Measuring spectroscopic redshifts for BL Lacertae (BL Lac) objects, a class of blazars, is challenging because their optical spectrum lacks, or has weak, emission lines (equivalent width <= 5 & Aring;). In this situation, alternative techniques are necessary for the estimation of distances to these sources. In this paper, we estimate the redshift by the photometric dropout technique for a sample of 64 blazars (59 BL Lacs and 5 blazar candidates of uncertain type). Two telescopes are utilized to observe the sample. The Ultraviolet/Optical Telescope on board Swift observes sources in uvw2, uvm2, uvw1, u, b, and v filters, while the ground-based SARA telescopes at Roque de los Muchachos, La Palma, Spain and Cerro Tololo, Chile observed sources in g ',r,' i ',z ' filters. We fit the photometric data with the LePHARE package and report four new high-z (z > 1.3) BL Lacs at 2.03(+0.07)(-0.05) , 1.84(+0.10)(-0.03) , 2.04(+0.16)(-0.14) , and 2.93(+0.01 )(-0.04)as well as upper limits for 50 sources. This work increased the number of high-z BL Lacs found by this method up to 23. The high-z sources are discussed in the context of the cosmic gamma-ray horizon, blazar sequence, Fermi blazar divide, and masquerading BL Lacs.

ABSTRACT We use Dark Energy Survey Year 3 (DES Y3) clusters with archival XMM–Newton and Chandra X-ray data to assess the centring performance of the redMaPPer cluster finder and to measure key richness observable scaling relations. We find that 10–20 per cent of redMaPPer clusters are miscentred, both when comparing to the X-ray peak position and to the visually identified central cluster galaxy. We find no significant difference in miscentring in bins of low versus high richness or redshift. The dominant reasons for miscentring include masked or missing data and the presence of other bright galaxies in the cluster. For half of the miscentred clusters, the correct central was one of the possible centrals identified by redMaPPer, while for ∼40 per cent of miscentred clusters, the correct central is not a redMaPPer member mostly due to masking. Additionally, we fit scaling relations of X-ray temperature and luminosity with richness. We find a TX–λ scatter of $0.21\pm 0.01$. While the scatter in TX–λ is consistent in redshift bins, we find modestly different slopes, with high-redshift clusters displaying a somewhat shallower relation. Splitting based on richness, we find a marginally larger scatter for our lowest richness bin, 20 < λ < 40. We note that the robustness of the scaling relations at lower richnesses is limited by the unknown selection function, but at λ > 75, we detect nearly all of the clusters falling within existing X-ray pointings. The X-ray properties of detected, serendipitous clusters are generally consistent with those of targeted clusters.

BL Lacertae (BL Lac) objects are a subclass of blazar, distinguished by their featureless optical spectrum. The featureless spectrum presents a challenge in measuring the redshift of the BL Lacs. In this paper, we measure the redshift of BL Lacs using the photometric dropout technique. The space-based telescope Swift and the ground-based SARA telescopes are employed to provide magnitudes in the uvw 2 , uvm 2 , uvw 1 , u , b , v , g ′ , r ′ , i ′ , and z ′ filters. We observe 60 BL Lacs and report reliable redshift upper limits for 41 of them. We discover three new high- z BL Lacs ( z > 1.3) at redshifts of 1.74 − 0.08 + 0.05 , 1.88 − 0.03 + 0.07 , and 2.10 − 0.04 + 0.03 , bringing the number of high- z BL Lacs found by this method up to 19. Discussions are made on the implications for the blazar sequence, the Fermi blazar divide, and the gamma-ray horizon based on an analysis of the 4LAC catalog and all high- z BL Lacs found with the photo- z technique.

ABSTRACT While collisionless cold dark matter models have been largely successful in explaining a wide range of observational data, some tensions still exist, and it remains possible that dark matter possesses a non-negligible level of self-interactions. In this paper, we investigate a possible observable consequence of self-interacting dark matter: offsets between the central galaxy and the centre of mass of its parent halo. We examine 23 relaxed galaxy clusters in a redshift range of 0.1–0.3 drawn from clusters in the Dark Energy Survey and the Sloan Digital Sky Survey which have archival Chandra X-ray data of sufficient depth for centre and relaxation determination. We find that most clusters in our sample show non-zero offsets between the X-ray centre, taken to be the centroid within the cluster core, and the central galaxy position. All of the measured offsets are larger, typically by an order of magnitude, than the uncertainty in the X-ray position due to Poisson noise. In all but six clusters, the measured offsets are also larger than the estimated, combined astrometric uncertainties in the X-ray and optical positions. A more conservative cut on concentration to select relaxed clusters marginally reduces but does not eliminate the observed offset. With our more conservative sample, we find an estimated median X-ray to central galaxy offset of $\mu = 6.0 ^{+ 1.4}_{- 1.5}$ kpc. Comparing to recent simulations, this distribution of offsets is consistent with some level of dark matter self-interaction, though further simulation work is needed to place constraints.

