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A psychometric evaluation of the NIH Toolbox fluid cognition tests adapted for Swahili and Dholuo languages in Kenyan children and adolescents
- Megan S. McHenry, Anna Roose, Emily Abuonji, Mark Nyalumbe, David Ayuku, George Ayodo, Tuan M. Tran, Aaron J. Kaat
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue 10 / December 2023
- Published online by Cambridge University Press:
- 22 November 2023, pp. 933-942
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Objective:
Our objective was to evaluate the psychometric properties of the culturally adapted NIH Toolbox African Languages® when used in Swahili and Dholuo-speaking children in western Kenya.
Method:Swahili-speaking participants were recruited from Eldoret and Dholuo-speaking participants from Ajigo; all were <14 years of age and enrolled in primary school. Participants completed a demographics questionnaire and five fluid cognition tests of the NIH Toolbox® African Languages program, including Flanker, Dimensional Change Card Sort (DCCS), Picture Sequence Memory, Pattern Comparison, and List Sorting tests. Statistical analyses examined aspects of reliability, including internal consistency (in both languages) and test–retest reliability (in Dholuo only).
Results:Participants included 479 children (n = 239, Swahili-speaking; n = 240, Dholuo-speaking). Generally, the tests had acceptable psychometric properties for research use within Swahili- and Dholuo-speaking populations (mean age = 10.5; SD = 2.3). Issues related to shape identification and accuracy over speed limited the utility of DCCS for many participants, with approximately 25% of children unable to match based on shape. These cultural differences affected outcomes of reliability testing among the Dholuo-speaking cohort, where accuracy improved across all five tests, including speed.
Conclusions:There is preliminary evidence that the NIH Toolbox ® African Languages potentially offers a valid assessment of development and performance using tests of fluid cognition in Swahili and Dholuo among research settings. With piloting underway across other diverse settings, future research should gather additional evidence on the clinical utility and acceptability of these tests, specifically through the establishment of norming data among Kenyan regions and evaluating these psychometric properties.
The Rapid ASKAP Continuum Survey III: Spectra and Polarisation In Cutouts of Extragalactic Sources (SPICE-RACS) first data release
- Alec J. M. Thomson, David McConnell, Emil Lenc, Timothy J. Galvin, Lawrence Rudnick, George Heald, Catherine L. Hale, Stefan W. Duchesne, Craig S. Anderson, Ettore Carretti, Christoph Federrath, B. M. Gaensler, Lisa Harvey-Smith, Marijke Haverkorn, Aidan W. Hotan, Yik Ki Ma, Tara Murphy, N. M. McClure-Griffiths, Vanessa A. Moss, Shane P. O’Sullivan, Wasim Raja, Amit Seta, Cameron L. Van Eck, Jennifer L. West, Matthew T. Whiting, Mark H. Wieringa
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 40 / 2023
- Published online by Cambridge University Press:
- 30 August 2023, e040
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The Australian SKA Pathfinder (ASKAP) radio telescope has carried out a survey of the entire Southern Sky at 887.5 MHz. The wide area, high angular resolution, and broad bandwidth provided by the low-band Rapid ASKAP Continuum Survey (RACS-low) allow the production of a next-generation rotation measure (RM) grid across the entire Southern Sky. Here we introduce this project as Spectral and Polarisation in Cutouts of Extragalactic sources from RACS (SPICE-RACS). In our first data release, we image 30 RACS-low fields in Stokes I, Q, U at 25$^{\prime\prime}$ angular resolution, across 744–1032 MHz with 1 MHz spectral resolution. Using a bespoke, highly parallelised, software pipeline we are able to rapidly process wide-area spectro-polarimetric ASKAP observations. Notably, we use ‘postage stamp’ cutouts to assess the polarisation properties of 105912 radio components detected in total intensity. We find that our Stokes Q and U images have an rms noise of $\sim$80 $\unicode{x03BC}$Jy PSF$^{-1}$, and our correction for instrumental polarisation leakage allows us to characterise components with $\gtrsim$1% polarisation fraction over most of the field of view. We produce a broadband polarised radio component catalogue that contains 5818 RM measurements over an area of $\sim$1300 deg$^{2}$ with an average error in RM of $1.6^{+1.1}_{-1.0}$ rad m$^{-2}$, and an average linear polarisation fraction $3.4^{+3.0}_{-1.6}$ %. We determine this subset of components using the conditions that the polarised signal-to-noise ratio is $>$8, the polarisation fraction is above our estimated polarised leakage, and the Stokes I spectrum has a reliable model. Our catalogue provides an areal density of $4\pm2$ RMs deg$^{-2}$; an increase of $\sim$4 times over the previous state-of-the-art (Taylor, Stil, Sunstrum 2009, ApJ, 702, 1230). Meaning that, having used just 3% of the RACS-low sky area, we have produced the 3rd largest RM catalogue to date. This catalogue has broad applications for studying astrophysical magnetic fields; notably revealing remarkable structure in the Galactic RM sky. We will explore this Galactic structure in a follow-up paper. We will also apply the techniques described here to produce an all-Southern-sky RM catalogue from RACS observations. Finally, we make our catalogue, spectra, images, and processing pipeline publicly available.
