scholarly journals What is the optimum design for my animal experiment?

2021 ◽  
Vol 5 (1) ◽  
pp. e100126
Author(s):  
Natasha A Karp ◽  
Derek Fry
Keyword(s):  
Experimental Design ◽  
Animal Experiment ◽  
Sex Bias ◽  
Benefit Analysis ◽  
Preclinical Research ◽  
Research Attention ◽  
Decision Points ◽  
Critical Issues ◽  
Graphical Summary ◽  
Animal Use

Within preclinical research, attention has focused on experimental design and how current practices can lead to poor reproducibility. There are numerous decision points when designing experiments. Ethically, when working with animals we need to conduct a harm–benefit analysis to ensure the animal use is justified for the scientific gain. Experiments should be robust, not use more or fewer animals than necessary, and truly add to the knowledge base of science. Using case studies to explore these decision points, we consider how individual experiments can be designed in several different ways. We use the Experimental Design Assistant (EDA) graphical summary of each experiment to visualise the design differences and then consider the strengths and weaknesses of each design. Through this format, we explore key and topical experimental design issues such as pseudo-replication, blocking, covariates, sex bias, inference space, standardisation fallacy and factorial designs. There are numerous articles discussing these critical issues in the literature, but here we bring together these topics and explore them using real-world examples allowing the implications of the choice of design to be considered. Fundamentally, there is no perfect experiment; choices must be made which will have an impact on the conclusions that can be drawn. We need to understand the limitations of an experiment’s design and when we report the experiments, we need to share the caveats that inherently exist.

scholarly journals Experimental replications in animal trials

2020 ◽  
pp. 002367722090761 ◽  
Author(s):  
Florian Frommlet ◽  
Georg Heinze
Keyword(s):  
Statistical Analysis ◽  
Experimental Design ◽  
Animal Models ◽  
Study Design ◽  
Recent Discussion ◽  
Preclinical Research ◽  
Animal Trials ◽  
Scientific Results

The recent discussion on the reproducibility of scientific results is particularly relevant for preclinical research with animal models. Within certain areas of preclinical research, there exists the tradition of repeating an experiment at least twice to demonstrate replicability. If the results of the first two experiments do not agree, then the experiment might be repeated a third time. Sometimes data of one representative experiment are shown; sometimes data from different experiments are pooled. However, there are hardly any guidelines about how to plan for such an experimental design or how to report the results obtained. This article provides a thorough statistical analysis of pre-planned experimental replications as they are currently often applied in practice and gives some recommendations about how to improve on study design and statistical analysis.

Software for designing rigorous and replicable preclinical research: The Experimental Design Accelerator

2019 ◽  
Vol 97 (9) ◽  
pp. 1043-1050
Author(s):  
David H. Malin ◽  
Scott A. Hetherington ◽  
Duyen M. Nghiem ◽  
Christopher P. Ward ◽  
Nicholas Kelling ◽  
...  
Keyword(s):  
Experimental Design ◽  
Preclinical Research

scholarly journals Neuro-Inflammation in Pediatric Traumatic Brain Injury—from Mechanisms to Inflammatory Networks

2019 ◽  
Vol 9 (11) ◽  
pp. 319 ◽  
Author(s):  
Erik Fraunberger ◽  
Michael J. Esser
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Imaging Techniques ◽  
Adult Population ◽  
Definitive Treatment ◽  
Preclinical Research ◽  
Research Attention ◽  
Neuro Inflammation ◽  
Long Term Impact ◽  
Pediatric Tbi

Compared to traumatic brain injury (TBI) in the adult population, pediatric TBI has received less research attention, despite its potential long-term impact on the lives of many children around the world. After numerous clinical trials and preclinical research studies examining various secondary mechanisms of injury, no definitive treatment has been found for pediatric TBIs of any severity. With the advent of high-throughput and high-resolution molecular biology and imaging techniques, inflammation has become an appealing target, due to its mixed effects on outcome, depending on the time point examined. In this review, we outline key mechanisms of inflammation, the contribution and interactions of the peripheral and CNS-based immune cells, and highlight knowledge gaps pertaining to inflammation in pediatric TBI. We also introduce the application of network analysis to leverage growing multivariate and non-linear inflammation data sets with the goal to gain a more comprehensive view of inflammation and develop prognostic and treatment tools in pediatric TBI.

