Search

Your search keyword '"Kahn, Steven A."' showing total 2,064 results
Start Over Author "Kahn, Steven A."
2,064 results on '"Kahn, Steven A."'

1. The Active Optics System on the Vera C. Rubin Observatory: Optimal Control of Degeneracy Among the Large Number of Degrees of Freedom

Author

Homar, Guillem Megias, Kahn, Steven M., Meyers, Joshua M., Crenshaw, John Franklin, and Thomas, Sandrine J.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The Vera C. Rubin Observatory is a unique facility for survey astronomy that will soon be commissioned and begin operations. Crucial to many of its scientific goals is the achievement of sustained high image quality, limited only by the seeing at the site. This will be maintained through an Active Optics System (AOS) that controls optical element misalignments and corrects mirror figure error to minimize aberrations caused by both thermal and gravitational distortions. However, the large number of adjustment degrees of freedom available on the Rubin Observatory introduces a range of degeneracies, including many that are \textit{noise-induced} due to imperfect measurement of the wavefront errors. We present a structured methodology for identifying these degeneracies through an analysis of image noise level. We also present a novel scaling strategy based on Truncated Singular Value Decomposition (TSVD) that mitigates the degeneracy, and optimally distributes the adjustment over the available degrees of freedom. Our approach ensures the attainment of optimal image quality, while avoiding excursions around the noise-induced subspace of degeneracies, marking a significant improvement over the previous techniques adopted for Rubin, which were based on an Optimal Integral Controller (OIC). This new approach is likely to also yield significant benefits for all telescopes that incorporate large numbers of degrees of freedom of adjustment., Comment: 19 pages, 8 figures, 4 tables. Submitted to ApJ

Published
2024

2. Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP).

Author

Li, Josephine, Perry, James, Jablonski, Kathleen, Srinivasan, Shylaja, Chen, Ling, Todd, Jennifer, Harden, Maegan, Mercader, Josep, Pan, Qing, Dawed, Adem, Yee, Sook Wah, Pearson, Ewan, Giacomini, Kathleen, Giri, Ayush, Hung, Adriana, Xiao, Shujie, Williams, L, Franks, Paul, Hanson, Robert, Kahn, Steven, Knowler, William, Pollin, Toni, and Florez, Jose

Subjects
Humans, Metformin, Diabetes Mellitus, Type 2, Genome-Wide Association Study, Prediabetic State, Genetic Variation, Polymorphism, Single Nucleotide
Abstract

Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 10-9). In the MET arm, rs144322333 near ENOSF1 (minor allele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, β = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10-12). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, β = -7.55 [95% CI -9.88, -5.22]; P = 3.2 × 10-10) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 10-4]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy.

Published
2023

4. Prompt Detection of Fast Optical Bursts with the Vera C. Rubin Observatory

Author

Homar, Guillem Megias, Meyers, Joshua E., and Kahn, Steven M.

Subjects
Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The transient optical sky has remained largely unexplored on very short timescales. While there have been some experiments searching for optical transients from minutes to years, none have had the capability to distinguish millisecond Fast Optical Bursts (FOB). Such very fast transients could be the optical counterparts of Fast Radio Bursts (FRB), the prompt emission from $\gamma$-Ray Bursts (GRB), or other previously unknown phenomena. Here, we investigate a novel approach to the serendipitous detection of FOBs, which relies on searching for anomalous spatial images. In particular, due to their short duration, the seeing distorted images of FOBs should look characteristically different than those of steady sources in a standard optical exposure of finite duration. We apply this idea to simulated observations with the Vera C. Rubin Observatory, produced by tracing individual photons through a turbulent atmosphere, and down through the optics and camera of the Rubin telescope. We compare these simulated images to steady-source star simulations in 15 s integrations, the nominal Rubin exposure time. We report the classification accuracy results of a Neural Network classifier for distinguishing FOBs from steady sources. From this classifier, we derive constraints in duration-intensity parameter space for unambiguously identifying FOBs in Rubin observations. We conclude with estimates of the total number of detections of FOB counterparts to FRBs expected during the 10-year Rubin Legacy Survey of Space and Time (LSST)., Comment: 7 pages, 4 figures, submitted to the Astrophysical Journal

Published
2023
Full Text
View/download PDF

7. Snowmass2021 Cosmic Frontier White Paper: Rubin Observatory after LSST

Author

Blum, Bob, Digel, Seth W., Drlica-Wagner, Alex, Habib, Salman, Heitmann, Katrin, Ishak, Mustapha, Jha, Saurabh W., Kahn, Steven M., Mandelbaum, Rachel, Marshall, Phil, Newman, Jeffrey A., Roodman, Aaron, and Stubbs, Christopher W.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, High Energy Physics - Phenomenology
Abstract

The Vera C. Rubin Observatory will begin the Legacy Survey of Space and Time (LSST) in 2024, spanning an area of 18,000 square degrees in six bands, with more than 800 observations of each field over ten years. The unprecedented data set will enable great advances in the study of the formation and evolution of structure and exploration of physics of the dark universe. The observations will hold clues about the cause for the accelerated expansion of the universe and possibly the nature of dark matter. During the next decade, LSST will be able to confirm or dispute if tensions seen today in cosmological data are due to new physics. New and unexpected phenomena could confirm or disrupt our current understanding of the universe. Findings from LSST will guide the path forward post-LSST. The Rubin Observatory will still be a uniquely powerful facility even then, capable of revealing further insights into the physics of the dark universe. These could be obtained via innovative observing strategies, e.g., targeting new probes at shorter timescales than with LSST, or via modest instrumental changes, e.g., new filters, or through an entirely new instrument for the focal plane. This White Paper highlights some of the opportunities in each scenario from Rubin observations after LSST., Comment: Contribution to Snowmass 2021

