8 results
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.
81030 Utilizing a synergistic drug combination to target relapsed/refractory FLT3 mutant AML
- LaQuita Jones, Katelyn Melgar, Scott Hoyt, Mark Wunderlich, Eric O’Brien, John Perentesis, Craig Thomas, Daniel Starczynowski
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- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, p. 100
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ABSTRACT IMPACT: This work will help to understand a novel therapeutic approach to a common type of acute myeloid leukemia. OBJECTIVES/GOALS: FMS-like tyrosine kinase 3 (or FLT3) mutations occur in ˜30% of acute myeloid leukemia (AML) cases. FLT3 tyrosine kinase domain (TKD) mutations are particularly important in relapsed/refractory FLT3 mutant AML, which portends poor prognosis. This study describes a therapeutic approach to overcoming resistance conferred by FLT3-TKD mutations. METHODS/STUDY POPULATION: To understand the efficacy of a novel type 1 FLT3 inhibitor (NCGC1481), as a monotherapy and combination therapy, several assays were utilized to interrogate functionality of these therapies. Cell lines and patient samples containing aspartate 835 to tyrosine mutations (D835Y, the most common TKD alteration) and phenylalanine 691 to leucine (F691L) were utilized to examine the effects of NCGC1481 with and without other targeted therapies like MEK inhibitors. Specifically, assays measuring viability, cell death using flow cytometry, in vitro clonogenicity, cellular signaling, and xenograft survival were examined in these FLT3-TKD AML models. Synergy was also measured using well described methods, which also allowed for appropriate dose finding for drug combination experiments. RESULTS/ANTICIPATED RESULTS: Our novel type 1 FLT3 inhibitor (NCGC1481) was particularly effective in the most common FLT3 TKD mutant, D835Y. NCGC1481 reduced viability and cell signaling, while also inducing cell death and prolonging xenograft survival in the FLT3-D835Y model system. In contrast, clinically approved FLT3 inhibitors were less effective at suppressing AML cells expressing FLT3-D835Y. In the case of FLT3-F691L, most of the FLT3 inhibitors tested, including NCGC1481, suppressed canonical FLT3 signaling, but did not significantly reduce viability or leukemic clonogenicity. However, when NCGC1481 was combined with other targeted agents like MEK inhibitors, at synergistic doses, eradication of the FLT3-F691L AML clone was substantially increased. DISCUSSION/SIGNIFICANCE OF FINDINGS: In AML, response to FLT3 inhibitor therapy is often short-lived, with resistance sometimes occurring via FLT3-TKD mutations. Given the dismal prognosis of relapsed FLT3 mutant AML, novel therapies are necessary. This study describes efficacy of a novel FLT3 inhibitor, along with its synergistic activity when combined with other targeted agents.
Contributors
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- By Cecil S. Ash, Paul Barach, Ulrike Buehner, M. Ross Bullock, Leonardo Canale, Henry G. Chou, Jeffrey A. Claridge, John J. Como, Armagan Dagal, Martin Dauber, James S. Davis, Shalini Dhir, François Donati, Roman Dudaryk, Richard P. Dutton, Talmage D. Egan, Yashar Eshraghi, John R. Fisgus, Jeff Gadsden, Sugantha Ganapathy, Mark A. Gerhardt, Inderjit Gill, Joseph F. Golob, Glenn P. Gravlee, Marcello Guglielmi, Jana Hambley, Peter Hebbard, Elena J. Holak, Khadil Hosein, Ken Johnson, Matthew A. Joy, George W. Kanellakos, Olga Kaslow, Arthur M. Lam, Vanetta Levesque, Jessica Anne Lovich-Sapola, M. Jocelyn Loy, Peter F. Mahoney, Donn Marciniak, Maureen McCunn, Craig C. McFarland, Maroun J. Mhanna, Timothy Moore, Cynthia Nguyen, Maxim Novikov, E. Orestes O’Brien, Ketan P. Parekh, Claire L. Park, Michael J. A. Parr, Elie Rizkala, Steven Roth, Alistair Royse, Colin Royse, Kasia Petelenz Rubin, David Ryan, Claire Sandstrom, Carl I. Schulman, Rishad Shaikh, Ranjita Sharma, Jeffrey H. Silverstein, Peter Slinger, Charles E. Smith, Christopher Smith, Paul Soeding, Rakesh V. Sondekoppam, P. David Soran, Eldar Søreide, Elizabeth A. Steele, Kristian Strand, Dennis M. Super, Kutaiba Tabbaa, Nicholas T. Tarmey, Joshua M. Tobin, Kalpana Tyagaraj, Heather A. Vallier, Sandra Werner, Earl Willis Weyers, William C. Wilson, Shoji Yokobori, Charles J. Yowler
- Edited by Charles E. Smith
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- Book:
- Trauma Anesthesia
- Published online:
- 05 April 2015
- Print publication:
- 09 April 2015, pp vii-x
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Chapter 11 - Renewable Energy
