63 results
Ten new insights in climate science 2022
- Maria A. Martin, Emmanuel A. Boakye, Emily Boyd, Wendy Broadgate, Mercedes Bustamante, Josep G. Canadell, Edward R. Carr, Eric K. Chu, Helen Cleugh, Szilvia Csevár, Marwa Daoudy, Ariane de Bremond, Meghnath Dhimal, Kristie L. Ebi, Clea Edwards, Sabine Fuss, Martin P. Girardin, Bruce Glavovic, Sophie Hebden, Marina Hirota, Huang-Hsiung Hsu, Saleemul Huq, Karin Ingold, Ola M. Johannessen, Yasuko Kameyama, Nilushi Kumarasinghe, Gaby S. Langendijk, Tabea Lissner, Shuaib Lwasa, Catherine Machalaba, Aaron Maltais, Manu V. Mathai, Cheikh Mbow, Karen E. McNamara, Aditi Mukherji, Virginia Murray, Jaroslav Mysiak, Chukwumerije Okereke, Daniel Ospina, Friederike Otto, Anjal Prakash, Juan M. Pulhin, Emmanuel Raju, Aaron Redman, Kanta K. Rigaud, Johan Rockström, Joyashree Roy, E. Lisa F. Schipper, Peter Schlosser, Karsten A. Schulz, Kim Schumacher, Luana Schwarz, Murray Scown, Barbora Šedová, Tasneem A. Siddiqui, Chandni Singh, Giles B. Sioen, Detlef Stammer, Norman J. Steinert, Sunhee Suk, Rowan Sutton, Lisa Thalheimer, Maarten van Aalst, Kees van der Geest, Zhirong Jerry Zhao
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- Journal:
- Global Sustainability / Volume 5 / 2022
- Published online by Cambridge University Press:
- 10 November 2022, e20
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Non-technical summary
We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C.
Technical summaryWe synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate–health horizon – some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C.
Social media summaryScience has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields.
Microscopic Identification of Micro-Organisms on Pre-Viking Swedish Hillfort Glass
- Jamie L. Weaver, Carolyn I. Pearce, Bruce Arey, Michele Conroy, Edward P. Vicenzi, Rolf Sjoblom, Robert J. Koestler, Paula T. DePriest, Thomas F. Lam, David K. Peeler, John S. McCloy, Albert A. Kruger
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- Journal:
- Microscopy and Microanalysis / Volume 24 / Issue S1 / August 2018
- Published online by Cambridge University Press:
- 01 August 2018, pp. 2136-2137
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- August 2018
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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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- Book:
- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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- By Agoston T. Agoston, Syed Z. Ali, Mahul B. Amin, Daniel A. Arber, Pedram Argani, Sylvia L. Asa, Rebecca N. Baergen, Zubair W. Baloch, Andrew M. Bellizzi, Kurt Benirschke, Allen Burke, Kenneth B. Calder, Karen L. Chang, Rebecca D. Chernock, Wang Cheung, Thomas V. Colby, Byron P. Croker, Ronald A. DeLellis, Edward F. DiCarlo, Ralph C. Eagle, Hormoz Ehya, Brett M. Elicker, Tarik M. Elsheikh, Robert E. Fechner, Linda D. Ferrell, Melina B. Flanagan, Douglas B. Flieder, Christopher S. Foster, Lillian Gaber, Karuna Garg, Kim R. Geisinger, Ryan M. Gill, Eric F. Glassy, David J. Glembocki, Zachary D. Goodman, Robert O. Greer, David J. Grignon, Gerardo E. Guiter, Kymberly A. Gyure, Ian S. Hagemann, Michael R. Henry, Jason L. Hornick, Ralph H. Hruban, Phyllis C. Huettner, Peter A. Humphrey, Olga B. Ioffe, Edward C. Klatt, Michael J. Klein, Ernest E. Lack, James N. Lampros, Lester J. Layfield, Robin D. LeGallo, Kevin O. Leslie, James S. Lewis, Virginia A. LiVolsi, Alberto M. Marchevsky, Anne Marie McNicol, Mitra Mehrad, Elizabeth Montgomery, Cesar A. Moran, Christopher A. Moskaluk, George J. Netto, G. Petur Nielsen, Robert D. Odze, Arthur S. Patchefsky, James W. Patterson, Elizabeth N. Pavlisko, John D. Pfeifer, Celeste N. Powers, Richard A. Prayson, Anja C. Roden, Victor L. Roggli, Andrew E. Rosenberg, Sherif Said, Margie A. Scott, Raja R. Seethala, Carlie S. Sigel, Jan F. Silverman, Bruce R. Smoller, Edward B. Stelow, Nora C. J. Sun, Mark W. Teague, Satish K. Tickoo, Thomas M. Ulbright, Paul E. Wakely, Jun Wang, Lawrence M. Weiss, Mark R. Wick, Howard H. Wu, Rhonda K. Yantiss, Charles Zaloudek, Yaxia Zhang, Xiaohui Sheila Zhao
- Edited by Mark R. Wick, University of Virginia, Virginia A. LiVolsi, University of Pennsylvania School of Medicine, John D. Pfeifer, Washington University School of Medicine, St Louis, Edward B. Stelow, University of Virginia, Paul E. Wakely, Jr
