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1. Supernova neutrino burst detection with the deep underground neutrino experiment

Author

B. Abi, R. Acciarri, M. A. Acero, G. Adamov, D. Adams, M. Adinolfi, Z. Ahmad, J. Ahmed, T. Alion, S. Alonso Monsalve, C. Alt, J. Anderson, C. Andreopoulos, M. P. Andrews, F. Andrianala, S. Andringa, A. Ankowski, M. Antonova, S. Antusch, A. Aranda-Fernandez, A. Ariga, L. O. Arnold, M. A. Arroyave, J. Asaadi, A. Aurisano, V. Aushev, D. Autiero, F. Azfar, H. Back, J. J. Back, C. Backhouse, P. Baesso, L. Bagby, R. Bajou, S. Balasubramanian, P. Baldi, B. Bambah, F. Barao, G. Barenboim, G. J. Barker, W. Barkhouse, C. Barnes, G. Barr, J. Barranco Monarca, N. Barros, J. L. Barrow, A. Bashyal, V. Basque, F. Bay, J. L. Bazo Alba, J. F. Beacom, E. Bechetoille, B. Behera, L. Bellantoni, G. Bellettini, V. Bellini, O. Beltramello, D. Belver, N. Benekos, F. Bento Neves, J. Berger, S. Berkman, P. Bernardini, R. M. Berner, H. Berns, S. Bertolucci, M. Betancourt, Y. Bezawada, M. Bhattacharjee, B. Bhuyan, S. Biagi, J. Bian, M. Biassoni, K. Biery, B. Bilki, M. Bishai, A. Bitadze, A. Blake, B. Blanco Siffert, F. D. M. Blaszczyk, G. C. Blazey, E. Blucher, J. Boissevain, S. Bolognesi, T. Bolton, M. Bonesini, M. Bongrand, F. Bonini, A. Booth, C. Booth, S. Bordoni, A. Borkum, T. Boschi, N. Bostan, P. Bour, S. B. Boyd, D. Boyden, J. Bracinik, D. Braga, D. Brailsford, A. Brandt, J. Bremer, C. Brew, E. Brianne, S. J. Brice, C. Brizzolari, C. Bromberg, G. Brooijmans, J. Brooke, A. Bross, G. Brunetti, N. Buchanan, H. Budd, D. Caiulo, P. Calafiura, J. Calcutt, M. Calin, S. Calvez, E. Calvo, L. Camilleri, A. Caminata, M. Campanelli, D. Caratelli, G. Carini, B. Carlus, P. Carniti, I. Caro Terrazas, H. Carranza, A. Castillo, C. Castromonte, C. Cattadori, F. Cavalier, F. Cavanna, S. Centro, G. Cerati, A. Cervelli, A. Cervera Villanueva, M. Chalifour, C. Chang, E. Chardonnet, A. Chatterjee, S. Chattopadhyay, J. Chaves, H. Chen, M. Chen, Y. Chen, D. Cherdack, C. Chi, S. Childress, A. Chiriacescu, K. Cho, S. Choubey, A. Christensen, D. Christian, G. Christodoulou, E. Church, P. Clarke, T. E. Coan, A. G. Cocco, J. A. B. Coelho, E. Conley, J. M. Conrad, M. Convery, L. Corwin, P. Cotte, L. Cremaldi, L. Cremonesi, J. I. Crespo-Anadón, E. Cristaldo, R. Cross, C. Cuesta, Y. Cui, D. Cussans, M. Dabrowski, H. da Motta, L. Da Silva Peres, C. David, Q. David, G. S. Davies, S. Davini, J. Dawson, K. De, R. M. De Almeida, P. Debbins, I. De Bonis, M. P. Decowski, A. de Gouvêa, P. C. De Holanda, I. L. De Icaza Astiz, A. Deisting, P. De Jong, A. Delbart, D. Delepine, M. Delgado, A. Dell-Acqua, P. De Lurgio, J. R. T. de Mello Neto, D. M. DeMuth, S. Dennis, C. Densham, G. Deptuch, A. De Roeck, V. De Romeri, J. J. De Vries, R. Dharmapalan, M. Dias, F. Diaz, J. S. Díaz, S. Di Domizio, L. Di Giulio, P. Ding, L. Di Noto, C. Distefano, R. Diurba, M. Diwan, Z. Djurcic, N. Dokania, M. J. Dolinski, L. Domine, D. Douglas, F. Drielsma, D. Duchesneau, K. Duffy, P. Dunne, T. Durkin, H. Duyang, O. Dvornikov, D. A. Dwyer, A. S. Dyshkant, M. Eads, D. Edmunds, J. Eisch, S. Emery, A. Ereditato, C. O. Escobar, L. Escudero Sanchez, J. J. Evans, E. Ewart, A. C. Ezeribe, K. Fahey, A. Falcone, C. Farnese, Y. Farzan, J. Felix, E. Fernandez-Martinez, P. Fernandez Menendez, F. Ferraro, L. Fields, A. Filkins, F. Filthaut, R. S. Fitzpatrick, W. Flanagan, B. Fleming, R. Flight, J. Fowler, W. Fox, J. Franc, K. Francis, D. Franco, J. Freeman, J. Freestone, J. Fried, A. Friedland, S. Fuess, I. Furic, A. P. Furmanski, A. Gago, H. Gallagher, A. Gallego-Ros, N. Gallice, V. Galymov, E. Gamberini, T. Gamble, R. Gandhi, R. Gandrajula, S. Gao, D. Garcia-Gamez, M. Á. García-Peris, S. Gardiner, D. Gastler, G. Ge, B. Gelli, A. Gendotti, S. Gent, Z. Ghorbani-Moghaddam, D. Gibin, I. Gil-Botella, C. Girerd, A. K. Giri, D. Gnani, O. Gogota, M. Gold, S. Gollapinni, K. Gollwitzer, R. A. Gomes, L. V. Gomez Bermeo, L. S. Gomez Fajardo, F. Gonnella, J. A. Gonzalez-Cuevas, M. C. Goodman, O. Goodwin, S. Goswami, C. Gotti, E. Goudzovski, C. Grace, M. Graham, E. Gramellini, R. Gran, E. Granados, A. Grant, C. Grant, D. Gratieri, P. Green, S. Green, L. Greenler, M. Greenwood, J. Greer, W. C. Griffith, M. Groh, J. Grudzinski, K. Grzelak, W. Gu, V. Guarino, R. Guenette, A. Guglielmi, B. Guo, K. K. Guthikonda, R. Gutierrez, P. Guzowski, M. M. Guzzo, S. Gwon, A. Habig, A. Hackenburg, H. Hadavand, R. Haenni, A. Hahn, J. Haigh, J. Haiston, T. Hamernik, P. Hamilton, J. Han, K. Harder, D. A. Harris, J. Hartnell, T. Hasegawa, R. Hatcher, E. Hazen, A. Heavey, K. M. Heeger, J. Heise, K. Hennessy, S. Henry, M. A. Hernandez Morquecho, K. Herner, L. Hertel, A. S. Hesam, J. Hewes, A. Higuera, T. Hill, S. J. Hillier, A. Himmel, J. Hoff, C. Hohl, A. Holin, E. Hoppe, G. A. Horton-Smith, M. Hostert, A. Hourlier, B. Howard, R. Howell, J. Huang, J. Hugon, G. Iles, N. Ilic, A. M. Iliescu, R. Illingworth, A. Ioannisian, R. Itay, A. Izmaylov, E. James, B. Jargowsky, F. Jediny, C. Jesùs-Valls, X. Ji, L. Jiang, S. Jiménez, A. Jipa, A. Joglekar, C. Johnson, R. Johnson, B. Jones, S. Jones, C. K. Jung, T. Junk, Y. Jwa, M. Kabirnezhad, A. Kaboth, I. Kadenko, F. Kamiya, G. Karagiorgi, A. Karcher, M. Karolak, Y. Karyotakis, S. Kasai, S. P. Kasetti, L. Kashur, N. Kazaryan, E. Kearns, P. Keener, K. J. Kelly, E. Kemp, W. Ketchum, S. H. Kettell, M. Khabibullin, A. Khotjantsev, A. Khvedelidze, D. Kim, B. King, B. Kirby, M. Kirby, J. Klein, K. Koehler, L. W. Koerner, S. Kohn, P. P. Koller, M. Kordosky, T. Kosc, U. Kose, V. A. Kostelecký, K. Kothekar, F. Krennrich, I. Kreslo, Y. Kudenko, V. A. Kudryavtsev, S. Kulagin, J. Kumar, R. Kumar, C. Kuruppu, V. Kus, T. Kutter, A. Lambert, K. Lande, C. E. Lane, K. Lang, T. Langford, P. Lasorak, D. Last, C. Lastoria, A. Laundrie, A. Lawrence, I. Lazanu, R. LaZur, T. Le, J. Learned, P. LeBrun, G. Lehmann Miotto, R. Lehnert, M. A. Leigui de Oliveira, M. Leitner, M. Leyton, L. Li, S. Li, S. W. Li, T. Li, Y. Li, H. Liao, C. S. Lin, S. Lin, A. Lister, B. R. Littlejohn, J. Liu, S. Lockwitz, T. Loew, M. Lokajicek, I. Lomidze, K. Long, K. Loo, D. Lorca, T. Lord, J. M. LoSecco, W. C. Louis, K. B. Luk, X. Luo, N. Lurkin, T. Lux, V. P. Luzio, D. MacFarland, A. A. Machado, P. Machado, C. T. Macias, J. R. Macier, A. Maddalena, P. Madigan, S. Magill, K. Mahn, A. Maio, A. Major, J. A. Maloney, G. Mandrioli, J. Maneira, L. Manenti, S. Manly, A. Mann, K. Manolopoulos, M. Manrique Plata, A. Marchionni, W. Marciano, D. Marfatia, C. Mariani, J. Maricic, F. Marinho, A. D. Marino, M. Marshak, C. Marshall, J. Marshall, J. Marteau, J. Martin-Albo, N. Martinez, D. A. Martinez Caicedo, S. Martynenko, K. Mason, A. Mastbaum, M. Masud, S. Matsuno, J. Matthews, C. Mauger, N. Mauri, K. Mavrokoridis, R. Mazza, A. Mazzacane, E. Mazzucato, E. McCluskey, N. McConkey, K. S. McFarland, C. McGrew, A. McNab, A. Mefodiev, P. Mehta, P. Melas, M. Mellinato, O. Mena, S. Menary, H. Mendez, A. Menegolli, G. Meng, M. D. Messier, W. Metcalf, M. Mewes, H. Meyer, T. Miao, G. Michna, T. Miedema, J. Migenda, R. Milincic, W. Miller, J. Mills, C. Milne, O. Mineev, O. G. Miranda, S. Miryala, C. S. Mishra, S. R. Mishra, A. Mislivec, D. Mladenov, I. Mocioiu, K. Moffat, N. Moggi, R. Mohanta, T. A. Mohayai, N. Mokhov, J. Molina, L. Molina Bueno, A. Montanari, C. Montanari, D. Montanari, L. M. Montano Zetina, J. Moon, M. Mooney, A. Moor, D. Moreno, B. Morgan, C. Morris, C. Mossey, E. Motuk, C. A. Moura, J. Mousseau, W. Mu, L. Mualem, J. Mueller, M. Muether, S. Mufson, F. Muheim, A. Muir, M. Mulhearn, H. Muramatsu, S. Murphy, J. Musser, J. Nachtman, S. Nagu, M. Nalbandyan, R. Nandakumar, D. Naples, S. Narita, D. Navas-Nicolás, N. Nayak, M. Nebot-Guinot, L. Necib, K. Negishi, J. K. Nelson, J. Nesbit, M. Nessi, D. Newbold, M. Newcomer, D. Newhart, R. Nichol, E. Niner, K. Nishimura, A. Norman, A. Norrick, R. Northrop, P. Novella, J. A. Nowak, M. Oberling, A. Olivares Del Campo, A. Olivier, Y. Onel, Y. Onishchuk, J. Ott, L. Pagani, S. Pakvasa, O. Palamara, S. Palestini, J. M. Paley, M. Pallavicini, C. Palomares, E. Pantic, V. Paolone, V. Papadimitriou, R. Papaleo, A. Papanestis, S. Paramesvaran, S. Parke, Z. Parsa, M. Parvu, S. Pascoli, L. Pasqualini, J. Pasternak, J. Pater, C. Patrick, L. Patrizii, R. B. Patterson, S. J. Patton, T. Patzak, A. Paudel, B. Paulos, L. Paulucci, Z. Pavlovic, G. Pawloski, D. Payne, V. Pec, S. J. M. Peeters, Y. Penichot, E. Pennacchio, A. Penzo, O. L. G. Peres, J. Perry, D. Pershey, G. Pessina, G. Petrillo, C. Petta, R. Petti, F. Piastra, L. Pickering, F. Pietropaolo, J. Pillow, J. Pinzino, R. Plunkett, R. Poling, X. Pons, N. Poonthottathil, S. Pordes, M. Potekhin, R. Potenza, B. V. K. S. Potukuchi, J. Pozimski, M. Pozzato, S. Prakash, T. Prakash, S. Prince, G. Prior, D. Pugnere, K. Qi, X. Qian, J. L. Raaf, R. Raboanary, V. Radeka, J. Rademacker, B. Radics, A. Rafique, E. Raguzin, M. Rai, M. Rajaoalisoa, I. Rakhno, H. T. Rakotondramanana, L. Rakotondravohitra, Y. A. Ramachers, R. Rameika, M. A. Ramirez Delgado, B. Ramson, A. Rappoldi, G. Raselli, P. Ratoff, S. Ravat, H. Razafinime, J. S. Real, B. Rebel, D. Redondo, M. Reggiani-Guzzo, T. Rehak, J. Reichenbacher, S. D. Reitzner, A. Renshaw, S. Rescia, F. Resnati, A. Reynolds, G. Riccobene, L. C. J. Rice, K. Rielage, Y. Rigaut, D. Rivera, L. Rochester, M. Roda, P. Rodrigues, M. J. Rodriguez Alonso, J. Rodriguez Rondon, A. J. Roeth, H. Rogers, S. Rosauro-Alcaraz, M. Rossella, J. Rout, S. Roy, A. Rubbia, C. Rubbia, B. Russell, J. Russell, D. Ruterbories, R. Saakyan, S. Sacerdoti, T. Safford, N. Sahu, P. Sala, N. Samios, M. C. Sanchez, D. A. Sanders, D. Sankey, S. Santana, M. Santos-Maldonado, N. Saoulidou, P. Sapienza, C. Sarasty, I. Sarcevic, G. Savage, V. Savinov, A. Scaramelli, A. Scarff, A. Scarpelli, T. Schaffer, H. Schellman, P. Schlabach, D. Schmitz, K. Scholberg, A. Schukraft, E. Segreto, J. Sensenig, I. Seong, A. Sergi, F. Sergiampietri, D. Sgalaberna, M. H. Shaevitz, S. Shafaq, M. Shamma, H. R. Sharma, R. Sharma, T. Shaw, C. Shepherd-Themistocleous, S. Shin, D. Shooltz, R. Shrock, L. Simard, N. Simos, J. Sinclair, G. Sinev, J. Singh, V. Singh, R. Sipos, F. W. Sippach, G. Sirri, A. Sitraka, K. Siyeon, D. Smargianaki, A. Smith, E. Smith, P. Smith, J. Smolik, M. Smy, P. Snopok, M. Soares Nunes, H. Sobel, M. Soderberg, C. J. Solano Salinas, S. Söldner-Rembold, N. Solomey, V. Solovov, W. E. Sondheim, M. Sorel, J. Soto-Oton, A. Sousa, K. Soustruznik, F. Spagliardi, M. Spanu, J. Spitz, N. J. C. Spooner, K. Spurgeon, R. Staley, M. Stancari, L. Stanco, H. M. Steiner, J. Stewart, B. Stillwell, J. Stock, F. Stocker, T. Stokes, M. Strait, T. Strauss, S. Striganov, A. Stuart, D. Summers, A. Surdo, V. Susic, L. Suter, C. M. Sutera, R. Svoboda, B. Szczerbinska, A. M. Szelc, R. Talaga, H. A. Tanaka, B. Tapia Oregui, A. Tapper, S. Tariq, E. Tatar, R. Tayloe, A. M. Teklu, M. Tenti, K. Terao, C. A. Ternes, F. Terranova, G. Testera, A. Thea, J. L. Thompson, C. Thorn, S. C. Timm, A. Tonazzo, M. Torti, M. Tórtola, F. Tortorici, D. Totani, M. Toups, C. Touramanis, J. Trevor, W. H. Trzaska, Y. T. Tsai, Z. Tsamalaidze, K. V. Tsang, N. Tsverava, S. Tufanli, C. Tull, E. Tyley, M. Tzanov, M. A. Uchida, J. Urheim, T. Usher, M. R. Vagins, P. Vahle, G. A. Valdiviesso, E. Valencia, Z. Vallari, J. W. F. Valle, S. Vallecorsa, R. Van Berg, R. G. Van de Water, D. Vanegas Forero, F. Varanini, D. Vargas, G. Varner, J. Vasel, G. Vasseur, K. Vaziri, S. Ventura, A. Verdugo, S. Vergani, M. A. Vermeulen, M. Verzocchi, H. Vieira de Souza, C. Vignoli, C. Vilela, B. Viren, T. Vrba, T. Wachala, A. V. Waldron, M. Wallbank, H. Wang, J. Wang, Y. Wang, K. Warburton, D. Warner, M. Wascko, D. Waters, A. Watson, P. Weatherly, A. Weber, M. Weber, H. Wei, A. Weinstein, D. Wenman, M. Wetstein, M. R. While, A. White, L. H. Whitehead, D. Whittington, M. J. Wilking, C. Wilkinson, Z. Williams, F. Wilson, R. J. Wilson, J. Wolcott, T. Wongjirad, K. Wood, L. Wood, E. Worcester, M. Worcester, C. Wret, W. Wu, Y. Xiao, G. Yang, T. Yang, N. Yershov, K. Yonehara, T. Young, B. Yu, J. Yu, R. Zaki, J. Zalesak, L. Zambelli, B. Zamorano, A. Zani, L. Zazueta, G. P. Zeller, J. Zennamo, K. Zeug, C. Zhang, M. Zhao, E. Zhivun, G. Zhu, E. D. Zimmerman, M. Zito, S. Zucchelli, J. Zuklin, V. Zutshi, and R. Zwaska