Published
2022

9. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Author

Abe, Mitsunori, Abhaichand, Rajpal K, Abhayaratna, Walter P, Abhyankar, Atul, Abidin, Imran B Zainal, Abou Assi, Hiba, Accini Mendoza, Jose L, Adas, Mine, Agaiby, John M, Agarwal, Devendra K, Agha, Maher, Ahmed, Azazuddin, Ahtiainen, Petteri, Aigner, Elmar, Ajay, Naik, Ali, Norsiah, Al-Karadsheh, Amer, Allison, Roy, Allison, Dale C, Alpenidze, Diana, Altuntas, Yuksel, Al-Zoebi, Ayham, Ambuj, Roy, Amerena, John, Anderson, Robert J, Ando, Toshiaki, Andrews, Robert, Antonova, Elizaveta, Appel, Karl-Friedrich, Arantes, Flávia B, Araz, Mustafa, Arbel, Yaron, Arenas León, José L, Argyrakopoulou, Georgia, Ariani, Mehrdad, Arias Mendoza, Maria A, Arif, Ahmed A, Arneja, Jaspal, Aroda, Vanita R, Aronne, Louis J, Arstall, Margaret, Asamoah, Njaimeh, Asanin, Milika, Audish, Hanid, Avram, Rodica, Badat, Aysha, Badiu, Corin V, Bakdash, Wa'el, Bakiner, Okan S, Bandezi, Vuyokazi N, Bang, Liew H, Bansal, Sandeep, Baranyai, Marietta, Barbarash, Olga, Barber, Mark, Barnum, Otis, Barone Rochette, Gilles, Bashkin, Amir, Baum, Seth, Bays, Harold E, Bazzoni Ruiz, Alberto E, Beckowski, Maciej, Beerachee, Yaswin, Bellary, Srikanth, Belousova, Lidia, Berk, Martin, Bernstein, Marc, Berra, Cesare, Beshay, Isaac, Bhagwat, Ajit, Bhan, Arti, Biggs, William C, Billings, Liana, Bitar, Fahed, Block, Bradley, Bo, Simona, Bogdanski, Pawel, Bolshakova, Olga O, Boshchenko, Alla A, Bosworth, Hayden, Botero Lopez, Rodrigo, Bôttcher, Morten, Bourgeois, Ronald, Brautigam, Donald, Breton, Cristian F, Broadley, Andrew, Brockmyre, Andrew P, Brodie, Steven K, Bucci, Marco, Budincevic, Hrvoje, Budoff, Matthew J, Buffman, Barry, Buljubasic, Nediljka, Buranapin, Supawan, Burgess, Lesley, Burguera, Bartolomé, Buriakovska, Olena, Buscemi, Silvio, Busch, Robert, Buse, John B, Buynak, Robert, Byrne, Maria, Caceaune, Elena, Cadena Bonfanti, Alberto J, Calinescu, Cornell V, Call, Robert S, Canecki Varzic, Silvija, Cannon, Kevin, Capehorn, Matt, Cariou, Bertrand, Carr, Jeffrey, Carrillo-Jimenez, Rodolfo, Casas, Marcelo, Castro, Almudena, Celik, Ahmet, Cercato, Cintia, Cermak, Ondrej, Cha, James Y, Chacon, Carolina, Chaicha-Brom, Tira, Chandra, Sandeep, Chettibi, Mohamed, Chevts, Julia, Christopher, Johann, Chrustowski, Witold, Cif, Adriana, Clark, Rebecca, Clark, Wayne, Clifford, Piers, Coetzee, Kathleen, Cogni, Giulia, Colao, Anna Maria, Colquhoun, David M, Concha, Mauricio, Condit, Jonathan, Constance, Christian, Constantin, Ciprian, Constantinescu, Silviana, Corbett, Clive, Cornett, George M, Correia, Marcelo, Cortinovis, Fiorenzo, Cosma, Dana, Creely, Steven, Cross, David, Curtis, Brian, Czochra, Wojciech, Daboul, Nizar Y, Dagdelen, Selcuk, D'agostino, Ronald, Dang, Cuong, Datta, Sudip, Davuluri, Ashwini K, Dawood, Saleem Y, De Jong, Douwe M, De La Cuesta, Carmen, De Los Rios Ibarra, Manuel O, De Pablo, Carmen, De Pauw, Michel, Dela Llana, Alexander, Delibasic, Maja, Delic-Brkljacic, Diana, Demicheli, Thibaud, Denger, Ralf J, Desai, Devang, Desai, Piyush, Desouza, Cyrus V, Dicker, Dror, Djenic, Nemanja, Dobson, Simon, Doi, Masayuki, Doran, Jesse A, Dorman, Reinhart, Dotta, Francesco, Dukes, Carl E, Duronto, Ernesto, Durst, Ronen, Dvoryashina, Irina V, Ebrahim, Iftikhar O, Eggebrecht, Holger, Egstrup, Kenneth, Ekinci, Elif I, Eliasson, Björn, Eliasson, Ken, Enache, Georgiana, Enculescu, Dan, English, Patrick, Ermakova, Polina, Ershova, Olga, Ezaki, Hirotaka, Ezhov, Marat, Farias, Eduardo, Farias, Javier M, Farsky, Pedro S, Ferreira, Daniel, Filteau, Pierre, Finneran, Matthew P, Folkens, Eric M, Fonseca, Alberto G, Fonseca, Luisa, Fordan, Steven, Fourie, Nyda, França, Sara, Franco, Denise R, Franek, Edward, Friedman, Keith, Frittitta, Lucia, Froer, Michael, Fuckar, Krunoslav, Fujii, Kenshi, Fujita, Ryoko, Fukushima, Yasushi, Fulat, Mohamed, Fulwani, Mahesh, Gajos, Grzegorz, Galyavich, Albert, Gambill, Michael L, Gandotra, Dheeraj, Winston, Gandy, Jr., Garcia Hernandez, Pedro A, García Reza, Raymundo, Garg, Naveen, Garg, Sandeep, Garvey, William T, Garza, Juan C, Gatta-Cherifi, Blandine, Gelev, Valeri, Geller, Steven A, Geohas, Jeffrey G, Georgiev, Borislav, Ghazi, Adline, Gilbert, Matthew P, Gilinskaya, Olga, Gislason, Gunnar, Gogas Yavuz, Dilek, González Albarrán, Olga, Gordeev, Ivan G, Gorton, Sidney C, Goudev, Assen, Gretland Valderhaug, Tone, Groenemeijer, Bjorn, Gul, Ibrahim, Gullestad, Lars, Gurieva, Irina, Guseva, Galina N, Hagenow, Andreas, Haluzik, Martin, Halvorsen, Sigrun, Hammoudi, Naima, Hanaoka, Keiichi, Hancu, Nicolae, Hanusch, Ursula, Harris, Kathleen, Harris, Barry, Hartleib, Michael, Hartman, Aaron N, Hata, Yoshiki, Heimer, Brian, Herman, Lee, Herzog, William, Hewitt, Eric, Heymer, Peter, Hiremath, Shirish, Hjelmesaeth, Joeran, Høgalmen, Rasmus Geir, Høivik, Hans Olav, Holmer, Helene, Horoshko, Olha, Houser, Patricia M, Hove, Jens D, Hsieh, I-Chang, Hulot, Jean-Sébastien, Hussein, Zanariah, Ilashchuk, Tetiana, Ilveskoski, Erkki, Ipatko, Irina, Iranmanesh, Ali, Isawa, Tsuyoshi, Issa, Moises, Iteld, Bruce, Iwasawa, Takamasa, Jabbar, Danish, Jackson, Richard A, Jackson-Voyzey, Ewart, Jacob, Stephan, Jaffrani, Naseem A, Jardula, Michael F, Jastreboff, Ania, Jensen, Svend E, Jerkins, Terri, Jimenez-Ramos, Silvia A, Jitendra Pal Singh, Sawhney, Johnson, Wallace, Joyce, John M, Jozefowska, Malgorzata, Jugnundan, Prakash, Jungmair, Wolfgang, Jurowiecki, Jaroslaw, Kadokami, Toshiaki, Kahali, Dhiman, Kahrmann, Gerd, Kaiser, Sergio E, Kalmucki, Piotr, Kanadasi, Mehmet, Kandath, David, Kania, Grzegorz, Kannan, J, Kapp, Cornelia, Karczmarczyk, Agnieszka, Kartalis, Athanasios, Kaser, Susanne, Kasim, Sazzli Shahlan, Kastelic, Richard, Kato, Toshiaki, Katova, Tzvetana, Kaul, Upendra, Kautzky-Willer, Alexandra, Kawanishi, Masahiro, Kayikcioglu, Meral, Kazakova, Elena E, Keeling, Philip, Kempe, Hans-Peter, Kereiakes, Dean J, Kerneis, Mathieu, Keski-Opas, Tiina, Khadra, Suhail, Khaisheva, Larisa, Kharakhulakh, Marina, Khlevchuk, Tatiana, Khoo, Jeffrey, Kiatchoosakun, Songsak, Kinoshita, Noriyuki, Kinoshita, Masaharu, Kitamura, Ryoji, Kiyosue, Arihiro, Klavina, Irina, Klein, Eric J, Klimsa, Zdenek, Klonoff, David, Klug, Eric, Kobalava, Zhanna, Kodera, Satoshi, Koga, Tokushi, Kokkinos, Alexander, Koleckar, Pavel, Könyves, László, Koren, Michael J, Kormann, Adrian P, Kostner, Karam, Kreutzmann, Kristin, Krishinan, Saravanan, Krishnasamy, Sathya S, Krivosheeva, Inga, Kruljac, Ivan, Kubicki, Ted, Kuchar, Ladislav, Kujawiak, Monika, Kunishige, Hideyuki, Kurtinecz, Melinda, Kurtz Lisboa, Hugo R, Kushnir, Mykola, Kyyak, Yulian, Lace, Arija, Lakka, Timo, Lalic, Nebojsa, Lalic, Katarina, Lambadiari, Vaia, Lanaras, Leonidas, Lang, Chim, Langlois, Marie-France, Lash, Joseph, Latkovskis, Gustavs, Lau, David, Lazcano Soto, José Roberto, Le Roux, Carel, Ledesma, Gilbert N, Lee, Li Yuan, Lee, Thung-Lip, Lee, Kelvin, Lehrke, Michael, Leite, Silmara O, Leksycka, Agata, Lenzmeier, Thomas, Leonetti, Frida, Leonidova, Viktoriia, Lepor, Norman, Leung, Melissa, Levchenko, Olena, Levins, Peter, Levy, Louis J, Lewis, Matthew, Liberopoulos, Evangelos, Liberty, Idit, Lindholm, Carl-Johan, Lingvay, Ildiko, Linhart, Ales, Liu, Ming-En, Liu, Jenny, Lofton, Holly, Logemann, Timothy, Lombaard, Johannes J, Lombard, Landman, Lorraine, Richard, Lovell, Charles F, Ludvik, Bernhard, Lukaszewicz, Monika, Lupkovics, Géza, Lupovitch, Steven, Lupu, Sirona, Lynch, Mary, Lysak, Zoreslava, Lysenko, Tatyana A, Maeda, Hajime, Maeda, Itaru, Mæng, Michael, Mahajan, Ajay U, Maher, Vincent, Maia, Lilia N, Makotoko, Ellen M, Malavazos, Alexis, Malecha, Jan, Malicherova, Emilia, Manita, Mamoru, Mannucci, Edoardo, Mareev, Viacheslav, Marin, Liliana, Markova, Tatiana, Marso, Steven P, Martens, F.M.A.C., Martinez, Cuper, Martinez Cano, Carlos A, Martins, Cristina, Masmiquel Comas, Luis, Matsumoto, Takashi, Mcdonald, Kenneth, Mcgowan, Barbara, Mcgrew, Frank, Mclean, Barry K, Mcpherson, David D, Merino Torres, Juan Francisco, Meyers, Peter, Meyhöfer, Sebastian, Mezquita Raya, Pedro, Milanova, Maria, Milicic, Davor, Miller, Gary, Mills, Richard E, Mîndrescu, Nicoleta M, Mingrone, Geltrude, Minkova, Dotska A, Mirani, Marco, Miras, Alexander, Mistodie, Cristina V, Mitomo, Satoru, Mittal, Sanjay, Miyake, Taiji, Miyamoto, Naomasa, Molony, David, Monteiro, Pedro, Mooe, Thomas, Moosa, Naeem, Morales Portillo, Cristobal, Morales Villegas, Enrique C, Morawski, Emily J, Morbey, Claire, Morin, Robert P, Morisaki, Kuniaki, Morosanu, Magdalena, Mosenzon, Ofri, Mostovoy, Yuriy, Munir, Iqbal, Muratori, Fabrizio, Murray, Ryan, Murthy, Avinash, Myint, Min, Myshanych, Galyna, Nafornita, Valerica, Nagano, Takuya, Nair, Sunil, Nakhle, Samer N, Natsuaki, Masahiro, Nayak, Bindu M, Nibouche, Djamel Eddine, Nicholls, Stephen, Nicolau, José C, Nicolescu, Georgiana, Nierop, Peter, Niskanen, Leo, Ntaios, George, Nygård, Ottar Kjell, Oaks, Joshua B, Obrezan, Andrey, O'donnell, Philip, Oguri, Mitsutoshi, Oguzhan, Abdurrahman, Oh, Fumiki, Ohsugi, Mitsuru, Okada, Yoshio, Okayama, Hideki, Onaca, Adriana, Onaka, Haruhiko, Oneil, Patrick, Ong, Tiong Kiam, Ong, Stephen, Ono, Yasuhiro, Opsahl, Paul J, Ostrowska, Lucyna, Oviedo, Alejandra, Ozdogan, Oner, Ozpelit, Ebru, Pagkalos, Emmanouil, Pagotto, Uberto, Páll, Dénes, Pandey, Amritanshu- Shekhar, Parkhomenko, Oleksandr, Parvathareddy, Krishna Malakondareddy, Patel, Minesh B, Patsilinakos, Sotirios, Paul, Neil, Pedersen, Sue, Pereira, Isabel, Pereira, Edward Scott, Perez Terns, Paula, Perez-Vargas, Elba A, Pergaeva, Yulia, Perkelvald, Alexander, Peskov, Andrey B, Peter, Jonathan, Peters, Karina, Petit, Catherine, Petrov, Ivo, Philis-Tsimikas, Athena, Pietilä, Mikko, Pinto, Fausto, Piros, Annamária, Piyayotai, Dilok, Platonov, Dmitriy, Poirier, Paul, Pop, Lavinia, Popa, Bogdan, Pop-Busui, Rodica, Poremba, John, Porto, Alejandro, Postadzhiyan, Arman, Pothineni, Ramesh B, Potu, Ranganatha P, Powell, Talessa, Prafulla, Kerkar G, Prager, Rudolf, Prakova-Teneva, Zhulieta R, Pratley, Richard E, Price, Hermione, Pulka, Grazyna, Pullman, John, Punt, Zelda E, Purighalla, Raman S, Purnell, Peter, Qureshi, Mansoor, Rabasa-Lhoret, Remi, Raikhel, Marina A, Rancane, Gita, Randeva, Harpal, Rasouli, Neda, Reurean Pintilei, Delia V, Reyes, Ciro R, Rezgale, Inga, Rice, Eva, Riley, Thaddeus H, Risser, Joseph A, Ristic, Arsen, Rivas Fernández, Margarita, Robbins, David, Robitaille, Yves, Rodbard, Helena W, Rodriguez Plazas, Jaime A, Römer, T.J., Rosen, Glenn, Rosman, Dr Azhari, Rossi, Paulo, Rudenko, Leonid, Ruffin, Omari, Ruhani, Anwar Irawan, Runev, Nikolay, Ruyatkin, Dmitriy, Ruzic, Alen, Ryabov, Vyacheslav V, Rydén, Lars, Saggar, Suraj, Sakamoto, Tomohiro, Salter, Tim, Samal, Aditya K, Samoilova, Yulia, Sanabria, Hugo D, Sancak, Seda, Sangrigoli, Renee, Sansanayudh, Nakarin, Santini, Ferruccio, Saraiva, José F, Sardinov, Ruslan, Sargeant, William, Sari, Ramazan, Sathananthan, Airani, Sathyapalan, Thozhukat, Sato, Atsushi, Sauter, Joachim, Sbraccia, Paolo, Schaap, J., Schaum, Thomas, Schiele, François, Scott, John, Segal Lieberman, Gabriella, Segner, Alexander, Senior, Roxy, Sergeeva-Kondrachenko, Marina Y, Serota, Harvey, Serusclat, Pierre, Sethi, Rishi, Shah, Manoj K, Shah, Neerav, Shalaev, Sergey, Sharma, Raj, Sharma, Sumeet, Shaydyuk, Oksana, Shea, Heidi C, Shechter, Michael, Shehadeh, Naim, Shirazi, Mitra, Shlesinger, Yshay, Shneker, Ayham, Shutemova, Elena, Siasos, Gerasimos, Siddiqui, Imran A, Sidey, Jennifer, Sigal, Felix, Sime, Iveta, Singh, Narendra, Siraj, Elias, Sivalingam, Kanagaratnam, Skoczylas, Grzegorz, Smith, Stephen K, Smolenskaya, Olga, Snyder, Brian, Sofer, Yael, Sofley, C.W., Solano, Royce, Sonmez, Yusuf A, Sorokin, Maxim, Soto González, Alfonso, Sotolongo, Carlos, Soufer, Joseph, Soyluk Selcukbiricik, Ozlem, Spaic, Tamara, Spriggs, Douglas, Sreenan, Seamus, Stahl, Hans-Detlev, Stamatelopoulos, Kimon, Stanislavchuk, Mykola, Stankovic, Goran, Stasek, Josef, Steg, Gabriel, Steindorf, Joerg, Stephan, Dominique, Stewart, John, Still, Christopher, St-Maurice, Francois, Stogowska-Nikiciuk, Barbara, Stoker, Jeff, Stokic, Edita, Strzelecka, Anna, Sturm, Kerstin, Sueyoshi, Atsushi, Sugiura, Toshiyuki, Sultan, Senan, Suplotova, Lyudmila A, Suwanagool, Arisara, Suwanwalaikorn, Sompongse, Sveklina, Tatiana, Swanson, Neil, Swart, Henk, Swenson, Bradley P, Szyprowska, Ewa, Tait, Graeme, Takács, Róbert, Takeuchi, Yuzo, Tamirisa, Aparna, Tanaka, Hideki, Tatovic, Danijela, Tellier, Guy, Teragawa, Hiroki, Teterovska, Dace, Thomas, Nihal, Thuan, Jean-Francois, Tinahones, Francisco, Tisheva-Gospodinova, Snezhanka, Toarba, Cristina, Todoriuk, Liudmyla, Tokmakova, Mariya, Tonstad, Serena, Toplak, Hermann, Tran, Henry, Tripathy, Devjit, Trusau, Aliaksandr, Tsabedze, Nqoba, Tsougos, Elias, Tsoukas, George M, Tuccinardi, Dario, Tuna, Mazhar M, Turatti, Luiz A, Tziomalos, Konstantinos, Udommongkol, Chesda, Ueda, Osamu, Ukkola, Olavi, Unubol, Mustafa, Urbach, Dorothea, Urina Triana, Miguel A, Usdan, Lisa, Vaidya, Bijay, Vale, Noah, Vallieres, Gerald, Van Beek, Andre P, Van De Borne, Philippe, Van Der Walt, Eugene, Van Der Zwaan, C., Van Nieuwenhuizen, Elane, Van Zyl, Louis, Vanduynhoven, Philippe, Varghese, Kiron, Vasileva, Svetla P, Vassilev, Dobrin, Vathesatogkit, Prin, Velychko, Valentyna, Vercammen, Chris, Verges, Bruno, Verma, Subodh, Verwerft, Jan, Vesela, Alica, Veselovskaya, Nadezhda G, Vettor, Roberto, Veze, Irina, Vijan, Vinod, Vijayaraghavan, Ram, Villarino, Adriana, Vincent, Royce, Vinogradova, Oksana, Vishlitzky, Victor, Vlad, Adrian, Vladu, Ionela Mihaela, Vo, Anthony, Von Engelhardt, Charlotte, Von Münchhausen, Candy, Vorobyeva, Olga, Vossenberg, T., Vrolix, Mathias, Vukicevic, Marjana, Vyshnyvetskyy, Ivan, Wadvalla, Shahid, Wagner, Jan, Wakeling, John, Wallace, James, Wan Mohamed, Wan Mohd Izani, Wander, Gurpreet S, Ward, Kathleen, Warren, Mark L, Watanabe, Atsuyuki, Weber, Bruce, Weintraub, Howard, Weisnagel, John, Welker, James, Wendisch, Ulrich, Wenocur, Howard S, Wierum, Craig, Wilding, John, William, Maged, Wilson, Pete, Wilson, Jonathan P, Wong, Yuk-Ki, Wongcharoen, Wanwarang, Wozniak, Iwona, Wu, Chau-Chung, Wyatt, Nell, Wynne, Alan, Yamaguchi, Hiroshi, Yamasaki, Masahiro, Yazici, Dilek, Yeh, Hung-I, Yotov, Yoto, Yuan, Qingyang, Zacher, Jeffrey, Zagrebelnaya, Olga, Zaidman, Cesar J, Zalevskaya, Alsu, Zarich, Stuart, Zatelli, Maria Chiara, Zeller, Helga, Zhdanova, Elena A, Zornitzki, Taiba, Zrazhevskiy, Konstantin, Zykov, Mikhail, Lincoff, A Michael, Ryan, Donna H, Colhoun, Helen M, Deanfield, John E, Emerson, Scott S, Kahn, Steven E, Kushner, Robert F, Plutzky, Jorge, Brown-Frandsen, Kirstine, Hovingh, G Kees, Hardt-Lindberg, Soren, Tornøe, Christoffer W, Deanfield, John, Scirica, Benjamin M, Ryan, Donna, Kosiborod, Mikhail N, Hardt-Lindberg, Søren, Frenkel, Ofir, Weeke, Peter E, Rasmussen, Søren, Lang, Chim C, and Urina-Triana, Miguel

Published
2024
Full Text
View/download PDF

11. Islet Autoimmunity is Highly Prevalent and Associated With Diminished β-Cell Function in Patients With Type 2 Diabetes in the Grade Study.

