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Well-being tradeoffs: Effect of loosening overnight restrictions on antimicrobial starts
- Michael E. Yarrington, Rebekah H. Wrenn, Justin Spivey, Christopher J. Shoff, Eileen K. Maziarz, S. Shaefer Spires, Nicholas A. Turner, Anthony Diez, Deverick J. Anderson, Rebekah W. Moehring
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 43 / Issue 2 / February 2022
- Published online by Cambridge University Press:
- 16 August 2021, pp. 255-257
- Print publication:
- February 2022
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Health Care for Mitochondrial Disorders in Canada: A Survey of Physicians
- Karen Paik, Matthew A. Lines, Pranesh Chakraborty, Sara D. Khangura, Maureen Latocki, Walla Al-Hertani, Catherine Brunel-Guitton, Aneal Khan, Blaine Penny, Cheryl Rockman-Greenberg, C. Anthony Rupar, Neal Sondheimer, Mark Tarnopolsky, Kylie Tingley, Doug Coyle, Sarah Dyack, Annette Feigenbaum, Michael T. Geraghty, Jane Gillis, Clara D. M. van Karnebeek, Jonathan B. Kronick, Julian Little, Murray Potter, Komudi Siriwardena, Rebecca Sparkes, Lesley A. Turner, Kumanan Wilson, Daniela Buhas, Beth K. Potter, in collaboration with the Canadian Inherited Metabolic Diseases Research Network
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 46 / Issue 6 / November 2019
- Published online by Cambridge University Press:
- 07 August 2019, pp. 717-726
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Background:
An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
Methods:We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
Results:We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
Conclusions:While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
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 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 E. Selzer, Stephanie Clarke, Leonardo G. Cohen, Gert Kwakkel, Robert H. Miller, Case Western Reserve University, Ohio
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- Book:
- Textbook of Neural Repair and Rehabilitation
- Published online:
- 05 June 2014
- Print publication:
- 24 April 2014, pp ix-xvi
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- By Lenard A. Adler, Pinky Agarwal, Rehan Ahmed, Jagga Rao Alluri, Fawaz Al-Mufti, Samuel Alperin, Michael Amoashiy, Michael Andary, David J. Anschel, Padmaja Aradhya, Vandana Aspen, Esther Baldinger, Jee Bang, George D. Baquis, John J. Barry, Jason J. S. Barton, Julius Bazan, Amanda R. Bedford, Marlene Behrmann, Lourdes Bello-Espinosa, Ajay Berdia, Alan R. Berger, Mark Beyer, Don C. Bienfang, Kevin M. Biglan, Thomas M. Boes, Paul W. Brazis, Jonathan L. Brisman, Jeffrey A. Brown, Scott E. Brown, Ryan R. Byrne, Rina Caprarella, Casey A. Chamberlain, Wan-Tsu W. Chang, Grace M. Charles, Jasvinder Chawla, David Clark, Todd J. Cohen, Joe Colombo, Howard Crystal, Vladimir Dadashev, Sarita B. Dave, Jean Robert Desrouleaux, Richard L. Doty, Robert Duarte, Jeffrey S. Durmer, Christyn M. Edmundson, Eric R. Eggenberger, Steven Ender, Noam Epstein, Alberto J. Espay, Alan B. Ettinger, Niloofar (Nelly) Faghani, Amtul Farheen, Edward Firouztale, Rod Foroozan, Anne L. Foundas, David Elliot Friedman, Deborah I. Friedman, Steven J. Frucht, Oded Gerber, Tal Gilboa, Martin Gizzi, Teneille G. Gofton, Louis J. Goodrich, Malcolm H. Gottesman, Varda Gross-Tsur, Deepak Grover, David A. Gudis, John J. Halperin, Maxim D. Hammer, Andrew R. Harrison, L. Anne Hayman, Galen V. Henderson, Steven Herskovitz, Caitlin Hoffman, Laryssa A. Huryn, Andres M. Kanner, Gary P. Kaplan, Bashar Katirji, Kenneth R. Kaufman, Annie Killoran, Nina Kirz, Gad E. Klein, Danielle G. Koby, Christopher P. Kogut, W. Curt LaFrance, Patrick J.M. Lavin, Susan W. Law, James L. Levenson, Richard B. Lipton, Glenn Lopate, Daniel J. Luciano, Reema Maindiratta, Robert M. Mallery, Georgios Manousakis, Alan Mazurek, Luis J. Mejico, Dragana Micic, Ali Mokhtarzadeh, Walter J. Molofsky, Heather E. Moss, Mark L. Moster, Manpreet Multani, Siddhartha Nadkarni, George C. Newman, Rolla Nuoman, Paul A. Nyquist, Gaia Donata Oggioni, Odi Oguh, Denis Ostrovskiy, Kristina Y. Pao, Juwen Park, Anastas F. Pass, Victoria S. Pelak, Jeffrey Peterson, John Pile-Spellman, Misha L. Pless, Gregory M. Pontone, Aparna M. Prabhu, Michael T. Pulley, Philip Ragone, Prajwal Rajappa, Venkat Ramani, Sindhu Ramchandren, Ritesh A. Ramdhani, Ramses Ribot, Heidi D. Riney, Diana Rojas-Soto, Michael Ronthal, Daniel M. Rosenbaum, David B. Rosenfield, Durga Roy, Michael J. Ruckenstein, Max C. Rudansky, Eva Sahay, Friedhelm Sandbrink, Jade S. Schiffman, Angela Scicutella, Maroun T. Semaan, Robert C. Sergott, Aashit K. Shah, David M. Shaw, Amit M. Shelat, Claire A. Sheldon, Anant M. Shenoy, Yelizaveta Sher, Jessica A. Shields, Tanya Simuni, Rajpaul Singh, Eric E. Smouha, David Solomon, Mehri Songhorian, Steven A. Sparr, Egilius L. H. Spierings, Eve G. Spratt, Beth Stein, S.H. Subramony, Rosa Ana Tang, Cara Tannenbaum, Hakan Tekeli, Amanda J. Thompson, Michael J. Thorpy, Matthew J. Thurtell, Pedro J. Torrico, Ira M. Turner, Scott Uretsky, Ruth H. Walker, Deborah M. Weisbrot, Michael A. Williams, Jacques Winter, Randall J. Wright, Jay Elliot Yasen, Shicong Ye, G. Bryan Young, Huiying Yu, Ryan J. Zehnder
- Edited by Alan B. Ettinger, Albert Einstein College of Medicine, New York, Deborah M. Weisbrot, State University of New York, Stony Brook
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- Book:
- Neurologic Differential Diagnosis
- Published online:
- 05 June 2014
- Print publication:
- 17 April 2014, pp xi-xx
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- By Bjarne F. Alsbjoern, Caroline M. Apovian, Danny Collins, Roland N. Dickerson, Timothy Eden, Peter Faber, Andrew J. Ferguson, David C. Frankenfield, Dympna Gallagher, Maria Gabriella Gentile, Wilson I. Gonsalves, Andrew M. Hetreed, Michael H. Hooper, Jan O. Jansen, Aminah Jatoi, Ying Ji, Ilya Kagan, Andrew J. Kerwin, Dong Wook Kim, Andrew A. Klein, Alistair Lee, Shaul Lev, Peter K. Linden, Paul E. Marik, Robert Martindale, Peter McCanny, Paolo Merlani, Shay Nanthakumaran, Michael S. Nussbaum, Andreas Perren, Carla Prado, Jean-Charles Preiser, Minha Rajput-Ray, Sumantra Ray, Nils Siegenthaler, Mario Siervo, Jonathan A. Silversides, Pierre Singer, John A. Tayek, Euan Thomson, Krista L. Turner, Malissa Warren, Stephen T. Webb, Patricia Wiesen
- Edited by Peter Faber, Mario Siervo, University of Newcastle upon Tyne
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- Book:
- Nutrition in Critical Care
- Published online:
- 05 April 2014
- Print publication:
- 06 March 2014, pp viii-xii
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5 - Revivalism and Preaching
- from Part II - The Religious Culture of American Methodism
- Edited by Jason E. Vickers, United Theological Seminary, Ohio
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- The Cambridge Companion to American Methodism
- Published online:
- 18 December 2013
- Print publication:
- 07 October 2013, pp 119-137
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- By Christopher J. Anderson, Candy Gunther Brown, Ted A. Campbell, Morris L. Davis, Wendy J. Deichmann, Dennis C. Dickerson, Maura Jane Farrelly, E. Brooks Holifield, Stan Ingersol, Douglas M. Koskela, Russell E. Richey, Douglas M. Strong, Michael K. Turner, Jason E. Vickers, Laceye C. Warner, Karen B. Westerfield Tucker, Andrew J. Wood, Jennifer L. Woodruff Tait
- Edited by Jason E. Vickers, United Theological Seminary, Ohio
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- Book:
- The Cambridge Companion to American Methodism
- Published online:
- 18 December 2013
- Print publication:
- 07 October 2013, pp xi-xiv
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- By Lassi Alvesalo, Alberto Anta, Juan Luis Arsuaga, Shara E. Bailey, Priscilla Bayle, José María Bermúdez de Castro, Tracy K. Betsinger, Luca Bondioli, Scott E. Burnett, Concepcion de la Rúa, William N. Duncan, Ryan M. Durner, Heather J.H. Edgar, Scott M. Fitzpatrick, Michael R. Fong, Ana Gracia-Téllez, Theresa M. Grieco, Debbie Guatelli-Steinberg, Tsunehiko Hanihara, Brian E. Hemphill, Leslea J. Hlusko, Michael W. Holmes, Jean-Jacques Hublin, Toby E. Hughes, John P. Hunter, Joel D. Irish, Kent M. Johnson, Sri Kuswandari, Christine Lee, John R. Lukacs, Roberto Macchiarelli, Laura Martín-Francés, Ignacio Martínez, María Martinón-Torres, Arnaud Mazurier, Yuji Mizoguchi, Stephanie Moormann, Greg C. Nelson, Stephen D. Ousley, Oliver T. Rizk, G. Richard Scott, Roman Schomberg, Kes Schroer, Christopher M. Stojanowski, Grant C. Townsend, Christy G. Turner, Theresia C. Weston, Bernard Wood, Clément Zanolli, Linhu Zhang
- Edited by G. Richard Scott, University of Alaska, Fairbanks, Joel D. Irish, Liverpool John Moores University
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- Book:
- Anthropological Perspectives on Tooth Morphology
- Published online:
- 05 March 2013
- Print publication:
- 21 February 2013, pp viii-xi
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- By Basem Abdelmalak, Joseph Abdelmalak, Alaa A. Abd-Elsayed, David L. Adams, Eric E. Adelman, Maged Argalious, Endrit Bala, Gene H. Barnett, Sheron Beltran, Andrew Bielaczyc, William Bingaman, James M. Blum, Alina Bodas, Vera Borzova, Richard Bowers, Adam Brown, Chad M. Brummett, Alexandra S. Bullough, James F. Burke, Juan P. Cata, Neeraj Chaudhary, Michael J. Claybon, Miguel Cruz, Milind Deogaonkar, Vikram Dhawan, Thomas Didier, D. John Doyle, Zeyd Ebrahim, Hesham Elsharkawy, Wael Ali Sakr Esa, Ehab Farag, Ryen D. Fons, Joseph J. Gemmete, Matt Giles, Phil Gillen, Goodarz Golmirzaie, Marcos Gomes, Lisa Grilly, Maged Guirguis, David W. Healy, Heather Hervey-Jumper, Shawn L. Hervey-Jumper, Paul E. Hilliard, Samuel A. Irefin, George K. Istaphanous, Teresa L. Jacobs, Ellen Janke, Greta Jo, James W. Jones, Rami Karroum, Allen Keebler, Stephen J. Kimatian, Colleen G. Koch, Robert Scott Kriss, Andrea Kurz, Jia Lin, Michael D. Maile, Negmeldeen F. Mamoun, Mariel Manlapaz, Edward Manno, Donn Marciniak, Piyush Mathur, Nicholas F. Marko, Matthew Martin, George A. Mashour, Marco Maurtua, Scott T. McCardle, Julie McClelland, Uma Menon, Paul S. Moor, Laurel E. Moore, Ruairi Moulding, Dileep R. Nair, Todd Nelson, Julie Niezgoda, Edward Noguera, Jerome O’Hara, Aditya S. Pandey, Mauricio Perilla, Paul Picton, Marc J. Popovich, J. Javier Provencio, Venkatakrishna Rajajee, Mohit Rastogi, Stacy Ritzman, Lauryn R. Rochlen, Leif Saager, Vivek Sabharwal, Oren Sagher, Kenneth Saliba, Milad Sharifpour, Lesli E. Skolarus, Paul Smythe, Wolf H. Stapelfeldt, William R. Stetler, Peter Stiles, Vijay Tarnal, Khoi D. Than, B. Gregory Thompson, Alparslan Turan, Christopher R. Turner, Justin Upp, Sumeet Vadera, Jennifer Vance, Anthony C. Wang, Robert J. Weil, Marnie B. Welch, Karen K. Wilkins, Erin S. Williams, George N. Youssef, Asma Zakaria, Sherif S. Zaky, Andrew Zura
- Edited by George A. Mashour, Ehab Farag
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- Book:
- Case Studies in Neuroanesthesia and Neurocritical Care
- Published online:
- 03 May 2011
- Print publication:
- 03 February 2011, pp x-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. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. 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Looking Backward, Looking Forward: MLA Members Speak
- April Alliston, Elizabeth Ammons, Jean Arnold, Nina Baym, Sandra L. Beckett, Peter G. Beidler, Roger A. Berger, Sandra Bermann, J.J. Wilson, Troy Boone, Alison Booth, Wayne C. Booth, James Phelan, Marie Borroff, Ihab Hassan, Ulrich Weisstein, Zack Bowen, Jill Campbell, Dan Campion, Jay Caplan, Maurice Charney, Beverly Lyon Clark, Robert A. Colby, Thomas C. Coleman III, Nicole Cooley, Richard Dellamora, Morris Dickstein, Terrell Dixon, Emory Elliott, Caryl Emerson, Ann W. Engar, Lars Engle, Kai Hammermeister, N. N. Feltes, Mary Anne Ferguson, Annie Finch, Shelley Fisher Fishkin, Jerry Aline Flieger, Norman Friedman, Rosemarie Garland-Thomson, Sandra M. Gilbert, Laurie Grobman, George Guida, Liselotte Gumpel, R. K. Gupta, Florence Howe, Cathy L. Jrade, Richard A. Kaye, Calhoun Winton, Murray Krieger, Robert Langbaum, Richard A. Lanham, Marilee Lindemann, Paul Michael Lützeler, Thomas J. Lynn, Juliet Flower MacCannell, Michelle A. Massé, Irving Massey, Georges May, Christian W. Hallstein, Gita May, Lucy McDiarmid, Ellen Messer-Davidow, Koritha Mitchell, Robin Smiles, Kenyatta Albeny, George Monteiro, Joel Myerson, Alan Nadel, Ashton Nichols, Jeffrey Nishimura, Neal Oxenhandler, David Palumbo-Liu, Vincent P. Pecora, David Porter, Nancy Potter, Ronald C. Rosbottom, Elias L. Rivers, Gerhard F. Strasser, J. L. Styan, Marianna De Marco Torgovnick, Gary Totten, David van Leer, Asha Varadharajan, Orrin N. C. Wang, Sharon Willis, Louise E. Wright, Donald A. Yates, Takayuki Yokota-Murakami, Richard E. Zeikowitz, Angelika Bammer, Dale Bauer, Karl Beckson, Betsy A. Bowen, Stacey Donohue, Sheila Emerson, Gwendolyn Audrey Foster, Jay L. Halio, Karl Kroeber, Terence Hawkes, William B. Hunter, Mary Jambus, Willard F. King, Nancy K. Miller, Jody Norton, Ann Pellegrini, S. P. Rosenbaum, Lorie Roth, Robert Scholes, Joanne Shattock, Rosemary T. VanArsdel, Alfred Bendixen, Alarma Kathleen Brown, Michael J. Kiskis, Debra A. Castillo, Rey Chow, John F. Crossen, Robert F. Fleissner, Regenia Gagnier, Nicholas Howe, M. Thomas Inge, Frank Mehring, Hyungji Park, Jahan Ramazani, Kenneth M. Roemer, Deborah D. Rogers, A. LaVonne Brown Ruoff, Regina M. Schwartz, John T. Shawcross, Brenda R. Silver, Andrew von Hendy, Virginia Wright Wexman, Britta Zangen, A. Owen Aldridge, Paula R. Backscheider, Roland Bartel, E. M. Forster, Milton Birnbaum, Jonathan Bishop, Crystal Downing, Frank H. Ellis, Roberto Forns-Broggi, James R. Giles, Mary E. Giles, Susan Blair Green, Madelyn Gutwirth, Constance B. Hieatt, Titi Adepitan, Edgar C. Knowlton, Jr., Emanuel Mussman, Sally Todd Nelson, Robert O. Preyer, David Diego Rodriguez, Guy Stern, James Thorpe, Robert J. Wilson, Rebecca S. Beal, Joyce Simutis, Betsy Bowden, Sara Cooper, Wheeler Winston Dixon, Tarek el Ariss, Richard Jewell, John W. Kronik, Wendy Martin, Stuart Y. McDougal, Hugo Méndez-Ramírez, Ivy Schweitzer, Armand E. Singer, G. Thomas Tanselle, Tom Bishop, Mary Ann Caws, Marcel Gutwirth, Christophe Ippolito, Lawrence D. Kritzman, James Longenbach, Tim McCracken, Wolfe S. Molitor, Diane Quantic, Gregory Rabassa, Ellen M. Tsagaris, Anthony C. Yu, Betty Jean Craige, Wendell V. Harris, J. Hillis Miller, Jesse G. Swan, Helene Zimmer-Loew, Peter Berek, James Chandler, Hanna K. Charney, Philip Cohen, Judith Fetterley, Herbert Lindenberger, Julia Reinhard Lupton, Maximillian E. Novak, Richard Ohmann, Marjorie Perloff, Mark Reynolds, James Sledd, Harriet Turner, Marie Umeh, Flavia Aloya, Regina Barreca, Konrad Bieber, Ellis Hanson, William J. Hyde, Holly A. Laird, David Leverenz, Allen Michie, J. Wesley Miller, Marvin Rosenberg, Daniel R. Schwarz, Elizabeth Welt Trahan, Jean Fagan Yellin
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Stafford Gorman Whittle Johnston
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Contents
- S. M. Roberts, University of Exeter, Nicholas J. Turner, University of Exeter, Andrew J. Willetts, University of Exeter, Michael K. Turner, University College London
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1 - An historical introduction to biocatalysis using enzymes and micro-organisms
- S. M. Roberts, University of Exeter, Nicholas J. Turner, University of Exeter, Andrew J. Willetts, University of Exeter, Michael K. Turner, University College London
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Summary
Background
Each year that passes sees increasing interest in the application of enzymes and micro-organisms as catalysts in organic chemistry. Well-received national reports on the potential growth of biotechnology, not to speak of numerous reviews of the topic of biotransformation itself, have described the advantages which biological catalysis can bring to complex organic syntheses. At this time it is indeed an exciting prospect for anyone who has a role to play in the development of this new technology. But occasionally a prospective participant, as well as a reviewer, ought to stand back and ask, Why has this explosion of interest happened now?
An answer to such a question often lies in the historical context from which technologies and their underlying science develop. This is a topic worthy of greater attention than it usually receives from practising scientists. A resort to scientific papers more than one or two decades old is frequently viewed as perverse, while to consult the scientific literature of the past century in search of a pertinent contemporary lesson is simply eccentric. Yet this old literature can be worth reading for the light it can shed on current research, quite apart from which, it is, more often than not, a pleasure to read.
The biochemistry of the late nineteenth century has an interesting connection with the manufacture of vitamin C. The basis of this process relied on the development of the concepts of fermentation and catalysis, but it emerged directly from a microbial oxidation described in a short paper written by Adrian Brown (1886a).
Preface
- S. M. Roberts, University of Exeter, Nicholas J. Turner, University of Exeter, Andrew J. Willetts, University of Exeter, Michael K. Turner, University College London
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Summary
Twenty years ago, only a handful of laboratories, some in industry and some in academia, were interested in using enzyme-catalysed reactions (biotransformations) in organic synthesis. At best those researchers were considered to be at the margin of mainstream synthetic organic chemistry; at worst they were considered to be downright odd.
In the 1980s there was an exponential increase in interest in the area of biotransformations. That worldwide increase in attention to this field of research can be assigned to several factors, including the perception and perseverance of the original researchers in the field, the increased availability of a wide variety of enzymes, and the realization that many families of enzymes will transform a wide range of unnatural compounds, as well as their natural substrates.
The utilization of enzymes in organic synthesis can be advantageous for several reasons:
Enzymes catalyse reactions under mild conditions with regard to temperature (ca. 37 °C), pressure (1 atm), and pH (ca. 7.0). The transformations are often remarkably energy-efficient when compared with the corresponding chemical processes.
Enzymes often promote highly chemoselective, regioselective, and stereoselective reactions, and being chiral catalysts, they are often able to generate optically active compounds. The increased awareness regarding the need to have optically pure compounds for such uses as Pharmaceuticals and agrichemicals (so as to avoid unnecessary toxicity and/or ecological damage) has been a significant driving force in the development and exploitation of non-natural enzyme-catalysed reactions.
[…]
4 - Useful intermediates and end-products obtained from biocatalysed oxidation and reduction reactions
- S. M. Roberts, University of Exeter, Nicholas J. Turner, University of Exeter, Andrew J. Willetts, University of Exeter, Michael K. Turner, University College London
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Summary
Introduction
As discussed in Chapter 1, there has been much interest, over many years, in oxidation and reduction reactions catalysed by micro-organisms. Processes for alcohol production and for the manufacture of vinegar and vitamin C have intrigued investigators for ages. Today there is great interest in discovering new whole-cell and isolated-enzyme-catalysed reactions of this type. As described in Chapter 3, the focus of the presentday work in this area is the production of compounds (often in optically active form) that might be useful as intermediates or end-products for the pharmaceutical, fragrance, flavour and agrichemical industries.
For many oxidation and reduction reactions it is often necessary to make a choice between using a whole-cell system or an isolated enzyme (with the requisite co-factors) for the biotransformation. In this area, factors that influence the choice often are much more complicated than those for hydrolysis reactions. The pros and cons of employing whole cells or partially purified oxidoreductase enzymes have been discussed in Chapter 2, and the salient features are summarized in Table 2.3. While the advantages and disadvantages will not be discussed in detail again, many of the points made earlier will recur in this discussion.
Reduction of ketones using whole cells
For example, consider one of the simplest reduction processes, namely the reduction of a ketone to a secondary alcohol. Of course, this can be accomplished chemically using sodium borohydride.
6 - The application of biocatalysis to the manufacture of fine chemicals
- S. M. Roberts, University of Exeter, Nicholas J. Turner, University of Exeter, Andrew J. Willetts, University of Exeter, Michael K. Turner, University College London
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Introduction
Biological catalysis has such a pervasive influence on the industries which are closely associated with our daily lives that it is difficult to contain a short review within sensible bounds. The traditional large-scale crafts associated with agriculture, the manufacture of foods and drinks, and the preparation and cleaning of fabrics all use biological catalysis. At the other extreme, biological catalysis has an important role to play in analytical chemistry. Enzymes are used to monitor the levels of metabolites as an important feature in the diagnosis and therapy of disease. These techniques have been extended to the use of enzymes to amplify the responses in antibodybased assays, as well as to mediate the detection of an environmental pollutant at an electrode. The same catalysts also play a role in the degradation of pollutants, which is, perhaps, simply an extension of the role of biochemistry applied to the traditional craft of cleaning.
However, it is the use of enzymes in the large-scale manufacture of synthetic organic chemicals which is the main topic of this chapter. The recent interest amongst organic chemists arises from the high degrees of specificity and selectivity that characterize enzyme catalysis. That this is a valuable resource in manufacture cannot be doubted, as judged by the value of the products which it produces. Nevertheless, the methodology should not be oversold. Biocatalysis has a part to play in the modern chemical industry, but it also has limits which it is necessary to understand.
Frontmatter
- S. M. Roberts, University of Exeter, Nicholas J. Turner, University of Exeter, Andrew J. Willetts, University of Exeter, Michael K. Turner, University College London
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5 - Useful intermediates and end-products obtained from biocatalysed carbon–carbon, carbon–oxygen, carbonnitrogen and carbon–chalcogen bond-forming reactions
- S. M. Roberts, University of Exeter, Nicholas J. Turner, University of Exeter, Andrew J. Willetts, University of Exeter, Michael K. Turner, University College London
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Introduction
This chapter deals with three important classes of biotransformations. Firstly, those enzymes that catalyse the stereoselective formation of carbon-carbon bonds will be examined. These enzymes, whose natural functions often are to degrade carbohydrate-like molecules, have proved to be versatile catalysts for C—C bond synthesis. Secondly, we shall look at those enzymes that mediate the formation of C—X bonds, where X = O, N, S, Hal (halogen). These enzymes are termed lyases (see Table 2.1) and often carry out very simple reactions (e.g. the addition of water to a double bond) with very high stereoselectivity and regioselectivity. Finally, the application of a range of enzymes (including C—C bond formation) to carbohydrate synthesis will be examined. This chapter will conclude with some examples of the ways in which multienzyme reactions can be constructed to enable highly complex molecules to be assembled in an efficient manner.
Enzyme–catalysed asymmetric carbon–carbon bond formation
Aldolases
The synthesis of carbon–carbon bonds, particularly with control of stereochemistry, has been an area of intense activity in recent years. Much attention has been focussed on the asymmetric aldol reaction, principally using stoichiometric quantities of a chiral auxiliary, but more recently in the catalytic mode. The use of aldolases for the asymmetric construction of carbon-carbon bonds presents a potentially useful complementary methodology.
The aldolases are a diverse class of enzymes that catalyse the coupling of a carbonyl-containing compound (nucleophile), containing one, two or three carbons, with an aldehyde (electrophile). In most cases the nucleophile is either pyruvic acid or dihydroxyacetone phosphate, whereas the electrophilic aldehyde is much more variable in structure.