Predicting sepsis severity at first clinical presentation:The role of endotypes and mechanistic signatures

BACKGROUND: Inter-individual variability during sepsis limits appropriate triage of patients. Identifying, at first clinical presentation, gene expression signatures that predict subsequent severity will allow clinicians to identify the most at-risk groups of patients and enable appropriate antibiotic use. METHODS: Blood RNA-Seq and clinical data were collected from 348 patients in four emergency rooms (ER) and one intensive-care-unit (ICU), and 44 healthy controls. Gene expression profiles were analyzed using machine learning and data mining to identify clinically relevant gene signatures reflecting disease severity, organ dysfunction, mortality, and specific endotypes/mechanisms. FINDINGS: Gene expression signatures were obtained that predicted severity/organ dysfunction and mortality in both ER and ICU patients with accuracy/AUC of 77–80%. Network analysis revealed these signatures formed a coherent biological program, with specific but overlapping mechanisms/pathways. Given the heterogeneity of sepsis, we asked if patients could be assorted into discrete groups with distinct mechanisms (endotypes) and varying severity. Patients with early sepsis could be stratified into five distinct and novel mechanistic endotypes, named Neutrophilic-Suppressive/NPS, Inflammatory/INF, Innate-Host-Defense/IHD, Interferon/IFN, and Adaptive/ADA, each based on ∼200 unique gene expression differences, and distinct pathways/mechanisms (e.g., IL6/STAT3 in NPS). Endotypes had varying overall severity with two severe (NPS/INF) and one relatively benign (ADA) groupings, consistent with reanalysis of previous endotype studies. A 40 gene-classification tool (accuracy=96%) and several gene-pairs (accuracy=89–97%) accurately predicted endotype status in both ER and ICU validation cohorts. INTERPRETATION: The severity and endotype signatures indicate that distinct immune signatures precede the onset of severe sepsis and lethality, providing a method to triage early sepsis patients

Reconstructing Native American Population History

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved1–5. One contentious issue is whether the settlement occurred via a single6–8 or multiple streams of migration from Siberia9–15. The pattern of dispersals within the Americas is also poorly understood. To address these questions at higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. We show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call “First American”. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan-speakers on both sides of the Panama Isthmus, who have ancestry from both North and South America

First M87 Event Horizon Telescope results. IX. Detection of near-horizon circular polarization

