Detection of a Star Forming Galaxy in the Center of a Low-Mass Galaxy Cluster

Brightest Cluster Galaxies (BCGs) residing in the centers of galaxy clusters are typically quenched giant ellipticals. A recent study hinted that star-forming galaxies with large disks, so-called superluminous spirals and lenticulars, are the BCGs of a subset of galaxy clusters. Based on the existing optical data it was not possible to constrain whether the superluminous disk galaxies reside at the center of galaxy clusters. In this work, we utilize XMM-Newton X-ray observations of five galaxy clusters to map the morphology of the intracluster medium (ICM), characterize the galaxy clusters, determine the position of the cluster center, and measure the offset between the cluster center and the superluminous disk galaxies. We demonstrate that one superluminous lenticular galaxy, 2MASX J10405643-0103584, resides at the center of a low-mass ($M_{\rm 500} = 10^{14} \ \rm{M_{\odot}}$) galaxy cluster. This represents the first conclusive evidence that a superluminous disk galaxy is the central BCG of a galaxy cluster. We speculate that the progenitor of 2MASX J10405643-0103584 was an elliptical galaxy, whose extended disk was re-formed due to the merger of galaxies. We exclude the possibility that the other four superluminous disk galaxies reside at the center of galaxy clusters, as their projected distance from the cluster center is $150-1070$ kpc, which corresponds to $(0.27-1.18)R_{\rm 500}$. We conclude that these clusters host quiescent massive elliptical galaxies at their center.Comment: 7 pages, 3 figures, accepted for publication in the Astrophysical Journa

The Double Galaxy Cluster A2465. III. X-Ray and Weak-lensing Observations

We report Chandra X-ray observations and optical weak-lensing measurements from Subaru/Suprime-Cam images of the double galaxy cluster A2465 (z = 0.245). The X-ray brightness data are fit to a β model to obtain the radial gas density profiles of the northeast (NE) and southwest (SW) subcomponents, which are seen to differ in structure. We determine core radii, central temperatures, the gas masses within r 500c, and the total masses for the broader NE and sharper SW components assuming hydrostatic equilibrium. There is no large X-ray excess between the two components. The central entropy of the NE subcluster is about two times higher than the SW. Along with its structural properties and an apparent radio halo that is a sign of a merger, this suggests that the NE component has undergone merging on its own. The weak-lensing analysis gives virial masses for each substructure, which compare well with earlier dynamical results. The derived outer mass contours of the SW sub-component from weak lensing are more irregular and extended than those of the NE. Although there is a weak enhancement and small offsets between X-ray gas and mass centers from weak lensing, the lack of large amounts of gas between the two subclusters indicates that A2465 is in a pre-merger state. We discuss star formation enhancement in this system resulting from its dynamics and shock-induced star formation scenarios. A dynamical model that is consistent with the observed cluster data, based on the FLASH program and the radial infall model, is constructed, where the subclusters currently separated by ∼1.2 Mpc are approaching each other at ∼2000 km s-1 and will meet in ∼0.4 Gyr. Based in part on data collected at the Subaru Telescope, which is operated by the National Astronomical Society of Japan

Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data

Objective To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus.Design Systematic review and meta-analysis of individual patient data.Data sources Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013.Eligibility Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival.Results the search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a 56% reduction in the risk of non-melanoma skin cancer (0.44, 0.30 to 0.63) compared with controls. the most pronounced effect was seen in patients who converted to sirolimus from an established immunosuppressive regimen, resulting in a reduction in risk of malignancy (0.34, 0.28 to 0.41), non-melanoma skin cancer (0.32, 0.24 to 0.42), and other cancers (0.52, 0.38 to 0.69). Sirolimus was associated with an increased risk of death (1.43, 1.21 to 1.71) compared with controls.Conclusions Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients. the benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus. Given the risk of mortality, however, the use of this drug does not seem warranted for most patients with kidney transplant. Further research is needed to determine if different populations, such as those at high risk of cancer, might benefit from sirolimus.PfizerOttawa Hosp, Res Inst, Ottawa, ON K1H 7W9, CanadaUniv Ottawa, Ottawa, ON, CanadaCairo Univ, Cairo Kidney Ctr, Cairo, EgyptLimites Med Res, Vacallo, SwitzerlandUniv Manitoba, Dept Pediat & Childs Hlth, Winnipeg, MB, CanadaLund Univ, Dept Nephrol & Transplantat, Malmo, SwedenUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, São Paulo, BrazilAddenbrookes Hosp, Dept Renal Med, Cambridge, EnglandNorthwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USAMaastricht Univ, Med Ctr, Maastricht, NetherlandsSt Louis Hosp, Dept Nephrol, Paris, FranceHosp JW Goethe, Div Nephrol, Frankfurt, GermanyUniv Munich, Dept Surg, Munich, GermanyGoethe Univ Frankfurt, JW Goethe Clin, Clin Dermatol Venerol & Allergol, Frankfurt, GermanyInst Klin Expt Med, Dept Nephrol, Prague, Czech RepublicUniv Cambridge, Addenbrookes Hosp, Dept Surg, NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, EnglandUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, São Paulo, BrazilWeb of Scienc

