Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening

Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. METHODS: In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. RESULTS: The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). CONCLUSIONS: Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy groupSupported by grants from Asociación Española contra el Cáncer (Fundación Científica and Junta de Barcelona), Instituto de Salud Carlos III (PI08/90717), FEDER funds, and Agència de Gestió d’Ajuts Universitaris i de Recerca (2009SGR849). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by Instituto de Salud Carlos III. In the Basque Country, the study received additional grants from Obra Social de Kutxa, Diputación Foral de Gipuzkoa (DFG 07/5), Departamento de Sanidad del Gobierno Vasco, EITB-Maratoia (BIO 07/ CA/19), and Acción Transversal contra el Cáncer del CIBERehd (2008). In Galicia, this work was supported by Dirección Xeral de Innovación e Xestión da Saúde Pública, Conselleria de Sanidade, and Xunta de Galicia. Eiken Chemical of Japan and its Spanish representatives, Palex Medical and Biogen Diagnóstica, donated supplies and automated analyzers used for FI

Effects of Impact and Target Parameters on the Results of a Kinetic Impactor: Predictions for the Double Asteroid Redirection Test (DART) Mission

The Double Asteroid Redirection Test (DART) spacecraft will impact into the asteroid Dimorphos on 2022 September 26 as a test of the kinetic impactor technique for planetary defense. The efficiency of the deflection following a kinetic impactor can be represented using the momentum enhancement factor, β, which is dependent on factors such as impact geometry and the specific target material properties. Currently, very little is known about Dimorphos and its material properties, which introduces uncertainty in the results of the deflection efficiency observables, including crater formation, ejecta distribution, and β. The DART Impact Modeling Working Group (IWG) is responsible for using impact simulations to better understand the results of the DART impact. Pre-impact simulation studies also provide considerable insight into how different properties and impact scenarios affect momentum enhancement following a kinetic impact. This insight provides a basis for predicting the effects of the DART impact and the first understanding of how to interpret results following the encounter. Following the DART impact, the knowledge gained from these studies will inform the initial simulations that will recreate the impact conditions, including providing estimates for potential material properties of Dimorphos and β resulting from DART’s impact. This paper summarizes, at a high level, what has been learned from the IWG simulations and experiments in preparation for the DART impact. While unknown, estimates for reasonable potential material properties of Dimorphos provide predictions for β of 1–5, depending on end-member cases in the strength regime

After DART: Using the First Full-scale Test of a Kinetic Impactor to Inform a Future Planetary Defense Mission

NASA’s Double Asteroid Redirection Test (DART) is the first full-scale test of an asteroid deflection technology. Results from the hypervelocity kinetic impact and Earth-based observations, coupled with LICIACube and the later Hera mission, will result in measurement of the momentum transfer efficiency accurate to ∼10% and characterization of the Didymos binary system. But DART is a single experiment; how could these results be used in a future planetary defense necessity involving a different asteroid? We examine what aspects of Dimorphos’s response to kinetic impact will be constrained by DART results; how these constraints will help refine knowledge of the physical properties of asteroidal materials and predictive power of impact simulations; what information about a potential Earth impactor could be acquired before a deflection effort; and how design of a deflection mission should be informed by this understanding. We generalize the momentum enhancement factor β, showing that a particular direction-specific β will be directly determined by the DART results, and that a related direction-specific β is a figure of merit for a kinetic impact mission. The DART β determination constrains the ejecta momentum vector, which, with hydrodynamic simulations, constrains the physical properties of Dimorphos’s near-surface. In a hypothetical planetary defense exigency, extrapolating these constraints to a newly discovered asteroid will require Earth-based observations and benefit from in situ reconnaissance. We show representative predictions for momentum transfer based on different levels of reconnaissance and discuss strategic targeting to optimize the deflection and reduce the risk of a counterproductive deflection in the wrong direction

After DART: Using the first full-scale test of a kinetic impactor to inform a future planetary defense mission

