A Cosmic Census of Radio Pulsars with the SKA

The Square Kilometre Array (SKA) will make ground breaking discoveries in pulsar science. In this chapter we outline the SKA surveys for new pulsars, as well as how we will perform the necessary follow-up timing observations. The SKA's wide field-of-view, high sensitivity, multi-beaming and sub-arraying capabilities, coupled with advanced pulsar search backends, will result in the discovery of a large population of pulsars. These will enable the SKA's pulsar science goals (tests of General Relativity with pulsar binary systems, investigating black hole theorems with pulsar-black hole binaries, and direct detection of gravitational waves in a pulsar timing array). Using SKA1-MID and SKA1-LOW we will survey the Milky Way to unprecedented depth, increasing the number of known pulsars by more than an order of magnitude. SKA2 will potentially find all the Galactic radio-emitting pulsars in the SKA sky which are beamed in our direction. This will give a clear picture of the birth properties of pulsars and of the gravitational potential, magnetic field structure and interstellar matter content of the Galaxy. Targeted searches will enable detection of exotic systems, such as the ~1000 pulsars we infer to be closely orbiting Sgr A*, the supermassive black hole in the Galactic Centre. In addition, the SKA's sensitivity will be sufficient to detect pulsars in local group galaxies. To derive the spin characteristics of the discoveries we will perform live searches, and use sub-arraying and dynamic scheduling to time pulsars as soon as they are discovered, while simultaneously continuing survey observations. The large projected number of discoveries suggests that we will uncover currently unknown rare systems that can be exploited to push the boundaries of our understanding of astrophysics and provide tools for testing physics, as has been done by the pulsar community in the past.Comment: 20 pages, 7 figures, to be published in: "Advancing Astrophysics with the Square Kilometre Array", Proceedings of Science, PoS(AASKA14)04

A Search for Pulsars around Sgr A* in the First Event Horizon Telescope Data Set

Full list of the authors: Torne, Pablo; Liu, Kuo; Eatough, Ralph P.; Wongphechauxsorn, Jompoj; Cordes, James M.; Desvignes, Gregory; De Laurentis, Mariafelicia; Kramer, Michael; Ransom, Scott M.; Chatterjee, Shami; Wharton, Robert; Karuppusamy, Ramesh; Blackburn, Lindy; Janssen, Michael; Chan, Chi-kwan; Crew, Geoffrey, B.; Matthews, Lynn D.; Goddi, Ciriaco; Rottmann, Helge; Wagner, Jan; Sánchez, Salvador; Ruiz, Ignacio; Abbate, Federico; Bower, Geoffrey C.; Salamanca, Juan J.; Gómez-Ruiz, Arturo I.; Herrera-Aguilar, Alfredo; Jiang, Wu; Lu, Ru-Sen; Pen, Ue-Li; Raymond, Alexander W.; Shao, Lijing; Shen, Zhiqiang; Paubert, Gabriel; Sanchez-Portal, Miguel; Kramer, Carsten; Castillo, Manuel; Navarro, Santiago; John, David; Schuster, Karl-Friedrich; Johnson, Michael D.; Rygl, Kazi L. J.; Akiyama, Kazunori; Alberdi, Antxon; Alef, Walter; Algaba, Juan Carlos; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Bach, Uwe; Baczko, Anne-Kathrin; Ball, David; Baloković, Mislav; Barrett, John; Bauböck, Michi; Benson, Bradford A.; Bintley, Dan; Blundell, Raymond; Bouman, Katherine L.; Boyce, Hope; Bremer, Michael; Brinkerink, Christiaan D.; Brissenden, Roger; Britzen, Silke; Broderick, Avery E.; Broguiere, Dominique; Bronzwaer, Thomas; Bustamante, Sandra; Byun, Do-Young; Carlstrom, John E.; Ceccobello, Chiara; Chael, Andrew; Chang, Dominic O.; Chatterjee, Koushik; Chen, Ming-Tang; Chen, Yongjun; Cheng, Xiaopeng; Cho, Ilje; Christian, Pierre; Conroy, Nicholas S.; Conway, John E.; Crawford, Thomas