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- Silverberg's Principles and Practice of Surgical Pathology and Cytopathology
- Published online:
- 13 March 2015
- Print publication:
- 26 March 2015, pp vii-x
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New Developments in Electroconvulsive Therapy and Magnetic Seizure Therapy
- Sarah H. Lisanby, Oscar Morales, Nancy Payne, Edward Kwon, Linda Fitzsimons, Bruce Luber, Mitchell S. Nobler, Harold A. Sackeim
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- CNS Spectrums / Volume 8 / Issue 7 / July 2003
- Published online by Cambridge University Press:
- 07 November 2014, pp. 529-536
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New findings regarding the mechanisms of action of electroconvulsive therapy (ECT) have led to novel developments in treatment technique to further improve this highly effective treatment for major depression. These new approaches include novel electrode placements, optimization of electrical stimulus parameters, and new methods for inducing more targeted seizures (eg, magnetic seizure therapy [MST]). MST is the use of transcranial magnetic stimulation to induce a seizure. Magnetic fields pass through tissue unimpeded, providing more control over the site and extent of stimulation than can be achieved with ECT. This enhanced control represents a means of focusing the treatment on target cortical structures thought to be essential to antidepressant response and reducing spread to medial temporal regions implicated in the cognitive side effects of ECT. MST is at an early stage of development. Preliminary results suggest that MST may have some advantages over ECT in terms of subjective side effects and acute cognitive functioning. Studies designed to address the antidepressant efficacy of MST are underway. As with all attempts to improve convulsive therapy technique, the clinical value of MST will need to be established through controlled clinical trials. This article reviews the experience to date with MST, and places this work in the broader context of other means of optimizing convulsive therapy in the treatment of depression.
Contributor affiliations
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- By Frank Andrasik, Melissa R. Andrews, Ana Inés Ansaldo, Evangelos G. Antzoulatos, Lianhua Bai, Ellen Barrett, Linamara Battistella, Nicolas Bayle, Michael S. Beattie, Peter J. Beek, Serafin Beer, Heinrich Binder, Claire Bindschaedler, Sarah Blanton, Tasia Bobish, Michael L. Boninger, Joseph F. Bonner, Chadwick B. Boulay, Vanessa S. Boyce, Anna-Katharine Brem, Jacqueline C. Bresnahan, Floor E. Buma, Mary Bartlett Bunge, John H. Byrne, Jeffrey R. Capadona, Stefano F. Cappa, Diana D. Cardenas, Leeanne M. Carey, S. Thomas Carmichael, Glauco A. P. Caurin, Pablo Celnik, Kimberly M. Christian, Stephanie Clarke, Leonardo G. Cohen, Adriana B. Conforto, Rory A. Cooper, Rosemarie Cooper, Steven C. Cramer, Armin Curt, Mark D’Esposito, Matthew B. Dalva, Gavriel David, Brandon Delia, Wenbin Deng, Volker Dietz, Bruce H. Dobkin, Marco Domeniconi, Edith Durand, Tracey Vause Earland, Georg Ebersbach, Jonathan J. Evans, James W. Fawcett, Uri Feintuch, Toby A. Ferguson, Marie T. Filbin, Diasinou Fioravante, Itzhak Fischer, Agnes Floel, Herta Flor, Karim Fouad, Richard S. J. Frackowiak, Peter H. Gorman, Thomas W. Gould, Jean-Michel Gracies, Amparo Gutierrez, Kurt Haas, C.D. Hall, Hans-Peter Hartung, Zhigang He, Jordan Hecker, Susan J. Herdman, Seth Herman, Leigh R. Hochberg, Ahmet Höke, Fay B. Horak, Jared C. Horvath, Richard L. Huganir, Friedhelm C. Hummel, Beata Jarosiewicz, Frances E. Jensen, Michael Jöbges, Larry M. Jordan, Jon H. Kaas, Andres M. Kanner, Noomi Katz, Matthew S. Kayser, Annmarie Kelleher, Gerd Kempermann, Timothy E. Kennedy, Jürg Kesselring, Fary Khan, Rachel Kizony, Jeffery D. Kocsis, Boudewijn J. Kollen, Hubertus Köller, John W. Krakauer, Hermano I. Krebs, Gert Kwakkel, Bradley Lang, Catherine E. Lang, Helmar C. Lehmann, Angelo C. Lepore, Glenn S. Le Prell, Mindy F. Levin, Joel M. Levine, David A. Low, Marilyn MacKay-Lyons, Jeffrey D. Macklis, Margaret Mak, Francine Malouin, William C. Mann, Paul D. Marasco, Christopher J. Mathias, Laura McClure, Jan Mehrholz, Lorne M. Mendell, Robert H. Miller, Carol Milligan, Beth Mineo, Simon W. Moore, Jennifer Morgan, Charbel E-H. Moussa, Martin Munz, Randolph J. Nudo, Joseph J. Pancrazio, Theresa Pape, Alvaro Pascual-Leone, Kristin