Concept: Design of experiments
Bargh et al. (2001) reported two experiments in which people were exposed to words related to achievement (e.g., strive, attain) or to neutral words, and then performed a demanding cognitive task. Performance on the task was enhanced after exposure to the achievement related words. Bargh and colleagues concluded that better performance was due to the achievement words having activated a “high-performance goal”. Because the paper has been cited well over 1100 times, an attempt to replicate its findings would seem warranted. Two direct replication attempts were performed. Results from the first experiment (n = 98) found no effect of priming, and the means were in the opposite direction from those reported by Bargh and colleagues. The second experiment followed up on the observation by Bargh et al. (2001) that high-performance-goal priming was enhanced by a 5-minute delay between priming and test. Adding such a delay, we still found no evidence for high-performance-goal priming (n = 66). These failures to replicate, along with other recent results, suggest that the literature on goal priming requires some skeptical scrutiny.
Although bulk protein turnover has been measured with the use of stable isotope labeled tracers for over half a century, it is only recently that the same approach has become applicable to the level of the proteome, permitting analysis of the turnover of many proteins instead of single proteins or an aggregated protein pool. The optimal experimental design for turnover studies is dependent on the nature of the biological system under study, which dictates the choice of precursor label, protein pool sampling strategy, and treatment of data. In this review we discuss different approaches and, in particular, explore how complexity in experimental design and data processing increases as we shift from unicellular to multicellular systems, in particular animals.
MOTIVATION: Biochemical reaction networks in the form of coupled ordinary differential equations (ODEs) provide a powerful modeling tool for understanding the dynamics of biochemical processes. During the early phase of modeling, scientists have to deal with a large pool of competing nonlinear models. At this point, discrimination experiments can be designed and conducted to obtain optimal data for selecting the most plausible model. Since biological ODE models have widely distributed parameters due to, e.g., biologic variability or experimental variations, model responses become distributed. Therefore, a robust optimal experimental design (OED) for model discrimination can be used to discriminate models based on their response probability distribution functions (PDFs). RESULTS: In this work we present an optimal control based methodology for designing optimal stimulus experiments aimed at robust model discrimination. For estimating the time-varying model response PDF, which results from the nonlinear propagation of the parameter PDF under the ODE dynamics, we suggest using the Sigma-Point approach. Using the model overlap (expected likelihood) as a robust discrimination criterion to measure dissimilarities between expected model response PDFs, we benchmark the proposed nonlinear design approach against linearization with respect to prediction accuracy and design quality for two nonlinear biological reaction networks. As we show, the Sigma-Point outperforms the linearization approach in the case of widely distributed parameter sets and/or existing multiple steady states. Since the Sigma-Point approach scales linearly with the number of model parameter, it can be applied to large systems for robust experimental planing. AVAILABILITY: An implementation of the method in MATLAB/AMPL is available at http://www.uni-magdeburg.de/ivt/svt/person/rf/roed.html. CONTACT: firstname.lastname@example.org SUPPLEMENTARY INFORMATION: Supplementary details and discussions are available at Bioinformatics online.
Zebrafish is fast becoming a species of choice in biomedical research for the investigation of functional and dysfunctional processes coupled with their genetic and pharmacological modulation. As with mammals, experimentation with zebrafish constitutes a complicated ethical issue that calls for the exploration of alternative testing methods to reduce the number of subjects, refine experimental designs, and replace live animals. Inspired by the demonstrated advantages of computational studies in other life science domains, we establish an authentic data-driven modelling framework to simulate zebrafish swimming in three dimensions. The model encapsulates burst-and-coast swimming style, speed modulation, and wall interaction, laying the foundations for in-silico experiments of zebrafish behaviour. Through computational studies, we demonstrate the ability of the model to replicate common ethological observables such as speed and spatial preference, and anticipate experimental observations on the correlation between tank dimensions on zebrafish behaviour. Reaching to other experimental paradigms, our framework is expected to contribute to a reduction in animal use and suffering.
The reliability of experimental findings depends on the rigour of experimental design. Here we show limited reporting of measures to reduce the risk of bias in a random sample of life sciences publications, significantly lower reporting of randomisation in work published in journals of high impact, and very limited reporting of measures to reduce the risk of bias in publications from leading United Kingdom institutions. Ascertainment of differences between institutions might serve both as a measure of research quality and as a tool for institutional efforts to improve research quality.
