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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, JeanMichel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, HsiChung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil TekolaAyele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 2 / August 2022
- Published online by Cambridge University Press:
- 04 May 2022, p. 494
- Print publication:
- August 2022
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 220 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 28 February 2022, pp. 219-228
- Print publication:
- April 2022
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Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
A Discussion of Aviezer Tucker's The Legacies of Totalitarianism: A Theoretical Framework
- Michael H. Bernhard
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- Journal:
- Perspectives on Politics / Volume 15 / Issue 2 / June 2017
- Published online by Cambridge University Press:
- 08 June 2017, pp. 540-541
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- June 2017
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The concept of totalitarianism emerged between the two world wars in twentieth-century Europe to become a central concept of Cold War social science designed to highlight similarities between the Nazi and Soviet regimes and implicitly to contrast these forms of dictatorship with liberal democracy. While in the 1960s and 1970s many critics challenged the concept’s Cold War uses as an ideology of “the West,” the idea of totalitarianism and later “post-totalitarianism” played important roles in East Central Europe, where they helped dissident intellectuals, academics, and activists both to understand and to challenge Soviet-style communism. The concept of “totalitarianism” remains heavily contested. But whatever one thinks about the concept’s social scientific validity, there can be no doubt that it played a crucial role in both the scholarship of communism and the public intellectual debates about the possibilities of post-communism. Aviezer Tucker’s The Legacies of Totalitarianism: A Theoretical Framework (Cambridge 2015) addresses many of these issues, and so we have invited a range of political scientists to comment on the book and the broader theme denoted by its title.
Contributors
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- By Michael Harris Bond, Xinyin Chen, Dov Cohen, Ella Daniel, Nancy Eisenberg, Doran C. French, Sigal Gabay, Pehr Granqvist, Aisha Griffith, Jessica Halliday Hardie, Lene Arnett Jensen, Hyeyoung Kang, Ariel Knafo, Hans-Joachim Kornadt, Reed W. Larson, Liman Man Wai Li, Junsheng Liu, Vivian Miu-Chi Lun, Sami Mahajna, Tina Malti, Boris Mayer, Kristina McDonald, Ramesh Chandra Mishra, Bernhard Nauck, Vinai Norasakkunkit, Lisa D. Pearce, Urip Purwono, Vikki Rompala, Fred Rothbaum, Kenneth H. Rubin, Julie A. Sallquist, Vassilis Saroglou, Shalom H. Schwartz, Rachel Seginer, Rivka Shir, Anja Steinbach, Gisela Trommsdorff, Yukiko Uchida, Li Wang, Yan Z. Wang, Ran Zilber
- Edited by Gisela Trommsdorff, Universität Konstanz, Germany, Xinyin Chen, University of Pennsylvania
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- Book:
- Values, Religion, and Culture in Adolescent Development
- Published online:
- 05 September 2012
- Print publication:
- 27 August 2012, pp xiii-xxiv
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Contributors
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- By Jane E. Adcock, Yahya Aghakhani, A. Anand, Eva Andermann, Frederick Andermann, Alexis Arzimanoglou, Sandrine Aubert, Nadia Bahi-Buisson, Carman Barba, Agatino Battaglia, Geneviève Bernard, Nadir E. Bharucha, Laurence A. Bindoff, William Bingaman, Francesca Bisulli, Thomas P. Bleck, Stewart G. Boyd, Andreas Brunklaus, Harry Bulstrode, Jorge G. Burneo, Laura Canafoglia, Laura Cantonetti, Roberto H. Caraballo, Fernando Cendes, Kevin E. Chapman, Patrick Chauvel, Richard F. M. Chin, H. T. Chong, Fahmida A. Chowdhury, Catherine J. Chu-Shore, Rolando Cimaz, Andrew J. Cole, Bernard Dan, Geoffrey Dean, Alessio De Ciantis, Fernando De Paolis, Rolando F. Del Maestro, Irissa M. Devine, Carlo Di Bonaventura, Concezio Di Rocco, Henry B. Dinsdale, Maria Alice Donati, François Dubeau, Michael Duchowny, Olivier