M.; Cruz-Osorio, Alejandro; Cui, Yuzhu; Dahale, Rohan; Davelaar, Jordy; Deane, Roger; Dempsey, Jessica; Dexter, Jason; Dhruv, Vedant; Doeleman, Sheperd S.; Dougal, Sean; Dzib, Sergio A.; Emami, Razieh; Falcke, Heino; Farah, Joseph; Fish, Vincent L.; Fomalont, Ed; Ford, H. Alyson; Foschi, Marianna; Fraga-Encinas, Raquel; Freeman, William T.; Friberg, Per; Fromm, Christian M.; Fuentes, Antonio; Galison, Peter; Gammie, Charles F.; García, Roberto; Gentaz, Olivier; Georgiev, Boris; Gold, Roman; Gómez, José L.; Gu, Minfeng; Gurwell, Mark; Hada, Kazuhiro; Haggard, Daryl; Haworth, Kari; Hecht, Michael H.; Hesper, Ronald; Heumann, Dirk; Ho, Luis C.; Ho, Paul; Honma, Mareki; Huang, Chih-Wei L.; Huang, Lei; Hughes, David H.; Ikeda, Shiro; Impellizzeri, C. M. Violette; Inoue, Makoto; Issaoun, Sara; James, David J.; Jannuzi, Buell T.; Jeter, Britton; Jiménez-Rosales, Alejandra; Jorstad, Svetlana; Joshi, Abhishek V.; Jung, Taehyun; Karami, Mansour; Kawashima, Tomohisa; Keating, Garrett K.; Kettenis, Mark; Kim, Dong-Jin; Kim, Jae-Young; Kim, Jongsoo; Kim, Junhan; Kino, Motoki; Koay, Jun Yi; Kocherlakota, Prashant; Kofuji, Yutaro; Koyama, Shoko; Krichbaum, Thomas P.; Kuo, Cheng-Yu; La Bella, Noemi; Lauer, Tod R.; Lee, Daeyoung; Lee, Sang-Sung; Leung, Po Kin; Levis, Aviad; Li, Zhiyuan; Lico, Rocco; Lindahl, Greg; Lindqvist, Michael; Lisakov, Mikhail; Liu, Jun; Liuzzo, Elisabetta; Lo, Wen-Ping; Lobanov, Andrei P.; Loinard, Laurent; Lonsdale, Colin J.; MacDonald, Nicholas R.; Mao, Jirong; Marchili, Nicola; Markoff, Sera; Marrone, Daniel P.; Marscher, Alan P.; Martí-Vidal, Iván; Matsushita, Satoki; Medeiros, Lia; Menten, Karl M.; Michalik, Daniel; Mizuno, Izumi; Mizuno, Yosuke; Moran, James M.; Moriyama, Kotaro; Moscibrodzka, Monika; Müller, Cornelia; Müller, Hendrik; Mus, Alejandro; Musoke, Gibwa; Myserlis, Ioannis; Nadolski, Andrew; Nagai, Hiroshi; Nagar, Neil M.; Nakamura, Masanori; Narayan, Ramesh; Narayanan, Gopal; Natarajan, Iniyan; Nathanail, Antonios; Neilsen, Joey; Neri, Roberto; Ni, Chunchong; Noutsos, Aristeidis; Nowak, Michael A.; Oh, Junghwan; Okino, Hiroki; Olivares, Héctor; Ortiz-León, Gisela N.; Oyama, Tomoaki; Özel, Feryal; Palumbo, Daniel C. M.; Paraschos, Georgios Filippos; Park, Jongho; Parsons, Harriet; Patel, Nimesh; Pesce, Dominic W.; Piétu, Vincent; Plambeck, Richard; PopStefanija, Aleksandar; Porth, Oliver; Pötzl, Felix M.; Prather, Ben; Preciado-López, Jorge A.; Psaltis, Dimitrios; Pu, Hung-Yi; Ramakrishnan, Venkatessh; Rao, Ramprasad; Rawlings, Mark G.; Rezzolla, Luciano; Ricarte, Angelo; Ripperda, Bart; Roelofs, Freek; Rogers, Alan; Ros, Eduardo; Romero-Cañizales, Cristina; Roshanineshat, Arash; Roy, Alan L.; Ruszczyk, Chet; Sánchez-Argüelles, David; Sasada, Mahito; Satapathy, Kaushik; Savolainen, Tuomas; Schloerb, F. Peter; Schonfeld, Jonathan; Small, Des; Sohn, Bong Won; SooHoo, Jason; Souccar, Kamal; Sun, He; Tetarenko, Alexandra J.; Tiede, Paul; Tilanus, Remo P. J.; Titus, Michael; Toscano, Teresa; Traianou, Efthalia; Trent, Tyler; Trippe, Sascha; Turk, Matthew; van Bemmel, Ilse; van Langevelde, Huib Jan; van Rossum, Daniel R.; Vos, Jesse; Ward-Thompson, Derek; Wardle, John; Weintroub, Jonathan; Wex, Norbert; Wielgus, Maciek; Wiik, Kaj; Witzel, Gunther; Wondrak, Michael F.; Wong, George N.; Wu, Qingwen; Yadlapalli, Nitika; Yamaguchi, Paul; Yfantis, Aristomenis; Yoon, Doosoo; Young, André; Young, Ken; Younsi, Ziri; Yu, Wei; Yuan, Feng; Yuan, Ye-Fei; Zensus, J. Anton; Zhang, Shuo; Zhao, Guang-Yao; Zhao, Shan-ShanIn 2017 the Event Horizon Telescope (EHT) observed the supermassive black hole at the center of the Milky Way, Sagittarius A* (Sgr A*), at a frequency of 228.1 GHz (λ = 1.3 mm). The fundamental physics tests that even a single