35 results
82 Behavioral, Emotional, and Adaptive Functioning in a Pediatric anti-NMDARE Population
- Madeline R King, Marie C McGrath, Ashley Higgins, Nina Hattiangadi Thomas
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 74-75
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Objective:
Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a complex, yet treatable autoimmune disorder characterized by a fairly abrupt onset of a constellation of symptoms attributable to diffuse brain dysfunction (Tarantino et al., 2021). Despite the potential for a severe disease course, most patients have a favorable outcome with substantial recovery (Dalmau et al., 2011; Titulaer et al., 2013). Nevertheless, there is limited literature discussing the long-term outcomes in patients with anti-NMDARE, particularly in pediatric patients. The primary objective of this study is to examine and describe behavioral, emotional, adaptive, and executive functioning outcomes in pediatric and young adult patients with this disease. This study also sought to provide information on the perceived health-related quality of life (HRQoL) of patients and their parents and investigate the impact of anti-NMDARE on parents and family functioning.
Participants and Methods:All individuals known to have been diagnosed and treated for anti-NMDARE at The Children’s Hospital of Philadelphia (CHOP) between January 1, 2005, and October 1, 2020, were contacted with both patients and their parents/guardians invited to participate. Eighteen pediatric patients between the ages of 6 and 26 and/or their parents/caregivers participated in the study. Of the 18 patients represented in the sample, 50% were white/Caucasian, and 67% were female. The mean duration of time since symptom onset was 7.1 years. Primary outcomes were measured through standardized questionnaires of emotional, behavioral, and adaptive functioning (BASC-3) and executive functioning (BRIEF2 or BRIEF-A). Secondary outcomes related to family functioning and HRQoL were measured through (PedsQL™ and PedsQL™ Family Impact Module.)
Results:All aggregate T-scores for the BASC and BRIEF placed children with anti-NMDARE within an age-appropriate range regarding behavioral, emotional, adaptive, and executive functioning outcomes. Children with anti-NMDARE were not found to have lower HRQoL compared to their healthy same-age peers. Moreover, parents of children with anti-NMDARE did not endorse a prolonged impact of this illness on family functioning and adjustment.
Conclusions:This study aimed to better understand the neurobehavioral profile and the long-term outcomes of children diagnosed with anti-NMDARE, with the ultimate goal of advancing understanding of this encephalitis. Consistent with findings from several reviewed studies on long-term follow-up, the present study suggests that most children with a history of anti-NMDARE show good functional recovery over time. However, data on the neurobehavioral sequelae, quality of life, and adaptive behavior in patients diagnosed with anti-NMDARE are still sparse, especially at pediatric age. In order to understand and learn to manage the needs of patients with anti-NMDARE, particularly regarding the impact this disease can have on daily life and school performance, additional neuropsychological research involving larger samples, longitudinal studies, and increased methodological consistency is required.
447 Characterization of the human iridocorneal angle in vivo using a custom design goniolens with OCT gonioscopy
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- Alessandra Carmichael-Martins, Thomas J. Gast, Stephen A. Burns, Brittany R. Walker, Brett J. King
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, p. 133
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OBJECTIVES/GOALS: The trabecular meshwork (TM) and Schlemm’s canal (SC), located within the iridocorneal angle (ICA), form the main outflow pathway and a major target for glaucoma treatments. We characterized the human ICA in vivo with Optical Coherence Tomography (OCT) imaging using a customized goniolens and a commercial OCT device (Heidelberg Spectralis). METHODS/STUDY POPULATION: Imaging these structures is difficult due to the optical limitations of imaging through the cornea at high angles. Therefore, a clinical gonioscopy lens was modified with a 12mm plano-convex lens placed on its anterior surface to focus light on the ICA structures, and capture returning light. Each subjects’ eye was anesthetized with 1 drop of Proparacaine 0.5%. The goniolens was coupled to the eye with gonio-gel and it was held by a 3D adjustable mount. OCT volume scans were acquired on 10 healthy subjects. The linear polarization of the OCT was rotated with a half-waveplate to measure dependence of the ICA landmarks on polarization orientation. RESULTS/ANTICIPATED RESULTS: The TM was seen in 9 of 10 subjects. Polarization rotation modified the brightness of the band of extracanalicular limbal lamina (BELL) and corneoscleral bands due to the birefringent nature of the collagenous structures, increasing the contrast of SC. SC width was 99 ± 20µm varying in size over space, including a subject with SC narrowing in the inferior-temporal quadrant. DISCUSSION/SIGNIFICANCE: This clinically suitable gonioscopic OCT approach has successfully been used to image the human ICA in 3D in vivo, providing detailed characterization of the TM and SC as well as enhancing their contrast against their birefringent backgrounds by rotating the polarization of the imaging beam.