M. Pearson-Fuhrhop, P. Hunter Peckham, Tamara L. Pelleshi, Catherine Verrier Piersol, Thomas Platz, Marcus Pohl, Dejan B. Popović, Andrew M. Poulos, Maulik Purohit, Hui-Xin Qi, Debbie Rand, Mahendra S. Rao, Josef P. Rauschecker, Aimee Reiss, Carol L. Richards, Keith M. Robinson, Melvyn Roerdink, John C. Rosenbek, Serge Rossignol, Edward S. Ruthazer, Arash Sahraie, Krishnankutty Sathian, Marc H. Schieber, Brian J. Schmidt, Michael E. Selzer, Mijail D. Serruya, Himanshu Sharma, Michael Shifman, Jerry Silver, Thomas Sinkjær, George M. Smith, Young-Jin Son, Tim Spencer, John D. Steeves, Oswald Steward, Sheela Stuart, Austin J. Sumner, Chin Lik Tan, Robert W. Teasell, Gareth Thomas, Aiko K. Thompson, Richard F. Thompson, Wesley J. Thompson, Erika Timar, Ceri T. Trevethan, Christopher Trimby, Gary R. Turner, Mark H. Tuszynski, Erna A. van Niekerk, Ricardo Viana, Difei Wang, Anthony B. Ward, Nick S. Ward, Stephen G. Waxman, Patrice L. Weiss, Jörg Wissel, Steven L. Wolf, Jonathan R. Wolpaw, Sharon Wood-Dauphinee, Ross D. Zafonte, Binhai Zheng, Richard D. Zorowitz
- Edited by Michael Selzer, Stephanie Clarke, Leonardo Cohen, Gert Kwakkel, Robert Miller, Case Western Reserve University, Ohio
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- Book:
- Textbook of Neural Repair and Rehabilitation
- Published online:
- 05 May 2014
- Print publication:
- 24 April 2014, pp ix-xvi
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Contributor affiliations
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- By Frank Andrasik, Melissa R. Andrews, Ana Inés Ansaldo, Evangelos G. Antzoulatos, Lianhua Bai, Ellen Barrett, Linamara Battistella, Nicolas Bayle, Michael S. Beattie, Peter J. Beek, Serafin Beer, Heinrich Binder, Claire Bindschaedler, Sarah Blanton, Tasia Bobish, Michael L. Boninger, Joseph F. Bonner, Chadwick B. Boulay, Vanessa S. Boyce, Anna-Katharine Brem, Jacqueline C. Bresnahan, Floor E. Buma, Mary Bartlett Bunge, John H. Byrne, Jeffrey R. Capadona, Stefano F. Cappa, Diana D. Cardenas, Leeanne M. Carey, S. Thomas Carmichael, Glauco A. P. Caurin, Pablo Celnik, Kimberly M. Christian, Stephanie Clarke, Leonardo G. Cohen, Adriana B. Conforto, Rory A. Cooper, Rosemarie Cooper, Steven C. Cramer, Armin Curt, Mark D’Esposito, Matthew B. Dalva, Gavriel David, Brandon Delia, Wenbin Deng, Volker Dietz, Bruce H. Dobkin, Marco Domeniconi, Edith Durand, Tracey Vause Earland, Georg Ebersbach, Jonathan J. Evans, James W. Fawcett, Uri Feintuch, Toby A. Ferguson, Marie T. Filbin, Diasinou Fioravante, Itzhak Fischer, Agnes Floel, Herta Flor, Karim Fouad, Richard S. J. Frackowiak, Peter H. Gorman, Thomas W. Gould, Jean-Michel Gracies, Amparo Gutierrez, Kurt Haas, C.D. Hall, Hans-Peter Hartung, Zhigang He, Jordan Hecker, Susan J. Herdman, Seth Herman, Leigh R. Hochberg, Ahmet Höke, Fay B. Horak, Jared C. Horvath, Richard L. Huganir, Friedhelm C. Hummel, Beata Jarosiewicz, Frances E. Jensen, Michael Jöbges, Larry M. Jordan, Jon H. Kaas, Andres M. Kanner, Noomi Katz, Matthew S. Kayser, Annmarie Kelleher, Gerd Kempermann, Timothy E. Kennedy, Jürg Kesselring, Fary Khan, Rachel Kizony, Jeffery D. Kocsis, Boudewijn J. Kollen, Hubertus Köller, John W. Krakauer, Hermano I. Krebs, Gert Kwakkel, Bradley Lang, Catherine E. Lang, Helmar C. Lehmann, Angelo C. Lepore, Glenn S. Le Prell, Mindy F. Levin, Joel M. Levine, David A. Low, Marilyn MacKay-Lyons, Jeffrey D. Macklis, Margaret Mak, Francine Malouin, William C. Mann, Paul D. Marasco, Christopher J. Mathias, Laura McClure, Jan Mehrholz, Lorne M. Mendell, Robert H. Miller, Carol Milligan, Beth Mineo, Simon W. Moore, Jennifer Morgan, Charbel E-H. Moussa, Martin Munz, Randolph J. Nudo, Joseph J. Pancrazio, Theresa Pape, Alvaro Pascual-Leone, Kristin M. Pearson-Fuhrhop, P. Hunter Peckham, Tamara L. Pelleshi, Catherine Verrier Piersol, Thomas Platz, Marcus Pohl, Dejan B. Popović, Andrew M. Poulos, Maulik Purohit, Hui-Xin Qi, Debbie Rand, Mahendra S. Rao, Josef P. Rauschecker, Aimee Reiss, Carol L. Richards, Keith M. Robinson, Melvyn Roerdink, John C. Rosenbek, Serge Rossignol, Edward S. Ruthazer, Arash Sahraie, Krishnankutty Sathian, Marc H. Schieber, Brian J. Schmidt, Michael E. Selzer, Mijail D. Serruya, Himanshu Sharma, Michael Shifman, Jerry Silver, Thomas Sinkjær, George M. Smith, Young-Jin Son, Tim Spencer, John D. Steeves, Oswald Steward, Sheela Stuart, Austin J. Sumner, Chin Lik Tan, Robert W. Teasell, Gareth Thomas, Aiko K. Thompson, Richard F. Thompson, Wesley J. Thompson, Erika Timar, Ceri T. Trevethan, Christopher Trimby, Gary R. Turner, Mark H. Tuszynski, Erna A. van Niekerk, Ricardo Viana, Difei Wang, Anthony B. Ward, Nick S. Ward, Stephen G. Waxman, Patrice L. Weiss, Jörg Wissel, Steven L. Wolf, Jonathan R. Wolpaw, Sharon Wood-Dauphinee, Ross D. Zafonte, Binhai Zheng, Richard D. Zorowitz
