Understanding enterprise data warehouses to support clinical and translational research: impact, sustainability, demand management, and accessibility.

Objectives: Healthcare organizations, including Clinical and Translational Science Awards (CTSA) hubs funded by the National Institutes of Health, seek to enable secondary use of electronic health record (EHR) data through an enterprise data warehouse for research (EDW4R), but optimal approaches are unknown. In this qualitative study, our goal was to understand EDW4R impact, sustainability, demand management, and accessibility.

Materials And Methods: We engaged a convenience sample of informatics leaders from CTSA hubs (n = 21) for semi-structured interviews and completed a directed content analysis of interview transcripts.

Maturity in enterprise data warehouses for research operations: Analysis of a pilot study.

Enterprise data warehouses for research (EDW4R) is a critical component of National Institutes of Health Clinical and Translational Science Award (CTSA) hubs. EDW4R operations have unique needs that require specialized skills and collaborations across multiple domains which limit the ability to apply existing models of information technology (IT) performance. Because of this uniqueness, we developed a new EDW4R maturity model based on prior qualitative study of operational practices for supporting EDW4Rs at CTSA hubs.

Understanding enterprise data warehouses to support clinical and translational research: enterprise information technology relationships, data governance, workforce, and cloud computing.

Objective: Among National Institutes of Health Clinical and Translational Science Award (CTSA) hubs, effective approaches for enterprise data warehouses for research (EDW4R) development, maintenance, and sustainability remain unclear. The goal of this qualitative study was to understand CTSA EDW4R operations within the broader contexts of academic medical centers and technology.

Materials And Methods: We performed a directed content analysis of transcripts generated from semistructured interviews with informatics leaders from 20 CTSA hubs.

Inflammatory cytokines TNF-α and IL-17 enhance the efficacy of cystic fibrosis transmembrane conductance regulator modulators.

Without cystic fibrosis transmembrane conductance regulator-mediated (CFTR-mediated) HCO3- secretion, airway epithelia of newborns with cystic fibrosis (CF) produce an abnormally acidic airway surface liquid (ASL), and the decreased pH impairs respiratory host defenses. However, within a few months of birth, ASL pH increases to match that in non-CF airways. Although the physiological basis for the increase is unknown, this time course matches the development of inflammation in CF airways.

Dissemination and continuous improvement of a CTSA-based software platform, SPARCRequest, using an open source governance model.

SPARCRequest© (Services, Pricing, & Application for Research Centers) is a web-based research management system that provides a modular and adaptable "electronic storefront" for research-related services. Developed by the South Carolina Clinical & Translational Research Institute at the Medical University of South Carolina, it was released as open source (OS) code in 2014. The adoption of SPARCRequest© accelerated in 2016, when, to ensure responsiveness to the needs of partners, its governance also became open.

Research IT maturity models for academic health centers: Early development and initial evaluation.

This paper proposes the creation and application of maturity models to guide institutional strategic investment in research informatics and information technology (research IT) and to provide the ability to measure readiness for clinical and research infrastructure as well as sustainability of expertise. Conducting effective and efficient research in health science increasingly relies upon robust research IT systems and capabilities. Academic health centers are increasing investments in health IT systems to address operational pressures, including rapidly growing data, technological advances, and increasing security and regulatory challenges associated with data access requirements.

Research Opportunities to Improve Neonatal Red Blood Cell Transfusion.

Red blood cell (RBC) transfusion is a common and lifesaving therapy for anemic neonates and infants, particularly among those born prematurely or undergoing surgery. However, evidence-based indications for when to administer RBCs and adverse effects of RBC transfusion on important outcomes including necrotizing enterocolitis, survival, and long-term neurodevelopmental impairment remain uncertain. In addition, blood-banking practices for preterm and term neonates and infants have been largely developed using studies from older children and adults.

Predictive factors and practice trends in red blood cell transfusions for very-low-birth-weight infants.

