Duncan Stiller

Senior Honors Projects

Few, if any, tribulations in the field of public health have managed to transcend the epidemiological transition from acute to chronic disease as malnutrition has. Officially, malnutrition is a category of diseases that includes micronutrient deficiency, under-nutrition (calories/protein), as well as excessive nutrition. The World Food Program estimates that 842 million people worldwide do not have access to enough food, approximately 146 million of which are children. The most serious types of hunger are known as Severe Acute Malnutrition (SAM) and Moderate Acute Malnutrition (MAM), with 20 million and 35 million respective cases each year occurring in children less than …

Antimicrobial Stewardship Program Prompts Increased And Earlier Infectious Diseases Consultation, Haley J. Morrill, M. Gaitanis, Kerry L. Laplante

Pharmacy Practice and Clinical Research Faculty Publications

A recent analysis demonstrated that infectious diseases (ID) specialty intervention was associated with decreased mortality and hospital readmission. These benefits were greatest if involvement occurred within two days of hospital admission. Antimicrobial stewardship programs should augment the services of an ID specialist team and promote formal consultation. Implementation of an antimicrobial stewardship program at the Providence Veterans Affairs Medical Center was associated with an increased number of consults (increase of 72.2%) and decreased time to consult (3.5 days sooner), which might also dramatically improve patient outcomes, including mortality and readmission rates.

Human Immune Responses To H. Pylori Hla Class Ii Epitopes Identified By Immunoinformatic Methods, Songhua Zhang, Joseph Desrosiers, Jose R. Aponte-Pieras, Kristen Dasilva, Loren D. Fast, Frances Terry, William D. Martin, Anne S. De Groot, Leonard Moise, Steven F. Moss

Institute for Immunology and Informatics Faculty Publications

H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity …

Cross-Conservation Of T-Cell Epitopes: Now Even More Relevant To (H7n9) Influenza Vaccine Design, Anne S. De Groot, Lenny Moise, Rui Liu, Andres H. Gutierrez, Frances Terry, Ousmane A. Koita, Ted M. Ross, William Martin

Institute for Immunology and Informatics Faculty Publications

A novel avian-origin H7N9 influenza strain emerged in China in April 2013. Since its re-emergence in October–November 2013, the number of reported cases has accelerated; more than 220 laboratory-confirmed cases and 112 deaths (case fatality rate of 20–30%) have been reported. The resurgence of H7N9 has re-emphasized the importance of making faster and more effective influenza vaccines than those that are currently available. Recombinant H7 hemagglutinin (H7-HA) vaccines have been produced, addressing the first problem. Unfortunately, these recombinant subunit vaccine products appear to have failed to address the second problem, influenza vaccine efficacy. Reported unadjuvanted H7N9 vaccine seroconversion rates were …

Comparative Effectiveness Of Linezolid And Vancomycin Among A National Veterans Affairs Cohort With Methicillin-Resistant Staphylococcus Aureus Pneumonia, Aisling R. Caffrey, J. Morrill, Laura A. Puzniak, Kerry L. Laplante

Pharmacy Practice and Clinical Research Faculty Publications

Study Objective: As variability in vancomycin dosing, susceptibility, and tolerability has driven the need to compare newer agents with vancomycin in real-world clinical settings, we sought to quantify the effectiveness of linezolid compared with vancomycin on clinical outcomes for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.

Design: Retrospective cohort study.

Data Source: Veterans Health Administration national databases.

Patients: Adults admitted to Veterans Affairs hospitals between January 2002 and September 2010 with diagnosis codes for MRSA and pneumonia, and who initiated and received at least 3 days of continuous intravenous vancomycin therapy (4943 patients) or intravenous or oral linezolid therapy …

Division Of Research And Economic Development Monthly Report For February 2014, Uri Division Of Research And Economic Development

Reports (Research and Economic Development)

The monthly reports include statistics for project proposals and awards received by individual academic and administrative departments at the University of Rhode Island.

Division Of Research And Economic Development Monthly Report For May 2014, Uri Division Of Research And Economic Development

Reports (Research and Economic Development)

The monthly reports include statistics for project proposals and awards received by individual academic and administrative departments at the University of Rhode Island.

Division Of Research And Economic Development Monthly Report For April 2014, Uri Division Of Research And Economic Development

Reports (Research and Economic Development)

The monthly reports include statistics for project proposals and awards received by individual academic and administrative departments at the University of Rhode Island.

