65 research outputs found

    Kiloparsec-scale Spatial Offsets in Double-peaked Narrow-line Active Galactic Nuclei. I. Markers for Selection of Compelling Dual Active Galactic Nucleus Candidates

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    Merger-remnant galaxies with kpc-scale separation dual active galactic nuclei (AGNs) should be widespread as a consequence of galaxy mergers and triggered gas accretion onto supermassive black holes, yet very few dual AGNs have been observed. Galaxies with double-peaked narrow AGN emission lines in the Sloan Digital Sky Survey are plausible dual AGN candidates, but their double-peaked profiles could also be the result of gas kinematics or AGN-driven outflows and jets on small or large scales. To help distinguish between these scenarios, we have obtained spatial profiles of the AGN emission via follow-up long-slit spectroscopy of 81 double-peaked narrow-line AGNs in SDSS at 0.03 < z < 0.36 using Lick, Palomar, and MMT Observatories. We find that all 81 systems exhibit double AGN emission components with ~kpc projected spatial separations on the sky, which suggests that they are produced by kpc-scale dual AGNs or kpc-scale outflows, jets, or rotating gaseous disks. In addition, we find that the subsample (58%) of the objects with spatially compact emission components may be preferentially produced by dual AGNs, while the subsample (42%) with spatially extended emission components may be preferentially produced by AGN outflows. We also find that for 32% of the sample the two AGN emission components are preferentially aligned with the host galaxy major axis, as expected for dual AGNs orbiting in the host galaxy potential. Our results both narrow the list of possible physical mechanisms producing the double AGN components, and suggest several observational criteria for selecting the most promising dual AGN candidates from the full sample of double-peaked narrow-line AGNs. Using these criteria, we determine the 17 most compelling dual AGN candidates in our sample.Comment: 12 pages, 8 figures, published in ApJ. Modified from original version to reflect referee's comment

    Help is available: Supporting mental wellness through peer health navigation with young black men who have sex with men with HIV

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    Young black men who have sex with men (YBMSM) with HIV experience disproportionate rates of trauma, incarceration, poverty, racial discrimination, and homophobia. The synergistic effects of these adverse experiences, along with increased rates of mental health disorders, increase their risk for poor health. To address this need, the study authors adapted a current HIV service model to include a peer-health navigation intervention (WITH U) to attend to behavioral health, health literacy, linkage to services, and psychosocial support for YBMSM with HIV. This longitudinal, mixed-methods, nonexperimental study reports on the mental health burden among participants and the association between participation in WITH U and mental wellness outcomes. Participants

    Integrative clinical transcriptome analysis reveals TMPRSS2-ERG dependency of prognostic biomarkers in prostate adenocarcinoma

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    In prostate adenocarcinoma (PCa), distinction between indolent and aggressive disease is challenging. Around 50% of PCa are characterized by TMPRSS2-ERG (T2E)-fusion oncoproteins defining two molecular subtypes (T2E-positive/negative). However, current prognostic tests do not differ between both molecular subtypes, which might affect outcome prediction. To investigate gene-signatures associated with metastasis in T2E-positive and T2E-negative PCa independently, we integrated tumor transcriptomes and clinicopathological data of two cohorts (total n = 783), and analyzed metastasis-associated gene- signatures regarding the T2E-status. Here, we show that the prognostic value of biomarkers in PCa critically depends on the T2E-status. Using gene-set enrichment analyses, we uncovered that metastatic T2E-positive and T2E-negative PCa arecharacterized by distinct gene-signatures. In addition, by testing genes shared by several functional gene-signatures for theirassociation with event-free survival in a validation cohort (n=272), we identifiedfive genes (ASPN,BGN,COL1A1,RRM2andTYMS)—three of which are included in commercially available prognostic tests—whose high expression was significantlyassociated with worse outcome exclusively in T2E-negative PCa. Among these genes,RRM2andTYMSwere validated byimmunohistochemistry in another validation cohort (n=135), and several of them proved to add prognostic information tocurrent clinicopathological predictors, such as Gleason score, exclusively for T2E-negative patients. No prognostic biomarkerswere identified exclusively for T2E-positive tumors. Collectively, our study discovers that the T2E-status, which ispersenot astrong prognostic biomarker, crucially determines the prognostic value of other biomarkers. Our data suggest that themolecular subtype needs to be considered when applying prognostic biomarkers for outcome prediction in PCa. What’s new? Genetic rearrangements involving androgen-regulated transmembrane protease serine 2 and genes from the ETS transcription factor family (T2E), most commonly ERG and ETV1, occur in half of prostate cancers but are currently not considered in risk predictions. The authors integrate clinical and transcriptomic data from multiple studies and show that the prognostic value of biomarkers critically depends on the T2E-status. They identify five biomarkers that predict negative outcome exclusively in T2E-negative prostate cancers, which has implications for outcome prediction based on the molecular subtype.Deutsche Forschungsgemeinschaft 391665916Deutsche Krebshilfe 70112257Dr Leopold and Carmen Ellinger FoundationDr Rolf M. Schwiete FoundationFriedrich-Baur FoundationGert and Susanna Mayer FoundationKind-Philipp FoundationMatthias-Lackas FoundationMehr LEBEN fur Krebskranke Kinder-Bettina-Brau-StiftungWilhelm Sander-Stiftung 2016.167.

