Mortality Differences Between Traditional Medicare and Medicare Advantage: A Risk-Adjusted Assessment Using Claims Data.

Medicare Advantage (MA) has grown rapidly since the Affordable Care Act; nearly one-third of Medicare beneficiaries now choose MA. An assessment of the comparative value of the 2 options is confounded by an apparent selection bias favoring MA, as reflected in mortality differences. Previous assessments have been hampered by lack of access to claims diagnosis data for the MA population. An indirect comparison of mortality as an outcome variable was conducted by modeling mortality on a traditional fee-for-service (FFS) Medicare data set, applying the model to an MA data set, and then evaluating the ratio of actual-to-predicted mortality in the MA data set. The mortality model adjusted for clinical conditions and demographic factors. Model development considered the effect of potentially greater coding intensity in the MA population. Further analysis calculated ratios for subpopulations. Predicted, risk-adjusted mortality was lower in the MA population than in FFS Medicare. However, the ratio of actual-to-predicted mortality (0.80) suggested that the individuals in the MA data set were less likely to die than would be predicted had those individuals been enrolled in FFS Medicare. Differences between actual and predicted mortality were particularly pronounced in low income (dual eligibility), nonwhite race, high morbidity, and Health Maintenance Organization (HMO) subgroups. After controlling for baseline clinical risk as represented by claims diagnosis data, mortality differences favoring MA over FFS Medicare persisted, particularly in vulnerable subgroups and HMO plans. These findings suggest that differences in morbidity do not fully explain differences in mortality between the 2 programs

Development of Functional and Molecular Correlates of Vaccine-Induced Protection for a Model Intracellular Pathogen, F. tularensis LVS

In contrast with common human infections for which vaccine efficacy can be evaluated directly in field studies, alternative strategies are needed to evaluate efficacy for slowly developing or sporadic diseases like tularemia. For diseases such as these caused by intracellular bacteria, serological measures of antibodies are generally not predictive. Here, we used vaccines varying in efficacy to explore development of clinically useful correlates of protection for intracellular bacteria, using Francisella tularensis as an experimental model. F. tularensis is an intracellular bacterium classified as Category A bioterrorism agent which causes tularemia. The primary vaccine candidate in the U.S., called Live Vaccine Strain (LVS), has been the subject of ongoing clinical studies; however, safety and efficacy are not well established, and LVS is not licensed by the U.S. FDA. Using a mouse model, we compared the in vivo efficacy of a panel of qualitatively different Francisella vaccine candidates, the in vitro functional activity of immune lymphocytes derived from vaccinated mice, and relative gene expression in immune lymphocytes. Integrated analyses showed that the hierarchy of protection in vivo engendered by qualitatively different vaccines was reflected by the degree of lymphocytes' in vitro activity in controlling the intramacrophage growth of Francisella. Thus, this assay may be a functional correlate. Further, the strength of protection was significantly related to the degree of up-regulation of expression of a panel of genes in cells recovered from the assay. These included IFN-γ, IL-6, IL-12Rβ2, T-bet, SOCS-1, and IL-18bp. Taken together, the results indicate that an in vitro assay that detects control of bacterial growth, and/or a selected panel of mediators, may ultimately be developed to predict the outcome of vaccine efficacy and to complement clinical trials. The overall approach may be applicable to intracellular pathogens in general

O-Antigen Delays Lipopolysaccharide Recognition and Impairs Antibacterial Host Defense in Murine Intestinal Epithelial Cells

Although Toll-like receptor (TLR) 4 signals from the cell surface of myeloid cells, it is restricted to an intracellular compartment and requires ligand internalization in intestinal epithelial cells (IECs). Yet, the functional consequence of cell-type specific receptor localization and uptake-dependent lipopolysaccharide (LPS) recognition is unknown. Here, we demonstrate a strikingly delayed activation of IECs but not macrophages by wildtype Salmonella enterica subsp. enterica sv. (S.) Typhimurium as compared to isogenic O-antigen deficient mutants. Delayed epithelial activation is associated with impaired LPS internalization and retarded TLR4-mediated immune recognition. The O-antigen-mediated evasion from early epithelial innate immune activation significantly enhances intraepithelial bacterial survival in vitro and in vivo following oral challenge. These data identify O-antigen expression as an innate immune evasion mechanism during apical intestinal epithelial invasion and illustrate the importance of early innate immune recognition for efficient host defense against invading Salmonella

Effects of Helicobacter suis γ-glutamyl transpeptidase on lymphocytes: modulation by glutamine and glutathione supplementation and outer membrane vesicles as a putative delivery route of the enzyme

