Childhood TB Surveillance: Bridging the Knowledge Gap to Inform Policy

Tuberculosis (TB) is a leading cause of death globally. Natural history studies show that young children are at particularly high risk of progression to active TB and severe, disseminated disease following infection. Despite this, high-quality regional and global surveillance data on the burden of childhood TB are lacking. We discuss the unique aspects of TB in children that make diagnosis and therefore surveillance challenging; the limitations of available surveillance data; other data which provide insights into the true burden of childhood TB. Improved surveillance is among the key research priorities identified for childhood TB, but progress to date has been slow. Recent advances in TB diagnostics, and standardized clinical diagnostic guidelines and case definitions, all provide opportunities for new strategies to improve surveillance. Better-quality data on the burden and trends of childhood TB will inform and improve both public health policy and clinical practice

The mass-metallicity relation of local active galaxies

We systematically measure the gas-phase metallicities and the mass-metallicity relation of a large sample of local active galaxies for the first time. Observed emission-line fluxes from the Sloan Digital Sky Survey (SDSS) are compared to a four-dimensional grid of photoionization models using the Bayesian parameter estimation code NebulaBayes. For the first time we take into account arbitrary mixing between HII region and narrow-line region (NLR) emission, and the models are also varied with metallicity, ionization parameter in the NLR, and the gas pressure. The active galactic nucleus (AGN) oxygen abundance is found to increase by $\Delta {\rm O/H} \sim 0.1$ dex as a function of host galaxy stellar mass over the range $10.1 < \log M_* / M_\odot < 11.3$. We also measure the metallicity and ionization parameter of 231000 star-forming galaxies for comparison with the sample of 7670 Seyfert 2 galaxies. A systematic offset in oxygen abundance of 0.09 dex is observed between the mass-metallicity relations of the star-forming and active galaxies. We investigate potential causes of the offset, including sample selection and the treatment in the models of diffuse ionized gas, pressure, and ionization parameter. We cannot identify the major cause(s), but suspect contributions due to deficiencies in modeling the ionizing spectra and the treatment of dust physics. Optical diagnostic diagrams are presented with the star-forming and Seyfert data colored by the inferred oxygen abundance, ionization parameter and gas pressure, clearly illustrating the trends in these quantities.Comment: 12 pages, 4 figures and 1 table; accepted for publication in Ap

Recombination phenotypes of the NCI-60 collection of human cancer cells

<p>Abstract</p> <p>Background</p> <p>The NCI-60 is a collection of tumor cell lines derived from a variety of human adult cancer tissue types and is commonly used for genetic analysis and screening of potential chemotherapeutic agents. We wanted to understand the contributions of specific mechanisms of genomic instability to the etiology of cancers represented by the NCI-60.</p> <p>Results</p> <p>We screened the NCI-60 for dysregulated homologous recombination by using the gene cluster instability (GCI) assay we pioneered, and for defects in base excision repair by sensitivity to 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). We identified subsets of the NCI-60 lines that either displayed the characteristic molecular signature of GCI or were sensitive to hmdUrd. With the exception of the NCI-H23 lung cancer line, these phenotypes were not found to overlap. None of the lines examined in either subset exhibited significant changes in the frequency of sister chromatid exchanges (SCE), neither did any of the lines in either subset exhibit microsatellite instability (MSI) indicative of defects in DNA mismatch repair.</p> <p>Conclusions</p> <p>Gene cluster instability, sensitivity to hmdUrd and sister chromatid exchange are mechanistically distinct phenomena. Genomic instability in the NCI-60 appears to involve only one mechanism of instability for each individual cell line.</p

Statistical Computations with AstroGrid and the Grid

We outline our first steps towards marrying two new and emerging technologies; the Virtual Observatory (e.g, AstroGrid) and the computational grid. We discuss the construction of VOTechBroker, which is a modular software tool designed to abstract the tasks of submission and management of a large number of computational jobs to a distributed computer system. The broker will also interact with the AstroGrid workflow and MySpace environments. We present our planned usage of the VOTechBroker in computing a huge number of n-point correlation functions from the SDSS, as well as fitting over a million CMBfast models to the WMAP data.Comment: Invited talk to appear in "Proceedings of PHYSTAT05: Statistical Problems in Particle Physics, Astrophysics and Cosmology

Interrogating Seyferts with NebulaBayes: Spatially probing the narrow-line region radiation fields and chemical abundances

NebulaBayes is a new Bayesian code that implements a general method of comparing observed emission-line fluxes to photoionization model grids. The code enables us to extract robust, spatially resolved measurements of abundances in the extended narrow line regions (ENLRs) produced by Active Galactic Nuclei (AGN). We observe near-constant ionization parameters but steeply radially-declining pressures, which together imply that radiation pressure regulates the ENLR density structure on large scales. Our sample includes four `pure Seyfert' galaxies from the S7 survey that have extensive ENLRs. NGC2992 shows steep metallicity gradients from the nucleus into the ionization cones. An {\it inverse} metallicity gradient is observed in ESO138-G01, which we attribute to a recent gas inflow or minor merger. A uniformly high metallicity and hard ionizing continuum are inferred across the ENLR of Mrk573. Our analysis of IC5063 is likely affected by contamination from shock excitation, which appears to soften the inferred ionizing spectrum. The peak of the ionizing continuum E_peak is determined by the nuclear spectrum and the absorbing column between the nucleus and the ionized nebula. We cannot separate variation in this intrinsic E_peak from the effects of shock or HII region contamination, but E_peak measurements nevertheless give insights into ENLR excitation. We demonstrate the general applicability of NebulaBayes by analyzing a nuclear spectrum from the non-active galaxy NGC4691 using a HII region grid. The NLR and HII region model grids are provided with NebulaBayes for use by the astronomical community.Comment: Accepted for publication in ApJ; 29 pages with 10 figures and 3 table