NASA's Double Asteroid Redirection Test (DART) is the first full-scale test of an asteroid deflection technology. Results from the hypervelocity kinetic impact and Earth-based observations, coupled with LICIACube and the later Hera mission, will result in measurement of the momentum transfer efficiency accurate to ~10% and characterization of the Didymos binary system. But DART is a single experiment; how could these results be used in a future planetary defense necessity involving a different asteroid? We examine what aspects of Dimorphos's response to kinetic impact will be constrained by DART results; how these constraints will help refine knowledge of the physical properties of asteroidal materials and predictive power of impact simulations; what information about a potential Earth impactor could be acquired before a deflection effort; and how design of a deflection mission should be informed by this understanding. We generalize the momentum enhancement factor $\beta$, showing that a particular direction-specific $\beta$ will be directly determined by the DART results, and that a related direction-specific $\beta$ is a figure of merit for a kinetic impact mission. The DART $\beta$ determination constrains the ejecta momentum vector, which, with hydrodynamic simulations, constrains the physical properties of Dimorphos's near-surface. In a hypothetical planetary defense exigency, extrapolating these constraints to a newly discovered asteroid will require Earth-based observations and benefit from in-situ reconnaissance. We show representative predictions for momentum transfer based on different levels of reconnaissance and discuss strategic targeting to optimize the deflection and reduce the risk of a counterproductive deflection in the wrong direction

After DART: Using the First Full-scale Test of a Kinetic Impactor to Inform a Future Planetary Defense Mission

After DART: Using the First Full-scale Test of a Kinetic Impactor to Inform a Future Planetary Defense Mission Thomas S. Statler 1 , Sabina D. Raducan 2 , Olivier S. Barnouin 3 , Mallory E. DeCoster 3 , Steven R. Chesley 4 , Brent Barbee 5 , Harrison F. Agrusa 6 , Saverio Cambioni 7 , Andrew F. Cheng 3 , Elisabetta Dotto 8 , Siegfried Eggl9 , Eugene G. Fahnestock 4 , Fabio Ferrari 2 , Dawn Graninger 3 , Alain Herique 10 , Isabel Herreros 11 , Masatoshi Hirabayashi 12,13 , Stavro Ivanovski 14 , Martin Jutzi 2 , Özgür Karatekin 15 , Alice Lucchetti 16 , Robert Luther 17 , Rahil Makadia 9 , Francesco Marzari 18 , Patrick Michel 19 , Naomi Murdoch 20 , Ryota Nakano13 , Jens Ormö 11 , Maurizio Pajola 16 , Andrew S. Rivkin3 , Alessandro Rossi 21 , Paul Sánchez 22 , Stephen R. Schwartz 23 , Stefania Soldini 24 , Damya Souami 19 , Angela Stickle 3 , Paolo Tortora 25 , Josep M. Trigo-Rodríguez 26,27 , Flaviane Venditti 28 , Jean-Baptiste Vincent 29 , and Kai Wünnemann 17,30 1 Planetary Defense Coordination Office and Planetary Science Division, NASA Headquarters, 300 Hidden Figures Way SW, Washington, DC 20546, USA [email protected] 2 Space Research and Planetary Sciences, Physics Institute, University of Bern, Bern, 3012, Switzerland 3 Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA 4 Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA 5 NASA Goddard Space Flight Center, Greenbelt, MD 20771, USA 6 Department of Astronomy, University of Maryland, College Park, MD 20742, USA 7 Department of Earth, Atmospheric & Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA 8 INAF-Osservatorio Astronomico di Roma, Rome, I-00078, Italy 9 Department of Aerospace Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA 10 Univ. Grenoble Alpes, CNRS, CNES, IPAG, F-38000 Grenoble, France 11 Centro de Astrobiología CSIC-INTA, Instituto Nacional de Técnica Aeroespacial, E-28850 Torrejón de Ardoz, Spain 12 Department of Geosciences, Auburn University, Auburn, AL 36849, USA 13 Department of Aerospace Engineering, Auburn University, Auburn, AL 36849, USA 14 INAF- Osservatorio Astronomico di Trieste, Trieste I-34143, Italy 15 Royal Observatory of Belgium, Belgium 16 INAF-Astronomical Observatory of Padova, Padova I-35122, Italy 17 Museum für Naturkunde—Leibniz Institute for Evolution and Biodiversity Science, Germany 18 University of Padova, Padova, Italy 19 Université Côte d’Azur, Observatoire de la Côte d’Azur, CNRS, Laboratoire Lagrange, Nice F-06304, France 20 Institut Supérieur de l’Aéronautique et de l’Espace (ISAE-SUPAERO), Université de Toulouse, Toulouse, France 21 IFAC-CNR, Sesto Fiorentino I-50019, Italy 22 Colorado Center for Astrodynamics Research, University of Colorado Boulder, Boulder, CO 80303, USA 23 Planetary Science Institute, Tucson, AZ 85719, USA 24 Department of Mechanical, Materials and Aerospace Engineering, University of Liverpool, Liverpool, UK 25 Alma Mater Studiorum—Università di Bologna, Department of Industrial Engineering, Interdepartmental Center for Industrial Research in Aerospace, Via Fontanelle 40—Forlì (FC)—I-47121, Italy 26 Institute of Space Sciences (ICE, CSIC), Cerdanyola del Vallès, E-08193 Barcelona, Catalonia, Spain 27 Institut d’Estudis Espacials de Catalunya (IEEC), Ed. Nexus, E-08034 Barcelona, Catalonia, Spain 28 Arecibo Observatory, University of Central Florida, HC-3 Box 53995, Arecibo, PR 00612, USA 29 German Aerospace Center, DLR Berlin, Germany 30 Freie Universität Berlin, Germany Received 2022 August 9; revised 2022 September 18; accepted 2022 September 22; published 2022 October 28 Abstract NASA’s Double Asteroid Redirection Test (DART) is the first full-scale test of an asteroid deflection technology. Results from the hypervelocity kinetic impact and Earth-based observations, coupled with LICIACube and the later Hera mission, will result in measurement of the momentum transfer efficiency accurate to ∼10% and characterization of the Didymos binary system. But DART is a single experiment; how could these results be used in a future planetary defense necessity involving a different asteroid? We examine what aspects of Dimorphos’s response to kinetic impact will be constrained by DART results; how these constraints will help refine knowledge of the physical properties of asteroidal materials and predictive power of impact simulations; what information about a potential Earth impactor could be acquired before a deflection effort; and how design of a deflection mission should be informed by this understanding. We generalize the momentum enhancement factor β, showing that a particular direction-specific β will be directly determined by the DART results, and that a related direction- specific β is a figure of merit for a kinetic impact mission. The DART β determination constrains the ejecta momentum vector, which, with hydrodynamic simulations, constrains the physical properties of Dimorphos’s near- surface. In a hypothetical planetary defense exigency, extrapolating these constraints to a newly discovered asteroid will require Earth-based observations and benefit from in situ reconnaissance. We show representative predictions for momentum transfer based on different levels of reconnaissance and discuss strategic targeting to optimize the deflection and reduce the risk of a counterproductive deflection in the wrong direction

