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38 Fine Motor Skills in Pediatric Frontal Lobe Epilepsy are Associated with Executive Dysfunction and ADHD Symptomatology
- Moshe Maiman, Madison Berl, Jennifer I Koop, Donald J Bearden, Katrina Boyer, Crystal M Cooper, Amanda M Decrow, Priscilla H. Duong, Patricia Espe-Pfeifer, Marsha Gabriel, Elise Hodges, Kelly A McNally, Andrew Molnar, Emily Olsen, Kim E Ono, Kristina E Patrick, Brianna Paul, Jonathan Romain, Leigh N Sepeta, Rebecca LH Stilp, Greta N Wilkening, Mike Zaccariello, Frank Zelko, Clemente Vega, Trey Moore, Szimonetta Mulati, Phillip Pearl, Jeffrey Bolton, Alyssa Ailion
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 37-38
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Objective:
Pediatric patients with frontal lobe epilepsy (FLE) have higher rates of attention deficit hyperactivity disorder (ADHD), as well as executive functioning (EF) and fine motor (FM) challenges. Relations between these constructs have been established in youth with ADHD and are supported by FM and EF skill involvement in frontal-subcortical systems. Still, they are not well understood in pediatric FLE. We hypothesized that poorer FM performance would be related to greater executive dysfunction and ADHD symptomatology in this group.
Participants and Methods:47 children and adolescents with FLE (AgeM=12.47, SD=5.18; IQM=84.07; SD=17.56; Age of Seizure OnsetM=6.85, SD=4.64; right-handed: n=34; left-handed: n=10; Unclear: n=3) were enrolled in the Pediatric Epilepsy Research Consortium dataset as part of their phase I epilepsy surgical evaluation. Participants were selected if they had unifocal FLE and completed the Lafayette Grooved Pegboard (GP). Seizure lateralization (left-sided: n=19; right-sided: n=26; bilateral: n=2) and localization were established via data (e.g., EEG, MRI) presented at a multidisciplinary team case conference. Patients completed neuropsychological measures of FM, attention, and EF. Parents also completed questionnaires inquiring about their child’s everyday EF and ADHD symptomatology. Correlational analyses were conducted to examine FM, EF, and ADHD relations.
Results:Dominant hand (DH) manual dexterity (GP) was related to parent-reported EF (Behavior Rating Inventory of Executive Function, Second Edition [BRIEF-2]-Global Executive Composite [GEC]: r(15) =-.70, p<.01, d=1.96). While not statistically significant, medium to large effect sizes were found for GP DH and parent-reported inattention (Behavior Assessment System for Children, Third Edition [BASC-3]-Attention Problems: r(12)=-.39, p=.17, d=.85) and hyperactivity/impulsivity (BASC-3-Hyperactivity: r(11)= -.44, p=.13, d=.98), as well as performance-based attention (Conners Continuous Performance Test, Third Edition -Omission Errors: r(12)=-.35, p=.22, d=.41), working memory (Wechsler Intelligence Scale for Children - Fifth Edition [WISC-V]-Digit Span [DS]: r(19)=.38, p=.09, d=.82) and cognitive flexibility (Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Category Switching: r(13)=.46, p=.08, d=1.04); this suggests that these relations may exist but that our study was underpowered to detect them. Non-dominant hand (NDH) manual dexterity was related to performance-based working memory (WISC-V-DS: r(19)=.50, p<.01, d=1.12) and cognitive flexibility (D-KEFS-Trails Making Test Number-Letter Switching: r(17)=.64, p<.01, d=1.67). Again, while underpowered, medium to large effect sizes were found for GP NDH and parent-reported EF (BRIEF-2 GEC: r(15) =-.45, p=.07, d=1.01) and performance-based phonemic fluency (D-KEFS-Letter Fluency: r(13)=.31, p=.20, d=.65).