Automated control and optimization of laser-driven ion acceleration
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- B. Loughran, M. J. V. Streeter, H. Ahmed, S. Astbury, M. Balcazar, M. Borghesi, N. Bourgeois, C. B. Curry, S. J. D. Dann, S. DiIorio, N. P. Dover, T. Dzelzainis, O. C. Ettlinger, M. Gauthier, L. Giuffrida, G. D. Glenn, S. H. Glenzer, J. S. Green, R. J. Gray, G. S. Hicks, C. Hyland, V. Istokskaia, M. King, D. Margarone, O. McCusker, P. McKenna, Z. Najmudin, C. Parisuaña, P. Parsons, C. Spindloe, D. R. Symes, A. G. R. Thomas, F. Treffert, N. Xu, C. A. J. Palmer
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- Journal:
- High Power Laser Science and Engineering / Volume 11 / 2023
- Published online by Cambridge University Press:
- 27 March 2023, e35
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The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.
Impact of rapid treatment of sheep lame with footrot on welfare and economics and farmer attitudes to lameness in sheep
- LE Green, J Kaler, GJ Wassink, EM King, R Grogono Thomas
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- Animal Welfare / Volume 21 / Issue S1 / May 2012
- Published online by Cambridge University Press:
- 01 January 2023, pp. 65-71
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This review article summarises the evidence for an effective management protocol for footrot to sheep, the welfare and economic benefits of such a protocol and its likely uptake by farmers. Over 90% of lameness in sheep in England is caused by Dichelobacter nodosus, the aetiological agent of footrot. Farmers can recognise lame sheep both from video clips and when examining their own sheep but make a separate decision about whether to catch lame sheep. Only farmers who catch and treat mildly lame sheep immediately report a low prevalence of lameness (< 5%). From a within-farm clinical trial, treatment of sheep lame with footrot with parenteral antibiotic and topical spray led to over 90% recovery from lameness within 10 days whilst only 25% of sheep treated with foot trimming and topical spray recovered in 10 days. In parallel, a within-farm clinical trial with approximately 800 ewes was run for 18 months to test the hypothesis that rapid appropriate treatment led to reduced prevalence of lameness. Ewes were stratified and randomly allocated to one of two groups. The prevalence and incidence of lameness decreased in the treatment group, where lame sheep were treated with parenteral and topical antibacterials within three days of being observed lame, but remained at approximately 8% in the control group where lame sheep were treated with trimming hoof horn and topical antibacterial spray when the farm shepherd considered them sufficiently lame. Sheep in the treatment group had a higher body condition and produced more lambs that grew faster. The net economic benefit to all sheep (whether lame or not) in 2006 was £6 per ewe put to the ram. A group of 265 farmers were asked about their satisfaction with methods to manage footrot. Satisfied farmers reported a prevalence of lameness of ≤ 5% and used rapid individual treatment. Dissatisfied farmers reported a prevalence of lameness of > 5% and used whole-flock footbathing and vaccination. Overall, farmers stated that their ideal managements would be footbathing and vaccination. One explanation for this apparent inconsistency is that farmers want effective vaccines and footbaths; an alternative explanation is that this is an example of cognitive dissonance, where subjects adopt a belief because it is their current practice despite evidence that it is not effective. We conclude that farmers can identify lame sheep and that rapid treatment of individual sheep lame with footrot with intramuscular and topical antibacterials is currently the most effective control of interdigital dermatitis and footrot in sheep but that in future effective measures that prevent footrot would be ideal.
Single-Dose Pharmacokinetics of Amphetamine Extended-Release Oral Suspension (AMPH EROS) in 6–12-Year-Old Children with ADHD
- Antonio Pardo, Ann C. Childress, Thomas R. King, Eman Rafla, Judith C. Kando
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, p. 163
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Methods
This Phase 1, open-label, single-dose, one-period, one-treatment PK study enrolled 12 children 6–12 y with ADHD. PK parameters for d- and l-amphetamine in plasma (Cmax, tmax, AUC0–8, and t1/2) were calculated and expressed as means, geometric means, and standard deviations. The primary endpoint was all objective PK measurements at 28 hours post-dose. PK was evaluated for 2 cohorts (6 pts ages 6–9 y and 6 pts aged 10–12 y). Safety was monitored continuously and assessed based on occurrence of adverse events.
ResultsA single dose of 10 mg (4 ml) AMPH EROS (2.5 mg/ml) administered under fasted conditions resulted in a rapid rise in mean plasma concentration in d-amphetamine, reaching maximum concentrations within 5 hours. The overall study population mean (SD) plasma AUC0–8 (d-amphetamine) was 1061.2 (309) h*ng/mL, and for l-amphetamine was 380.5 (112) h*ng/mL. The mean maximum concentration (Cmax) for the overall study population was 54.91 ng/mL and 17.1 (5.2) ng/mL for d- and l-amphetamine, respectively. The overall study population median time to maximum concentrations (Tmax) for d-amphetamine were reached at 3.4 hours, and for l-amphetamine at 4.1 hours. The elimination half-life (t1/2) for the entire study cohort was 10.6 (2.0) hours for d-amphetamine, and 12.5 (3.2) hours for l-amphetamine. Directionally, a higher mean Cmax, AUC0–8, AUCt, and median Tmax were observed in the younger (6 to 9-year-old) age group, and this result was consistent with both the d- and l-amphetamine enantiomers. The mean elimination t1/2 for both d- and l-amphetamine was higher in the older cohort (10–12 years) than in the 6 to 12-year-olds. Study drug was well-tolerated by the subjects in this study. Two TEAEs were reported in one subject TEAEs (diarrhea and rash on legs) occurred approximately 12 hours postdose.