Author

Brooks-Worrell, Barbara, Hampe, Christiane S, Hattery, Erica G, Palomino, Brenda, Zangeneh, Sahar Z, Utzschneider, Kristina, Kahn, Steven E, Larkin, Mary E, Johnson, Mary L, Mather, Kieren J, Younes, Naji, Rasouli, Neda, Desouza, Cyrus, Cohen, Robert M, Park, Jean Y, Florez, Hermes J, Valencia, Willy Marcos, Shojaie, Ali, Palmer, Jerry P, Balasubramanyam, Ashok, Crandall, Jill P, McKee, Melissa Diane, Brown-Friday, Janet, Xhori, Entila, Ballentine-Cargill, Keisha, Duran, Sally, Lukin, Jennifer, Beringher, Stephanie, Gonzalez de la Torre, Susana, Phillips, Lawrence, Burgess, Elizabeth, Olson, Darin, Rhee, Mary, Wilson, Peter, Raines, Tasha Stephanie, Costello, Julie, Gullett, Chona, Maher-Albertelli, Maxine, Morehead, Folayan, Mungara, Radhika, Person, Saranjit, Savoye, Louise, Sibymon, Mabil, Tanukonda, Sridhar, White, Carol Ann, Holloway, Leah, Adams, Cynthia, Ross, April, Gonzalez Hattery, Erica, Gaba, Ruchi, Montes, Graciela, Wright, Charlyne, Hollander, Priscilla, Roe, Erin, Uy, Analyn, Burt, Polly, Estrada, Lorie, Chionh, Kris, Ismail-Beigi, Faramarz, Falck-Ytter, Corinna, Sayyed Kassem, Laure, Sood, Ajay, Tiktin, Margaret, Cramer, Bethany, Iacoboni, Jacalyn, Kononets, Maria V, Kulow, Tanya, Newman, Cynthia, Stancil, Katherine A, Sanders, Cristina, Tucker, Lisa, Werner, Amanda, Krol, Adrienne, McPhee, Gloria, Patel, Christine, Colosimo, Linda, Goland, Robin, Pring, James, Kringas, Patricia, Tejada, Jessica, Hausheer, Camille, Schneier, Harvey, Gumpel, Kelly, Kirpitch, Amanda, Green, Jennifer B, AbouAssi, Hiba, Chatterjee, Ranee, Feinglos, Mark N, English Jones, Jennifer, Khan, Shubi A, Kimpel, Jeanne B, Zimmer, Ronna P, Furst, Mary, Satterwhite, Barbara M, Thacker, Connie, Evans Kreider, Kathryn, Lteif, Amale, and Hamilton, Tonya

Subjects
Biomedical and Clinical Sciences, Immunology, Autoimmune Disease, Clinical Research, Diabetes, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, GRADE Beta-cell Ancillary Study Network, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Islet autoimmunity may contribute to β-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study to the Glycemia Reduction Approaches in Diabetes-A Comparative Effectiveness (GRADE) Study, we investigated the prevalence of cellular and humoral islet autoimmunity in patients with T2D duration 4·0±3·0 y, HbA1c 7·5±0·5% on metformin alone. We measured T cell autoreactivity against islet proteins, islet autoantibodies against GAD65, IA2, ZnT8, and β-cell function. Cellular islet autoimmunity was present in 41·3%, humoral islet autoimmunity in 13·5%, and both in 5·3%. β-cell function calculated as iAUC-CG and ΔC-peptide(0- 30)/Δglucose(0-30) from an oral glucose tolerance test was lower among T cell-positives (T+) than T cell-negatives (T-) using two different adjustments for insulin sensitivity (iAUC-CG: 13·2% [95% CI 0·3, 24·4%] or 11·4% [95% CI 0·4, 21·2%] lower; ΔC-peptide(0-30)/Δglucose(0-30)) 19% [95% CI 3·1, 32·3%] or 17·7% [95% CI 2·6, 30·5%] lower). T+ patients had 17% higher HbA1c (95% CI 0·07, 0·28) and 7·7 mg/dL higher fasting plasma glucose levels (95% CI 0·2,15·3) than T- patients. We conclude that islet autoimmunity is much more prevalent in T2D patients than previously reported. T cell-mediated autoimmunity is associated with diminished β-cell function and worse glycemic control.

Published
2022

15. Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS‐CVOT design and baseline characteristics

Author

Nicholls, Stephen J., Bhatt, Deepak L, Buse, John B, Prato, Stefano Del, Kahn, Steven E, Lincoff, A Michael, McGuire, Darren K, Nauck, Michael A, Nissen, Steven E, Sattar, Naveed, Zinman, Bernard, Zoungas, Sophia, Basile, Jan, Bartee, Amy, Miller, Debra, Nishiyama, Hiroshi, Pavo, Imre, Weerakkody, Govinda, Wiese, Russell J, and D'Alessio, David

Published
2024
Full Text
View/download PDF

16. The LSST DESC DC2 Simulated Sky Survey

Author

LSST Dark Energy Science Collaboration, Abolfathi, Bela, Alonso, David, Armstrong, Robert, Aubourg, Éric, Awan, Humna, Babuji, Yadu N., Bauer, Franz Erik, Bean, Rachel, Beckett, George, Biswas, Rahul, Bogart, Joanne R., Boutigny, Dominique, Chard, Kyle, Chiang, James, Claver, Chuck F., Cohen-Tanugi, Johann, Combet, Céline, Connolly, Andrew J., Daniel, Scott F., Digel, Seth W., Drlica-Wagner, Alex, Dubois, Richard, Gangler, Emmanuel, Gawiser, Eric, Glanzman, Thomas, Gris, Phillipe, Habib, Salman, Hearin, Andrew P., Heitmann, Katrin, Hernandez, Fabio, Hložek, Renée, Hollowed, Joseph, Ishak, Mustapha, Ivezić, Željko, Jarvis, Mike, Jha, Saurabh W., Kahn, Steven M., Kalmbach, J. Bryce, Kelly, Heather M., Kovacs, Eve, Korytov, Danila, Krughoff, K. Simon, Lage, Craig S., Lanusse, François, Larsen, Patricia, Guillou, Laurent Le, Li, Nan, Longley, Emily Phillips, Lupton, Robert H., Mandelbaum, Rachel, Mao, Yao-Yuan, Marshall, Phil, Meyers, Joshua E., Moniez, Marc, Morrison, Christopher B., Nomerotski, Andrei, O'Connor, Paul, Park, HyeYun, Park, Ji Won, Peloton, Julien, Perrefort, Daniel, Perry, James, Plaszczynski, Stéphane, Pope, Adrian, Rasmussen, Andrew, Reil, Kevin, Roodman, Aaron J., Rykoff, Eli S., Sánchez, F. Javier, Schmidt, Samuel J., Scolnic, Daniel, Stubbs, Christopher W., Tyson, J. Anthony, Uram, Thomas D., Villarreal, Antonia, Walter, Christopher W., Wiesner, Matthew P., Wood-Vasey, W. Michael, and Zuntz, Joe

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We describe the simulated sky survey underlying the second data challenge (DC2) carried out in preparation for analysis of the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) by the LSST Dark Energy Science Collaboration (LSST DESC). Significant connections across multiple science domains will be a hallmark of LSST; the DC2 program represents a unique modeling effort that stresses this interconnectivity in a way that has not been attempted before. This effort encompasses a full end-to-end approach: starting from a large N-body simulation, through setting up LSST-like observations including realistic cadences, through image simulations, and finally processing with Rubin's LSST Science Pipelines. This last step ensures that we generate data products resembling those to be delivered by the Rubin Observatory as closely as is currently possible. The simulated DC2 sky survey covers six optical bands in a wide-fast-deep (WFD) area of approximately 300 deg^2 as well as a deep drilling field (DDF) of approximately 1 deg^2. We simulate 5 years of the planned 10-year survey. The DC2 sky survey has multiple purposes. First, the LSST DESC working groups can use the dataset to develop a range of DESC analysis pipelines to prepare for the advent of actual data. Second, it serves as a realistic testbed for the image processing software under development for LSST by the Rubin Observatory. In particular, simulated data provide a controlled way to investigate certain image-level systematic effects. Finally, the DC2 sky survey enables the exploration of new scientific ideas in both static and time-domain cosmology., Comment: 39 pages, 19 figures, version accepted for publication in ApJS

Published
2020
Full Text
View/download PDF

17. Surviving Sepsis After Burn Campaign

Author

Greenhalgh, David G., Hill, David M., Burmeister, David M., Gus, Eduardo I., Cleland, Heather, Padiglione, Alex, Holden, Dane, Huss, Fredrik, Chew, Michelle S., Kubasiak, John C., Burrell, Aidan, Manzanares, William, Gómez, María Chacón, Yoshimura, Yuya, Sjöberg, Folke, Xie, Wei-Guo, Egipto, Paula, Lavrentieva, Athina, Jain, Arpana, Miranda-Altamirano, Ariel, Raby, Ed, Aramendi, Ignacio, Sen, Soman, Chung, Kevin K., Alvarez, Renata Jennifer Quintana, Han, Chunmao, Matsushima, Asako, Elmasry, Moustafa, Liu, Yan, Donoso, Carlos Segovia, Bolgiani, Alberto, Johnson, Laura S., Vana, Luiz Philipe Molina, de Romero, Rosario Valdez Duval, Allorto, Nikki, Abesamis, Gerald, Luna, Virginia Nuñez, Gragnani, Alfredo, González, Carolina Bonilla, Basilico, Hugo, Wood, Fiona, Jeng, James, Li, Andrew, Singer, Mervyn, Luo, Gaoxing, Palmieri, Tina, Kahn, Steven, Joe, Victor, and Cartotto, Robert

Published
2023
Full Text
View/download PDF

18. The LSST DESC DC2 Simulated Sky Survey

Author

Abolfathi, Bela, Alonso, David, Armstrong, Robert, Aubourg, Éric, Awan, Humna, Babuji, Yadu N, Bauer, Franz Erik, Bean, Rachel, Beckett, George, Biswas, Rahul, Bogart, Joanne R, Boutigny, Dominique, Chard, Kyle, Chiang, James, Claver, Chuck F, Cohen-Tanugi, Johann, Combet, Céline, Connolly, Andrew J, Daniel, Scott F, Digel, Seth W, Drlica-Wagner, Alex, Dubois, Richard, Gangler, Emmanuel, Gawiser, Eric, Glanzman, Thomas, Gris, Phillipe, Habib, Salman, Hearin, Andrew P, Heitmann, Katrin, Hernandez, Fabio, Hložek, Renée, Hollowed, Joseph, Ishak, Mustapha, Ivezić, Željko, Jarvis, Mike, Jha, Saurabh W, Kahn, Steven M, Kalmbach, J Bryce, Kelly, Heather M, Kovacs, Eve, Korytov, Danila, Krughoff, K Simon, Lage, Craig S, Lanusse, François, Larsen, Patricia, Le Guillou, Laurent, Li, Nan, Longley, Emily Phillips, Lupton, Robert H, Mandelbaum, Rachel, Mao, Yao-Yuan, Marshall, Phil, Meyers, Joshua E, Moniez, Marc, Morrison, Christopher B, Nomerotski, Andrei, O’Connor, Paul, Park, HyeYun, Park, Ji Won, Peloton, Julien, Perrefort, Daniel, Perry, James, Plaszczynski, Stéphane, Pope, Adrian, Rasmussen, Andrew, Reil, Kevin, Roodman, Aaron J, Rykoff, Eli S, Sánchez, F Javier, Schmidt, Samuel J, Scolnic, Daniel, Stubbs, Christopher W, Tyson, J Anthony, Uram, Thomas D, Villarreal, Antonio, Walter, Christopher W, Wiesner, Matthew P, Wood-Vasey, W Michael, and Zuntz, Joe

Subjects
Astronomical Sciences, Physical Sciences, Cosmology, N-body simulations, Sky surveys, astro-ph.IM, astro-ph.CO, Astronomical and Space Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Physical Chemistry (incl. Structural), Astronomy & Astrophysics, Astronomical sciences
Abstract

We describe the simulated sky survey underlying the second data challenge (DC2) carried out in preparation for analysis of the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) by the LSST Dark Energy Science Collaboration (LSST DESC). Significant connections across multiple science domains will be a hallmark of LSST; the DC2 program represents a unique modeling effort that stresses this interconnectivity in a way that has not been attempted before. This effort encompasses a full end-to-end approach: starting from a large N-body simulation, through setting up LSST-like observations including realistic cadences, through image simulations, and finally processing with Rubin's LSST Science Pipelines. This last step ensures that we generate data products resembling those to be delivered by the Rubin Observatory as closely as is currently possible. The simulated DC2 sky survey covers six optical bands in a wide-fast-deep area of approximately 300 deg2, as well as a deep drilling field of approximately 1 deg2. We simulate 5 yr of the planned 10 yr survey. The DC2 sky survey has multiple purposes. First, the LSST DESC working groups can use the data set to develop a range of DESC analysis pipelines to prepare for the advent of actual data. Second, it serves as a realistic test bed for the image processing software under development for LSST by the Rubin Observatory. In particular, simulated data provide a controlled way to investigate certain image-level systematic effects. Finally, the DC2 sky survey enables the exploration of new scientific ideas in both static and time domain cosmology.