The Efficacy of Individualized, Community-Based Physical Activity to Aid Smoking Cessation: A Randomized Controlled Trial
- Michelle B. Stockton, Kenneth D. Ward, Barbara S. McClanahan, Mark W. Vander Weg, Mace Coday, Nancy Wilson, George Relyea, Mary C. Read, Stephanie Connelly, Karen C. Johnson, Haniki Mohamed
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- Journal:
- Journal of Smoking Cessation / Volume 2023 / 2023
- Published online by Cambridge University Press:
- 01 January 2024, e4
- Print publication:
- 2023
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Objective. The efficacy of individualized, community-based physical activity as an adjunctive smoking cessation treatment to enhance long-term smoking cessation rates was evaluated for the Lifestyle Enhancement Program (LEAP). Methods. The study was a two-arm, parallel-group, randomized controlled trial. All participants (n = 392) received cessation counseling and a nicotine patch and were randomized to physical activity (n = 199; YMCA membership and personalized exercise programming from a health coach) or an equal contact frequency wellness curriculum (n = 193). Physical activity treatment was individualized and flexible (with each participant selecting types of activities and intensity levels and being encouraged to exercise at the YMCA and at home, as well as to use “lifestyle” activity). The primary outcome (biochemically verified prolonged abstinence at 7-weeks (end of treatment) and 6- and 12-months postcessation) and secondary outcomes (7-day point prevalent tobacco abstinence (PPA), total minutes per week of leisure time physical activity and strength training) were assessed at baseline, 7 weeks, 6 months, and 12 months. Results. Prolonged abstinence in the physical activity and wellness groups was 19.6% and 25.4%, respectively, at 7-weeks, 15.1% and 16.6% at 6-months, and 14.1% and 17.1% at 12 months (all between-group P values >0.18). Similarly, PPA rates did not differ significantly between groups at any follow-up. Change from baseline leisure-time activity plus strength training increased significantly in the physical activity group at 7 weeks (P = 0.04). Across treatment groups, an increase in the number of minutes per week in strength training from baseline to 7 weeks predicted prolonged abstinence at 12 months (P ≤ 0.001). Further analyses revealed that social support, fewer years smoked, and less temptation to smoke were associated with prolonged abstinence over 12 months in both groups. Conclusions. Community-based physical activity programming, delivered as adjunctive treatment with behavioral/pharmacological cessation treatment, did not improve long-term quit rates compared to adjunctive wellness counseling plus behavioral/pharmacological cessation treatment. This trial is registered with https://beta.clinicaltrials.gov/study/NCT00403312, registration no. NCT00403312.