Legends for Supplementary Figures S1-S5.

Supplementary Figures S1-2, Tables S1-3. Figure S1. Comparison of the number of high confidence, non-synonymous somatic point mutations/indels and high level copy number alterations (CNAs) by tumor grade. Figure S2. Copy number plots of representative benign and borderline phyllodes tumors. Table S2: Somatic non-synonymous mutations identified in FFPE phyllodes tumors subjected to targeted next generation sequencing. Table S3: Detailed information about identified somatic non-synonymous mutations.

Sanger sequencing validation of next generation sequencing (NGS) variant calls ; Alternative view of integrative molecular profiling heatmap ; p16 expression via immunohistochemistry ; Kaplan-Meier analysis of histologic subtypes of PeSCCA ; Comparison of prioritized molecular alterations in penile (PN) squamous cell carcinomas (SCCA) compared to other SCCAs .

Clinicopathologic data for all profiled penile squamous cell carcinoma (PeSCCA) samples ; Sequencing data for all profiled penile squamous cell carcinoma (PeSCCA) samples ; Detailed somatic variant information from PeSCCA profiled by next generation sequenicng ; PeSCCA HPV genotyping and p16 immunohistochemistry (IHC) results .

<p>Description of additional methods and procedures used in the study. Also includes Supplementary References.</p>

Including millimeter-wave (mm-wave) data in multi-wavelength studies of the variability of active galactic nuclei (AGN) can provide insights into AGN physics that are not easily accessible at other wavelengths. We demonstrate in this work the potential of cosmic microwave background (CMB) telescopes to provide long-term, high-cadence mm-wave AGN monitoring over large fractions of sky. We report on a pilot study using data from the SPTpol instrument on the South Pole Telescope (SPT), which was designed to observe the CMB at arcminute and larger angular scales. Between 2013 and 2016, SPTpol was used primarily to observe a single 500 deg^2 field, covering the entire field several times per day with detectors sensitive to radiation in bands centered at 95 and 150 GHz. We use SPT 150 GHz observations to create AGN light curves, and we compare these mm-wave light curves to those at other wavelengths, in particular gamma-ray and optical. In this Letter, we focus on a single source, PKS 2326-502, which has extensive, day-timescale monitoring data in gamma-ray, optical, and now mm-wave between 2013 and 2016. We find PKS 2326-502 to be in a flaring state in the first two years of this monitoring, and we present a search for evidence of correlated variability between mm-wave, optical R band, and gamma-ray observations. This pilot study is paving the way for AGN monitoring with current and upcoming CMB experiments such as SPT-3G, Simons Observatory, and CMB-S4, including multi-wavelength studies with facilities such as VRO-LSST.

ABSTRACT We measure the velocity dispersions of clusters of galaxies selected by the red-sequence Matched-filter Probabilistic Percolation (redMaPPer) algorithm in the first three years of data from the Dark Energy Survey (DES), allowing us to probe cluster selection and richness estimation, λ, in light of cluster dynamics. Our sample consists of 126 clusters with sufficient spectroscopy for individual velocity dispersion estimates. We examine the correlations between cluster velocity dispersion, richness, X-ray temperature, and luminosity, as well as central galaxy velocity offsets. The velocity dispersion–richness relation exhibits a bimodal distribution. The majority of clusters follow scaling relations between velocity dispersion, richness, and X-ray properties similar to those found for previous samples; however, there is a significant population of clusters with velocity dispersions that are high for their richness. These clusters account for roughly 22 per cent of the λ < 70 systems in our sample, but more than half (55 per cent) of λ < 70 clusters at z > 0.5. A couple of these systems are hot and X-ray bright as expected for massive clusters with richnesses that appear to have been underestimated, but most appear to have high velocity dispersions for their X-ray properties likely due to line-of-sight structure. These results suggest that projection effects contribute significantly to redMaPPer selection, particularly at higher redshifts and lower richnesses. The redMaPPer determined richnesses for the velocity dispersion outliers are consistent with their X-ray properties, but several are X-ray undetected and deeper data are needed to understand their nature.

Several proposed models for dark matter posit the existence of self-interaction processes that can impact the shape of dark matter halos, making them more spherical than the ellipsoidal halos of collisionless dark matter. One method of probing the halo shapes, and thus the strength of the dark matter self-interaction, is by measuring the shape of the X-ray gas that traces the gravitational potential in relaxed elliptical galaxies. In this work we identify a sample of 11 relaxed, isolated elliptical galaxies and measure the ellipticity of the gravitating matter using X-ray images from the XMM-Newton and Chandra telescopes. We explore a variety of different mass configurations and find that the dark matter halos of these galaxies have ellipticities around epsilon approximate to 0.2 - 0.5. While we find non-negligible scatter in the ellipticity distribution, our results are consistent with some degree of self-interaction at the scale of sigma/m similar to 1 cm(2)/g, yet they also remain compatible with a cold dark matter scenario. We additionally demonstrate how our results can be used to directly constrain specific dark matter models and discuss implications for current and future simulations of self-interacting dark matter models.