- Edited by Michael E. Selzer, Stephanie Clarke, Leonardo G. Cohen, Gert Kwakkel, Robert H. Miller, Case Western Reserve University, Ohio
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- Book:
- Textbook of Neural Repair and Rehabilitation
- Published online:
- 05 June 2014
- Print publication:
- 24 April 2014, pp ix-xvi
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Notes on Contributors
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- By E. Jennifer Ashworth, J. L. Berggren, Charles Burnett, Joan Cadden, Bruce S. Eastwood, Edward Grant, Danielle Jacquart, Elaheh Kheirandish, Tomomi Kinukawa, Walter Roy Laird, Y. Tzvi Langermann, David C. Lindberg, Stephen C. McCcluskey, A. George Molland, Robert G. Morrison, William R. Newman, John North, Vivian Nutton, George Ovitt, Katharine Park, F. Jamil Ragep, Karen Meier Reeds, Emilie Savage-Smith, Michael H. Shank, Katherine H. Tachau, Anne Tihon, David Woodward
- David C. Lindberg, Michael H. Shank
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- Book:
- The Cambridge History of Science
- Published online:
- 05 September 2013
- Print publication:
- 07 October 2013, pp xvii-xxii
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Chapter 17 - Flow Cytometry Multiplexed Screening Methodologies
- from Section Four - Chemical Genomics Assays and Screens
- Edited by Haian Fu, Emory University, Atlanta
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- Book:
- Chemical Genomics
- Published online:
- 05 June 2012
- Print publication:
- 13 February 2012, pp 232-244
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Summary
High-content analytical methodologies are increasingly becoming integrated into the screening phase of the discovery pipeline for small molecule modulators of biological targets. The iterative analysis among targets with related functions or among a series of interacting targets can be replaced with multiplexing approaches whereby multiple targets are analyzed simultaneously in the same well against the same compound or even against a mixture of compounds in the same well. It has become practical to use the multiparameter optical capabilities of the flow cytometer for the discovery of active small molecules from compound libraries by high-throughput screening (HTS). In this chapter, we present the fundamental principles of flow cytometry–based multiplex methods, including assay design and data analysis, with specific examples of cell-based and bead-based assays and a discussion of the added value of multiplex data sets.
Overview
Over the past two decades, HTS methodologies (generally defined as testing ten thousand to one hundred thousand compounds per day, depending on the technology) have become an essential part of discovery science for novel drugs and biological probes within the pharmaceutical, biotech, and academic research communities [1–3]. Technologies that are inherently capable of multiparametric measurements, including microscopy and flow cytometry, are well suited to produce high-content, high-complexity data by obtaining multiple data points from each well in a microtiter plate or other high-density format. In multiplex applications, information content is further enriched by obtaining data for each parameter on multiple targets. The advantages, compared with single-point iterative assays, include a substantial savings in time and reagents and the ability to produce rich data sets under conditions that can be optimized for statistical rigor and data quality for multiple targets simultaneously. For example, multiplex analysis among a family of related targets, which often exhibit similar biochemical and pharmacologic properties, produces selectivity screens in a single well with inherent consistency. Furthermore, the conditions in each well are normalized across targets for any number of parameters, and counterscreens for artifacts can be rigorously examined. Table 17.1 is a comparison of characteristics between single-target and multiplexed assays that summarizes the advantages for each approach.