Published
2021

19. Association of Baseline Characteristics With Insulin Sensitivity and β-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort.

Author

Rasouli, Neda, Younes, Naji, Utzschneider, Kristina M, Inzucchi, Silvio E, Balasubramanyam, Ashok, Cherrington, Andrea L, Ismail-Beigi, Faramarz, Cohen, Robert M, Olson, Darin E, DeFronzo, Ralph A, Herman, William H, Lachin, John M, Kahn, Steven E, Crandall, Jill P, McKee, Melissa Diane, Brown-Friday, Janet, Xhori, Entila, Ballentine-Cargill, Keisha, Duran, Sally, Lukin, Jennifer, Beringher, Stephanie, de la torre, Susana Gonzalez, Phillips, Lawrence, Burgess, Elizabeth, Olson, Darin, Rhee, Mary, Wilson, Peter, Raines, Tasha Stephanie, Costello, Julie, Gullett, Chona, Maher-Albertelli, Maxine, Morehead, Folayan, Mungara, Radhika, Person, Saranjit, Savoye, Louise, Sibymon, Mabil, Tanukonda, Sridhar, Ann White, Carol, Holloway, Leah, Adams, Cynthia, Ross, April, Gonzalez, Erica, Wright, Charlyne, Hollander, Priscilla, Roe, Erin, Uy, Analyn, Burt, Polly, Estrada, Lorie, Chionh, Kris, Falck-Ytter, Corinna, Kassem, Laure Sayyed, Sood, Ajay, Tiktin, Margaret, Cramer, Bethany, Iacoboni, Jacalyn, Kononets, Maria V, Kulow, Tanya, Newman, Cynthia, Stancil, Katherine A, Sanders, Cristina, Tucker, Lisa, Werner, Amanda, Krol, Adrienne, McPhee, Gloria, Patel, Christine, Colosimo, Linda, Goland, Robin, Pring, James, Kringas, Patricia, Tejada, Jessica, Hausheer, Camille, Schneier, Harvey, Gumpel, Kelly, Kirpitch, Amanda, Green, Jennifer B, AbouAssi, Hiba, Chatterjee, Ranee, Feinglos, Mark N, Jones, Jennifer English, Khan, Shubi A, Kimpel, Jeanne B, Zimmer, Ronna P, Furst, Mary, Satterwhite, Barbara M, Thacker, Connie R, Kreider, Kathryn Evans, Mather, Kieren J, Lteif, Amale, Hamilton, Tonya, Patel, Nick, Riera, Gabriela, Jackson, Marcia, Pirics, Vivian, Howard, Devin, Aguillar, Danielle, Hurt, Sloan, Bergenstal, Richard, and Carlson, Anders

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Prevention, Diabetes, Metabolic and endocrine, Blood Glucose, C-Peptide, Child, Child, Preschool, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Infant, Insulin, Insulin Resistance, Male, GRADE Research Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveWe investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA1c) and the associations with selected phenotypic characteristics.Research design and methodsThis is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosed

Published
2021

21. Low concentration IL-1β promotes islet amyloid formation by increasing hIAPP release from humanised mouse islets in vitro

Author

Templin, Andrew T, Mellati, Mahnaz, Meier, Daniel T, Esser, Nathalie, Hogan, Meghan F, Castillo, Joseph J, Akter, Rehana, Raleigh, Daniel P, Zraika, Sakeneh, Hull, Rebecca L, and Kahn, Steven E

Subjects
Public Health, Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Amyloidosis, Animals, Humans, Insulin, Insulin-Secreting Cells, Interleukin-1beta, Islet Amyloid Polypeptide, Mice, hIAPP, IL-1 beta, Islet amyloid, Type 2 diabetes, IL-1β, Paediatrics and Reproductive Medicine, Public Health and Health Services, Endocrinology & Metabolism, Clinical sciences, Public health
Abstract

Aims/hypothesisAggregation of the beta cell secretory product human islet amyloid polypeptide (hIAPP) results in islet amyloid deposition, a pathological feature of type 2 diabetes. Amyloid formation is associated with increased levels of islet IL-1β as well as beta cell dysfunction and death, but the mechanisms that promote amyloid deposition in situ remain unclear. We hypothesised that physiologically relevant concentrations of IL-1β stimulate beta cell islet amyloid polypeptide (IAPP) release and promote amyloid formation.MethodsWe used a humanised mouse model of endogenous beta cell hIAPP expression to examine whether low (pg/ml) concentrations of IL-1β promote islet amyloid formation in vitro. Amyloid-forming islets were cultured for 48 h in the presence or absence of IL-1β with or without an IL-1β neutralising antibody. Islet morphology was assessed by immunohistochemistry and islet mRNA expression, hormone content and release were also quantified. Cell-free thioflavin T assays were used to monitor hIAPP aggregation kinetics in the presence and absence of IL-1β.ResultsTreatment with a low concentration of IL-1β (4 pg/ml) for 48 h increased islet amyloid prevalence (93.52 ± 3.89% vs 43.83 ± 9.67% amyloid-containing islets) and amyloid severity (4.45 ± 0.82% vs 2.16 ± 0.50% amyloid area/islet area) in hIAPP-expressing mouse islets in vitro. This effect of IL-1β was reduced when hIAPP-expressing islets were co-treated with an IL-1β neutralising antibody. Cell-free hIAPP aggregation assays showed no effect of IL-1β on hIAPP aggregation in vitro. Low concentration IL-1β did not increase markers of the unfolded protein response (Atf4, Ddit3) or alter proIAPP processing enzyme gene expression (Pcsk1, Pcsk2, Cpe) in hIAPP-expressing islets. However, release of IAPP and insulin were increased over 48 h in IL-1β-treated vs control islets (IAPP 0.409 ± 0.082 vs 0.165 ± 0.051 pmol/5 islets; insulin 87.5 ± 8.81 vs 48.3 ± 17.3 pmol/5 islets), and this effect was blocked by co-treatment with IL-1β neutralising antibody.Conclusions/interpretationUnder amyloidogenic conditions, physiologically relevant levels of IL-1β promote islet amyloid formation by increasing beta cell release of IAPP. Neutralisation of this effect of IL-1β may decrease the deleterious effects of islet amyloid formation on beta cell function and survival.

Published
2020

23. Evidence for gene-smoking interactions for hearing loss and deafness in Japanese American families

Author

Wan, Jia Y, Cataby, Christina, Liem, Andrew, Jeffrey, Emily, Norden-Krichmar, Trina M, Goodman, Deborah, Santorico, Stephanie A, Edwards, Karen L, Group, American Diabetes Association GENNID Study, Boerwinkle, Eric, Buse, John, DeFronzo, Ralph, Ehrmann, David, Elbein, Steven C, Fujimoto, Wilfred, Kahn, Steven E, Hanis, Craig L, Mulivor, Richard A, Beck, Jeanne C, Norris, Jill, Permutt, M Alan, Behn, Philip, Raffel, Leslie, and Robbins, David C

Subjects
Clinical Research, Human Genome, Diabetes, Tobacco Smoke and Health, Genetics, Tobacco, Prevention, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Cancer, Adaptor Proteins, Signal Transducing, Adult, Aged, Asian, Cyclic Nucleotide Phosphodiesterases, Type 7, Deafness, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Hearing, Humans, Japan, Male, Membrane Proteins, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Prevalence, Repressor Proteins, Risk Assessment, Risk Factors, Smoking, United States, Gene-environment interaction, Genome-wide linkage, Hearing loss, Family, Linkage, American Diabetes Association GENNID Study Group, Clinical Sciences, Neurosciences, Medical Physiology, Otorhinolaryngology
Abstract

BackgroundThis study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models.ResultsAfter adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (odds ratio (OR) = 4.58; 95% Confidence Interval (CI): (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR = 5.22; 95% CI: (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identified when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21).ConclusionsTo our knowledge this was the first report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these findings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies.

Published
2020

24. Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors

Author

Merino, Jordi, Jablonski, Kathleen A, Mercader, Josep M, Kahn, Steven E, Chen, Ling, Harden, Maegan, Delahanty, Linda M, Araneta, Maria Rosario G, Walford, Geoffrey A, Jacobs, Suzanne BR, Ibebuogu, Uzoma N, Franks, Paul W, Knowler, William C, Florez, Jose C, Bray, George A, Gadde, Kishore, Chatellier, Annie, Arceneaux, Jennifer, Dragg, Amber, Duncan, Crystal, Greenway, Frank L, Hsia, Daniel, Levy, Erma, Lockett, Monica, Ryan, Donna H, Ehrmann, David, Matulik, Margaret J, Czech, Kirsten, DeSandre, Catherine, Goldstein, Barry J, Furlong, Kevin, Smith, Kellie A, Wildman, Wendi, Pepe, Constance, Goldberg, Ronald B, Calles, Jeanette, Ojito, Juliet, Castillo-Florez, Sumaya, Florez, Hermes J, Giannella, Anna, Lara, Olga, Veciana, Beth, Haffner, Steven M, Hazuda, Helen P, Montez, Maria G, Hattaway, Kathy, Lorenzo, Carlos, Martinez, Arlene, Walker, Tatiana, Hamman, Richard F, Dabelea, Dana, Testaverde, Lisa, Anderson, Denise, Bouffard, Alexis, Jenkins, Tonya, Lenz, Dione, Perreault, Leigh, Price, David W, Steinke, Sheila C, Horton, Edward S, Poirier, Catherine S, Swift, Kati, Caballero, Enrique, Fargnoli, Barbara, Guidi, Ashley, Guido, Mathew, Jackson, Sharon D, Lambert, Lori, Lawton, Kathleen E, Ledbury, Sarah, Sansoucy, Jessica, Spellman, Jeanne, Montgomery, Brenda K, Fujimoto, Wilfred, Knopp, Robert H, Lipkin, Edward W, Morgan-Taggart, Ivy, Murillo, Anne, Taylor, Lonnese, Thomas, April, Tsai, Elaine C, Trence, Dace, Kitabchi, Abbas E, Dagogo-Jack, Samuel, Murphy, Mary E, Taylor, Laura, Dolgoff, Jennifer, Clark, Debra, Ibebuogu, Uzoma, Lambeth, Helen, Ricks, Harriet, Rutledge, Lily MK, Soberman, Judith E, Molitch, Mark E, Metzger, Boyd E, Johnson, Mariana K, Giles, Mimi M, Larsen, Diane, and Pen, Samsam C

Subjects
Biomedical and Clinical Sciences, Diabetes, Clinical Research, Atherosclerosis, Clinical Trials and Supportive Activities, Cardiovascular, Heart Disease, Prevention, Heart Disease - Coronary Heart Disease, Nutrition, Obesity, Metabolic and endocrine, Good Health and Well Being, Adult, Cardiovascular Diseases, Coronary Artery Disease, Diabetes Mellitus, Type 2, Exercise, Exercise Therapy, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Life Style, Male, Metabolic Syndrome, Metformin, Middle Aged, Prediabetic State, Preventive Health Services, Risk Factors, United States, Diabetes Prevention Program Research Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.

Published
2020

25. Unveiling the Rich and Diverse Universe of Subsecond Astrophysics through LSST Star Trails

Author

Thomas, David, Kahn, Steven M., Bianco, Federica B., Ivezić, Željko, Raiteri, Claudia M., Possenti, Andrea, Peterson, John R., Burke, Colin J., Blum, Robert D., Jacoby, George H., Howell, Steve B., and Madejski, Grzegorz

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

We present a unique method that allows the LSST to scan the sky for stellar variability on short timescales. The operational component of the strategy requires LSST to take star trail images. The image processing component uses deep learning to sift for transient events on timescales down to 10 ms. We advocate for enabling this observing mode with LSST, as coupling this capability with the LSST's tremendous 319.5 m$^2$deg$^2$ etendue will produce the first wide area optical survey of the universe on these timescales. We explain how these data will advance both planned lines of investigation and enable new research in the areas of stellar flares, cataclysmic variables, active galactic nuclei, Kuiper Belt objects, gamma-ray bursts, and fast radio bursts.

