The OneFlorida Data Trust: a centralized,translational research data infrastructure of statewide scope

The OneFlorida Data Trust is a centralized research patient data repository created and managed by the OneFlorida Clinical Research Consortium (“OneFlorida”). It comprises structured electronic health record (EHR), administrative claims, tumor registry, death, and other data on 17.2 million individuals who received healthcare in Florida between January 2012 and the present. Ten healthcare systems in Miami, Orlando, Tampa, Jacksonville, Tallahassee, Gainesville, and rural areas of Florida contribute EHR data, covering the major metropolitan regions in Florida. Deduplication of patients is accomplished via privacy-preserving entity resolution (precision 0.97–0.99, recall 0.75), thereby linking patients’ EHR, claims, and death data. Another unique feature is the establishment of mother-baby relationships via Florida vital statistics data. Research usage has been significant, including major studies launched in the National Patient-Centered Clinical Research Network (“PCORnet”), where OneFlorida is 1 of 9 clinical research networks. The Data Trust’s robust, centralized, statewide data are a valuable and relatively unique research resource.     

PDCD2 functions in cancer cell proliferation and predicts relapsed leukemia

PDCD2 is an evolutionarily conserved eukaryotic protein with unknown function. The Drosophila PDCD2 ortholog Zfrp8 has an essential function in fly hematopoiesis. Zfrp8 mutants exhibit marked lymph gland hyperplasia that results from increased proliferation of partially differentiated hemocytes, suggesting Zfrp8 may participate in cell growth. Based on the above observations we have focused on the role of PDCD2 in human cancer cell proliferation and hypothesized that aberrant PDCD2 expression may be characteristic of human malignancies. We report that PDCD2 is highly expressed in human acute leukemia cells as well as in normal hematopoietic progenitors. PDCD2 knockdown in cancer cells impairs their proliferation, but not viability relative to parental cells, supporting the notion that PDCD2 overexpression facilitates cancer cell growth. Prospective analysis of PDCD2 in acute leukemia patients indicates PDCD2 RNA expression correlates with disease status and is a significant predictor of clinical relapse. PDCD2’s role in cell proliferation and its high expression in human malignancies make it an attractive, novel potential molecular target for new anti-cancer therapies.     

Brainstem encephalitis: etiologies, treatment, and predictors of outcome

Brainstem encephalitis (BE) is an uncommon condition. We sought to characterize clinical presentations, etiologies, response to treatment, and predictors of outcome. We performed a retrospective review of non–HIV infected patients diagnosed with BE at Johns Hopkins Hospital (January 1997–April 2010). We characterized clinical and paraclinical features, and used regression models to assess associations with poor outcome. BE was diagnosed in 81 patients. An etiology was identified in 58 of 81 (71.6 %) of cases, most of which were confirmed or probable inflammatory/autoimmune conditions. Of the remaining 23 cases in which a specific diagnosis remained undefined, clinical presentation, CSF, neuroimaging studies, and outcomes were similar to the inflammatory/autoimmune group. Brain biopsy identified a specific diagnosis in 7 of 14 patients (50 %). Fifteen patients (18.5 %) either died or had a poor outcome. In multivariate logistic regression models, a higher CSF protein (per 5 mg/dl, OR = 1.11, 95 % CI: 1.03–1.20), a higher CSF glucose (per 5 mg/dl, OR = 1.36, 95 % CI: 1.09–1.70), and higher serum glucose (per 5 mg/dl, OR = 1.27, 95 % CI: 1.06–1.52) were independently associated with increased odds of poor outcome. Inflammatory and non-infectious conditions accounted for most cases of BE. Higher CSF protein and glucose were independently associated with poor outcome. In immunocompetent patients with BE of undefined etiology despite extensive investigation, a trial of immunosuppressive treatment may be warranted, though deterioration clinically or on magnetic resonance imaging should prompt a brain biopsy.     

