Loss of chromosome 3q is a prognostic marker in fusion-negative rhabdomyosarcoma

PURPOSE: Soft tissue sarcomas (STS) are rare mesenchymal neoplasms that frequently show complex chromosomal aberrations such as amplifications or deletions of DNA sequences or even whole chromosomes. We recently found that gain of chromosome (chr) 8 is associated with worse overall survival (OS) in STS as a group. We therefore aimed to investigate the overall copy number profile of rhabdomyosarcoma (RMS) to evaluate for prognostic signatures. METHODS: Fluorescence in situ hybridization (FISH) testing was performed on a cohort of STS to assess for chr8 gain. Copy number variation (CNV) data from the National Cancer Institute were analyzed to assess for prognostically significant CNV aberrations in RESULTS: Chr8 gain is a highly prevalent CNV in embryonal RMS and shows slightly improved prognosis. Meanwhile, loss of chr3q was associated with worse outcome in FN-RMS compared with FP-RMS. CONCLUSION: The pathogenesis of STS including FN-RMS remains poorly understood, emphasizing the need for new therapeutic advances and adequate risk stratification. Our data demonstrate that loss of chr3q is associated with poor OS in FN-RMS, supporting it as an important tool for risk stratification

Randomized Trial of a Health Coaching Intervention to Enhance Retention in Care: California Collaborative Treatment Group 594.

Poor linkage, engagement and retention remain significant barriers in achieving HIV treatment goals in the US. HIV-infected persons entering or re-entering care across three Southern California academic HIV clinics, were randomized (1:1) to an Active, Linkage, Engagement, Retention and Treatment (ALERT) specialist for outreach and health coaching, or standard of care (SOC). The primary outcome of time to loss to follow up (LTFU) was compared using Cox proportional hazards regression modeling. No differences in the median time to LTFU (81.7 for ALERT versus 93.6 weeks for SOC; HR 1.27; p = 0.40), or time to ART initiation was observed (N = 116). Although, ALERT participants demonstrated worsening depressive symptomatology from baseline to week 48 compared to SOC (p = 0.02). The ALERT intervention did not improve engagement and retention in HIV care over SOC. Further studies are needed to determine how best to apply resources to improve retention and engagement

Scanning For Dark Matter Subhalos in Hubble Space Telescope Imaging of 54 Strong Lenses

The cold dark matter (DM) model predicts that every galaxy contains thousands of DM subhalos; almost all other DM models include a physical process that smooths away the subhalos. The subhalos are invisible, but could be detected via strong gravitational lensing, if they lie on the line of sight to a multiply-imaged background source, and perturb its apparent shape. We present a predominantly automated strong lens analysis framework, and scan for DM subhalos in Hubble Space Telescope imaging of 54 strong lenses. We identify two compelling DM subhalo candidates (including one previously found in SLACS0946+1006), where a subhalo is favoured after every systematic test we perform. We find that the detectability of subhalos depends upon the assumed parametric form for the lens galaxy's mass distribution. Comparing fits which assume several more complex mass models reveals $8$ additional (generally lower mass) DM subhalo candidates worthy of further study, and the removal of 7 false positives. We identify 38 non-detections, which are vital to building up enough statistical power to test DM models. Future work will apply even more flexible models to the results of this study, to constrain different DM models. Our full analysis results are available at https://github.com/Jammy2211/autolens_subhalo.Comment: 25 Pages, 15 Figure

Beyond the bulge–halo conspiracy? Density profiles of early-type galaxies from extended-source strong lensing

Observations suggest that the dark matter and stars in early-type galaxies ‘conspire’ to produce a surprisingly simple distribution of total mass, ρ(r) ∝ ρ−γ, with γ ≈ 2. We measure the distribution of mass in 48 early-type galaxies that gravitationally lens a resolved background source. By fitting the source light in every pixel of images from the Hubble Space Telescope, we find a mean ⟨γ⟩=2.075+0.023−0.024 with an intrinsic scatter between galaxies of σγ=0.172+0.022−0.032 for the overall sample. This is consistent with and has similar precision to traditional techniques that employ spectroscopic observations to supplement lensing with mass estimates from stellar dynamics. Comparing measurements of γ for individual lenses using both techniques, we find a statistically insignificant correlation of −0.150+0.223−0.217 between the two, indicating a lack of statistical power or deviations from a power-law density in certain lenses. At fixed surface mass density, we measure a redshift dependence, ∂⟨γ⟩/z=0.345+0.322−0.296⁠, that is consistent with traditional techniques for the same sample of Sloan Lens ACS and GALaxy-Lyα EmitteR sYstems (GALLERY) lenses. Interestingly, the consistency breaks down when we measure the dependence of γ on the surface mass density of a lens galaxy. We argue that this is tentative evidence for an inflection point in the total mass-density profile at a few times the galaxy effective radius – breaking the conspiracy

Recreational swimmers' exposure to Vibrio vulnificus and Vibrio parahaemolyticus in the Chesapeake Bay, Maryland, USA