439 The effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on hypoxic-ischemic injury in newborn rats
- Melanie Gail Wiley, Catrina Sims-Robinson, Heather A. Boger, Dorothea D. Jenkins, Mark S. George, Ralph H. Johnson
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- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue s1 / April 2022
- Published online by Cambridge University Press:
- 19 April 2022, p. 86
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OBJECTIVES/GOALS: Neonatal hypoxic-ischemic encephalopathy (HIE) is an acute neurologic syndrome where decreased blood flow and oxygen to the brain causes acute and chronic brain dysfunction. The only proven neuroprotective intervention for HIE is hypothermia treatment started within 6 hours of birth and 50% of survivors have long-term deficits. METHODS/STUDY POPULATION: Pre-clinical adult stroke studies demonstrated that vagus nerve stimulation (VNS) has anti-inflammatory effects and attenuates brain damage. Transcutaneous auricular VNS (taVNS) is safe and feasible in infants and may improve the motor skill of bottle feeding. We hypothesize that a combined hypothermia-taVNS treatment shortly after HIE birth will have neuroprotective effects, improve motor function, attenuate infarct volume inflammation compared to hypothermia alone. The HIE model includes ligation of the right common carotid artery in postnatal day 7 (P7) rats followed by 90min hypoxia (8% oxygen) and 2hr hypothermia. taVNS or sham taVNS was administered using a bipolar electrode placed on the auricular concha region for 30min, [30sec trains, 0.5msec duration, 20Hz frequency, followed by 4.5min breaks] RESULTS/ANTICIPATED RESULTS: Experimental groups include +HIE/+taVNS, +HIE/-taVNS, and -HIE/-taVNS. To assess motor function, grasping reflex and forelimb grip strength tasks were assessed prior to surgery through P10. Infarct volume was assessed at 72h after injury by staining coronal sections with cresyl-violet. Thirty-four rat pups underwent surgery with an 8.82% mortality rate. taVNS was well tolerated by the P7 rats when delivered below perceptual threshold (0.4-1.1mA). There was no difference in elementary motor function or infarct volume between any group. DISCUSSION/SIGNIFICANCE: Future studies will include 2.5hr hypoxia for a more severe brain injury and a -HIE/+taVNS control group. These initial pre-clinical studies in neonates are important in determining whether taVNS may translate as a treatment to improve outcomes after neonatal HIE.
Implementation of SARS-CoV-2 Monoclonal Antibody Infusion Sites at Three Medical Centers in the United States: Strengths and Challenges Assessment to Inform COVID-19 Pandemic and Future Public Health Emergency Use
- Anastasia S. Lambrou, John T. Redd, Miles A. Stewart, Kaitlin Rainwater-Lovett, Jonathan K. Thornhill, Lynn Hayes, Gina Smith, George M. Thorp, Christian Tomaszewski, Adolphe Edward, Natalia Elías Calles, Mark Amox, Steven Merta, Tiffany Pfundt, Victoria Callahan, Adam Tewell, Helga Scharf-Bell, Samuel Imbriale, Jeffrey D. Freeman, Michael Anderson, Robert P. Kadlec
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- Journal:
- Disaster Medicine and Public Health Preparedness / Volume 17 / 2023
- Published online by Cambridge University Press:
- 14 January 2022, e112
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Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.
Repetitive Transcranial Magnetic Stimulation for Tobacco Treatment in Cancer Patients: A Preliminary Report of a One-Week Treatment
- Xingbao Li, Benjamin A. Toll, Matthew J. Carpenter, Paul J. Nietert, Morgan Dancy, Mark S. George, Renee Bittoun
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- Journal:
- Journal of Smoking Cessation / Volume 2022 / 2022
- Published online by Cambridge University Press:
- 01 January 2024, e9
- Print publication:
- 2022
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Background. Smoking cessation represents a significant opportunity to improve cancer survival rates, reduces the risk of cancer treatment complications, and improves quality of life. However, about half of cancer patients who smoke continue to smoke despite the availability of several treatments. Previous studies demonstrate that repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) decreases cue craving, reduces cigarette consumption, and increases the quit rate in tobacco use disorder. We investigated whether 5 sessions of rTMS can be safely and efficaciously used for smoking cessation in cancer patients. Methods. We enrolled 11 treatment-seeking smokers with cancer (>5 cigarettes per day) in a randomized, double-blind, sham-controlled proof-of-concept study. Participants received 5 daily sessions of active 10 Hz rTMS of the left DLPFC (3000 pulses per session) or sham rTMS and were followed up for 1 month via phone assessments. Main outcomes included reductions in the number of smoked-cigarettes per day (primary) and craving (secondary). Adverse effects were reported daily by participants. Results. Seven of 11 participants completed 5 sessions of rTMS over one week. Compared to sham treatment (n = 4), the active rTMS (n = 3) exhibited modest effects overtime on smoking (Cohen’s f2 effect size of 0.16) and large effects on cue craving (Cohen’s f2 = 0.40). No serious side effects related to rTMS were reported in the treatment. Conclusions. Five sessions of daily rTMS over the left DLPFC might benefit cancer patients who smoke cigarettes. However, further evidence is needed to determine with more certainty its therapeutic effect and adverse effects for cancer patients who smoke cigarettes.
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.