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract The deep underground neutrino experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE’s ability to constrain the $$\nu _e$$ ν e spectral parameters of the neutrino burst will be considered.

Published
2021
Full Text
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2. Prospects for beyond the Standard Model physics searches at the Deep Underground Neutrino Experiment

Author

B. Abi, R. Acciarri, M. A. Acero, G. Adamov, D. Adams, M. Adinolfi, Z. Ahmad, J. Ahmed, T. Alion, S. Alonso Monsalve, C. Alt, J. Anderson, C. Andreopoulos, M. P. Andrews, F. Andrianala, S. Andringa, A. Ankowski, M. Antonova, S. Antusch, A. Aranda-Fernandez, A. Ariga, L. O. Arnold, M. A. Arroyave, J. Asaadi, A. Aurisano, V. Aushev, D. Autiero, F. Azfar, H. Back, J. J. Back, C. Backhouse, P. Baesso, L. Bagby, R. Bajou, S. Balasubramanian, P. Baldi, B. Bambah, F. Barao, G. Barenboim, G. J. Barker, W. Barkhouse, C. Barnes, G. Barr, J. Barranco Monarca, N. Barros, J. L. Barrow, A. Bashyal, V. Basque, F. Bay, J. L. Bazo Alba, J. F. Beacom, E. Bechetoille, B. Behera, L. Bellantoni, G. Bellettini, V. Bellini, O. Beltramello, D. Belver, N. Benekos, F. Bento Neves, J. Berger, S. Berkman, P. Bernardini, R. M. Berner, H. Berns, S. Bertolucci, M. Betancourt, Y. Bezawada, M. Bhattacharjee, B. Bhuyan, S. Biagi, J. Bian, M. Biassoni, K. Biery, B. Bilki, M. Bishai, A. Bitadze, A. Blake, B. Blanco Siffert, F. D. M. Blaszczyk, G. C. Blazey, E. Blucher, J. Boissevain, S. Bolognesi, T. Bolton, M. Bonesini, M. Bongrand, F. Bonini, A. Booth, C. Booth, S. Bordoni, A. Borkum, T. Boschi, N. Bostan, P. Bour, S. B. Boyd, D. Boyden, J. Bracinik, D. Braga, D. Brailsford, A. Brandt, J. Bremer, C. Brew, E. Brianne, S. J. Brice, C. Brizzolari, C. Bromberg, G. Brooijmans, J. Brooke, A. Bross, G. Brunetti, N. Buchanan, H. Budd, D. Caiulo, P. Calafiura, J. Calcutt, M. Calin, S. Calvez, E. Calvo, L. Camilleri, A. Caminata, M. Campanelli, D. Caratelli, G. Carini, B. Carlus, P. Carniti, I. Caro Terrazas, H. Carranza, A. Castillo, C. Castromonte, C. Cattadori, F. Cavalier, F. Cavanna, S. Centro, G. Cerati, A. Cervelli, A. Cervera Villanueva, M. Chalifour, C. Chang, E. Chardonnet, A. Chatterjee, S. Chattopadhyay, J. Chaves, H. Chen, M. Chen, Y. Chen, D. Cherdack, C. Chi, S. Childress, A. Chiriacescu, K. Cho, S. Choubey, A. Christensen, D. Christian, G. Christodoulou, E. Church, P. Clarke, T. E. Coan, A. G. Cocco, J. A. B. Coelho, E. Conley, J. M. Conrad, M. Convery, L. Corwin, P. Cotte, L. Cremaldi, L. Cremonesi, J. I. Crespo-Anadón, E. Cristaldo, R. Cross, C. Cuesta, Y. Cui, D. Cussans, M. Dabrowski, H. da Motta, L. Da Silva Peres, C. David, Q. David, G. S. Davies, S. Davini, J. Dawson, K. De, R. M. De Almeida, P. Debbins, I. De Bonis, M. P. Decowski, A. de Gouvêa, P. C. De Holanda, I. L. De Icaza Astiz, A. Deisting, P. De Jong, A. Delbart, D. Delepine, M. Delgado, A. Dell’Acqua, P. De Lurgio, J. R. T. de Mello Neto, D. M. DeMuth, S. Dennis, C. Densham, G. Deptuch, A. De Roeck, V. De Romeri, J. J. De Vries, R. Dharmapalan, M. Dias, F. Diaz, J. S. Díaz, S. Di Domizio, L. Di Giulio, P. Ding, L. Di Noto, C. Distefano, R. Diurba, M. Diwan, Z. Djurcic, N. Dokania, M. J. Dolinski, L. Domine, D. Douglas, F. Drielsma, D. Duchesneau, K. Duffy, P. Dunne, T. Durkin, H. Duyang, O. Dvornikov, D. A. Dwyer, A. S. Dyshkant, M. Eads, D. Edmunds, J. Eisch, S. Emery, A. Ereditato, C. O. Escobar, L. Escudero Sanchez, J. J. Evans, E. Ewart, A. C. Ezeribe, K. Fahey, A. Falcone, C. Farnese, Y. Farzan, J. Felix, E. Fernandez-Martinez, P. Fernandez Menendez, F. Ferraro, L. Fields, A. Filkins, F. Filthaut, R. S. Fitzpatrick, W. Flanagan, B. Fleming, R. Flight, J. Fowler, W. Fox, J. Franc, K. Francis, D. Franco, J. Freeman, J. Freestone, J. Fried, A. Friedland, S. Fuess, I. Furic, A. P. Furmanski, A. Gago, H. Gallagher, A. Gallego-Ros, N. Gallice, V. Galymov, E. Gamberini, T. Gamble, R. Gandhi, R. Gandrajula, S. Gao, D. Garcia-Gamez, M. Á. García-Peris, S. Gardiner, D. Gastler, G. Ge, B. Gelli, A. Gendotti, S. Gent, Z. Ghorbani-Moghaddam, D. Gibin, I. Gil-Botella, C. Girerd, A. K. Giri, D. Gnani, O. Gogota, M. Gold, S. Gollapinni, K. Gollwitzer, R. A. Gomes, L. V. Gomez Bermeo, L. S. Gomez Fajardo, F. Gonnella, J. A. Gonzalez-Cuevas, M. C. Goodman, O. Goodwin, S. Goswami, C. Gotti, E. Goudzovski, C. Grace, M. Graham, E. Gramellini, R. Gran, E. Granados, A. Grant, C. 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Zazueta, G. P. Zeller, J. Zennamo, K. Zeug, C. Zhang, M. Zhao, Y. Zhao, E. Zhivun, G. Zhu, E. D. Zimmerman, M. Zito, S. Zucchelli, J. Zuklin, V. Zutshi, and R. Zwaska

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE’s sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.

Published
2021
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3. Long-baseline neutrino oscillation physics potential of the DUNE experiment