Event Horizon Telescope (EHT) observations have revealed a bright ring of emission around the supermassive black hole at the center of the M87 galaxy. EHT images in linear polarization have further identified a coherent spiral pattern around the black hole, produced from ordered magnetic fields threading the emitting plasma. Here we present the first analysis of circular polarization using EHT data, acquired in 2017, which can potentially provide additional insights into the magnetic fields and plasma composition near the black hole. Interferometric closure quantities provide convincing evidence for the presence of circularly polarized emission on event-horizon scales. We produce images of the circular polarization using both traditional and newly developed methods. All methods find a moderate level of resolved circular polarization across the image (〈|v|〉 < 3.7%), consistent with the low image-integrated circular polarization fraction measured by the Atacama Large Millimeter/submillimeter Array (|vint| < 1%). Despite this broad agreement, the methods show substantial variation in the morphology of the circularly polarized emission, indicating that our conclusions are strongly dependent on the imaging assumptions because of the limited baseline coverage, uncertain telescope gain calibration, and weakly polarized signal. We include this upper limit in an updated comparison to general relativistic magnetohydrodynamic simulation models. This analysis reinforces the previously reported preference for magnetically arrested accretion flow models. We find that most simulations naturally produce a low level of circular polarization consistent with our upper limit and that Faraday conversion is likely the dominant production mechanism for circular polarization at 230 GHz in M87*.ACKNOWLEDGEMENTS : The Event Horizon Telescope Collaboration thanks the following organizations and programs: the Academia Sinica; the Academy of Finland (AKA, projects 274477, 284495, 312496, 315721); the Agencia Nacional de Investigación y Desarrollo (ANID), Chile via NCN19_058 (TITANs), Fondecyt 1221421 and BASAL FB210003; 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; “la Caixa” Foundation (ID 100010434) through fellowship codes LCF/ BQ/DI22/11940027 and LCF/BQ/DI22/11940030; 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, 263356); the Colfuturo Scholarship; 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 the 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 Research Council (ERC) Synergy Grant “BlackHoleCam: Imaging the Event Horizon of Black Holes” (grant 610058); 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 FAPESP (Fundação de Amparo á Pesquisa do Estado de São Paulo) under grant 2021/01183-8; 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-SSW-SLH057, QYZDJ-SSW-SYS008, ZDBS-LY-SLH011); the Leverhulme Trust Early Career Research Fellowship; the Max-Planck-Gesellschaft (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, 23K03453); 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-M-001-013, 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-M-003-007-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 HSTHF2- 51431.001-A and 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 NASA, under contract NAS5-26555; the National Institute of Natural Sciences (NINS) of Japan; the National Key Research and Development Program of China (grants 2016YFA0400704, 2017YFA0402703, 2016YFA0400702); the National Science Foundation (NSF, grants AST-0096454, AST-0352953, AST-0521233, AST-0705062, AST-0905844, AST-0922984, AST-1126433, AST-1140030, DGE-1144085, AST-1207704, AST-1207730, AST-1207752, MRI-1228509, OPP-1248097, AST-1310896, AST-1440254, AST-1555365, AST-1614868, AST-1615796, AST-1715061, AST-1716327, OISE-1743747, AST-1816420, AST-1935980, AST-2034306, AST-2307887); NSF Astronomy and Astrophysics Postdoctoral Fellowship (AST-1903847); the Natural Science Foundation of China (grants 11650110427, 10625314, 11721303, 11725312, 11873028, 11933007, 11991052, 11991053, 12192220, 12192223, 12273022); 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, 2022R1 C1C1005255); 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-BC21, AYA2016-80889-P, PID2019-108995GB-C21, PID2020- 117404GB-C21); the University of Pretoria for financial aid in the provision of the new Cluster Server nodes and SuperMicro (USA) for a SEEDING GRANT approved toward these nodes in 2020; the Shanghai Municipality orientation program of basic research for international scientists (grant No. 22JC1410600); 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 Spanish Ministry for Science and Innovation grant CEX2021-001131-S funded by MCIN/AEI/10.13039/501100011033; 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. We thank the staff at the participating observatories, correlation centers, and institutions for their enthusiastic support. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2016.1.01154.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 NRAO is a facility of the NSF operated under cooperative agreement by AUI. 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; the ASTROVIVES FEDER infrastructure, with project code IDIFEDER-2021- 086; and the computing cluster of Shanghai VLBI correlator supported by the Special Fund for Astronomy from the Ministry of Finance in China. We also thank the Center for Computational Astrophysics, National Astronomical Observatory of Japan. This work was supported by FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao 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 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. The LMT is a project operated by the Instituto Nacional de Astrófisica, Óptica, y Electrónica (Mexico) and the University of Massachusetts at Amherst (USA). 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 (Max-Planck- Gesellschaft, Germany), and IGN (Instituto Geográfico Nacional, Spain). 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. This work used the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant ACI-1548562, and CyVerse, supported by NSF grants DBI- 0735191, DBI-1265383, and DBI-1743442. The XSEDE Stampede2 resource at TACC was allocated through TGAST170024 and TG-AST080026N. The XSEDE JetStream resource at PTI and TACC was allocated through AST170028. This research is part of the Frontera computing project at the Texas Advanced Computing Center through the Frontera Large-Scale Community Partnerships allocation AST20023. Frontera is made possible by National Science Foundation award OAC-1818253. This research was done using services provided by the OSG Consortium (Pordes et al. 2007; Sfiligoi et al. 2009), which is supported by the National Science Foundation award Nos. 2030508 and 1836650. Additional work used ABACUS2.0, which is part of the eScience center at Southern Denmark University. Simulations were also performed on the SuperMUC cluster at the LRZ in Garching, on the LOEWE cluster in CSC in Frankfurt, on the HazelHen cluster at the HLRS in Stuttgart, and on the Pi2.0 and Siyuan Mark-I at Shanghai Jiao Tong University. The computer resources of the Finnish IT Center for Science (CSC) and the Finnish Computing Competence Infrastructure (FCCI) project are acknowledged. This research was enabled in part by support provided by Compute Ontario (http://computeontario. ca), Calcul Quebec (http://www.calculquebec.ca), and Compute Canada (http://www.computecanada.ca). 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 opensource 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. This research has made use of NASAʼs Astrophysics Data System. We gratefully acknowledge the support provided by the extended staff of the ALMA, 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. We thank Martin Shepherd for the addition of extra features in the Difmap software that were used for the CLEAN imaging results presented in this paper. We acknowledge the significance that Maunakea, where the SMA and JCMT EHT stations are located, has for the indigenous Hawaiian people. FACILITIES : EHT, ALMA, APEX, IRAM:30m, JCMT, LMT, SMA, ARO:SMT, SPT. SOFTWARE : AIPS (Greisen 2003), ParselTongue (Kettenis et al. 2006), GNU Parallel (Tange 2011), eht-imaging (Chael et al. 2016), DIFMAP (Shepherd 2011), Numpy (Harris et al. 2020), Scipy (Virtanen et al. 2020), Pandas (McKinney 2010), Astropy (The Astropy Collaboration et al. 2013, 2018), Jupyter (Kluyver et al. 2016), Matplotlib (Hunter 2007), THEMIS (Broderick et al. 2020a), DMC (Pesce 2021), polsolve (Martí-Vidal et al. 2021), HARM (Gammie et al. 2003; Noble et al. 2006), IPOLE (Noble et al. 2007; Mościbrodzka & Gammie 2018).https://iopscience.iop.org/journal/2041-8205am2024PhysicsNon