Translation and Cultural Adaptation of NIH Toolbox Cognitive Tests into Swahili and Dholuo Languages for Use in Children in Western Kenya
- Megan M. Duffey, David Ayuku, George Ayodo, Emily Abuonji, Mark Nyalumbe, Amy K. Giella, Julie N. Hook, Tuan M. Tran, Megan S. McHenry
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- Journal:
- Journal of the International Neuropsychological Society / Volume 28 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 24 May 2021, pp. 414-423
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Objectives:
Performing high-quality and reliable cognitive testing requires significant resources and training. As a result, large-scale studies involving cognitive testing are difficult to perform in low- and middle-income settings, limiting access to critical knowledge to improve academic achievement and economic production in these populations. The NIH Toolbox® is a collection of cognitive, motor, sensory, and emotional tests that can be administered and scored using an iPad® tablet, reducing the need for training and quality monitoring; and thus, it is a potential solution to this problem.
Methods:We describe our process for translation and cultural adaptation of the existing NIH Toolbox tests of fluid cognition into the Swahili and Dholuo languages for use in children aged 3–14 years in western Kenya. Through serial forward and back translations, cognitive interviews, group consensus, outside feedback, and support from the NIH Toolbox team, we produced translated tests that have both face validity and linguistic validation.
Results:During our cognitive interviews, we found that the five chosen tests (one each of attention, cognitive flexibility, working memory, episodic memory, and processing speed) were generally well understood by children aged 7–14 years in our chosen populations. The cognitive interviews informed alterations in translation as well as slight changes in some images to culturally adapt the tests.
Conclusions:This study describes the process by which we translated five fluid cognition tests from the NIH Toolbox into the Swahili and Dholuo languages. The finished testing application will be available for future studies, including a pilot study for assessment of psychometric properties.
Data quality methods through remote source data verification auditing: results from the Congenital Cardiac Research Collaborative
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- Joelle A. Pettus, Amy L. Pajk, Andrew C. Glatz, Christopher J. Petit, Bryan H. Goldstein, Athar M. Qureshi, George T. Nicholson, Jeffery J. Meadows, Jeffrey D. Zampi, Mark A. Law, Shabana Shahanavaz, Michael S. Kelleman, Courtney M. McCracken, the Congenital Cardiac Research Collaborative
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- Journal:
- Cardiology in the Young / Volume 31 / Issue 11 / November 2021
- Published online by Cambridge University Press:
- 17 March 2021, pp. 1829-1834
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Background:
Multicentre research databases can provide insights into healthcare processes to improve outcomes and make practice recommendations for novel approaches. Effective audits can establish a framework for reporting research efforts, ensuring accurate reporting, and spearheading quality improvement. Although a variety of data auditing models and standards exist, barriers to effective auditing including costs, regulatory requirements, travel, and design complexity must be considered.
Materials and methods:The Congenital Cardiac Research Collaborative conducted a virtual data training initiative and remote source data verification audit on a retrospective multicentre dataset. CCRC investigators across nine institutions were trained to extract and enter data into a robust dataset on patients with tetralogy of Fallot who required neonatal intervention. Centres provided de-identified source files for a randomised 10% patient sample audit. Key auditing variables, discrepancy types, and severity levels were analysed across two study groups, primary repair and staged repair.
Results:Of the total 572 study patients, data from 58 patients (31 staged repairs and 27 primary repairs) were source data verified. Amongst the 1790 variables audited, 45 discrepancies were discovered, resulting in an overall accuracy rate of 97.5%. High accuracy rates were consistent across all CCRC institutions ranging from 94.6% to 99.4% and were reported for both minor (1.5%) and major discrepancies type classifications (1.1%).
Conclusion:Findings indicate that implementing a virtual multicentre training initiative and remote source data verification audit can identify data quality concerns and produce a reliable, high-quality dataset. Remote auditing capacity is especially important during the current COVID-19 pandemic.