Helicobacter (H.) suis colonizes the stomach of the majority of pigs as well as a minority of humans worldwide. Infection causes chronic inflammation in the stomach of the host, however without an effective clearance of the bacteria. Currently, no information is available about possible mechanisms H. suis utilizes to interfere with the host immune response. This study describes the effect on various lymphocytes of the γ-glutamyl transpeptidase (GGT) from H. suis. Compared to whole cell lysate from wild-type H. suis, lysate from a H. suis ggt mutant strain showed a decrease of the capacity to inhibit Jurkat T cell proliferation. Incubation of Jurkat T cells with recombinantly expressed H. suis GGT resulted in an impaired proliferation, and cell death was shown to be involved. A similar but more pronounced inhibitory effect was also seen on primary murine CD4+ T cells, CD8+ T cells, and CD19+ B cells. Supplementation with known GGT substrates was able to modulate the observed effects. Glutamine restored normal proliferation of the cells, whereas supplementation with reduced glutathione strengthened the H. suis GGT-mediated inhibition of proliferation. H. suis GGT treatment abolished secretion of IL-4 and IL-17 by CD4+ T cells, without affecting secretion of IFN-γ. Finally, H. suis outer membrane vesicles (OMV) were identified as a possible delivery route of H. suis GGT to lymphocytes residing in the deeper mucosal layers. Thus far, this study is the first to report that the effects on lymphocytes of this enzyme, not only important for H. suis metabolism but also for that of other Helicobacter species, depend on the degradation of two specific substrates: glutamine and reduced glutatione. This will provide new insights into the pathogenic mechanisms of H. suis infection in particular and infection with gastric helicobacters in general

Search of the early O3 LIGO data for continuous gravitational waves from the Cassiopeia A and Vela Jr. supernova remnants

