13 results
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.
3 - Introduction to the Patient Interview
- Edited by Audrey Walker, Albert Einstein College of Medicine, New York, Steven Schlozman, Jonathan Alpert, Albert Einstein College of Medicine, New York
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- Introduction to Psychiatry
- Published online:
- 22 July 2021
- Print publication:
- 12 August 2021, pp 38-69
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Summary
Interviewing patients is one of the most rewarding aspects of clinical psychiatry. It offers an opportunity to get to know someone, to find clues to diagnosis, and to relieve suffering. The psychiatric interview thus functions as an alliance-building process, diagnostic procedure, and therapeutic intervention. While this may sound complex, the interview process can be simplified by learning to approach it with the proper attitude. This can be considered analogous to helping a young musician learn how to have proper posture at the piano or to hold a violin and bow correctly. Without a good feel for the instrument, and without the appropriate perspective for learning what the music is about, the simple drilling of scales and fingerings will be misguided. Similarly, in the psychiatric interview, one must have a proper attitude toward the patient to be of the most help. The key qualities of this approach are curiosity, respect, and caring. If you notice obstacles to feeling interested in or caring about the patient, do not despair – such attitudes can be cultivated (see the section on empathy and compassion later in this chapter).
Importance of Participant-Centricity and Trust for a Sustainable Medical Information Commons
- Amy L. McGuire, Mary A. Majumder, Angela G. Villanueva, Jessica Bardill, Juli M. Bollinger, Eric Boerwinkle, Tania Bubela, Patricia A. Deverka, Barbara J. Evans, Nanibaa' A. Garrison, David Glazer, Melissa M. Goldstein, Henry T. Greely, Scott D. Kahn, Bartha M. Knoppers, Barbara A. Koenig, J. Mark Lambright, John E. Mattison, Christopher O'Donnell, Arti K. Rai, Laura L. Rodriguez, Tania Simoncelli, Sharon F. Terry, Adrian M. Thorogood, Michael S. Watson, John T. Wilbanks, Robert Cook-Deegan
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- Journal:
- Journal of Law, Medicine & Ethics / Volume 47 / Issue 1 / Spring 2019
- Published online by Cambridge University Press:
- 01 January 2021, pp. 12-20
- Print publication:
- Spring 2019
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Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.
2092 A multicenter study of fecal microbiota transplantation for Clostridium difficile infection in children
- Maribeth R. Nicholson, Erin Alexander, Mark Bartlett, Penny Becker, Zev Davidovics, Elizabeth E. Knackstedt, Michael Docktor, Michael Dole, Grace Felix, Jonathan Gisser, Suchitra Hourigan, Kyle Jensen, Jess Kaplan, Judith Kelsen, Melissa Kennedy, Sahil Khanna, McKenzie Leier, Jeffery Lewis, Ashley Lodarek, Sonia Michail, Paul Mitchell, Maria Oliva‐Hemker, Tiffany Patton, Karen Queliza, Namita Singh, Aliza Solomon, David Suskind, Steven Werlin, Richard Kellermayer, Stacy Kahn
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- Journal:
- Journal of Clinical and Translational Science / Volume 2 / Issue S1 / June 2018
- Published online by Cambridge University Press:
- 21 November 2018, p. 64
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OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.
The development of a localised HIV epidemic and the associated excess mortality burden in a rural area of South Africa
- P. Mee, K. Kahn, C.W. Kabudula, R.G. Wagner, F. X. Gómez-Olivé, S. Madhavan, Mark A. Collinson, S.M. Tollman, P. Byass
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- Journal:
- Global Health, Epidemiology and Genomics / Volume 1 / 2016
- Published online by Cambridge University Press:
- 23 March 2016, e7
- Print publication:
- 2016
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The human immunodeficiency virus (HIV) epidemic in South Africa rapidly developed into a major pandemic. Here we analyse the development of the epidemic in a rural area of the country. The data used were collected between 1992 and 2013 in a longitudinal population survey, the Agincourt Health and Demographic Surveillance Study, in the northeast of the country. Throughout the period of study mortality rates were similar in all villages, suggesting that there were multiple index cases evenly spread geographically. These were likely to have been returning migrant workers. For those aged below 39 years the HIV mortality rate was higher for women, above this age it was higher for men. This indicates the protective effect of greater access to HIV testing and treatment among older women. The recent convergence of mortality rates for Mozambicans and South Africans indicates that the former refugee population are being assimilated into the host community. More than 60% of the deaths occurring in this community between 1992 and 2013 could be attributed directly or indirectly to HIV. Recently there has been an increasing level of non-HIV mortality which has important implications for local healthcare provision. This study demonstrates how evidence from longitudinal analyses can support healthcare planning.