Contributors
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- By Dag Aarsland, Adrià Arboix, Carlos Bazán, James T. Becker, Sylvie Belleville, Kevin M. Biglan, Sandra E. Black, Mariana Blanco, Rémi W. Bouchard, Bruce J. Brew, David J. Burn, Leonardo Caixeta, Richard Camicioli, Paulo Caramelli, Neil Cashman, Nicholas W. S. Davies, Yan Deschaintre, Rachel S. Doody, Bruno Dubois, Uwe Ehrt, Stephane Epelbaum, Ryan V. V. Evans, Joseph M. Ferrara, Bruno Franchi, Morris Freedman, Anders Gade, Serge Gauthier, Marta Grau-Olivares, Matthew E. Growdon, Will Guest, Marie Christie Guiot, Shahul Hameed, Mirna Lie Hosogi-Senaha, Ging-Yuek Robin Hsiung, Masamichi Ikawa, Rajive Jassal, Vesna Jelic, Peter Johannsen, Edward S. Johnson, Mary M. Kenan, Bert-Jan Kerklaan, Benjamin Lam, Gabriel C. Léger, Gabriel Leonard, Emilie Lepage, Irene Litvan, Oscar L. Lopez, Ian R. A. Mackenzie, Mario Masellis, Fodi Massoud, Paige Moorhouse, John C. Morris, Taim Muayqil, Yannick Nadeau, Inger Nennesmo, Jørgen E. Nielsen, Ricardo Nitrini, Sven-Eric Pålhagen, Robert Perry, Gerald Pfeffer, Machiel Pleizier, Steffen Plickert, Gil D. Rabinovici, Philippe H. Robert, Lothar Resch, Gustavo C. Román, Maxime Ros, Pedro Rosa-Neto, Aiman Sanosi, Philip Scheltens, Christian Schmidt, Eric Schmidt, Jean-Paul Soucy, Jette Stokholm, David Summers, Rawan Tarawneh, Louis Verret, Huali Wang, Bengt Winblad, Makoto Yoneda, Xin Yu, Inga Zerr
- Edited by Serge Gauthier, McGill University, Montréal, Pedro Rosa-Neto, McGill University, Montréal
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- Book:
- Case Studies in Dementia
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- 16 May 2011
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- 21 April 2011, pp viii-xiv
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. 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Nicholson, George W. E. Nickelsburg, Tatyana Nikolskaya, Damayanthi M. A. Niles, Bertil Nilsson, Nyambura Njoroge, Fidelis Nkomazana, Mary Beth Norton, Christian Nottmeier, Sonene Nyawo, Anthère Nzabatsinda, Edward T. Oakes, Gerald O'Collins, Daniel O'Connell, David W. Odell-Scott, Mercy Amba Oduyoye, Kathleen O'Grady, Oyeronke Olajubu, Thomas O'Loughlin, Dennis T. Olson, J. Steven O'Malley, Cephas N. Omenyo, Muriel Orevillo-Montenegro, César Augusto Ornellas Ramos, Agbonkhianmeghe E. Orobator, Kenan B. Osborne, Carolyn Osiek, Javier Otaola Montagne, Douglas F. Ottati, Anna May Say Pa, Irina Paert, Jerry G. Pankhurst, Aristotle Papanikolaou, Samuele F. Pardini, Stefano Parenti, Peter Paris, Sung Bae Park, Cristián G. Parker, Raquel Pastor, Joseph Pathrapankal, Daniel Patte, W. Brown Patterson, Clive Pearson, Keith F. Pecklers, Nancy Cardoso Pereira, David Horace Perkins, Pheme Perkins, Edward N. Peters, Rebecca Todd Peters, Bishop Yeznik Petrossian, Raymond Pfister, Peter C. 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Rubenstein, Rosemary Radford Ruether, Markku Ruotsila, John E. Rybolt, Risto Saarinen, John Saillant, Juan Sanchez, Wagner Lopes Sanchez, Hugo N. Santos, Gerhard Sauter, Gloria L. Schaab, Sandra M. Schneiders, Quentin J. Schultze, Fernando F. Segovia, Turid Karlsen Seim, Carsten Selch Jensen, Alan P. F. Sell, Frank C. Senn, Kent Davis Sensenig, Damían Setton, Bal Krishna Sharma, Carolyn J. Sharp, Thomas Sheehan, N. Gerald Shenk, Christian Sheppard, Charles Sherlock, Tabona Shoko, Walter B. Shurden, Marguerite Shuster, B. Mark Sietsema, Batara Sihombing, Neil Silberman, Clodomiro Siller, Samuel Silva-Gotay, Heikki Silvet, John K. Simmons, Hagith Sivan, James C. Skedros, Abraham Smith, Ashley A. Smith, Ted A. Smith, Daud Soesilo, Pia Søltoft, Choan-Seng (C. S.) Song, Kathryn Spink, Bryan Spinks, Eric O. Springsted, Nicolas Standaert, Brian Stanley, Glen H. Stassen, Karel Steenbrink, Stephen J. Stein, Andrea Sterk, Gregory E. Sterling, Columba Stewart, Jacques Stewart, Robert B. Stewart, Cynthia Stokes Brown, Ken Stone, Anne Stott, Elizabeth Stuart, Monya Stubbs, Marjorie Hewitt Suchocki, David Kwang-sun Suh, Scott W. Sunquist, Keith Suter, Douglas Sweeney, Charles H. Talbert, Shawqi N. Talia, Elsa Tamez, Joseph B. Tamney, Jonathan Y. Tan, Yak-Hwee Tan, Kathryn Tanner, Feiya Tao, Elizabeth S. Tapia, Aquiline Tarimo, Claire Taylor, Mark Lewis Taylor, Bishop Abba Samuel Wolde Tekestebirhan, Eugene TeSelle, M. Thomas Thangaraj, David R. Thomas, Andrew Thornley, Scott Thumma, Marcelo Timotheo da Costa, George E. “Tink” Tinker, Ola Tjørhom, Karen Jo Torjesen, Iain R. Torrance, Fernando Torres-Londoño, Archbishop Demetrios [Trakatellis], Marit Trelstad, Christine Trevett, Phyllis Trible, Johannes Tromp, Paul Turner, Robert G. Tuttle, Archbishop Desmond Tutu, Peter Tyler, Anders Tyrberg, Justin Ukpong, Javier Ulloa, Camillus Umoh, Kristi Upson-Saia, Martina Urban, Monica Uribe, Elochukwu Eugene Uzukwu, Richard Vaggione, Gabriel Vahanian, Paul Valliere, T. J. Van Bavel, Steven Vanderputten, Peter Van der Veer, Huub Van de Sandt, Louis Van Tongeren, Luke A. Veronis, Noel Villalba, Ramón Vinke, Tim Vivian, David Voas, Elena Volkova, Katharina von Kellenbach, Elina Vuola, Timothy Wadkins, Elaine M. Wainwright, Randi Jones Walker, Dewey D. Wallace, Jerry Walls, Michael J. Walsh, Philip Walters, Janet Walton, Jonathan L. Walton, Wang Xiaochao, Patricia A. Ward, David Harrington Watt, Herold D. Weiss, Laurence L. Welborn, Sharon D. Welch, Timothy Wengert, Traci C. West, Merold Westphal, David Wetherell, Barbara Wheeler, Carolinne White, Jean-Paul Wiest, Frans Wijsen, Terry L. Wilder, Felix Wilfred, Rebecca Wilkin, Daniel H. Williams, D. Newell Williams, Michael A. Williams, Vincent L. Wimbush, Gabriele Winkler, Anders Winroth, Lauri Emílio Wirth, James A. Wiseman, Ebba Witt-Brattström, Teofil Wojciechowski, John Wolffe, Kenman L. Wong, Wong Wai Ching, Linda Woodhead, Wendy M. Wright, Rose Wu, Keith E. Yandell, Gale A. Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- The Cambridge Dictionary of Christianity
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- 05 August 2012
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- 20 September 2010, pp xi-xliv
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28 - Hereditary aceruloplasminemia
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- By James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, University of Utah School of Medicine, Salt Lake City, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
- James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
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- Handbook of Iron Overload Disorders
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- 01 June 2011
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- 22 July 2010, pp 284-289
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Summary
Hereditary aceruloplasminemia (OMIM #604290) is a rare autosomal recessive disorder due to mutations of Cp, the gene that encodes the copper-binding protein ceruloplasmin (Cp). The first report of hereditary aceruloplasminemia was published in 1987 in Japan. The patient was a 52-year-old woman who had a movement disorder that resembled Parkinson's disease, blepharospasm, retinal degeneration, and diabetes mellitus. Her serum immunofixation test revealed that her serum Cp concentration was very low. Computed tomography scanning revealed increased amounts of iron in her basal ganglia and liver. Subsequent histologic evaluation confirmed that there was increased iron in her basal ganglia and substantia nigra and in her liver, without increased copper.
The frequency of homozygosity for deleterious Cp mutations in non-consanguineous marriages in Japan was estimated to be 1 per 2,000,000 population. Aceruloplasminemia has been reported in several countries including Japan, China, Ireland, Belgium, France, Italy, and the US. More Japanese patients have been reported than any other nationality. Altogether, about 60 patients with hereditary aceruloplasminemia have been described.
Ceruloplasmin (Cp) biochemistry
Cp is a plasma metalloprotein, an alpha-2 glycoprotein polypeptide of 1046 amino acids. A member of the multi-copper oxidase enzyme family, Cp is the principal copper transport protein in plasma. Cp is synthesized in hepatocytes where it binds copper, and is thereafter secreted into plasma. About 95% of circulating plasma copper is bound to Cp; the remainder is bound to albumin, precuprein, and complexes of copper and amino acids. Each Cp molecule can bind and transport six atoms of copper.
Plate section
- James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
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- Handbook of Iron Overload Disorders
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- 01 June 2011
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- 22 July 2010, pp -
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31 - Neuroferritinopathies
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- By James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, University of Utah School of Medicine, Salt Lake City, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
- James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
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- Handbook of Iron Overload Disorders
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- 01 June 2011
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- 22 July 2010, pp 299-303
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Summary
Neuroferritinopathy (OMIM #606159), also known as adult-onset basal ganglia disease, is a progressive movement disorder caused by mutations in the coding region of the ferritin light chain gene (FTL, chromosome 19q13.3–q13.4). Persons with neuroferritinopathy have abnormal ferritin light chain polypeptide, decreased serum ferritin concentrations, and accumulation of iron in the basal ganglia. Curtis and colleagues first described this syndrome in an English kinship in 2001. They also coined the commonly used term “neuroferritinopathy.” Subsequent identification and study of other subjects have revealed additional observations on the genotypes, phenotypes, and epidemiology associated with neuroferritinopathy.