partially_open1412sìWe present directed searches for continuous gravitational waves from the neutron stars in the Cassiopeia A (Cas A) and Vela Jr. supernova remnants. We carry out the searches in the LIGO detector data from the first six months of the third Advanced LIGO and Virgo observing run using the weave semicoherent method, which sums matched-filter detection-statistic values over many time segments spanning the observation period. No gravitational wave signal is detected in the search band of 20–976 Hz for assumed source ages greater than 300 years for Cas A and greater than 700 years for Vela Jr. Estimates from simulated continuous wave signals indicate we achieve the most sensitive results to date across the explored parameter space volume, probing to strain magnitudes as low as ∼6.3×10^−26 for Cas A and ∼5.6×10^−26 for Vela Jr. at frequencies near 166 Hz at 95% efficiency.openAbbott, R.; Abbott, T. D.; Acernese, F.; Ackley, K.; Adams, C.; Adhikari, N.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agarwal, D.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Albanesi, S.; Allocca, A.; Altin, P. A.; Amato, A.; Anand, C.; Anand, S.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Andrade, T.; Andres, N.; Andrić, T.; Angelova, S. V.; Ansoldi, S.; Antelis, J. M.; Antier, S.; Appert, S.; Arai, K.; Araya, M. C.; Areeda, J. S.; Arène, M.; Arnaud, N.; Aronson, S. M.; Arun, K. G.; Asali, Y.; Ashton, G.; Assiduo, M.; Aston, S. M.; Astone, P.; Aubin, F.; Austin, C.; Babak, S.; Badaracco, F.; Bader, M. K. M.; Badger, C.; Bae, S.; Baer, A. M.; Bagnasco, S.; Bai, Y.; Baird, J.; Ball, M.; Ballardin, G.; Ballmer, S. W.; Balsamo, A.; Baltus, G.; Banagiri, S.; Bankar, D.; Barayoga, J. C.; Barbieri, C.; Barish, B. C.; Barker, D.; Barneo, P.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Bawaj, M.; Bayley, J. C.; Baylor, A. C.; Bazzan, M.; Bécsy, B.; Bedakihale, V. M.; Bejger, M.; Belahcene, I.; Benedetto, V.; Beniwal, D.; Bennett, T. F.; Bentley, J. D.; BenYaala, M.; Bergamin, F.; Berger, B. K.; Bernuzzi, S.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Beveridge, D.; Bhandare, R.; Bhardwaj, U.; Bhattacharjee, D.; Bhaumik, S.; Bilenko, I. A.; Billingsley, G.; Bini, S.; Birney, R.; Birnholtz, O.; Biscans, S.; Bischi, M.; Biscoveanu, S.; Bisht, A.; Biswas, B.; Bitossi, M.; Bizouard, M.-A.; Blackburn, J. K.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bobba, F.; Bode, N.; Boer, M.; Bogaert, G.; Boldrini, M.; Bonavena, L. D.; Bondu, F.; Bonilla, E.; Bonnand, R.; Booker, P.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, N.; Bose, S.; Bossilkov, V.; Boudart, V.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Bramley, A.; Branch, A.; Branchesi, M.; Brau, J. E.; Breschi, M.; Briant, T.; Briggs, J. H.; Brillet, A.; Brinkmann, M.; Brockill, P.; Brooks, A. F.; Brooks, J.; Brown, D. D.; Brunett, S.; Bruno, G.; Bruntz, R.; Bryant, J.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buscicchio, R.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Bustillo, J. Calderón; Callaghan, J. D.; Callister, T. A.; Calloni, E.; Cameron, J.; Camp, J. B.; Canepa, M.; Canevarolo, S.; Cannavacciuolo, M.; Cannon, K. C.; Cao, H.; Capote, E.; Carapella, G.; Carbognani, F.; Carlin, J. B.; Carney, M. F.; Carpinelli, M.; Carrillo, G.; Carullo, G.; Carver, T. L.; Diaz, J. Casanueva; Casentini, C.; Castaldi, G.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Ceasar, M.; Cella, G.; Cerdá-Durán, P.; Cesarini, E.; Chaibi, W.; Chakravarti, K.; Subrahmanya, S. Chalathadka; Champion, E.; Chan, C.-H.; Chan, C.; Chan, C. L.; Chan, K.; Chandra, K.; Chanial, P.; Chao, S.; Charlton, P.; Chase, E. A.; Chassande-Mottin, E.; Chatterjee, C.; Chatterjee, Debarati; Chatterjee, Deep; Chaturvedi, M.; Chaty, S.; Chen, H. Y.; Chen, J.; Chen, X.; Chen, Y.; Chen, Z.; Cheng, H.; Cheong, C. K.; Cheung, H. Y.; Chia, H. Y.; Chiadini, F.; Chiarini, G.; Chierici, R.; Chincarini, A.; Chiofalo, M. L.; Chiummo, A.; Cho, G.; Cho, H. S.; Choudhary, R. K.; Choudhary, S.; Christensen, N.; Chu, Q.; Chua, S.; Chung, K. W.; Ciani, G.; Ciecielag, P.; Cieślar, M.; Cifaldi, M.; Ciobanu, A. A.; Ciolfi, R.; Cipriano, F.; Cirone, A.; Clara, F.; Clark, E. N.; Clark, J. A.; Clarke, L.; Clearwater, P.; Clesse, S.; Cleva, F.; Coccia, E.; Codazzo, E.; Cohadon, P.