Author

B. Abi, R. Acciarri, M. A. Acero, G. Adamov, D. Adams, M. Adinolfi, Z. Ahmad, J. Ahmed, T. Alion, S. Alonso Monsalve, C. Alt, J. Anderson, C. Andreopoulos, M. P. Andrews, F. Andrianala, S. Andringa, A. Ankowski, M. Antonova, S. Antusch, A. Aranda-Fernandez, A. Ariga, L. O. Arnold, M. A. Arroyave, J. Asaadi, A. Aurisano, V. Aushev, D. Autiero, F. Azfar, H. Back, J. J. Back, C. Backhouse, P. Baesso, L. Bagby, R. Bajou, S. Balasubramanian, P. Baldi, B. Bambah, F. Barao, G. Barenboim, G. J. Barker, W. Barkhouse, C. Barnes, G. Barr, J. Barranco Monarca, N. Barros, J. L. Barrow, A. Bashyal, V. Basque, F. Bay, J. L. Bazo Alba, J. F. Beacom, E. Bechetoille, B. Behera, L. Bellantoni, G. Bellettini, V. Bellini, O. Beltramello, D. Belver, N. Benekos, F. Bento Neves, J. Berger, S. Berkman, P. Bernardini, R. M. Berner, H. Berns, S. Bertolucci, M. Betancourt, Y. Bezawada, M. Bhattacharjee, B. Bhuyan, S. Biagi, J. Bian, M. Biassoni, K. Biery, B. Bilki, M. Bishai, A. Bitadze, A. Blake, B. Blanco Siffert, F. D. M. Blaszczyk, G. C. Blazey, E. Blucher, J. Boissevain, S. Bolognesi, T. Bolton, M. Bonesini, M. Bongrand, F. Bonini, A. Booth, C. Booth, S. Bordoni, A. Borkum, T. Boschi, N. Bostan, P. Bour, S. B. Boyd, D. Boyden, J. Bracinik, D. Braga, D. Brailsford, A. Brandt, J. Bremer, C. Brew, E. Brianne, S. J. Brice, C. Brizzolari, C. Bromberg, G. Brooijmans, J. Brooke, A. Bross, G. Brunetti, N. Buchanan, H. Budd, D. Caiulo, P. Calafiura, J. Calcutt, M. Calin, S. Calvez, E. Calvo, L. Camilleri, A. Caminata, M. Campanelli, D. Caratelli, G. Carini, B. Carlus, P. Carniti, I. Caro Terrazas, H. Carranza, A. Castillo, C. Castromonte, C. Cattadori, F. Cavalier, F. Cavanna, S. Centro, G. Cerati, A. Cervelli, A. Cervera Villanueva, M. Chalifour, C. Chang, E. Chardonnet, A. Chatterjee, S. Chattopadhyay, J. Chaves, H. Chen, M. Chen, Y. Chen, D. Cherdack, C. Chi, S. Childress, A. Chiriacescu, K. Cho, S. Choubey, A. Christensen, D. Christian, G. Christodoulou, E. Church, P. Clarke, T. 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LoSecco, W. C. Louis, K. B. Luk, X. Luo, N. Lurkin, T. Lux, V. P. Luzio, D. MacFarland, A. A. Machado, P. Machado, C. T. Macias, J. R. Macier, A. Maddalena, P. Madigan, S. Magill, K. Mahn, A. Maio, J. A. Maloney, G. Mandrioli, J. Maneira, L. Manenti, S. Manly, A. Mann, K. Manolopoulos, M. Manrique Plata, A. Marchionni, W. Marciano, D. Marfatia, C. Mariani, J. Maricic, F. Marinho, A. D. Marino, M. Marshak, C. Marshall, J. Marshall, J. Marteau, J. Martin-Albo, N. Martinez, D. A. Martinez Caicedo, S. Martynenko, K. Mason, A. Mastbaum, M. Masud, S. Matsuno, J. Matthews, C. Mauger, N. Mauri, K. Mavrokoridis, R. Mazza, A. Mazzacane, E. Mazzucato, E. McCluskey, N. McConkey, K. S. McFarland, C. McGrew, A. McNab, A. Mefodiev, P. Mehta, P. Melas, M. Mellinato, O. Mena, S. Menary, H. Mendez, A. Menegolli, G. Meng, M. D. Messier, W. Metcalf, M. Mewes, H. Meyer, T. Miao, G. Michna, T. Miedema, J. Migenda, R. Milincic, W. Miller, J. Mills, C. Milne, O. Mineev, O. G. Miranda, S. Miryala, C. S. 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Reggiani-Guzzo, T. Rehak, J. Reichenbacher, S. D. Reitzner, A. Renshaw, S. Rescia, F. Resnati, A. Reynolds, G. Riccobene, L. C. J. Rice, K. Rielage, Y. Rigaut, D. Rivera, L. Rochester, M. Roda, P. Rodrigues, M. J. Rodriguez Alonso, J. Rodriguez Rondon, A. J. Roeth, H. Rogers, S. Rosauro-Alcaraz, M. Rossella, J. Rout, S. Roy, A. Rubbia, C. Rubbia, B. Russell, J. Russell, D. Ruterbories, R. Saakyan, S. Sacerdoti, T. Safford, N. Sahu, P. Sala, N. Samios, M. C. Sanchez, D. A. Sanders, D. Sankey, S. Santana, M. Santos-Maldonado, N. Saoulidou, P. Sapienza, C. Sarasty, I. Sarcevic, G. Savage, V. Savinov, A. Scaramelli, A. Scarff, A. Scarpelli, T. Schaffer, H. Schellman, P. Schlabach, D. Schmitz, K. Scholberg, A. Schukraft, E. Segreto, J. Sensenig, I. Seong, A. Sergi, F. Sergiampietri, D. Sgalaberna, M. H. Shaevitz, S. Shafaq, M. Shamma, H. R. Sharma, R. Sharma, T. Shaw, C. Shepherd-Themistocleous, S. Shin, D. Shooltz, R. Shrock, L. Simard, N. Simos, J. Sinclair, G. Sinev, J. Singh, V. 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P. Zeller, J. Zennamo, K. Zeug, C. Zhang, M. Zhao, E. Zhivun, G. Zhu, E. D. Zimmerman, M. Zito, S. Zucchelli, J. Zuklin, V. Zutshi, and R. Zwaska

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5 $$\sigma $$ σ , for all $$\delta _{\mathrm{CP}}$$ δ CP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3 $$\sigma $$ σ (5 $$\sigma $$ σ ) after an exposure of 5 (10) years, for 50% of all $$\delta _{\mathrm{CP}}$$ δ CP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to $$\sin ^{2} 2\theta _{13}$$ sin 2 2 θ 13 to current reactor experiments.

Published
2020
Full Text
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4. Deep Underground Neutrino Experiment (DUNE) Near Detector Conceptual Design Report

Author

A. Abed Abud, B. Abi, R. Acciarri, M. A. Acero, G. Adamov, D. Adams, M. Adinolfi, A. Aduszkiewicz, Z. Ahmad, J. Ahmed, T. Alion, S. Alonso Monsalve, M. Alrashed, C. Alt, A. Alton, P. Amedo, J. Anderson, C. Andreopoulos, M. P. Andrews, F. Andrianala, S. Andringa, N. Anfimov, A. Ankowski, M. Antonova, S. Antusch, A. Aranda-Fernandez, A. Ariga, L. O. Arnold, M. A. Arroyave, J. Asaadi, A. Aurisano, V. Aushev, D. Autiero, M. Ayala-Torres, F. Azfar, A. Back, H. Back, J. J. Back, C. Backhouse, P. Baesso, I. Bagaturia, L. Bagby, S. Balasubramanian, P. Baldi, B. Baller, B. Bambah, F. Barao, G. Barenboim, G. J. Barker, W. Barkhouse, C. Barnes, G. Barr, J. Barranco Monarca, N. Barros, J. L. Barrow, A. Basharina-Freshville, A. Bashyal, V. Basque, E. Belchior, J. B. R. Battat, F. Battisti, F. Bay, J. L. Bazo Alba, J. F. Beacom, E. Bechetoille, B. Behera, L. Bellantoni, G. Bellettini, V. Bellini, O. Beltramello, D. Belver, N. Benekos, F. Bento Neves, S. Berkman, P. Bernardini, R. M. Berner, H. Berns, S. Bertolucci, M. Betancourt, A. Betancur Rodríguez, M. Bhattacharjee, S. Bhuller, B. Bhuyan, S. Biagi, J. Bian, M. Biassoni, K. Biery, B. Bilki, M. Bishai, A. Bitadze, A. Blake, F. D. M. Blaszczyk, G. C. Blazey, E. Blucher, J. Boissevain, S. Bolognesi, T. Bolton, L. Bomben, M. Bonesini, M. Bongrand, F. Bonini, A. Booth, C. Booth, S. Bordoni, A. Borkum, T. Boschi, N. Bostan, P. Bour, C. Bourgeois, S. B. Boyd, D. Boyden, J. Bracinik, D. Braga, D. Brailsford, A. Brandt, J. Bremer, C. Brew, E. Brianne, S. J. Brice, C. Brizzolari, C. Bromberg, G. Brooijmans, J. Brooke, A. Bross, G. Brunetti, M. Brunetti, N. Buchanan, H. Budd, I. Cagnoli, D. Caiulo, P. Calafiura, J. Calcutt, M. Calin, S. Calvez, E. Calvo, A. Caminata, M. Campanelli, K. Cankocak, D. Caratelli, G. Carini, B. Carlus, P. Carniti, I. Caro Terrazas, H. Carranza, T. Carroll, J. F. Castaño Forero, A. Castillo, C. Castromonte, E. Catano-Mur, C. Cattadori, F. Cavalier, F. Cavanna, S. Centro, G. Cerati, A. Cervelli, A. 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Kim, B. King, B. Kirby, M. Kirby, J. Klein, K. Koehler, L. W. Koerner, S. Kohn, P. P. Koller, L. Kolupaeva, M. Kordosky, T. Kosc, U. Kose, V. A. Kostelecký, K. Kothekar, F. Krennrich, I. Kreslo, Y. Kudenko, V. A. Kudryavtsev, S. Kulagin, J. Kumar, P. Kumar, R. Kumar, P. Kunze, N. Kurita, C. Kuruppu, V. Kus, T. Kutter, A. Lambert, B. Land, K. Lande, C. E. Lane, K. Lang, T. Langford, J. Larkin, P. Lasorak, D. Last, C. Lastoria, A. Laundrie, G. Laurenti, A. Lawrence, I. Lazanu, R. LaZur, T. Le, S. Leardini, J. Learned, P. LeBrun, T. LeCompte, G. Lehmann Miotto, R. Lehnert, M. A. Leigui de Oliveira, M. Leitner, L. Li, S. W. Li, T. Li, Y. Li, H. Liao, C. S. Lin, Q. Lin, S. Lin, A. Lister, B. R. Littlejohn, J. Liu, S. Lockwitz, T. Loew, M. Lokajicek, I. Lomidze, K. Long, K. Loo, D. Lorca, T. Lord, J. M. LoSecco, W. C. Louis, X. G. Lu, K. B. Luk, X. Luo, N. Lurkin, T. Lux, V. P. Luzio, D. MacFarlane, A. A. Machado, P. Machado, C. T. Macias, J. R. Macier, A. Maddalena, A. Madera, P. Madigan, S. Magill, K. Mahn, A. Maio, A. Major, J. A. Maloney, G. Mandrioli, R. C. Mandujano, J. Maneira, L. Manenti, S. Manly, A. Mann, K. Manolopoulos, M. Manrique Plata, V. N. Manyam, L. Manzanillas, M. Marchan, A. Marchionni, W. Marciano, D. Marfatia, C. Mariani, J. Maricic, R. Marie, F. Marinho, A. D. Marino, D. Marsden, M. Marshak, C. M. Marshall, J. Marshall, J. Marteau, J. Martin-Albo, N. Martinez, D. A. Martinez Caicedo, S. Martynenko, K. Mason, A. Mastbaum, M. Masud, S. Matsuno, J. Matthews, C. Mauger, N. Mauri, K. Mavrokoridis, I. Mawby, R. Mazza, A. Mazzacane, E. Mazzucato, T. McAskill, E. McCluskey, N. McConkey, K. S. McFarland, C. McGrew, A. McNab, A. Mefodiev, P. Mehta, P. Melas, O. Mena, S. Menary, H. Mendez, D. P. Méndez, A. Menegolli, G. Meng, M. D. Messier, W. Metcalf, T. Mettler, M. Mewes, H. Meyer, T. Miao, G. Michna, T. Miedema, J. Migenda, V. Mikola, R. Milincic, W. Miller, J. Mills, C. Milne, O. Mineev, O. G. Miranda, S. Miryala, C. S. Mishra, S. R. Mishra, A. Mislivec, D. Mladenov, I. Mocioiu, K. Moffat, N. Moggi, R. Mohanta, T. A. Mohayai, N. Mokhov, J. Molina, L. Molina Bueno, A. Montanari, C. Montanari, D. Montanari, E. Montagna, L. M. Montano Zetina, J. Moon, M. Mooney, A. F. Moor, D. Moreno, C. Morris, C. Mossey, E. Motuk, C. A. Moura, J. Mousseau, W. Mu, L. Mualem, J. Mueller, M. Muether, S. Mufson, F. Muheim, A. Muir, M. Mulhearn, D. Munford, H. Muramatsu, S. Murphy, J. Musser, J. Nachtman, S. Nagu, M. Nalbandyan, R. Nandakumar, D. Naples, S. Narita, D. Navas-Nicolás, A. Navrer-Agasson, N. Nayak, M. Nebot-Guinot, K. Negishi, J. K. Nelson, J. Nesbit, M. Nessi, D. Newbold, M. Newcomer, D. Newhart, H. Newton, M. Niccolo, R. Nichol, F. Nicolas-Arnaldos, M. Nicoletta, E. Niner, K. Nishimura, A. Norman, A. Norrick, R. Northrop, P. Novella, J. A. Nowak, M. Oberling, J. P. Ochoa-Ricoux, A. Olivares Del Campo, A. Olivier, A. Olshevskiy, Y. Onel, Y. Onishchuk, J. Ott, L. Pagani, S. Pakvasa, G. Palacio, O. Palamara, S. Palestini, J. M. Paley, M. Pallavicini, C. Palomares, J. L. Palomino-Gallo, E. Pantic, V. Paolone, V. Papadimitriou, R. Papaleo, A. Papanestis, S. Paramesvaran, S. Parke, Z. Parsa, M. Parvu, S. Pascoli, L. Pasqualini, J. Pasternak, J. Pater, C. Patrick, L. Patrizii, R. B. Patterson, S. J. Patton, T. Patzak, A. Paudel, B. Paulos, L. Paulucci, Z. Pavlovic, G. Pawloski, D. Payne, V. Pec, S. J. M. Peeters, E. Pennacchio, A. Penzo, O. L. G. Peres, J. Perry, D. Pershey, G. Pessina, G. Petrillo, C. Petta, R. Petti, F. Piastra, L. Pickering, F. Pietropaolo, R. Plunkett, R. Poling, X. Pons, N. Poonthottathil, F. Poppi, S. Pordes, J. Porter, M. Potekhin, R. Potenza, B. V. K. S. Potukuchi, J. Pozimski, M. Pozzato, S. Prakash, T. Prakash, S. Prince, D. Pugnere, X. Qian, M. C. Queiroga Bazetto, J. L. Raaf, V. Radeka, J. Rademacker, B. Radics, A. Rafique, E. Raguzin, M. Rai, M. Rajaoalisoa, I. Rakhno, A. Rakotonandrasana, L. Rakotondravohitra, Y. A. Ramachers, R. Rameika, M. A. Ramirez Delgado, B. Ramson, A. Rappoldi, G. Raselli, P. Ratoff, S. Raut, R. F. Razakamiandra, J. S. Real, B. Rebel, M. Reggiani-Guzzo, T. Rehak, J. Reichenbacher, S. D. Reitzner, H. Rejeb Sfar, A. Renshaw, S. Rescia, F. Resnati, A. Reynolds, C. Riccio, G. Riccobene, L. C. J. Rice, J. Ricol, A. Rigamonti, Y. Rigaut, D. Rivera, L. Rochester, M. Roda, P. Rodrigues, M. J. Rodriguez Alonso, E. Rodriguez Bonilla, J. Rodriguez Rondon, S. Rosauro-Alcaraz, M. Rosenberg, P. Rosier, B. Roskovec, M. Rossella, J. Rout, P. Roy, S. Roy, A. Rubbia, C. Rubbia, F. C. Rubio, B. Russell, D. Ruterbories, R. Saakyan, S. Sacerdoti, T. Safford, R. Sahay, N. Sahu, P. Sala, N. Samios, O. Samoylov, M. C. Sanchez, D. A. Sanders, D. Sankey, S. Santana, M. Santos-Maldonado, N. Saoulidou, P. Sapienza, C. Sarasty, I. Sarcevic, G. Savage, V. Savinov, A. Scaramelli, A. Scarff, A. Scarpelli, T. Schaffer, H. Schellman, P. Schlabach, D. Schmitz, K. Scholberg, A. Schukraft, E. Segreto, J. Sensenig, I. Seong, A. Sergi, D. Sgalaberna, M. H. Shaevitz, S. Shafaq, M. Shamma, R. Sharankova, H. R. Sharma, R. Sharma, T. Shaw, C. Shepherd-Themistocleous, S. Shin, D. Shooltz, R. Shrock, L. Simard, F. Simon, N. Simos, J. Sinclair, G. Sinev, J. Singh, V. Singh, R. Sipos, F. W. Sippach, G. Sirri, A. Sitraka, K. Siyeon, K. Skarpaas VIII, A. Smith, E. Smith, P. Smith, J. Smolik, M. Smy, E. L. Snider, P. Snopok, M. Soares Nunes, H. Sobel, M. Soderberg, C. J. Solano Salinas, S. Söldner-Rembold, S. Soleti, N. Solomey, V. Solovov, W. E. Sondheim, M. Sorel, J. Soto-Oton, A. Sousa, K. Soustruznik, F. Spagliardi, M. Spanu, J. Spitz, N. J. C. Spooner, K. Spurgeon, R. Staley, M. Stancari, L. Stanco, R. Stanley, R. Stein, H. M. Steiner, J. Stewart, B. Stillwell, J. Stock, F. Stocker, T. Stokes, M. Strait, T. Strauss, S. Striganov, A. Stuart, J. G. Suarez, H. Sullivan, D. Summers, A. Surdo, V. Susic, L. Suter, C. M. Sutera, R. Svoboda, B. Szczerbinska, A. M. Szelc, R. Talaga, H. A. Tanaka, B. Tapia Oregui, A. Tapper, S. Tariq, E. Tatar, R. Tayloe, A. M. Teklu, M. Tenti, K. Terao, C. A. Ternes, F. Terranova, G. Testera, A. Thea, J. L. Thompson, C. Thorn, S. C. Timm, J. Todd, A. Tonazzo, D. Torbunov, M. Torti, M. Tortola, F. Tortorici, D. Totani, M. Toups, C. Touramanis, N. Tosi, R. Travaglini, J. Trevor, S. Trilov, W. H. Trzaska, Y. T. Tsai, Z. Tsamalaidze, K. V. Tsang, N. Tsverava, S. Tufanli, C. Tull, E. Tyley, M. Tzanov, M. A. Uchida, J. Urheim, T. Usher, S. Uzunyan, M. R. Vagins, P. Vahle, G. A. Valdiviesso, E. Valencia, P. Valerio, Z. Vallari, J. W. F. Valle, S. Vallecorsa, R. Van Berg, R. G. Van de Water, F. Varanini, D. Vargas, G. Varner, J. Vasel, S. Vasina, G. Vasseur, N. Vaughan, K. Vaziri, S. Ventura, A. Verdugo, S. Vergani, M. A. Vermeulen, M. Verzocchi, M. Vicenzi, H. Vieira de Souza, C. Vignoli, C. Vilela, B. Viren, T. Vrba, T. Wachala, A. V. Waldron, M. Wallbank, H. Wang, J. Wang, L. Wang, M. H. L. S. Wang, Y. Wang, K. Warburton, D. Warner, M. Wascko, D. Waters, A. Watson, P. Weatherly, A. Weber, M. Weber, H. Wei, A. Weinstein, D. Wenman, M. Wetstein, A. White, L. H. Whitehead, D. Whittington, M. J. Wilking, C. Wilkinson, Z. Williams, F. Wilson, R. J. Wilson, J. Wolcott, T. Wongjirad, A. Wood, K. Wood, E. Worcester, M. Worcester, C. Wret, W. Wu, Y. Xiao, E. Yandel, G. Yang, K. Yang, S. Yang, T. Yang, A. Yankelevich, N. Yershov, K. Yonehara, T. Young, B. Yu, H. Yu, J. Yu, W. Yuan, R. Zaki, J. Zalesak, L. Zambelli, B. Zamorano, A. Zani, L. Zazueta, G. Zeit, G. P. Zeller, J. Zennamo, K. Zeug, C. Zhang, M. Zhao, E. Zhivun, G. Zhu, P. Zilberman, E. D. Zimmerman, M. Zito, S. Zucchelli, J. Zuklin, V. Zutshi, R. Zwaska, and On behalf of the DUNE Collaboration