Published
2018

27. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Author

Deanfield, John, Verma, Subodh, Scirica, Benjamin M, Kahn, Steven E, Emerson, Scott S, Ryan, Donna, Lingvay, Ildiko, Colhoun, Helen M, Plutzky, Jorge, Kosiborod, Mikhail N, Hovingh, G Kees, Hardt-Lindberg, Søren, Frenkel, Ofir, Weeke, Peter E, Rasmussen, Søren, Goudev, Assen, Lang, Chim C, Urina-Triana, Miguel, Pietilä, Mikko, Lincoff, A Michael, Abe, Mitsunori, Abhaichand, Rajpal K, Abhayaratna, Walter P, Abhyankar, Atul, Abidin, Imran B Zainal, Abou Assi, Hiba, Accini Mendoza, Jose L, Adas, Mine, Agaiby, John M, Agarwal, Devendra K, Agha, Maher, Ahmed, Azazuddin, Ahtiainen, Petteri, Aigner, Elmar, Ajay, Naik, Ali, Norsiah, Al-Karadsheh, Amer, Allison, Roy, Allison, Dale C, Alpenidze, Diana, Altuntas, Yuksel, Al-Zoebi, Ayham, Ambuj, Roy, Amerena, John, Anderson, Robert J, Ando, Toshiaki, Andrews, Robert, Antonova, Elizaveta, Appel, Karl-Friedrich, Arantes, Flávia B, Araz, Mustafa, Arbel, Yaron, Arenas León, José L, Argyrakopoulou, Georgia, Ariani, Mehrdad, Arias Mendoza, Maria A, Arif, Ahmed A, Arneja, Jaspal, Aroda, Vanita R, Aronne, Louis J, Arstall, Margaret, Asamoah, Njaimeh, Asanin, Milika, Audish, Hanid, Avram, Rodica, Badat, Aysha, Badiu, Corin V, Bakdash, Wa'el, Bakiner, Okan S, Bandezi, Vuyokazi N, Bang, Liew H, Bansal, Sandeep, Baranyai, Marietta, Barbarash, Olga, Barber, Mark, Barnum, Otis, Barone Rochette, Gilles, Bashkin, Amir, Baum, Seth, Bays, Harold E, Bazzoni Ruiz, Alberto E, Beckowski, Maciej, Beerachee, Yaswin, Bellary, Srikanth, Belousova, Lidia, Berk, Martin, Bernstein, Marc, Berra, Cesare, Beshay, Isaac, Bhagwat, Ajit, Bhan, Arti, Biggs, William C, Billings, Liana, Bitar, Fahed, Block, Bradley, Bo, Simona, Bogdanski, Pawel, Bolshakova, Olga O, Boshchenko, Alla A, Bosworth, Hayden, Botero Lopez, Rodrigo, Bôttcher, Morten, Bourgeois, Ronald, Brautigam, Donald, Breton, Cristian F, Broadley, Andrew, Brockmyre, Andrew P, Brodie, Steven K, Bucci, Marco, Budincevic, Hrvoje, Budoff, Matthew J, Buffman, Barry, Buljubasic, Nediljka, Buranapin, Supawan, Burgess, Lesley, Burguera, Bartolomé, Buriakovska, Olena, Buscemi, Silvio, Busch, Robert, Buse, John B, Buynak, Robert, Byrne, Maria, Caceaune, Elena, Cadena Bonfanti, Alberto J, Calinescu, Cornell V, Call, Robert S, Canecki Varzic, Silvija, Cannon, Kevin, Capehorn, Matt, Cariou, Bertrand, Carr, Jeffrey, Carrillo-Jimenez, Rodolfo, Casas, Marcelo, Castro, Almudena, Celik, Ahmet, Cercato, Cintia, Cermak, Ondrej, Cha, James Y, Chacon, Carolina, Chaicha-Brom, Tira, Chandra, Sandeep, Chettibi, Mohamed, Chevts, Julia, Christopher, Johann, Chrustowski, Witold, Cif, Adriana, Clark, Rebecca, Clark, Wayne, Clifford, Piers, Coetzee, Kathleen, Cogni, Giulia, Colao, Anna Maria, Colquhoun, David M, Concha, Mauricio, Condit, Jonathan, Constance, Christian, Constantin, Ciprian, Constantinescu, Silviana, Corbett, Clive, Cornett, George M, Correia, Marcelo, Cortinovis, Fiorenzo, Cosma, Dana, Creely, Steven, Cross, David, Curtis, Brian, Czochra, Wojciech, Daboul, Nizar Y, Dagdelen, Selcuk, D'agostino, Ronald, Dang, Cuong, Datta, Sudip, Davuluri, Ashwini K, Dawood, Saleem Y, De Jong, Douwe M, De La Cuesta, Carmen, De Los Rios Ibarra, Manuel O, De Pablo, Carmen, De Pauw, Michel, Dela Llana, Alexander, Delibasic, Maja, Delic-Brkljacic, Diana, Demicheli, Thibaud, Denger, Ralf J, Desai, Devang, Desai, Piyush, Desouza, Cyrus V, Dicker, Dror, Djenic, Nemanja, Dobson, Simon, Doi, Masayuki, Doran, Jesse A, Dorman, Reinhart, Dotta, Francesco, Dukes, Carl E, Duronto, Ernesto, Durst, Ronen, Dvoryashina, Irina V, Ebrahim, Iftikhar O, Eggebrecht, Holger, Egstrup, Kenneth, Ekinci, Elif I, Eliasson, Björn, Eliasson, Ken, Enache, Georgiana, Enculescu, Dan, English, Patrick, Ermakova, Polina, Ershova, Olga, Ezaki, Hirotaka, Ezhov, Marat, Farias, Eduardo, Farias, Javier M, Farsky, Pedro S, Ferreira, Daniel, Filteau, Pierre, Finneran, Matthew P, Folkens, Eric M, Fonseca, Alberto G, Fonseca, Luisa, Fordan, Steven, Fourie, Nyda, França, Sara, Franco, Denise R, Franek, Edward, Friedman, Keith, Frittitta, Lucia, Froer, Michael, Fuckar, Krunoslav, Fujii, Kenshi, Fujita, Ryoko, Fukushima, Yasushi, Fulat, Mohamed, Fulwani, Mahesh, Gajos, Grzegorz, Galyavich, Albert, Gambill, Michael L, Gandotra, Dheeraj, Winston, Gandy, Garcia Hernandez, Pedro A, García Reza, Raymundo, Garg, Naveen, Garg, Sandeep, Garvey, William T, Garza, Juan C, Gatta-Cherifi, Blandine, Gelev, Valeri, Geller, Steven A, Geohas, Jeffrey G, Georgiev, Borislav, Ghazi, Adline, Gilbert, Matthew P, Gilinskaya, Olga, Gislason, Gunnar, Gogas Yavuz, Dilek, González Albarrán, Olga, Gordeev, Ivan G, Gorton, Sidney C, Goudev, Assen, Gretland Valderhaug, Tone, Groenemeijer, Bjorn, Gul, Ibrahim, Gullestad, Lars, Gurieva, Irina, Guseva, Galina N, Hagenow, Andreas, Haluzik, Martin, Halvorsen, Sigrun, Hammoudi, Naima, Hanaoka, Keiichi, Hancu, Nicolae, Hanusch, Ursula, Harris, Kathleen, Harris, Barry, Hartleib, Michael, Hartman, Aaron N, Hata, Yoshiki, Heimer, Brian, Herman, Lee, Herzog, William, Hewitt, Eric, Heymer, Peter, Hiremath, Shirish, Hjelmesaeth, Joeran, Høgalmen, Rasmus Geir, Høivik, Hans Olav, Holmer, Helene, Horoshko, Olha, Houser, Patricia M, Hove, Jens D, Hsieh, I-Chang, Hulot, Jean-Sébastien, Hussein, Zanariah, Ilashchuk, Tetiana, Ilveskoski, Erkki, Ipatko, Irina, Iranmanesh, Ali, Isawa, Tsuyoshi, Issa, Moises, Iteld, Bruce, Iwasawa, Takamasa, Jabbar, Danish, Jackson, Richard A, Jackson-Voyzey, Ewart, Jacob, Stephan, Jaffrani, Naseem A, Jardula, Michael F, Jastreboff, Ania, Jensen, Svend E, Jerkins, Terri, Jimenez-Ramos, Silvia A, Jitendra Pal Singh, Sawhney, Johnson, Wallace, Joyce, John M, Jozefowska, Malgorzata, Jugnundan, Prakash, Jungmair, Wolfgang, Jurowiecki, Jaroslaw, Kadokami, Toshiaki, Kahali, Dhiman, Kahrmann, Gerd, Kaiser, Sergio E, Kalmucki, Piotr, Kanadasi, Mehmet, Kandath, David, Kania, Grzegorz, Kannan, J, Kapp, Cornelia, Karczmarczyk, Agnieszka, Kartalis, Athanasios, Kaser, Susanne, Kasim, Sazzli Shahlan, Kastelic, Richard, Kato, Toshiaki, Katova, Tzvetana, Kaul, Upendra, Kautzky-Willer, Alexandra, Kawanishi, Masahiro, Kayikcioglu, Meral, Kazakova, Elena E, Keeling, Philip, Kempe, Hans-Peter, Kereiakes, Dean J, Kerneis, Mathieu, Keski-Opas, Tiina, Khadra, Suhail, Khaisheva, Larisa, Kharakhulakh, Marina, Khlevchuk, Tatiana, Khoo, Jeffrey, Kiatchoosakun, Songsak, Kinoshita, Noriyuki, Kinoshita, Masaharu, Kitamura, Ryoji, Kiyosue, Arihiro, Klavina, Irina, Klein, Eric J, Klimsa, Zdenek, Klonoff, David, Klug, Eric, Kobalava, Zhanna, Kodera, Satoshi, Koga, Tokushi, Kokkinos, Alexander, Koleckar, Pavel, Könyves, László, Koren, Michael J, Kormann, Adrian P, Kostner, Karam, Kreutzmann, Kristin, Krishinan, Saravanan, Krishnasamy, Sathya S, Krivosheeva, Inga, Kruljac, Ivan, Kubicki, Ted, Kuchar, Ladislav, Kujawiak, Monika, Kunishige, Hideyuki, Kurtinecz, Melinda, Kurtz Lisboa, Hugo R, Kushnir, Mykola, Kyyak, Yulian, Lace, Arija, Lakka, Timo, Lalic, Nebojsa, Lalic, Katarina, Lambadiari, Vaia, Lanaras, Leonidas, Lang, Chim, Langlois, Marie-France, Lash, Joseph, Latkovskis, Gustavs, Lau, David, Lazcano Soto, José Roberto, Le Roux, Carel, Ledesma, Gilbert N, Lee, Li Yuan, Lee, Thung-Lip, Lee, Kelvin, Lehrke, Michael, Leite, Silmara O, Leksycka, Agata, Lenzmeier, Thomas, Leonetti, Frida, Leonidova, Viktoriia, Lepor, Norman, Leung, Melissa, Levchenko, Olena, Levins, Peter, Levy, Louis J, Lewis, Matthew, Liberopoulos, Evangelos, Liberty, Idit, Lindholm, Carl-Johan, Lingvay, Ildiko, Linhart, Ales, Liu, Ming-En, Liu, Jenny, Lofton, Holly, Logemann, Timothy, Lombaard, Johannes J, Lombard, Landman, Lorraine, Richard, Lovell, Charles F, Ludvik, Bernhard, Lukaszewicz, Monika, Lupkovics, Géza, Lupovitch, Steven, Lupu, Sirona, Lynch, Mary, Lysak, Zoreslava, Lysenko, Tatyana A, Maeda, Hajime, Maeda, Itaru, Mæng, Michael, Mahajan, Ajay U, Maher, Vincent, Maia, Lilia N, Makotoko, Ellen M, Malavazos, Alexis, Malecha, Jan, Malicherova, Emilia, Manita, Mamoru, Mannucci, Edoardo, Mareev, Viacheslav, Marin, Liliana, Markova, Tatiana, Marso, Steven P, Martens, F.M.A.C., Martinez, Cuper, Martinez Cano, Carlos A, Martins, Cristina, Masmiquel Comas, Luis, Matsumoto, Takashi, Mcdonald, Kenneth, Mcgowan, Barbara, Mcgrew, Frank, Mclean, Barry K, Mcpherson, David D, Merino Torres, Juan Francisco, Meyers, Peter, Meyhöfer, Sebastian, Mezquita Raya, Pedro, Milanova, Maria, Milicic, Davor, Miller, Gary, Mills, Richard E, Mîndrescu, Nicoleta M, Mingrone, Geltrude, Minkova, Dotska A, Mirani, Marco, Miras, Alexander, Mistodie, Cristina V, Mitomo, Satoru, Mittal, Sanjay, Miyake, Taiji, Miyamoto, Naomasa, Molony, David, Monteiro, Pedro, Mooe, Thomas, Moosa, Naeem, Morales Portillo, Cristobal, Morales Villegas, Enrique C, Morawski, Emily J, Morbey, Claire, Morin, Robert P, Morisaki, Kuniaki, Morosanu, Magdalena, Mosenzon, Ofri, Mostovoy, Yuriy, Munir, Iqbal, Muratori, Fabrizio, Murray, Ryan, Murthy, Avinash, Myint, Min, Myshanych, Galyna, Nafornita, Valerica, Nagano, Takuya, Nair, Sunil, Nakhle, Samer N, Natsuaki, Masahiro, Nayak, Bindu M, Nibouche, Djamel Eddine, Nicholls, Stephen, Nicolau, José C, Nicolescu, Georgiana, Nierop, Peter, Niskanen, Leo, Ntaios, George, Nygård, Ottar Kjell, Oaks, Joshua B, Obrezan, Andrey, O'donnell, Philip, Oguri, Mitsutoshi, Oguzhan, Abdurrahman, Oh, Fumiki, Ohsugi, Mitsuru, Okada, Yoshio, Okayama, Hideki, Onaca, Adriana, Onaka, Haruhiko, Oneil, Patrick, Ong, Tiong Kiam, Ong, Stephen, Ono, Yasuhiro, Opsahl, Paul J, Ostrowska, Lucyna, Oviedo, Alejandra, Ozdogan, Oner, Ozpelit, Ebru, Pagkalos, Emmanouil, Pagotto, Uberto, Páll, Dénes, Pandey, Amritanshu- Shekhar, Parkhomenko, Oleksandr, Parvathareddy, Krishna Malakondareddy, Patel, Minesh B, Patsilinakos, Sotirios, Paul, Neil, Pedersen, Sue, Pereira, Isabel, Pereira, Edward Scott, Perez Terns, Paula, Perez-Vargas, Elba A, Pergaeva, Yulia, Perkelvald, Alexander, Peskov, Andrey B, Peter, Jonathan, Peters, Karina, Petit, Catherine, Petrov, Ivo, Philis-Tsimikas, Athena, Pietilä, Mikko, Pinto, Fausto, Piros, Annamária, Piyayotai, Dilok, Platonov, Dmitriy, Poirier, Paul, Pop, Lavinia, Popa, Bogdan, Pop-Busui, Rodica, Poremba, John, Porto, Alejandro, Postadzhiyan, Arman, Pothineni, Ramesh B, Potu, Ranganatha P, Powell, Talessa, Prafulla, Kerkar G, Prager, Rudolf, Prakova-Teneva, Zhulieta R, Pratley, Richard E, Price, Hermione, Pulka, Grazyna, Pullman, John, Punt, Zelda E, Purighalla, Raman S, Purnell, Peter, Qureshi, Mansoor, Rabasa-Lhoret, Remi, Raikhel, Marina A, Rancane, Gita, Randeva, Harpal, Rasouli, Neda, Reurean Pintilei, Delia V, Reyes, Ciro R, Rezgale, Inga, Rice, Eva, Riley, Thaddeus H, Risser, Joseph A, Ristic, Arsen, Rivas Fernández, Margarita, Robbins, David, Robitaille, Yves, Rodbard, Helena W, Rodriguez Plazas, Jaime A, Römer, T.J., Rosen, Glenn, Rosman, Dr Azhari, Rossi, Paulo, Rudenko, Leonid, Ruffin, Omari, Ruhani, Anwar Irawan, Runev, Nikolay, Ruyatkin, Dmitriy, Ruzic, Alen, Ryabov, Vyacheslav V, Rydén, Lars, Saggar, Suraj, Sakamoto, Tomohiro, Salter, Tim, Samal, Aditya K, Samoilova, Yulia, Sanabria, Hugo D, Sancak, Seda, Sangrigoli, Renee, Sansanayudh, Nakarin, Santini, Ferruccio, Saraiva, José F, Sardinov, Ruslan, Sargeant, William, Sari, Ramazan, Sathananthan, Airani, Sathyapalan, Thozhukat, Sato, Atsushi, Sauter, Joachim, Sbraccia, Paolo, Schaap, J., Schaum, Thomas, Schiele, François, Scott, John, Segal Lieberman, Gabriella, Segner, Alexander, Senior, Roxy, Sergeeva-Kondrachenko, Marina Y, Serota, Harvey, Serusclat, Pierre, Sethi, Rishi, Shah, Manoj K, Shah, Neerav, Shalaev, Sergey, Sharma, Raj, Sharma, Sumeet, Shaydyuk, Oksana, Shea, Heidi C, Shechter, Michael, Shehadeh, Naim, Shirazi, Mitra, Shlesinger, Yshay, Shneker, Ayham, Shutemova, Elena, Siasos, Gerasimos, Siddiqui, Imran A, Sidey, Jennifer, Sigal, Felix, Sime, Iveta, Singh, Narendra, Siraj, Elias, Sivalingam, Kanagaratnam, Skoczylas, Grzegorz, Smith, Stephen K, Smolenskaya, Olga, Snyder, Brian, Sofer, Yael, Sofley, C.W., Solano, Royce, Sonmez, Yusuf A, Sorokin, Maxim, Soto González, Alfonso, Sotolongo, Carlos, Soufer, Joseph, Soyluk Selcukbiricik, Ozlem, Spaic, Tamara, Spriggs, Douglas, Sreenan, Seamus, Stahl, Hans-Detlev, Stamatelopoulos, Kimon, Stanislavchuk, Mykola, Stankovic, Goran, Stasek, Josef, Steg, Gabriel, Steindorf, Joerg, Stephan, Dominique, Stewart, John, Still, Christopher, St-Maurice, Francois, Stogowska-Nikiciuk, Barbara, Stoker, Jeff, Stokic, Edita, Strzelecka, Anna, Sturm, Kerstin, Sueyoshi, Atsushi, Sugiura, Toshiyuki, Sultan, Senan, Suplotova, Lyudmila A, Suwanagool, Arisara, Suwanwalaikorn, Sompongse, Sveklina, Tatiana, Swanson, Neil, Swart, Henk, Swenson, Bradley P, Szyprowska, Ewa, Tait, Graeme, Takács, Róbert, Takeuchi, Yuzo, Tamirisa, Aparna, Tanaka, Hideki, Tatovic, Danijela, Tellier, Guy, Teragawa, Hiroki, Teterovska, Dace, Thomas, Nihal, Thuan, Jean-Francois, Tinahones, Francisco, Tisheva-Gospodinova, Snezhanka, Toarba, Cristina, Todoriuk, Liudmyla, Tokmakova, Mariya, Tonstad, Serena, Toplak, Hermann, Tran, Henry, Tripathy, Devjit, Trusau, Aliaksandr, Tsabedze, Nqoba, Tsougos, Elias, Tsoukas, George M, Tuccinardi, Dario, Tuna, Mazhar M, Turatti, Luiz A, Tziomalos, Konstantinos, Udommongkol, Chesda, Ueda, Osamu, Ukkola, Olavi, Unubol, Mustafa, Urbach, Dorothea, Urina Triana, Miguel A, Usdan, Lisa, Vaidya, Bijay, Vale, Noah, Vallieres, Gerald, Van Beek, Andre P, Van De Borne, Philippe, Van Der Walt, Eugene, Van Der Zwaan, C., Van Nieuwenhuizen, Elane, Van Zyl, Louis, Vanduynhoven, Philippe, Varghese, Kiron, Vasileva, Svetla P, Vassilev, Dobrin, Vathesatogkit, Prin, Velychko, Valentyna, Vercammen, Chris, Verges, Bruno, Verma, Subodh, Verwerft, Jan, Vesela, Alica, Veselovskaya, Nadezhda G, Vettor, Roberto, Veze, Irina, Vijan, Vinod, Vijayaraghavan, Ram, Villarino, Adriana, Vincent, Royce, Vinogradova, Oksana, Vishlitzky, Victor, Vlad, Adrian, Vladu, Ionela Mihaela, Vo, Anthony, Von Engelhardt, Charlotte, Von Münchhausen, Candy, Vorobyeva, Olga, Vossenberg, T., Vrolix, Mathias, Vukicevic, Marjana, Vyshnyvetskyy, Ivan, Wadvalla, Shahid, Wagner, Jan, Wakeling, John, Wallace, James, Wan Mohamed, Wan Mohd Izani, Wander, Gurpreet S, Ward, Kathleen, Warren, Mark L, Watanabe, Atsuyuki, Weber, Bruce, Weintraub, Howard, Weisnagel, John, Welker, James, Wendisch, Ulrich, Wenocur, Howard S, Wierum, Craig, Wilding, John, William, Maged, Wilson, Pete, Wilson, Jonathan P, Wong, Yuk-Ki, Wongcharoen, Wanwarang, Wozniak, Iwona, Wu, Chau-Chung, Wyatt, Nell, Wynne, Alan, Yamaguchi, Hiroshi, Yamasaki, Masahiro, Yazici, Dilek, Yeh, Hung-I, Yotov, Yoto, Yuan, Qingyang, Zacher, Jeffrey, Zagrebelnaya, Olga, Zaidman, Cesar J, Zalevskaya, Alsu, Zarich, Stuart, Zatelli, Maria Chiara, Zeller, Helga, Zhdanova, Elena A, Zornitzki, Taiba, Zrazhevskiy, Konstantin, Zykov, Mikhail, Lincoff, A Michael, Ryan, Donna H, Colhoun, Helen M, Deanfield, John E, Emerson, Scott S, Kahn, Steven E, Kushner, Robert F, Plutzky, Jorge, Brown-Frandsen, Kirstine, Hovingh, G Kees, Hardt-Lindberg, Soren, and Tornøe, Christoffer W