An Unusual Todd’s Phenomenon: Post-Ictal Prosopagnosia
- Rebecca S. George, R. Mark Sadler, David B. Clarke
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 48 / Issue 5 / September 2021
- Published online by Cambridge University Press:
- 04 December 2020, pp. 730-731
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Proliferation of Faulty Materials Data Analysis in the Literature
- Matthew R. Linford, Vincent S. Smentkowski, John T. Grant, C. Richard Brundle, Peter M.A. Sherwood, Mark C. Biesinger, Jeff Terry, Kateryna Artyushkova, Alberto Herrera-Gómez, Sven Tougaard, William Skinner, Jean-Jacques Pireaux, Christopher F. McConville, Christopher D. Easton, Thomas R. Gengenbach, George H. Major, Paul Dietrich, Andreas Thissen, Mark Engelhard, Cedric J. Powell, Karen J. Gaskell, Donald R. Baer
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- Journal:
- Microscopy and Microanalysis / Volume 26 / Issue 1 / February 2020
- Published online by Cambridge University Press:
- 17 January 2020, pp. 1-2
- Print publication:
- February 2020
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2036 Extracellular matrix as a novel approach to glioma therapy
- Mark H. Murdock, Jordan T. Chang, George S. Hussey, Nduka M. Amankulor, Johnathan A. Engh, Stephen F. Badylak
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- Journal of Clinical and Translational Science / Volume 2 / Issue S1 / June 2018
- Published online by Cambridge University Press:
- 21 November 2018, pp. 11-12
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OBJECTIVES/SPECIFIC AIMS: Gliomas are the most lethal and common primary tumor type in the central nervous system across all age groups; affected adults have a life expectancy of just 14 months. As glioma cells invade the surrounding normal parenchyma they remodel the composition and ultrastructure of the surrounding extracellular matrix (ECM), suggesting that the native (i.e., “normal”) microenvironment is not ideal for their survival and proliferation. Recent reports describe suppressive and/or lethal effects of mammalian ECM hydrogels derived from normal (nonneoplastic) sources upon various cancer types. ECM-based bioscaffolds placed at sites of neoplastic tissue resection in humans have never been reported to facilitate cancer recurrence. The objective of the present research is to evaluate mammalian ECM as a novel approach to glioma therapy. METHODS/STUDY POPULATION: ECM hydrogels from porcine dermis, small intestine, and urinary bladder were produced as described previously. Primary glioma cells were graciously supplied by Drs. Nduka Amankulor and Johnathan Engh, and U-87 MG were ordered through ATCC. Cells were plated onto tissue culture plastic at ~60% confluence and allowed to attach for 24 hours before treatment. The saline-soluble fraction (SSF) of ECM was obtained by mixing lyophilized, comminuted ECM with 0.9% saline for 24 hours then filtering the resulting mixture through a 10 kDa molecular weight cutoff column. All assays and kits were followed according to the manufacturer’s instructions. Cell viability was measured via MTT assay (Vybrant® MTT Cell Proliferation Assay, Invitrogen) and by live/dead staining (LIVE/DEAD® Cell Imaging Kit, Invitrogen). Time lapse videos were created by taking images every 20 minutes for 18 hours (phase-contrast) or every 10 minutes for 12 hours (darkfield). NucView reagent was ordered from Biotium. Temozolomide was ordered through Abmole. All in vivo work was conducted according to protocols approved by the University of Pittsburgh’s IACUC office. RESULTS/ANTICIPATED RESULTS: ECM hydrogels derived from porcine dermis, small intestine, or urinary bladder all decreased the viability of primary glioma cells in vitro, with urinary bladder extracellular matrix (UBM) having the most dramatic effects. The SSF of UBM (UBM-SSF), devoid of the fibrillar, macromolecular components of ECM, was sufficient to recapitulate this detrimental effect upon neoplastic cells in vitro and was used for the remainder of the experiments described herein. In a cell viability assay normalized to the media treatment, non-neoplastic CHME5 and N1E-115 cells scored 103% and 114% after 48 hours when treated with UBM-SSF and 2 primary high-grade glioma cell types scored 17% and 30.5% with UBM-SSF (n=2). Phase-contrast time-lapse video showed CHME5 and HFF thriving in the presence of UBM-SSF for 18 hours while most primary glioma cells shriveled and died within this time. Darkfield time-lapse video of wells containing Nucview dye, fluorescent upon cleavage by active caspase-3, confirmed that within 12 hours most primary glioma cells underwent apoptosis while CHME5 and HFF did not. In culture with primary astrocytes, high grade primary glioma cells, and U-87 MG glioma cells for 24 hours, UBM-SSF was found to significantly increase the population of primary astrocytes compared with media (p<0.05) while decreasing the 2 glioma cell types to approximately one-third as many cells as the media control (p<0.0001). A dose-response of temozolomide from 0 to 10,000 μM showed that when treating 2 non-neoplastic cell types (CHME5 and HFF) and 2 types of primary glioma cell there was no difference in survivability at any concentration. Contrasted to this, a dose-response of UBM-SSF from 350 to 7000 μg/mL showed that the non-neoplastic cells survived significantly better than the glioma cells at concentrations of 875 μg/mL and upward (p<0.05). In preliminary animal experiments, large primary glioma tumors in the flanks of athymic nude mice were resected and replaced with either UBM SSF or Matrigel (an ECM product of neoplastic cell origin). After 7 days the resection sites with UBM-SSF had little tumor regrowth if any compared with the dramatic recurrence seen in the Matrigel injection sites (n=2). In a separate survival study comparing PBS to UBM-SSF injections in the flank-resection model, all animals given PBS had to be sacrificed at 9, 11, and 11 days (n=3) whereas animals given UBM-SSF were sacrificed at 15, 24, and 39 days (n=3), indicating a moderate increase in survival due to the UBM-SSF. DISCUSSION/SIGNIFICANCE OF IMPACT: Since the introduction of the pan-cytotoxic chemotherapeutic agent TMZ in 2005, the standard of care for patients with glioblastoma multiforme has not improved. These findings indicate that non-neoplastic ECM contains potent bioactive regulators capable of abrogating malignancy. Our in vitro data suggest these molecules appear to have no deleterious effect on non-neoplastic cells while specifically inducing apoptosis in glioma cells. Our in vivo data suggest that these molecules may be useful in delaying glioma recurrence, thus resulting in extended lifespan. Delivering soluble fractions of ECM to a tumor site may represent a novel approach to glioma therapy, sidestepping traditional cytotoxic therapies in favor of utilizing putative endogenous anti-tumor pathways.
An Examination of the Composition and Microstructure of Coarse Intermetallic Particles in AA2099-T8, Including Li Detection
- Colin M. MacRae, Anthony E. Hughes, James S. Laird, A. M. Glenn, Nicholas C. Wilson, Aaron Torpy, Mark A. Gibson, Xiaorong Zhou, Nick Birbilis, George E. Thompson
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- Journal:
- Microscopy and Microanalysis / Volume 24 / Issue 4 / August 2018
- Published online by Cambridge University Press:
- 18 June 2018, pp. 325-341
- Print publication:
- August 2018
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Electron and proton microprobes, along with electron backscatter diffraction (EBSD) analysis were used to study the microstructure of the contemporary Al–Cu–Li alloy AA2099-T8. In electron probe microanalysis, wavelength and energy dispersive X-ray spectrometry were used in parallel with soft X-ray emission spectroscopy (SXES) to characterize the microstructure of AA2099-T8. The electron microprobe was able to identify five unique compositions for constituent intermetallic (IM) particles containing combinations of Al, Cu, Fe, Mn, and Zn. A sixth IM type was found to be rich in Ti and B (suggesting TiB2), and a seventh IM type contained Si. EBSD patterns for the five constituent IM particles containing Al, Cu, Fe, Mn, and Zn indicated that they were isomorphous with four phases in the 2xxx series aluminium alloys including Al6(Fe, Mn), Al13(Fe, Mn)4 (two slightly different compositions), Al37Cu2Fe12 and Al7Cu2Fe. SXES revealed that Li was present in some constituent IM particles. Al SXES mapping revealed an Al-enriched (i.e., Cu, Li-depleted) zone in the grain boundary network. From the EBSD analysis, the kernel average misorientation map showed higher levels of localized misorientation in this region, suggesting greater deformation or stored energy. Proton-induced X-ray emission revealed banding of the TiB2 IM particles and Cu inter-band enrichment.
Rapid-onset clozapine-induced loss of glycaemic control: Case report
- Alejandro Porras-Segovia, Amir Krivoy, Mark Horowitz, George Thomas, Mark Bolstridge, Dragos Ion, Sukhwinder S. Shergill
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- Journal:
- BJPsych Open / Volume 3 / Issue 3 / May 2017
- Published online by Cambridge University Press:
- 02 January 2018, pp. 138-140
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Clozapine has proved to be an effective antipsychotic for the treatment of refractory schizophrenia – characterised by the persistence of symptoms despite optimal treatment trials with at least two different antipsychotics at adequate dose and duration – but its use is hampered by adverse effects. The development of clozapine-induced diabetes is commonly considered to arise as part of a metabolic syndrome, associated with weight gain, and thus evolves slowly. We present the case of an individual with refractory schizophrenia and metformin-controlled diabetes who developed rapid-onset insulin-dependent hyperglycaemia immediately after starting clozapine. Given the refractory nature of his illness, the decision was made to continue clozapine and manage the diabetes. This case supports the existence of a more direct mechanism by which clozapine alters glycaemic control, aside from the more routine slow development of a metabolic syndrome.