pulsar orbiting Sgr A* would enable motivate searching for pulsars in EHT data sets. The high observing frequency means that pulsars—which typically exhibit steep emission spectra—are expected to be very faint. However, it also negates pulse scattering, an effect that could hinder pulsar detections in the Galactic center. Additionally, magnetars or a secondary inverse Compton emission could be stronger at millimeter wavelengths than at lower frequencies. We present a search for pulsars close to Sgr A* using the data from the three most sensitive stations in the EHT 2017 campaign: the Atacama Large Millimeter/submillimeter Array, the Large Millimeter Telescope, and the IRAM 30 m Telescope. We apply three detection methods based on Fourier-domain analysis, the fast folding algorithm, and single-pulse searches targeting both pulsars and burst-like transient emission. We use the simultaneity of the observations to confirm potential candidates. No new pulsars or significant bursts were found. Being the first pulsar search ever carried out at such high radio frequencies, we detail our analysis methods and give a detailed estimation of the sensitivity of the search. We conclude that the EHT 2017 observations are only sensitive to a small fraction (≲2.2%) of the pulsars that may exist close to Sgr A*, motivating further searches for fainter pulsars in the region. © 2023. The Author(s). Published by the American Astronomical Society.We are grateful to the anonymous referee for the review and providing suggestions that improved the manuscript. We thank the staff at the participating observatories and correlator centers that made possible the EHT 2017 observations. P.T. thanks Pablo Mellado and William Robertson for their support through several stages of the data reduction in the IRAM servers. R.P.E. is funded 175 As an example, typical spectroscopic observations use a sampling time longer than ∼100 ms, which “dilutes” many of the fast periodic signals detected in a microsecond-order sampled data. 176 At low radio frequencies, the de-dispersion step in a pulsar searching algorithm smears the power of broadband local signals, decreasing their impact in the detection of celestial signals by allowing us to discern which broadband signals have traveled though the interstellar medium. 19 The Astrophysical Journal, 959:14 (27pp), 2023 December 10 Torne et al. by the Chinese Academy of Sciences President’s International Fellowship Initiative, grant No. 2021FSM0004. S.M.R. is a CIFAR Fellow and is supported by the NSF Physics Frontiers Center awards 1430284 and 2020265. This work was supported by the European Research Council Synergy Grant “BlackHoleCam: Imaging the Event Horizon of Black Holes” (grant 610058). This paper makes use of the following ALMA data: ADS/JAO.ALMA#2016.1.01404.V. ALMA is a partnership of the European Southern Observatory (ESO; Europe, representing its member states), NSF, and National Institutes of Natural Sciences of Japan, together with National Research Council (Canada), Ministry of Science and Technology (MOST; Taiwan), Academia Sinica Institute of Astronomy and Astrophysics (ASIAA; Taiwan), and Korea Astronomy and Space Science Institute (KASI; Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, Associated Universities, Inc. (AUI)/NRAO, and the National Astronomical Observatory of Japan (NAOJ). The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. The LMT is a project operated by the Instituto Nacional de Astrófisica, Óptica, y Electrónica (Mexico) and the University of Massachusetts at Amherst (USA). This work is partly based on observations carried out with the IRAM 30 m Telescope under project No. 084-17. The IRAM 30 m Telescope on Pico Veleta, Spain is operated by IRAM and supported by CNRS (Centre National de la Recherche Scientifique, France), MPG (MaxPlanck-Gesellschaft, Germany), and IGN (Instituto Geográfico Nacional, Spain). This research has made use of NASA’s Astrophysics Data System Bibliographic Services. Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. The Event Horizon Telescope Collaboration thanks the following organizations and programs: the Academia Sinica; the Academy of Finland (projects 274477, 284495, 312496, and 315721); the Agencia Nacional de Investigación y Desarrollo (ANID), Chile via NCN19_058 (TITANs) and Fondecyt 1221421, the Alexander von Humboldt Stiftung; an Alfred P. Sloan Research Fellowship; Allegro, the European ALMA Regional Centre node in the Netherlands, the NL astronomy research network NOVA and the astronomy institutes of the University of Amsterdam, Leiden University and Radboud University; the ALMA North America Development Fund; the Astrophysics and High Energy Physics program by MCIN (with funding from European Union NextGenerationEU, PRTR-C17I1); the Black Hole Initiative, which is funded by grants from the John Templeton Foundation and the Gordon and Betty Moore Foundation (although the opinions expressed in this work are those of the author(s) and do not necessarily reflect the views of these Foundations); the Brinson Foundation; Chandra DD7-18089X and TM6-17006X; the China Scholarship Council; the China Postdoctoral Science Foundation fellowships (2020M671266, 2022M712084); Consejo Nacional de Ciencia y Tecnología (CONACYT, Mexico, projects U0004- 246083, U0004-259839, F0003-272050, M0037-279006, F0003- 281692, 104497, 275201, and 263356); the Consejería de Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucía (grant P18-FR-1769), the Consejo Superior de Investigaciones Científicas (grant 2019AEP112); the Delaney Family via the Delaney Family John A. Wheeler Chair at Perimeter Institute; Dirección General de Asuntos del Personal Académico-Universidad Nacional Autónoma de México (DGAPA-UNAM, projects IN112417 and IN112820); the Dutch Organization for Scientific Research (NWO) for VICI award (grant 639.043.513), grant OCENW.KLEIN.113 and the Dutch black hole Consortium (with project No. NWA 1292.19.202) of the research program the National Science Agenda; the Dutch National Supercomputers, Cartesius and Snellius (NWO grant 2021.013); the EACOA Fellowship awarded by the East Asia Core Observatories Association, which consists of the Academia Sinica Institute of Astronomy and Astrophysics, the National Astronomical Observatory of Japan, Center for Astronomical Mega-Science, Chinese Academy of Sciences, and the Korea Astronomy and Space Science Institute; the European Union Horizon 2020 research and innovation program under grant agreements RadioNet (No 730562) and M2FINDERS (No 101018682); the Horizon ERC Grants 2021 program under grant agreement No. 101040021; the Generalitat Valenciana (grants APOSTD/2018/177 and ASFAE/2022/018) and GenT Program (project CIDEGENT/ 2018/021); MICINN Research Project PID2019-108995GB-C22; the European Research Council for advanced grant “JETSET: Launching, propagation and emission of relativistic jets from binary mergers and across mass scales” (grant No. 884631); the Institute for Advanced Study; the Istituto Nazionale di Fisica Nucleare (INFN) sezione di Napoli, iniziative specifiche TEONGRAV; the International Max Planck Research School for Astronomy and Astrophysics at the Universities of Bonn and Cologne; DFG research grant “Jet physics on horizon scales and beyond” (grant No. FR 4069/2-1); Joint Columbia/Flatiron Postdoctoral Fellowship, research