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Search Results: 1 - 10 of 568980 matches for " Douglas E. A. White "
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A Comparison of Patient Satisfaction with Emergency Department Opt-In and Opt-Out Rapid HIV Screening
Douglas A. E. White,Alicia N. Scribner,Maria E. Martin,Stacy Tsai
AIDS Research and Treatment , 2012, DOI: 10.1155/2012/904916
Abstract: Study objective. To compare patient satisfaction with emergency department (ED) opt-in and opt-out HIV screening. Methods. We conducted a survey in an urban ED that provided rapid HIV screening using opt-in (February 1, 2007–July 31, 2007) and opt-out (August 1, 2007–January 31, 2008) approaches. We surveyed a convenience sample of patients that completed screening in each phase. The primary outcome was patient satisfaction with HIV screening. Results. There were 207 and 188 completed surveys during the opt-in and opt-out phases, respectively. The majority of patients were satisfied with both opt-in screening (95%, 95% confidence interval [CI] = 92–98) and opt-out screening (94%, 95% CI = 89–97). Satisfaction ratings were similar between opt-in and opt-out phases even after adjusting for age, gender, race/ethnicity, and test result (adjusted odds ratio 1.3, 95% CI = 0.5–3.1). Conclusions. Emergency department patient satisfaction with opt-in and opt-out HIV screening is similarly high. 1. Introduction 1.1. Background In 2006 the Centers for Disease Control and Prevention (CDC) published revised recommendations for HIV testing in health-care settings, which included emergency departments (EDs) [1]. Prior to these recommendations, the standard approach included opt-in HIV screening (in which patients are offered an HIV test and assent is required), separate written consent, and pre- and posttest counseling. The revised recommendations include using an opt-out approach to screening and removing requirements for test counseling and separate written informed consent as strategies to reduce barriers to testing and to make testing a routine part of care. With opt-out HIV screening, patients are notified that HIV testing will be performed unless they decline and consent for testing is integrated into the general ED consent process. Pretest counseling and risk assessment are not recommended, and written informational materials can replace posttest counseling and risk reduction strategies for patients that test negative. Access to clinical care and support services continue to be essential for patients with positive HIV test results [1]. The CDC recommends an opt-out approach for several reasons. By integrating opt-out screening into general consent, the screening process is streamlined and routinized. Patients may perceive the process to be less stigmatizing because they do not feel “singled out” for testing [1, 2]. It is hoped that adopting opt-out screening methodologies will increase screening rates. This is supported by the finding that, in some clinical
MCAM: Multiple Clustering Analysis Methodology for Deriving Hypotheses and Insights from High-Throughput Proteomic Datasets
Kristen M. Naegle,Roy E. Welsch,Michael B. Yaffe,Forest M. White,Douglas A. Lauffenburger
PLOS Computational Biology , 2011, DOI: 10.1371/journal.pcbi.1002119
Abstract: Advances in proteomic technologies continue to substantially accelerate capability for generating experimental data on protein levels, states, and activities in biological samples. For example, studies on receptor tyrosine kinase signaling networks can now capture the phosphorylation state of hundreds to thousands of proteins across multiple conditions. However, little is known about the function of many of these protein modifications, or the enzymes responsible for modifying them. To address this challenge, we have developed an approach that enhances the power of clustering techniques to infer functional and regulatory meaning of protein states in cell signaling networks. We have created a new computational framework for applying clustering to biological data in order to overcome the typical dependence on specific a priori assumptions and expert knowledge concerning the technical aspects of clustering. Multiple clustering analysis methodology (‘MCAM’) employs an array of diverse data transformations, distance metrics, set sizes, and clustering algorithms, in a combinatorial fashion, to create a suite of clustering sets. These sets are then evaluated based on their ability to produce biological insights through statistical enrichment of metadata relating to knowledge concerning protein functions, kinase substrates, and sequence motifs. We applied MCAM to a set of dynamic phosphorylation measurements of the ERRB network to explore the relationships between algorithmic parameters and the biological meaning that could be inferred and report on interesting biological predictions. Further, we applied MCAM to multiple phosphoproteomic datasets for the ERBB network, which allowed us to compare independent and incomplete overlapping measurements of phosphorylation sites in the network. We report specific and global differences of the ERBB network stimulated with different ligands and with changes in HER2 expression. Overall, we offer MCAM as a broadly-applicable approach for analysis of proteomic data which may help increase the current understanding of molecular networks in a variety of biological problems.
Urine Collection in the Emergency Department: What Really Happens in There?
