Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

BackgroundIn the Prostate Cancer Prevention Trial, finasteride selectively suppressed low-grade prostate cancer and significantly reduced the incidence of prostate cancer in men treated with finasteride compared with placebo. However, an apparent increase in high-grade disease was also observed among men randomized to finasteride. We aimed to determine why and hypothesized that there is a grade-dependent response to finasteride.MethodsFrom 2007 to 2012, we randomized dynamically by intranet-accessible software 183 men with localized prostate cancer to receive 5mg finasteride or placebo daily in a double-blind study during the 4-6weeks preceding prostatectomy. As the primary end point, the expression of a predefined molecular signature (ERβ, UBE2C, SRD5A2, and VEGF) differentiating high- and low-grade tumors in Gleason grade (GG) 3 areas of finasteride-exposed tumors from those in GG3 areas of placebo-exposed tumors, adjusted for Gleason score (GS) at prostatectomy, was compared. We also determined androgen receptor (AR) levels, Ki-67, and cleaved caspase 3 to evaluate the effects of finasteride on the expression of its downstream target, cell proliferation, and apoptosis, respectively. The expression of these markers was also compared across grades between and within treatment groups. Logistic regression was used to assess the expression of markers.FindingsWe found that the predetermined molecular signature did not distinguish GG3 from GG4 areas in the placebo group. However, AR expression was significantly lower in the GG4 areas of the finasteride group than in those of the placebo group. Within the finasteride group, AR expression was also lower in GG4 than in GG3 areas, but not significantly. Expression of cleaved caspase 3 was significantly increased in both GG3 and GG4 areas in the finasteride group compared to the placebo group, although it was lower in GG4 than in GG3 areas in both groups.InterpretationWe showed that finasteride's effect on apoptosis and AR expression is tumor grade dependent after short-term intervention. This may explain finasteride's selective suppression of low-grade tumors observed in the PCPT

The Inter-organizational Business Case in ES Implementations: Exploring the Impact of Coordination Structures and Their Properties

Developing the business case (BC) for an inter-organizational network is a major challenge. Factors like competition and differences in semantics between actors influence the stakeholders’ willingness to share information necessary for the BC development. In this paper we develop an exploratory framework showing the effect that coordination structure and project scope have on the development of a shared BC. We defined several coordination properties, such as competition, decision making location and decision power that mitigate this effect. We applied the framework in a case study where a BC is developed for an inter-organizational network. Our findings show that current BC development methods need to be re-stated and complemented by extra tools and interventions to support stakeholders in the inter-organizational specific setting

Multiple Front Propagation Into Unstable States

The dynamics of transient patterns formed by front propagation in extended nonequilibrium systems is considered. Under certain circumstances, the state left behind a front propagating into an unstable homogeneous state can be an unstable periodic pattern. It is found by a numerical solution of a model of the Fr\'eedericksz transition in nematic liquid crystals that the mechanism of decay of such periodic unstable states is the propagation of a second front which replaces the unstable pattern by a another unstable periodic state with larger wavelength. The speed of this second front and the periodicity of the new state are analytically calculated with a generalization of the marginal stability formalism suited to the study of front propagation into periodic unstable states. PACS: 47.20.Ky, 03.40.Kf, 47.54.+rComment: 12 page

GAMBE: Thermal neutron detection system based on a sandwich configuration of silicon semiconductor detector coupled with neutron reactive material

© 2019 Elsevier Ltd Silicon semiconductor detectors are used efficiently for neutron detection when coated with a suitable material. They detect secondary reaction products resulting from the interaction of thermal neutrons with a neutron sensitive material such as 6 LiF. In the present work, the efficiency of the thermal neutron detector system, GAMBE, is discussed. This detector system based on two silicon sensors of 1 cm 2 active area and a layer of 6 LiF (1.5±0.6) mg/cm 2 thick in a sandwich configuration. This arrangement achieves total and coincidence detection efficiency of (4.1±0.5)% and (0.9±0.3)% respectively. The coincidence method defines a true neutron hit by the simultaneous signal recorded by the two sensors facing the conversion film. This coincidence methodology is applied to enhance the rejection factor of fake hits due to high gamma background conditions up to 10 8 as discussed in previous work. Geant simulation indicates that total and coincidence detection efficiency up to 55% and 18% are possible using an advanced design of stacked detectors

The Close AGN Reference Survey (CARS) A massive multi-phase outflow impacting the edge-on galaxy HE 1353-1917

Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Open Access funding provided by Max Planck Society.Context. Galaxy-wide outflows driven by star formation and/or an active galactic nucleus (AGN) are thought to play a crucial rule in the evolution of galaxies and the metal enrichment of the inter-galactic medium. Direct measurements of these processes are still scarce and new observations are needed to reveal the nature of outflows in the majority of the galaxy population. Aims. We combine extensive, spatially-resolved, multi-wavelength observations, taken as part of the Close AGN Reference Survey (CARS), for the edge-on disc galaxy HE 1353-1917 in order to characterise the impact of the AGN on its host galaxy via outflows and radiation. Methods. Multi-color broad-band photometry was combined with spatially-resolved optical, near-infrared (NIR) and sub-mm and radio observations taken with the Multi-Unit Spectroscopy Explorer (MUSE), the Near-infrared Integral Field Spectrometer (NIFS), the Atacama Large Millimeter Array (ALMA), and the Karl G. Jansky Very Large Array (VLA) to map the physical properties and kinematics of the multi-phase interstellar medium. Results. We detect a biconical extended narrow-line region ionised by the luminous AGN orientated nearly parallel to the galaxy disc, extending out to at least 25 kpc. The extra-planar gas originates from galactic fountains initiated by star formation processes in the disc, rather than an AGN outflow, as shown by the kinematics and the metallicity of the gas. Nevertheless, a fast, multi-phase, AGN-driven outflow with speeds up to 1000 km s(-1) is detected close to the nucleus at 1 kpc distance. A radio jet, in connection with the AGN radiation field, is likely responsible for driving the outflow as confirmed by the energetics and the spatial alignment of the jet and multi-phase outflow. Evidence for negative AGN feedback suppressing the star formation rate (SFR) is mild and restricted to the central kpc. But while any SFR suppression must have happened recently, the outflow has the potential to greatly impact the future evolution of the galaxy disc due to its geometrical orientation. Conclusions.. Our observations reveal that low-power radio jets can play a major role in driving fast, multi-phase, galaxy-scale outflows even in radio-quiet AGN. Since the outflow energetics for HE 1353-1917 are consistent with literature, scaling relation of AGN-driven outflows the contribution of radio jets as the driving mechanisms still needs to be systematically explored.© B. Husemann et al. 2019We thank the referee for providing very valuable comments, which significantly improved the quality of the manuscript. MK acknowledges support from DLR grant 50OR1802. GRT acknowledges support from the NASA through Einstein Postdoctoral Fellowship Award Number PF-150128, issued by the Chandra X-ray Observatory Center, which is operated by the Smithsonian Astrophysical Observatory for and on behalf of NASA under contract NAS8-03060. MG is supported by the Lyman Spitzer Jr. Fellowship (Princeton University) and by NASA Chandra grants GO7-18121X/GO8-19104X. SMC acknowledges support from the Australian Research Council (DP190102714). We thank Alex Markowitz for helpful discussions on the RGS data in the context of warm absorbers. The work of SAB, CPO and MS was supported by a generous grant from the Natural Sciences and Engineering Research Council of Canada. Based on observations collected at the European Organization for Astronomical Research in the Southern Hemisphere under ESO programme 095. B-0015(A). Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), National Research Council (Canada), CONICYT (Chile), Ministerio de Ciencia, Tecnologia e Innovacion Productiva (Argentina), Ministerio da Ciencia, Tecnologia e Inovacao (Brazil), and Korea Astronomy and Space Science Institute (Republic of Korea). Based on observations obtained at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministerio da Ciencia, Tecnologia, Inovacoes e Comunicacoes (MCTIC) do Brasil, the U.S. National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU). Based on observations collected at the German-Spanish Astronomical Center, Calar Alto, jointly operated by the Max-Planck-Institut fur Astronomie Heidelberg and the Instituto de Astrofiica de Andaluci (CSIC). This paper makes use of the following ALMA data: ADS/JAO.ALMA#2016.1.00952. S. ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada), MOST and ASIAA (Taiwan), and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO and NAOJ. This work is based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and NASA. The VLA is operated by the National Radio Astronomy Observatory, a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA. This publication makes use of data products from the Wide-field Infrared Survey Explorer, which is a joint project of the University of California, Los Angeles, and the Jet Propulsion Laboratory/California Institute of Technology, funded by the National Aeronautics and Space Administration. This research has made use of the NASA/IPAC Infrared Science Archive, which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. The Pan-STARRS1 Surveys (PS1) and the PS1 public science archive have been made possible through contributions by the Institute for Astronomy, the University of Hawaii, the Pan-STARRS Project Office, the Max-Planck Society and its participating institutes, the Max Planck Institute for Astronomy, Heidelberg and the Max Planck Institute for Extraterrestrial Physics, Garching, The Johns Hopkins University, Durham University, the University of Edinburgh, the Queen's University Belfast, the Harvard-Smithsonian Center for Astrophysics, the Las Cumbres Observatory Global Telescope Network Incorporated, the National Central University of Taiwan, the Space Telescope Science Institute, the National Aeronautics and Space Administration under Grant No. NNX08AR22G issued through the Planetary Science Division of the NASA Science Mission Directorate, the National Science Foundation Grant No. AST-1238877, the University of Maryland, Eotvos Lorand University (ELTE), the Los Alamos National Laboratory, and the Gordon and Betty Moore Foundation. This work is based in part on observations made with the Galaxy Evolution Explorer (GALEX). GALEX is a NASA Small Explorer, whose mission was developed in cooperation with the Centre National d'Etudes Spatiales (CNES) of France and the Korean Ministry of Science and Technology. GALEX is operated for NASA by the California Institute of Technology under NASA contract NAS5-98034

Organisational barriers to the facilitation of overseas volunteering and training placements in the NHS

Background Undertaking a period of voluntary work or a professional placement overseas has long been a feature of medical training in the UK. There are now a number of high profile National Health Service (NHS) initiatives aimed at increasing access to such opportunities for staff at all levels. We present findings from a qualitative study involving a range of NHS staff and other stakeholders which explored barriers to participation in these activities. Methods A grounded theory methodology was drawn upon to conduct thematic based analysis. Our data included in-depth, semi-structured interviews with a range of returned volunteers, non-volunteers and other stakeholders (n=51) who were, or had been, employed by the NHS. Results There are significant barriers to placement and volunteering activity stemming from structural and organisational shortcomings within the NHS. Difficulties in filling clinical roles has a significant impact on the ability of staff to plan and undertake independent placements. There is currently no clearly defined pathway within the NHS by which the majority of grades can apply for, or organise, a period of overseas voluntary or professional placement activity. There were divergent views on the relevance and usefulness of overseas professional placements. Conclusions We argue that in the context of current UK policy initiatives aimed at facilitating overseas volunteer and professional placement activity, urgent attention needs to be given to the structural and organisational framework within which such initiatives will be required to work