Influence of Detection Method and Study Area Scale on Syphilis Cluster Identification in North Carolina

Identifying geographical clusters of sexually transmitted infections can aid in targeting prevention and control efforts. However, detectable clusters can vary between detection methods because of different underlying assumptions. Furthermore, because disease burden is not geographically homogenous, the reference population is sensitive to the study area scale, affecting cluster outcomes. We investigated the influence of cluster detection method and geographical scale on syphilis cluster detection in Mecklenburg County, North Carolina

Preliminary Results on HAT-P-4, TrES-3, XO-2, and GJ 436 from the NASA EPOXI Mission

EPOXI (EPOCh + DIXI) is a NASA Discovery Program Mission of Opportunity using the Deep Impact flyby spacecraft. The EPOCh (Extrasolar Planet Observation and Characterization) Science Investigation will gather photometric time series of known transiting exoplanet systems from January through August 2008. Here we describe the steps in the photometric extraction of the time series and present preliminary results of the first four EPOCh targets.Comment: 4 pages, 2 figures. To appear in the Proceedings of the 253rd IAU Symposium: "Transiting Planets", May 2008, Cambridge, M

Regulatory T-Cells and Associated Pathways in Metastatic Renal Cell Carcinoma (mRCC) Patients Undergoing DC-Vaccination and Cytokine-Therapy

Purpose: To evaluate CD4+CD25+FOXP3+ T regulatory cells (TREG) and associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of metastatic renal cell carcinoma (mRCC) patients and healthy volunteers. We subsequently investigated the effects of immunotherapy on circulating TREG combining an extensive phenotype examination, DNA methylation analysis and global transcriptome analysis. Design: Eighteen patients with mRCC and twelve volunteers (controls) were available for analysis. TREG phenotype was examined using flow cytometry (FCM). TREG were also quantified by analyzing the epigenetic status of the FOXP3 locus using methylation specific PCR. As a third approach, RNA of the PBL was hybridized to Affymetrix GeneChip Human Gene 1.0 ST Arrays and the gene signatures were explored using pathway analysis. Results We observed higher numbers of TREG in pre-treatment PBL of mRCC patients compared to controls. A significant increase in TREG was detected in all mRCC patients after the two cycles of immunotherapy. The expansion of TREG was significantly higher in non-responders than in responding patients. Methylation specific PCR confirmed the FCM data and circumvented the variability and subjectivity of the FCM method. Gene Set Enrichment Analysis (GSEA) of the microarray data showed significant enrichment of FOXP3 target genes, CTLA-4 and TGF-ß associated pathways in the patient cohort. Conclusion: Immune monitoring of the peripheral blood and tumor tissue is important for a wide range of diseases and treatment strategies. Adoption of methodology for quantifying TREG with the least variability and subjectivity will enhance the ability to compare and interpret findings across studies

Examining the Auroral Ionosphere in Three Dimensions Using Reconstructed 2D Maps of Auroral Data to Drive the 3D GEMINI Model

We use the Geospace Environment Model of Ion-Neutral Interactions (GEMINI) to create three-dimensional, time-dependent simulations of auroral ionospheric parameters in the localized, several 100 km region surrounding auroral arcs observed during a winter 2017 sounding rocket campaign, resolving three-dimensional features of fine-scale (km) flow structures in the vicinity of an auroral arc. The three-dimensional calculations of GEMINI allow (with sufficient driving data) auroral current closure to be investigated without idealizing assumptions of sheet-like structures or height integrated ionospheres. Datamaps for two nearly sheet-like arcs are reconstructed from replications of the Isinglass sounding rocket campaign data, and combined with camera-based particle inversions into a set of driving inputs to run the 3D time-dependent model. Comparisons of model results to radar density profiles and to in situ magnetometry observations are presented. Slices of volumetric current, flow, and conductance structures from model outputs are used to interpret closure currents in an auroral arc region, and are compared to original in situ measurements for verification. The predominant source of return current region field aligned current closure for these slow time variation events is seen to be from the conductance gradients, including the Hall. The importance of the versus terms in the determination of the current structure provides a more complicated picture than a previous GEMINI study, which relied predominantly on the divergence of the electric field to determine current structure. Sensitivity of data-driven model results to details of replication and reconstruction processes are discussed, with improvements outlined for future work

Suboptimal clinical response to ciprofloxacin in patients with enteric fever due to Salmonella spp. with reduced fluoroquinolone susceptibility: a case series

