In three simulation investigations, we examined the statistical properties of several different randomization-test procedures for analyzing the data from single-case multiple-baseline intervention studies. Two procedures (Wampold-Worsham and Revusky) are associated with single fixed intervention start points and three are associated with randomly determined intervention start points. Of the latter three, one (Koehler-Levin) is an existing procedure that has been previously examined and the other two (modified Revusky and restricted Marascuilo-Busk) are modifications and extensions of existing procedures. All five procedures were found to maintain their Type I error probabilities at acceptable levels. In most of the conditions investigated here, two of the random start-point procedures (Koehler-Levin and restricted Marascuilo-Busk) were more powerful than the others with respect to detecting immediate abrupt intervention effects. For designs in which it is not possible to include the same series lengths for all cases, either the modified Revusky or restricted Marascuilo-Busk procedure is recommended.
The complex of tropomyosin and troponin binds to actin and inhibits activation of myosin ATPase activity and force production of striated muscles at low free Ca 2+ concentrations. Ca 2+ stimulates ATP activity, and at subsaturating actin concentrations, the binding of NEM-modified S1 to actintropomyosin-troponin increases the rate of ATP hydrolysis even further. We show here that the Δ14 mutation of troponin T, associated with familial hypertrophic cardiomyopathy, results in an increase in ATPase rate like that seen with wild-type troponin in the presence of NEM-S1. The enhanced ATPase activity was not due to a decreased incorporation of mutant troponin T with troponin I and troponin C to form an active troponin complex. The activating effect was more prominent with a hybrid troponin (skeletal TnI, TnC, and cardiac TnT) than with all cardiac troponin. Thus it appears that changes in the troponin-troponin contacts that result from mutations or from forming hybrids stabilize a more active state of regulated actin. An analysis of the effect of the Δ14 mutation on the equilibrium binding of S1-ADP to actin was consistent with stabilization of an active state of actin. This change in activation may be important in the development of cardiac disease.Muscle contraction is a cyclic interaction of myosin and actin driven by the hydrolysis of ATP. Regulation of ATP hydrolysis in mammalian cardiac and skeletal muscle is mediated by four actin-associated proteins. Tropomyosin binds to seven actin monomers, and each tropomyosin is bound to a troponin complex consisting of troponin I, troponin T, and troponin C (TnI, 1 TnT, and TnC, respectively). The ATPase rate of myosin, in the presence of regulated actin, is cooperatively activated by Ca 2+ and by ATP-free forms of myosin. The rate of ATPase activity in the absence of Ca 2+ is low. Ca 2+ increases the k cat by ~18-fold and decreases the concentration of actin required for 50% activity by about 2-fold (1, 2). The ATPase rate can be increased further (≈8-fold) by the binding of "activating" myosin (myosin-ADP, nucleotide- † Supported by NIH Grant AR40540 (to J.M.C.), a grant from the American Heart Association (to S.F.), and NIH Grant HL63974 (to P.B.C.). A preliminary report of these data was presented at the 45th Annual Biophysical Meeting, Baltimore, MD, February 2004. * Corresponding author. Tel: 252-744-2973. E-mail:chalovichj@mail.ecu.edu.. ‡ East Carolina University. § Medical School Hannover. || Florida State University.1 Abbreviations: EDTA, ethylenediaminetetraacetic acid; EGTA, ethylene glycol bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid; MOPS, 3-(N-morpholino)propanesulfonic acid; NEM, N-ethylmaleimide; regulated actin, actin-tropomyosin-troponin; S1, myosin subfragment 1; SD, standard deviation; SEM, standard error of the mean; TnT, troponin T; TnI, troponin I; TnC, troponin C. NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2006 January 25. Published in final edited form as:Biochemistry. 2004 December 7; 43(...
Forty years ago, Eugene Edgington developed a single-case AB intervention design-andanalysis procedure based on a random determination of the point at which the B phase would start. In the present simulation studies encompassing a variety of AB-type contexts, it is demonstrated that by also randomizing the order in which the A and B phases are administered, a researcher can markedly increase the procedure's statistical power.
A number of randomization statistical procedures have been developed to analyze the results from single-case multiple-baseline intervention investigations. In a previous simulation study, comparisons of the various procedures revealed distinct differences among them in their ability to detect immediate abrupt intervention effects of moderate size, with some procedures (typically those with randomized intervention start points) exhibiting power that was both respectable and superior to other procedures (typically those with single fixed intervention start points). In Investigation 1 of the present follow-up simulation study, we found that when the same randomization-test procedures were applied to either delayed abrupt or immediate gradual intervention effects: (1) the powers of all of the procedures were severely diminished; and (2) in contrast to the previous study's results, the single fixed intervention start-point procedures generally outperformed those with randomized intervention start points. In Investigation 2 we additionally demonstrated that if researchers are able to successfully anticipate the specific alternative effect types, it is possible for them to formulate adjusted versions of the original randomization-test procedures that can recapture substantial proportions of the lost powers. Multiple-Baseline Randomization Tests 3 Additional Comparisons of Randomization-Test Procedures for Single-Case Multiple-Baseline Designs: Alternative Effect Types Over the past several years single-case research methodology and associated dataanalysis procedures have elevated their scientific "credibility" (Levin, 1994) among educational and psychological intervention researchers (see, for example, Kratochwill et al., 2013; and Kratochwill & Levin, 2014). The once-common single-case two-and three-phase AB and ABA designs, respectively, are now considered to be lacking scientific validity (Kratochwill et al., 2013) and so designs such as the ABAB "reversal" design, the alternate treatments design, and the multiple-baseline design have been advocated in their stead. Of these, many single-case intervention researchers (including the present authors) believe that the systematically staggered multiple-baseline design possesses the strongest internal-validity characteristics of all commonly adopted single-case designs in terms of its ability to document causal relationships between interventions and outcomes (see, for example, Horner & Odom, 2014; and Levin, 1992). Yet, despite the high methodological marks accorded to single-case designs such as the multiple baseline, even greater scientific credibility can be attained through an interventionist's implementation of various forms of design randomization and data-analysis randomization to enhance the research's internal validity and statistical conclusion validity, respectively (Kratochwill & Levin, 2010). To emphasize the enhanced scientific credibility that accrues to single-case designs through researcher-managed randomization and control, and consistent with Shadish, C...
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