Improving PTSD/Substance Abuse Treatment in the VA: A Survey of Providers

We surveyed 205 Veterans Affairs (VA) staff on treatment of posttraumatic stress disorder (PTSD), substance use disorder (SUD), and the combination (PTSD/SUD). The survey was anonymous and VA‐wide. PTSD/SUD was perceived as more difficult to treat than either disorder alone; gratification in the work was stronger than difficulty (for PTSD, SUD, and PTSD/SUD); and difficulty and gratification appeared separate constructs. Respondents endorsed views that represent expert treatment for the comorbidity; however, there was also endorsement of “myths.” Thus, there is a need for more training, policy clarifications, service integration, and adaptations for veterans returning from Iraq and Afghanistan. Limitations are described. (Am J Addict 2010;19:257–263)     

Nonadditive effects of PAHs on Early Vertebrate Development: mechanisms and implications for risk assessment.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants. Traditionally, much of the research has focused on the carcinogenic potential of specific PAHs, such as benzo(a)pyrene, but recent studies using sensitive fish models have shown that exposure to PAHs alters normal fish development. Some PAHs can induce a teratogenic phenotype similar to that caused by planar halogenated aromatic hydrocarbons, such as dioxin. Consequently, mechanism of action is often equated between the two classes of compounds. Unlike dioxins, however, the developmental toxicity of PAH mixtures is not necessarily additive. This is likely related to their multiple mechanisms of toxicity and their rapid biotransformation by CYP1 enzymes to metabolites with a wide array of structures and potential toxicities. This has important implications for risk assessment and management as the current approach for complex mixtures of PAHs usually assumes concentration addition. In this review we discuss our current knowledge of teratogenicity caused by single PAH compounds and by mixtures and the importance of these latest findings for adequately assessing risk of PAHs to humans and wildlife. Throughout, we place particular emphasis on research on the early life stages of fish, which has proven to be a sensitive and rapid developmental model to elucidate effects of hydrocarbon mixtures.     

Stable pessimistic attributions interact with socioeconomic status to influence blood pressure and vulnerability to hypertension

We investigated the relationship of pessimistic attributional style (specifically, stable attributions for negative events) and socioeconomic status (SES) to cardiovascular and catecholamine profiles in a biracial sample of 37 postmenopausal women (aged 39-64 years) not taking hormone replacement therapy (HRT). Blood pressure (BP) variation in response to the demands of daily life was assessed by 24-hour ambulatory monitoring on a typical workday. Subjects were classified into groups by stable pessimistic attributions (high vs. low pessimism) and by SES (high vs. low). Significant SES x pessimism interactions were found. Low SES/high pessimism women demonstrated higher systolic BP (SBP) during the day, evening, and sleep periods of 24-hour ambulatory monitoring compared with the other three groups. A greater proportion of this group was in the hypertensive range (> or = 140/90 mm Hg) compared with the other groups (57% vs. 8%-29%). Low SES/high pessimism women also reported reduced available social support compared with the other three groups.     

Cleaning frequency and the microbial load in ice-cream

This study investigates the efficacy of a 62 h cleaning frequency in the manufacturing of ice-cream. Various product and product contact surfaces were sampled progressively throughout the time period between cleaning cycles, and analyzed for microbial growth. The coliform and standard plate counts (SPC) of these samples did not vary significantly over time after 0, 24, 48, or 62 h from Cleaning in Place (CiP). Data for product contact surfaces were significant for the SPC representing sample locations. Some of the variables in cleaning practices had significant influence on microbial loads. An increase in the number of flavors manufactured caused a decrease in SPC within the 24 h interval, but by the 48 h interval the SPC increased. More washouts within the first 24 h interval were favorable, as indicated by decreased SPC. The more frequently the liquefier was sanitized within the 62 h interval, the lower the SPC. This study indicates that food safety was not compromised and safety practices were effectively implemented throughout the process.