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4329 Investigating the role of Klotho in neurocognitive outcomes, brain volumes, and white matter changes in pediatric brain tumor survivors
- Caleb Simpeh Edwards, Schuyler Stoller, Sol Savchuk, Christian Rodrigo Ugaz Valencia, Liz Tong, Andreas Rauschecker, Dena Dubal, Cassie Kline, Sabine Mueller
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, p. 98
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OBJECTIVES/GOALS: Klotho is a protein linked to improved cognition in aging adults. A specific KLOTHO gene variant, KL-VS, increases circulating levels of Klotho. The current study aims to identify if the KL-VS haplotype and Klotho levels are associated with improved neurocognition in pediatric brain tumor survivors. METHODS/STUDY POPULATION: We are actively accruing pediatric brain tumor patients at UCSF alongside an existing multi-institutional cohort study investigating radiation-induced vasculopathies and cognitive outcomes in this population. Normal controls are being enrolled in parallel. Each patient undergoes: 1) single nucleotide polymorphism genotyping to identify KL-VS haplotype status, 2) enzyme-linked immunosorbent assays to measure circulating Klotho, 3) neurocognitive assessments with a computer-based, validated Cogstate battery, and 4) brain volume and white matter lesion segmentation analyses using MRI sequences obtained as part of routine care. RESULTS/ANTICIPATED RESULTS: Genotyping has been performed on 99 enrolled patients. KL-VS heterozygosity was seen in 22.7% of patients. To date, KL-VS status is not associated with neurocognitive outcomes at baseline or Year 1 testing. Association between KL-VS status, circulating Klotho levels, neurocognitive outcomes, brain volume and white matter lesion segmentation analyses is ongoing. We hypothesize that elevated Klotho levels will be associated with improved neurocognition, increased brain volumes in regions of interest and decreased white matter lesion volumes. DISCUSSION/SIGNIFICANCE OF IMPACT: If circulating Klotho leads to improved neurocognition in pediatric brain tumor survivors, Klotho levels might serve as a prognostic biomarker. Furthermore, as Klotho is being investigated for therapeutic indications, it may represent an intervention to prevent cognitive deficits in these patients.
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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- By Osvaldo P. Almeida, Rebecca Anglin, Vivek Benegal, Margaret N. Berry, Nash N. Boutros, Henry Brodaty, Alan S. Brown, Monte S. Buchsbaum, William Burke, Kim Burns, Stanley V. Catts, Vibeke S. Catts, Jennifer M. Connolly, David L. Copolov, Louisa Degenhardt, Stewart L. Einfeld, Anthony Feinstein, Matt P. Galloway, Bangalore N. Gangadhar, Wayne Hall, Malcolm Hopwood, Michael D. Jibson, Ripu D. Jindal, David J. Kavanagh, Sophie Kavanagh, Matcheri S. Keshavan, Ennapadam S. Krishnamoorthy, Rajeev Kumar, Alexander F. Kurz, Nicola T. Lautenschlager, Edward C. Lauterbach, Leslie Lester-Burns, Lyn-May Lim, Jeffrey C. L. Looi, Michael Mazurek, Serge A. Mitelman, Ramon Mocellin, Bryan Mowry, Kim T. Mueser, Anand K. Pandurangi, Eric M. Pihlgren, Seethalakshmi Ramanathan, Patricia I. Rosebush, Perminder S. Sachdev, Richard D. Sanders, Vandana Shashi, Arabella Smith, Sergio E. Starkstein, Ezra S. Susser, Rajiv Tandon, Jagadisha Thirthalli, Bruce J. Tonge, Julian Trollor, Dennis Velakoulis, Mark Walterfang, Jane Zhang
- Edited by Perminder S. Sachdev, University of New South Wales, Sydney, Matcheri S. Keshavan
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- Secondary Schizophrenia
- Published online:
- 05 August 2011
- Print publication:
- 04 February 2010, pp vii-xii
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Effect of Healthcare-Acquired Infection on Length of Hospital Stay and Cost
- Nicholas Graves, Diana Weinhold, Edward Tong, Frances Birrell, Shane Doidge, Prabha Ramritu, Kate Halton, David Lairson, Michael Whitby
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 28 / Issue 3 / March 2007
- Published online by Cambridge University Press:
- 02 January 2015, pp. 280-292
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- March 2007
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Objective.
To estimate the independent effect of a single lower respiratory tract infection, urinary tract infection, or other healthcare-acquired infection on length-of-stay and variable costs and to demonstrate the bias from omitted variables that is present in previous estimates.
Design.Prospective cohort study.
Setting.A tertiary care referral hospital and regional district hospital in southeast Queensland, Australia.
Patients.Adults aged 18 years or older with a minimum inpatient stay of 1 night who were admitted to selected clinical specialities.
Results.Urinary tract infection was not associated with an increase in length of hospital stay or variable costs. Lower respiratory tract infection was associated with an increase of 2.58 days in the hospital and variable costs of AU$24, whereas other types of infection were associated with an increased length of stay of 2.61 days but not with variable costs. Many other factors were found to be associated with increased length of stay and variable costs alongside healthcare-acquired infection. The exclusion of these variables caused a positive bias in the estimates of the costs of healthcare-acquired infection.
Conclusions.The existing literature may overstate the costs of healthcare-acquired infection because of bias, and the existing estimates of excess costs may not make intuitive sense to clinicians and policy makers. Accurate estimates of the costs of healthcare-acquired infection should be made and used in appropriately designed decision-analytic economic models (ie, cost-effectiveness models) that will make valid and believable predictions of the economic value of increased infection control.
Robust Parametric Modeling for Improved Segmentation of Complex Tumor Microvasculature from Multiphoton Microscopy Data
- James Alexander Tyrrell, Vijay Mahadevan, Ricky Tong, Badri Roysam, Edward B. Brown, Rakesh K. Jain
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- Journal:
- Microscopy and Microanalysis / Volume 10 / Issue S02 / August 2004
- Published online by Cambridge University Press:
- 01 August 2004, pp. 176-177
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- August 2004
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Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.
Photoluminescence Study of Energy Transfer Processes in Erbium Doped AlxGal−xAs Grown by MBE
- Tong Zhang, J. Sun, N.V. Edwards, D.E. Moxey, R.M. Kolbas, P.J. Caldwell
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- MRS Online Proceedings Library Archive / Volume 301 / 1993
- Published online by Cambridge University Press:
- 21 February 2011, 257
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- 1993
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Sharp photoluminescence from the intra-4f shell of Er3+ is observed from erbium doped AlxGal-xAs (0 ≤x ≤ 1) grown by molecular beam epitaxy. The intensity of the luminescence from the erbium is strongly dependent on the aluminum composition with a maximum at x ≈ 0.6. We will present a model that explains the variation in intensity based on the energy transfer coupling efficiency between the host semiconductor and the optically active erbium ions. The coupling efficiency is dominated by the alignment or misalignment of the erbium energy levels with the energy bands of the host semiconductor and by the excess carrier lifetime in the host. The data and model, which are presented here for the first time, are consistent with our previous work on the effects of co-doping with Be or Si and with other workers' measurements of thermal quenching in rare earth doped semiconductors.