ConclusionsThis study confirmed that the PK profile of AMPH EROS in 6 to 12-year-olds provided a consistent, predictable extended-release profile in a highly titratable liquid formulation, and this finding was relatively consistent and directionally predictable between the age groups assessed, with higher maximum concentrations and AUCs and shorter elimination half-lives noted in the younger population, with no anomalous parameters demonstrated, and no untoward or unexpected safety issues noted.
FundingTris Pharma, Inc.
Comparative Bioavailability of Amphetamine Extended-Release Oral Suspension and Extended-Release Mixed Amphetamine Salts
- Antonio Pardo, Mohammed Bouhajib, Eman Rafla, Thomas R. King, Judith C. Kando
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, p. 163
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Purpose
This open-label, single-dose, randomized, two-period, two-treatment, two-sequence, crossover study evaluated the comparative bioavailability between amphetamine extended-release oral suspension (treatment A: AMPH EROS, Dyanavel XR 2.5 mg/mL, 18.8 mg amphetamine base per 7.5 mL) and extended-release mixed amphetamine salts (treatment B: ER MAS, Adderall XR 30 mg capsules, equivalent to 18.8 mg amphetamine base per capsule) after a single dose in healthy adult subjects, under fasted conditions.
MethodsThe crossover design allowed for intra-subject PK comparisons. Relative comparable bioavailability was determined by a statistical comparison of the AUC and Cmax parameters for both d- and l-amphetamine, where the geometric mean ratios for AUC and Cmax were within the 90% confidence limits (80.0%–125.0%) to determine comparable bioavailability between test products. Subjects in sequence 1 received treatment A followed by B; subjects in sequence 2 received treatment B followed by treatment A. PK samples were obtained at 0 (pre-dose) through 60 hours post-dose. The safety assessment was based on reported frequency and severity of adverse events.
ResultsThirty (30) subjects were enrolled and 28 completed. The mean age of subjects was 35 years, with a mean BMI of 25.9 kg/m2. Most subjects were Male (63.3%) and Black (56.7%). The geometric mean ratios for Cmax and all AUC measurements were within the 80–125% bound indicating comparable bioavailability between both test products. Both test products were generally well-tolerated with no serious AEs reported.
ConclusionsThe bioavailability of a single 7.5 mL dose of AMPH EROS 2.5 mg/mL was comparable to a single 30 mg capsule dose of ER MAS. AMPH EROS (both d- and l-amphetamine) showed equivalent peak and overall exposure to ER MAS under fasted conditions.
FundingTris Pharma, Inc.
78595 Assessing the influence of comorbidities in patients undergoing sternal reconstruction following cardiac surgery: a single institution's 15 year review
- Edgar Soto, Pallavi A. Kumbla, Ryan Restrepo, Thomas K. Delay, Shadi K Awad, Sherry Collawn, Jorge de la Torre, Brad Denney, Jobe R Fix, John H Grant, Ali Kilic, Timothy W King, Prasanth Patcha, James Davies, Luis O Vasconez, Rene P. Myers
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- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, p. 124
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ABSTRACT IMPACT: Current practice guidelines offer a variety of treatment options for sternal reconstruction but complications and infections remain a serious surgical problem. This work seeks to provide a comprehensive picture of the com-morbidities and reconstructive methods that lead to success and improve patient outcomes. OBJECTIVES/GOALS: Patients that undergo cardiac surgery via the median sternotomy approach are at risk of wound complications that require repair. We seek to evaluate how outcomes of sternal reconstruction are influenced by patient comorbidities, flap usage and internal mammary artery grafts and methods of sternal closure. METHODS/STUDY POPULATION: We identified patients between 2005 and 2020 who underwent sternotomy followed by debridement and flap coverage at our institution. Comorbidities, method of reconstruction, demographic data, surgical history, and other factors pertaining to mortality and morbidity were collected. The data will then be analyzed to identify population characteristics using logistic regression variables to determine univariate and adjusted multivariable measures of association with mortality. We present the pre-liminary data analyzed using chi-square and one-way anova in R. RESULTS/ANTICIPATED RESULTS: In this study we present a preliminary characterization of one institution’s sternal reconstruction patient outcomes with a variety of reconstruction methods including pectoralis advancement flaps, omental flaps and latissumus dorsi flaps. Notable preoperative comorbidities include 50% of patients > age 60, 18% with diabetes mellitus, 18 % with diagnosed hypertension, 18% with COPD, and 9% with a smoking history DISCUSSION/SIGNIFICANCE OF FINDINGS: In an evolving cardiothoracic landscape, clinical characteristics of patients being treated for sternal reconstructive surgery present a moving target. Understanding current risk factors, preoperative management and timing for aggressive surgical treatment offers an opportunity to update treatment protocol and maximize successful outcomes.
A single-dose, comparative bioavailability study comparing amphetamine extended-release oral suspension with extended-release mixed amphetamine salts capsules
- Antonio Pardo, Mohammed Bouhajib, Thomas R. King, Eman Rafla, Judith C. Kando
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- Journal:
- CNS Spectrums / Volume 27 / Issue 3 / June 2022
- Published online by Cambridge University Press:
- 03 December 2020, pp. 309-314
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Background
To evaluate the relative bioavailability of a single dose of amphetamine extended-release oral suspension (AMPH EROS) compared with a single dose of extended-release mixed amphetamine salts (ER MAS) in healthy, fasted adult subjects.