Dulac, Monika Eisermann, Brent Elliott, Bernt A. Engelsen, Kevin Farrell, Natalio Fejerman, Rosalie E. Ferner, Silvana Franceschetti, Robert Friedlander, Antonio Gambardella, Hector H. Garcia, Serena Gasperini, Lorenzo Genitori, Gioia Gioi, Flavio Giordano, Leif Gjerstad, Daniel G. Glaze, Howard P. Goodkin, Sidney M. Gospe, Andrea Grassi, William P. Gray, Renzo Guerrini, Marie-Christine Guiot, William Harkness, Andrew G. Herzog, Linda Huh, Margaret J. Jackson, Thomas S. Jacques, Anna C. Jansen, Sigmund Jenssen, Michael R. Johnson, Dorothy Jones-Davis, Reetta Kälviäinen, Peter W. Kaplan, John F. Kerrigan, Autumn Marie Klein, Matthias Koepp, Edwin H. Kolodny, Kandan Kulandaivel, Ruben I. Kuzniecky, Ahmed Lary, Yolanda Lau, Anna-Elina Lehesjoki, Maria K. Lehtinen, Holger Lerche, Michael P. T. Lunn, Snezana Maljevic, Mark R. Manford, Carla Marini, Bindu Menon, Giulia Milioli, Eli M. Mizrahi, Manish Modi, Márcia Elisabete Morita, Manuel Murie-Fernandez, Vivek Nambiar, Lina Nashef, Vincent Navarro, Aidan Neligan, Ruth E. Nemire, Charles R. J. C. Newton, John O'Donavan, Hirokazu Oguni, Teiichi Onuma, Andre Palmini, Eleni Panagiotakaki, Pasquale Parisi, Elena Parrini, Liborio Parrino, Ignacio Pascual-Castroviejo, M. Scott Perry, Perrine Plouin, Charles E. Polkey, Suresh S. Pujar, Karthik Rajasekaran, R. Eugene Ramsey, Rahul Rathakrishnan, Roberta H. Raven, Guy M. Rémillard, David Rosenblatt, M. Elizabeth Ross, Abdulrahman Sabbagh, P. Satishchandra, Swati Sathe, Ingrid E. Scheffer, Philip A. Schwartzkroin, Rod C. Scott, Frédéric Sedel, Michelle J. Shapiro, Elliott H. Sherr, Michael Shevell, Simon D. Shorvon, Adrian M. Siegel, Gagandeep Singh, S. Sinha, Barbara Spacca, Waney Squier, Carl E. Stafstrom, Bernhard J. Steinhoff, Andrea Taddio, Gianpiero Tamburrini, C. T. Tan, Raymond Y. L. Tan, Erik Taubøll, Robert W. Teasell, Mario Giovanni Terzano, Federica Teutonico, Suzanne A. Tharin, Elizabeth A. Thiele, Pierre Thomas, Paolo Tinuper, Dorothée Kasteleijn-Nolst Trenité, Sumeet Vadera, Pierangelo Veggiotti, Jean-Pierre Vignal, J. M. Walshe, Elizabeth J. Waterhouse, David Watkins, Ruth E. Williams, Yue-Hua Zhang, Benjamin Zifkin, Sameer M. Zuberi
- Edited by Simon D. Shorvon, Frederick Andermann, Renzo Guerrini
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- Book:
- The Causes of Epilepsy
- Published online:
- 05 March 2012
- Print publication:
- 14 April 2011, pp ix-xvi
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List of Contributors
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- By Harold P. Adams, Colum F. Amory, Anne Angelillo-Scherrer, Irena Anselm, Marcel Arnold, Robert W. Baloh, Ralf W. Baumgartner, José Biller, Valérie Biousse, Matthias Bischof, Julien Bogousslavsky, Natan M. Bornstein, Marie Germaine Bousser, Robin L. Brey, John C. M. Brust, Alan Bryer, Olivier Calvetti, Louis R. Caplan, José Castillo, Hugues Chabriat, Chin-Sang Chung, Charlotte Cordonnier, Steven C. Cramer, Luís Cunha, Rima M. Dafer, John F. Dashe, Cyrus K. Dastur, Antonio Dávalos, Larry E. Davis, Patricia Davis, Stephen M. Davis, Jan L. De Bleecker, Michael A. De Georgia, Amir R. Dehdashti, Oscar H. Del Brutto, Jacques L. De Reuck, Hans-Christoph Diener, Kathleen B. Digre, Vivian U. Fritz, Nancy Futrell, Bhuwan P. Garg, Philip B. Gorelick, Glenn D. Graham, Alexander Y. Gur, John J. Halperin, Michael Hennerici, Isabel Lestro Henriques, Roberto C. Heros, Daniel B. Hier, Lorenz Hirt, Joanna C. Jen, Taro Kaibara, Sumit Kapoor, Sarosh M. Katrak, Siddharth Kharkar, Walter J. Koroshetz, Monisha Kumar, Sandeep Kumar, Emre Kumral, Tobias Kurth, Rogelio Leira, Steven R. Levine, Didier Leys, Doris Lin, Jonathan Lipton, Alfredo M. Lopez-Yunez, Betsy B. Love, Ayrton Roberto Massaro, Heinrich P. Mattle, Manu Mehdiratta, John H. Menkes, Philippe Metellus, Reto Meuli, Patrik Michel, Panayiotis Mitsias, Jorge Moncayo-Gaete, Julien Morier, Krassen Nedeltchev, Bernhard Neundörfer, Olukemi A. Olugemo, Nikolaos I. H. Papamitsakis, Stephen D. Reck, Luca Regli, Marc D. Reichhart, Daniele Rigamonti, Michael J. Rivkin, E. Steve Roach, Jose F. Roldan, David Z. Rose, Daniel M. Rosenbaum, N. Paul Rosman, Elayna O. Rubens, Sean I. Savitz, Marc Schapira, Robert J. Schwartzman, Magdy Selim, Yukito Shinohara, Aneesh B. Singhal, Michael A. Sloan, Barney J. Stern, Mathias Sturzenegger, Oriana Thompson, A. Wesley Thevathasan, Jonathan D. Trobe, Michael Varner, Dana Védy, Jorge Vidaurre, Engin Y. Yilmaz, Khaled Zamel, Mathieu Zuber