Conclusions:Our findings suggest that FM, EF, and ADHD are related in youth with FLE; however, these relations appear to vary by skill and hand. We posit that our findings are due in part to the frontal-cerebellar networks given their anatomic proximity between frontal motor areas and the dorsolateral prefrontal cortex - as well as their shared functional involvement in these networks. Future studies should evaluate the predictive validity of initial FM skills for later executive dysfunction and ADHD symptomatology in FLE. If such relations emerge, contributions of early FM interventions on EF development should be examined. Further replication of these findings with a larger sample is warranted.
Hyperglycemia in pregnancy and developmental outcomes in children at 18–60 months of age: the PANDORA Wave 1 study
- Angela Titmuss, Anita D’Aprano, Federica Barzi, Alex D.H. Brown, Anna Wood, Christine Connors, Jacqueline A. Boyle, Elizabeth Moore, Kerin OʼDea, Jeremy Oats, H. David McIntyre, Paul Zimmet, Jonathan E. Shaw, Maria E. Craig, Louise J. Maple-Brown
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- Journal:
- Journal of Developmental Origins of Health and Disease / Volume 13 / Issue 6 / December 2022
- Published online by Cambridge University Press:
- 04 April 2022, pp. 695-705
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This study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.
PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.
After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental “concern” (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77–15.80; GDM OR 3.96, 95% CI 1.55–10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05–6.98; GDM OR 2.54, 95% CI 1.17–5.54) domains, as well as increased “risk” (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85–15.39; GDM OR 4.86, 95% CI 1.95–12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11–0.69) after adjustment for maternal hyperglycemia.
Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.
Airy Beams for Light-sheet Microscopy
- Jonathan Nylk, Zhengyi Yang, Miguel Preciado, Michael Mazilu, Tom Vettenburg, Clara Coll-Llado, David E. K. Ferrier, Tomas Cizmar, Frank. J. Gunn-Moore, Kishan Dholakia
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- Journal:
- Microscopy and Microanalysis / Volume 21 / Issue S3 / August 2015
- Published online by Cambridge University Press:
- 23 September 2015, pp. 1723-1724
- Print publication:
- August 2015
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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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Building a National Model of Public Mental Health Preparedness and Community Resilience: Validation of a Dual-Intervention, Systems-Based Approach
- O. Lee McCabe, Natalie L. Semon, Carol B. Thompson, Jeffrey M. Lating, George S. Everly, Jr, Charlene J. Perry, Suzanne Straub Moore, Adrian M. Mosley, Jonathan M. Links
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- Journal:
- Disaster Medicine and Public Health Preparedness / Volume 8 / Issue 6 / December 2014
- Published online by Cambridge University Press:
- 08 December 2014, pp. 511-526
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Objective
Working within a series of partnerships among an academic health center, local health departments (LHDs), and faith-based organizations (FBOs), we validated companion interventions to address community mental health planning and response challenges in public health emergency preparedness.
MethodsWe implemented the project within the framework of an enhanced logic model and employed a multi-cohort, pre-test/post-test design to assess the outcomes of 1-day workshops in psychological first aid (PFA) and guided preparedness planning (GPP). The workshops were delivered to urban and rural communities in eastern and midwestern regions of the United States. Intervention effectiveness was based on changes in relevant knowledge, skills, and attitudes (KSAs) and on several behavioral indexes.
ResultsSignificant improvements were observed in self-reported and objectively measured KSAs across all cohorts. Additionally, GPP teams proved capable of producing quality drafts of basic community disaster plans in 1 day, and PFA trainees confirmed upon follow-up that their training proved useful in real-world trauma contexts. We documented examples of policy and practice changes at the levels of local and state health departments.