Bradley W. Frazee,Kenneth Frausto,Bitou Cisse,Douglas E. A. White
Western Journal of Emergency Medicine : Integrating Emergency Care with Population Health , 2012,
Abstract: Introduction: In women with suspected urinary tract infection (UTI), a non-contaminated voidedspecimen is considered important for valid urinalysis and culture results. We assess whethermidstream parted-labia catch (MSPC) instructions were provided by nurses, understood, andperformed correctly, according to the patient.Methods: We conducted a cross-sectional survey of English- and Spanish-speaking female patientssubmitting voided urine samples for urinalysis for suspected UTI. The survey was conducted in apublic teaching hospital emergency department (ED) from June to December 2010, beginning 2months after development and dissemination of a nursing MSPC instructions protocol. Researchassistants administered the survey within 2 hours of urine collection. Nurses were unaware of thestudy purpose.Results: Of 129 patients approached, 74 (57%) consented and were included in the analysis.Median age was 35; 44% were Latino. Regarding instructions from nurses, patients reported thefollowing: 45 (61%; 95% CI 50-72%) received any instructions; of whom 37 (82%; 95% CI 71-93%)understood them completely. Sixteen (36%; 95% CI 22-51%) were instructed to collect midstream;and 7 (16%; 95% CI 6-29%) to part the labia. Regardless of receiving or understanding instructions,33 (45%; 95% CI 33-57%) reported actually collecting midstream, and 11 (15%, 95% CI 8-25%)parting the labia.Conclusion: In this ED, instructions for MSPC urine collection frequently were not given, despite anursing protocol, and patients rarely performed the essential steps. An evidence-based approachto urine testing in the ED that considers urine collection technique, is needed.
Spatial Pattern Dynamics of 3D Stem Cell Loss of Pluripotency via Rules-Based Computational Modeling
Douglas E. White,Melissa A. Kinney,Todd C. McDevitt,Melissa L. Kemp
PLOS Computational Biology , 2013, DOI: 10.1371/journal.pcbi.1002952
Abstract: Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into cells from all germ lineages, making them a potentially robust cell source for regenerative medicine therapies, but difficulties in predicting and controlling ESC differentiation currently limit the development of therapies and applications from such cells. A common approach to induce the differentiation of ESCs in vitro is via the formation of multicellular aggregates known as embryoid bodies (EBs), yet cell fate specification within EBs is generally considered an ill-defined and poorly controlled process. Thus, the objective of this study was to use rules-based cellular modeling to provide insight into which processes influence initial cell fate transitions in 3-dimensional microenvironments. Mouse embryonic stem cells (D3 cell line) were differentiated to examine the temporal and spatial patterns associated with loss of pluripotency as measured through Oct4 expression. Global properties of the multicellular aggregates were accurately recapitulated by a physics-based aggregation simulation when compared to experimentally measured physical parameters of EBs. Oct4 expression patterns were analyzed by confocal microscopy over time and compared to simulated trajectories of EB patterns. The simulations demonstrated that loss of Oct4 can be modeled as a binary process, and that associated patterns can be explained by a set of simple rules that combine baseline stochasticity with intercellular communication. Competing influences between Oct4+ and Oct4? neighbors result in the observed patterns of pluripotency loss within EBs, establishing the utility of rules-based modeling for hypothesis generation of underlying ESC differentiation processes. Importantly, the results indicate that the rules dominate the emergence of patterns independent of EB structure, size, or cell division. In combination with strategies to engineer cellular microenvironments, this type of modeling approach is a powerful tool to predict stem cell behavior under a number of culture conditions that emulate characteristics of 3D stem cell niches.