Subjects
neutrino, near detector, neutrino oscillations, Deep Underground Neutrino Experiment, DUNE, Physics, QC1-999, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

The Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents.

Published
2021
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8. Introduction

Author

Li, Zongzhi, primary, Moore, Adrian T., additional, and Samuel R., Staley, additional

Published
2021
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14. The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians:A Mendelian randomization study

Author

Maria-Carolina Borges, Phillip Haycock, Jie Zheng, Gibran Hemani, Laurence J Howe, A Floriaan Schmidt, James R Staley, R Thomas Lumbers, Albert Henry, Rozenn N Lemaitre, Tom R Gaunt, Michael V Holmes, George Davey Smith, Aroon D Hingorani, and Deborah A Lawlor

Subjects
Asian People, Cardiovascular Diseases, Fatty Acids, Genetics, Humans, General Medicine, Mendelian Randomization Analysis, Molecular Biology, Polymorphism, Single Nucleotide, Genetics (clinical)
Abstract

Despite early interest, the evidence linking fatty acids to cardiovascular diseases remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the aetiology of several cardiovascular disease endpoints in up to 1,153,768 European and 212,453 East Asian ancestry individuals. As instruments, we selected single nucleotide polymorphisms (SNP) mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple cardiovascular diseases, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low- density lipoprotein (LDL)-cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that genetically-determined PUFA and MUFA biosynthesis are involved in the aetiology of cardiovascular diseases and suggest LDL-cholesterol as a potential mediating trait between PUFA biosynthesis and cardiovascular diseases risk.

Published
2022

15. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

Author

Liam Gaziano, Luanluan Sun, Matthew Arnold, Steven Bell, Kelly Cho, Stephen K. Kaptoge, Rebecca J. Song, Stephen Burgess, Daniel C. Posner, Katja Mosconi, Cassianne Robinson-Cohen, Amy M. Mason, Thomas R. Bolton, Ran Tao, Elias Allara, Petra Schubert, Lingyan Chen, James R. Staley, Natalie Staplin, Servet Altay, Pilar Amiano, Volker Arndt, Johan Ärnlöv, Elizabeth L.M. Barr, Cecilia Björkelund, Jolanda M.A. Boer, Hermann Brenner, Edoardo Casiglia, Paolo Chiodini, Jackie A. Cooper, Josef Coresh, Mary Cushman, Rachel Dankner, Karina W. Davidson, Renate T. de Jongh, Chiara Donfrancesco, Gunnar Engström, Heinz Freisling, Agustín Gómez de la Cámara, Vilmundur Gudnason, Graeme J. Hankey, Per-Olof Hansson, Alicia K. Heath, Ewout J. Hoorn, Hironori Imano, Simerjot K. Jassal, Rudolf Kaaks, Verena Katzke, Jussi Kauhanen, Stefan Kiechl, Wolfgang Koenig, Richard A. Kronmal, Cecilie Kyrø, Deborah A. Lawlor, Börje Ljungberg, Conor MacDonald, Giovanna Masala, Christa Meisinger, Olle Melander, Conchi Moreno Iribas, Toshiharu Ninomiya, Dorothea Nitsch, Børge G. Nordestgaard, Charlotte Onland-Moret, Luigi Palmieri, Dafina Petrova, Jose Ramón Quirós Garcia, Annika Rosengren, Carlotta Sacerdote, Masaru Sakurai, Carmen Santiuste, Matthias B. Schulze, Sabina Sieri, Johan Sundström, Valérie Tikhonoff, Anne Tjønneland, Tammy Tong, Rosario Tumino, Ioanna Tzoulaki, Yvonne T. van der Schouw, W.M. Monique Verschuren, Henry Völzke, Robert B. Wallace, S. Goya Wannamethee, Elisabete Weiderpass, Peter Willeit, Mark Woodward, Kazumasa Yamagishi, Raul Zamora-Ros, Elvis A. Akwo, Saiju Pyarajan, David R. Gagnon, Philip S. Tsao, Sumitra Muralidhar, Todd L. Edwards, Scott M. Damrauer, Jacob Joseph, Lisa Pennells, Peter W.F. Wilson, Seamus Harrison, Thomas A. Gaziano, Michael Inouye, Colin Baigent, Juan P. Casas, Claudia Langenberg, Nick Wareham, Elio Riboli, J.Michael Gaziano, John Danesh, Adriana M. Hung, Adam S. Butterworth, Angela M. Wood, Emanuele Di Angelantonio, Anna Koettgen, Jonathan Shaw, Robert Atkins, Paul Zimmet, Peter Whincup, Johann Willeit, Christoph Leitner, Anne Tybjaerg-Hansen, Peter Schnohr, Shoaib Afzal, David Lora Pablos, Cristina Martin Arriscado, Carmen Romero Ferreiro, Hannah Stocker, Ben Schöttker, Bernd Holleczek, Angela Chetrit, Lennart Welin, Kurt Svärdsudd, Lauren Lissner, Dominique Hange, Kirsten Mehlig, Dorothea Nagel, Paul E. Norman, Osvaldo Almeida, Leon Flicker, Jun Hata, Takanori Honda, Yoshihiko Furuta, Hiroyasu Iso, Akihiko Kitamura, Isao Muraki, Jukka T. Salonen, Tomi-Pekka Tuomainen, E. M. van Zutphen, N. M. van Schoor, Cinzia Lo Noce, Richard Kronmal, Georg Lappas, Peter M. Nilsson, Bo Hedblad, Jonathan Shaffer, Joseph Schwartz, Daichi Shimbo, Shinichi Sato, Mina Hayama-Terada, Simerjot Jassal, Thor Aspelund, Bolli Thorsson, Gunnar Sigurdsson, Layal Chaker, Kamran M. Ikram, Maryam Kavousi, Hugh Tunstall-Pedoe, Günay Can, Hüsniye Yüksel, Uğur Özkan, Hideaki Nakagawa, Yuko Morikawa, Masao Ishizaki, Edith Feskens, Johanna M Geleijnse, Daan Kromhout, Internal Medicine, Neurology, Epidemiology, Bell, Steven [0000-0001-6774-3149], Posner, Daniel C [0000-0002-3056-6924], Mason, Amy M [0000-0002-8019-0777], Allara, Elias [0000-0002-1634-8330], Staplin, Natalie [0000-0003-4482-4418], Arndt, Volker [0000-0001-9320-8684], Ärnlöv, Johan [0000-0002-6933-4637], Barr, Elizabeth LM [0000-0003-4284-1716], Boer, Jolanda MA [0000-0002-9714-4304], Brenner, Hermann [0000-0002-6129-1572], Casiglia, Edoardo [0000-0002-0003-3289], Chiodini, Paolo [0000-0003-0139-2264], Coresh, Josef [0000-0002-4598-0669], Cushman, Mary [0000-0002-7871-6143], Davidson, Karina W [0000-0002-9162-477X], de Jongh, Renate T [0000-0001-8414-3938], Engström, Gunnar [0000-0002-8618-9152], de la Cámara, Agustín Gómez [0000-0001-6827-6319], Gudnason, Vilmundur [0000-0001-5696-0084], Hankey, Graeme J [0000-0002-6044-7328], Hansson, Per-Olof [0000-0001-6323-0506], Heath, Alicia K [0000-0001-6517-1300], Hoorn, Ewout J [0000-0002-8738-3571], Imano, Hironori [0000-0002-6661-4254], Katzke, Verena [0000-0002-6509-6555], Kiechl, Stefan [0000-0002-9836-2514], Koenig, Wolfgang [0000-0002-2064-9603], Kronmal, Richard A [0000-0002-9897-7076], Kyrø, Cecilie [0000-0002-9083-8960], Ljungberg, Börje [0000-0002-4121-3753], MacDonald, Conor [0000-0002-4989-803X], Masala, Giovanna [0000-0002-5758-9069], Ninomiya, Toshiharu [0000-0003-1345-9032], Nordestgaard, Børge G [0000-0002-1954-7220], Onland-Moret, Charlotte [0000-0002-2360-913X], Palmieri, Luigi [0000-0002-4298-2642], Rosengren, Annika [0000-0002-5409-6605], Schulze, Matthias B [0000-0002-0830-5277], Sieri, Sabina [0000-0001-5201-172X], Sundström, Johan [0000-0003-2247-8454], Tikhonoff, Valérie [0000-0001-7846-0101], Tong, Tammy [0000-0002-0284-8959], Tzoulaki, Ioanna [0000-0002-4275-9328], van der Schouw, Yvonne T [0000-0002-4605-435X], Wannamethee, S Goya [0000-0001-9484-9977], Weiderpass, Elisabete [0000-0003-2237-0128], Willeit, Peter [0000-0002-1866-7159], Woodward, Mark [0000-0001-9800-5296], Yamagishi, Kazumasa [0000-0003-3301-5519], Zamora-Ros, Raul [0000-0002-6236-6804], Gagnon, David R [0000-0002-6367-3179], Tsao, Philip S [0000-0001-7274-9318], Edwards, Todd L [0000-0003-4318-6119], Damrauer, Scott M [0000-0001-8009-1632], Joseph, Jacob [0000-0002-7279-4896], Pennells, Lisa [0000-0002-8594-3061], Gaziano, Thomas A [0000-0002-5985-345X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nick [0000-0003-1422-2993], Hung, Adriana M [0000-0002-3203-1608], Butterworth, Adam S [0000-0002-6915-9015], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Gaziano, Liam, Sun, Luanluan, Arnold, Matthew, Bell, Steven, Cho, Kelly, Kaptoge, Stephen K, Song, Rebecca J, Burgess, Stephen, Posner, Daniel C, Mosconi, Katja, Robinson-Cohen, Cassianne, Mason, Amy M, Bolton, Thomas R, Tao, Ran, Allara, Elia, Schubert, Petra, Chen, Lingyan, Staley, James R, Staplin, Natalie, Altay, Servet, Amiano, Pilar, Arndt, Volker, Ärnlöv, Johan, Barr, Elizabeth L M, Björkelund, Cecilia, Boer, Jolanda M A, Brenner, Hermann, Casiglia, Edoardo, Chiodini, Paolo, Cooper, Jackie A, Coresh, Josef, Cushman, Mary, Dankner, Rachel, Davidson, Karina W, de Jongh, Renate T, Donfrancesco, Chiara, Engström, Gunnar, Freisling, Heinz, de la Cámara, Agustín Gómez, Gudnason, Vilmundur, Hankey, Graeme J, Hansson, Per-Olof, Heath, Alicia K, Hoorn, Ewout J, Imano, Hironori, Jassal, Simerjot K, Kaaks, Rudolf, Katzke, Verena, Kauhanen, Jussi, Kiechl, Stefan, Koenig, Wolfgang, Kronmal, Richard A, Kyrø, Cecilie, Lawlor, Deborah A, Ljungberg, Börje, Macdonald, Conor, Masala, Giovanna, Meisinger, Christa, Melander, Olle, Moreno Iribas, Conchi, Ninomiya, Toshiharu, Nitsch, Dorothea, Nordestgaard, Børge G, Onland-Moret, Charlotte, Palmieri, Luigi, Petrova, Dafina, Garcia, Jose Ramón Quiró, Rosengren, Annika, Sacerdote, Carlotta, Sakurai, Masaru, Santiuste, Carmen, Schulze, Matthias B, Sieri, Sabina, Sundström, Johan, Tikhonoff, Valérie, Tjønneland, Anne, Tong, Tammy, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T, Monique Verschuren, W M, Völzke, Henry, Wallace, Robert B, Wannamethee, S Goya, Weiderpass, Elisabete, Willeit, Peter, Woodward, Mark, Yamagishi, Kazumasa, Zamora-Ros, Raul, Akwo, Elvis A, Pyarajan, Saiju, Gagnon, David R, Tsao, Philip S, Muralidhar, Sumitra, Edwards, Todd L, Damrauer, Scott M, Joseph, Jacob, Pennells, Lisa, Wilson, Peter W F, Harrison, Seamu, Gaziano, Thomas A, Inouye, Michael, Baigent, Colin, Casas, Juan P, Langenberg, Claudia, Wareham, Nick, Riboli, Elio, Gaziano, J Michael, Danesh, John, Hung, Adriana M, Butterworth, Adam S, Wood, Angela M, Di Angelantonio, Emanuele, Internal medicine, AMS - Ageing & Vitality, AMS - Musculoskeletal Health, Amsterdam Gastroenterology Endocrinology Metabolism, Epidemiology and Data Science, APH - Aging & Later Life, and APH - Personalized Medicine