MethodsThe study population consisted of healthy adult volunteers. The study drug used in this study was 7.5 mL of 2.5 mg/mL AMPH EROS equivalent to 18.8 mg of amphetamine base administered after an overnight fast of at least 10 hours. AMPH EROS comprises a 3.2:1 enantiomeric ratio of d-amphetamine to l-amphetamine. The reference product was one 30 mg ER MAS capsule (equivalent to 18.8 mg of amphetamine base). Relative bioavailability between the products was determined by a statistical comparison of the area under the curve and maximum concentration (Cmax) for d-amphetamine and l-amphetamine. PK (PK) blood samples were collected prior to dosing (0-hour) and at 1, 2, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 12, 14, 16, 24, 36, 48, and 60 hours after drug administration, totaling 20 samples in each period.
ResultsThe mean subject age was 35.0 (standard deviation ±8) years, and the overall study population comprised 19 (63.3%) males and 11 (36.7%) females. The contrasts for geometric mean ratios for all assessed PK parameters (for both l- and d-amphetamine) between the test article AMPH EROS and reference product ER MAS fell within the prescribed 80% to 125% limits.
ConclusionsThe overall PK profile of single-dose AMPH EROS 7.5 mL was found to be comparable with a single dose of oral ER MAS 30 mg.
179 Palatability Assessment of a New Amphetamine Extended-Release Tablet Formulation
- Barry K. Herman, Thomas R. King, Judith C. Kando, Antonio Pardo
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, p. 313
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Background:
In 2016, the US FDA issued an industry guidance document “Quality Attribute Considerations for Chewable Tablets” which describes the quality attributes to be considered when developing chewable tablets. It includes recommendations on selection of acceptance criteria for measuring palatability (having a taste acceptable to the patient or has adequate masking). These data are now recommended as part of ANDA submissions. Palatability is a known positive contributing factor to drug adherence and persistence. We summarize here palatability data for a new amphetamine extended-release tablet (Dyanavel XR® Extended Release Tablet; AMPH ER TAB).
Methods:This was a 2-arm preplanned secondary analysis from a comparative bioavailability study: single-dose AMPH ER TAB 20 mg chewed under fasting (Treatment A) and fed (Treatment B) conditions. Subjects rated the palatability of AMPH ER TAB (Treatments A+B) through a 5-question palatability questionnaire. The questions included in the palatability questionnaire were as follows:
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1. Oral sensation/mouth feel of the drug product
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2. Taste of the drug product
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3. How strong is the taste?
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4. Aftertaste of the product
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5. How strong is the aftertaste?
Subjects completed the questionnaire within 10 minutes from the time of drug administration, which was evaluated and scored according to the rubric below:
Q1, Q2, Q4: palatability- Very unpleasant (score of 1), Unpleasant (2), No sensation or mouthfeel (3), Pleasant (4), and Very pleasant (5)
Q3, Q5 (Taste/aftertaste strength): Very strong (score of 1), Strong (2), Moderate (3), Mild (4), No aftertaste (5).
Scores of 1-2 for both categories were Negative; score of 3 was Neutral, and 4-5 were Positive.
Results:35 subjects comprised the palatability dataset (completed one question on the questionnaire). In the palatability analysis, for treatments A and B, most of the subjects rated the oral sensation/mouth feel of AMPH ER TAB (Question 1) and the taste of AMPH ER TAB (Question 2) as positive (pleasant to very pleasant) (70.1% and 83.6%, respectively).
When evaluating taste strength (Question 3): 43.3% rated the strength as positive (mild/no taste) and 43.3% of subjects rated the strength as neutral (moderate taste). Also, 82.1% rated the aftertaste of AMPH ER TAB (Question 4) as positive (pleasant/very pleasant) and 52.2% rated the strength of the aftertaste as positive (mild/no taste).
Conclusion:Most subjects rated the oral sensation and taste as pleasant or very pleasant, whether chewed under fasted conditions or after a meal. With respect to the taste strength, most subjects rated it as moderate (chewed under fasted conditions) or mild/no taste (chewed after a meal). Aftertaste was rated as pleasant or very pleasant in most subjects, with the strength as moderate (chewed under fasted conditions) or mild/no aftertaste (chewed after a meal). AMPH ER Tablets provided an overall pleasant taste and mouthfeel experience for patients.
Funding Acknowledgements: Tris Pharma, Inc.
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Single-dose pharmacokinetics of amphetamine extended-release tablets compared with amphetamine extended-release oral suspension
- Antonio Pardo, Judith C. Kando, Thomas R. King, Eman Rafla, Barry K. Herman
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- Journal:
- CNS Spectrums / Volume 25 / Issue 6 / December 2020
- Published online by Cambridge University Press:
- 22 January 2020, pp. 774-781
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Objective
Evaluate the relative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB.