A Gammaherpesvirus Cooperates with Interferon-alpha/beta-Induced IRF2 to Halt Viral Replication, Control Reactivation, and Minimize Host Lethality
Pratyusha Mandal,Bridgette E. Krueger,Darby Oldenburg,Katherine A. Andry,R. Suzanne Beard,Douglas W. White,Erik S. Barton
PLOS Pathogens , 2011, DOI: 10.1371/journal.ppat.1002371
Abstract: The gammaherpesviruses, including Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), establish latency in memory B lymphocytes and promote lymphoproliferative disease in immunocompromised individuals. The precise immune mechanisms that prevent gammaherpesvirus reactivation and tumorigenesis are poorly defined. Murine gammaherpesvirus 68 (MHV68) is closely related to EBV and KSHV, and type I (alpha/beta) interferons (IFNαβ) regulate MHV68 reactivation from both B cells and macrophages by unknown mechanisms. Here we demonstrate that IFNβ is highly upregulated during latent infection, in the absence of detectable MHV68 replication. We identify an interferon-stimulated response element (ISRE) in the MHV68 M2 gene promoter that is bound by the IFNαβ-induced transcriptional repressor IRF2 during latency in vivo. The M2 protein regulates B cell signaling to promote establishment of latency and reactivation. Virus lacking the M2 ISRE (ISREΔ) overexpresses M2 mRNA and displays uncontrolled acute replication in vivo, higher latent viral load, and aberrantly high reactivation from latency. These phenotypes of the ISREΔ mutant are B-cell-specific, require IRF2, and correlate with a significant increase in virulence in a model of acute viral pneumonia. We therefore identify a mechanism by which a gammaherpesvirus subverts host IFNαβ signaling in a surprisingly cooperative manner, to directly repress viral replication and reactivation and enforce latency, thereby minimizing acute host disease. Since we find ISREs 5′ to the major lymphocyte latency genes of multiple rodent, primate, and human gammaherpesviruses, we propose that cooperative subversion of IFNαβ-induced IRFs to promote latent infection is an ancient strategy that ensures a stable, minimally-pathogenic virus-host relationship.
Self-Reported Ethnicity and Genetic Ancestry in Relation to Oral Cancer and Pre-Cancer in Puerto Rico
Esther Erdei, Huiping Sheng, Erika Maestas, Amanda Mackey, Kirsten A. White, Lin Li, Yan Dong, Justin Taylor, Marianne Berwick, Douglas E. Morse
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023950
Abstract: Background Hispanics are known to be an extremely diverse and genetically admixed ethnic group. The lack of methodologies to control for ethnicity and the unknown admixture in complex study populations of Hispanics has left a gap in understanding certain cancer disparity issues. Incidence rates for oral and pharyngeal cancer (OPC) in Puerto Rico are among the highest in the Western Hemisphere. We conducted an epidemiological study to examine risk and protective factors, in addition to possible genetic susceptibility components, for oral cancer and precancer in Puerto Rico. Methodology/Principal Findings We recruited 310 Puerto Rico residents who had been diagnosed with either an incident oral squamous cell carcinoma, oral precancer, or benign oral condition. Participants completed an in-person interview and contributed buccal cells for DNA extraction. ABI Biosystem Taqman? primer sets were used for genotyping 12 ancestry informative markers (AIMs). Ancestral group estimates were generated using maximum likelihood estimation software (LEADMIX), and additional principal component analysis was carried out to detect population substructures. We used unconditional logistic regression to assess the contribution of ancestry to the risk of being diagnosed with either an oral cancer or precancer while controlling for other potential confounders. The maximum likelihood estimates showed that study participants had a group average ancestry contribution of 69.9% European, 24.5% African, and 5.7% detectable Native American. The African and Indigenous American group estimates were significantly higher than anticipated. Neither self-identified ethnicity nor ancestry markers showed any significant associations with oral cancer/precancer risk in our study. Conclusions/Significance The application of ancestry informative markers (AIMs), specifically designed for Hispanics, suggests no hidden population substructure is present based on our sampling and provides a viable approach for the evaluation and control of ancestry in future studies involving Hispanic populations.
Cytokines and Tumor Metastasis Gene Variants in Oral Cancer and Precancer in Puerto Rico
Esther Erdei, Li Luo, Huiping Sheng, Erika Maestas, Kirsten A. M. White, Amanda Mackey, Yan Dong, Marianne Berwick, Douglas E. Morse
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079187
Abstract: Objectives A cross-sectional epidemiological study explored genetic susceptibility to oral precancer and cancer in Puerto Rico (PR). Materials and Methods Three hundred three individuals with a benign oral condition, oral precancer (oral epithelial hyperplasia/hyperkeratosis, oral epithelial dysplasia), or oral squamous cell carcinoma (SCCA) were identified via PR pathology laboratories. A standardized, structured questionnaire obtained information on epidemiological variables; buccal cells were collected for genetic analysis. Genotyping was performed using Taqman? assays. Allelic frequencies of single nucleotide polymorphisms (SNPs) were evaluated in cytokine genes and genes influencing tumor metastasis. Risk estimates for a diagnosis of oral precancer or SCCA while having a variant allele were generated using logistic regression. Adjusted models controlled for age, gender, ancestry, education, smoking and alcohol consumption. Results Relative to persons with a benign oral lesion, individuals with homozygous recessive allelic variants of tumor necrosis factor (TNF-α) ?238 A/G SNP had a reduced odds of having an oral precancer (ORadjusted = 0.15; 95% CI 0.03–0.70). The transforming growth factor beta-1 (TGFβ-1 ?509 C/T) polymorphism was inversely associated with having an oral SCCA among persons homozygous for the recessive variant (ORcrude = 0.27; 95% CI 0.09–0.79). The matrix metalloproteinase gene (MMP-1) variant, rs5854, was associated with oral SCCA; participants with even one variant allele were more likely to have oral SCCA (ORadjusted = 2.62, 95% CI 1.05–6.53) compared to people with ancestral alleles. Conclusion Our exploratory analyses suggest that genetic alterations in immune system genes and genes with metastatic potential are associated with oral precancer and SCCA risk in PR.