at the Flatiron Institute is supported by the Simons Foundation; the Japan Ministry of Education, Culture, Sports, Science and Technology (MEXT; grant JPMXP1020200109); the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for JSPS Research Fellowship (JP17J08829); the Joint Institute for Computational Fundamental Science, Japan; the Key Research Program of Frontier Sciences, Chinese Academy of Sciences (CAS, grants QYZDJ-SSWSLH057, QYZDJSSW-SYS008, ZDBS-LY-SLH011); the Leverhulme Trust Early Career Research Fellowship; the Max-PlanckGesellschaft (MPG); the Max Planck Partner Group of the MPG and the CAS; the MEXT/JSPS KAKENHI (grants 18KK0090, JP21H01137, JP18H03721, JP18K13594, 18K03709, JP19K14761, 18H01245, 25120007); the Malaysian Fundamental Research Grant Scheme (FRGS) FRGS/1/2019/STG02/UM/ 02/6; the MIT International Science and Technology Initiatives (MISTI) Funds; the Ministry of Science and Technology (MOST) of Taiwan (103-2119-M-001-010-MY2, 105-2112-M-001-025- MY3, 105-2119-M-001-042, 106-2112-M-001-011, 106-2119-M001-013, 106-2119-M-001-027, 106-2923-M-001-005, 107-2119- M-001-017, 107-2119-M-001-020, 107-2119-M-001-041, 107- 2119-M-110-005, 107-2923-M-001-009, 108-2112-M-001-048, 108-2112-M-001-051, 108-2923-M-001-002, 109-2112-M-001- 025, 109-2124-M-001-005, 109-2923-M-001-001, 110-2112-M003-007-MY2, 110-2112-M-001-033, 110-2124-M-001-007, and 110-2923-M-001-001); the Ministry of Education (MoE) of Taiwan Yushan Young Scholar Program; the Physics Division, National Center for Theoretical Sciences of Taiwan; the National Aeronautics and Space Administration (NASA, Fermi Guest Investigator grant 80NSSC20K1567, NASA Astrophysics Theory Program grant 80NSSC20K0527, NASA NuSTAR award 80NSSC20K0645); NASA Hubble Fellowship grants HST-HF2- 51431.001-A, HST-HF2-51482.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for 20 The Astrophysical Journal, 959:14 (27pp), 2023 December 10 Torne et al. NASA, under contract NAS5-26555; the National Institute of Natural Sciences (NINS) of Japan; the National Key Research and Development Program of China (grant 2016YFA0400704, 2017YFA0402703, 2016YFA0400702); the National Science Foundation (NSF, grants AST-0096454, AST-0352953, AST0521233, AST-0705062, AST-0905844, AST-0922984, AST1126433, AST-1140030, DGE-1144085, AST-1207704, AST1207730, AST-1207752, MRI-1228509, OPP-1248097, AST1310896, AST-1440254, AST-1555365, AST-1614868, AST1615796, AST-1715061, AST-1716327, AST-1716536, OISE1743747, AST-1816420, AST-1935980, AST-2034306); NSF Astronomy and Astrophysics Postdoctoral Fellowship (AST1903847); the Natural Science Foundation of China (grants 11650110427, 10625314, 11721303, 11725312, 11873028, 11933007, 11991052, 11991053, 12192220, 12192223); the Natural Sciences and Engineering Research Council of Canada (NSERC, including a Discovery Grant and the NSERC Alexander Graham Bell Canada Graduate Scholarships-Doctoral Program); the National Youth Thousand Talents Program of China; the National Research Foundation of Korea (the Global PhD Fellowship Grant: grants NRF-2015H1A2A1033752, the Korea Research Fellowship Program: NRF-2015H1D3A1066561, Brain Pool Program: 2019H1D3A1A01102564, Basic Research Support Grant 2019R1F1A1059721, 2021R1A6A3A01086420, 2022R1C1C1005255); Netherlands Research School for Astronomy (NOVA) Virtual Institute of Accretion (VIA) postdoctoral fellowships; Onsala Space Observatory (OSO) national infrastructure, for the provisioning of its facilities/observational support (OSO receives funding through the Swedish Research Council under grant 2017-00648); the Perimeter Institute for Theoretical Physics (research at Perimeter Institute is supported by the