A dosimetric comparison of craniospinal irradiation using TomoDirect radiotherapy, TomoHelical radiotherapy and 3D conventional radiotherapy
- Shirley W. S. Tsang, Mark Collins, Jacky T. L. Wong, George Chiu
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- Journal of Radiotherapy in Practice / Volume 16 / Issue 4 / December 2017
- Published online by Cambridge University Press:
- 22 June 2017, pp. 391-402
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Aim
The purpose of this study was to dosimetrically compare TomoDirect, TomoHelical and linear accelerator-based 3D-conformal radiotherapy (Linac-3DCRT) for craniospinal irradiation (CSI) in the treatment of medulloblastoma.
MethodsFive CSI patients were replanned with Linac-3DCRT, TomoHelical, TomoDirect-3DCRT and TomoDirect-intensity-modulated radiotherapy (IMRT). Dose of 36 Gy in 20 fractions was prescribed to the planning target volume (PTV). Homogeneity index (HI), non-target integral dose (NTID), dose–volume histograms, organs-at-risk (OARs) Dmax, Dmean and treatment times were compared.
ResultsTomoHelical achieved the best PTV homogeneity compared with Linac-3DCRT, TomoDirect-3DCRT and TomoDirect-IMRT (HI of 3·6 versus 20·9, 8·7 and 9·4%, respectively). TomoDirect-IMRT achieved the lowest NTID compared with TomoDirect-3DCRT, TomoHelical and Linac-3DCRT (141 J versus 151 J, 181 J and 250 J), indicating least biological damage to normal tissues. TomoHelical plans achieved the lowest Dmax in all organs except the breasts, and lowest Dmean for most OARs, except in laterally situated OARs, where TomoDirect triumphed. Beam-on time was longest for TomoHelical, followed by TomoDirect and Linac-3DCRT.
FindingsTomoDirect has the potential to lower NTID and shorten treatment times compared with TomoHelical. It reduces PTV inhomogeneity and better spares OARs compared with Linac-3DCRT. Therefore, TomoDirect may be a CSI treatment alternative to TomoHelical and in place of Linac-3DCRT.
Integration of Glyphosate and Quizalofop with Tillage for Quackgrass (Elytrigia repens) Management in Continuous Annual Crop and Legume Plowdown Rotations
- A. Lloyd Darwent, George W. Clayton, James C. Drabble, Peter F. Mills, Mark S. Wolynetz
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- Weed Technology / Volume 10 / Issue 4 / December 1996
- Published online by Cambridge University Press:
- 12 June 2017, pp. 923-930
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A field study was conducted from 1987 to 1992 to determine the effectiveness of several treatments consisting of combinations of glyphosate and/or quizalofop with tillage to control quackgrass in legume plowdown and continuous annual crop rotations. The treatments were imposed on the quackgrass in 1987 and/or 1988, evaluated in 1989 (cycle 1), reimposed on the same plots in 1990 and/or 1991 and re-evaluated in 1992 (cycle 2). Where continuous barley was grown, glyphosate applied at 0.45 kg/ha before seeding in 1987 (cycle 1) and 1990 (cycle 2), and combined with fall tillage in the first two years of each cycle, reduced quackgrass shoot density and rhizome dry weight by more than 96%. In a legume plowdown rotation, consisting of barley underseeded to red clover followed by plowdown and barley in subsequent years, quackgrass was reduced by a similar amount by glyphosate at 0.45 kg/ha applied in 1987 and 1990 before seeding or in 1988 and 1991 at 5 d before or 6 wk after red clover plowdown. Quackgrass reduction from all of these treatments was as effective as the labelled rate of glyphosate (0.90 kg/ha) applied at the same times, and also as effective as glyphosate applied at 0.45 kg/ha in combination with tillage in a year of fallow. Without fall tillage the efficacy of glyphosate applied before seeding was reduced. Quizalofop at 0.20 kg/ha applied to canola in a rotation of canola followed by two years of barley, reduced quackgrass, but was less effective than glyphosate treatments with fall tillage. Reducing quackgrass populations resulted in significant increases in crop yields.