Pregnancy's Stronghold on the Vaginal Microbiome
Marina R. S. Walther-António, Patricio Jeraldo, Margret E. Berg Miller, Carl J. Yeoman, Karen E. Nelson, Brenda A. Wilson, Bryan A. White, Nicholas Chia, Douglas J. Creedon
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098514
Abstract: Objective To assess the vaginal microbiome throughout full-term uncomplicated pregnancy. Methods Vaginal swabs were obtained from twelve pregnant women at 8-week intervals throughout their uncomplicated pregnancies. Patients with symptoms of vaginal infection or with recent antibiotic use were excluded. Swabs were obtained from the posterior fornix and cervix at 8–12, 17–21, 27–31, and 36–38 weeks of gestation. The microbial community was profiled using hypervariable tag sequencing of the V3–V5 region of the 16S rRNA gene, producing approximately 8 million reads on the Illumina MiSeq. Results Samples were dominated by a single genus, Lactobacillus, and exhibited low species diversity. For a majority of the patients (n = 8), the vaginal microbiome was dominated by Lactobacillus crispatus throughout pregnancy. Two patients showed Lactobacillus iners dominance during the course of pregnancy, and two showed a shift between the first and second trimester from L. crispatus to L. iners dominance. In all of the samples only these two species were identified, and were found at an abundance of higher than 1% in this study. Comparative analyses also showed that the vaginal microbiome during pregnancy is characterized by a marked dominance of Lactobacillus species in both Caucasian and African-American subjects. In addition, our Caucasian subject population clustered by trimester and progressed towards a common attractor while African-American women clustered by subject instead and did not progress towards a common attractor. Conclusion Our analyses indicate normal pregnancy is characterized by a microbiome that has low diversity and high stability. While Lactobacillus species strongly dominate the vaginal environment during pregnancy across the two studied ethnicities, observed differences between the longitudinal dynamics of the analyzed populations may contribute to divergent risk for pregnancy complications. This helps establish a baseline for investigating the role of the microbiome in complications of pregnancy such as preterm labor and preterm delivery.
Comparative Genomic Assessment of Novel Broad-Spectrum Targets for Antibacterial Drugs
Thomas A. White,Douglas B. Kell
Comparative and Functional Genomics , 2004, DOI: 10.1002/cfg.411
Abstract: Single and multiple resistance to antibacterial drugs currently in use is spreading, since they act against only a very small number of molecular targets; finding novel targets for anti-infectives is therefore of great importance. All protein sequences from three pathogens (Staphylococcus aureus, Mycobacterium tuberculosis and Escherichia coli O157:H7 EDL993) were assessed via comparative genomics methods for their suitability as antibacterial targets according to a number of criteria, including the essentiality of the protein, its level of sequence conservation, and its distribution in pathogens, bacteria and eukaryotes (especially humans). Each protein was scored and ranked based on weighted variants of these criteria in order to prioritize proteins as potential novel broad-spectrum targets for antibacterial drugs. A number of proteins proved to score highly in all three species and were robust to variations in the scoring system used. Sensitivity analysis indicated the quantitative contribution of each metric to the overall score. After further analysis of these targets, tRNA methyltransferase (trmD) and translation initiation factor IF-1 (infA) emerged as potential and novel antimicrobial targets very worthy of further investigation. The scoring strategy used might be of value in other areas of post-genomic drug discovery.
Comparative analysis of the vaginal microbiome in health and disease
Bryan A White, Andres M Gomez, Mengfei Ho, Margret Berg Miller, Susan M Thomas, Carl J Yeoman, Suleyman Yildirim, Douglas J Creedon, Tony L Goldberg, Steven R Leigh, Karen E Nelson, Rebecca M Stumpf, Brenda A Wilson
Genome Biology , 2011, DOI: 10.1186/gb-2011-12-s1-i17
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