Abstract

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure.

Published
2024
Full Text
View/download PDF

28. LBP-032 Semaglutide improves cardiovascular outcomes in patients with high risk for metabolic dysfunction-associated steatohepatitis-a subgroup analysis from the SELECT trial

Author

Meyhöfer, Sebastian, primary, Cariou, Bertrand, additional, Cercato, Cintia, additional, Colhoun, Helen, additional, Duun-Henriksen, Anne, additional, Kliers, Iris, additional, Lincoff, A. Michael, additional, Lingvay, Ildiko, additional, Long, Michelle, additional, Newsome, Philip N., additional, Nicholls, Stephen, additional, De Los Angeles Quiroga Pelaez, Maria, additional, Santini, Ferruccio, additional, Sanyal, Arun J., additional, and Kahn, Steven, additional

Published
2024
Full Text
View/download PDF

29. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial

Author

Colhoun, Helen M., primary, Lingvay, Ildiko, additional, Brown, Paul M., additional, Deanfield, John, additional, Brown-Frandsen, Kirstine, additional, Kahn, Steven E., additional, Plutzky, Jorge, additional, Node, Koichi, additional, Parkhomenko, Alexander, additional, Rydén, Lars, additional, Wilding, John P. H., additional, Mann, Johannes F. E., additional, Tuttle, Katherine R., additional, Idorn, Thomas, additional, Rathor, Naveen, additional, and Lincoff, A. Michael, additional

Published
2024
Full Text
View/download PDF

30. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial

Author

Ryan, Donna H., primary, Lingvay, Ildiko, additional, Deanfield, John, additional, Kahn, Steven E., additional, Barros, Eric, additional, Burguera, Bartolome, additional, Colhoun, Helen M., additional, Cercato, Cintia, additional, Dicker, Dror, additional, Horn, Deborah B., additional, Hovingh, G. Kees, additional, Jeppesen, Ole Kleist, additional, Kokkinos, Alexander, additional, Lincoff, A. Michael, additional, Meyhöfer, Sebastian M., additional, Oral, Tugce Kalayci, additional, Plutzky, Jorge, additional, van Beek, André P., additional, Wilding, John P. H., additional, and Kushner, Robert F., additional

Published
2024
Full Text
View/download PDF

31. #2496 Effect of semaglutide on kidney outcomes in people with overweight or obesity and established cardiovascular disease in the SELECT trial

Author

Colhoun, Helen M, primary, Lingvay, Ildiko, additional, Brown, Paul M, additional, Deanfield, John, additional, Brown-Frandsen, Kirstine, additional, Kahn, Steven E, additional, Plutzky, Jorge, additional, Node, Koichi, additional, Parkhomenko, Alexander, additional, Rydén, Lars, additional, Wilding, John P H, additional, Mann, Johannes F E, additional, Tuttle, Katherine R, additional, Idorn, Thomas, additional, Rathor, Naveen, additional, and Lincoff, A Michael, additional