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

Background: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. Methods: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. Results: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5–6.6), 9.4 (95% CI, 8.5–10.6), and 14 months (95% CI, 11.8–16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3–8.1), 12.7 (95% CI, 11.3–14.3), and 18.3 months (95% CI, 14.6–24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591–0.631) and 0.673 (95% CI, 0.636–0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). Conclusions: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design

Human Hereditary Cardiomyopathy Shares a Genetic Substrate With Bicuspid Aortic Valve.

The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes. We used CRISPR-Cas9 gene editing to generate mice harboring a nonsense or a missense MIB1 mutation that are both found in LVNC families. We also generated mice separately carrying these MIB1 mutations plus 5 additional cosegregating variants in the ASXL3, APCDD1, TMX3, CEP192, and BCL7A genes identified in these LVNC families by whole exome sequencing. Histological, developmental, and functional analyses of these mouse models were carried out by echocardiography and cardiac magnetic resonance imaging, together with gene expression profiling by RNA sequencing of both selected engineered mouse models and human induced pluripotent stem cell-derived cardiomyocytes. Potential biochemical interactions were assayed in vitro by coimmunoprecipitation and Western blot. Mice homozygous for the MIB1 nonsense mutation did not survive, and the mutation caused LVNC only in heteroallelic combination with a conditional allele inactivated in the myocardium. The heterozygous MIB1 missense allele leads to bicuspid aortic valve in a NOTCH-sensitized genetic background. These data suggest that development of LVNC is influenced by genetic modifiers present in affected families, whereas valve defects are highly sensitive to NOTCH haploinsufficiency. Whole exome sequencing of LVNC families revealed single-nucleotide gene variants of ASXL3, APCDD1, TMX3, CEP192, and BCL7A cosegregating with the MIB1 mutations and LVNC. In experiments with mice harboring the orthologous variants on the corresponding Mib1 backgrounds, triple heterozygous Mib1 Apcdd1 Asxl3 mice showed LVNC, whereas quadruple heterozygous Mib1 Cep192 Tmx3;Bcl7a mice developed bicuspid aortic valve and other valve-associated defects. Biochemical analysis suggested interactions between CEP192, BCL7A, and NOTCH. Gene expression profiling of mutant mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes revealed increased cardiomyocyte proliferation and defective morphological and metabolic maturation. These findings reveal a shared genetic substrate underlying LVNC and bicuspid aortic valve in which MIB1-NOTCH variants plays a crucial role in heterozygous combination with cosegregating genetic modifiers.This study was supported by grants PID2019-104776RB-I00 and PID2020-120326RB-I00, CB16/11/00399 (CIBER CV) financed by MCIN/AEI/10.13039/501100011033, a grant from the Fundación BBVA (Ref. BIO14_298), and a grant from Fundació La Marató de TV3 (Ref. 20153431) to J.L.d.l.P. M.S.-A. was supported by a PhD contract from the Severo Ochoa Predoctor-al Program (SVP-2014-068723) of the MCIN/AEI/10.13039/501100011033. J.R.G.-B. was supported by SEC/FEC-INV-BAS 21/021. A.R. was funded by grants from MCIN (PID2021123925OB-I00), TerCel (RD16/0011/0024), AGAUR (2017-SGR-899), and Fundació La Marató de TV3 (201534-30). J.M.P.-P. was supported by RTI2018-095410-B-I00 (MCIN) and PY2000443 (Junta de Andalucía). B.I. was supported by the European Commission (H2020-HEALTH grant No. 945118) and by MCIN (PID2019-107332RB-I00). DO’R was sup-ported by the Medical Research Council (MC-A658-5QEB0) and KAMcG by the British Heart Foundation (RG/19/6/34387, RE/18/4/34215). The cost of this publication was supported in part with funds from the European Regional Devel-opment Fund. The Centro Nacional de Investigaciones Cardiovasculares is sup-ported by the ISCIII, the MCIN, and the Pro Centro Nacional de Investigaciones Cardiovasculares Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020001041-S) financed by MCIN/AEI/10.13039/501100011033. For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising.S