The Event Horizon Telescope image of the Quasar NRAO 530

We report on the observations of the quasar NRAO 530 with the Event Horizon Telescope (EHT) on 2017 April 5−7, when NRAO 530 was used as a calibrator for the EHT observations of Sagittarius A*. At z=0.902, this is the most distant object imaged by the EHT so far. We reconstruct the first images of the source at 230 GHz, at an unprecedented angular resolution of ∼20 μas, both in total intensity and in linear polarization (LP).We do not detect source variability, allowing us to represent the whole data set with static images. The images reveal a bright feature located on the southern end of the jet, which we associate with the core. The feature is linearly polarized, with a fractional polarization of ∼5%– 8%, and it has a substructure consisting of two components. Their observed brightness temperature suggests that the energy density of the jet is dominated by the magnetic field. The jet extends over 60 μas along a position angle∼−28°. It includes two features with orthogonal directions of polarization (electric vector position angle), parallel and perpendicular to the jet axis, consistent with a helical structure of the magnetic field in the jet. The outermost feature has a particularly high degree of LP, suggestive of a nearly uniform magnetic field. Future EHT observations will probe the variability of the jet structure on microarcsecond scales, while simultaneous multiwavelength monitoring will provide insight into the high-energy emission origin.ACKNOWLEDGEMENTS : The Event Horizon Telescope Collaboration thanks the following organizations and programs: the Academia Sinica; the Academy of Finland (projects 274477, 284495, 312496, 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 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); Chandra DD7-18089X and TM6-17006X; the China Scholarship Council; China Postdoctoral Science Foundation fellowship (2020M671266); Consejo Nacional de Ciencia y Tecnología (CONACYT, Mexico, projects U0004- 246083, U0004-259839, F0003-272050, M0037-279006, F0003-281692, 104497, 275201, 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) VICI award (grant 639.043.513) and grant OCENW.KLEIN.113; 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 Research Council (ERC) Synergy Grant “BlackHoleCam: Imaging the Event Horizon of Black Holes” (grant 610058); 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 postdoctoral grant APOSTD/2018/177 and GenT Program (project CIDEGENT/ 2018/021); MICINN Research Project PID2019-108995GBC22; 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 Japanese Government (Monbukagakusho: MEXT) Scholarship; 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-SSW-SLH057, QYZDJS SW-SYS008, ZDBS-LY-SLH011); the Leverhulme Trust Early Career Research Fellowship; the Max-Planck-Gesell schaft (MPG); the Max Planck Partner Group of the MPG and the CAS; the MEXT/JSPS KAKENHI (grants 18KK0090, JP21H01137, JP18H03721, JP18K13594, 18K03709, JP19K1 4761, 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-M-001-013, 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-M-003-007-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 grants 80NSSC20K1567 and 80NSSC22K1571, 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 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, 2016YFA040 0702); the National Science Foundation (NSF, grants AST- 0096454, AST-0352953, AST-0521233, AST-0705062, AST- 0905844, AST-0922984, AST-1126433, AST-1140030, DGE- 1144085, AST-1207704, AST-1207730, AST-1207752, MRI- 1228509, OPP-1248097, AST-1310896, AST-1440254, AST- 1555365, AST-1614868, AST-1615796, AST-1715061, AST- 1716327, AST-1716536, OISE-1743747, AST-1816420, AST- 1935980, AST-2034306); NSF Astronomy and Astrophysics Postdoctoral Fellowship (AST-1903847); the Natural Science Foundation of China (grants 11650110427, 10625314, 11721303, 11725312, 11873028, 11933007, 11991052, 119910 53, 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, PID 2019-108995GB-C21, PID2020-117404GB-C21); the University of Pretoria for financial aid in the provision of the new Cluster Server nodes and SuperMicro (USA) for a 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. We thank the staff at the participating observatories, correlation centers, and institutions for their enthusiastic support. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2016.1.01154.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 NRAO is a facility of the NSF operated under cooperative agreement by AUI. 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 supported by FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao 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 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. The LMT is a project operated by the Instituto Nacional de Astrófisica, Óptica, y Electrónica (Mexico) and the University of Massachusetts at Amherst (USA). 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 (Max-Planck- Gesellschaft, Germany) and IGN (Instituto Geográfico Nacional, Spain). 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. This work used the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant ACI-1548562, and CyVerse, supported by NSF grants DBI- 0735191, DBI-1265383, and DBI-1743442. XSEDE Stampede2 resource at TACC was allocated through TGAST170024 and TG-AST080026N. XSEDE JetStream resource at PTI and TACC was allocated through AST170028. This research is part of the Frontera computing project at the Texas Advanced Computing Center through the Frontera Large-Scale Community Partnerships allocation AST20023. Frontera is made possible by National Science Foundation award OAC-1818253. This research was carried out using resources provided by the Open Science Grid, which is supported by the National Science Foundation and the U.S. Department of Energy Office of Science. Additional work used ABACUS2.0, which is part of the eScience center at Southern Denmark University. Simulations were also performed on the SuperMUC cluster at the LRZ in Garching, on the LOEWE cluster in CSC in Frankfurt, on the HazelHen cluster at the HLRS in Stuttgart, and on the Pi2.0 and Siyuan Mark-I at Shanghai Jiao Tong University. The computer resources of the Finnish IT Center for Science (CSC) and the Finnish Computing Competence Infrastructure (FCCI) project are acknowledged. This research was enabled in part by support provided by Compute Ontario (http://computeontario.ca), Calcul Quebec (http://www.calculquebec.ca), and Compute Canada (http://www.computecanada.ca). 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 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. This research has made use of NASA’s Astrophysics Data System. 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. We thank Martin Shepherd for the addition of extra features in the Difmap software that were used for the CLEAN imaging results presented in this paper. We acknowledge the significance and cultural reverance that Maunakea, where the SMA and JCMT EHT stations are located, has always held within the indigenous Hawaiian people. SOFTWARE : DIFMAP (Shepherd 1997), Matplotlib (Hunter 2007), DiFX (Deller et al. 2011), NumPy (van der Walt et al. 2011), eht-imaging (Chael et al. 2016), PolConvert (Martí-Vidal et al. 2016), SMILI (Akiyama et al. 2017), EHT-HOPS (Blackburn et al. 2019), Themis (Broderick et al. 2020a), DMC (Pesce 2021).https://iopscience.iop.org/journal/0004-637Xam2024PhysicsNon