296 Background: Expression-based molecular subtypes thought to be intrinsic in bladder cancer have been widely reported, carrying important potential clinical treatment implications. Histologically, bladder cancers are also heterogeneous diseases, with a large portion of urothelial carcinomas exhibiting divergent differentiation. Previous subtyping efforts have been carried out using predominantly fresh frozen tissue samples, potentially obscuring this known differentiation heterogeneity. Methods: Here we performed targeted multiplexed, amplicon-based DNA and RNA sequencing on 100 formalin-fixed paraffin-embedded (FFPE) bladder cancer samples (including 12 paired urothelial / squamous lesions). High-confidence somatic point mutations, short insertions/deletions (indels), and copy number alterations were detected using the DNA component of the Oncomine Comprehensive Assay (OCP). Targeted RNA sequencing was carried out using a custom Ampliseq panel comprised of 8 housekeeping genes and 103 target genes assessing major transcriptional programs as identified from publically available data. Results: By DNA analysis, we observe frequent TP53 (35%) and activating hotspot PIK3CA (23%) somatic mutations across the cohort, as well as targetable high-level (log-2 copy number ratio > = 1.5) focal amplifications of ERBB2 (3%) or EGFR (3%) in a subset of samples. We report a novel approach for detecting sub-gene copy-number alterations, and confirm several detectable multi-exon losses using whole transcriptome RNA sequencing. Pairing targeted RNA expression analysis with DNA-based alterations, we show high level expression of EGFR and ERBB2 in focally-amplified samples. Most importantly, we show that despite identical prioritized somatic genomic alterations, we observe divergent expression-based profiles in 3 of 12 (25%) paired urothelial and squamous samples. Conclusions: Taken together, these results highlight the importance of molecular heterogeneity in bladder cancer and suggest important considerations for using existing expression-based clustering approaches to guide clinical treatment decisions.

No AccessJournal of UrologyUrological Survey1 Nov 2018Re: Frequent PD-L1 Expression in Primary and Metastatic Penile Squamous Cell Carcinoma: Potential Opportunities for Immunotherapeutic Approaches Sam S. ChangMD Sam S. ChangSam S. Chang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.08.005AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Frequent PD-L1 Expression in Primary and Metastatic Penile Squamous Cell Carcinoma: Potential Opportunities for Immunotherapeutic Approaches." The Journal of Urology, 200(5), pp. 943–944 © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 200Issue 5November 2018Page: 943-944 Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sam S. Chang More articles by this author Expand All Advertisement PDF downloadLoading ...

Several somatic mutations specific to aldosterone-producing adenomas (APAs) have been described. A small proportion of adrenocortical carcinomas (ACCs) are associated with hyperaldosteronism, either primary aldosteronism or hyperreninemic hyperaldosteronism. However, it is unknown whether they harbor mutations of the same spectrum as APAs. The objective of this study is to describe the clinical phenotype and molecular genotype of ACCs with hyperaldosteronism, particularly the analysis for common APA-associated genetic changes. Patients were identified by retrospective chart review at a specialized referral center and by positive staining for CYP11B2 of tissue microarrays. Twenty-five patients with ACC and hyperaldosteronism were initially identified by retrospective chart review, and tissue for further analysis was available on 13 tumors. Seven patients were identified by positive staining for CYP11B2 in a tissue microarray, of which two were already identified in the initial chart review. Therefore, a total number of 18 patients with a diagnosis of ACC and features of either primary aldosteronism or hyperreninemic hyperaldosteronism were therefore included in the final study. Mutational status for a select list of oncogenes, tumor suppressor genes and genes known to carry mutations in APAs were analyzed by next-generation sequencing. Review of clinical data suggested autonomous aldosterone production in the majority of cases, while for some cases, hyperreninemic hyperaldosteronism was the more likely mechanism. The mutational landscape of ACCs associated with hyperaldosteronism was not different from ACCs with a different hormonal phenotype. None of the ACCs harbored mutations of known APA-associated genes, suggesting an alternative mechanism conferring aldosterone production.