Other mutations of the FTL coding region segregate with a syndrome that comprises hyperferritinemia, absence of iron overload, and absence of ocular cataracts. Mutations of the iron-responsive element of FTL cause a different clinical syndrome characterized by elevated levels of otherwise normal ferritin, cataracts due to ferritin light-chain deposition in the ocular lens, and absence of neurological abnormalities (Chapter 17).
History
In 2001, Curtis and colleagues described late-onset autosomal dominant dystonia that segregated with FTL 460insA in an English kinship. In 2003, Chinnery, Curtis, and colleagues reported a French family in which some members had a similar clinical disorder and the same FTL mutation. In 2007, Chinnery and colleagues compiled observations in 41 patients with neuroferritinopathy and FTL 460insA. They presented between the ages of 38 and 58 years; some had chorea, others had focal dystonia, and others had an akinetic rigid Parkinsonian syndrome. Brain imaging showed basal ganglia cavitation that was confirmed at necropsy.
Contents
- James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
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- Handbook of Iron Overload Disorders
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- 01 June 2011
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- 22 July 2010, pp v-vi
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12 - Hemochromatosis associated with ferroportin gene (SLC40A1) mutations
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- By James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, University of Utah School of Medicine, Salt Lake City, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
- James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
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- Handbook of Iron Overload Disorders
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- 01 June 2011
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- 22 July 2010, pp 171-180
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Summary
Mutations in the SLC40A1 (FPN1) gene that encodes ferroportin (OMIM *604653) cause an uncommon, heterogeneous group of iron overload disorders characterized by an autosomal dominant pattern of inheritance (OMIM #606069). Ferroportin hemochromatosis has been described worldwide in a variety of race/ethnicity groups. SLC40A1 mutations cause two major iron overload phenotype patterns, each depending on the particular mutation and its effect on the function of the transcribed ferroportin protein. In many ferroportin hemochromatosis kinships, serum iron measures and complications of iron overload typical of other types of hemochromatosis are relatively uncommon. The collective term “ferroportin disease” or “hemochromatosis type 4” is sometimes used to describe the clinical manifestations of ferroportin mutations.
History
In 1990, an autosomal dominant form of hemochromatosis was reported in a Melanesian pedigree from the Solomon Islands. All affected individuals had serum iron measures and a pattern of liver iron staining similar to those of HFE hemochromatosis, although linkage of this disorder to chromosome 6p was excluded. In 1999, Pietrangelo and colleagues reported a large Italian family that included persons with an iron overload condition that occurred in pattern consistent with autosomal dominant inheritance. Based on microsatellite marker analyses, this disorder was also not linked to chromosome 6p. In 2001, Njajou and colleagues identified the SLC40A1 mutation N144H associated with autosomal dominant hemochromatosis in a large multi-generation family from the Netherlands.
23 - Iron overload associated with pyruvate kinase deficiency
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- By James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, University of Utah School of Medicine, Salt Lake City, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
- James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
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- Book:
- Handbook of Iron Overload Disorders
- Published online:
- 01 June 2011
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- 22 July 2010, pp 251-253
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Summary
Pyruvate kinase (PK) deficiency (OMIM #266200) is caused by mutations in the PKLR gene that encodes PK (chromosome 1q21). This disorder is the most common erythrocyte enzyme defect that causes hereditary non-spherocytic hemolytic anemia. It is transmitted as an autosomal recessive trait. On the basis of gene frequency, it was estimated that the prevalence of homozygous PK deficiency is 51 cases per million in the US white population. Based on data in a health registry, it was estimated that the prevalence of PK deficiency in northern England is 3.3 per million. PK deficiency has a worldwide distribution, but may be more common among individuals of northern European descent. Herein, the pathophysiology of PK deficiency is discussed. The clinical manifestations of this disorder are reviewed with emphasis on the complication of iron overload.
Etiology and pathogenesis
Mature erythrocytes depend on the glycolytic production of adenosine triphosphate (ATP) to meet metabolic requirements. Deficiencies in several glycolytic enzymes can result in hemolytic anemia. These types of hemolytic anemia are not associated with a distinctive morphologic abnormality of erythrocytes, and thus are known collectively as congenital non-spherocytic hemolytic anemias. Most of these disorders are rare and are transmitted as autosomal recessive disorders.
PK deficiency is the most common erythrocyte glycolytic enzymopathy. The predominant PK isoenzyme present in erythrocytes is the R form, encoded by PKLR. Multiple mutations can lead to PK deficiency, and the type of mutation may determine in part the severity of the clinical phenotype.