-F.; Cohen, D. E.; Cohen, L.; Colleoni, M.; Collette, C. G.; Colombo, A.; Colpi, M.; Compton, C. M.; Constancio, M.; Conti, L.; Cooper, S. J.; Corban, P.; Corbitt, T. R.; Cordero-Carrión, I.; Corezzi, S.; Corley, K. R.; Cornish, N.; Corre, D.; Corsi, A.; Cortese, S.; Costa, C. A.; Cotesta, R.; Coughlin, M. W.; Coulon, J.-P.; Countryman, S. T.; Cousins, B.; Couvares, P.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Creighton, J. D. E.; Creighton, T. D.; Criswell, A. W.; Croquette, M.; Crowder, S. G.; Cudell, J. R.; Cullen, T. J.; Cumming, A.; Cummings, R.; Cunningham, L.; Cuoco, E.; Curyło, M.; Dabadie, P.; Canton, T. Dal; Dall’Osso, S.; Dálya, G.; Dana, A.; DaneshgaranBajastani, L. M.; D’Angelo, B.; Danilishin, S.; D’Antonio, S.; Danzmann, K.; Darsow-Fromm, C.; Dasgupta, A.; Datrier, L. E. H.; Datta, S.; Dattilo, V.; Dave, I.; Davier, M.; Davies, G. S.; Davis, D.; Davis, M. C.; Daw, E. J.; Dean, R.; DeBra, D.; Deenadayalan, M.; Degallaix, J.; De Laurentis, M.; Deléglise, S.; Del Favero, V.; De Lillo, F.; De Lillo, N.; Del Pozzo, W.; DeMarchi, L. M.; De Matteis, F.; D’Emilio, V.; Demos, N.; Dent, T.; Depasse, A.; De Pietri, R.; De Rosa, R.; De Rossi, C.; DeSalvo, R.; De Simone, R.; Dhurandhar, S.; Díaz, M. C.; Diaz-Ortiz, M.; Didio, N. A.; Dietrich, T.; Di Fiore, L.; Di Fronzo, C.; Di Giorgio, C.; Di Giovanni, F.; Di Giovanni, M.; Di Girolamo, T.; Di Lieto, A.; Ding, B.; Di Pace, S.; Di Palma, I.; Di Renzo, F.; Divakarla, A. K.; Dmitriev, A.; Doctor, Z.; D’Onofrio, L.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Drago, M.; Driggers, J. C.; Drori, Y.; Ducoin, J.-G.; Dupej, P.; Durante, O.; D’Urso, D.; Duverne, P.-A.; Dwyer, S. E.; Eassa, C.; Easter, P. J.; Ebersold, M.; Eckhardt, T.; Eddolls, G.; Edelman, B.; Edo, T. B.; Edy, O.; Effler, A.; Eichholz, J.; Eikenberry, S. S.; Eisenmann, M.; Eisenstein, R. A.; Ejlli, A.; Engelby, E.; Errico, L.; Essick, R. C.; Estellés, H.; Estevez, D.; Etienne, Z.; Etzel, T.; Evans, M.; Evans, T. M.; Ewing, B. E.; Fafone, V.; Fair, H.; Fairhurst, S.; Farah, A. M.; Farinon, S.; Farr, B.; Farr, W. M.; Farrow, N. W.; Fauchon-Jones, E. J.; Favaro, G.; Favata, M.; Fays, M.; Fazio, M.; Feicht, J.; Fejer, M. M.; Fenyvesi, E.; Ferguson, D. L.; Fernandez-Galiana, A.; Ferrante, I.; Ferreira, T. A.; Fidecaro, F.; Figura, P.; Fiori, I.; Fishbach, M.; Fisher, R. P.; Fittipaldi, R.; Fiumara, V.; Flaminio, R.; Floden, E.; Fong, H.; Font, J. A.; Fornal, B.; Forsyth, P. W. F.; Franke, A.; Frasca, S.; Frasconi, F.; Frederick, C.; Freed, J. P.; Frei, Z.; Freise, A.; Frey, R.; Fritschel, P.; Frolov, V. V.; Fronzé, G. G.; Fulda, P.; Fyffe, M.; Gabbard, H. A.; Gadre, B. U.; Gair, J. R.; Gais, J.; Galaudage, S.; Gamba, R.; Ganapathy, D.; Ganguly, A.; Gaonkar, S. G.; Garaventa, B.; García-Núñez, C.; García-Quirós, C.; Garufi, F.; Gateley, B.; Gaudio, S.; Gayathri, V.; Gemme, G.; Gennai, A.; George, J.; Gerberding, O.; Gergely, L.; Gewecke, P.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, Shaon; Ghosh, Shrobana; Giacomazzo, B.; Giacoppo, L.; Giaime, J. A.; Giardina, K. D.; Gibson, D. R.; Gier, C.; Giesler, M.; Giri, P.; Gissi, F.; Glanzer, J.; Gleckl, A. E.; Godwin, P.; Goetz, E.; Goetz, R.; Gohlke, N.; Goncharov, B.; González, G.; Gopakumar, A.; Gosselin, M.; Gouaty, R.; Gould, D. W.; Grace, B.; Grado, A.; Granata, M.; Granata, V.; Grant, A.; Gras, S.; Grassia, P.; Gray, C.; Gray, R.; Greco, G.; Green, A. C.; Green, R.; Gretarsson, A. M.; Gretarsson, E. M.; Griffith, D.; Griffiths, W.; Griggs, H. L.; Grignani, G.; Grimaldi, A.; Grimm, S. J.; Grote, H.; Grunewald, S.; Gruning, P.; Guerra, D.; Guidi, Gianluca; Guimaraes, A. R.; Guixé, G.; Gulati, H. K.; Guo, H.-K.; Guo, Y.; Gupta, Anchal; Gupta, Anuradha; Gupta, P.; Gustafson, E. K.; Gustafson, R.; Guzman, F.; Haegel, L.; Halim, O.; Hall, E. D.; Hamilton, E. Z.; Hammond, G.; Haney, M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hannuksela, O.; Hansen, H.; Hansen, T. J.; Hanson, J.; Harder, T.; Hardwick, T.; Haris, K.; Harms, J.; Harry, G. M.; Harry, I. W.; Hartwig, D.; Haskell, B.; Hasskew, R. K.; Haster, C.-J.; Haughian, K.; Hayes, F. J.; Healy, J.; Heidmann, A.; Heidt, A.; Heintze, M. C.; Heinze, J.; Heinzel, J.; Heitmann, H.; Hellman, F.; Hello, P.; Helmling-Cornell, A. F.