Division Of Research And Economic Development Monthly Report For June 2014, Uri Division Of Research And Economic Development

Reports (Research and Economic Development)

The monthly reports include statistics for project proposals and awards received by individual academic and administrative departments at the University of Rhode Island.

Choppi: A Web Tool For The Analysis Of Immunogenicity Risk From Host Cell Proteins In Cho-Based Protein Production, Chris Bailey-Kellogg, Andres H. Gutiérrez, Leonard Moise, Frances Terry, William D. Martin, Anne S. De Groot

Institute for Immunology and Informatics Faculty Publications

Despite high quality standards and continual process improvements in manufacturing, host cell protein (HCP) process impurities remain a substantial risk for biological products. Even at low levels, residual HCPs can induce a detrimental immune response compromising the safety and efficacy of a biologic. Consequently, advanced-stage clinical trials have been cancelled due to the identification of antibodies against HCPs. To enable earlier and rapid assessment of the risks in Chinese Hamster Ovary (CHO)-based protein production of residual CHO protein impurities (CHOPs), we have developed a web tool called CHOPPI, for CHO Protein Predicted Immunogenicity. CHOPPI integrates information regarding the possible presence …

Hcv Epitope, Homologous To Multiple Human Protein Sequences, Induces A Regulatory T Cell Response In Infected Patients, Phyllis T. Losikoff, Sasmita Mishra, Francis Terry, Andres Gutierrez, Matt T. Ardito, Loren Fast, Martha Nevola, William D. Martin, Chris Bailey-Kellogg, Anne S. De Groot, Stephen H. Gregory

Institute for Immunology and Informatics Faculty Publications

Background & Aims: Spontaneous resolution of hepatitis C virus (HCV) infections depends upon a broad T cell response to multiple viral epitopes. Most patients fail to clear infections spontaneously, however, and develop chronic disease. The elevated number and function of CD3⁺CD4⁺CD25⁺FoxP3⁺ regulatory T_(reg) cells in HCV-infected patients suggest the role of T_reg cells in impaired viral clearance. The factors contributing to increased T_reg cell activity in chronic hepatitis C cases remain to be delineated.

Methods: Immunoinformatics tools were used to predict promiscuous, highly-conserved HLA-DRB1- restricted immunogenic consensus sequences …

Effect Of Temperature On Feeding Period Of Larval Blacklegged Ticks (Acari: Ixodidae) On Eastern Fence Lizards, Eric L. Rulison, Roger A. Lebrun, Howard S. Ginsberg

Plant Sciences and Entomology Faculty Publications

Ambient temperature can influence tick development time, and can potentially affect tick interactions with pathogens and with vertebrate hosts. We studied the effect of ambient temperature on duration of attachment of larval blacklegged ticks, Ixodes scapularis Say, to eastern fence lizards, Sceloporus undulatus (Bosc & Daudin). Feeding periods of larvae that attached to lizards under preferred temperature conditions for the lizards (WARM treatment: temperatures averaged 36.6°C at the top of the cage and 25.8°C at the bottom, allowing behavioral thermoregulation) were shorter than for larvae on lizards held under cool conditions (COOL treatment temperatures averaged 28.4°C at top of cage …

Integrated Assessment Of Predicted Mhc Binding And Cross-Conservation With Self Reveals Patterns Of Viral Camouflage, Lu He, Anne S. Degroot, Andres H. Gutierrez, William D. Martin, Lenny Moise, Chris Bailey-Kellogg

Institute for Immunology and Informatics Faculty Publications

Background

Immune recognition of foreign proteins by T cells hinges on the formation of a ternary complex sandwiching a constituent peptide of the protein between a major histocompatibility complex (MHC) molecule and a T cell receptor (TCR). Viruses have evolved means of "camouflaging" themselves, avoiding immune recognition by reducing the MHC and/or TCR binding of their constituent peptides. Computer-driven T cell epitope mapping tools have been used to evaluate the degree to which particular viruses have used this means of avoiding immune response, but most such analyses focus on MHC-facing 'agretopes'. Here we set out a new means of evaluating …

Vaxcelerate Ii: Rapid Development Of A Self-Assembling Vaccine For Lassa Fever, Pierre Leblanc, Leonard Moise, Cybelle Luza, Kanawat Chantaralawan, Lynchy Lezeau, Jianping Yuan, Mary Field, Daniel Richer, Christine Boyle, William D. Martin, Jordan B. Fishman, Eric A. Berg, David Baker, Brandon Zeigler, Dale E. Mais, William Taylor, Russell Coleman, H. Shaw Warren, Jeffrey A. Gelfand, Anne S. De Groot, Timothy Brauns, Mark C. Poznansky