ConclusionsGiven appropriate guidance, LHDs and FBOs can implement an effective and potentially scalable model for promoting disaster mental health preparedness and community resilience, with implications for positive translational impact.(Disaster Med Public Health Preparedness. 2014;8:511-526)
Rapid collapse of a population of Dieffenbachia spp., plants used for tadpole-rearing by a poison-dart frog (Oophaga pumilio) in a Costa Rican rain forest
- Mark J. McKone, Jonathan W. Moore, Christopher W. Harbison, Ian C. Holmen, Hillary C. Lyons, Kristine M. Nachbor, Julia L. Michalak, Maurine Neiman, Julia L. Nicol, George R. Wheeler
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- Journal:
- Journal of Tropical Ecology / Volume 30 / Issue 6 / November 2014
- Published online by Cambridge University Press:
- 04 September 2014, pp. 615-619
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Amphibian populations have been declining worldwide, with multiple potential causes. At La Selva field station in north-eastern Costa Rica, previous work has shown that populations of many amphibians have decreased significantly since the 1970s, especially in primary forest. Starting in 1998, we investigated one of the most common frog species at La Selva, the poison-dart frog Oophaga pumilio (= Dendrobates pumilio). In a survey of 50 plots of 100 m2 in 1998, adult frogs were 4.6 times more abundant in secondary forest than in primary forest. Tadpoles were found only in secondary-forest plots. Almost all (89%) of the tadpoles were found in leaf axils of Dieffenbachia spp., which were much more abundant in secondary-forest than in primary-forest plots. The greater abundance of Dieffenbachia spp. in secondary forest was confirmed in a broad survey of ~11 km of trails within La Selva in 2002. When the same trails were resampled in 2012, Dieffenbachia spp. had been extirpated from 72% of the 50-m segments where plants were present in 2002; abundance was greatly reduced in the few trail segments where any Dieffenbachia spp. remained in 2012. The loss of Dieffenbachia spp., especially in secondary forest, removed the species most often used by O. pumilio for tadpole rearing. Based on counts of calling frogs in 2010, there was no difference in O. pumilio abundance in primary versus secondary forest, in striking contrast to multiple earlier surveys that found much greater frog abundance in secondary forest. We propose that the reason for the rapid decline in Dieffenbachia spp. is herbivory by the collared peccary (Pecari tajacu), which has increased in abundance at La Selva in recent years. A likely consequence is continued reduction in O. pumilio populations.
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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- 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. 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- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- Book:
- The Cambridge Dictionary of Christianity
- Published online:
- 05 August 2012
- Print publication:
- 20 September 2010, pp xi-xliv
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4 - NMR in fragment-based drug discovery
- from PART I - STRUCTURAL BIOLOGY
- Edited by Kenneth M. Merz, Jr, University of Florida, Dagmar Ringe, Brandeis University, Massachusetts, Charles H. Reynolds
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- Drug Design
- Published online:
- 06 July 2010
- Print publication:
- 31 May 2010, pp 41-58
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Summary
AN INTRODUCTION TO FRAGMENT-BASED LEAD DISCOVERY
For decades, molecular starting points for drug discovery have been found by screening large numbers of natural and synthetic compounds for biological activity in phenotypic and biochemical assays. Then, beginning in the mid to late 1990s, several pharmaceutical groups developed new approaches [such as structure/activity relationship by nuclear magnetic resonance (SAR by NMR), the SHAPES strategy, and needle screening] in which simple, low-molecular-weight compounds were screened for binding to the target of interest, and these relatively weak binding molecules were then used to systematically construct larger, more potent, drug leads. Such small screening molecules are now commonly called fragments and the related processes collectively called fragment-based lead discovery (FBLD).
NMR was the first experimental method used to screen fragments, and although a variety of other techniques (including x-ray crystallography, surface plasmon resonance, high concentration bioassays, and mass spectroscopy) have also been applied, NMR is still the most widely used. This chapter reviews the use of NMR for FBLD, beginning with an explanation of the principles behind fragment screening. NMR screening methods are then described, followed by a series of examples that illustrate the process through which fragment screening hits are converted into leads.