Background: Red blood cell (RBC) transfusions in very-low-birth-weight (VLBW) infants, while common, carry risk. Our objective was to determine clinical predictors of and trends in RBC transfusions among VLBW infants.

Methods: RBC transfusion practice and its clinical predictors in 1,750 VLBW (≤1,500 g) infants were analyzed in a single-center cohort across sequential epochs: 2000-2004 (Epoch 1), 2005-2009 (Epoch 2), and 2010-2013 (Epoch 3).

Effect of deep tissue incision on pH responses of afferent fibers and dorsal root ganglia innervating muscle.

Background: Understanding the mechanisms underlying deep tissue pain in the postoperative period is critical to improve therapies. Using the in vitro plantar flexor digitorum brevis muscle-nerve preparation and patch clamp recordings from cultured dorsal root ganglia neurons innervating incised and unincised muscle, the authors investigated responses to various pH changes.

Methods: Incision including the plantar flexor digitorum brevis muscle or sham operation was made in the rat hind paw.

Resistance to fluid shear stress is a conserved biophysical property of malignant cells.

During metastasis, cancer cells enter the circulation in order to gain access to distant tissues, but how this fluid microenvironment influences cancer cell biology is poorly understood. A longstanding view is that circulating cancer cells derived from solid tissues may be susceptible to damage from hemodynamic shear forces, contributing to metastatic inefficiency. Here we report that compared to non-transformed epithelial cells, transformed cells are remarkably resistant to fluid shear stress (FSS) in a microfluidic protocol, exhibiting a biphasic decrease in viability when subjected to a series of millisecond pulses of high FSS.

Mailed fecal immunochemical tests plus educational materials to improve colon cancer screening rates in Iowa Research Network (IRENE) practices.

Introduction: Only about half of all eligible Americans have been screened for colorectal cancer (CRC). The objective of this study was to test whether mailed educational materials and a fecal immunochemical test (FIT), with or without a scripted telephone reminder, led to FIT testing. In addition, we compared changes in attitudes toward, readiness for, and barriers to screening from baseline to follow-up after education about screening.

Epithelial-to-mesenchymal transition in prostate cancer: paradigm or puzzle?

The lethal consequences of prostate cancer are related to its metastasis to other organ sites. Epithelial-to-mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm to explain invasive and metastatic behavior during cancer progression. EMT is a normal physiologic process by which cells of epithelial origin convert into cells bearing mesenchymal characteristics.

Bile and pancreatic juice exclusion activates acinar stress kinases and exacerbates gallstone pancreatitis.

Bile and pancreatic juice exclusion from gut activates acinar stress kinases and exacerbates gallstone pancreatitis as evidenced by the ameliorating effects of replacement therapy in an experimental model of duct ligation-induced acute pancreatitis. In the early stages of gallstone pancreatitis, bile-pancreatic juice cannot enter the gut. Enteral exclusion worsens pancreatitis by causing feedback hyperstimulation of the exocrine pancreas that activates acinar cell stress kinases.

Increased oxidative stress created by adenoviral MnSOD or CuZnSOD plus BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) inhibits breast cancer cell growth.

Superoxide dismutases (SODs) have been found to decrease tumor formation and angiogenesis. SOD gene therapy, as with many other gene transfer strategies, may not completely inhibit tumor growth on its own. Thus, concomitant therapies are necessary to completely control the spread of this disease.

Evaluation of Etest and disk diffusion methods compared with broth microdilution antifungal susceptibility testing of clinical isolates of Candida spp. against posaconazole.

We performed Etest, disk diffusion, and broth microdilution susceptibility testing of 2,171 clinical isolates of Candida spp. against posaconazole. By using provisional breakpoints for comparison purposes only, the categorical agreement between the agar-based methods and broth microdilution results ranged from 93 to 98%, with <1% very major errors.

In vitro susceptibilities of Candida spp. to caspofungin: four years of global surveillance.

Caspofungin is being used increasingly as therapy for invasive candidiasis. Prospective sentinel surveillance for emergence of in vitro resistance to caspofungin among invasive Candida spp. isolates is indicated.

Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells.

Respiratory syncytial virus (RSV) preferentially infects airway epithelial cells, causing bronchiolitis, upper respiratory infections, asthma exacerbations, chronic obstructive pulmonary disease exacerbations, and pneumonia in immunocompromised hosts. A replication intermediate of RSV is dsRNA. This is an important ligand for both the innate immune receptor, TLR3, and protein kinase R (PKR).

Pyocyanin and its precursor phenazine-1-carboxylic acid increase IL-8 and intercellular adhesion molecule-1 expression in human airway epithelial cells by oxidant-dependent mechanisms.

Pseudomonas aeruginosa secretes numerous factors that alter host cell function and may contribute to disease pathogenesis. Among recognized virulence factors is the redox-active phenazine pyocyanin. We have recently demonstrated that the precursor for pyocyanin, phenazine-1-carboxylic acid (PCA), increases oxidant formation and alters gene expression in human airway epithelial cells.

Bile-pancreatic juice exclusion increases p38MAPK activation and TNF-alpha production in ligation-induced acute pancreatitis in rats.

Unlabelled: Acute pancreatitis is associated with stress kinase activation and cytokine production. We hypothesize that bile-pancreatic juice exclusion activates p38(MAPK) and induces TNF-alpha production in ligation-induced acute pancreatitis. We compared rats with 1-3 h of duct ligation, duct ligation with duodenal bile-pancreatic juice replacement from a donor rat, and sham operation.

Mechanism of acute pancreatitis exacerbation by enteral bile-pancreatic juice exclusion.

Using an original model, the donor rat model, we previously showed that bile-pancreatic juice exclusion from gut exacerbates ligation-induced acute pancreatitis. Here, we examine the mechanism by which bile-pancreatic juice exclusion from gut exacerbates acute pancreatitis. In the first part of the study we test the hypothesis that Na taurocholate and trypsin are components of bile-pancreatic juice that exacerbate acute pancreatitis when excluded.

Twelve years of fluconazole in clinical practice: global trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida.

We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI) isolates of Candida spp. collected from 250 medical centres in 32 nations over a 10-year period from 1992 through 2001. The species included 3401 C.

Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin.

Airway epithelial cells are unresponsive to endotoxin (lipopolysaccharide (LPS)) exposure under normal conditions. This study demonstrates that respiratory syncytial virus (RSV) infection results in increased sensitivity to this environmental exposure. Infection with RSV results in increased expression of Toll-like receptor (TLR) 4 mRNA, protein, and increased TLR4 membrane localization.

Presumed antepartum amniotic fluid embolism.

Background: Amniotic fluid embolism is seldom recognized in nonperipartum patients. The pathophysiology is uncertain and diagnosis imprecise, making management after stabilization difficult.

Case: A 37-year-old woman at 28 weeks' gestation presented with signs and symptoms consistent with amniotic fluid embolism including disseminated intravascular coagulopathy.

Hyperoxia induces macrophage cell cycle arrest by adhesion-dependent induction of p21Cip1 and activation of the retinoblastoma protein.

Hyperoxia induces growth arrest, apoptosis, necrosis, and morphological changes (spreading and adhesion) in various types of cells. The mechanism of hyperoxia-induced cell growth arrest has not been well elucidated, especially in macrophages. One possible mechanism is a role of cell adhesion in hyperoxia-induced cell cycle arrest.

Activities of fluconazole and voriconazole against 1,586 recent clinical isolates of Candida species determined by Broth microdilution, disk diffusion, and Etest methods: report from the ARTEMIS Global Antifungal Susceptibility Program, 2001.

The ARTEMIS Global Antifungal Susceptibility Program (ARTEMIS Program) was initiated in 2001 to provide focused surveillance of the activities of fluconazole and voriconazole against Candida spp. isolated from blood and other normally sterile sites. A total of 1,586 episodes of infection were detected at 61 international study sites.