Postemergence herbicide application timing effects on annual grass control and corn (Zea mays) grain yield
- Larry S. Tapia, Thomas T. Bauman, Robert G. Harvey, James J. Kells, George Kapusta, Mark M. Loux, William E. Lueschen, Michael D. K. Owen, Larry H. Hageman, Stephen D. Strachan
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- Weed Science / Volume 45 / Issue 1 / February 1997
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- 12 June 2017, pp. 138-143
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Giant foxtail, woolly cupgrass, and wild-proso millet infest millions of hectares of land devoted to corn production in the midwestern U.S. Control of these species and effects on corn grain yield were evaluated at various timings using POST applications of nicosulfuron vs. applications of various PRE herbicides at 17 locations across the midwestern U.S. in 1992 and 1993. Nicosulfuron applied to 5 to 10 cm giant foxtail and woolly cupgrass provided greater control than that observed with selected PRE herbicides. Giant foxtail control with nicosulfuron averaged 88%, and control of woolly cupgrass averaged 77% across all sites. Nicosulfuron, applied to 5 to 10 cm wild-proso millet, provided a level of control similar to that of selected PRE herbicides. Corn grain yield was greater when giant foxtail was controlled POST with nicosulfuron vs. PRE control with selected soil-applied herbicides. Corn grain yields were similar when nicosulfuron was applied POST to 5 to 10 cm woolly cupgrass or wild-proso millet vs. PRE control of these grass weeds. Across a broad range of geographical locations, nicosulfuron, applied POST to 5 to 10 cm tall grass, provided greater or similar levels of weed control vs. the selected PRE herbicides, with no deleterious effect on grain yield.
Characterization of an EST Database for the Perennial Weed Leafy Spurge: An Important Resource for Weed Biology Research
- James V. Anderson, David P. Horvath, Wun S. Chao, Michael E. Foley, Alvaro G. Hernandez, Jyothi Thimmapuram, Lie Liu, George L. Gong, Mark Band, Ryan Kim, Mark A. Mikel
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- Weed Science / Volume 55 / Issue 3 / June 2007
- Published online by Cambridge University Press:
- 20 January 2017, pp. 193-203
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Genomics programs in the weed science community have not developed as rapidly as that of other crop, horticultural, forestry, and model plant systems. Development of genomic resources for selected model weeds are expected to enhance our understanding of weed biology, just as they have in other plant systems. In this report, we describe the development, characteristics, and information gained from an expressed sequence tag (EST) database for the perennial weed leafy spurge. ESTs were obtained using a normalized cDNA library prepared from a comprehensive collection of tissues. During the EST characterization process, redundancy was minimized by periodic subtractions of the normalized cDNA library. A sequencing success rate of 88% yielded 45,314 ESTs with an average read length of 671 nucleotides. Using bioinformatic analysis, the leafy spurge EST database was assembled into 23,472 unique sequences representing 19,015 unigenes (10,293 clusters and 8,722 singletons). Blast similarity searches to the GenBank nonredundant protein database identified 18,186 total matches, of which 14,205 were nonredundant. These data indicate that 77.4% of the 23,472 unique sequences and 74.7% of the 19,015 unigenes are similar to other known proteins. Further bioinformatics analysis indicated that 2,950, or 15.5%, of the unigenes have previously not been identified suggesting that some may be novel to leafy spurge. Functional classifications assigned to leafy spurge unique sequences using Munich Information Center for Protein or Gene Ontology were proportional to functional classifications for genes of arabidopsis, with the exception of unclassified or unknowns and transposable elements which were significantly reduced in leafy spurge. Although these EST resources have been developed for the purpose of constructing high-density leafy spurge microarrays, they are already providing valuable information related to sugar metabolism, cell cycle regulation, dormancy, terpenoid secondary metabolism, and flowering.
PeakForce Scanning Electrochemical Microscopy with Nanoelectrode Probes
- Zhuangqun Huang, Peter De Wolf, Rakesh Poddar, Chunzeng Li, Andreas Mark, Michael R. Nellist, Yikai Chen, Jingjing Jiang, Georg Papastavrou, Shannon W. Boettcher, Chengxiang Xiang, Bruce S. Brunschwig
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- Journal:
- Microscopy Today / Volume 24 / Issue 6 / November 2016
- Published online by Cambridge University Press:
- 26 October 2016, pp. 18-25
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- November 2016
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Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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