Archeological patrimony spatial data infrastructure implementation: Tolmo de Minateda

En este artículo se presenta la solución desarrollada para una Infraestructura de Datos Espaciales Arqueológica incorporando productos geomáticos de muy alta resolución. El caso de estudio principal es el Parque Arqueológico del Tolmo de Minateda (Hellín, Albacete). Entre la información geográfica de alta resolución publicada se incluyen ortoimágenes, modelos digitales de superficie, nubes de puntos y el marco de referencia topográfico. En el artículo se describe el instrumental y la metodología empleadas en su producción. La IDE implementada intenta cumplir los estándares aplicables, integrando entre sus componentes un visualizador, un directorio de servicios, y un catálogo de metadatos de datos y servicios. Entre las características que diferencian al visualizador desarrollado de los convencionales en las IDE destaca la particularidad de permitir desplegar visualizadores 3D de algunos productos geomáticos, nubes de puntos y modelos texturizados. También se integra gestión de usuarios para controlar la información accesible en función de cada perfil. Finalmente, en el propio visor se incorporan herramientas de descarga de productos geomáticos. Para el proyecto se ha desarrollado un portal web a modo de gestor de contenidos disponible en: http://www.archaeo3dwebgis.com. Para la presentación del proyecto se ha preparado un vídeo accesible desde la propia web del proyecto o mediante el enlace: https://vimeo.com/242930977.In this article we present the solution developed for an Archeological SDI including very high resolution geomatic respurces. The main study case is the Archaeological Park of Tolmo de Minateda (Hellín, Albacete). High resolution published geographical information includes orthoimages, digital surface models, point clouds and the topographic reference frame. This article describes the instruments and methodology used in its production. The implemented SDI tries to be comnformant with applicable standards, integrating in its components a viewer, a services directory, and a catalog of data and services metadata. Among the characteristics that differentiate the developed visewer from the usual ones in other SDIs, it is remarkable the possibility of open 3D viewers for some geomatics products, point clouds and textured models. User management is also integrated to control the information accessible according to each profile. Finally, geomatic products download tools are incorporated into the viewer. For the project, a web portal has been developed as a content manager available at: http://www.archaeo3dwebgis.com. For the presentation of the project, a video has been prepared and it is accessible from the project website or through the link: https://vimeo.com/242930977

Correlations in the (Sub)millimeter background from ACTxBLAST

We present measurements of the auto- and cross-frequency correlation power spectra of the cosmic (sub)millimeter background at: 250, 350, and 500 um (1200, 860, and 600 GHz) from observations made with the Balloon-borne Large Aperture Submillimeter Telescope, BLAST; and at 1380 and 2030 um (218 and 148 GHz) from observations made with the Atacama Cosmology Telescope, ACT. The overlapping observations cover 8.6 deg^2 in an area relatively free of Galactic dust near the south ecliptic pole (SEP). The ACT bands are sensitive to radiation from the CMB, the Sunyaev-Zel'dovich (SZ) effect from galaxy clusters, and to emission by radio and dusty star-forming galaxies (DSFGs), while the dominant contribution to the BLAST bands is from DSFGs. We confirm and extend the BLAST analysis of clustering with an independent pipeline, and also detect correlations between the ACT and BLAST maps at over 25sigma significance, which we interpret as a detection of the DSFGs in the ACT maps. In addition to a Poisson component in the cross-frequency power spectra, we detect a clustered signal at >4sigma, and using a model for the DSFG evolution and number counts, we successfully fit all our spectra with a linear clustering model and a bias that depends only on redshift and not on scale. Finally, the data are compared to, and generally agree with, phenomenological models for the DSFG population. This study represents a first of its kind, and demonstrates the constraining power of the cross-frequency correlation technique to constrain models for the DSFGs. Similar analyses with more data will impose tight constraints on future models.Comment: 17 pages, 11 figure