Mapping Zika virus infection using geographical information systems in Tolima, Colombia, 2015-2016 [version 1; referees: 2 approved]

Objective: Geographical information systems (GIS) have been extensively used for the development of epidemiological maps of tropical diseases, however not yet specifically for Zika virus (ZIKV) infection. Methods: Surveillance case data of the ongoing epidemics of ZIKV in the Tolima department, Colombia (2015-2016) were used to estimate cumulative incidence rates (cases/100,000 pop.) to develop the first maps in the department and its municipalities, including detail for the capital, Ibagué. The GIS software used was Kosmo Desktop 3.0RC1®. Two thematic maps were developed according to municipality and communes incidence rates. Results: Up to March 5, 2016, 4,094 cases of ZIKV were reported in Tolima, for cumulated rates of 289.9 cases/100,000 pop. (7.95% of the country). Burden of ZIKV infection has been concentrated in its east area, where municipalities have reported >500 cases/100,000 pop. These municipalities are bordered by two other departments, Cundinamarca (3,778 cases) and Huila (5,338 cases), which also have high incidences of ZIKV infection. Seven municipalities of Tolima ranged from 250-499.99 cases/100,000 pop., of this group five border with high incidence municipalities (>250), including the capital, where almost half of the reported cases of ZIKV in Tolima are concentrated. Conclusions: Use of GIS-based epidemiological maps helps to  guide decisions for the prevention and control of diseases that represent significant issues in the region and the country, but also in emerging conditions such as ZIKV

The genetics of Mexico recapitulates Native American substructure and affects biomedical traits

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide

Resolving the Inner Parsec of the Blazar J1924–2914 with the Event Horizon Telescope

The blazar J1924–2914 is a primary Event Horizon Telescope (EHT) calibrator for the Galactic center's black hole Sagittarius A*. Here we present the first total and linearly polarized intensity images of this source obtained with the unprecedented 20 μas resolution of the EHT. J1924–2914 is a very compact flat-spectrum radio source with strong optical variability and polarization. In April 2017 the source was observed quasi-simultaneously with the EHT (April 5–11), the Global Millimeter VLBI Array (April 3), and the Very Long Baseline Array (April 28), giving a novel view of the source at four observing frequencies, 230, 86, 8.7, and 2.3 GHz. These observations probe jet properties from the subparsec to 100 pc scales. We combine the multifrequency images of J1924–2914 to study the source morphology. We find that the jet exhibits a characteristic bending, with a gradual clockwise rotation of the jet projected position angle of about 90° between 2.3 and 230 GHz. Linearly polarized intensity images of J1924–2914 with the extremely fine resolution of the EHT provide evidence for ordered toroidal magnetic fields in the blazar compact core

Resolving the Inner Parsec of the Blazar J1924–2914 with the Event Horizon Telescope

The blazar J1924–2914 is a primary Event Horizon Telescope (EHT) calibrator for the Galactic center's black hole Sagittarius A*. Here we present the first total and linearly polarized intensity images of this source obtained with the unprecedented 20 μas resolution of the EHT. J1924–2914 is a very compact flat-spectrum radio source with strong optical variability and polarization. In April 2017 the source was observed quasi-simultaneously with the EHT (April 5–11), the Global Millimeter VLBI Array (April 3), and the Very Long Baseline Array (April 28), giving a novel view of the source at four observing frequencies, 230, 86, 8.7, and 2.3 GHz. These observations probe jet properties from the subparsec to 100 pc scales. We combine the multifrequency images of J1924–2914 to study the source morphology. We find that the jet exhibits a characteristic bending, with a gradual clockwise rotation of the jet projected position angle of about 90° between 2.3 and 230 GHz. Linearly polarized intensity images of J1924–2914 with the extremely fine resolution of the EHT provide evidence for ordered toroidal magnetic fields in the blazar compact core