MethodsHealthy volunteers (18–55 years) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover study design was used. Plasma samples were collected each period predose and at time points to 60 hours postdose. d- and l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-∞, and Cmax. Comparative relative bioavailability between formulations was determined when ratios were within 80% and 125%. Safety was also assessed.
ResultsThirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 100.68% to 108.08%, AUC0-∞: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; l: AUC0-t: 100.31% to 108.57%, AUC0-∞: 101.27% to 111.09%, Cmax: 98.2% to 103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 5.00 hours (with a range of 2.00–9.00 hours). AMPH ER TAB chewed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 99.23% to 106.62%, AUC0-∞: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: AUC0-t: 98.16% to 106.35%, AUC0-∞: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours (with a range of 3.00-7.00 hours). PK results were similar for patients in the fasted and fed groups, indicative of no presence of food effect. No serious adverse events (AEs) were reported, overall AE profiles between the tablet and oral suspension were comparable without any unanticipated safety concerns.
ConclusionsSingle doses of AMPH ER TAB for both d- and l-amphetamine demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL under fasted conditions when chewed and swallowed whole, and demonstrated equivalent peak and overall exposure without apparent food effect. AMPH ER TAB was well-tolerated and consistent with adverse events noted in other amphetamine formulations.
87 Efficacy Measures in an Open-label Dose-Optimization of an Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder
- Andrew Cutler, Antonio Pardo, Thomas R. King, Judith C. Kando, Barry K. Herman
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, pp. 218-219
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Objectives
Report the efficacy of open-label amphetamine extended-release oral suspension (AMPH EROS) for the treatment of children with ADHD.
AMPH EROS has a 1-hr onset of effect and a duration of action of 13hours and was approved by FDA for treatment of ADHD in children aged 6–17 years based on a double-blind, placebo-controlled efficacy and safety study in children aged 6–12 years with ADHD. A significant treatment difference in change from pre-dose SKAMP-combined score was observed at the primary endpoint of 4hours post-dose (p<0.0001) and each post-dose time point assessed (1, 2, 4, 6, 8, 10, 12, 13hours).
Data reported here are from the 5-week, open-label dose optimization period. These efficacy data support the primary endpoint result.
MethodsMales and females aged 6 to 12 years with ADHD enrolled and began open-label treatment with 2.5 mg or 5mg/day of AMPH EROS titrated in 2.5–10mg/day increments until optimal dose (maximum 20mg/day). Doses could be decreased for tolerability. Subjects took morning AMPH EROS for 5weeks. Other efficacy outcomes during the open-label dose optimization phase: ADHD-RS (ADHD-Rating Scale), CGI-S (Clinical Global Impression of Severity), CGI-I (CGI-of Improvement) and CPRS (Conners’ Parent Rating Scale). All subjects were assessed for safety.
ResultsFor the ITT population (n=99): treatment with AMPH EROS was associated with a mean change in ADHD-RS-IV (baseline to end of the open-label dose optimization; week 6) of 28.2 (±9.03) (Baseline score = 41.3±7.95). 90.9% of subjects had a change from baseline to open-label week 6 of ≥50% in the ADHD-RS-IV total score and were defined as responders. The CGI-S scores decreased continuously from baseline, with a high 4.8 at baseline to a low of 2.0 at open-label week 6. The percentage of subjects classified as moderately ill or greater correspondingly decreased from 97% at Baseline to 1% at open-label week 6. The decrease in the CGI-I over the study was similar to the change in CGI-S scores. CPRS for most categories decreased continuously from Baseline to open-label week 6. Mean change from baseline to open-label week 6 on the CPRS inattention T-score subscale was –25.3 (±14.38) and –24.4 (±13.87).
Adverse events (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings and headache.
ConclusionAMPH EROS was effective in reducing symptoms of ADHD in this open-label dose optimization. The AE profile of AMPH EROS was consistent with those of other amphetamine products.
Funding Acknowledgements: This work was funded by Tris Pharma, Inc.
31 A Modified-Release Drug Delivery Technology Containing Amphetamine-Ion Exchange Complexes
- Barry K. Herman, Thomas R. King, Judith C. Kando, Antonio Pardo
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, p. 191
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The proprietary, immediate and extended drug delivery technologyLiquiXR® utilizes an ion-exchange resin that complexes with amphetamine or any active moiety that can be protonated and is water-soluble. The active ingredient of the drug product forms a complex with an ion exchange polymer of the resin resulting in micron-sized particles. A portion of these particles is then coated with an aqueous, pH-independent polymer designed to provide sustained release of drug product. The polymer coating applied to the ion-exchange resin particles is of varying thickness, allowing for extended release of active drug while uncoated particles provide for immediate release of drug.
The micron-sized particles lend themselves to being formulated into an appropriate dosage form: solid/chewable tablet, liquid suspension, orally disintegrating tablet, film, or capsules. Active ingredient of drug product is subsequently released from the dosage form in millions of particles, with release driven by a combination of ion exchange and diffusion. After drug release, the ion-exchange resin particles are excreted in the feces.