BackgroundPrognostic biomarkers for localized prostate cancer (PCa) could improve personalized medicine. Our group previously identified a panel of differentially methylated CpGs in primary tumor tissue that predict disease aggressiveness, and here we further validate these biomarkers.MethodsPyrosequencing was used to assess CpG methylation of eight biomarkers previously identified using the HumanMethylation450 array; CpGs with strongly correlated (r >0.70) results were considered technically validated. Logistic regression incorporating the validated CpGs and Gleason sum was used to define and lock a final model to stratify men with metastatic‐lethal versus non‐recurrent PCa in a training dataset. Coefficients from the final model were then used to construct a DNA methylation score, which was evaluated by logistic regression and Receiver Operating Characteristic (ROC) curve analyses in an independent testing dataset.ResultsFive CpGs were technically validated and all were retained (P < 0.05) in the final model. The 5‐CpG and Gleason sum coefficients were used to calculate a methylation score, which was higher in men with metastatic‐lethal progression (P = 6.8 × 10−6) in the testing dataset. For each unit increase in the score there was a four‐fold increase in risk of metastatic‐lethal events (odds ratio, OR = 4.0, 95%CI = 1.8–14.3). At 95% specificity, sensitivity was 74% for the score compared to 53% for Gleason sum alone. The score demonstrated better prediction performance (AUC = 0.91; pAUC = 0.037) compared to Gleason sum alone (AUC = 0.87; pAUC = 0.025).ConclusionsThe DNA methylation score improved upon Gleason sum for predicting metastatic‐lethal progression and holds promise for risk stratification of men with aggressive tumors. This prognostic score warrants further evaluation as a tool for improving patient outcomes.

Solitary fibrous tumors (SFTs) of the head and neck are uncommon. Lesions previously diagnosed in the head and neck as hemangiopericytomas (HPCs), giant cell angiofibromas (GCAs), and orbital fibrous histiocytomas (OFHs) are now recognized as within the expanded spectrum of SFTs. To better understand the clinicopathologic profile of head and neck SFTs, we performed a multi-institutional study of 88 examples. There was no sex predilection (F:M ratio 1.2), and the median patient age was 52 years (range: 15 to above 89 y). The sinonasal tract and orbit were the most common sites involved (30% and 25%), followed by the oral cavity and salivary glands (15% and 14%). Original diagnoses included HPC (25%), SFT (67%), and OFH (6%), with 1 SFT and 1 OFH noted as showing GCA-like morphology. On review, the predominant histologic pattern was classic SFT-like in 53% and cellular (former HPC-like) in 47%; lipomatous differentiation (8%) and GCA-like pattern (7%) were less prevalent. Subsets demonstrated nuclear atypia (23%), epithelioid morphology (15%), or coagulative necrosis (6%). Infiltrative growth (49%) and osseous invasion (82%) were prevalent among evaluable cases. Of the 48 SFTs with follow-up (median: 43 mo), 19 showed recurrence (40%). Of these, 4 patients were alive with disease and 4 dead of disease. Size and mitotic rate were negative prognosticators using a joint prognostic proportional hazards regression model. Three patients experienced metastasis, to lungs, parotid, bone, and skull base, including one case showing overtly sarcomatous "dedifferentiation." As a group, SFTs present in a wide anatomic and morphologic spectrum in the head and neck. Only rare examples metastasize or cause death from disease. However, the fairly high local recurrence rate underscores their aggressive potential and highlights the importance of prospective recognition.

Solitary fibrous tumors (SFTs) of the head and neck are uncommon. Lesions previously diagnosed in the head and neck as hemangiopericytomas (HPCs), giant cell angiofibromas (GCAs), and orbital fibrous histiocytomas (OFHs) are now recognized as within the expanded spectrum of SFTs. To better understand the clinicopathologic profile of head and neck SFTs, we performed a multi-institutional study of 88 examples. There was no sex predilection (F:M ratio 1.2), and the median patient age was 52 years (range: 15 to above 89 y). The sinonasal tract and orbit were the most common sites involved (30% and 25%), followed by the oral cavity and salivary glands (15% and 14%). Original diagnoses included HPC (25%), SFT (67%), and OFH (6%), with 1 SFT and 1 OFH noted as showing GCA-like morphology. On review, the predominant histologic pattern was classic SFT-like in 53% and cellular (former HPC-like) in 47%; lipomatous differentiation (8%) and GCA-like pattern (7%) were less prevalent. Subsets demonstrated nuclear atypia (23%), epithelioid morphology (15%), or coagulative necrosis (6%). Infiltrative growth (49%) and osseous invasion (82%) were prevalent among evaluable cases. Of the 48 SFTs with follow-up (median: 43 mo), 19 showed recurrence (40%). Of these, 4 patients were alive with disease and 4 dead of disease. Size and mitotic rate were negative prognosticators using a joint prognostic proportional hazards regression model. Three patients experienced metastasis, to lungs, parotid, bone, and skull base, including one case showing overtly sarcomatous “dedifferentiation.” As a group, SFTs present in a wide anatomic and morphologic spectrum in the head and neck. Only rare examples metastasize or cause death from disease. However, the fairly high local recurrence rate underscores their aggressive potential and highlights the importance of prospective recognition.