Subjects
kidney disease, General Practice, Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program, Coronary Disease, coronary disease, Kidney, Malalties coronàries, 1117 Public Health and Health Services, Coronary diseases, SDG 3 - Good Health and Well-being, cardiovascular disease, Risk Factors, Physiology (medical), Diabetes Mellitus, Humans, Cardiac and Cardiovascular Systems, Prospective Studies, 1102 Cardiorespiratory Medicine and Haematology, Kardiologi, Kidney diseases, Malalties cardiovasculars, Cardiovascular Diseases, Kidney Diseases, Stroke, 1103 Clinical Sciences, Mendelian Randomization Analysis, kidney diseases, stroke, Allmänmedicin, Cardiovascular diseases, Cardiovascular System & Hematology, Malalties del ronyó, Cardiology and Cardiovascular Medicine, cardiovascular diseases
Abstract

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Published
2022

16. Effects of Nutrient Level and Growth Rate on the Conjugation Process That Transfers Mobile Antibiotic Resistance Genes in Continuous Cultures

Author

Mohammadreza Shafieifini, Yuepeng Sun, Zachery R. Staley, Jean-Jack Riethoven, and Xu Li

Subjects
Bacteria, Ecology, Public and Environmental Health Microbiology, Water, Drug Resistance, Microbial, Nutrients, Tetracycline, Wastewater, Applied Microbiology and Biotechnology, Anti-Bacterial Agents, Genes, Bacterial, Escherichia coli, Humans, Ecosystem, Food Science, Biotechnology
Abstract

Bacteria in the effluent of wastewater treatment plants (WWTPs) can transfer antibiotic resistance genes (ARGs) to the bacteria in receiving water through conjugation; however, there is a lack of quantitative assessment of this phenomenon in continuous cultures. Our objective was to determine the effects of background nutrient levels in river water column and growth rates of bacteria on the conjugation frequency of ARGs from effluent bacteria to river bacteria, as well as on the resulting resistance level (i.e., MICs) of the river bacteria. Chemostats were employed to simulate the discharge points of WWTPs into rivers, where effluent bacteria (donor cells) meet river bacteria (recipient cells). Both donor and recipient cells were Escherichia coli cells, and the donor cells were constructed by filter mating with bacteria in the effluent of a local WWTP. Results showed that higher bacterial growth rate (0.45 h(−1) versus 0.15 h(−1)) led to higher conjugation frequencies (10(−4) versus 10(−6) transconjugant per recipient). The nutrient level also significantly affected the conjugation frequency, albeit to a lesser extent than the growth rate. The MIC against tetracycline increased from 2 mg/L in the recipient to 64 to 128 mg/L in transconjugants. In comparison, the MIC only increased to as high as 8 mg/L in mutants. Whole-genome sequencing showed that the tet-containing plasmid in both the donor and the transconjugant cells also occur in other fecal bacterial genera. The quantitative information obtained from this study can inform hazard identification related to the proliferation of wastewater-associated ARGs in surface water. IMPORTANCE WWTPs have been regarded as an important hot spot of ARGs. The discharge point of WWTP effluent, where ARGs may be horizontally transferred from bacteria of treated wastewater to bacteria of receiving water, is an important interface between the human-dominated ecosystem and the natural environment. The use of batch cultures in previous studies cannot adequately simulate the nutrient conditions and growth rates in receiving water. In this study, chemostats were employed to simulate the continuous growth of bacteria in receiving water. Furthermore, the experimental setup allowed for separate investigations on the effects of nutrient levels (i.e., simulating background nutrients in river water) and bacterial growth rates on conjugation frequencies and resulting resistance levels. The study generates statistically sound ecological data that can be used to estimate the risk of wastewater-originated ARGs as part of the One Health framework.

Published
2022

17. DNA methylation signatures of adolescent victimization: analysis of a longitudinal monozygotic twin sample

Author

Joe Burrage, Chloe C. Y. Wong, Georgina Mansell, Helen L. Fisher, Radhika Kandaswamy, Eilis Hannon, Susanna Roberts, Karen Sugden, Ehsan Pishva, Jonathan Mill, Benjamin Williams, Andrea Danese, Louise Arseneault, Aisha Dahir, and James R Staley

Subjects
0301 basic medicine, Epigenomics, Cancer Research, animal structures, longitudinal, Adolescent, Monozygotic twin, Biology, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, Humans, Epigenetics, Child, Molecular Biology, adversity, Crime Victims, Genetics, DNA methylation, epigenetics, fungi, victimization, twins, Twins, Monozygotic, Adolescence, 030104 developmental biology, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Research Article, Research Paper, Genome-Wide Association Study
Abstract

Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome by controlling for genetic variation, age, gender, and shared environmental exposures. We conducted longitudinal epigenome-wide association analyses (EWAS) on DNA methylation (DNAm) profiles of 118 monozygotic (MZ) twin pairs from the Environmental Risk study with and without severe adolescent victimization generated using buccal DNA collected at ages 5, 10 and 18, and the Illumina EPIC array. Additionally, we performed cross-sectional EWAS on age-18 blood and buccal DNA from the same individuals to elucidate tissue-specific signatures of severe adolescent victimization. Our analyses identified 20 suggestive differentially methylated positions (DMPs) (P

Published
2020

18. The Human Health Implications of Antibiotic Resistance in Environmental Isolates from Two Nebraska Watersheds

Author

Linsey Donner, Zachery R. Staley, Jonathan Petali, Jodi Sangster, Xu Li, Wayne Mathews, Daniel Snow, Adina Howe, Michelle Soupir, and Shannon Bartelt-Hunt

Subjects
Microbiology (medical), General Immunology and Microbiology, Ecology, Bacteria, Physiology, Water, Nebraska, Cell Biology, Wastewater, Anti-Bacterial Agents, Infectious Diseases, Genes, Bacterial, Drug Resistance, Bacterial, Genetics, Animals, Humans
Abstract

One Health field-based approaches are needed to connect the occurrence of antibiotics present in the environment with the presence of antibiotic resistance genes (ARGs) in Gram-negative bacteria that confer resistance to antibiotics important in for both veterinary and human health. Water samples from two Nebraska watersheds influenced by wastewater effluent and agricultural runoff were tested for the presence of antibiotics used in veterinary and human medicine. The water samples were also cultured to identify the bacteria present. Of those bacteria isolated, the Gram-negative rods capable of causing human infections had antimicrobial susceptibility testing and whole-genome sequencing (WGS) performed to identify ARGs present. Of the 211 bacterial isolates identified, 37 belonged to pathogenic genera known to cause human infections. Genes conferring resistance to beta-lactams, aminoglycosides, fosfomycins, and quinolones were the most frequently detected ARGs associated with horizontal gene transfer (HGT) in the watersheds. WGS also suggest recent HGT events involving ARGs transferred between watershed isolates and bacteria of human and animal origins. The results of this study demonstrate the linkage of antibiotics and bacterial ARGs present in the environment with potential human and/or veterinary health impacts.

Published
2022

19. Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases

Author

Hannah M. Martin, Yi Liu, Tom R. Gaunt, Michael V. Holmes, Matthew R. Nelson, Jie Zheng, Benjamin B. Sun, Stephen Burgess, George Davey Smith, Jamie Robinson, John Danesh, James R Staley, Shan Luo, Robert A. Scott, Pau Erola, Karol Estrada, Dawn M. Waterworth, Gibran Hemani, Benjamin Elsworth, Alex Gutteridge, Valeriia Haberland, Charles Laurin, Heiko Runz, Denis Baird, Venexia M Walker, Tom G. Richardson, Mark R. Hurle, Jimmy Z. Liu, Joseph C. Maranville, Adam S. Butterworth, Philip C Haycock, James Yarmolinsky, Rita Santos, Linda McCarthy, Zheng, Jie [0000-0002-6623-6839], Haberland, Valeriia [0000-0002-3874-0683], Robinson, Jamie [0000-0001-8721-6514], Richardson, Tom G [0000-0002-7918-2040], Elsworth, Benjamin [0000-0001-7328-4233], Sun, Benjamin B [0000-0001-6347-2281], Smith, George Davey [0000-0002-1407-8314], Butterworth, Adam S [0000-0002-6915-9015], Hemani, Gibran [0000-0003-0920-1055], Scott, Robert A [0000-0003-3634-3016], Gaunt, Tom R [0000-0003-0924-3247], and Apollo - University of Cambridge Repository

Subjects
Proteomics, Linkage disequilibrium, Proteome, Genome-wide association study, Computational biology, 030204 cardiovascular system & hematology, Phenome, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Mendelian randomization, Human proteome project, Genetics, Humans, Genetic Predisposition to Disease, health care economics and organizations, Genetic association, 030304 developmental biology, 0303 health sciences, Drug discovery, High-throughput screening, Colocalization, Mendelian Randomization Analysis, Blood Proteins, Phenotype, 3. Good health, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here, we estimated the effects of 1002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130 (31.5%) were not supported by results of colocalization analyses, suggesting that genetic confounding due to linkage disequilibrium (LD) is widespread in naive phenome-wide association studies of proteins. Combining MR and colocalization evidence in cis-only analyses, we identified 111 putatively causal effects between 65 proteins and 52 disease-related phenotypes (www.epigraphdb.org/pqtl/). Evaluation of data from historic drug development programmes showed that target-indication pairs with MR and colocalization support were more likely to be approved, evidencing the value of our approach in identifying and prioritising potential therapeutic targets.

Published
2020

20. Antibiotic-resistant Enterococcus species in marine habitats: A review

Author

Valerie J. Harwood, Brian R. McMinn, Zachery R. Staley, Warish Ahmed, and Asja Korajkic

Subjects
Veterinary medicine, medicine.drug_class, business.industry, Health, Toxicology and Mutagenesis, 0208 environmental biotechnology, Antibiotics, Public Health, Environmental and Occupational Health, Marine habitats, Sewage, 02 engineering and technology, 010501 environmental sciences, Biology, biology.organism_classification, 01 natural sciences, 020801 environmental engineering, Antibiotic resistance, Enterococcus, Ampicillin, medicine, Environmental Chemistry, Vancomycin, business, Feces, 0105 earth and related environmental sciences, medicine.drug
Abstract

Antibiotic-resistant Enterococcus (ARE) are among leading causes of nosocomial infections worldwide. Enterococcus spp. are ubiquitous in sewage, which can contaminate surface waters via many pathways, providing a route of exposure for humans. This review focuses on ARE in marine and estuarine habitats, including marine animals. Phylogenetic confirmation of the genus Enterococcus and intermediate or full resistance to clinically relevant antibiotics were inclusion criteria. The proportion of resistant isolates varied greatly among antibiotics, for example, 24.2% for ampicillin and 2.4% for vancomycin. The water column contained the highest proportion of ARE observations (18.8%), followed by animal feces and tissues (14.8%), sediment (9.4%), and sand (2.0%). The proportion of multidrug-resistant isolates was the greatest in animal tissue and fecal samples, followed by water and sediments. This review indicates that clinically relevant ARE are present in marine/estuarine habitats and that animals may be important reservoirs.