Achievement of the planetary defense investigations of the Double Asteroid Redirection Test (DART) mission

NASA's Double Asteroid Redirection Test (DART) mission was the first to demonstrate asteroid deflection, and the mission's Level 1 requirements guided its planetary defense investigations. Here, we summarize DART's achievement of those requirements. On 2022 September 26, the DART spacecraft impacted Dimorphos, the secondary member of the Didymos near-Earth asteroid binary system, demonstrating an autonomously navigated kinetic impact into an asteroid with limited prior knowledge for planetary defense. Months of subsequent Earth-based observations showed that the binary orbital period was changed by –33.24 minutes, with two independent analysis methods each reporting a 1σ uncertainty of 1.4 s. Dynamical models determined that the momentum enhancement factor, β, resulting from DART's kinetic impact test is between 2.4 and 4.9, depending on the mass of Dimorphos, which remains the largest source of uncertainty. Over five dozen telescopes across the globe and in space, along with the Light Italian CubeSat for Imaging of Asteroids, have contributed to DART's investigations. These combined investigations have addressed topics related to the ejecta, dynamics, impact event, and properties of both asteroids in the binary system. A year following DART's successful impact into Dimorphos, the mission has achieved its planetary defense requirements, although work to further understand DART's kinetic impact test and the Didymos system will continue. In particular, ESA's Hera mission is planned to perform extensive measurements in 2027 during its rendezvous with the Didymos–Dimorphos system, building on DART to advance our knowledge and continue the ongoing international collaboration for planetary defense

Effects of impact and target parameters on the results of a kinetic impactor: predictions for the Double Asteroid Redirection Test (DART) mission