2 - Normal iron absorption and metabolism
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- By James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, University of Utah School of Medicine, Salt Lake City, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
- James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
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- Handbook of Iron Overload Disorders
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- 01 June 2011
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- 22 July 2010, pp 10-27
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Summary
Iron is essential to life because it is the central oxygen ligand in the heme proteins hemoglobin and myoglobin. Accordingly, there are many interactions between iron homeostasis and oxygen regulation and delivery. Iron is also required for cytochrome P-450 enzyme oxidative metabolism and DNA synthesis. In health, body iron content is controlled by absorption that responds to iron losses and the rate of erythropoiesis. Multiple mechanisms provide functional feedback control of iron homeostasis, tissue oxygen sensing and delivery, and the tempo of red blood cell production. The physiologic capacity to excrete iron is very limited. Thus, body iron content is regulated almost entirely by controlled absorption. This chapter reviews the basic physiologic and molecular characteristics of iron metabolism and homeostasis, and their pertinence to iron overload disorders.
Iron physiology
Normal iron homeostasis is maintained by absorption of iron from the diet that precisely balances iron loss, and by controlled iron distribution in the body. Normal healthy adults have 4000–5000 mg of iron (Table 2.1). Daily iron loss occurs due to perspiration, desquamation from skin, and minor injuries, and from the gastrointestinal tract. The rate of this unavoidable iron loss is proportional to body iron stores. Women lose additional iron due to menstruation, pregnancy and childbirth, and lactation. Overall, daily iron losses in adult men and post-menopausal women are approximately 1.0 mg and in menstruating women approximately 1.5 mg. The median iron loss ascribable to pregnancy is 500 mg.
20 - Divalent metal transporter-1 (SLC11A2) iron overload
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- By James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, University of Utah School of Medicine, Salt Lake City, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
- James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
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- Book:
- Handbook of Iron Overload Disorders
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- 01 June 2011
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- 22 July 2010, pp 228-232
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Summary
Divalent metal transporter-1 (DMT1) is a member of the “natural-resistance-associated macrophage protein” (Nramp) family. DMT1 is upregulated by dietary iron deficiency, is expressed strongly on the microvillus membranes of duodenal enterocytes at the villus tips, and is a key mediator of iron absorption. DMT1 also mediates iron transfer from endosomes into the cytosol of developing erythroid cells. The SLC11A2 gene that encodes DMT1 is located on chromosome 12q13 (OMIM *604653).
In 1964, Shahidi and colleagues described a brother and sister of French-Canadian descent who had hypochromic, microcytic anemia. These siblings also had elevated serum iron concentrations, massive deposition of iron in hepatocytes, and absence of stainable iron in the bone marrow. These children apparently had no defect in transferrin or heme synthesis. Two of their siblings appeared to have normal iron phenotypes. In 2004 and 2005, Priwitzerova and colleagues described a Czech female in a consanguineous kinship who came to medical attention at age 3 months because she had a syndrome of abnormal iron metabolism characterized by severe hypochromic, microcytic anemia, erythroid hyperplasia, abnormal erythroid maturation, elevated serum iron concentration, normal to slightly increased serum ferritin level, and markedly increased serum transferrin receptor levels. In 2005, Mims and colleagues reported that this woman was homozygous for a mutation in SLC11A2.
Clinical description
Clinical observations in patients with two SLC11A2 mutations are limited. In one case, left ventricular hypertrophy was detected before birth, and birth weight was low. Pallor is presumed to have been present in all reported cases.
10 - Porphyria cutanea tarda
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- By James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, University of Utah School of Medicine, Salt Lake City, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
- James C. Barton, University of Alabama, Birmingham, Corwin Q. Edwards, Pradyumna D. Phatak, University of Rochester Medical Center, New York, Robert S. Britton, St Louis University, Missouri, Bruce R. Bacon, St Louis University, Missouri
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- Book:
- Handbook of Iron Overload Disorders
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- 01 June 2011
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- 22 July 2010, pp 160-168
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Summary
Porphyrias are disorders caused by heritable or acquired deficiency of an enzyme that is required for the normal synthesis of heme. A ring structure, heme is formed by the insertion of an iron atom into protoporphyrin in the final step of the porphyrin synthesis pathway. The usual presenting symptoms and signs of porphyrias are either skin photosensitivity or neurovisceral symptoms and signs. Three types of porphyria are characterized by a predominance of photosensitivity (porphyria cutanea tarda (PCT), congenital erythropoietic porphyria, and erythropoietic protoporphyria). Two types of porphyria are characterized mainly by neurovisceral symptoms and signs (acute intermittent porphyria and aminolevulinate dehydratase deficiency). The two remaining types of porphyria are characterized by both photosensitivity and neurovisceral symptoms and signs (hereditary coproporphyria and variegate porphyria). The seven main types of porphyria, the associated enzyme deficiency, the mode of inheritance, and the major presenting symptoms and signs are displayed in Table 10.1. The only type of porphyria discussed here is PCT, the most common of all porphyrias.
Porphyria cutanea tarda (PCT)
PCT is estimated to occur in about 1 per 5000 to 25,000 individuals in the general population. PCT is caused by decreased specific activity of the uroporphyrinogen decarboxylase enzyme, the fifth enzyme in the heme synthesis pathway. Three types of PCT can be identified on the basis of decreased activity of the uroporphyrinogen decarboxylase enzyme (URO-D) in liver cells or in erythrocytes.