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennes, E.; Hennig, J.; Hennig, M. H.; Hernandez, A. G.; Vivanco, F. Hernandez; Heurs, M.; Hild, S.; Hill, P.; Hines, A. S.; Hochheim, S.; Hofman, D.; Hohmann, J. N.; Holcomb, D. G.; Holland, N. A.; Hollows, I. J.; Holmes, Z. J.; Holt, K.; Holz, D. E.; Hopkins, P.; Hough, J.; Hourihane, S.; Howell, E. J.; Hoy, C. G.; Hoyland, D.; Hreibi, A.; Hsu, Y.; Huang, Y.; Hübner, M. T.; Huddart, A. D.; Hughey, B.; Hui, V.; Husa, S.; Huttner, S. H.; Huxford, R.; Huynh-Dinh, T.; Idzkowski, B.; Iess, A.; Ingram, C.; Isi, M.; Isleif, K.; Iyer, B. R.; JaberianHamedan, V.; Jacqmin, T.; Jadhav, S. J.; Jadhav, S. P.; James, A. L.; Jan, A. Z.; Jani, K.; Janquart, J.; Janssens, K.; Janthalur, N. N.; Jaranowski, P.; Jariwala, D.; Jaume, R.; Jenkins, A. C.; Jenner, K.; Jeunon, M.; Jia, W.; Johns, G. R.; Jones, A. W.; Jones, D. I.; Jones, J. D.; Jones, P.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Juste, V.; Kalaghatgi, C. V.; Kalogera, V.; Kamai, B.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kao, Y.; Kapadia, S. J.; Kapasi, D. P.; Karat, S.; Karathanasis, C.; Karki, S.; Kashyap, R.; Kasprzack, M.; Kastaun, W.; Katsanevas, S.; Katsavounidis, E.; Katzman, W.; Kaur, T.; Kawabe, K.; Kéfélian, F.; Keitel, D.; Key, J. S.; Khadka, S.; Khalili, F. Y.; Khan, S.; Khazanov, E. A.; Khetan, N.; Khursheed, M.; Kijbunchoo, N.; Kim, C.; Kim, J. C.; Kim, K.; Kim, W. S.; Kim, Y.-M.; Kimball, C.; Kinley-Hanlon, M.; Kirchhoff, R.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Knee, A. M.; Knowles, T. D.; Knyazev, E.; Koch, P.; Koekoek, G.; Koley, S.; Kolitsidou, P.; Kolstein, M.; Komori, K.; Kondrashov, V.; Kontos, A.; Koper, N.; Korobko, M.; Kovalam, M.; Kozak, D. B.; Kringel, V.; Krishnendu, N. V.; Królak, A.; Kuehn, G.; Kuei, F.; Kuijer, P.; Kumar, A.; Kumar, P.; Kumar, Rahul; Kumar, Rakesh; Kuns, K.; Kuwahara, S.; Lagabbe, P.; Laghi, D.; Lalande, E.; Lam, T. L.; Lamberts, A.; Landry, M.; Lane, B. B.; Lang, R. N.; Lange, J.; Lantz, B.; La Rosa, I.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lecoeuche, Y. K.; Lee, H. M.; Lee, H. W.; Lee, J.; Lee, K.; Lehmann, J.; Lemaître, A.; Leroy, N.; Letendre, N.; Levesque, C.; Levin, Y.; Leviton, J. N.; Leyde, K.; Li, A. K. Y.; Li, B.; Li, J.; Li, T. G. F.; Li, X.; Linde, F.; Linker, S. D.; Linley, J. N.; Littenberg, T. B.; Liu, J.; Liu, K.; Liu, X.; Llamas, F.; Llorens-Monteagudo, M.; Lo, R. K. L.; Lockwood, A.; London, L. T.; Longo, A.; Lopez, D.; Portilla, M. Lopez; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lott, T. P.; Lough, J. D.; Lousto, C. O.; Lovelace, G.; Lucaccioni, J. F.; Lück, H.; Lumaca, D.; Lundgren, A. P.; Lynam, J. E.; Macas, R.; MacInnis, M.; Macleod, D. M.; MacMillan, I. A. O.; Macquet, A.; Hernandez, I. Magaña; Magazzù, C.; Magee, R. M.; Maggiore, R.; Magnozzi, M.; Mahesh, S.; Majorana, E.; Makarem, C.; Maksimovic, I.; Maliakal, S.; Malik, A.; Man, N.; Mandic, V.; Mangano, V.; Mango, J. L.; Mansell, G. L.; Manske, M.; Mantovani, M.; Mapelli, M.; Marchesoni, F.; Marion, F.; Mark, Z.; Márka, S.; Márka, Z.; Markakis, C.; Markosyan, A. S.; Markowitz, A.; Maros, E.; Marquina, A.; Marsat, S.; Martelli, F.; Martin, I. W.; Martin, R. M.; Martinez, M.; Martinez, V. A.; Martinez, V.; Martinovic, K.; Martynov, D. V.; Marx, E. J.; Masalehdan, H.; Mason, K.; Massera, E.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matas, A.; Mateu-Lucena, M.; Matichard, F.; Matiushechkina, M.; Mavalvala, N.; McCann, J. J.; McCarthy, R.; McClelland, D. E.; McClincy, P. K.; McCormick, S.; McCuller, L.; McGhee, G. I.; McGuire, S. C.; McIsaac, C.; McIver, J.; McRae, T.; McWilliams, S. T.; Meacher, D.; Mehmet, M.; Mehta, A. K.; Meijer, Q.; Melatos, A.; Melchor, D. A.; Mendell, G.; Menendez-Vazquez, A.; Menoni, C. S.; Mercer, R. A.; Mereni, L.; Merfeld, K.; Merilh, E. L.; Merritt, J. D.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Meyers, P. M.; Meylahn, F.; Mhaske, A.; Miani, A.; Miao, H.; Michaloliakos, I.; Michel, C.; Middleton, H.; Milano, L.; Miller, A.; Miller, A. L.; Miller, B.; Millhouse, M.; Mills, J. C.; Milotti, E.; Minazzoli, O.; Minenkov, Y.; Mir, Ll. M.; Miravet-Tenés, M.; Mishra, C.; Mishra, T.; Mistry, T.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Mo, Geoffrey; Moguel, E.; Mogushi, K.; Mohapatra, S. R. P.; Mohite, S. R.; Molina, I.; Molina-Ruiz, M.; Mondin, M.; Montani, M.; Moore, C. J.; Moraru, D.; Morawski, F.; More, A.; Moreno, C.; Moreno, G.; Morisaki, S.; Mours, B.; Mow-Lowry, C. M.; Mozzon, S.; Muciaccia, F.