- Edited by Louis R. Caplan, Julien Bogousslavsky
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- Book:
- Uncommon Causes of Stroke
- Published online:
- 06 January 2010
- Print publication:
- 09 October 2008, pp ix-xiv
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Contributors
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- By Claude Alain, Amy F. T. Arnsten, Lars Bäckman, Malcolm A. Binns, Sandra E. Black, S. Thomas Carmichael, Keith D. Cicerone, Maurizio Corbetta, Bruce Crosson, Jeffrey L. Cummings, Deirdre R. Dawson, Michael deRiesthal, Roger A. Dixon, Laura Eggermont, Kirk I. Erickson, Anthony Feinstein, Susan M. Fitzpatrick, Fu Qiang Gao, Douglas D. Garrett, Omar Ghaffar, Robbin Gibb, Elizabeth L. Glisky, Martha L. Glisky, Leslie J. Gonzalez Rothi, Cheryl L. Grady, Carol Greenwood, Gerri Hanten, Richard G. Hunter, Masud Husain, Narinder Kapur, Bryan Kolb, Arthur F. Kramer, Susan A. Leon, Harvey S. Levin, Brian Levine, Nadina Lincoln, Thomas W. McAllister, Edward McAuley, Bruce S. McEwen, David M. Morris, Stephen E. Nadeau, Roshan das Nair, Matthew Parrott, Jennie Ponsford, George P. Prigatano, Joel Ramirez, John M. Ringman, Ian H. Robertson, Amy D. Rodriguez, John C. Rosenbek, Bernhard Ross, Erik Scherder, Victoria Singh-Curry, Trudi Stickland, Donald T. Stuss, Edward Taub, Gary R. Turner, Harry V. Vinters, Samuel Weiss, John Whyte, Barbara A. Wilson, Gordon Winocur, J. Martin Wojtowicz
- Edited by Donald T. Stuss, University of Toronto, Gordon Winocur, University of Toronto, Ian H. Robertson, Trinity College, Dublin
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- Book:
- Cognitive Neurorehabilitation
- Published online:
- 05 September 2015
- Print publication:
- 11 September 2008, pp ix-xiv
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Prenatally undernourished rats show increased preference for wheel running v. lever pressing for food in a choice task
- Jennifer L. Miles, Jason Landon, Michael Davison, Christian U. Krägeloh, Nichola M. Thompson, Christopher M. Triggs, Bernhard H. Breier
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- Journal:
- British Journal of Nutrition / Volume 101 / Issue 6 / 28 March 2009
- Published online by Cambridge University Press:
- 02 September 2008, pp. 902-908
- Print publication:
- 28 March 2009
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Maternal nutrition during pregnancy has a significant influence in establishing patterns of metabolism and postnatal behaviours in offspring, and therefore shapes their risk of developing disorders in later life. Although it is well established that a mismatch between food consumption and energy expenditure leads to obesity and metabolic dysregulation, little research has investigated the biological origin of such behaviour. We conducted the present experiments to investigate effects of early-life nutrition on preference between wheel running and lever pressing for food during adult life. To address this issue we employed a well-established experimental approach in the rat which has shown that offspring of mothers undernourished during pregnancy develop obesity and metabolic disorders when kept under standard laboratory conditions. Using this experimental approach, two studies were conducted where offspring of ad libitum-fed dams and dams undernourished throughout pregnancy were given the choice between wheel running and pressing a response lever for food. Across subsequent conditions, the rate at which the response lever provided food was varied from 0·22 to 6·0 (study 1) and 0·19 to 3·0 (study 2) pellets per min. Compared with the control group, offspring from dams undernourished during pregnancy showed a consistently greater preference for running over lever pressing for food throughout both experiments of the study. The results of the present study provide experimental evidence that a mother's nutrition during pregnancy can result in a long-term shift in her offspring's lifestyle choices that are relevant to obesity prevention. Such a shift, if endorsed, will have substantial and wide-ranging health consequences throughout the lifespan.
27 - The developmental environment: influences on subsequent cognitive function and behaviour
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- By Jason Landon, University of Auckland, Michael Davison, University of Auckland, Bernhard H. Breier, University of Auckland
- Edited by Peter Gluckman, University of Auckland, Mark Hanson, University of Southampton
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- Book:
- Developmental Origins of Health and Disease
- Published online:
- 08 August 2009
- Print publication:
- 20 April 2006, pp 370-378
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Summary
Introduction
The concept of the developmental origins of adult disease was initially based on epidemiological observations relating evidence of a constrained fetal environment to a greater risk of metabolic and cardiovascular disorders in adult life. It was later recognised that those at greatest risk also have an increased propensity to developing obesity in childhood and during adult life (Barker and Osmond 1988, Hales and Barker 1992, Gluckman and Hanson 2004). The interest in the later effects of early environmental events has since been generalised to include possible prenatal effects on offspring behaviour and cognition. In this chapter, we review the existing human and animal literature on the early-life influences on offspring cognitive function and behaviour.
Human studies
Recently, interest has grown in the possibility of a relation between birthweight and subsequent cognitive function. Early research focused on comparisons between individuals of low birthweight (LBW) or small for gestational age (SGA) and those with normal birthweights (e.g., Ounsted et al. 1983, Pharoah et al. 1994, Strauss 2000). These studies showed that LBW and SGA individuals had an increased incidence of neurological deficits and/or poorer cognitive skills throughout childhood. Subsequent research has examined whether this relationship persists across the normal range of birthweights (e.g. Sorenson et al. 1997, Matte et al. 2001, Richards et al. 2001, 2002, Shenkin et al. 2001, Jefferis et al. 2002). The consensus from this research is that the relationship does hold across the range of normal birthweights, but that the effect is small.
Conformational flexibility in the apolipoprotein E amino-terminal domain structure determined from three new crystal forms: Implications for lipid binding
- BRENT W. SEGELKE, MICHAEL FORSTNER, MARK KNAPP, SERGEI D. TRAKHANOV, SEAN PARKIN, YVONNE M. NEWHOUSE, HENRY D. BELLAMY, KARL H. WEISGRABER, BERNHARD RUPP
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- Journal:
- Protein Science / Volume 9 / Issue 5 / May 2000
- Published online by Cambridge University Press:
- 01 May 2000, pp. 886-897
- Print publication:
- May 2000
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An amino-terminal fragment of human apolipoprotein E3 (residues 1–165) has been expressed and crystallized in three different crystal forms under similar crystallization conditions. One crystal form has nearly identical cell dimensions to the previously reported orthorhombic (P212121) crystal form of the amino-terminal 22 kDa fragment of apolipoprotein E (residues 1–191). A second orthorhombic crystal form (P212121 with cell dimensions differing from the first form) and a trigonal (P3121) crystal form were also characterized. The structures of the first orthorhombic and the trigonal form were determined by seleno-methionine multiwavelength anomalous dispersion, and the structure of the second orthorhombic form was determined by molecular replacement using the structure from the trigonal form as a search model. A combination of modern experimental and computational techniques provided high-quality electron-density maps, which revealed new features of the apolipoprotein E structure, including an unambiguously traced loop connecting helices 2 and 3 in the four-helix bundle and a number of multiconformation side chains. The three crystal forms contain a common intermolecular, antiparallel packing arrangement. The electrostatic complimentarity observed in this antiparallel packing resembles the interaction of apolipoprotein E with the monoclonal antibody 2E8 and the low density lipoprotein receptor. Superposition of the model structures from all three crystal forms reveals flexibility and pronounced kinks in helices near one end of the four-helix bundle. This mobility at one end of the molecule provides new insights into the structural changes in apolipoprotein E that occur with lipid association.
Hungary's Negotiated Revolution: Economic Reform, Social Change, and Political Succession, 1957–1990. By Rudolf L. Tökés. Cambridge: Cambridge University Press, 1996. 544p. $64.25 cloth, $24.95 paper.
- Michael H. Bernhard
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- Journal:
- American Political Science Review / Volume 91 / Issue 3 / September 1997
- Published online by Cambridge University Press:
- 01 August 2014, pp. 773-774
- Print publication:
- September 1997
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