Institute for Immunology and Informatics Faculty Publications

Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d. A self-assembling vaccine is …

Purification Of A Serine Protease And Evidence For A Protein C Activator From The Saliva Of The Tick, Ixodes Scapularis, Sivakamasundari Pichu, José M.C. Ribeiro, Thomas N. Mather, Ivo M.B. Francischetti

Plant Sciences and Entomology Faculty Publications

The saliva of ticks is critical to their survival as parasites and hematophagous animals. In this study, we have purified an enzyme with trypsin-like activity from the saliva of the tick vector of Lyme Disease, Ixodes scapularis. This enzyme, named as IXOSP (I. scapularis salivary serine protease), is a 29.9 kDa molecule with N-terminus FPxMVxLRIKxR. A BLAST search identified IXOSP as a secreted serine protease (AAY66740) with a conserved catalytic triad His, Asp, and Ser. In vitro studies demonstrated that IXOSP cleaves chromogenic substrates with arginine in the P₁ position, by a mechanism inhibited by PMSF or …

Searching For The Determinants Of Climate Change Interest, Patrick Cavanagh, Corey Lang, Xinran Li, Haoran Miao, John David Ryder

Environmental and Natural Resource Economics Faculty Publications

A meaningful CO2 mitigation policy is unlikely at the national level in the United States. What is currently happening and what is much more likely to occur in the future is city and regional level efforts of mitigation and adaptation. This paper aims to understand the geographic and socioeconomic characteristics of metropolitan areas and regions that lead to engagement with the issue of climate change. We use geographically explicit, internet search data from Google to measure information seeking behavior, which we take to translate into engagement, attention and interest. Our spatial hotspot analysis creates a map that potentially could be …

A High Throughput Mhc Ii Binding Assay For Quantitative Analysis Of Peptide Epitopes, Regina Salvat, Leonard Moise, Chris Bailey-Kellogg, Karl E. Griswold

Cell and Molecular Biology Faculty Publications

Biochemical assays with recombinant human MHC II molecules can provide rapid, quantitative insights into immunogenic epitope identification, deletion, or design^1,2. Here, a peptide-MHC II binding assay is scaled to 384-well format. The scaled down protocol reduces reagent costs by 75% and is higher throughput than previously described 96-well protocols^1,3-5. Specifically, the experimental design permits robust and reproducible analysis of up to 15 peptides against one MHC II allele per 384-well ELISA plate. Using a single liquid handling robot, this method allows one researcher to analyze approximately ninety test peptides in triplicate over a range of eight …

Health Studies Program Newsletter For 2014, Uri Health Studies Program

Public Health Department Publications

The 2014 issue of “Health-e-Newsletter,” a periodical focused on the Health Studies Program events, faculty research and highlights of student achievements.

Synthesis And Biological Evaluation Of 5′-O-Dicarboxylic Fatty Acyl Monoester Derivatives Of Anti-Hiv Nucleoside Reverse Transcriptase Inhibitors, Bhanu Pemmaraju, Hitesh K. Agarwal, Donghoon Oh, Karen W. Buckheit, Robert W. Buckheit Jr., Rakesh Tiwari, Keykavous Parang

Biomedical and Pharmaceutical Sciences Faculty Publications

A number of 5′-O-dicarboxylic fatty acyl monoester derivatives of 3′-azido-3′-deoxythymidine (zidovudine, AZT), 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine, d4T), and 3′-fluoro-3′-deoxythymidine (alovudine, FLT) were synthesized to improve the lipophilicity and potentially the cellular delivery of parent polar 2′,3′-dideoxynucleoside (ddN) analogs. The compounds were evaluated for their anti-HIV activity. Three different fatty acids with varying chain length of suberic acid (octanedioic acid), sebacic acid (decanedioic acid), and dodecanedioic acid were used for the conjugation with the nucleosides. The compounds were evaluated for anti-HIV activity and cytotoxicity. All dicarboxylic ester conjugates of nucleosides exhibited significantly higher anti-HIV activity than that of the corresponding parent …

Epidemiology Of Pneumococcal Disease In A National Cohort Of Older Adults, Haley J. Morrill, Aisling R. Caffrey, Eunsun Noh, Kerry L. Laplante

Pharmacy Practice and Clinical Research Faculty Publications

Introduction: Streptococcus pneumoniae is a major cause of morbidity and mortality. We sought to describe the epidemiology of non-invasive and invasive pneumococcal disease in a national Veterans Affairs population.