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, Soma; Mukherjee, Subroto; Mukherjee, Suvodip; Mukund, N.; Mullavey, A.; Munch, J.; Muñiz, E. A.; Murray, P. G.; Musenich, R.; Muusse, S.; Nadji, S. L.; Nagar, A.; Napolano, V.; Nardecchia, I.; Naticchioni, L.; Nayak, B.; Nayak, R. K.; Neil, B. F.; Neilson, J.; Nelemans, G.; Nelson, T. J. N.; Nery, M.; Neubauer, P.; Neunzert, A.; Ng, K. Y.; Ng, S. W. S.; Nguyen, C.; Nguyen, P.; Nguyen, T.; Nichols, S. A.; Nissanke, S.; Nitoglia, E.; Nocera, F.; Norman, M.; North, C.; Nuttall, L. K.; Oberling, J.; O’Brien, B. D.; O’Dell, J.; Oelker, E.; Oganesyan, G.; Oh, J. J.; Oh, S. H.; Ohme, F.; Ohta, H.; Okada, M. A.; Olivetto, C.; Oram, R.; O’Reilly, B.; Ormiston, R. G.; Ormsby, N. D.; Ortega, L. F.; O’Shaughnessy, R.; O’Shea, E.; Ossokine, S.; Osthelder, C.; Ottaway, D. J.; Overmier, H.; Pace, A. E.; Pagano, G.; Page, M. A.; Pagliaroli, G.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pan, H.; Panda, P. K.; Pang, P. T. H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Panther, F. H.; Paoletti, F.; Paoli, A.; Paolone, A.; Park, H.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patel, M.; Pathak, M.; Patricelli, B.; Patron, A. S.; Paul, S.; Payne, E.; Pedraza, M.; Pegoraro, M.; Pele, A.; Penn, S.; Perego, A.; Pereira, A.; Pereira, T.; Perez, C. J.; Périgois, C.; Perkins, C. C.; Perreca, A.; Perriès, S.; Petermann, J.; Petterson, D.; Pfeiffer, H. P.; Pham, K. A.; Phukon, K. S.; Piccinni, O. J.; Pichot, M.; Piendibene, M.; Piergiovanni, F.; Pierini, L.; Pierro, V.; Pillant, G.; Pillas, M.; Pilo, F.; Pinard, L.; Pinto, I. M.; Pinto, M.; Piotrzkowski, K.; Pirello, M.; Pitkin, M. D.; Placidi, E.; Planas, L.; Plastino, W.; Pluchar, C.; Poggiani, R.; Polini, E.; Pong, D. Y. T.; Ponrathnam, S.; Popolizio, P.; Porter, E. K.; Poulton, R.; Powell, J.; Pracchia, M.; Pradier, T.; Prajapati, A. K.; Prasai, K.; Prasanna, R.; Pratten, G.; Principe, M.; Prodi, G. A.; Prokhorov, L.; Prosposito, P.; Prudenzi, L.; Puecher, A.; Punturo, M.; Puosi, F.; Puppo, P.; Pürrer, M.; Qi, H.; Quetschke, V.; Quitzow-James, R.; Raab, F. J.; Raaijmakers, G.; Radkins, H.; Radulesco, N.; Raffai, P.; Rail, S. X.; Raja, S.; Rajan, C.; Ramirez, K. E.; Ramirez, T. D.; Ramos-Buades, A.; Rana, J.; Rapagnani, P.; Rapol, U. D.; Ray, A.; Raymond, V.; Raza, N.; Razzano, M.; Read, J.; Rees, L. A.; Regimbau, T.; Rei, L.; Reid, S.; Reid, S. W.; Reitze, D. H.; Relton, P.; Renzini, A.; Rettegno, P.; Rezac, M.; Ricci, F.; Richards, D.; Richardson, J. W.; Richardson, L.; Riemenschneider, G.; Riles, K.; Rinaldi, S.; Rink, K.; Rizzo, M.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rodriguez, S.; Rolland, L.; Rollins, J. G.; Romanelli, M.; Romano, R.; Romel, C. L.; Romero-Rodríguez, A.; Romero-Shaw, I. M.; Romie, J. H.; Ronchini, S.; Rosa, L.; Rose, C. A.; Rosińska, D.; Ross, M. P.; Rowan, S.; Rowlinson, S. J.; Roy, S.; Roy, Santosh; Roy, Soumen; Rozza, D.; Ruggi, P.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadiq, J.; Sakellariadou, M.; Salafia, O. S.; Salconi, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sanchez, E. J.; Sanchez, J. H.; Sanchez, L. E.; Sanchis-Gual, N.; Sanders, J. R.; Sanuy, A.; Saravanan, T. R.; Sarin, N.; Sassolas, B.; Satari, H.; Sathyaprakash, B. S.; Sauter, O.; Savage, R. L.; Sawant, D.; Sawant, H. L.; Sayah, S.; Schaetzl, D.; Scheel, M.; Scheuer, J.; Schiworski, M.; Schmidt, P.; Schmidt, S.; Schnabel, R.; Schneewind, M.; Schofield, R. M. S.; Schönbeck, A.; Schulte, B. W.; Schutz, B. F.; Schwartz, E.; Scott, J.; Scott, S. M.; Seglar-Arroyo, M.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Seo, E. G.; Sequino, V.; Sergeev, A.; Setyawati, Y.; Shaffer, T.; Shahriar, M. S.; Shams, B.; Sharma, A.; Sharma, P.; Shawhan, P.; Shcheblanov, N. S.; Shikauchi, M.; Shoemaker, D. H.; Shoemaker, D. M.; ShyamSundar, S.; Sieniawska, M.; Sigg, D.; Singer, L. P.; Singh, D.; Singh, N.; Singha, A.; Sintes, A. M.; Sipala, V.; Skliris, V.; Slagmolen, B. J. J.; Slaven-Blair, T. J.; Smetana, J.; Smith, J. R.; Smith, R. J. E.; Soldateschi, J.; Somala, S. N.; Son, E. J.; Soni, K.; Soni, S.; Sordini, V.; Sorrentino, F.; Sorrentino, N.; Soulard, R.; Souradeep, T.; Sowell, E.; Spagnuolo, V.; Spencer, A. P.; Spera, M.; Srinivasan, R.; Srivastava, A. K.; Srivastava, V.; Staats, K.; Stachie, C.; Steer, D. A.; Steinlechner, J.; Steinlechner, S.; Stops, D. J.; Stover, M.; Strain, K. A.; Strang, L. C.; Stratta, G.; Strunk, A.; Sturani, R.; Stuver, A. L.; Sudhagar, S.; Sudhir, V.; Suh, H. G.; Summerscales, T. Z.; Sun, H.; Sun, L.; Sunil, S.; Sur, A.; Suresh, J.; Sutton, P. J.; Swinkels, B. L.; Szczepańczyk, M. J.; Szewczyk, P.; Tacca, M.; Tait, S. C.; Talbot, C. J.; Talbot, C.; Tanasijczuk, A. J.; Tanner, D. B.; Tao, D.; Tao, L.; Martín, E. N. Tapia