Contributors
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- By Robert S. Anderson, (Mary) Colleen Bhalla, Michelle Blanda, Christopher Carpenter, Chris Chauhan, Paul L. DeSandre, Maura Dickinson, Jonathan A. Edlow, Dany Elsayegh, Kara Iskyan Geren, Peter J. Gruber, Jin H. Han, Marianne Haughey, Teresita M. Hogan, Ula Hwang, Lindsay Jin, Michael P. Jones, Joseph H. Kahn, Keli M. Kwok, Denise Law, Megan M. Leo, Stephen Y. Liang, Judith A. Linden, Brendan G. Magauran Jr, Joseph P. Martinez, Amal Mattu, Karen M. May, Aileen McCabe, Kerry K. McCabe, Jolion McGreevy, Ron Medzon, Ravi K. Murthy, Aneesh T. Narang, Lauren M. Nentwich, David E. Newman-Toker, Jonathan S. Olshaker, Joseph R. Pare, Thomas Perera, Joanna Piechniczek-Buczek, Jesse M. Pines, Timothy Platts-Mills, Suzanne Michelle Rhodes, Lynne Rosenberg, Mark Rosenberg, Todd C. Rothenhaus, Kristine Samson, Arthur B. Sanders, Jeffrey I. Schneider, Rishi Sikka, Kirk A. Stiffler, Morsal R. Tahouni, Mary E. Tanski, Abel Wakai, Scott T. Wilber, Deborah R. Wong
- Edited by Joseph H. Kahn, Brendan G. Magauran, Jr, Jonathan S. Olshaker
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- Book:
- Geriatric Emergency Medicine
- Published online:
- 05 January 2014
- Print publication:
- 16 January 2014, pp vii-x
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Summary for Policy Makers
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- By Thomas B. Johansson, Lund University, Nebojsa Nakicenovic, International Institute for Applied Systems Analysis and Vienna University of Technology, Anand Patwardhan, Indian Institute of Technology-Bombay), Luis Gomez-Echeverri, International Institute for Applied Systems Analysis, Rangan Banerjee, Indian Institute of Technology, Sally M. Benson, Stanford University, Daniel H. Bouille, Bariloche Foundation, Abeeku Brew-Hammond, Kwame Nkrumah University of Science and Technology, Aleh Cherp, Central European University, Suani T. Coelho, National Reference Center on Biomass, University of São Paulo, Lisa Emberson, Stockholm Environment Institute, University of York, Maria Josefina Figueroa, Technical University, Arnulf Grubler, International Institute for Applied Systems Analysis, Austria and Yale University, Kebin He, Tsinghua University, Mark Jaccard, Simon Fraser University, Suzana Kahn Ribeiro, Federal University of Rio de Janeiro, Stephen Karekezi, AFREPREN/FWD, Eric D. Larson, Princeton University and Climate Central, Zheng Li, Tsinghua University, Susan McDade, United Nations Development Programme), Lynn K. Mytelka, United Nations University-MERIT, Shonali Pachauri, International Institute for Applied Systems Analysis, Keywan Riahi, International Institute for Applied Systems Analysis, Johan Rockström, Stockholm Environment Institute, Stockholm University, Hans-Holger Rogner, International Atomic Energy Agency, Joyashree Roy, Jadavpur University, Robert N. Schock, World Energy Council, UK and Center for Global Security Research, Ralph Sims, Massey University, Kirk R. Smith, University of California, Wim C. Turkenburg, Utrecht University, Diana Ürge-Vorsatz, Central European University, Frank von Hippel, Princeton University, Kurt Yeager, Electric Power Research Institute and Galvin Electricity Initiative
- Global Energy Assessment Writing Team
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- Book:
- Global Energy Assessment
- Published online:
- 05 September 2012
- Print publication:
- 27 August 2012, pp 3-30
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Summary
Introduction
Energy is essential for human development and energy systems are a crucial entry point for addressing the most pressing global challenges of the 21st century, including sustainable economic and social development, poverty eradication, adequate food production and food security, health for all, climate protection, conservation of ecosystems, peace and security. Yet, more than a decade into the 21st century, current energy systems do not meet these challenges.
A major transformation is therefore required to address these challenges and to avoid potentially catastrophic future consequences for human and planetary systems. The Global Energy Assessment (GEA) demonstrates that energy system change is the key for addressing and resolving these challenges. The GEA identifies strategies that could help resolve the multiple challenges simultaneously and bring multiple benefits. Their successful implementation requires determined, sustained and immediate action.
Transformative change in the energy system may not be internally generated; due to institutional inertia, incumbency and lack of capacity and agility of existing organizations to respond effectively to changing conditions. In such situations clear and consistent external policy signals may be required to initiate and sustain the transformative change needed to meet the sustainability challenges of the 21st century.
The industrial revolution catapulted humanity onto an explosive development path, whereby, reliance on muscle power and traditional biomass was replaced mostly by fossil fuels. In 2005, some 78% of global energy was based on fossil energy sources that provided abundant and ever cheaper energy services to more than half the people in the world.
Technical Summary
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- By Thomas B. Johansson, Lund University, Nebojsa Nakicenovic, International Institute for Applied Systems Analysis and Vienna University of Technology, Anand Patwardhan, Indian Institute of Technology, Luis Gomez-Echeverri, International Institute for Applied Systems Analysis, Doug J. Arent, National Renewable Energy Laboratory, Rangan Banerjee, Indian Institute of Technology, Sally M. Benson, Stanford University, Daniel H. Bouille, Bariloche Foundation, Abeeku Brew-Hammond, Kwame Nkrumah University of Science and Technology, Aleh Cherp, Central European University, Suani T. Coelho, National Reference Center on Biomass, University of São Paulo, Lisa Emberson, Stockholm Environment Institute, University of York, Maria Josefina Figueroa, Technical University, Arnulf Grubler, International Institute for Applied Systems Analysis, Austria and Yale University, Kebin He, Tsinghua University, Mark Jaccard, Simon Fraser University, Suzana Kahn Ribeiro, Federal University of Rio de Janeiro, Stephen Karekezi, AFREPREN/FWD, Eric D. Larson, Princeton University and Climate Central, Zheng Li, Tsinghua University, Susan McDade, United Nations Development Programme, Lynn K. Mytelka, United Nations University-MERIT, Shonali Pachauri, International Institute for Applied Systems Analysis, Keywan Riahi, International Institute for Applied Systems Analysis, Johan Rockström, Stockholm Environment Institute, Stockholm University, Hans-Holger Rogner, International Atomic Energy Agency, Joyashree Roy, Jadavpur University, Robert N. Schock, World Energy Council, UK and Center for Global Security Research, Ralph Sims, Massey University, Kirk R. Smith, University of California, Wim C. Turkenburg, Utrecht University, Diana Ürge-Vorsatz, Central European University, Frank von Hippel, Princeton University, Kurt Yeager, Electric Power Research Institute and Galvin Electricity Initiative
- Global Energy Assessment Writing Team
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- Book:
- Global Energy Assessment
- Published online:
- 05 September 2012
- Print publication:
- 27 August 2012, pp 31-94
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Summary
Introduction
Energy is essential for human development and energy systems are a crucial entry point for addressing the most pressing global challenges of the 21st century, including sustainable economic, and social development, poverty eradication, adequate food production and food security, health for all, climate protection, conservation of ecosystems, peace, and security. Yet, more than a decade into the 21st century, current energy systems do not meet these challenges.
In this context, two considerations are important. The first is the capacity and agility of the players within the energy system to seize opportunities in response to these challenges. The second is the response capacity of the energy system itself, as the investments are long-term and tend to follow standard financial patterns, mainly avoiding risks and price instabilities. This traditional approach does not embrace the transformation needed to respond properly to the economic, environmental, and social sustainability challenges of the 21st century.
A major transformation is required to address these challenges and to avoid potentially catastrophic consequences for human and planetary systems. The GEA identifies strategies that could help resolve the multiple challenges simultaneously and bring multiple benefits. Their successful implementation requires determined, sustained, and immediate action.
The industrial revolution catapulted humanity onto an explosive development path, whereby reliance on muscle power and traditional biomass was replaced mostly by fossil fuels. In 2005, approximately 78% of global energy was based on fossil energy sources that provided abundant and ever cheaper energy services to more than half the world's population.
Contributors
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- By Ashok Agarwal, Carrie Bedient, Nick Brook, Michelle Catenacci, Ying Cheong, Francisco Domínguez, Thomas Elliott, Sandro C. Esteves, Tommaso Falcone, Gabriel de la Fuente, Eugene Galdones, Juan A. Garcia-Velasco, David K. Gardner, Tamara Garrido, Robert B. Gilchrist, Georg Griesinger, Roy Homburg, Jeanine Cieslak Janzen, Mark T. Johnson, Jennifer Kahn, David L. Keefe, Efstratios M Kolibianakis, Laurie J. McKenzie, Nick Macklon, David Meldrum, Ashley R. Mott, Tetsunori Mukaida, Zsolt Peter Nagy, Edurne Novella-Maestre, Chris O’Neill, Chikaharo Oka, Steven F. Palta, Lewis K. Pannell, Antonio Pellicer, Valeria Pugni, Botros R. M. B. Rizk, Christopher B. Rizk, Claude Robert, Denny Sakkas, Hassan N. Sallam, William B. Schoolcraft, Lonnie D. Shea, Carlos Simón, Manuela Simoni, Marc-Andre Sirard, Johan E. J. Smitz, Eric S. Surrey, Jan Tesarik, Raquel Mendoza Tesarik, Jeremy G. Thompson, Andrew J. Watson, Teresa K. Woodruff
- Edited by David K. Gardner, University of Melbourne, Botros R. M. B. Rizk, University of South Alabama, Tommaso Falcone
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- Book:
- Human Assisted Reproductive Technology
- Published online:
- 16 May 2011
- Print publication:
- 31 March 2011, pp ix-xii
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How Americans Responded: A Study of Public Reactions to 9/11/01
- Michael Traugott, Ted Brader, Deborah Coral, Richard Curtin, David Featherman, Robert Groves, Martha Hill, James Jackson, Thomas Juster, Robert Kahn, Courtney Kennedy, Donald Kinder, Beth-Ellen Pennell, Matthew Shapiro, Mark Tessler, David Weir, Robert Willis
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- Journal:
- PS: Political Science & Politics / Volume 35 / Issue 3 / September 2002
- Published online by Cambridge University Press:
- 11 September 2002, pp. 511-516
- Print publication:
- September 2002
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On the afternoon of Tuesday, September 11, 2001, a group of social scientists at the Institute for Social Research (ISR) gathered to consider how they might employ their talents to help the country after the shocking events of that morning. The group included economists, political scientists, psychologists, sociologists, demographers, and survey methodologists. Based upon their previous research experience, each of them proposed hypotheses on aspects of American life and individuals' morale and behavior that were most likely to be affected. While they were relatively confident about expected relationships in the short term, we were uncertain about how temporary or permanent these changes might be or how intertwined and mutually reinforcing they could become.
8 - Platelet receptors for thrombin
- from PART I - PHYSIOLOGY
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- By Lawrence F. Brass, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA, Marina Molino, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy, Peter J. O'Brien, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA, Mark Kahn, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA
- Edited by Paolo Gresele, Università degli Studi di Perugia, Italy, Clive P. Page, Valentin Fuster, Jos Vermylen, Universiteitsbibliotheek-K.U., Leuven
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- Book:
- Platelets in Thrombotic and Non-Thrombotic Disorders
- Published online:
- 10 May 2010
- Print publication:
- 30 May 2002, pp 113-126
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Summary
Introduction
Thrombin is one of the most potent agonists that platelets will encounter in vivo, but unlike most of the others it is a protease. For years after thrombin was shown to be a platelet activator as well as an effector in the clotting cascade, the precise mechanism by which it activates platelets remained obscure. Binding studies demonstrated high affinity interactions with several sites on the platelet surface, including glycoprotein (GP) Ibα, but efforts to establish that any of these constituted a receptor in the signalling sense were not entirely successful. Substrates on the platelet surface for proteolytic cleavage by thrombin were also identified, including GP V, but cleavage of these sites did not appear to be required for platelet activation by thrombin. Before discussing the receptors that have been identified, it is worth considering what some of the criteria might be for establishing a protein as a true signalling receptor for thrombin. Such criteria would include (i) demonstrating its presence on the platelet surface, (ii) showing that it was a substrate for thrombin or closely associated with a substrate for thrombin, (iii) demonstrating an association of the candidate receptor with mediators or effectors for intracellular signalling cascades, (iv) showing that expression of the candidate receptor could render a cell that was otherwise unresponsive to thrombin capable of responding, and (v) showing that blocking, dismantling or otherwise removing the candidate receptor would reduce platelet responses to thrombin.