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274 Early life antibiotic exposure and genetic risk in neurodevelopmental disorders: effects on neurogenesis, the gut microbiome, and behavior
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- Courtney R. McDermott, Anya Mirmaglesi, Zhan Gao, Katherine Kimbark, Christiana Ntim, Xuesong Zhang, Xiaofeng Zhou, James H. Millonig, Emanuel DiCicco-Bloom
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, p. 82
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OBJECTIVES/GOALS: Our long-term goal is to understand how both genetic and environmental (GxE) factors contribute to neurodevelopmental disorders (NDDs) so that we may potentially intervene in disease pathogenesis and design therapies to address functional deficiencies. METHODS/STUDY POPULATION: Our studies use a novel GxE model to determine how cephalosporin antibiotic exposure alters the gut microbiome, hippocampal neurogenesis, and behavior in the genetically vulnerable 16p11.2 microdeletion (16pDel) mouse. This mouse models one of the most frequently observed genetic risk variants implicated in NDDs, including ~1% of autism diagnoses. Wildtype and 16pDel littermates were exposed to saline or the cephalosporin, cefdinir, from postnatal days 5-9. We quantified changes in gut microbiota composition using 16S rRNA gene sequencing and utilized immunoblotting, immunohistochemistry, and bulk RNA gene sequencing to assess changes in hippocampal neurogenesis. An additional cohort of saline or cefdinir-exposed mice were subjected to a behavioral battery to assess changes in sociability and anxiety. RESULTS/ANTICIPATED RESULTS: We leveraged the next-generation microbiome bioinformatics platform, Quantitative Insights Into Microbial Ecology 2 (QIIME2) to analyze 16S rRNA gene sequencing datasets of P13 cecal samples from saline- and cefdinir-exposed mice. We found successful perturbations to the gut microbiome following early life cefdinir exposure. Further, we found a robust 50% reduction in hippocampal cyclin E protein in cefdinir-exposed 16pDel male mice, which was replicated in a second independent experiment. This reduction extended to the S-phase cell entry and general stem cell population, quantified by EdU+ and Ki67+ cell numbers, respectively. Lastly, in our first cohort of mice for behavioral studies, we found reduced sociability and increased anxiety-like behaviors in cefdinir-exposed mice. DISCUSSION/SIGNIFICANCE: The findings from this GxE model will provide mechanistic insights into the causes of NDDs; they may inform practice guidelines so as to reduce this environmental exposure; and may suggest interventions like probiotics for those at risk in order to overcome altered gut microbiome composition and restore hippocampal neurogenesis defects.
Chapter 6 - A Survey of National Trends in Psychiatric Patients Found Incompetent to Stand Trial: Reasons for the Reinstitutionalization of People with Serious Mental Illness in the United States
- from Part I - Introduction/Description of the Problem
- Edited by Katherine Warburton, University of California, Davis, Stephen M. Stahl, University of California, San Diego
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- Book:
- Decriminalizing Mental Illness
- Published online:
- 19 October 2021
- Print publication:
- 07 January 2021, pp 53-59
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Summary
Recent information indicates that the number of forensic patients in state hospitals has been increasing, largely driven by an increase in patients referred as incompetent to stand trial (IST). The surge in referrals for the evaluation and restoration of patients found IST is taxing state hospital systems, as well as the jails that must care for these patients when state hospitals are unable to accommodate the increased referrals. Many state mental health authorities are facing litigation pressure to admit IST patients more quickly, raising concerns about overcrowding and reinstitutionalization. Little is known about these national trends of increasing IST populations, and even less is known about what is driving them. This survey was intended to broaden the understanding of IST population trends on a national level.
Chapter 9 - A Longitudinal Description of Incompetent to Stand Trial Admissions to a State Hospital
- from Part I - Introduction/Description of the Problem
- Edited by Katherine Warburton, University of California, Davis, Stephen M. Stahl, University of California, San Diego
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- Book:
- Decriminalizing Mental Illness
- Published online:
- 19 October 2021
- Print publication:
- 07 January 2021, pp 79-96
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Summary
According to the US Supreme Court, all individuals charged with a crime must be competent to stand trial (CST). As defined in Dusky v. US, competency requires that defendants have the ability to consult with their attorney with a reasonable degree of rationality and possess a rational as well as factual understanding of the legal proceedings. The precise number of CST evaluations conducted each year is unknown. The oft-reported figure of 60,000 provided by Bonnie and Grisso is an estimate based on the number of felony indictments coupled with the estimated percentage of referrals for competency evaluations made by the courts in the 1990s. Later work has suggested a much higher number.
Development of the Response to Fearful Situations Scale
- Katherine A. McDermott, Kristin Fitch, Kirsten H. Dillon, Nora E. Mueller, Corinne N. Carlton, Norman B. Schmidt, Jesse R. Cougle
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- Journal:
- Behavioural and Cognitive Psychotherapy / Volume 48 / Issue 6 / November 2020
- Published online by Cambridge University Press:
- 28 July 2020, pp. 688-704
- Print publication:
- November 2020
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Background:
Most measures of anxious avoidance are limited to disorder-specific mechanisms and ignore the measurement of courage/approach responding in confronting fearful situations.