San; Taranto, C.; Tasson, J. D.; Tenorio, R.; Terhune, J. E.; Terkowski, L.; Thirugnanasambandam, M. P.; Thomas, M.; Thomas, P.; Thompson, J. E.; Thondapu, S. R.; Thorne, K. A.; Thrane, E.; Tiwari, Shubhanshu; Tiwari, Srishti; Tiwari, V.; Toivonen, A. M.; Toland, K.; Tolley, A. E.; Tonelli, M.; Torres-Forné, A.; Torrie, C. I.; e Melo, I. Tosta; Töyrä, D.; Trapananti, A.; Travasso, F.; Traylor, G.; Trevor, M.; Tringali, M. C.; Tripathee, A.; Troiano, L.; Trovato, A.; Trozzo, L.; Trudeau, R. J.; Tsai, D. S.; Tsai, D.; Tsang, K. W.; Tse, M.; Tso, R.; Tsukada, L.; Tsuna, D.; Tsutsui, T.; Turbang, K.; Turconi, M.; Ubhi, A. S.; Udall, R. P.; Ueno, K.; Unnikrishnan, C. S.; Urban, A. L.; Utina, A.; Vahlbruch, H.; Vajente, G.; Vajpeyi, A.; Valdes, G.; Valentini, M.; Valsan, V.; van Bakel, N.; van Beuzekom, M.; van den Brand, J. F. J.; Van Den Broeck, C.; Vander-Hyde, D. C.; van der Schaaf, L.; van Heijningen, J. V.; Vanosky, J.; van Remortel, N.; Vardaro, M.; Vargas, A. F.; Varma, V.; Vasúth, M.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venneberg, J.; Venugopalan, G.; Verkindt, D.; Verma, P.; Verma, Y.; Veske, D.; Vetrano, F.; Vicere', Andrea; Vidyant, S.; Viets, A. D.; Vijaykumar, A.; Villa-Ortega, V.; Vinet, J.-Y.; Virtuoso, A.; Vitale, S.; Vo, T.; Vocca, H.; von Reis, E. R. G.; von Wrangel, J. S. A.; Vorvick, C.; Vyatchanin, S. P.; Wade, L. E.; Wade, M.; Wagner, K. J.; Walet, R. C.; Walker, M.; Wallace, G. S.; Wallace, L.; Walsh, S.; Wang, J. Z.; Wang, W. H.; Ward, R. L.; Warner, J.; Was, M.; Washington, N. Y.; Watchi, J.; Weaver, B.; Webster, S. A.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Weldon, G.; Weller, C. M.; Wellmann, F.; Wen, L.; Weßels, P.; Wette, K.; Whelan, J. T.; White, D. D.; Whiting, B. F.; Whittle, C.; Wilken, D.; Williams, D.; Williams, M. J.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wilson, D. J.; Winkler, W.; Wipf, C. C.; Wlodarczyk, T.; Woan, G.; Woehler, J.; Wofford, J. K.; Wong, I. C. F.; Wu, D. S.; Wysocki, D. M.; Xiao, L.; Yamamoto, H.; Yang, F. W.; Yang, L.; Yang, Yang; Yang, Z.; Yap, M. J.; Yeeles, D. W.; Yelikar, A. B.; Ying, M.; Yoo, J.; Yu, Hang; Yu, Haocun; Zadrożny, A.; Zanolin, M.; Zelenova, T.; Zendri, J.-P.; Zevin, M.; Zhang, J.; Zhang, L.; Zhang, T.; Zhang, Y.; Zhao, C.; Zhao, G.; Zhao, Yue; Zhou, R.; Zhou, Z.; Zhu, X. J.; Zimmerman, A. B.; Zucker, M. E.; Zweizig, J.Abbott, R.; Abbott, T.  D.; Acernese, F.; Ackley, K.; Adams, C.; Adhikari, N.; Adhikari, R.  X.; Adya, V.  B.; Affeldt, C.; Agarwal, D.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O.  D.; Aiello, L.; Ain, A.; Ajith, P.; Albanesi, S.; Allocca, A.; Altin, P.  A.; Amato, A.; Anand, C.; Anand, S.; Ananyeva, A.; Anderson, S.  B.; Anderson, W.  G.; Andrade, T.; Andres, N.; Andrić, T.; Angelova, S.  V.; Ansoldi, S.; Antelis, J.  M.; Antier, S.; Appert, S.; Arai, K.; Araya, M.  C.; Areeda, J.  S.; Arène, M.; Arnaud, N.; Aronson, S.  M.; Arun, K.  G.; Asali, Y.; Ashton, G.; Assiduo, M.; Aston, S.  M.; Astone, P.; Aubin, F.; Austin, C.; Babak, S.; Badaracco, F.; Bader, M.  K.  M.; Badger, C.; Bae, S.; Baer, A.  M.; Bagnasco, S.; Bai, Y.; Baird, J.; Ball, M.; Ballardin, G.; Ballmer, S.  W.; Balsamo, A.; Baltus, G.; Banagiri, S.; Bankar, D.; Barayoga, J.  C.; Barbieri, C.; Barish, B.  C.; Barker, D.; Barneo, P.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Barton, M.  A.; Bartos, I.; Bassiri, R.; Basti, A.; Bawaj, M.; Bayley, J.  C.; Baylor, A.  C.; Bazzan, M.; Bécsy, B.; Bedakihale, V.  M.; Bejger, M.; Belahcene, I.; Benedetto, V.; Beniwal, D.; Bennett, T.  F.; Bentley, J.  D.; Benyaala, M.; Bergamin, F.; Berger, B.  K.; Bernuzzi, S.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Beveridge, D.; Bhandare, R.; Bhardwaj, U.; Bhattacharjee, D.; Bhaumik, S.; Bilenko, I.  A.; Billingsley, G.; Bini, S.; Birney, R.; Birnholtz, O.; Biscans, S.; Bischi, M.; Biscoveanu, S.; Bisht, A.; Biswas, B.; Bitossi,