An Analysis of a Stable Period in the Northumberland Benthic Fauna-1973–80
- John B. Buchanan, Robin Brachi, Graeme Christie, J. Jonathan Moore
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- Journal:
- Journal of the Marine Biological Association of the United Kingdom / Volume 66 / Issue 3 / August 1986
- Published online by Cambridge University Press:
- 11 May 2009, pp. 659-670
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In the period 1973–80, the infauna at the standard 55 m station exhibited a high degree of persistence stability. The period was characterized by a stable biennial cycle in total numbers of individuals and substantial stability in species ranking. The biennial cycle was associated with density dependent mortality which appears as the principal controlling factor of the community. Evidence is discussed in support of the hypothesis that the density dependent mortality is due to interspecific and intraspecific competition, in a food limiting environment, between species with rather broad niche overlaps.
A Broad Review of Variability and Persistence in the Northumberland Benthic Fauna – 1971–85
- John B. Buchanan, J. Jonathan Moore
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- Journal:
- Journal of the Marine Biological Association of the United Kingdom / Volume 66 / Issue 3 / August 1986
- Published online by Cambridge University Press:
- 11 May 2009, pp. 641-657
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The long-term monitoring of two stations, 55 and 80 m depth, from 1971 to 1985 shows clear evidence of periods of stability interspersed with periods of change. These periods were identified by several different multivariate methods and persistence stability was quantified by the use of a between years similarity index. A short period of change at the shallow station, 1972–3, was followed by a prolonged period of stability 1974–80. The period 1981–3 witnessed a second period of change with rising total numbers and biomass with some evidence of a downward reversal in 1984–5. The deep station exhibited an essentially similar response except that the stable period 1974–80 was broken into two sub-periods 1974–6 and 1978–80 due to sequential changes in the dominant species which were regarded as evidence of biological interaction with the activities of the polychaete Ophelina acuminata possibly playing a key role. The shallow station showed little evidence of biological interaction and the majority of the species have exhibited similar responses throughout. The general rise in numbers and biomass at both stations is regarded as evidence of intermittent changes in organic flux to the bottom from the water column. The winter temperature fluctuations were shown to have short-term, but significant, effects on the diversity of the communities, bringing about year to year changes in the equitability and dominance.
NMR study of Ni2+ binding to the H-N-H endonuclease domain of colicin E9
- JONATHAN P. HANNAN, SARA B.-M. WHITTAKER, SHARON L. DAVY, ULRIKE C. KÜHLMANN, ANSGAR J. POMMER, ANDREW M. HEMMINGS, RICHARD JAMES, COLIN KLEANTHOUS, GEOFFREY R. MOORE
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- Journal:
- Protein Science / Volume 8 / Issue 8 / August 1999
- Published online by Cambridge University Press:
- 01 August 1999, pp. 1711-1713
- Print publication:
- August 1999
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Ni2+ affinity columns are widely used for protein purification, but they carry the risk that Ni2+ ions may bind to the protein, either adventitiously or at a physiologically important site. Dialysis against ethylenediaminetetraacetic acid (EDTA) is normally used to remove metal ions bound adventitiously to proteins; however, this approach does not always work. Here we report that a bacterial endonuclease, the DNase domain of colicin E9, binds Ni2+ acquired from Ni2+ affinity columns, and appears to bind [Ni(EDTA)(H2O)n]2− at low ionic strength. NMR was used to detect the presence of both Ni2+ coordinated to amino acid side chains and [Ni(EDTA)(H2O)n]2−. Dialysis against ≥0.2 M NaCl was required to remove the [Ni(EDTA)(H2O)n]2−. The NMR procedure we have used to characterize the presence of Ni2+ and [Ni(EDTA)(H2O)n]2− should be applicable to other proteins where there is the possibility of binding paramagnetic metal ions that are present to expedite protein purification. In the present case, the binding of Ni2+ seems likely to be physiologically relevant, and the NMR data complement recent X-ray crystallographic evidence concerning the number of histidine ligands to bound Ni2+.