Government of Canada through the Department of Innovation, Science and Economic Development and by the Province of Ontario through the Ministry of Research, Innovation and Science); the Princeton Gravity Initiative; the Spanish Ministerio de Ciencia e Innovación (grants PGC2018-098915-B-C21, AYA2016-80889-P, PID2019-108995GB-C21, and PID2020- 117404GB-C21); the University of Pretoria for financial aid in the provision of the new Cluster Server nodes and SuperMicro (USA) for an SEEDING grant approved toward these nodes in 2020; the Shanghai Pilot Program for Basic Research, Chinese Academy of Science, Shanghai Branch (JCYJ-SHFY-2021-013); the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía (SEV-2017-0709); the Spinoza Prize SPI 78-409; the South African Research Chairs Initiative, through the South African Radio Astronomy Observatory (SARAO, grant ID 77948), which is a facility of the National Research Foundation (NRF), an agency of the Department of Science and Innovation (DSI) of South Africa; the Toray Science Foundation; the Swedish Research Council (VR); the US Department of Energy (USDOE) through the Los Alamos National Laboratory (operated by Triad National Security, LLC, for the National Nuclear Security Administration of the USDOE (contract 89233218CNA000001); and the YCAA Prize Postdoctoral Fellowship. This research used resources of the Oak Ridge Leadership Computing Facility at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under contract No. DE-AC05-00OR22725. We also thank the Center for Computational Astrophysics, National Astronomical Observatory of Japan. The computing cluster of Shanghai VLBI correlator supported by the Special Fund for Astronomy from the Ministry of Finance in China is acknowledged. This work was partially supported by FAPESP (Fundação de Amparo á Pesquisa do Estado de São Paulo) under grant 2021/01183-8. APEX is a collaboration between the Max-Planck-Institut für Radioastronomie (Germany), ESO, and the Onsala Space Observatory (Sweden). The SMT is operated by the Arizona Radio Observatory, a part of the Steward Observatory of the University of Arizona, with financial support of operations from the State of Arizona and financial support for instrumentation development from the NSF. Support for SPT participation in the EHT is provided by the National Science Foundation through award OPP-1852617 to the University of Chicago. Partial support is also provided by the Kavli Institute of Cosmological Physics at the University of Chicago. The SPT hydrogen maser was provided on loan from the GLT, courtesy of ASIAA. The SMA is a joint project between the SAO and ASIAA and is funded by the Smithsonian Institution and the Academia Sinica. The JCMT is operated by the East Asian Observatory on behalf of the NAOJ, ASIAA, and KASI, as well as the Ministry of Finance of China, Chinese Academy of Sciences, and the National Key Research and Development Program (No. 2017YFA0402700) of China and Natural Science Foundation of China grant 11873028. Additional funding support for the JCMT is provided by the Science and Technologies Facility Council (UK) and participating universities in the UK and Canada. We acknowledge the significance that Maunakea, where the SMA and JCMT EHT stations are located, has for the indigenous Hawaiian people. The EHTC has received generous donations of FPGA chips from Xilinx Inc., under the Xilinx University Program. The EHTC has benefited from technology shared under an open-source license by the Collaboration for Astronomy Signal Processing and Electronics Research (CASPER). The EHT project is grateful to T4Science and Microsemi for their assistance with Hydrogen Masers. We gratefully acknowledge the support provided by the extended staff of the ALMA, both from the inception of the ALMA Phasing Project through the observational campaigns of 2017 and 2018. We would like to thank A. Deller and W. Brisken for EHT-specific support with the use of DiFX. Facilities: ALMA, LMT, IRAM:30m. Software: MPIvdif2psrfits, PRESTO (Ransom 2011), RIPTIDE (Morello et al. 2020), NUMPY (Harris et al. 2020), SCIPY (Virtanen et al. 2020), MATPLOTLIB (Hunter 2007), TEMPO (Nice et al. 2015), SIGPYPROC (Lorimer 2011)