The release characteristics of LiquiXR allow for customized, sustained release of active drug ∼24hours post dose. Mechanistically, drug particles enter the gastrointestinal (GI) tract. As positively-charged ions from GI fluids diffuse across the coating, it displaces drug ions from product and they diffuse through the coating and into the GI fluids for absorption. As the coating is of variable thickness, some drug product takes longer to diffuse and absorb, providing for the delayed drug release characteristics.
The LiquiXR drug delivery technology has already been successfully utilized in the development of treatment options (liquid suspension and chewable tablet) that offer rapid absorption and sustained plasma levels after once-daily dosing. LiquiXR is utilized in Dyanavel® XR (amphetamine extended-release oral suspension; AMPH EROS), which is indicated for treatment of ADHD. It comprises 2.5mg/mL amphetamine base and uses LiquiXR technology to provide an immediate release component followed by an extended-release profile.
Efficacy of AMPH EROS was established in children 6 to 12 yr in a Phase 3, placebo-controlled laboratory classroom study. In that study, ADHD symptoms in children on an individually optimized dose of amphetamine (range 10–20mg/day) were statistically significantly improved compared with symptoms in children treated with placebo. For children treated with AMPH EROS, onset of effect was demonstrated at 1hour after dosing, and efficacy was observed through 13hr post-dose. The effect size (ES) was comparable to ES demonstrated for other psychostimulants tested in studies using a similar design. The efficacy data reported for AMPH EROS provides an excellent example of the potential utility and clinical application for other active drug products requiring an immediate and extended release profile.
Funding Acknowledgements: Support provided by Tris Pharma, Inc.
89 A Novel, Modified-Release Drug Delivery Technology Containing Amphetamine-Ion Exchange Complexes
- Barry K. Herman, Thomas R. King, Judith C. Kando, Antonio Pardo
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, p. 220
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The proprietary immediate and extended drug delivery technology LiquiXR™ utilizes an ion-exchange resin that complexes with amphetamine or any other active moiety that can be protonated and is water-soluble. The active drug product forms a complex with ion-exchange polymers contained in the resin, which is then formed into micron-sized particles. Some of these particles are coated with an aqueous, pH-independent polymer designed to provide immediate or sustained release of active drug product. The polymer coating applied to the ion-exchange resin particles is of varying thickness, allowing for programmed, extended release of active drug product. Solid, coating-free particles provide for immediate release of active drug product.
The micron-sized particles are formulated into an appropriate dosage form (solid or chewable tablet, liquid suspension, orally disintegrating tablet, film, or capsules). Active drug product is subsequently released from the dosage form in millions of particles, with the release driven by a combination of ion exchange and diffusion. After drug release, the ion-exchange resin is excreted in the feces.
The release characteristics of LiquiXR™ are programmable and allow for a customized, sustained release of active drug product for up to 24hours post-dose. Mechanistically, drug particles enter the gastrointestinal tract. As positively-charged ions from gastrointestinal (GI) fluids diffuse across the coating, ionically-charged drug product diffuses through the coating and into the GI fluids for absorption. As the coating is of variable thickness, some drug product takes longer to diffuse and absorb, providing for the programmable delayed drug release characteristic.
The LiquiXR™ drug delivery technology is utilized in Dyanavel® XR (amphetamine extended-release oral suspension; AMPH EROS), which is indicated for the treatment of attention-deficit hyperactivity disorder. It comprises 2.5mg/mL amphetamine base complexed with LiquiXR technology to provide an immediate release component followed by an extended-release profile. The efficacy of AMPH EROS was established in children ages 6 to 12 years in a Phase 3, placebo-controlled laboratory classroom study. In that study, attention-deficit/hyperactivity disorder (ADHD) symptoms in children on an individually optimized dose of amphetamine (range 10–20mg/day) were statistically significantly improved compared with symptoms in children treated with placebo. For children treated with AMPH EROS, onset of effect was demonstrated at 1hour after dosing, and efficacy was observed through 13hours post-dose. The effect size was comparable to effect sizes demonstrated for other psychostimulants tested in studies using a similar design. The efficacy data reported for AMPH EROS provides an excellent example of the potential utility and clinical application for other active drug products requiring an immediate release and extended release profile.
Funding Acknowledgements: This work was funded by Tris Pharma, Inc.
32 Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension (AMPH EROS) in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder
- Ann C. Childress, Antonio Pardo, Thomas R. King, Judith C. Kando, Barry K. Herman
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, pp. 191-192
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Objective
To determine whether amphetamine extended-release oralsuspension (AMPH EROS) has an onset of effect at 30minutes postdose inchildren with ADHD.
MethodsThis randomized, double-blind, 2-treatment, 2-sequence, placebo-controlled crossover pilot study enrolled subjects aged 6 to 12 years withattention-deficit/hyperactivity disorder (ADHD) and ADHD-Rating Scale-5 scores of ≥90th percentile for sex and age. A dose of 5 to 20mg/day of AMPH EROS was determined during a 1-week open-label phase based on medication history, symptom control, and tolerability. Subjects completed a practice laboratory classroom then received one day of double-blind active drug or placebo each in random sequence during 2 double-blind laboratory classroom days. Subjects completed the first double-blind laboratory classroom session, returned to open label drug for 5days then crossed over on day 6 during a second double-blind laboratory classroom session. DB dose was fixed at AMPH EROS 15, 17.5, or 20mg . The primary endpoint was change from predose in the Swanson, Kotkin, Agler, M-Flynn, Pelham rating scale-combined score (SKAMP-C) at 30minutes postdose on two DB days. The key secondary endpoint was change from predose in the SKAMP-C score at 3hours postdose for AMPH EROS compared with placebo. Safety assessments included vital signs and adverse events.