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- By Wim Turkenburg, Utrecht University, Doug J. Arent, National Renewable Energy laboratory, Ruggero Bertani, Enel Green Power S.p.A., Andre Faaij, Utrecht University, Maureen Hand, National Renewable Energy Laboratory, Wolfram Krewitt, German Air and Space Agency, Eric D. Larson, Princeton University and Climate Central, John Lund, Geo-Heat Center, Oregon Institute of Technology, Mark Mehos, National Renewable Energy Laboratory, Tim Merrigan, National Renewable Energy Laboratory, Catherine Mitchell, University of Exeter, José Roberto Moreira, Biomass Users Network, Wim Sinke, Energy Research Centre of the Netherlands, Virginia Sonntag-O'Brien, REN21, Bob Thresher, National Renewable Energy Laboratory, Wilfried van Sark, Utrecht University, Eric Usher, United Nations Environment Programme, Dan Bilello, National Renewable Energy Laboratory, Helena Chum, National Renewable Energy Laboratory, Diana Kraft, REN21, Philippe Lempp, German Development Ministry, Jeff Logan, National Renewable Energy Laboratory, Lau Saili, International Hydropower Association, Niels B. Schulz, International Institute for Applied systems Analysis, Austria and Imperial College, Aaron Smith, National Renewable Energy Laboratory, Richard Taylor, International Hydropower Association, Craig Turchi, National Renewable Energy Laboratory, Jürgen Schmid, Fraunhofer Institute for Wind Energy and Energy System Technology
- Global Energy Assessment Writing Team
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- Book:
- Global Energy Assessment
- Published online:
- 05 September 2012
- Print publication:
- 27 August 2012, pp 761-900
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Summary
Executive Summary
Renewable energy sources – including biomass, geothermal, ocean, solar, and wind energy, as well as hydropower – have a huge potential to provide energy services for the world. The renewable energy resource base is sufficient to meet several times the present world energy demand and potentially even 10 to 100 times this demand. This chapter includes an in-depth examination of technologies to convert these renewable energy sources to energy carriers that can be used to fulfill our energy needs, including their installed capacity, the amount of energy carriers they produced in 2009, the current state of market and technology development, their economic and financial feasibility in 2009 and in the near future, as well as major issues they may face relative to their sustainability or implementation.
Present uses of renewable energy
Since 1990 the energy provided from renewable sources worldwide has risen at an average rate of nearly 2% a year, but in recent years this rate has increased to about 5% annually (see Figure 11.1.) As a result, the global contribution of renewables has increased from about 74 EJ in 2005 to about 89 EJ in 2009 and represents now 17% of global primary energy supply (528 EJ, see Figure 11.2). Most of this renewable energy comes from the traditional use of biomass (about 39 EJ) and larger-scale hydropower (about 30 EJ), while other renewable technologies provided about 20 EJ.
Summary for Policymakers
- from Section II
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- By Simon K. Allen, Vicente Barros, Ian Burton, Diarmid Campbell-Lendrum, Omar-Dario Cardona, Susan L. Cutter, O. Pauline Dube, Kristie L. Ebi, Christopher B. Field, John W. Handmer, Padma N. Lal, Allan Lavell, Katharine J. Mach, Michael D. Mastrandrea, Gordon A. McBean, Reinhard Mechler, Tom Mitchell, Neville Nicholls, Karen L. O'Brien, Taikan Oki, Michael Oppenheimer, Mark Pelling, Gian-Kasper Plattner, Roger S. Pulwarty, Sonia I. Seneviratne, Thomas F. Stocker, Maarten K. van Aalst, Carolina S. Vera, Thomas J. Wilbanks
- Edited by Christopher B. Field, Vicente Barros, Thomas F. Stocker, Qin Dahe
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- Book:
- Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation
- Published online:
- 05 August 2012
- Print publication:
- 28 May 2012, pp 3-22
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Summary
Context
This Summary for Policymakers presents key findings from the Special Report on Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation (SREX). The SREX approaches the topic by assessing the scientific literature on issues that range from the relationship between climate change and extreme weather and climate events (‘climate extremes’) to the implications of these events for society and sustainable development. The assessment concerns the interaction of climatic, environmental, and human factors that can lead to impacts and disasters, options for managing the risks posed by impacts and disasters, and the important role that non-climatic factors play in determining impacts. Box SPM.1 defines concepts central to the SREX.