Published
2024
Full Text
View/download PDF

36. The LSST Dark Energy Science Collaboration (DESC) Science Requirements Document

Author

The LSST Dark Energy Science Collaboration, Mandelbaum, Rachel, Eifler, Tim, Hložek, Renée, Collett, Thomas, Gawiser, Eric, Scolnic, Daniel, Alonso, David, Awan, Humna, Biswas, Rahul, Blazek, Jonathan, Burchat, Patricia, Chisari, Nora Elisa, Dell'Antonio, Ian, Digel, Seth, Frieman, Josh, Goldstein, Daniel A., Hook, Isobel, Ivezić, Željko, Kahn, Steven M., Kamath, Sowmya, Kirkby, David, Kitching, Thomas, Krause, Elisabeth, Leget, Pierre-François, Marshall, Philip J., Meyers, Joshua, Miyatake, Hironao, Newman, Jeffrey A., Nichol, Robert, Rykoff, Eli, Sanchez, F. Javier, Slosar, Anže, Sullivan, Mark, and Troxel, M. A.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The Large Synoptic Survey Telescope (LSST) Dark Energy Science Collaboration (DESC) will use five cosmological probes: galaxy clusters, large scale structure, supernovae, strong lensing, and weak lensing. This Science Requirements Document (SRD) quantifies the expected dark energy constraining power of these probes individually and together, with conservative assumptions about analysis methodology and follow-up observational resources based on our current understanding and the expected evolution within the field in the coming years. We then define requirements on analysis pipelines that will enable us to achieve our goal of carrying out a dark energy analysis consistent with the Dark Energy Task Force definition of a Stage IV dark energy experiment. This is achieved through a forecasting process that incorporates the flowdown to detailed requirements on multiple sources of systematic uncertainty. Future versions of this document will include evolution in our software capabilities and analysis plans along with updates to the LSST survey strategy., Comment: 32 pages + 60 pages of appendices. This is v1.0.2 of the DESC SRD, an internal collaboration document that is being made public and is not planned for submission to a journal. Data products for reproducing key plots are available on Zenodo, https://doi.org/10.5281/zenodo.1409815 ; see "Executive Summary and User Guide" for how to use and cite those products

Published
2018

37. Searching for Sub-Second Stellar Variability with Wide-Field Star Trails and Deep Learning

Author

Thomas, David and Kahn, Steven M

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

We present a method that enables wide field ground-based telescopes to scan the sky for sub-second stellar variability. The method has operational and image processing components. The operational component is to take star trail images. Each trail serves as a light curve for its corresponding source and facilitates sub-exposure photometry. We train a deep neural network to identify stellar variability in wide-field star trail images. We use the Large Synoptic Survey Telescope (LSST) Photon Simulator to generate simulated star trail images and include transient bursts as a proxy for variability. The network identifies transient bursts on timescales down to 10 milliseconds. We argue that there are multiple fields of astrophysics that can be advanced by the unique combination of time resolution and observing throughput that our method offers.

Published
2018
Full Text
View/download PDF

39. Scientific Synergy Between LSST and Euclid

Author

Rhodes, Jason, Nichol, Robert C., Aubourg, Éric, Bean, Rachel, Boutigny, Dominique, Bremer, Malcolm N., Capak, Peter, Cardone, Vincenzo, Carry, Benoît, Conselice, Christopher J., Connolly, Andrew J., Cuillandre, Jean-Charles, Hatch, N. A., Helou, George, Hemmati, Shoubaneh, Hildebrandt, Hendrik, Hložek, Renée, Jones, Lynne, Kahn, Steven, Kiessling, Alina, Kitching, Thomas, Lupton, Robert, Mandelbaum, Rachel, Markovic, Katarina, Marshall, Phil, Massey, Richard, Maughan, Ben J., Melchior, Peter, Mellier, Yannick, Newman, Jeffrey A., Robertson, Brant, Sauvage, Marc, Schrabback, Tim, Smith, Graham P., Strauss, Michael A., Taylor, Andy, and Von Der Linden, Anja

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

Euclid and the Large Synoptic Survey Telescope (LSST) are poised to dramatically change the astronomy landscape early in the next decade. The combination of high cadence, deep, wide-field optical photometry from LSST with high resolution, wide-field optical photometry and near-infrared photometry and spectroscopy from Euclid will be powerful for addressing a wide range of astrophysical questions. We explore Euclid/LSST synergy, ignoring the political issues associated with data access to focus on the scientific, technical, and financial benefits of coordination. We focus primarily on dark energy cosmology, but also discuss galaxy evolution, transient objects, solar system science, and galaxy cluster studies. We concentrate on synergies that require coordination in cadence or survey overlap, or would benefit from pixel-level co-processing that is beyond the scope of what is currently planned, rather than scientific programs that could be accomplished only at the catalog level without coordination in data processing or survey strategies. We provide two quantitative examples of scientific synergies: the decrease in photo-z errors (benefitting many science cases) when high resolution Euclid data are used for LSST photo-z determination, and the resulting increase in weak lensing signal-to-noise ratio from smaller photo-z errors. We briefly discuss other areas of coordination, including high performance computing resources and calibration data. Finally, we address concerns about the loss of independence and potential cross-checks between the two missions and potential consequences of not collaborating., Comment: 33 pages, 7 figures, to appear in ApJS, revised with additional references and minor corrections

Published
2017
Full Text
View/download PDF

40. LSST: From Science Drivers to Reference Design and Anticipated Data Products

Author

Ivezić, Željko, Kahn, Steven M, Tyson, J Anthony, Abel, Bob, Acosta, Emily, Allsman, Robyn, Alonso, David, AlSayyad, Yusra, Anderson, Scott F, Andrew, John, Angel, James Roger P, Angeli, George Z, Ansari, Reza, Antilogus, Pierre, Araujo, Constanza, Armstrong, Robert, Arndt, Kirk T, Astier, Pierre, Aubourg, Éric, Auza, Nicole, Axelrod, Tim S, Bard, Deborah J, Barr, Jeff D, Barrau, Aurelian, Bartlett, James G, Bauer, Amanda E, Bauman, Brian J, Baumont, Sylvain, Bechtol, Ellen, Bechtol, Keith, Becker, Andrew C, Becla, Jacek, Beldica, Cristina, Bellavia, Steve, Bianco, Federica B, Biswas, Rahul, Blanc, Guillaume, Blazek, Jonathan, Blandford, Roger D, Bloom, Josh S, Bogart, Joanne, Bond, Tim W, Booth, Michael T, Borgland, Anders W, Borne, Kirk, Bosch, James F, Boutigny, Dominique, Brackett, Craig A, Bradshaw, Andrew, Brandt, William Nielsen, Brown, Michael E, Bullock, James S, Burchat, Patricia, Burke, David L, Cagnoli, Gianpietro, Calabrese, Daniel, Callahan, Shawn, Callen, Alice L, Carlin, Jeffrey L, Carlson, Erin L, Chandrasekharan, Srinivasan, Charles-Emerson, Glenaver, Chesley, Steve, Cheu, Elliott C, Chiang, Hsin-Fang, Chiang, James, Chirino, Carol, Chow, Derek, Ciardi, David R, Claver, Charles F, Cohen-Tanugi, Johann, Cockrum, Joseph J, Coles, Rebecca, Connolly, Andrew J, Cook, Kem H, Cooray, Asantha, Covey, Kevin R, Cribbs, Chris, Cui, Wei, Cutri, Roc, Daly, Philip N, Daniel, Scott F, Daruich, Felipe, Daubard, Guillaume, Daues, Greg, Dawson, William, Delgado, Francisco, Dellapenna, Alfred, de Peyster, Robert, de Val-Borro, Miguel, Digel, Seth W, Doherty, Peter, Dubois, Richard, Dubois-Felsmann, Gregory P, Durech, Josef, Economou, Frossie, Eifler, Tim, Eracleous, Michael, Emmons, Benjamin L, and Neto, Angelo Fausti

Subjects
Astronomical Sciences, Physical Sciences, astrometry, cosmology: observations, Galaxy: general, methods: observational, stars: general, surveys, astro-ph, Astronomical and Space Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Physical Chemistry (incl. Structural), Astronomy & Astrophysics, Astronomical sciences, Particle and high energy physics, Space sciences
Abstract

We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the solar system, exploring the transient optical sky, and mapping the Milky Way. LSST will be a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachón in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg 2 field of view, a 3.2-gigapixel camera, and six filters (ugrizy) covering the wavelength range 320-1050 nm. The project is in the construction phase and will begin regular survey operations by 2022. About 90% of the observing time will be devoted to a deep-wide-fast survey mode that will uniformly observe a 18,000 deg 2 region about 800 times (summed over all six bands) during the anticipated 10 yr of operations and will yield a co-added map to r ∼27.5. These data will result in databases including about 32 trillion observations of 20 billion galaxies and a similar number of stars, and they will serve the majority of the primary science programs. The remaining 10% of the observing time will be allocated to special projects such as Very Deep and Very Fast time domain surveys, whose details are currently under discussion. We illustrate how the LSST science drivers led to these choices of system parameters, and we describe the expected data products and their characteristics.

Published
2019

41. Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial.

Author

Kahn, Steven E., Deanfield, John E., Jeppesen, Ole Kleist, Emerson, Scott S., Boesgaard, Trine Welløv, Colhoun, Helen M., Kushner, Robert F., Lingvay, Ildiko, Burguera, Bartolome, Gajos, Grzegorz, Horn, Deborah Bade, Hramiak, Irene M., Jastreboff, Ania M., Kokkinos, Alexander, Maeng, Michael, Matos, Ana Laura S.A., Tinahones, Francisco J., Lincoff, A. Michael, and Ryan, Donna H.

Subjects
*SEMAGLUTIDE, *OVERWEIGHT persons, *HYPERGLYCEMIA, *DIABETES, *CARDIOVASCULAR diseases, *OBESITY, *BODY weight
Abstract

OBJECTIVE: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes. RESEARCH DESIGN AND METHODS: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c <6.5%) were randomized to receive subcutaneous semaglutide (2.4 mg weekly) or placebo. Major glycemic outcomes were HbA1c and proportions achieving biochemical normoglycemia (HbA1c <5.7%) and progressing to biochemical diabetes (HbA1c ≥6.5%). RESULTS: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference of −0.32 percentage points (95% CI −0.33 to −0.30; −3.49 mmol/mol [−3.66 to −3.32]) and with the difference favoring semaglutide throughout the study (P < 0.0001). Body weight plateaued at 65 weeks and was 8.9% lower with semaglutide. At week 156, a greater proportion treated with semaglutide were normoglycemic (69.5% vs. 35.8%; P < 0.0001) and a smaller proportion had biochemical diabetes by week 156 (1.5% vs. 6.9%; P < 0.0001). The number needed to treat was 18.5 to prevent a case of diabetes. Both regression and progression were dependent on glycemia at baseline, with the magnitude of weight reduction important in mediating 24.5% of progression and 27.1% of regression. CONCLUSIONS: In people with preexisting cardiovascular disease and overweight or obesity but without diabetes, long-term semaglutide increases regression to biochemical normoglycemia and reduces progression to biochemical diabetes but does not slow glycemic progression over time. 6357437865112 dc240491video1 Video 1. This image is from a video available online at https://bcove.video/3WedKuq. American Diabetes Association 84th Scientific Sessions: SELECT Trial—New Looks at Glycemia, Inflammation, and Heart Failure. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

42. Semaglutide and Cardiovascular Outcomes by Baseline HbA1c and Change in HbA1c in People With Overweight or Obesity but Without Diabetes in SELECT.

Author

Lingvay, Ildiko, Deanfield, John, Kahn, Steven E., Weeke, Peter E., Toplak, Hermann, Scirica, Benjamin M., Rydén, Lars, Rathor, Naveen, Plutzky, Jorge, Morales, Cristobal, Lincoff, A. Michael, Lehrke, Michael, Jeppesen, Ole Kleist, Gajos, Grzegorz, Colhoun, Helen M., Cariou, Bertrand, and Ryan, Donna

Subjects
SEMAGLUTIDE, OVERWEIGHT persons, MAJOR adverse cardiovascular events, GLYCOSYLATED hemoglobin, OBESITY
Abstract

OBJECTIVE: To evaluate the cardiovascular effects of semaglutide by baseline glycated hemoglobin (HbA1c) and change in HbA1c in a prespecified analysis of Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT). RESEARCH DESIGN AND METHODS: In SELECT, people with overweight or obesity and atherosclerotic cardiovascular disease without diabetes were randomized to weekly semaglutide 2.4 mg or placebo. The primary end point of first major adverse cardiovascular event (MACE) (cardiovascular mortality, nonfatal myocardial infarction, or stroke) was reduced by 20% with semaglutide versus placebo. Analysis of outcomes included first MACE, its individual components, expanded MACE (cardiovascular mortality, nonfatal myocardial infarction, or stroke; coronary revascularization; or hospitalization for unstable angina), a heart failure composite (heart failure hospitalization or urgent medical visit or cardiovascular mortality), coronary revascularization, and all-cause mortality by baseline HbA1c subgroup and categories of HbA1c change (<−0.3, −0.3 to 0.3, and >0.3 percentage points) from baseline to 20 weeks using the intention-to-treat principle with Cox proportional hazards. RESULTS: Among 17,604 participants (mean age 61.6 years, 72.3% male), baseline HbA1c was <5.7% for 33.5%, 5.7% to <6.0% for 34.6%, and 6.0% to <6.5% for 31.9%. Cardiovascular risk reduction with semaglutide versus placebo was not shown to be different across baseline HbA1c groups and was consistent with that of the overall study for all end points, except all-cause mortality. Cardiovascular outcomes were also consistent across subgroups of HbA1c change. CONCLUSIONS: In people with overweight or obesity and established atherosclerotic cardiovascular disease but not diabetes, semaglutide reduced cardiovascular events irrespective of baseline HbA1c or change in HbA1c. Thus, semaglutide is expected to confer cardiovascular benefits in people with established atherosclerotic cardiovascular disease who are normoglycemic at baseline and/or in those without HbA1c improvements. 6357437865112 dc240764video1 Video 1. This image is from a video available online at https://bcove.video/3WedKuq. American Diabetes Association 84th Scientific Sessions: SELECT Trial—New Looks at Glycemia, Inflammation, and Heart Failure. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

43. Increased Genetic Risk for β-Cell Failure Is Associated With β-Cell Function Decline in People With Prediabetes.

Author

Billings, Liana K., Jablonski, Kathleen A., Pan, Qing, Florez, Jose C., Franks, Paul W., Goldberg, Ronald B., Hivert, Marie-France, Kahn, Steven E., Knowler, William C., Lee, Christine G., Merino, Jordi, Huerta-Chagoya, Alicia, Mercader, Josep M., Raghavan, Sridharan, Shi, Zhuqing, Srinivasan, Shylaja, Xu, Jianfeng, and Udler, Miriam S.