Child's play:Temporal discourse, counterpower, and environmental politics

No abstract available

Gestational Vulnerability to Ozone Air Pollution - A Placental Story

About 99% of the global population resides in areas with air pollution surpassing World Health Organization standards. Air pollution is associated with adverse neonatal health outcomes such as low fetal birth weight and an increased risk for maternal pre-eclampsia. A particularly reactive air pollutant is ozone, which forms reactive oxygen species that induce cellular damage. Research exists on the dispersion of reactive oxygen species through the bloodstream leading to fetal vulnerability during pregnancy, specifically via the placenta. Yet, placental and fetal development is a temporal process with varied susceptibility to negative gestational outcomes. To addressing this gap, our laboratory utilized non-targeted proteomic analysis of amniotic fluid collected at term after either gestational day (GD) 10 or GD20 ozone exposure. Results provided a comprehensive list of proteins that indicated distinct outcome phenotypes. The acute GD20 exposure resulted in a potent acute-phase increase in antioxidant factors while the subacute GD10 exposure had a greater influence of growth factors. In follow-up, selected markers of these phenotypes will be assessed within matched placentas. Relevant to the antioxidant GD20 response, we will assess superoxide dismutase 1 (SOD1) and catalase, which catalyze superoxide and hydrogen peroxide, respectively. Per the GD10 subacute response, connective tissue growth factor (CTGF) is produced by cells involved with structure and stabilization of the ECM and affects cellular growth, migration, adhesion, and vascularization. Together with CTGF, collagen T1A2 plays a vital role in the extracellular matrix (ECM) and has been linked to pregnancy complications such as miscarriage, gestational diabetes, and preeclampsia. To assess differential impacts on the placental vasculature, we will be investigating vascular endothelial cell adhesion molecule 1 (VCAM-1) and vascular endothelial cadherin (VE-Cadherin), which have both been identified as biomarkers of preeclampsia. In our experiments, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of ozone (O3) or filtered air (FA) via whole-body inhalation at GD10 or GD20 while control animals received a sham filtered air exposure at both times. Placentas were collected and snap-frozen at GD21 followed by thin-sectioning using a frozen microtome and formaldehyde fixation. Primary antibodies to our protein targets are incubated overnight at 4C followed by secondary alexa-fluor conjugated antibodies to allow for multi-channel immunofluorescence detection. Images are generated on a Zeiss Axio Imager.M2 microscope at 200x magnification. Ongoing experiments are set at optimizing primary antibody concentrations. The experimental design involves creating three wells of two sample placental tissues per slide that are prepared and marked with primary and then secondary antibodies specific to the protein of interest. Each well contains a different dilution of the antibody that yields different fluorescence. Densitometric analysis is used to determine the concentration with the greatest signal-to-noise ratio. Once optimized, antibodies will be co-imaged on placenta tissues across five replicate animal exposure per experimental group. Quantification of mean fluorescence intensity will then be tabulated across decidual, labyrinth and chorionic placental lamina. Results will be assessed using analysis of variance with post-hoc testing for group differences. Expected outcomes will demonstrate the relationship between prior amniotic fluid proteomic findings and effects within the placenta while differentiating placental vulnerability across windows of gestation. These findings will prove significant in understanding outcomes at term for both the mother and fetus when exposed to ozone pollution.https://scholarscompass.vcu.edu/uresposters/1432/thumbnail.jp

Evaluation of temperature–pulse centile charts in identifying serious bacterial illness: observational cohort study

BACKGROUND: Distinguishing serious bacterial infection (SBI) from milder/self-limiting infections is often difficult. Interpretation of vital signs is confounded by the effect of temperature on pulse and respiratory rate. Temperature-pulse centile charts have been proposed to improve the predictive value of pulse rate in the clinical assessment of children with suspected SBI. OBJECTIVES: To assess the utility of proposed temperature-pulse centile charts in the clinical assessment of children with suspected SBI. STUDY DESIGN AND PARTICIPANTS: The predictive value for SBI of temperature-pulse centile categories, pulse centile categories and Advanced Paediatric Life Support (APLS) defined tachycardia were compared among 1360 children aged 3 months to 10 years presenting with suspected infection to a hospital emergency department (ED) in England; and among 325 children who presented to hospitals in the UK with meningococcal disease. MAIN OUTCOME MEASURE: SBI. RESULTS: Among children presenting to the ED, 55 (4.0%) had SBI. Pulse centile category, but not temperature-pulse centile category, was strongly associated with risk of SBI (p=0.0005 and 0.288, respectively). APLS defined tachycardia was also strongly associated with SBI (OR 2.90 (95% CI 1.60 to 5.26), p=0.0002). Among children with meningococcal disease, higher pulse and temperature-pulse centile categories were both associated with more severe disease (p=0.004 and 0.041, respectively). CONCLUSIONS: Increased pulse rate is an important predictor of SBI, supporting National Institute for Health and Clinical Excellence recommendations that pulse rate be routinely measured in the assessment of febrile children. Temperature-pulse centile charts performed more poorly than pulse alone in this study. Further studies are required to evaluate their utility in monitoring the clinical progress of sick children over time