Methods: We conducted a retrospective study in older patients (aged ≥50 years) with positive pneumococcal cultures from any site within the United States between 2002 and 2011. We described outpatient and inpatient pneumococcal disease incidence per 100,000 clinic visits/hospitalizations. Repeat cultures within a 30-day period were considered to represent the same episode. To describe the epidemiology of serious pneumococcal infections (bacteremia, meningitis, pneumonia), we assessed demographics, clinical characteristics, and risk factors …

Worth The Weight: Using Inverse Probability Weighted Cox Models In Aids Research, Ashley L. Buchanan, G. Hudgens, Stephen R. Cole, Bryan Lau, Adaora A. Adimora

Pharmacy Practice and Clinical Research Faculty Publications

Survival analysis methods such as Cox regression can be used in infectious disease research to compare the timing of clinical events between treatment or exposure groups. Randomized clinical trials are the gold standard for estimating the effect of a treatment or exposure on a survival time endpoint. However, clinical trials are not always ethical or feasible. In that case, inference about the effect of interest might be attempted using data from observational studies. Unfortunately, observational studies may be riddled with confounding which can cast doubt on the validity of the results. In this tutorial, we demonstrate how inverse probability weighted …

Predictors Of Clinical Success Among A National Veterans Affairs Cohort With Methicillin-Resistant Staphylococcus Aureus Pneumonia, Aisling R. Caffrey, J. Morrill, Laura A. Puzniak, Kerry L. Laplante

Pharmacy Practice and Clinical Research Faculty Publications

Background: The treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is exceedingly complicated, which is concerning because of the high mortality rate associated with the infection. Identification of independent predictors of clinical success can optimize patient care by assisting clinicians in treatment decisions.

Objectives: We sought to identify independent predictors of clinical success in a national Veterans Affairs (VA) cohort of MRSA pneumonia patients.

Methods: A nested case-control study was conducted among a cohort of VA patients with MRSA pneumonia receiving linezolid or vancomycin between January 2002 and September 2010. Cases included those demonstrating clinical success, defined as discharge from …

Hiv Viremia And Incidence Of Non-Hodgkin Lymphoma In Patients Successfully Treated With Antiretroviral Therapy, Chad J. Achenbach, Ashley L. Buchanan, Stephen R. Cole, Lifang Hou, Michael J. Mugavero, Heidi M. Crane, Richard D. Moore, Richard H. Haubrich, Satish Gopal, Joseph J. Eron, Peter W. Hunt, Benigno Rodriguez, Kenneth Mayer, Michael S. Saag, Mari M. Kiahata

Pharmacy Practice and Clinical Research Faculty Publications

Background: The incidence of non-Hodgkin lymphoma (NHL) in human immunodeficiency virus (HIV)–infected patients remains high despite treatment with antiretroviral therapy (ART).

Methods: We evaluated NHL incidence in HIV-infected patients followed in the Centers for AIDS Research Network of Integrated Clinical Systems who started combination ART and achieved suppression of HIV. We estimated the hazard ratio for NHL by time-varying HIV viremia categories, accounting for time-varying CD4 cell count using marginal structural models.

Results: We observed 37 incident NHL diagnoses during 21 607 person-years of follow-up in 6036 patients (incidence rate, 171 per 100 000 person-years; 95% confidence interval [CI], 124–236). …

Characterization Of The Probiotic Mechanism Of Phaeobacter Gallaeciensis S4 Against Bacterial Pathogens, Wenjing Zhao

Open Access Dissertations

Infections by pathogenic marine bacteria are a major problem for both the shellfish and finfish aquaculture industries, causing severe disease and high mortality, which seriously affect aquaculture production and cause significant economic loss. Marine pathogens like Vibrio tubiashii and Roseovarius crassostreae frequently cause disease in a variety of shellfish. With the understanding that the use of antibiotics in large-scale aquaculture leads to the development and transfer of antibiotic resistance, investigation of probiotic approaches for the prevention of infectious disease has become important. In manuscript I, screening of bacterial isolates from Rhode Island marine organisms and environment using agar-based assay methods …