Published
2020

21. A robust and efficient method for Mendelian randomization with hundreds of genetic variants

Author

James R Staley, Christopher N. Foley, Joanna M. M. Howson, Stephen Burgess, Elias Allara, Burgess, Stephen [0000-0001-5365-8760], Allara, Elias [0000-0002-1634-8330], Howson, Joanna MM [0000-0001-7618-0050], Apollo - University of Cambridge Repository, Howson, Joanna M M [0000-0001-7618-0050], and Howson, Joanna M. M. [0000-0001-7618-0050]

Subjects
0301 basic medicine, Epidemiology, General Physics and Astronomy, Coronary Disease, Body Mass Index, Correlation, Prognostic markers, 0302 clinical medicine, Risk Factors, 692/308/174, lcsh:Science, Molecular Epidemiology, Multidisciplinary, Instrumental variable, Genetic Pleiotropy, 631/208/205, 3. Good health, Phenotype, Research Design, Mean squared error, Science, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 631/443/592/2727, 03 medical and health sciences, 692/53/2422, Genetic variation, Mendelian randomization, Humans, Genetic Predisposition to Disease, Risk factor, Genetic Association Studies, Triglycerides, Genetic association study, Models, Genetic, Mechanism (biology), Cholesterol, HDL, Genetic Variation, Reproducibility of Results, General Chemistry, Cardiovascular genetics, Cholesterol, LDL, Mendelian Randomization Analysis, 030104 developmental biology, Diabetes Mellitus, Type 2, lcsh:Q, 030217 neurology & neurosurgery
Abstract

Mendelian randomization (MR) is an epidemiological technique that uses genetic variants to distinguish correlation from causation in observational data. The reliability of a MR investigation depends on the validity of the genetic variants as instrumental variables (IVs). We develop the contamination mixture method, a method for MR with two modalities. First, it identifies groups of genetic variants with similar causal estimates, which may represent distinct mechanisms by which the risk factor influences the outcome. Second, it performs MR robustly and efficiently in the presence of invalid IVs. Compared to other robust methods, it has the lowest mean squared error across a range of realistic scenarios. The method identifies 11 variants associated with increased high-density lipoprotein-cholesterol, decreased triglyceride levels, and decreased coronary heart disease risk that have the same directions of associations with various blood cell traits, suggesting a shared mechanism linking lipids and coronary heart disease risk mediated via platelet aggregation., Mendelian randomization (MR) is a method for inferring causal relationships between risk factors and outcomes via associated genetic variants. Here, Burgess et al. develop the contamination mixture method which yields robust MR results in the presence of invalid instrumental variables and groups variants by their effect estimates.

Published
2020

22. Coding and regulatory variants are associated with serum protein levels and disease

Author

Valur Emilsson, Valborg Gudmundsdottir, Alexander Gudjonsson, Thorarinn Jonmundsson, Brynjolfur G. Jonsson, Mohd A. Karim, Marjan Ilkov, James R. Staley, Elias F. Gudmundsson, Lenore J. Launer, Jan H. Lindeman, Nicholas M. Morton, Thor Aspelund, John R. Lamb, Lori L. Jennings, Vilmundur Gudnason, Emilsson, Valur [0000-0001-9982-0524], Gudmundsdottir, Valborg [0000-0002-7459-1603], Jonmundsson, Thorarinn [0000-0001-9158-0087], Gudmundsson, Elias F [0000-0002-7661-4872], Launer, Lenore J [0000-0002-3238-7612], Morton, Nicholas M [0000-0001-8218-8462], Aspelund, Thor [0000-0002-7998-5433], Jennings, Lori L [0000-0001-5130-8417], Gudnason, Vilmundur [0000-0001-5696-0084], and Apollo - University of Cambridge Repository

Subjects
Proteomics, Male, Genotype, Proteome, Science, 631/208/205/2138, 45/43, Iceland, General Physics and Astronomy, 631/45/475, Genome-wide association studies, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, 82/80, Prognostic markers, 692/53/2422, Humans, Disease, Exome, Genetic Predisposition to Disease, Aged, Multidisciplinary, article, General Chemistry, Blood Proteins, Female
Abstract

Circulating proteins can be used to diagnose and predict disease-related outcomes. A deep serum proteome survey recently revealed close associations between serum protein networks and common disease. In the current study, 54,469 low-frequency and common exome-array variants were compared to 4782 protein measurements in the serum of 5343 individuals from the AGES Reykjavik cohort. This analysis identifies a large number of serum proteins with genetic signatures overlapping those of many diseases. More specifically, using a study-wide significance threshold, we find that 2021 independent exome array variants are associated with serum levels of 1942 proteins. These variants reside in genetic loci shared by hundreds of complex disease traits, highlighting serum proteins’ emerging role as biomarkers and potential causative agents of a wide range of diseases., Finding the genetic basis of protein expression can elucidate the genetic mechanisms of disease. Here, the authors link low-frequency and common DNA sequence variants to thousands of serum proteins, finding genetic overlap between circulating proteins and a wide range of common diseases.

Published
2022

29. Travel demand management

Author

Zongzhi Li, R Staley Samuel, and Adrian T. Moore

Subjects
Demand management, Business, Environmental economics
Published
2021

31. A robust mean and variance test with application to high-dimensional phenotypes

Author

Frank Windmeijer, Kate Tilling, George Davey Smith, James R Staley, Matthew Suderman, and Matthew Lyon

Subjects
Epigenomics, Epidemiology, 03 medical and health sciences, 0302 clinical medicine, ARIES, Statistics, Medicine, Humans, Joint location-and-scale test, Categorical variable, 030304 developmental biology, Genetic association, 0303 health sciences, DNA methylation, business.industry, Variability test, Contrast (statistics), Gestational age, DNA Methylation, ALSPAC, Fetal Blood, Outcome (probability), Test (assessment), Phenotype, 030220 oncology & carcinogenesis, business, Type I and type II errors, Genome-Wide Association Study
Abstract

Most studies of continuous health-related outcomes examine differences in mean levels (location) of the outcome by exposure. However, identifying effects on the variability (scale) of an outcome, and combining tests of mean and variability (location-and-scale), could provide additional insights into biological mechanisms. A joint test could improve power for studies of high-dimensional phenotypes, such as epigenome-wide association studies of DNA methylation at CpG sites. One possible cause of heterogeneity of variance is a variable interacting with exposure in its effect on outcome, so a joint test of mean and variability could help in the identification of effect modifiers. Here, we review a scale test, based on the Brown-Forsythe test, for analysing variability of a continuous outcome with respect to both categorical and continuous exposures, and develop a novel joint location-and-scale score (JLSsc) test. These tests were compared to alternatives in simulations and used to test associations of mean and variability of DNA methylation with gender and gestational age using data from the Accessible Resource for Integrated Epigenomics Studies (ARIES). In simulations, the Brown-Forsythe and JLSsc tests retained correct type I error rates when the outcome was not normally distributed in contrast to the other approaches tested which all had inflated type I error rates. These tests also identified > 7500 CpG sites for which either mean or variability in cord blood methylation differed according to gender or gestational age. The Brown-Forsythe test and JLSsc are robust tests that can be used to detect associations not solely driven by a mean effect.

Published
2021

32. Stockpiling versus Composting: Effectiveness in Reducing Antibiotic-Resistant Bacteria and Resistance Genes in Beef Cattle Manure

Author

Bryan L. Woodbury, Shannon L. Bartelt-Hunt, Daniel D. Snow, Zachery R. Staley, Bing Wang, Xu Li, Amy M. Schmidt, and Bobbi S. Stromer

Subjects
Manure storage, 010501 environmental sciences, Beef cattle, 01 natural sciences, Applied Microbiology and Biotechnology, complex mixtures, Toxicology, 03 medical and health sciences, Soil, Antibiotic resistance, Bacterial Proteins, Drug Resistance, Bacterial, Animals, 0105 earth and related environmental sciences, 0303 health sciences, Ecology, biology, Resistance (ecology), Bacteria, 030306 microbiology, Public and Environmental Health Microbiology, Composting, fungi, Stockpile, biology.organism_classification, Manure, Anti-Bacterial Agents, Biodegradation, Environmental, Cattle, Food Science, Biotechnology, Antibiotic resistance genes
Abstract

Manure storage methods can affect the concentration and prevalence of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in cattle manure prior to land application. The objective of this study was to compare stockpiling and composting with respect to their effectiveness in reducing ARB and ARGs in beef cattle manure in a field-scale study. Field experiments were conducted in different seasons with different bulking agents for composting. For both the winter-spring cycle and the summer-fall cycle, ARB concentrations declined below the limit of quantification rapidly in both composting piles and stockpiles; however, ARB prevalence was significantly greater in the composting piles than in the stockpiles. This was likely due to the introduction of ARB from bulking agents. There was no significant change in ARG concentrations between initial and final concentrations for either manure storage treatment during the winter-spring cycle, but a significant reduction of the ARGs erm(B), tet(O), and tet(Q) over time was observed for both the composting pile and stockpile during the summer-fall cycle. Results from this study suggest that (i) bulking agent may be an important source of ARB and ARGs for composting; (ii) during cold months, the heterogeneity of the temperature profile in composting piles could result in poor ARG reduction; and (iii) during warm months, both stockpiling and composting can be effective in reducing ARG abundance. IMPORTANCE Proper treatment of manure is essential to reduce the spread of antibiotic resistance and protect human health. Stockpiling and composting are two manure storage methods which can reduce antibiotic-resistant bacteria and resistance genes, although few field-scale studies have examined the relative efficiency of each method. This study examined the ability of both methods in both winter-spring and summer-fall cycles, while also accounting for heterogeneity within field-scale manure piles. This study determined that bulking agents used in composting could contribute antibiotic-resistant bacteria and resistance genes. Additionally, seasonal variation could hinder the efficacy of composting in colder months due to heterogeneity in temperature within the pile; however, in warmer months, either method of manure storage could be effective in reducing the spread of antibiotic resistance.

Published
2021

34. Sclerostin Downregulation Globally by Naturally Occurring Genetic Variants, or Locally in Atherosclerotic Plaques, Does Not Associate With Cardiovascular Events in Humans

Author

Ciara Vangjeli, James R Staley, Peter Hall, Martin Armstrong, Rogely W. Boyce, Alison Wolfreys, Ian D. van Koeverden, Gerard Pasterkamp, Remi Okoye, Gill Holdsworth, and James R. Turk

Subjects
0301 basic medicine, medicine.medical_specialty, GENETICS, Endocrinology, Diabetes and Metabolism, Population, Romosozumab, Down-Regulation, 030209 endocrinology & metabolism, Bone resorption, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Bone Density, Internal medicine, medicine, Humans, Orthopedics and Sports Medicine, PHENOMEWIDE ASSOCIATION STUDY, Myocardial infarction, education, SCLEROSTIN, Stroke, Aged, Bone mineral, Aged, 80 and over, education.field_of_study, Alendronate, business.industry, Fibrous cap, Original Articles, Middle Aged, medicine.disease, Plaque, Atherosclerotic, CARDIOVASCULAR, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, chemistry, Cardiovascular Diseases, Sclerostin, Female, Original Article, business, BONE MINERAL DENSITY, SOST
Abstract

Inhibition of sclerostin increases bone formation and decreases bone resorption, leading to increased bone mass, bone mineral density, and bone strength and reduced fracture risk. In a clinical study of the sclerostin antibody romosozumab versus alendronate in postmenopausal women (ARCH), an imbalance in adjudicated serious cardiovascular (CV) adverse events driven by an increase in myocardial infarction (MI) and stroke was observed. To explore whether there was a potential mechanistic plausibility that sclerostin expression, or its inhibition, in atherosclerotic (AS) plaques may have contributed to this imbalance, sclerostin was immunostained in human plaques to determine whether it was detected in regions relevant to plaque stability in 94 carotid and 50 femoral AS plaques surgically collected from older female patients (mean age 69.6 ± 10.4 years). Sclerostin staining was absent in most plaques (67%), and when detected, it was of reduced intensity compared with normal aorta and was located in deeper regions of the plaque/wall but was not observed in areas considered relevant to plaque stability (fibrous cap and endothelium). Additionally, genetic variants associated with lifelong reduced sclerostin expression were explored for associations with phenotypes including those related to bone physiology and CV risk factors/events in a population‐based phenomewide association study (PheWAS). Natural genetic modulation of sclerostin by variants with a significant positive effect on bone physiology showed no association with lifetime risk of MI or stroke. These data do not support a causal association between the presence of sclerostin, or its inhibition, in the vasculature and increased risk of serious cardiovascular events. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Published
2021

35. The EWAS Catalog: a database of epigenome-wide association studies

Author

Thomas Battram, Paul Yousefi, Gemma Crawford, Claire Prince, Mahsa Sheikhali Babaei, Gemma Sharp, Charlie Hatcher, María Jesús Vega-Salas, Sahar Khodabakhsh, Oliver Whitehurst, Ryan Langdon, Luke Mahoney, Hannah R. Elliott, Giulia Mancano, Matthew A. Lee, Sarah H. Watkins, Abigail C. Lay, Gibran Hemani, Tom R. Gaunt, Caroline L. Relton, James R. Staley, Matthew Suderman, Elliott, Hannah R., Lay, Abigail C., Gaunt, Tom R., Relton, Caroline L., and Staley, James R.

Subjects
Medicine (miscellaneous), ALSPAC, General Biochemistry, Genetics and Molecular Biology, Bristol Population Health Science Institute
Abstract

Epigenome-wide association studies (EWAS) seek to quantify associations between traits/exposures and DNA methylation measured at thousands or millions of CpG sites across the genome. In recent years, the increase in availability of DNA methylation measures in population-based cohorts and case-control studies has resulted in a dramatic expansion of the number of EWAS being performed and published. To make this rich source of results more accessible, we have manually curated a database of CpG-trait associations (with p-4) from published EWAS, each assaying over 100,000 CpGs in at least 100 individuals. From January 7, 2022, The EWAS Catalog contained 1,737,746 associations from 2,686 EWAS. This includes 1,345,398 associations from 342 peer-reviewed publications. In addition, it also contains summary statistics for 392,348 associations from 427 EWAS, performed on data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Gene Expression Omnibus (GEO). The database is accompanied by a web-based tool and R package, giving researchers the opportunity to query EWAS associations quickly and easily, and gain insight into the molecular underpinnings of disease as well as the impact of traits and exposures on the DNA methylome. The EWAS Catalog data extraction team continue to update the database monthly and we encourage any EWAS authors to upload their summary statistics to our website. Details of how to upload data can be found here: http://www.ewascatalog.org/upload. The EWAS Catalog is available at http://www.ewascatalog.org.