ResultsEighteen subjects were enrolled in the study (14 males and 4 females) with a mean age of 9 years. At both 30minutes and 3hours postdose, changes from baseline in SKAMP-C for AMPH EROS vs. placebo were statistically significant (p<0.01 and p=0.0002, respectively) with corresponding effect sizes of 0.96 and 1.57. Adverse events (>10%) during the open-label phase included upper respiratory tract infection, fatigue, upper abdominal pain, headache, decreased appetite, and affect lability.
ConclusionsAMPH EROS was effective in reducing ADHD symptoms at 30minutes postdose. AEs were mild or moderate and consistent with those of other extended-release amphetamines.
Funding Acknowledgements: Support was provided by Tris Pharma, Inc.
Evaluating the Economic Risk of Herbicide-Based Weed Management Systems in Corn and Soybean Using Stochastic Dominance Testing
- Thomas R. Hoverstad, Gregg A. Johnson, Jeffrey L. Gunsolus, Robert P. King
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- Journal:
- Weed Technology / Volume 20 / Issue 2 / June 2006
- Published online by Cambridge University Press:
- 20 January 2017, pp. 422-429
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Herbicide evaluation trials are typically conducted with the objective of rating herbicide efficacy and assessing crop yield loss. There is little if any attempt to quantify the economic risk associated with each treatment. The objective of this research was to use second-degree stochastic dominance to evaluate the economic stability of corn and soybean weed management systems between two contrasting environments. Weed management systems were evaluated in small-plot replicated trials over a 3-yr time period at two locations in southern Minnesota. One location (Waseca) had a slightly cooler and wetter environment than the second location (Lamberton). The Waseca location also had higher weed density and greater weed species diversity. Adjusted returns from weed management were calculated for each system by measuring economic returns, as determined by deducting weed management costs from the product of crop price and grain yield. Stochastic dominance is a technique that considers the entire distribution of net returns from weed management and compares these cumulative distributions as a basis for analyzing risk. Climate, soils, and weed diversity dictated differences in risk efficiency and effectiveness of the various weed management systems evaluated between the Waseca and Lamberton sites. Stochastic dominance testing is a useful tool for understanding long-term risk across environments. Results can be used to develop effective long-term weed management systems that minimize risk while maximizing profit potential.
Risk-Efficiency Criteria for Evaluating Economics of Herbicide-Based Weed Management Systems in Corn
- Thomas R. Hoverstad, Jeffrey L. Gunsolus, Gregg A. Johnson, Robert P. King
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- Journal:
- Weed Technology / Volume 18 / Issue 3 / September 2004
- Published online by Cambridge University Press:
- 20 January 2017, pp. 687-697
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Evaluation of economic outcome associated with a given weed management system is an important component in the decision-making process within crop production systems. The objective of this research was to investigate how risk-efficiency criteria could be used to improve herbicide-based weed management decision making, assuming different risk preferences among growers. Data were obtained from existing weed management trials in corn conducted at the University of Minnesota Southern Research and Outreach Center at Waseca. Weed control treatments represented a range of practices including one-pass soil-applied, one-pass postemergence, and sequential combinations of soil and postemergence herbicide application systems. Analysis of risk efficiency across 23 herbicide-based weed control treatments was determined with the mean variance and stochastic dominance techniques. We show how these techniques can result in different outcomes for the decision maker, depending on risk attitudes. For example, mean variance and stochastic dominance techniques are used to evaluate risk associated with one- vs. two-pass herbicide treatments with and without cultivation. Based on these analyses, it appears that a one-pass system is preferred by a risk-averse grower. However, we argue that this may not be the best option considering potential changes in weed emergence patterns, application timing concerns, etc. The techniques for economic analysis of weed control data outlined in this article will help growers match herbicide-based weed management systems to their own production philosophies based on economic risk.
Pollen Analysis of Fossil Packrat Middens from the Sonoran Desert
- James E. King, Thomas R. Van Devender
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- Quaternary Research / Volume 8 / Issue 2 / September 1977
- Published online by Cambridge University Press:
- 20 January 2017, pp. 191-204
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Pollen contained in 22 fossil packrat middens from the Sonoran Desert provides a complementary, but differing, view of the paleoenvironment from that derived by analysis of the associated plant macrofossils. The regional component of the pollen data is in sharp contrast to the locally oriented macrofossils. A total of 84 macrofossil taxa and 47 pollen taxa were identified; only 18 taxa were common to both. The low Index of Similarity, 0.4, indicates that the two sources of fossil information are providing different sets of paleobotanical data. When combined with plant macrofossils and good radiocarbon dating control, the pollen spectra derived from fossil middens are compatable with other paleoenvironmental sequences.