Accidental carbon monoxide poisoning presenting without a history of exposure: A case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The synovial and blood monocyte DNA methylomes mirror prognosis, evolution and treatment in early arthritis

Identifying predictive biomarkers at early stages of early inflammatory arthritis is crucial for starting appropriate therapies to avoid poor outcomes. Monocytes and macrophages, largely associated with arthritis, are contributors and sensors of inflammation through epigenetic modifications. In this study, we investigated associations between clinical features and DNA methylation in blood and synovial fluid (SF) monocytes in a prospective cohort of early inflammatory arthritis patients. Undifferentiated arthritis (UA) blood monocyte DNA methylation profiles exhibited significant alterations in comparison with those from healthy donors. We identified additional differences both in blood and SF monocytes after comparing UA patients grouped by their future outcomes, good versus poor. Patient profiles in subsequent visits revealed a reversion towards a healthy level in both groups, those requiring disease-modifying antirheumatic drugs (DMARDs) and those that remitted spontaneously. Changes in disease activity between visits also impacted DNA methylation, partially concomitant in the SF of UA and in blood monocytes of rheumatoid arthritis patients. Epigenetic similarities between arthritis types allow a common prediction of disease activity. Our results constitute a resource of DNA methylation-based biomarkers of poor prognosis, disease activity and treatment efficacy in early untreated UA patients for the personalized clinical management of early inflammatory arthritis patients

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy.Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients.Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi.Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems.The Instituto de Salud Carlos III.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved

The Relative Composition of the Inflammatory Infiltrate as an Additional Tool for Synovial Tissue Classification

10.1371/journal.pone.0072494PLoS ONE88-POLN

A Measurement of Rb using a Double Tagging Method

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A Measurement of the Product Branching Ratio f(b->Lambda_b).BR(Lambda_b->Lambda X) in Z0 Decays

The product branching ratio, f(b->Lambda_b).BR(Lambda_b->Lambda X), where Lambda_b denotes any weakly-decaying b-baryon, has been measured using the OPAL detector at LEP. Lambda_b are selected by the presence of energetic Lambda particles in bottom events tagged by the presence of displaced secondary vertices. A fit to the momenta of the Lambda particles separates signal from B meson and fragmentation backgrounds. The measured product branching ratio is f(b->Lambda_b).BR(Lambda_b->Lambda X) = (2.67+-0.38(stat)+0.67-0.60(sys))% Combined with a previous OPAL measurement, one obtains f(b->Lambda_b).BR(Lambda_b->Lambda X) = (3.50+-0.32(stat)+-0.35(sys))%.Comment: 16 pages, LaTeX, 3 eps figs included, submitted to the European Physical Journal