Published
2021

36. A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits

Author

Paul D. W. Kirk, James R Staley, Benjamin B. Sun, Stephen Burgess, Philip G. Breen, Joanna M. M. Howson, Christopher N. Foley, Foley, Christopher N [0000-0002-0970-2610], Kirk, Paul DW [0000-0002-5931-7489], Burgess, Stephen [0000-0001-5365-8760], Howson, Joanna MM [0000-0001-7618-0050], Apollo - University of Cambridge Repository, Foley, Christopher N. [0000-0002-0970-2610], Kirk, Paul D. W. [0000-0002-5931-7489], and Howson, Joanna M. M. [0000-0001-7618-0050]

Subjects
0301 basic medicine, Linkage disequilibrium, 45/41, 45/43, General Physics and Astronomy, Coronary Disease, Genome-wide association study, 030204 cardiovascular system & hematology, Genome-wide association studies, Linkage Disequilibrium, 0302 clinical medicine, Risk Factors, Pleiotropy, 129, 0303 health sciences, Multidisciplinary, 030305 genetics & heredity, Functional genomics, Genomics, Trait, 139, Algorithms, 141, Science, Quantitative Trait Loci, 631/208/205/2138, Computational biology, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 38, 82/80, 03 medical and health sciences, 692/4019/592/2727, Humans, Genetic Predisposition to Disease, Gene, 030304 developmental biology, Genetic association, 45, Computational Biology, Reproducibility of Results, Multiple traits, Colocalization, Cardiovascular genetics, General Chemistry, 030104 developmental biology, 631/114/794, 631/208/191, 119, Software, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have identified thousands of genomic regions affecting complex diseases. The next challenge is to elucidate the causal genes and mechanisms involved. One approach is to use statistical colocalization to assess shared genetic aetiology across multiple related traits (e.g. molecular traits, metabolic pathways and complex diseases) to identify causal pathways, prioritize causal variants and evaluate pleiotropy. We propose HyPrColoc (Hypothesis Prioritisation for multi-trait Colocalization), an efficient deterministic Bayesian algorithm using GWAS summary statistics that can detect colocalization across vast numbers of traits simultaneously (e.g. 100 traits can be jointly analysed in around 1 s). We perform a genome-wide multi-trait colocalization analysis of coronary heart disease (CHD) and fourteen related traits, identifying 43 regions in which CHD colocalized with ≥1 trait, including 5 previously unknown CHD loci. Across the 43 loci, we further integrate gene and protein expression quantitative trait loci to identify candidate causal genes., Statistical colocalisation is a method to identify causal genes and shared genetic aetiology across traits. Here, the authors describe HyPrColoc, an efficient Bayesian divisive clustering algorithm which integrates summary statistics from genome-wide association studies to detect clusters of colocalised traits from large numbers of traits.

Published
2021

37. Off-Campus Colloquia as Immersive Study and Active Learning: Capitaf, Milton and Rose Friedman’s Home

Author

Signè Thomas and Samuel R. Staley

Subjects
Rose (mathematics), media_common.quotation_subject, Reading (process), Active learning, Wife, Sociology, Visual arts, media_common
Abstract

In this paper, two facilitators of an off-campus colloquia series examine its effectiveness as an alternative to study-abroad programs. The paper evaluates a week-long seminar in political economy held in the Vermont mountains at Capitaf, the former summer home of Nobel Prize-winning economist Milton Friedman and his wife, Rose. The colloquium is structured to foster active learning by combining intensive reading and discussion of Friedman’s critical writings, and immerse students in the place where the economist conducted most of his writing in the late 1960s and 1970s. More than 60 undergraduate students have experienced the program. The program has had a deep, lasting impact on students, as revealed through open-end comments and responses to post-colloquium assessments.

Published
2021

38. MendelianRandomization v0.5.0: updates to an R package for performing Mendelian randomization analyses using summarized data [version 2; peer review: 1 approved, 2 approved with reservations]

Author

Jim R. Broadbent, Christopher N. Foley, Andrew J. Grant, Amy M. Mason, James R. Staley, and Stephen Burgess

Subjects
lcsh:R, lcsh:Medicine, lcsh:Q, lcsh:Science
Abstract

The MendelianRandomization package is a software package written for the R software environment that implements methods for Mendelian randomization based on summarized data. In this manuscript, we describe functions that have been added to the package or updated in recent years. These features can be divided into four categories: robust methods for Mendelian randomization, methods for multivariable Mendelian randomization, functions for data visualization, and the ability to load data into the package seamlessly from the PhenoScanner web-resource. We provide examples of the graphical output produced by the data visualization commands, as well as syntax for obtaining suitable data and performing a Mendelian randomization analysis in a single line of code.

Published
2020

39. Genetic and atherosclerotic plaque immunohistochemical analyses do not associate reduced sclerostin expression with cardiovascular events

Author

Rogely W. Boyce, Gerard Pasterkamp, Remi Okoye, James R Staley, James R. Turk, Martin Armstrong, Alison Wolfreys, Ian D. van Koeverden, Peter Hall, Gill Holdsworth, and Ciara Vangjeli

Subjects
Bone mineral, education.field_of_study, medicine.medical_specialty, business.industry, Fibrous cap, Population, Romosozumab, medicine.disease, Bone resorption, chemistry.chemical_compound, medicine.anatomical_structure, Endocrinology, chemistry, Internal medicine, medicine, Sclerostin, Myocardial infarction, education, business, Stroke
Abstract

The sclerostin antibody romosozumab increases bone formation and decreases bone resorption, leading to increased bone mass, bone mineral density and bone strength, and reduced fracture risk. In a clinical study versus alendronate in postmenopausal women (ARCH), an imbalance in adjudicated serious cardiovascular (CV) events driven by an increase in myocardial infarction (MI) and stroke was observed.To investigate whether inhibition of sclerostin in atherosclerotic plaques may have contributed to this imbalance, sclerostin was immunostained in human plaques to determine whether it was detected in regions relevant to plaque stability. Additionally, genetic variants associated with lifelong reduced sclerostin expression were explored for associations with phenotypes including those related to bone physiology and CV risk factors/events in a population-based phenome-wide association study (PheWAS).Sclerostin expression was absent (67%) or reduced in atherosclerotic plaques and when present was in deeper regions of the plaque/wall and not in areas considered relevant to plaque stability (fibrous cap and endothelium). Natural genetic modulation of sclerostin by variants with a significant positive effect on bone physiology showed no association with lifetime risk of MI or stroke. These data do not support a causal association between sclerostin inhibition and increased risk of serious cardiovascular events.

Published
2020

40. Antibiotic-Resistant

Author

Asja, Korajkic, Brian R, McMinn, Zachery R, Staley, Warish, Ahmed, and Valerie J, Harwood

Subjects
Article
Abstract

Antibiotic-resistant Enterococcus (ARE) are among leading causes of nosocomial infections worldwide. Enterococcus spp. are ubiquitous in sewage, which can contaminate surface waters via many pathways, providing a route of exposure for humans. This review focuses on ARE in marine and estuarine habitats, including marine animals. Phylogenetic confirmation of the genus Enterococcus and intermediate or full resistance to clinically relevant antibiotics were inclusion criteria. The proportion of resistant isolates varied greatly among antibiotics, for example, 24.2% for ampicillin and 2.4% for vancomycin. The water column contained the highest proportion of ARE observations (18.8%), followed by animal feces and tissues (14.8%), sediment (9.4%), and sand (2.0%). The proportion of multidrug-resistant isolates was the greatest in animal tissue and fecal samples, followed by water and sediments. This review indicates that clinically relevant ARE are present in marine/estuarine habitats and that animals may be important reservoirs.

Published
2020

41. Neutrino interaction classification with a convolutional neural network in the DUNE far detector

Author

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C., Goodwin, O., Goswami, S., Gotti, C., Goudzovski, E., Grace, C., Graham, M., Gramellini, E., Gran, R., Granados, E., Grant, A., Grant, C., Gratieri, D., Green, P., Green, S., Greenler, L., Greenwood, M., Greer, J., Griffith, W. C., Groh, M., Grudzinski, J., Grzelak, K., Gu, W., Guarino, V., Guenette, R., Guglielmi, A., Guo, B., Guthikonda, K. K., Gutierrez, R., Guzowski, P., Guzzo, M. M., Gwon, S., Habig, A., Hackenburg, A., Hadavand, H., Haenni, R., Hahn, A., Haigh, J., Haiston, J., Hamernik, T., Hamilton, P., Han, J., Harder, K., Harris, D. A., Hartnell, J., Hasegawa, T., Hatcher, R., Hazen, E., Heavey, A., Heeger, K. M., Heise, J., Hennessy, K., Henry, S., Hernandez Morquecho, M. A., Herner, K., Hertel, L., Hesam, A. S., Hewes, J., Higuera, A., Hill, T., Hillier, S. J., Himmel, A., Hoff, J., Hohl, C., Holin, A., Hoppe, E., Horton-Smith, G. A., Hostert, M., Hourlier, A., Howard, B., Howell, R., Huang, J., Hugon, J., Iles, G., Ilic, N., Iliescu, A. M., Illingworth, R., Ioannisian, A., Itay, R., Izmaylov, A., James, E., Jargowsky, B., Jediny, F., Jesus-Valls, C., Ji, X., Jiang, L., Jimenez, S., Jipa, A., Joglekar, A., Johnson, C., Johnson, R., Jones, B., Jones, S., Jung, C. K., Junk, T., Jwa, Y., Kabirnezhad, M., Kaboth, A., Kadenko, I., Kamiya, F., Karagiorgi, G., Karcher, A., Karolak, M., Karyotakis, Y., Kasai, S., Kasetti, S. P., Kashur, L., Kazaryan, N., Kearns, E., Keener, P., Kelly, K. J., Kemp, E., Ketchum, W., Kettell, S. H., Khabibullin, M., Khotjantsev, A., Khvedelidze, A., Kim, D., King, B., Kirby, B., Kirby, M., Klein, J., Koehler, K., Koerner, L. W., Kohn, S., Koller, P. P., Kordosky, M., Kosc, T., Kose, U., Kostelecky, V. A., Kothekar, K., Krennrich, F., Kreslo, I., Kudenko, Y., Kudryavtsev, V. A., Kulagin, S., Kumar, J., Kumar, R., Kuruppu, C., Kus, V., Kutter, T., Lambert, A., Lande, K., Lane, C. E., Lang, K., Langford, T., Lasorak, P., Last, D., Lastoria, C., Laundrie, A., Lawrence, A., Lazanu, I., Lazur, R., Le, T., Learned, J., Lebrun, P., Lehmann Miotto, G., Lehnert, R., Leigui De Oliveira, M. A., Leitner, M., Leyton, M., Li, L., Li, S., Li, S. W., Li, T., Li, Y., Liao, H., Lin, C. S., Lin, S., Lister, A., Littlejohn, B. R., Liu, J., Lockwitz, S., Loew, T., Lokajicek, M., Lomidze, I., Long, K., Loo, K., Lorca, D., Lord, T., Losecco, J. M., Louis, W. C., Luk, K. B., Luo, X., Lurkin, N., Lux, T., Luzio, V. P., Macfarland, D., Machado, A. A., Machado, P., Macias, C. T., Macier, J. R., Maddalena, A., Madigan, P., Magill, S., Mahn, K., Maio, A., Maloney, J. A., Mandrioli, G., Maneira, J., Manenti, L., Manly, S., Mann, A., Manolopoulos, K., Manrique Plata, M., Marchionni, A., Marciano, W., Marfatia, D., Mariani, C., Maricic, J., Marinho, F., Marino, A. D., Marshak, M., Marshall, C., Marshall, J., Marteau, J., Martin-Albo, J., Martinez, N., Martinez Caicedo, D. A., Martynenko, S., Mason, K., Mastbaum, A., Masud, M., Matsuno, S., Matthews, J., Mauger, C., Mauri, N., Mavrokoridis, K., Mazza, R., Mazzacane, A., Mazzucato, E., Mccluskey, E., Mcconkey, N., Mcfarland, K. S., Mcgrew, C., Mcnab, A., Mefodiev, A., Mehta, P., Melas, P., Mellinato, M., Mena, O., Menary, S., Mendez, H., Menegolli, A., Meng, G., Messier, M. D., Metcalf, W., Mewes, M., Meyer, H., Miao, T., Michna, G., Miedema, T., Migenda, J., Milincic, R., Miller, W., Mills, J., Milne, C., Mineev, O., Miranda, O. G., Miryala, S., Mishra, C. S., Mishra, S. R., Mislivec, A., Mladenov, D., Mocioiu, I., Moffat, K., Moggi, N., Mohanta, R., Mohayai, T. A., Mokhov, N., Molina, J., Molina Bueno, L., Montanari, A., Montanari, C., Montanari, D., Montano Zetina, L. M., Moon, J., Mooney, M., Moor, A., Moreno, D., Morgan, B., Morris, C., Mossey, C., Motuk, E., Moura, C. 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D., Zito, M., Zucchelli, S., Zuklin, J., Zutshi, V., Zwaska, R., Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), AstroParticule et Cosmologie (APC (UMR_7164)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire de l'Accélérateur Linéaire (LAL), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Laboratoire d'Annecy de Physique des Particules (LAPP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), DUNE, XENON (IHEF, IoP, FNWI), ATLAS (IHEF, IoP, FNWI), Abi, B, Acciarri, R, Acero, M, Adamov, G, Adams, D, Adinolfi, M, Ahmad, Z, Ahmed, J, Alion, T, Alonso Monsalve, S, Alt, C, Anderson, J, Andreopoulos, C, Andrews, M, Andrianala, F, Andringa, S, 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Davies, G, Davini, S, Dawson, J, De, K, De Almeida, R, Debbins, P, De Bonis, I, Decowski, M, De Gouvea, A, De Holanda, P, De Icaza Astiz, I, Deisting, A, De Jong, P, Delbart, A, Delepine, D, Delgado, M, Dell'Acqua, A, De Lurgio, P, De Mello Neto, J, Demuth, D, Dennis, S, Densham, C, Deptuch, G, De Roeck, A, De Romeri, V, De Vries, J, Dharmapalan, R, Dias, M, Diaz, F, Diaz, J, Di Domizio, S, Di Giulio, L, Ding, P, Di Noto, L, Distefano, C, Diurba, R, Diwan, M, Djurcic, Z, Dokania, N, Dolinski, M, Domine, L, Douglas, D, Drielsma, F, Duchesneau, D, Duffy, K, Dunne, P, Durkin, T, Duyang, H, Dvornikov, O, Dwyer, D, Dyshkant, A, Eads, M, Edmunds, D, Eisch, J, Emery, S, Ereditato, A, Escobar, C, Escudero Sanchez, L, Evans, J, Ewart, E, Ezeribe, A, Fahey, K, Falcone, A, Farnese, C, Farzan, Y, Felix, J, Fernandez-Martinez, E, Fernandez Menendez, P, Ferraro, F, Fields, L, Filkins, A, Filthaut, F, Fitzpatrick, R, Flanagan, W, Fleming, B, Flight, R, Fowler, J, Fox, W, Franc, J, Francis, K, Franco, D, Freeman, J, Freestone, J, Fried, J, Friedland, A, Fuess, S, Furic, I, Furmanski, A, Gago, A, Gallagher, H, Gallego-Ros, A, Gallice, N, Galymov, V, Gamberini, E, Gamble, T, Gandhi, R, Gandrajula, R, Gao, S, Garcia-Carballeira, F, Garcia-Gamez, D, Garcia-Peris, M, Gardiner, S, Gastler, D, Ge, G, Gelli, B, Gendotti, A, Gent, S, Ghorbani-Moghaddam, Z, Gibin, D, Gil-Botella, I, Girerd, C, Giri, A, Gnani, D, Gogota, O, Gold, M, Gollapinni, S, Gollwitzer, K, Gomes, R, Gomez Bermeo, L, Gomez Fajardo, L, Gonnella, F, Gonzalez-Cuevas, J, Goodman, M, Goodwin, O, Goswami, S, Gotti, C, Goudzovski, E, Grace, C, Graham, M, Gramellini, E, Gran, R, Granados, E, Grant, A, Grant, C, Gratieri, D, Green, P, Green, S, Greenler, L, Greenwood, M, Greer, J, Griffith, W, Groh, M, Grudzinski, J, Grzelak, K, Gu, W, Guarino, V, Guenette, R, Guglielmi, A, Guo, B, Guthikonda, K, Gutierrez, R, Guzowski, P, Guzzo, M, Gwon, S, Habig, A, Hackenburg, A, Hadavand, H, Haenni, R, Hahn, A, Haigh, J, Haiston, J, Hamernik, 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Tapia Oregui B., Tapper A., Tariq S., Tatar E., Tayloe R., Teklu A.M., Tenti M., Terao K., Ternes C.A., Terranova F., Testera G., Thea A., Thompson J.L., Thorn C., Timm S.C., Tonazzo A., Torti M., Tortola M., Tortorici F., Totani D., Toups M., Touramanis C., Trevor J., Trzaska W.H., Tsai Y.T., Tsamalaidze Z., Tsang K.V., Tsverava N., Tufanli S., Tull C., Tyley E., Tzanov M., Uchida M.A., Urheim J., Usher T., Vagins M.R., Vahle P., Valdiviesso G.A., Valencia E., Vallari Z., Valle J.W.F., Vallecorsa S., Van Berg R., Van De Water R.G., Vanegas Forero D., Varanini F., Vargas D., Varner G., Vasel J., Vasseur G., Vaziri K., Ventura S., Verdugo A., Vergani S., Vermeulen M.A., Verzocchi M., Vieira De Souza H., Vignoli C., Vilela C., Viren B., Vrba T., Wachala T., Waldron A.V., Wallbank M., Wang H., Wang J., Wang Y., Warburton K., Warner D., Wascko M., Waters D., Watson A., Weatherly P., Weber A., Weber M., Wei H., Weinstein A., Wenman D., Wetstein M., While M.R., White A., Whitehead L.H., Whittington D., Wilking M.J., Wilkinson C., Williams Z., Wilson F., Wilson R.J., Wolcott J., Wongjirad T., Wood K., Wood L., Worcester E., Worcester M., Wret C., Wu W., Xiao Y., Yang G., Yang T., Yershov N., Yonehara K., Young T., Yu B., Yu J., Zaki R., Zalesak J., Zambelli L., Zamorano B., Zani A., Zazueta L., Zeller G.P., Zennamo J., Zeug K., Zhang C., Zhao M., Zhivun E., Zhu G., Zimmerman E.D., Zito M., Zucchelli S., Zuklin J., Zutshi V., Zwaska R., UAM. Departamento de Física Teórica, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Ministerio de Ciencia, Innovación y Universidades (España)

Subjects
Neutrino Oscillations. Neutrino detectors, Physics - Instrumentation and Detectors, Physics::Instrumentation and Detectors, far detector, 01 natural sciences, Physics, Particles & Fields, High Energy Physics - Experiment, charged current, High Energy Physics - Experiment (hep-ex), [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Particle Physics Experiments, Muon neutrino, neutrino/e: particle identification, Neutrino detectors, Detectors and Experimental Techniques, physics.ins-det, Charged current, neutrino: interaction, Informática, Physics, Telecomunicaciones, Neutrino oscillations, Neutrino interactions, neural network, DUNE, Deep Underground Neutrino Experiment, Instrumentation and Detectors (physics.ins-det), Experiment (hep-ex), Neutrino detector, Physical Sciences, CP violation, Neutrino, Particle Physics - Experiment, Particle physics, data analysis method, 530 Physics, neural network, Astrophysics::High Energy Astrophysical Phenomena, CONSERVATION, FOS: Physical sciences, Astronomy & Astrophysics, Deep Learning, neutrino: deep underground detector, neutrino physics, 0103 physical sciences, Object Detection, CP: violation, Deep Underground Neutrino Experiment, High Energy Physics, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Neutrinos, 010306 general physics, Neutrino oscillation, neutrino/mu: particle identification, IOU, Science & Technology, DUNE, Neutrino interactions, 010308 nuclear & particles physics, hep-ex, High Energy Physics::Phenomenology, Física, Neutrino Interaction, Detector, 530 Physik, sensitivity, efficiency, High Energy Physics::Experiment, Electron neutrino
Abstract

The Deep Underground Neutrino Experiment is a next-generation neutrino oscillation experiment that aims to measure CP-violation in the neutrino sector as part of a wider physics program. A deep learning approach based on a convolutional neural network has been developed to provide highly efficient and pure selections of electron neutrino and muon neutrino charged-current interactions. The electron neutrino (antineutrino) selection efficiency peaks at 90% (94%) and exceeds 85% (90%) for reconstructed neutrino energies between 2–5 GeV. The muon neutrino (antineutrino) event selection is found to have a maximum efficiency of 96% (97%) and exceeds 90% (95%) efficiency for reconstructed neutrino energies above 2 GeV. When considering all electron neutrino and antineutrino interactions as signal, a selection purity of 90% is achieved. These event selections are critical to maximize the sensitivity of the experiment to CP-violating effects., Fermi Research Alliance, LLC (FRA) DE-AC02-07CH11359, National Council for Scientific and Technological Development (CNPq), Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ), FAPEG, Brazil, Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Canada Foundation for Innovation, Institute of Particle Physics, Canada, Natural Sciences and Engineering Research Council of Canada (NSERC), CERN, Ministry of Education, Youth & Sports - Czech Republic Czech Republic Government, ERDF, European Union, H2020-EU, European Union, MSCA, European Union, Centre National de la Recherche Scientifique (CNRS), French Atomic Energy Commission, Istituto Nazionale di Fisica Nucleare (INFN), Portuguese Foundation for Science and Technology European Commission, NRF, South Korea, Comunidad de Madrid, La Caixa Foundation, Spanish Government, State Secretariat for Education, Research and Innovation, Switzerland, Swiss National Science Foundation (SNSF), Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK), Royal Society of London, UKRI/STFC, United Kingdom, United States Department of Energy (DOE), National Science Foundation (NSF)

Published
2020

42. Coding and regulatory variants affect serum protein levels and common disease

Author

Nicholas M. Morton, Alexander Gudjonsson, Thor Aspelund, Elias F. Gudmundsson, Vilmundur Gudnason, Valur Emilsson, Mohd Anisul Karim, James R Staley, Brynjolfur G. Jonsson, Lenore J. Launer, Marjan Ilkov, John Lamb, Jan H.N. Lindeman, Valborg Gudmundsdottir, and Lori L. Jennings

Subjects
Genetics, Common disease, Cohort, Complex disease, Serum protein, medicine, Cancer, Biology, Affect (psychology), medicine.disease, Blood proteins, Exome
Abstract

Circulating proteins are prognostic for human outcomes including cancer, heart failure, brain trauma and brain amyloid plaque burden. A deep serum proteome survey recently revealed close associations of serum protein networks and common diseases. The present study reveals unprecedented number of individual serum proteins that overlap genetic signatures of diseases emanating from different tissues of the body. Here, 54,469 low-frequency and common exome-array variants were compared with 4782 protein measurements in the serum of 5343 individuals of the deeply annotated AGES Reykjavik cohort. Using a study-wide significant threshold, 2019 independent exome array variants affecting levels of 2135 serum proteins were identified. These variants overlapped genetic loci for hundreds of complex disease traits, emphasizing the emerging role for serum proteins as biomarkers of and potential causative agents of multiple diseases.

Published
2020

43. The ecobiomics project: advancing metagenomics assessment of soil health and freshwater quality in Canada

Author

David Konkin, Cynthia Watson, Oliver Lung, Donna Lee Fancy, Nicholas H. Ogden, Ian King, Erik J. S. Emilson, Satpal Bilkhu, Janet A. Condie, Teresita M. Porter, Jérôme Comte, Armand Séguin, Alex Bush, John R. Lawrence, Nellie Gagné, Lori A. Phillips, Donald J. Baird, Royce Steeves, David Paré, Susan B. Watson, Izhar U. H. Khan, Lisa A. Venier, Iyad Kandalaft, Wen Chen, Sophie Crevecoeur, Guillaume J. Bilodeau, James Macklin, Zachery R. Staley, Thomas A. Edge, Christine Lowe, Matthew J. Meier, Teodor Veres, Joel Sachs, David P. Kreutzweiser, Christine Martineau, David R. Lapen, L.A. Beaudette, Glen Newton, Nazir El-Kayssi, and Charles W. Greer

Subjects
Canada, Environmental Engineering, 010504 meteorology & atmospheric sciences, Environmental change, Biodiversity, Genomics, Fresh Water, 010501 environmental sciences, 01 natural sciences, water quality, Soil, microbiomes, Environmental monitoring, Environmental Chemistry, Animals, Humans, Environmental impact assessment, Microbiome, invertebrate biodiversity, Waste Management and Disposal, 0105 earth and related environmental sciences, metagenomics, soil health, business.industry, Environmental resource management, Pollution, Geography, Metagenomics, Water quality, business
Abstract

Transformative advances in metagenomics are providing an unprecedented ability to characterize the enormous diversity of microorganisms and invertebrates sustaining soil health and water quality. These advances are enabling a better recognition of the ecological linkages between soil and water, and the biodiversity exchanges between these two reservoirs. They are also providing new perspectives for understanding microorganisms and invertebrates as part of interacting communities (i.e. microbiomes and zoobiomes), and considering plants, animals, and humans as holobionts comprised of their own cells as well as diverse microorganisms and invertebrates often acquired from soil and water. The Government of Canada's Genomics Research and Development Initiative (GRDI) launched the Ecobiomics Project to coordinate metagenomics capacity building across federal departments, and to apply metagenomics to better characterize microbial and invertebrate biodiversity for advancing environmental assessment, monitoring, and remediation activities. The Project has adopted standard methods for soil, water, and invertebrate sampling, collection and provenance of metadata, and nucleic acid extraction. High-throughput sequencing is located at a centralized sequencing facility. A centralized Bioinformatics Platform was established to enable a novel government-wide approach to harmonize metagenomics data collection, storage and bioinformatics analyses. Sixteen research projects were initiated under Soil Microbiome, Aquatic Microbiome, and Invertebrate Zoobiome Themes. Genomic observatories were established at long-term environmental monitoring sites for providing more comprehensive biodiversity reference points to assess environmental change.

Published
2020

44. Liverpool start-up

Author

Samuel R. Staley

Subjects
History, Economic history, Start up
Published
2020

45. The Beatles and Economics

Author

Samuel R. Staley

Subjects
Entrepreneurship, Popular music, Political economy, Political science, Popular culture, Context (language use), Mindset, Organizational theory, Economic globalization, Human capital
Abstract

The Beatles are considered the most influential popular music act of the twentieth century, widely recognized for their influence on popular culture. The inability of other bands and artists to imitate their fame has prompted questions such as: How did the Beatles become so successful? What factors contributed to their success? Why did they break up? The Beatles and Economics: Entrepreneurship, Innovation, and the Making of a Cultural Revolution answers these questions using the lens of economic analysis. Economics provides the prism for explaining why their success—while legendary in scale—is not mythic. This book explores how the band’s commercial achievements were intimately tied to the larger context of economic globalization and rebuilding post-World War II. It examines how the Beatles’ time in Hamburg is best understood as an investment in human capital, and why the entrepreneurial growth mindset was critical to establishing a scalable market niche and sustaining the Beatles’ ability to lead and shape emerging markets in entertainment and popular music. Later chapters consider how the economics of decision making and organizational theory helps us to understand the band’s break-up at its economic peak. This essential text is of interest to anyone interested in the economic dynamics and social forces that shape cultural change.

Published
2020

46. The black swan of popular music?

Author

Samuel R. Staley

Subjects
Popular music, media_common.quotation_subject, Art history, Art, Black swan theory, media_common
Published
2020

49. A second coming?

Author

Samuel R. Staley

Subjects
Second Coming, History, Economic history
Published
2020

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