The character and severity of impacts from climate extremes depend not only on the extremes themselves but also on exposure and vulnerability. In this report, adverse impacts are considered disasters when they produce widespread damage and cause severe alterations in the normal functioning of communities or societies. Climate extremes, exposure, and vulnerability are influenced by a wide range of factors, including anthropogenic climate change, natural climate variability, and socioeconomic development (Figure SPM.1). Disaster risk management and adaptation to climate change focus on reducing exposure and vulnerability and increasing resilience to the potential adverse impacts of climate extremes, even though risks cannot fully be eliminated (Figure SPM.2). Although mitigation of climate change is not the focus of this report, adaptation and mitigation can complement each other and together can significantly reduce the risks of climate change. [SYR AR4, 5.3]
Contributors
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- By Joanne R. Adler, David A. Alexander, Laurence Alison, Catherine C. Ayoub, Peter Banister, Anthony R. Beech, Amanda Biggs, Julian Boon, Adrian Bowers, Neil Brewer, Eric Broekaert, Paula Brough, Jennifer M. Brown, Kevin Browne, Elizabeth A. Campbell, David Canter, Michael Carlin, Shihning Chou, Martin A. Conway, Claire Cooke, David Cooke, Ilse Derluyn, Robert J. Edelmann, Vincent Egan, Tom Ellis, Marie Eyre, David P. Farrington, Seena Fazel, Daniel B. Fishman, Victoria Follette, Katarina Fritzon, Elizabeth Gilchrist, Nathan D. Gillard, Renée Gobeil, Agnieszka Golec de Zavala, Jane Goodman-Delahunty, Lynsey Gozna, Don Grubin, Gisli H. Gudjonsson, Helinä Häkkänen-Nyholm, Guy Hall, Nathan Hall, Roisin Hall, Sean Hammond, Leigh Harkins, Grant T. Harris, Camilla Herbert, Robert D. Hoge, Todd E. Hogue, Clive R. Hollin, Lorraine Hope, Miranda A. H. Horvath, Kevin Howells, Carol A. Ireland, Jane L. Ireland, Mark Kebbell, Michael King, Bruce D. Kirkcaldy, Heidi La Bash, Cara Laney, William R. Lindsay, Elizabeth F. Loftus, L. E. Marshall, W. L. Marshall, James McGuire, Neil McKeganey, T. M. McMillan, Mary McMurran, Joav Merrick, Becky Milne, Joanne M. Nadkarni, Claire Nee, M. D. O’Brien, William O’Donohue, Darragh O’Neill, Jane Palmer, Adria Pearson, Derek Perkins, Devon L. L. Polaschek, Louise E. Porter, Charlotte C. Powell, Graham E. Powell, Martine Powell, Christine Puckering, Ethel Quayle, Vernon L. Quinsey, Marnie E. Rice, Randall Richardson-Vejlgaard, Richard Rogers, Louis B Schlesinger, Carolyn Semmler, G. A. Serran, Ralph C. Serin, John L. Taylor, Max Taylor, Brian Thomas-Peter, Paul A. Tiffin, Graham Towl, Rosie Travers, Arlene Vetere, Graham Wagstaff, Helen Wakeling, Fiona Warren, Brandon C. Welsh, David Wexler, Margaret Wilson, Dan Yarmey, Susan Young
- Edited by Jennifer M. Brown, London School of Economics and Political Science, Elizabeth A. Campbell, University of Glasgow
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- Book:
- The Cambridge Handbook of Forensic Psychology
- Published online:
- 06 July 2010
- Print publication:
- 29 April 2010, pp xix-xxiii
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9 - Ethnography, communication and support for design
- Edited by Paul Luff, King's College London, Jon Hindmarsh, King's College London, Christian Heath, King's College London
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- Book:
- Workplace Studies
- Published online:
- 05 May 2010
- Print publication:
- 15 August 2000, pp 187-214
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Summary
Design is a distributed social process, and, as such, communication plays a vital role.
(Erickson, 1996: 32)Ethnography, workplace studies and design: the problem of communication
Since the late 1980s, and much to the surprise of many of its practitioners, ethnography has risen to a position of some prominence within CSCW research (Bentley et al., 1992; Hughes et al., 1994). This rise has not, of course, gone unchallenged; even from relatively sympathetic critics serious questions have been raised, and quite rightly, about the value of the approach in actually informing system design (see e.g. Plowman et al., 1995). Although this criticism is well taken, it does point to a problem recognised from the outset, namely, how are the results of ethnographic field studies to be conveyed to designers? In fact, there are a host of problems involving, for example, the scope of the design, the size of the design team, the stage of the design and more (see Hughes et al., 1994). Such communication problems have been at the heart of system design for some years even before ethnography and workplace studies came on the scene, and in this connection the ‘story’ related by Cooper et al. (1995) – though pertaining to designers and users – can be adapted to portray something of the state of affairs between fieldworkers and designers:
Systems design used to be done by a bunch of techies, deep deep deep within some head office building somewhere. Here they would build their system. Test it, test it, test it, until they were sure it would work, and then they would throw it over this great high brick wall, and hope that the user would catch it, on the other side.
A methodological requirement in the investigation of “knowledge”
- Mark John O'Brien
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- Journal:
- Behavioral and Brain Sciences / Volume 22 / Issue 5 / October 1999
- Published online by Cambridge University Press:
- 01 October 1999, pp. 779-780
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The modernist and scientific juxtaposition of object and subject are inappropriate when investigating the nature of “knowledge.” This commentary argues that the usual methodological dichotomy fails when it is applied to the domain of “knowledge.” The two instead coalesce within the topic itself, demanding the most careful self-awareness.