Subjects
TYPE 2 diabetes, PREDIABETIC state
Abstract

Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the association of T2D pPS with diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin, or placebo arms. Associations were tested with general linear models and Cox regression with adjustment for age, sex, and principal components. Sensitivity analyses included adjustment for BMI. Higher β-cell pPS was associated with lower insulinogenic index and corrected insulin response at 1-year follow-up with adjustment for baseline measures (effect per pPS SD −0.04, P = 9.6 × 10−7, and −8.45 μU/mg, P = 5.6 × 10−6, respectively) and with increased diabetes incidence with adjustment for BMI at nominal significance (hazard ratio 1.10 per SD, P = 0.035). The liver/lipid pPS was associated with reduced 1-year baseline-adjusted triglyceride levels (effect per SD −4.37, P = 0.001). There was no significant interaction between T2D pPS and randomized groups. The remaining pPS were associated with baseline measures only. We conclude that despite interventions for diabetes prevention, participants with a high genetic burden of the β-cell cluster pPS had worsening in measures of β-cell function. Article Highlights: Process-specific genetic scores (partitioned polygenic scores [pPS]) help explain clinical heterogeneity in type 2 diabetes, but whether they inform differential response to diabetes prevention strategies is unknown. In the Diabetes Prevention Program clinical trial, we examined pPS for associations with longitudinal glycemic measures and type 2 diabetes development. Higher β-cell pPS was associated with reduced baseline and even further reduced 1-year β-cell function despite diabetes prevention interventions. Diabetes prevention interventions may not optimally prevent β-cell function decline in people with genetic susceptibility for β-cell dysfunction, which may contribute to the heterogeneity seen in progression of diabetes development. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

44. Chronic kidney disease attenuates the plasma metabolome response to insulin

Author

Roshanravan, Baback, Zelnick, Leila R, Djucovic, Daniel, Gu, Haiwei, Alvarez, Jessica A, Ziegler, Thomas R, Gamboa, Jorge L, Utzschneider, Kristina, Kestenbaum, Bryan, Himmelfarb, Jonathan, Kahn, Steven E, Raftery, Daniel, and de Boer, Ian H

Subjects
Kidney Disease, Clinical Research, Diabetes, Nutrition, Aetiology, 2.1 Biological and endogenous factors, Renal and urogenital, Metabolic and endocrine, Aged, Amino Acids, Blood Glucose, Cross-Sectional Studies, Female, Glomerular Filtration Rate, Glucose Clamp Technique, Healthy Volunteers, Humans, Insulin, Insulin Resistance, Male, Metabolome, Metabolomics, Middle Aged, Mitochondria, Renal Insufficiency, Chronic, Amino acid metabolism, Metabolism, Nephrology
Abstract

Chronic kidney disease (CKD) leads to decreased sensitivity to the metabolic effects of insulin, contributing to protein energy wasting and muscle atrophy. Targeted metabolomics profiling during hyperinsulinemic-euglycemic insulin clamp testing may help identify aberrant metabolic pathways contributing to insulin resistance in CKD. Using targeted metabolomics profiling, we examined the plasma metabolome in 95 adults without diabetes in the fasted state (58 with CKD, 37 with normal glomerular filtration rate [GFR]) who underwent hyperinsulinemic-euglycemic clamp. We assessed heterogeneity in fasting metabolites and the response to insulin to identify potential metabolic pathways linking CKD with insulin resistance. Baseline differences and effect modification by CKD status on changes with insulin clamp testing were adjusted for confounders. Mean GFR among participants with CKD was 37.3 compared with 89.3 ml/min per 1.73 m2 among controls. Fasted-state differences between CKD and controls included abnormalities in tryptophan metabolism, ubiquinone biosynthesis, and the TCA cycle. Insulin infusion markedly decreased metabolite levels, predominantly amino acids and their metabolites. CKD was associated with attenuated insulin-induced changes in nicotinamide, arachidonic acid, and glutamine/glutamate metabolic pathways. Metabolomics profiling suggests disruption in amino acid metabolism and mitochondrial function as putative manifestations or mechanisms of the impaired anabolic effects of insulin in CKD.

Published
2018

45. Prevalence of distal symmetrical polyneuropathy by Diabetes Prevention Program treatment group, diabetes status, duration of diabetes, and cumulative glycemic exposure

Author

G. Lee, Christine, primary, Ciarleglio, Adam, primary, L. Edelstein, Sharon, primary, P. Crandall, Jill, primary, Dabelea, Dana, primary, Goldberg, Ronald B., primary, E. Kahn, Steven, primary, C. Knowler, William, primary, T. Ma, Maxwell, primary, H. White, Neil, primary, and H. Herman, William, primary

Published
2024
Full Text
View/download PDF

46. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial

Author

Ahmann, Andrew J, Arora, Samir, Ball, Eric M, Calderon, Rafael B, Butuk, David J, Chaychi, Leila, Chen, Michael C, Curtis, Brian M, Chochinov, Ronald, Chow, Christopher, Cone, Clancy L, Connery, Lisa, Cortes-Maisonet, Gregorio A, de Souza, Jose, Dungan, Kathleen, Bradley, David, Frias, Juan P, Gabra, Nashwa, Gaudiani, Linda, Herandez-Vazquez, Luis, Hsia, Stanley H, Jardula, Michael R, Klein, Eric J, Kutner, Mark E, Loy, Juan, Miranda, Francisco G, Nunez, Lazaro D, Mujica-Baella, Miguel, Murray, Alexander V, Oliver, Michael J, Oritz-Carrasquillo, Ramon, Palal, Betsy, Parke, Michael T, Philis-Tsimikas, Athena, Purighalla, Raman S, Rosenstock, Julio, Sathananthan, Airani, Shelton, Courtney, Sivalingam, Kanagaratnam, Sorial, Ehab, Soufer, Joseph, Stacey, Helen L, Stonesifer, Larry D, Stringam, Stanley, Van, Joanna T, Vazquez-Tanus, Jose B, Reyes, Ramon, Welch, Michelle, Karimjee, Najmuddin, Martin, Earl E, Arif, Ahmed, Jennings, Timothy W, Fraser, Neil J, Bhargava, Anuj, Wynne, Alan G, Davidson, Evelyne, Billings, Liana, Barranco-Santana, Elizabeth A, Dever, Michael E, Walsh, Patrick, Cho, Austina, Chu, James W, Shubrook, Jay, Knouse, Albert B, Nadar, Venkatesh, Lewy-Alterbaum, Lorena, Lillestol, Michael J, Humiston, Daniel J, White, Alexander J, Mayfield, Ronald K, Bitar, Fahed G, Cereto, Fernando, de la Cuesta, Carmen, De Teresa Parreno, Luis, Jodar Gimeno, Esteban, Mezquita-Raya, Pedro, Morales Portillo, Cristobal J, Quesada Charneco, Miguel, Tinahones Madueno, Francisco J, Tofe Povedano, Santiago, Vazquez, Luis, Fajardo Montañana, Carmen, Soto Gonzalez, Alfonso, Mistodie, Cristina, Szilagyi, Iosif, Filimon, Adriana, Mindrescu, Nicoleta M, Pop, Lavinia, Pascu, Marlena, Negrisanu, Gabriela D, Ciomos, Daniela, Neacsu, Valentina, Thury-Burileanu, Amalia, Liberty, Idit, Stern, Naftali, Sofer, Yael, Sack, Jessica, Shimon, Ilan, Tirosh, Amir, Ishay, Avraham, Mosenzon Ninio, Ofri, Shehadeh, Naim, Wainstein, Julio, Darawsha, Mahmud, Skripova, Dasa, Pavleova, Eva, Donicova, Viera, Kubincova, Ludmila, Sosovec, Dalibor, Merciakova, Martina, El Boreky, Fadia, St-Amour, Eric, Yared, Zeina, Blouin, Francois, Ajala, Buki, Aggarwal, Naresh K, Bajaj, Harpreet, Tailor, Chetna, Egan, Alan, O'Mahony, John, St.Onge, Natasha, Conway, James R, Akerman Augusto, Gustavo, Borges, Joao L C, Gomes Cerqueira, Maria José A, Franco, Denise R, Franco Hirakawa, Tatiana, Souza, Filipe D, Hissa, Miguel N, Pechmann, Luciana M, Calil Salim, Camila P, Russo, Luis Augusto T, Siqueira, Joselita, Sassone, Sonia A, Glenny, Jorge A, Koretzky, Martín, Aizenberg, Diego, Steinacher, Andrea, Solis, Silvana E, Nardone, Lucrecia, Perez Manghi, Federico C, Orio, Silvia I, Gelersztein, Elizabeth, Fretes, José O, Calella, Pedro R F, Zaidman, Cesar J, Chertkoff, Alejandro, Salzberg, Susana, Majul, Claudio R, Nevarez, Luis A, Violante Ortiz, Rafael M, Banda Elizondo, Ramiro G, Arjona Villicaña, Ruy D, Gonzalez Galvez, Guillermo, Calvo, Cesar G, Koscianski, Andrzej, Rudzki, Henryk, Stankiewicz, Andrzej W, Sowinski, Dariusz, Krzyzagorska, Ewa, Jozefowska, Malgorzata, Matyjaszek-Matuszek, Beata, Franek, Edward, Skokowska, Ewa, Modzelewska, Anna, Szyprowska, Ewa, Simpson, Richard W, Gilfillan, Christopher, Colquhoun, David M, Davis, Timothy M, Morbey, Claire, McCarthy, Shannon E, Kaur, Kamal, Kemp, Laurence, Shea, Antony J, Khalimov, Yuriy Sh, Miroshnichenko, Olga A, Dvoryashina, Irina V, Karpova, Irina A, Kunitsyna, Marina A, Vorokhobina, Natalia V, Galstyan, Gagik R, Bondar, Irina A., Filippov, Evgeniy V, Ershova, Olga B, Ou, Horng-Yih, Tseng, Shih-Ting, Chen, Jung-Fu, Tien, Kai-Jen, Huang, Chien-Ning, Chen, Ching-Chu, Hwu, Chii-Min, Hsia, Te-Lin, Doupis, John, Pagkalos, Emmanouil, Mouslech, Zadalla, Bargiota, Alexandra, Kotsa, Kalliopi, Del Prato, Stefano, Kahn, Steven E, Pavo, Imre, Weerakkody, Govinda J, Yang, Zhengyu, Riesmeyer, Jeffrey S, Heine, Robert J, and Wiese, Russell J

Published
2021
Full Text
View/download PDF

48. GAD65Abs Are Not Associated With Beta-Cell Dysfunction in Patients With T2D in the GRADE Study

Author

Hampe, Christiane S, primary, Shojaie, Ali, additional, Brooks-Worrell, Barbara, additional, Dibay, Sepideh, additional, Utzschneider, Kristina, additional, Kahn, Steven E, additional, Larkin, Mary E, additional, Johnson, Mary L, additional, Younes, Naji, additional, Rasouli, Neda, additional, Desouza, Cyrus, additional, Cohen, Robert M, additional, Park, Jean Y, additional, Florez, Hermes J, additional, Valencia, Willy Marcos, additional, Palmer, Jerry P, additional, and Balasubramanyam, Ashok, additional

Published
2024
Full Text
View/download PDF

49. Longitudinal effects of glucose-lowering medications on β-cell responses and insulin sensitivity in type 2 diabetes: The GRADE randomized clinical trial

Author

Rasouli, Neda, primary, Younes, Naji, primary, Ghosh, Alokananda, primary, Albu, Jeanine, primary, Cohen, Robert M., primary, DeFronzo, Ralph A., primary, Diaz, Elsa, primary, Sayyed Kassem, Laure, primary, Luchsinger, José A., primary, McGill, Janet B., primary, I. Sivitz, William, primary, Tamborlane, William V., primary, Utzschneider, Kristina M., primary, and Kahn, Steven E., primary

Published
2024
Full Text
View/download PDF

50. Impact of insulin sensitivity and β-cell function over time on glycemic outcomes in the GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness) Study: differential treatment effects of dual therapy.

Author

M Utzschneider, Kristina, primary, Younes, Naji, primary, M Butera, Nicole, primary, Balasubramanyam, Ashok, primary, M Bergenstal, Richard, primary, Barzilay, Joshua, primary, DeSouza, Cyrus, primary, DeFronzo, Ralph A., primary, Elasy, Tom, primary, Krakoff, Jonathan, primary, E Kahn, Steven, primary, Rasouli, Neda, primary, Valencia, Willy M., primary, and I Sivitz, William, primary

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results