Vibrio vulnificus and Vibrio parahaemolyticus are ubiquitous in the marine–estuarine environment, but the magnitude of human non-ingestion exposure to these waterborne pathogens is largely unknown. We evaluated the magnitude of dermal exposure to V. vulnificus and V. parahaemolyticus among swimmers recreating in Vibrio-populated waters by conducting swim studies at four swimming locations in the Chesapeake Bay in 2009 and 2011. Volunteers (n = 31) swam for set time periods, and surface water (n = 25) and handwash (n = 250) samples were collected. Samples were analyzed for Vibrio concentrations using quantitative PCR. Linear and logistic regressions were used to evaluate factors associated with recreational exposures. Mean surface water V. vulnificus and V. parahaemolyticus concentrations were 1128 CFU mL⁻¹ (95% confidence interval (CI): 665.6, 1591.4) and 18 CFU mL⁻¹ (95% CI: 9.8, 26.1), respectively, across all sampling locations. Mean Vibrio concentrations in handwash samples (V. vulnificus, 180 CFU cm⁻² (95% CI: 136.6, 222.5); V. parahaemolyticus, 3 CFU cm⁻² (95% CI: 2.4, 3.7)) were significantly associated with Vibrio concentrations in surfacewater (V. vulnificus, p < 0.01; V. parahaemolyticus, p < 0.01), but not with salinity or temperature (V. vulnificus, p = 0.52, p = 0.17; V. parahaemolyticus, p = 0.82, p = 0.06). Handwashing reduced V. vulnificus and V. parahaemolyticus on subjects' hands by approximately one log (93.9%, 89.4%, respectively). It can be concluded that when Chesapeake Bay surface waters are characterized by elevated concentrations of Vibrio, swimmers and individuals working in those waters could experience significant dermal exposures to V. vulnificus and V. parahaemolyticus, increasing their risk of infection.This is the publisher’s final pdf. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/environment-internationalKeywords: Vibrio parahaemolyticus, Recreational exposure, Vibrio vulnificus, Chesapeake Bay, Exposure assessment, Waterborne illnes

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

The Chandra Source Catalog

The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public ACIS imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents <~ 30''. The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports scientific analysis using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1 sigma uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of <~ 1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively.Comment: To appear in The Astrophysical Journal Supplement Series, 53 pages, 27 figure

Toxicology in the Fast Lane: Application of High-Throughput Bioassays to Detect Modulation of Key Enzymes and Receptors

BackgroundLegislation at state, federal, and international levels is requiring rapid evaluation of the toxicity of numerous chemicals. Whole-animal toxicologic studies cannot yield the necessary throughput in a cost-effective fashion, leading to a critical need for a faster and more cost-effective toxicologic evaluation of xenobiotics.ObjectivesWe tested whether mechanistically based screening assays can rapidly provide information on the potential for compounds to affect key enzymes and receptor targets, thus identifying those compounds requiring further in-depth analysis.MethodsA library of 176 synthetic chemicals was prepared and examined in a high-throughput screening (HTS) manner using nine enzyme-based and five receptor-based bioassays.ResultsAll the assays have high Z' values, indicating good discrimination among compounds in a reliable fashion, and thus are suitable for HTS assays. On average, three positive hits were obtained per assay. Although we identified compounds that were previously shown to inhibit a particular enzyme class or receptor, we surprisingly discovered that triclosan, a microbiocide present in personal care products, inhibits carboxylesterases and that dichlone, a fungicide, strongly inhibits the ryanodine receptors.ConclusionsConsidering the need to rapidly screen tens of thousands of anthropogenic compounds, our study shows the feasibility of using combined HTS assays as a novel approach toward obtaining toxicologic data on numerous biological end points. The HTS assay approach is very useful to quickly identify potentially hazardous compounds and to prioritize them for further in-depth studies

A Gene Expression Signature of Invasive Potential in Metastatic Melanoma Cells

BACKGROUND: We are investigating the molecular basis of melanoma by defining genomic characteristics that correlate with tumour phenotype in a novel panel of metastatic melanoma cell lines. The aim of this study is to identify new prognostic markers and therapeutic targets that might aid clinical cancer diagnosis and management. PRINCIPAL FINDINGS: Global transcript profiling identified a signature featuring decreased expression of developmental and lineage specification genes including MITF, EDNRB, DCT, and TYR, and increased expression of genes involved in interaction with the extracellular environment, such as PLAUR, VCAN, and HIF1a. Migration assays showed that the gene signature correlated with the invasive potential of the cell lines, and external validation by using publicly available data indicated that tumours with the invasive gene signature were less melanocytic and may be more aggressive. The invasion signature could be detected in both primary and metastatic tumours suggesting that gene expression conferring increased invasive potential in melanoma may occur independently of tumour stage. CONCLUSIONS: Our data supports the hypothesis that differential developmental gene expression may drive invasive potential in metastatic melanoma, and that melanoma heterogeneity may be explained by the differing capacity of melanoma cells to both withstand decreased expression of lineage specification genes and to respond to the tumour microenvironment. The invasion signature may provide new possibilities for predicting which primary tumours are more likely to metastasize, and which metastatic tumours might show a more aggressive clinical course

Statistical Characterization of the Chandra Source Catalog

The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray sources in a total area of ~0.75% of the entire sky, using data from ~3,900 separate ACIS observations of a multitude of different types of X-ray sources. In order to maximize the scientific benefit of such a large, heterogeneous data-set, careful characterization of the statistical properties of the catalog, i.e., completeness, sensitivity, false source rate, and accuracy of source properties, is required. Characterization efforts of other, large Chandra catalogs, such as the ChaMP Point Source Catalog (Kim et al. 2007) or the 2 Mega-second Deep Field Surveys (Alexander et al. 2003), while informative, cannot serve this purpose, since the CSC analysis procedures are significantly different and the range of allowable data is much less restrictive. We describe here the characterization process for the CSC. This process includes both a comparison of real CSC results with those of other, deeper Chandra catalogs of the same targets and extensive simulations of blank-sky and point source populations.Comment: To be published in the Astrophysical Journal Supplement Series (Fig. 52 replaced with a version which astro-ph can convert to PDF without issues.