Population of Merging Compact Binaries Inferred Using Gravitational Waves through GWTC-3

We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star-black hole mergers. We infer the binary neutron star merger rate to be between 10 and 1700 Gpc-3 yr-1 and the neutron star-black hole merger rate to be between 7.8 and 140 Gpc-3 yr-1, assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and 44 Gpc-3 yr-1 at a fiducial redshift (z=0.2). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to (1+z)κ with κ=2.9-1.8+1.7 for z≲1. Using both binary neutron star and neutron star-black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from 1.2-0.2+0.1 to 2.0-0.3+0.3M⊙. We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of 8.3-0.5+0.3 and 27.9-1.8+1.9M⊙. While we continue to find that the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately 60M⊙, which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below χi≈0.25. While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidence of antialigned spins among the binary population. We observe an increase in spin magnitude for systems with more unequal-mass ratio. We also observe evidence of misalignment of spins relative to the orbital angular momentum

The population of merging compact binaries inferred using gravitational waves through GWTC-3

We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 $\rm{Gpc^{-3} yr^{-1}}$ and 1700 $\rm{Gpc^{-3} yr^{-1}}$ and the NSBH merger rate to be between 7.8 $\rm{Gpc^{-3}\, yr^{-1}}$ and 140 $\rm{Gpc^{-3} yr^{-1}}$ , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 $\rm{Gpc^{-3}\, yr^{-1}}$ and 44 $\rm{Gpc^{-3}\, yr^{-1}}$ at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from $1.2^{+0.1}_{-0.2} M_\odot$ to $2.0^{+0.3}_{-0.3} M_\odot$. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 $M_\odot$. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above $\sim 60 M_\odot$. The rate of BBH mergers is observed to increase with redshift at a rate proportional to $(1+z)^{\kappa}$ with $\kappa = 2.9^{+1.7}_{-1.8}$ for $z\lesssim 1$. Observed black hole spins are small, with half of spin magnitudes below $\chi_i \simeq 0.25$. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio

All-sky search for long-duration gravitational-wave bursts in the third Advanced LIGO and Advanced Virgo run

After the detection of gravitational waves from compact binary coalescences, the search for transient gravitational-wave signals with less well-defined waveforms for which matched filtering is not well suited is one of the frontiers for gravitational-wave astronomy. Broadly classified into “short” ≲1  s and “long” ≳1  s duration signals, these signals are expected from a variety of astrophysical processes, including non-axisymmetric deformations in magnetars or eccentric binary black hole coalescences. In this work, we present a search for long-duration gravitational-wave transients from Advanced LIGO and Advanced Virgo’s third observing run from April 2019 to March 2020. For this search, we use minimal assumptions for the sky location, event time, waveform morphology, and duration of the source. The search covers the range of 2–500 s in duration and a frequency band of 24–2048 Hz. We find no significant triggers within this parameter space; we report sensitivity limits on the signal strength of gravitational waves characterized by the root-sum-square amplitude hrss as a function of waveform morphology. These hrss limits improve upon the results from the second observing run by an average factor of 1.8

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure