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Patterns, predictors, and patient-reported reasons for antidepressant discontinuation in the WHO World Mental Health Surveys
- Alan E. Kazdin, Meredith G. Harris, Irving Hwang, Nancy A. Sampson, Dan J. Stein, Maria Carmen Viana, Daniel V. Vigo, Chi-Shin Wu, Sergio Aguilar-Gaxiola, Jordi Alonso, Corina Benjet, Ronny Bruffaerts, José Miguel Caldas-Almeida, Graça Cardoso, Elisa Caselani, Stephanie Chardoul, Alfredo Cía, Peter de Jonge, Oye Gureje, Josep Maria Haro, Elie G. Karam, Viviane Kovess-Masfety, Fernando Navarro-Mateu, Marina Piazza, José Posada-Villa, Kate M. Scott, Juan Carlos Stagnaro, Margreet ten Have, Yolanda Torres, Cristian Vladescu, Ronald C. Kessler
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- Journal:
- Psychological Medicine / Volume 54 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 14 September 2023, pp. 67-78
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Background
Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation.
MethodsFace-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months.
Results10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation.
ConclusionDropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.
Description of antibiotic use variability among US nursing homes using electronic health record data
- Sarah Kabbani, Stanley W. Wang, Laura L. Ditz, Katryna A. Gouin, Danielle Palms, Theresa A. Rowe, David Y. Hyun, Nancy W. Chi, Nimalie D. Stone, Lauri A. Hicks
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 1 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 07 December 2021, e58
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Background:
Antibiotics are frequently prescribed in nursing homes; national data describing facility-level antibiotic use are lacking. The objective of this analysis was to describe variability in antibiotic use in nursing homes across the United States using electronic health record orders.
Methods:A retrospective cohort study of antibiotic orders for 309,884 residents in 1,664 US nursing homes in 2016 were included in the analysis. Antibiotic use rates were calculated as antibiotic days of therapy (DOT) per 1,000 resident days and were compared by type of stay (short stay ≤100 days vs long stay >100 days). Prescribing indications and the duration of nursing home-initiated antibiotic orders were described. Facility-level correlations of antibiotic use, adjusting for resident health and facility characteristics, were assessed using multivariate linear regression models.
Results:In 2016, 54% of residents received at least 1 systemic antibiotic. The overall rate of antibiotic use was 88 DOT per 1,000 resident days. The 3 most common antibiotic classes prescribed were fluoroquinolones (18%), cephalosporins (18%), and urinary anti-infectives (9%). Antibiotics were most frequently prescribed for urinary tract infections, and the median duration of an antibiotic course was 7 days (interquartile range, 5–10). Higher facility antibiotic use rates correlated positively with higher proportions of short-stay residents, for-profit ownership, residents with low cognitive performance, and having at least 1 resident on a ventilator. Available facility-level characteristics only predicted a small proportion of variability observed (Model R2 version 0.24 software).
Conclusions:Using electronic health record orders, variability was found among US nursing-home antibiotic prescribing practices, highlighting potential opportunities for targeted improvement of prescribing practices.
Antidepressant use in low- middle- and high-income countries: a World Mental Health Surveys report
- Alan E. Kazdin, Chi-Shin Wu, Irving Hwang, Victor Puac-Polanco, Nancy A. Sampson, Ali Al-Hamzawi, Jordi Alonso, Laura Helena Andrade, Corina Benjet, José-Miguel Caldas-de-Almeida, Giovanni de Girolamo, Peter de Jonge, Silvia Florescu, Oye Gureje, Josep M. Haro, Meredith G. Harris, Elie G. Karam, Georges Karam, Viviane Kovess-Masfety, Sing Lee, John J. McGrath, Fernando Navarro-Mateu, Daisuke Nishi, Bibilola D. Oladeji, José Posada-Villa, Dan J. Stein, T. Bedirhan Üstün, Daniel V. Vigo, Zahari Zarkov, Alan M. Zaslavsky, Ronald C. Kessler, the WHO World Mental Health Survey collaborators
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- Journal:
- Psychological Medicine / Volume 53 / Issue 4 / March 2023
- Published online by Cambridge University Press:
- 23 September 2021, pp. 1583-1591
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Background
The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.
MethodsFace-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.
Results3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.
ConclusionADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.
Evaluation of Electronic Health Record and Long-Term Care Pharmacy Data for Tracking and Reporting Antibiotic Use in the United States
- Matthew Hudson, Katryna Gouin, Stanley Wang, Manjiri Kulkarni, Mary Beckerson, Laura Ditz, Stephen Creasy, Marti Wdowicki, Nancy Chi, Lauri Hicks, Sarah Kabbani
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 1 / Issue S1 / July 2021
- Published online by Cambridge University Press:
- 29 July 2021, pp. s13-s14
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Background: Antibiotics are frequently prescribed in nursing homes, often inappropriately. Data sources are needed to facilitate measurement and reporting of antibiotic use to inform antibiotic stewardship efforts. Previous analyses have shown that the type of nursing-home stay, that is, short stay (<100 days), is a strong predictor of high antibiotic use compared to longer nursing-home stays. The study objective was to compare 2 different data sources, electronic health record (EHR) and long-term care (LTC) pharmacy data, for surveillance of antibiotic use and type of nursing-home stay. Methods: EHR and pharmacy data during 2017 were included from 1,933 and 1,348 US-based nursing homes, respectively. We compared data elements available in each data source for antibiotic use reporting. In each data set, we attempted to describe antibiotic use as the proportion of residents on an antibiotic, days-of-therapy (DOT) per 1,000 resident days (RD), and distribution of antibiotic course duration, overall and at the facility level. Facility proportion of short-stay and long-stay (>100 days) nursing-home residents were calculated using admission dates and census data in the EHR data set and a payor variable in the pharmacy data set (Figure 1). The 2 data sources also provided antibiotic characteristics, including antibiotic class, agent, and route of administration. The deidentified nature of facility data prevented direct comparison of antibiotic use measures between facilities. Results: The EHR and pharmacy data sets contained 381,382 and 326,713 residents, respectively (Table 1). Within the EHR, 51% of residents were prescribed an antibiotic in 2017, at a median rate of 77 DOT per 1,000 RD. In the LTC pharmacy, 46% of residents were prescribed an antibiotic at a median rate of 79 DOT per 1,000 RD (Table 1). Short-stay residents contributed a smaller proportion of total RDs in the EHR relative to the pharmacy cohort (21% vs 50%, respectively). Conclusions: Nursing-home antibiotic use data obtained from EHR and pharmacy vendors can be used for calculating antibiotic use measures, which is important for antibiotic use reporting and facility-level tracking to identify opportunities for improving prescribing practices and provide facility-level benchmarks. Further validation of both data sources in the same facilities is needed to compare antibiotic use rates and to determine the most appropriate proxy for type of nursing-home stay for facility-level risk adjustment of antibiotic use rates.
Funding: No
Disclosures: None
Figure 1.
Table 1.
Toward measuring effective treatment coverage: critical bottlenecks in quality- and user-adjusted coverage for major depressive disorder
- Daniel Vigo, Josep Maria Haro, Irving Hwang, Sergio Aguilar-Gaxiola, Jordi Alonso, Guilherme Borges, Ronny Bruffaerts, Jose Miguel Caldas-de-Almeida, Giovanni de Girolamo, Silvia Florescu, Oye Gureje, Elie Karam, Georges Karam, Viviane Kovess-Masfety, Sing Lee, Fernando Navarro-Mateu, Akin Ojagbemi, Jose Posada-Villa, Nancy A. Sampson, Kate Scott, Juan Carlos Stagnaro, Margreet ten Have, Maria Carmen Viana, Chi-Shin Wu, Somnath Chatterji, Pim Cuijpers, Graham Thornicroft, Ronald C. Kessler
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- Journal:
- Psychological Medicine / Volume 52 / Issue 10 / July 2022
- Published online by Cambridge University Press:
- 20 October 2020, pp. 1948-1958
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Background
Major depressive disorder (MDD) is a leading cause of morbidity and mortality. Shortfalls in treatment quantity and quality are well-established, but the specific gaps in pharmacotherapy and psychotherapy are poorly understood. This paper analyzes the gap in treatment coverage for MDD and identifies critical bottlenecks.
MethodsSeventeen surveys were conducted across 15 countries by the World Health Organization-World Mental Health Surveys Initiative. Of 35 012 respondents, 3341 met DSM-IV criteria for 12-month MDD. The following components of effective treatment coverage were analyzed: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) adequate severity-specific combination of both.
ResultsMDD prevalence was 4.8% (s.e., 0.2). A total of 41.8% (s.e., 1.1) received any mental health services, 23.2% (s.e., 1.5) of which was deemed effective. This 90% gap in effective treatment is due to lack of utilization (58%) and inadequate quality or adherence (32%). Critical bottlenecks are underutilization of psychotherapy (26 percentage-points reduction in coverage), underutilization of psychopharmacology (13-point reduction), inadequate physician monitoring (13-point reduction), and inadequate drug-type (10-point reduction). High-income countries double low-income countries in any mental health service utilization, adequate pharmacotherapy, adequate psychotherapy, and adequate combination of both. Severe cases are more likely than mild-moderate cases to receive either adequate pharmacotherapy or psychotherapy, but less likely to receive an adequate combination.
ConclusionsDecision-makers need to increase the utilization and quality of pharmacotherapy and psychotherapy. Innovations such as telehealth for training and supervision plus non-specialist or community resources to deliver pharmacotherapy and psychotherapy could address these bottlenecks.
Integrating Novel Microscopy into Battery Research: From Atomic Resolution to In Situ and Functional Imaging
- Miaofang Chi, Cheng Ma, Andy Lupini, Karren More, Cewen Nan, Jeff Sakamoto, Nancy Dudney
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- Journal:
- Microscopy and Microanalysis / Volume 23 / Issue S1 / July 2017
- Published online by Cambridge University Press:
- 04 August 2017, pp. 1998-1999
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- July 2017
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A “Hidden” Mesoscopic Feature Revealed By Electron Microscopy Could Facilitate Ion Transport In Solid Electrolytes
- Cheng Ma, Yongqiang Cheng, Ce-Wen Nan, Nancy Dudney, Karren L. More, Miaofang Chi
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- Journal:
- Microscopy and Microanalysis / Volume 22 / Issue S3 / July 2016
- Published online by Cambridge University Press:
- 25 July 2016, pp. 1308-1309
- Print publication:
- July 2016
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- By Michael Harris Bond, Xinyin Chen, Dov Cohen, Ella Daniel, Nancy Eisenberg, Doran C. French, Sigal Gabay, Pehr Granqvist, Aisha Griffith, Jessica Halliday Hardie, Lene Arnett Jensen, Hyeyoung Kang, Ariel Knafo, Hans-Joachim Kornadt, Reed W. Larson, Liman Man Wai Li, Junsheng Liu, Vivian Miu-Chi Lun, Sami Mahajna, Tina Malti, Boris Mayer, Kristina McDonald, Ramesh Chandra Mishra, Bernhard Nauck, Vinai Norasakkunkit, Lisa D. Pearce, Urip Purwono, Vikki Rompala, Fred Rothbaum, Kenneth H. Rubin, Julie A. Sallquist, Vassilis Saroglou, Shalom H. Schwartz, Rachel Seginer, Rivka Shir, Anja Steinbach, Gisela Trommsdorff, Yukiko Uchida, Li Wang, Yan Z. Wang, Ran Zilber
- Edited by Gisela Trommsdorff, Universität Konstanz, Germany, Xinyin Chen, University of Pennsylvania
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- Values, Religion, and Culture in Adolescent Development
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- 05 September 2012
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- 27 August 2012, pp xiii-xxiv
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Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys
- Ronald C. Kessler, Katie A. McLaughlin, Jennifer Greif Green, Michael J. Gruber, Nancy A. Sampson, Alan M. Zaslavsky, Sergio Aguilar-Gaxiola, Ali Obaid Alhamzawi, Jordi Alonso, Matthias Angermeyer, Corina Benjet, Evelyn Bromet, Somnath Chatterji, Giovanni de Girolamo, Koen Demyttenaere, John Fayyad, Silvia Florescu, Gilad Gal, Oye Gureje, Josep Maria Haro, Chi-yi Hu, Elie G. Karam, Norito Kawakami, Sing Lee, Jean-Pierre Lépine, Johan Ormel, José Posada-Villa, Rajesh Sagar, Adley Tsang, T. Bedirhan Üstün, Svetlozar Vassilev, Maria Carmen Viana, David R. Williams
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- Journal:
- The British Journal of Psychiatry / Volume 197 / Issue 5 / November 2010
- Published online by Cambridge University Press:
- 02 January 2018, pp. 378-385
- Print publication:
- November 2010
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Background
Although significant associations of childhood adversities with adult mental disorders are widely documented, most studies focus on single childhood adversities predicting single disorders.
AimsTo examine joint associations of 12 childhood adversities with first onset of 20 DSM–IV disorders in World Mental Health (WMH) Surveys in 21 countries.
MethodNationally or regionally representative surveys of 51 945 adults assessed childhood adversities and lifetime DSM–IV disorders with the WHO Composite International Diagnostic Interview (CIDI).
ResultsChildhood adversities were highly prevalent and interrelated. Childhood adversities associated with maladaptive family functioning (e.g. parental mental illness, child abuse, neglect) were the strongest predictors of disorders. Co-occurring childhood adversities associated with maladaptive family functioning had significant subadditive predictive associations and little specificity across disorders. Childhood adversities account for 29.8% of all disorders across countries.
ConclusionsChildhood adversities have strong associations with all classes of disorders at all life-course stages in all groups of WMH countries. Long-term associations imply the existence of as-yet undetermined mediators.
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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. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. Douglas Meeks, Monica Jyotsna Melanchthon, Ilie Melniciuc-Puica, Everett Mendoza, Raymond A. Mentzer, William W. Menzies, Ina Merdjanova, Franziska Metzger, Constant J. Mews, Marvin Meyer, Carol Meyers, Vasile Mihoc, Gunner Bjerg Mikkelsen, Maria Inêz de Castro Millen, Clyde Lee Miller, Bonnie J. Miller-McLemore, Alexander Mirkovic, Paul Misner, Nozomu Miyahira, R. W. L. Moberly, Gerald Moede, Aloo Osotsi Mojola, Sunanda Mongia, Rebeca Montemayor, James Moore, Roger E. Moore, Craig E. Morrison O.Carm, Jeffry H. Morrison, Keith Morrison, Wilson J. Moses, Tefetso Henry Mothibe, Mokgethi Motlhabi, Fulata Moyo, Henry Mugabe, Jesse Ndwiga Kanyua Mugambi, Peggy Mulambya-Kabonde, Robert Bruce Mullin, Pamela Mullins Reaves, Saskia Murk Jansen, Heleen L. Murre-Van den Berg, Augustine Musopole, Isaac M. T. Mwase, Philomena Mwaura, Cecilia Nahnfeldt, Anne Nasimiyu Wasike, Carmiña Navia Velasco, Thulani Ndlazi, Alexander Negrov, James B. Nelson, David G. Newcombe, Carol Newsom, Helen J. Nicholson, George W. E. Nickelsburg, Tatyana Nikolskaya, Damayanthi M. A. Niles, Bertil Nilsson, Nyambura Njoroge, Fidelis Nkomazana, Mary Beth Norton, Christian Nottmeier, Sonene Nyawo, Anthère Nzabatsinda, Edward T. Oakes, Gerald O'Collins, Daniel O'Connell, David W. Odell-Scott, Mercy Amba Oduyoye, Kathleen O'Grady, Oyeronke Olajubu, Thomas O'Loughlin, Dennis T. Olson, J. Steven O'Malley, Cephas N. Omenyo, Muriel Orevillo-Montenegro, César Augusto Ornellas Ramos, Agbonkhianmeghe E. Orobator, Kenan B. Osborne, Carolyn Osiek, Javier Otaola Montagne, Douglas F. Ottati, Anna May Say Pa, Irina Paert, Jerry G. Pankhurst, Aristotle Papanikolaou, Samuele F. Pardini, Stefano Parenti, Peter Paris, Sung Bae Park, Cristián G. Parker, Raquel Pastor, Joseph Pathrapankal, Daniel Patte, W. Brown Patterson, Clive Pearson, Keith F. Pecklers, Nancy Cardoso Pereira, David Horace Perkins, Pheme Perkins, Edward N. Peters, Rebecca Todd Peters, Bishop Yeznik Petrossian, Raymond Pfister, Peter C. 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Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- Book:
- The Cambridge Dictionary of Christianity
- Published online:
- 05 August 2012
- Print publication:
- 20 September 2010, pp xi-xliv
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33 - High-throughput RNA interference
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- By Howard Y. Chang, Departments of Biochemistry and Dermatology, Stanford University School of Medicine, Nancy N. Wang, Departments of Biochemistry and Dermatology, Stanford University School of Medicine, Jen-Tsan Chi, Departments of Biochemistry and Dermatology, Stanford University School of Medicine
- Edited by Krishnarao Appasani, GeneExpression Systems, Inc., Massachusetts
- Foreword by Andrew Fire, Stanford University, California, Marshall Nirenberg
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- Book:
- RNA Interference Technology
- Published online:
- 31 July 2009
- Print publication:
- 17 January 2005, pp 470-479
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Summary
Introduction
RNA interference (RNAi) is an evolutionarily conserved pathway of gene silencing that identifies and destroys mRNA sequences derived from selfish repetitive or viral sequences. The mechanisms and physiologic functions of RNAi pathways are discussed in Section 1. Because RNAi can be triggered by exogenously supplied double-stranded RNA (dsRNA) molecules, in principle one can effectively silence the expression of a gene and infer its physiologic function given its sequence. RNAi analysis on a genome-wide scale is a versatile and powerful tool that holds great promise in functional annotation of the human genome and in acceleration of drug target discovery and validation. The rapid advances to date have illustrated that high-throughput RNAi can complement genetic studies in traditional model organisms to extend our understanding and probe the mechanisms of well-studied pathways. In this chapter, we will focus on emerging methodologies and issues surrounding high-throughput RNAi in mammalian systems, and highlight the potential advances and pitfalls with these new technologies.
Generation of genome-wide RNAi reagents
In order to silence each gene in the genome using RNAi, the first step is to create the appropriate library of dsRNA reagents. In Caenorhabditis elegans and Drosophila melanogaster, long segments of dsRNA are readily taken up by the animal or tissue culture cells, respectively, and genome-wide RNAi libraries can be constructed by annealing complementary RNAs synthesized from both strands of the same cDNA.