BACKGROUND: Salmonella spp. with reduced susceptibility to fluoroquinolones have higher than usual MICs to these agents but are still considered "susceptible" by NCCLS criteria. Delayed treatment response to fluoroquinolones has been noted, especially in cases of enteric fever due to such strains. We reviewed the ciprofloxacin susceptibility and clinical outcome of our recent enteric fever cases. METHODS: Salmonella enterica Serotype Typhi (S. Typhi) and Serotype Paratyphi (S. Paratyphi) blood culture isolates (1998–2002) were tested against nalidixic acid by disk diffusion (DD) and agar dilution (AD) and to ciprofloxacin by AD using NCCLS methods and interpretive criteria. Reduced fluoroquinolone susceptibility was defined as a ciprofloxacin MIC of 0.125–1.0 mg/L. The clinical records of patients treated with ciprofloxacin for isolates with reduced fluoroquinolone susceptibility were reviewed. RESULTS: Seven of 21 (33%) S. Typhi and S. Paratyphi isolates had reduced susceptibility to fluoroquinolones (MIC range 0.125–0.5 mg/L). All 7 were nalidixic acid resistant by DD (no zone) and by AD (MIC 128- >512 mg/L). The other 14 isolates were nalidixic acid susceptible and fully susceptible to ciprofloxacin (MIC range 0.015–0.03 mg/L). Five of the 7 cases were treated initially with oral ciprofloxacin. One patient remained febrile on IV ciprofloxacin until cefotaxime was added, with fever recurrence when cefotaxime was discontinued. Two continued on oral or IV ciprofloxacin alone but had prolonged fevers of 9–10 days duration, one was switched to IV beta-lactam therapy after remaining febrile for 3 days on oral/IV ciprofloxacin and one was treated successfully with oral ciprofloxacin. Four of the 5 required hospitalization. CONCLUSIONS: Our cases provide further evidence that reduced fluoroquinolone susceptibility of S. Typhi and S. Paratyphi is clinically significant. Laboratories should test extra-intestinal Salmonella spp. for reduced fluoroquinolone susceptibility

Geomasking sensitive health data and privacy protection: an evaluation using an E911 database

Geomasking is used to provide privacy protection for individual address information while maintaining spatial resolution for mapping purposes. Donut geomasking and other random perturbation geomasking algorithms rely on the assumption of a homogeneously distributed population to calculate displacement distances, leading to possible under-protection of individuals when this condition is not met. Using household data from 2007, we evaluated the performance of donut geomasking in Orange County, North Carolina. We calculated the estimated k-anonymity for every household based on the assumption of uniform household distribution. We then determined the actual k-anonymity by revealing household locations contained in the county E911 database. Census block groups in mixed-use areas with high population distribution heterogeneity were the most likely to have privacy protection below selected criteria. For heterogeneous populations, we suggest tripling the minimum displacement area in the donut to protect privacy with a less than 1% error rate

Progression of a large syphilis outbreak in rural North Carolina through space and time: Application of a Bayesian Maximum Entropy graphical user interface

In 2001, the primary and secondary syphilis incidence rate in rural Columbus County, North Carolina was the highest in the nation. To understand the development of syphilis outbreaks in rural areas, we developed and used the Bayesian Maximum Entropy Graphical User Interface (BMEGUI) to map syphilis incidence rates from 1999–2004 in seven adjacent counties in North Carolina. Using BMEGUI, incidence rate maps were constructed for two aggregation scales (ZIP code and census tract) with two approaches (Poisson and simple kriging). The BME maps revealed the outbreak was initially localized in Robeson County and possibly connected to more urban endemic cases in adjacent Cumberland County. The outbreak spread to rural Columbus County in a leapfrog pattern with the subsequent development of a visible low incidence spatial corridor linking Roberson County with the rural areas of Columbus County. Though the data are from the early 2000s, they remain pertinent, as the combination of spatial data with the extensive sexual network analyses, particularly in rural areas gives thorough insights which have not been replicated in the past two decades. These observations support an important role for the connection of micropolitan areas with neighboring rural areas in the spread of syphilis. Public health interventions focusing on urban and micropolitan areas may effectively limit syphilis indirectly in nearby rural areas

Regulatory T-Cells and Associated Pathways in Metastatic Renal Cell Carcinoma (mRCC) Patients Undergoing DC-Vaccination and Cytokine-Therapy

To evaluate CD4(+)CD25(+)FOXP3(+) T regulatory cells (T(REG)) and associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of metastatic renal cell carcinoma (mRCC) patients and healthy volunteers. We subsequently investigated the effects of immunotherapy on circulating T(REG) combining an extensive phenotype examination, DNA methylation analysis and global transcriptome analysis

Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, Interferon-α and dendritic cell vaccine

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 7 (2012): e50221, doi:10.1371/journal.pone.0050221.Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer. We examined peripheral blood lymphocyte (PBL) gene expression as a biomarker of illness and treatment effect using the Affymetrix Human Gene ST1 platform in patients with metastatic renal cell carcinoma (mRCC) who received combined treatment with IL-2, interferon-?-2a and dendritic cell vaccine. We examined gene expression, cytokine levels in patient serum and lymphocyte subsets as determined by flow cytometry (FCM). Pre-treatment PBLs from patients with mRCC exhibit a gene expression profile and serum cytokine profile consistent with inflammation and proliferation not found in healthy donors (HD). PBL gene expression from patients with mRCC showed increased mRNA of genes involved with T-cell and TREG-cell activation pathways, which was also reflected in lymphocyte subset distribution. Overall, PBL gene expression post-treatment (POST) was not significantly different than pre-treatment (PRE). Nevertheless, treatment related changes in gene expression (post-treatment minus pre-treatment) revealed an increased expression of T-cell and B-cell receptor signaling pathways in responding (R) patients compared to non-responding (NR) patients. In addition, we observed down-regulation of TREG-cell pathways post-treatment in R vs. NR patients. While exploratory in nature, this study supports the hypothesis that enhanced inflammatory cytotoxic pathways coupled with blunting of the regulatory pathways is necessary for effective anti-cancer activity associated with immune therapy. This type of analysis can potentially identify additional immune therapeutic targets in patients with mRCC.This work was supported by grants from the National Institutes of Health (RO1 CA5648, R21CA112761, P20RR016437, and P30CA023108)