The Double Asteroid Redirection Test (DART) spacecraft will impact into the asteroid Dimorphos on September 26, 2022 as a test of the kinetic impactor technique for planetary defense. The efficiency of the deflection following a kinetic impactor can be represented using the momentum enhancement factor, Beta, which is dependent on factors such as impact geometry and the specific target material properties. Currently, very little is known about Dimorphos and its material properties that introduces uncertainty in the results of the deflection efficiency observables, including crater formation, ejecta distribution, and Beta. The DART Impact Modeling Working Group (IWG) is responsible for using impact simulations to better understand the results of the DART impact. Pre-impact simulation studies also provide considerable insight into how different properties and impact scenarios affect momentum enhancement following a kinetic impact. This insight provides a basis for predicting the effects of the DART impact and the first understanding of how to interpret results following the encounter. Following the DART impact, the knowledge gained from these studies will inform the initial simulations that will recreate the impact conditions, including providing estimates for potential material properties of Dimorphos and Beta resulting from DARTs impact. This paper summarizes, at a high level, what has been learned from the IWG simulations and experiments in preparation for the DART impact. While unknown, estimates for reasonable potential material properties of Dimorphos provide predictions for Beta of 1-5, depending on end-member cases in the strength regime.This work was supported by the DART mission, NASA contract No. 80MSFC20D0004. This work has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 870377 (project, NEO-MAPP) and from the French space agency CNES and the CNRS through the MITI interdisciplinary programs. We gratefully acknowledge the developers of iSALE-2D (www.isale-code.de) including Dirk Elbeshausen, Boris Ivanov, and Jay Melosh. This work was supported by the Italian Space Agency (ASI) within the LICIACube project (ASI-INAF agreement AC n.2019-31-HH.0; C.B. and C.M.S. appreciate support by the German Research Foundation (DFG) project 39848852. Alice Lucchetti, Maurizio Pajola, and all other coauthors from the LICIACube team acknowledge financial support from Agenzia Spaziale Italiana (ASI, contract No. 2019-31-HH.0). J.O. and I.H. were supported by the Spanish State Research Agency (AEI) Project No. MDM-2017-0737 Unidad de Excelencia “María de Maeztu”—Centro de Astrobiología (CSIC-INTA). They are also grateful for all logistical support provided by Instituto Nacional de Técnica Aeroespacial (INTA). Parts of this work were performed under the auspices of the US Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. LLNLJRNL-831475. This work was supported in part by a Chick Keller Postdoctoral Fellowship through the Center for Space and Earth Science at Los Alamos National Laboratory. Parts of this work were supported by the Advanced Simulation and Computing (ASC)—Threat Reduction and ASC—Planetary Defense programs. Los Alamos National Laboratory, an affirmative action/equal opportunity employer, is operated by Triad National Security, LLC, for the National Nuclear Security Administration of the US Department of Energy under contract 89233218NCA000001. LA-UR-22-21164

Wilms' tumor protein induces an epithelial-mesenchymal hybrid differentiation state in clear cell renal cell carcinoma

The Wilms' tumor transcription factor (WT1) was originally classified as a tumor suppressor, but it is now known to also be associated with cancer progression and poor prognosis in several malignancies. WT1 plays an essential role in orchestrating a developmental process known as mesenchymal-to-epithelial transition (MET) during kidney development, but also induces the reverse process, epithelial-to-mesenchymal transition (EMT) during heart development. WT1 is not expressed in the adult kidney, but shows elevated expression in clear cell renal cell carcinoma (ccRCC). However, the role of WT1 in this disease has not been characterized. In this study, we demonstrate that WT1 is upregulated in ccRCC cells that are deficient in the expression of the von Hippel-Lindau tumor suppressor protein (VHL). We found that WT1 transcriptionally activated Snail, a master transcriptional repressor that is known to induce EMT. Although Snail represses E-cadherin and induces mesenchymal characteristics, we found partial maintenance of E-cadherin and associated epithelial characteristics in kidney cells and ccRCC cells that express WT1, since WT1 upregulates E-cadherin expression and competes with Snail repression. These findings support a novel paradigm in which WT1 induces an epithelial-mesenchymal hybrid transition (EMHT), characterized by Snail up-regulation with E-cadherin maintenance, a tumor cell differentiation state in which cancer cells keep both EMT and MET characteristics which may promote tumor cell plasticity and tumor progression.NIH grants P20GM103464 (Dr. Thomas Shaffer), DK56216 and the Nemours Foundation (A.K. Rajasekaran), SAF2010-16089 (A.G. de Herreros