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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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- By Rony A. Adam, Gloria Bachmann, Nichole M. Barker, Randall B. Barnes, John Bennett, Inbar Ben-Shachar, Jonathan S. Berek, Sarah L. Berga, Monica W. Best, Eric J. Bieber, Frank M. Biro, Shan Biscette, Anita K. Blanchard, Candace Brown, Ronald T. Burkman, Joseph Buscema, John E. Buster, Michael Byas-Smith, Sandra Ann Carson, Judy C. Chang, Annie N. Y. Cheung, Mindy S. Christianson, Karishma Circelli, Daniel L. Clarke-Pearson, Larry J. Copeland, Bryan D. Cowan, Navneet Dhillon, Michael P. Diamond, Conception Diaz-Arrastia, Nicole M. Donnellan, Michael L. Eisenberg, Eric Eisenhauer, Sebastian Faro, J. Stuart Ferriss, Lisa C. Flowers, Susan J. Freeman, Leda Gattoc, Claudine Marie Gayle, Timothy M. Geiger, Jennifer S. Gell, Alan N. Gordon, Victoria L. Green, Jon K. Hathaway, Enrique Hernandez, S. Paige Hertweck, Randall S. Hines, Ira R. Horowitz, Fred M. Howard, William W. Hurd, Fidan Israfilbayli, Denise J. Jamieson, Carolyn R. Jaslow, Erika B. Johnston-MacAnanny, Rohna M. Kearney, Namita Khanna, Caroline C. King, Jeremy A. King, Ira J. Kodner, Tamara Kolev, Athena P. Kourtis, S. Robert Kovac, Ertug Kovanci, William H. Kutteh, Eduardo Lara-Torre, Pallavi Latthe, Herschel W. Lawson, Ronald L. Levine, Frank W. Ling, Larry I. Lipshultz, Steven D. McCarus, Robert McLellan, Shruti Malik, Suketu M. Mansuria, Mohamed K. Mehasseb, Pamela J. Murray, Saloney Nazeer, Farr R. Nezhat, Hextan Y. S. Ngan, Gina M. Northington, Peggy A. Norton, Ruth M. O'Regan, Kristiina Parviainen, Resad P. Pasic, Tanja Pejovic, K. Ulrich Petry, Nancy A. Phillips, Ashish Pradhan, Elizabeth E. Puscheck, Suneetha Rachaneni, Devon M. Ramaeker, David B. Redwine, Robert L. Reid, Carla P. Roberts, Walter Romano, Peter G. Rose, Robert L. Rosenfield, Shon P. Rowan, Mack T. Ruffin, Janice M. Rymer, Evis Sala, Ritu Salani, Joseph S. Sanfilippo, Mahmood I. Shafi, Roger P. Smith, Meredith L. Snook, Thomas E. Snyder, Mary D. Stephenson, Thomas G. Stovall, Richard L. Sweet, Philip M. Toozs-Hobson, Togas Tulandi, Elizabeth R. Unger, Denise S. Uyar, Marion S. Verp, Rahi Victory, Tamara J. Vokes, Michelle J. Washington, Katharine O'Connell White, Paul E. Wise, Frank M. Wittmaack, Miya P. Yamamoto, Christine Yu, Howard A. Zacur
- Edited by Eric J. Bieber, Joseph S. Sanfilippo, University of Pittsburgh, Ira R. Horowitz, Emory University, Atlanta, Mahmood I. Shafi
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- Clinical Gynecology
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- 05 April 2015
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- 23 April 2015, pp viii-xiv
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Coordinated Microanalyses of Seven Particles of Probable Interstellar Origin from the Stardust Mission.
- Andrew J. Westphal, Rhonda M. Stroud, Hans A. Bechtel, Frank E. Brenker, Anna L. Butterworth, George J. Flynn, David R. Frank, Zack Gainsforth, Jon K. Hillier, Frank Postberg, Alexandre S. Simionovici, Veerle J. Sterken, Carlton Allen, David Anderson, Asna Ansari, Saˇsa Bajt, Ron K. Bastien, Nabil Bassim, John Bridges, Donald E. Brownlee, Mark Burchell, Manfred Burghammer, Hitesh Changela, Peter Cloetens, Andrew M. Davis, Ryan Doll, Christine Floss, Eberhard Gru¨n, Philipp R. Heck, Peter Hoppe, Bruce Hudson, Joachim Huth, Anton Kearsley, Ashley J. King, Barry Lai, Jan Leitner, Laurence Lemelle, Ariel Leonard, Hugues Leroux, Robert Lettieri, William Marchant, Larry R. Nittler, Ryan Ogliore, Wei Jia Ong, Mark C. Price, Scott A. Sandford, Juan-Angel Sans Tresseras, Sylvia Schmitz, Tom Schoonjans, Kate Schreiber, Geert Silversmit, Vicente A. Solé, Ralf Srama, Frank Stadermann, Thomas Stephan, Julien Stodolna, Stephen Sutton, Mario Trieloff, Peter Tsou, Tolek Tyliszczak, Bart Vekemans, Laszlo Vincze, Joshua Von Korff, Naomi Wordsworth, Daniel Zevin, Michael E. Zolensky
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- Microscopy and Microanalysis / Volume 20 / Issue S3 / August 2014
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- 27 August 2014, pp. 1692-1693
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- August 2014
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