Aims:The purpose of the present study was to construct and validate a self-report assessment of the tendency towards avoidant or approach responding in fearful situations, the Response to Fearful Situations Scale (RFSS).
Method and Results:In Study 1 (n = 241), exploratory factor analysis resulted in two factors, avoidance and approach. Study 2 (n = 423) replicated the two-factor structure and established test–re-test reliability. In Study 3 (n = 44), the RFSS demonstrated predictive validity on a behavioural avoidance task. In Studies 4 (n = 253) and 5 (n = 256), the RFSS was associated with clinical symptoms above existing measures of avoidance.
Discussion:These results validate the use of the RFSS as a transdiagnostic measure of avoidance and approach.
Effects of a school readiness intervention on electrophysiological indices of external response monitoring in children in foster care
- Jacqueline Bruce, Katherine C. Pears, Jennifer Martin McDermott, Nathan A. Fox, Philip A. Fisher
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- Journal:
- Development and Psychopathology / Volume 33 / Issue 3 / August 2021
- Published online by Cambridge University Press:
- 03 June 2020, pp. 832-842
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This study examined the impact of a school readiness intervention on external response monitoring in children in foster care. Behavioral and event-related potential (ERP) data were collected during a flanker task from children who received the Kids In Transition to School (KITS) Program (n = 26) and children who received services as usual (n = 19) before and after the intervention. While there were no significant group differences on the behavioral data, the ERP data for the two groups of children significantly differed. Specifically, in contrast to the children who received services as usual, the children who received the KITS Program displayed greater amplitude differences between positive and negative performance feedback over time for the N1, which reflects early attention processes, and feedback-related negativity, which reflects evaluation processes. In addition, although the two groups did not differ on amplitude differences between positive and negative performance feedback for these ERP components before the intervention, the children who received the KITS Program displayed greater amplitude differences than the children who received services as usual after the intervention. These results suggest that the KITS Program had an effect on responsivity to external performance feedback, which may be beneficial during the transition into kindergarten.
A survey of national trends in psychiatric patients found incompetent to stand trial: reasons for the reinstitutionalization of people with serious mental illness in the United States
- Katherine Warburton, Barbara E. McDermott, Anthony Gale, Stephen M. Stahl
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 09 January 2020, pp. 245-251
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Objective.
Recent information indicates that the number of forensic patients in state hospitals has been increasing, largely driven by an increase in patients referred to state hospitals as incompetent to stand trial (IST). This survey was intended to broaden the understanding of IST population trends on a national level.
Methods.The authors developed a 30-question survey to gather specific information on IST commitments in each state and the District of Columbia. The survey was administered to all 50 states and the District of Columbia via email. Specific individuals identified as primary administrators responsible for the care and evaluation of IST admissions in each state were contacted.
Results.A total of 50 out of the 51 jurisdictions contacted completed the survey. Fully 82% of states indicated that referrals for competency evaluation were increasing. Additionally, 78% of respondents thought referrals for competency restoration were increasing. When asked to rank factors that led to an increase, the highest ranked response was inadequate general mental health services in the community. Inadequate crisis services were the second ranked reason. Inadequate number of inpatient psychiatric beds in the community was the third highest, with inadequate assertive community treatment services ranking fourth.
Conclusions.Understanding the national trend and causes behind the recent surge in referrals for IST admissions will benefit states searching for ways to remedy this crisis. Our survey indicates most states are facing this issue, and that it is largely related to insufficient services in the community.
A longitudinal description of incompetent to stand trial admissions to a state hospital
- Barbara E. McDermott, Katherine Warburton, Chloe Auletta-Young
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 02 October 2019, pp. 223-236
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Objective.
Evidence is clear that the nation is experiencing an increasing number of incompetent to stand trial (IST) admissions to state hospitals. As a result, defendants in need of treatment can wait in jail for weeks for admission for restoration. This study was conducted to better understand this growing population and to inform hospital administration about the characteristics of IST admissions.
Methods.The study was conducted at the Department of State Hospitals (DSH) facility in Napa (DSH-Napa), a 1200-bed primarily forensic inpatient psychiatric facility located in northern California. The records of patients found IST and admitted to DSH-Napa for restoration of competence between the dates of 1/1/2009 and 12/31/2016 were eligible for inclusion in the study.
Results.There were a total of 3158 unduplicated IST admissions available during the specified time period. Our data indicate that the number of admissions with more than 15 prior arrests increased significantly, from 17.7% in 2009 to 46.4% in 2016. In contrast, the percent of patients reporting prior inpatient psychiatric hospitalization evidenced a consistent decrease over time from over 76% in 2009 to less than 50% in 2016.
Conclusion.Our data add to the body of literature on the potential causes of the nationwide increase in competency referrals. The literature is clear that jails and prisons are now the primary provider of the nation’s mental health care. Our data suggest that another system has assumed this role: state hospitals and other providers charged with restoring individuals to competence.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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