Biologists determine experimental effects by perturbing biological entities or units. When done appropriately, independent replication of the entity-intervention pair contributes to the sample size (N) and forms the basis of statistical inference. If the wrong entity-intervention pair is chosen, an experiment cannot address the question of interest. We surveyed a random sample of published animal experiments from 2011 to 2016 where interventions were applied to parents and effects examined in the offspring, as regulatory authorities provide clear guidelines on replication with such designs. We found that only 22% of studies (95% CI = 17%-29%) replicated the correct entity-intervention pair and thus made valid statistical inferences. Nearly half of the studies (46%, 95% CI = 38%-53%) had pseudoreplication while 32% (95% CI = 26%-39%) provided insufficient information to make a judgement. Pseudoreplication artificially inflates the sample size, and thus the evidence for a scientific claim, resulting in false positives. We argue that distinguishing between biological units, experimental units, and observational units clarifies where replication should occur, describe the criteria for genuine replication, and provide concrete examples of in vitro, ex vivo, and in vivo experimental designs.
Gervais & Norenzayan (2012) reported in Science a series of 4 experiments in which manipulations intended to foster analytic thinking decreased religious belief. We conducted a precise, large, multi-site pre-registered replication of one of these experiments. We observed little to no effect of the experimental manipulation on religious belief (d = 0.07 in the wrong direction, 95% CI[-0.12, 0.25], N = 941). The original finding does not seem to provide reliable or valid evidence that analytic thinking causes a decrease in religious belief.
There is growing concern that poor experimental design and lack of transparent reporting contribute to the frequent failure of pre-clinical animal studies to translate into treatments for human disease. In 2010, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were introduced to help improve reporting standards. They were published in PLOS Biology and endorsed by funding agencies and publishers and their journals, including PLOS, Nature research journals, and other top-tier journals. Yet our analysis of papers published in PLOS and Nature journals indicates that there has been very little improvement in reporting standards since then. This suggests that authors, referees, and editors generally are ignoring guidelines, and the editorial endorsement is yet to be effectively implemented.
Many studies have shown that students learn better when they are given repeated exposures to different concepts in a way that is shuffled or interleaved, rather than blocked (e.g., Rohrer Educational Psychology Review, 24, 355-367, 2012). The present study explored the effects of interleaving versus blocking on learning French pronunciations. Native English speakers learned several French words that conformed to specific pronunciation rules (e.g., the long “o” sound formed by the letter combination “eau,” as in bateau), and these rules were presented either in blocked fashion (bateau, carreau, fardeau … mouton, genou, verrou … tandis, verglas, admis) or in interleaved fashion (bateau, mouton, tandis, carreau, genou, verglas …). Blocking versus interleaving was manipulated within subjects (Experiments 1-3) or between subjects (Experiment 4), and participants' pronunciation proficiency was later tested through multiple-choice tests (Experiments 1, 2, and 4) or a recall test (Experiment 3). In all experiments, blocking benefited the learning of pronunciations more than did interleaving, and this was true whether participants learned only 4 words per rule (Experiments 1-3) or 15 words per rule (Experiment 4). Theoretical implications of these findings are discussed.
PURPOSE: To compare the short-term effects of a neurodynamic sliding technique versus control condition on hamstring flexibility in healthy, asymptomatic male soccer players. SUBJECTS: Twenty-eight young male soccer players from Palencia, Spain (mean age 20.7 yrs ± 1.0, range 19-22) with decreased hamstring muscle flexibility. METHODS: Subjects were randomly assigned to one of two groups: neurodynamic sliding intervention or no intervention control. Each subject’s dominant leg was measured for straight leg raise (SLR) range of motion (ROM) pre- and post-intervention. Subjects received interventions as per group allocation over a 1 week period. Data were analyzed with a 2 (intervention: neurodynamic and control) × 2 (time: pre and post) factorial ANOVA with repeated measures and appropriate post-hoc analyses. RESULTS: A significant interaction was observed between intervention and time for hamstring extensibility, F(1,26) = 159.187, p < .0005. There was no difference between the groups at the start, p = .743; however, at the end of the study, the groups were significantly different with more range of motion in the group that received neurodynamic interventions, p = .001. The group that received neurodynamic interventions improved significantly over time (p < .001), whereas the control group did not (p = .684). CONCLUSION: Findings suggest that a neurodynamic sliding technique can increase hamstring flexibility in healthy, male soccer players.