    Inspiralling Supermassive Black Holes: A New Signpost for Galaxy Mergers

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    We present a new technique for observationally identifying galaxy mergers spectroscopically rather than through host galaxy imaging. Our technique exploits the dynamics of supermassive black holes (SMBHs) powering active galactic nuclei (AGNs) in merger-remnant galaxies. Because structure in the universe is built up through galaxy mergers and nearly all galaxies host a central SMBH, some galaxies should possess two SMBHs near their centers as the result of a recent merger. These SMBHs spiral to the center of the resultant merger-remnant galaxy, and one or both of the SMBHs may power AGNs. Using the DEEP2 Galaxy Redshift Survey, we have examined 1881 red galaxies, of which 91 exhibit [O III] and Hbeta emission lines indicative of Seyfert 2 activity. Of these, 32 AGNs have [O III] emission-line redshifts significantly different from the redshifts of the host galaxies' stars, corresponding to velocity offsets of ~50 km/s to ~300 km/s. Two of these AGNs exhibit double-peaked [O III] emission lines, while the remaining 30 AGNs each exhibit a single set of velocity-offset [O III] emission lines. After exploring a variety of physical models for these velocity offsets, we argue that the most likely explanation is inspiralling SMBHs in merger-remnant galaxies. Based on this interpretation, we find that roughly half of the red galaxies hosting AGNs are also merger remnants, which implies that mergers may trigger AGN activity in red galaxies. The AGN velocity offsets we find imply a merger fraction of ~30% and a merger rate of ~3 mergers/Gyr for red galaxies at redshifts 0.34 < z < 0.82.Comment: 10 pages, 4 figures, published in ApJ. Modified from original version to reflect referee's comment

    Deficiency of annexins A5 and A6 induces complex changes in the transcriptome of growth plate cartilage but does not inhibit the induction of mineralization

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    Initiation of mineralization during endochondral ossification is a multistep process and has been assumed to correlate with specific interactions of annexins A5 and A6 and collagens. However, skeletal development appears to be normal in mice deficient for either A5 or A6, and the highly conserved structures led to the assumption that A5 and A6 may fulfill redundant functions. We have now generated mice deficient of both proteins. These mice were viable and fertile and showed no obvious abnormalities. Assessment of skeletal elements using histologic, ultrastructural, and peripheral quantitative computed tomographic methods revealed that mineralization and development of the skeleton were not significantly affected in mutant mice. Otherwise, global gene expression analysis showed subtle changes at the transcriptome level of genes involved in cell growth and intermediate metabolism. These results indicate that annexins A5 and A6 may not represent the essential annexins that promote mineralization in vivo

    To Explain or Not to Explain?—Artificial Intelligence Explainability in Clinical Decision Support Systems

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    Explainability for artificial intelligence (AI) in medicine is a hotly debated topic. Our paper presents a review of the key arguments in favor and against explainability for AI-powered Clinical Decision Support System (CDSS) applied to a concrete use case, namely an AI-powered CDSS currently used in the emergency call setting to identify patients with life-threatening cardiac arrest. More specifically, we performed a normative analysis using socio-technical scenarios to provide a nuanced account of the role of explainability for CDSSs for the concrete use case, allowing for abstractions to a more general level. Our analysis focused on three layers: technical considerations, human factors, and the designated system role in decision-making. Our findings suggest that whether explainability can provide added value to CDSS depends on several key questions: technical feasibility, the level of validation in case of explainable algorithms, the characteristics of the context in which the system is implemented, the designated role in the decision-making process, and the key user group(s). Thus, each CDSS will require an individualized assessment of explainability needs and we provide an example of how such an assessment could look like in practice

    Integrative clinical transcriptome analysis reveals TMPRSS2‐ERG dependency of prognostic biomarkers in prostate adenocarcinoma

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    In prostate adenocarcinoma (PCa), distinction between indolent and aggressive disease is challenging. Around 50% of PCa are characterized by TMPRSS2‐ERG (T2E)‐fusion oncoproteins defining two molecular subtypes (T2E‐positive/negative). However, current prognostic tests do not differ between both molecular subtypes, which might affect outcome prediction. To investigate gene‐signatures associated with metastasis in T2E‐positive and T2E‐negative PCa independently, we integrated tumor transcriptomes and clinicopathological data of two cohorts (total n = 783), and analyzed metastasis‐associated gene‐signatures regarding the T2E‐status. Here, we show that the prognostic value of biomarkers in PCa critically depends on the T2E‐status. Using gene‐set enrichment analyses, we uncovered that metastatic T2E‐positive and T2E‐negative PCa are characterized by distinct gene‐signatures. In addition, by testing genes shared by several functional gene‐signatures for their association with event‐free survival in a validation cohort (n = 272), we identified five genes (ASPN, BGN, COL1A1, RRM2 and TYMS)—three of which are included in commercially available prognostic tests—whose high expression was significantly associated with worse outcome exclusively in T2E‐negative PCa. Among these genes, RRM2 and TYMS were validated by immunohistochemistry in another validation cohort (n = 135), and several of them proved to add prognostic information to current clinicopathological predictors, such as Gleason score, exclusively for T2E‐negative patients. No prognostic biomarkers were identified exclusively for T2E‐positive tumors. Collectively, our study discovers that the T2E‐status, which is per se not a strong prognostic biomarker, crucially determines the prognostic value of other biomarkers. Our data suggest that the molecular subtype needs to be considered when applying prognostic biomarkers for outcome prediction in PCa
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