130 research outputs found

    Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transpot project-demonstration act system definition

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    The 1985 ACT airplane is the Final Active Controls Technology (ACT) Airplane with the addition of three-axis fly by wire. Thus it retains all the efficiency features of the full ACT system plus the weight and cost savings accruing from deletion of the mechanical control system. The control system implements the full IAAC spectrum of active controls except flutter-mode control, judged essentially nonbeneficial, and incorporates new control surfaces called flaperons to make the most of wing-load alleviation. This redundant electronic system is conservatively designed to preserve the extreme reliability required of crucial short-period pitch augmentation, which provides more than half of the fuel savings

    Comprehensive T wave Morphology Assessment in a Randomized Clinical Study of Dofetilide, Quinidine, Ranolazine, and Verapamil

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    Background Congenital long QT syndrome type 2 (abnormal hERG potassium channel) patients can develop flat, asymmetric, and notched T waves. Similar observations have been made with a limited number of hERG-blocking drugs. However, it is not known how additional calcium or late sodium block, that can decrease torsade risk, affects T wave morphology. Methods and Results Twenty-two healthy subjects received a single dose of a pure hERG blocker (dofetilide) and 3 drugs that also block calcium or sodium (quinidine, ranolazine, and verapamil) as part of a 5-period, placebo-controlled cross-over trial. At pre-dose and 15 time-points post-dose, ECGs and plasma drug concentration were assessed. Patch clamp experiments were performed to assess block of hERG, calcium (L-type) and late sodium currents for each drug. Pure hERG block (dofetilide) and strong hERG block with lesser calcium and late sodium block (quinidine) caused substantial T wave morphology changes (P<0.001). Strong late sodium current and hERG block (ranolazine) still caused T wave morphology changes (P<0.01). Strong calcium and hERG block (verapamil) did not cause T wave morphology changes. At equivalent QTc prolongation, multichannel blockers (quinidine and ranolazine) caused equal or greater T wave morphology changes compared with pure hERG block (dofetilide). Conclusions T wave morphology changes are directly related to amount of hERG block; however, with quinidine and ranolazine, multichannel block did not prevent T wave morphology changes. A combined approach of assessing multiple ion channels, along with ECG intervals and T wave morphology may provide the greatest insight into drug-ion channel interactions and torsade de pointes risk

    Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Current and advanced act control system definition study. Volume 2: Appendices

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    The current status of the Active Controls Technology (ACT) for the advanced subsonic transport project is investigated through analysis of the systems technical data. Control systems technologies under examination include computerized reliability analysis, pitch axis fly by wire actuator, flaperon actuation system design trade study, control law synthesis and analysis, flutter mode control and gust load alleviation analysis, and implementation of alternative ACT systems. Extensive analysis of the computer techniques involved in each system is included

    Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

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    Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

    Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Current and advanced act control system definition study, volume 1

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    An active controls technology (ACT) system architecture was selected based on current technology system elements and optimal control theory was evaluated for use in analyzing and synthesizing ACT multiple control laws. The system selected employs three redundant computers to implement all of the ACT functions, four redundant smaller computers to implement the crucial pitch-augmented stability function, and a separate maintenance and display computer. The reliability objective of probability of crucial function failure of less than 1 x 10 to the -9th power per flight of 1 hr can be met with current technology system components, if the software is assumed fault free and coverage approaching 1.0 can be provided. The optimal control theory approach to ACT control law synthesis yielded comparable control law performance much more systematically and directly than the classical s-domain approach. The ACT control law performance, although somewhat degraded by the inclusion of representative nonlinearities, remained quite effective. Certain high-frequency gust-load alleviation functions may require increased surface rate capability

    Who Believes in Me? The Effect of Student-Teacher Demographic Match on Teacher Expectations

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    Teachers are an important source of information for traditionally disadvantaged students. However, little is known about how teachers form expectations and whether they are systematically biased. We investigate whether student-teacher demographic mismatch affects high school teachers’ expectations for students’ educational attainment. Using a student fixed effects strategy that exploits expectations data from two teachers per student, we find that non-black teachers of black students have significantly lower expectations than do black teachers. These effects are larger for black male students and math teachers. Our findings add to a growing literature on the role of limited information in perpetuating educational attainment gaps

    Assessment of an in silico mechanistic model for proarrhythmia risk prediction under the CiPA initiative

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    International Council on Harmonization S7B and E14 regulatory guidelines are sensitive but not specific for predicting which drugs are proarrhythmic. In response, the Comprehensive In Vitro Proarrhythmia Assay (CiPA) was proposed that integrates multi-ion channel pharmacology data in vitro into a human cardiomyocyte model in silico for proarrhythmia risk assessment. Previously, we reported the model optimization and proarrhythmia metric selection based on CiPA training drugs. In this study, we report the application of the prespecified model and metric to independent CiPA validation drugs. Over two validation datasets, the CiPA model performance meets all pre-specified measures for ranking and classifying validation drugs, and outperforms alternatives, despite some in vitro data differences between the two datasets due to different experimental conditions and quality control procedures This suggests that the current CiPA model/metric is fit for regulatory use, and standard experimental protocols and quality control criteria could increase the model prediction accuracy even further

    SoTL Lab: Undergraduate student-faculty collaborative research in teaching and learning in CSD

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    The University of Wisconsin-Eau Claire Communication Sciences and Disorders SoTL Lab was designed to provide hands-on research experiences to undergraduate students on a large scale. Student reflections on experiences within the SoTL Lab identify the value of collaboration, development of confidence, and exposure to the entire research process as key outcomes. These experiences foster development of research skills and may lead students to consider academic careers
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