Experimental design as a source of sex bias in social psychology

Sex Roles ◽  
1977 ◽  
Vol 3 (2) ◽  
pp. 117-128 ◽  
Author(s):  
Wendy McKenna ◽  
Suzanne J. Kessler
Keyword(s):  
Social Psychology ◽  
Experimental Design ◽  
Sex Bias

Outstanding Challenges in Scientific Research on Mindfulness and Meditation

2017 ◽  
Vol 13 (1) ◽  
pp. 62-65 ◽  
Author(s):  
Richard J. Davidson ◽  
Cortland J. Dahl
Keyword(s):  
Scientific Research ◽  
Future Research ◽  
Research Attention ◽  
Contemplative Practices ◽  
Large N ◽  
Key Points ◽  
Critical Issues ◽  
Key Issues ◽  
Future Work ◽  
Made In

Van Dam et al. raise a number of critical issues in contemporary research on mindfulness and meditation and offer a prescriptive agenda for future work in this area. While we agree with all of the key points made in their article, there are a number of important issues omitted that are central to a comprehensive agenda for future research in this area. This commentary highlights five key points: (a) Many of the key methodological issues the article raises are not specific to research on mindfulness; (b) contemplative practices are varied, and the landscape of modern scientific research has evolved to focus almost exclusively on one or two types of practice to the exclusion of other forms of practice that are potentially highly impactful; (c) mindfulness and related contemplative practices were not originally developed to treat disease; (d) key issues of duration, intensity and spacing of practice, and the extent to which formal meditation practice is required or whether practice can be piggybacked onto other non–cognitively demanding activities of daily living (e.g., commuting) remain as among the most important practical questions for disseminating these practices more widely, yet have received scant serious research attention; and (e) the use of mobile technology in both disseminating contemplative training and assessing its impact is going to be required to solve some of the key methodological challenges in this area including standardizing training across sites and addressing individual differences (which will require very large- N studies).

scholarly journals BEHAVIORAL AND CULTURAL ACCOUNTS OF CORRUPTION IN THE INTERFACE BETWEEN PUBLIC OFFICER AND CLIENT

2017 ◽  
Vol 13 (1) ◽  
Author(s):  
Tete Kobla Agbota ◽  
Ingunn Sandaker ◽  
Lucas Couto De Carvalho ◽  
Kalliu Couto
Keyword(s):  
Social Sciences ◽  
Cultural Practices ◽  
Analytic Framework ◽  
Research Attention ◽  
The Social ◽  
Behavior Analysts ◽  
Critical Issues ◽  
Corrupt Behavior

This paper applies a behavior analytic framework to examine corrupt behavior. With this article, we heed to the call made some decades ago to behavior analysts to extend the interests and strategies of their discipline into domains traditionally assigned to the social sciences. This article has three objectives: First, to examine corruption as behavioral and cultural phenomena; Second is to draw the attention of the social sciences community to the potentials of behavior analytic tools to investigate corrupt behavior; Third, to appeal to behavior analysts to direct some research attention to corruption, which is one of the most critical issues of the twenty-first century.Keywords: corruption, Contingencies, Metacontingencies, Cultural practices, Culture.

Safety Issues in Local/Short Haul Trucking: The Drivers' Perspective

1998 ◽  
Vol 42 (17) ◽  
pp. 1185-1189 ◽  
Author(s):  
Richard J. Hanowski ◽  
Walter W. Wierwille ◽  
Andrew W. Gellatly ◽  
Ronald R. Knipling ◽  
Robert Carroll
Keyword(s):  
Experimental Design ◽  
Focus Groups ◽  
Time Pressure ◽  
Causal Factors ◽  
Safety Issues ◽  
Safety Critical ◽  
Follow Up Study ◽  
Critical Issues

Focus groups were conducted to gain an understanding, from the local/short haul (L/SH) drivers' perspective, of the general safety concerns related to L/SH trucking and, specifically, the degree to which fatigue plays a role. Eleven focus groups were held in eight cities, across five states. Eighty-two L/SH drivers participated. Much of the focus group activity involved discussions of critical incidents that drivers had either learned about or had personally experienced. One of the purposes of this discussion was to generate a list of causal factors that would highlight safety-critical issues in the L/SH industry. Across all sessions, the top five critical issues/causal factors, ranked in terms of importance, were: (1) Problems Caused by Drivers of Light Vehicles, (2) Stress Due to Time Pressure, (3) Inattention, (4) Problems Caused by Roadway/Dock Design, and (5) Fatigue. These findings are being incorporated into the experimental design of a follow-up study where L/SH driving data will be collected in situ.

scholarly journals Valid statistical approaches for clustered data: A Monte Carlo simulation study

2020 ◽  
Author(s):  
Kristen A. McLaurin ◽  
Amanda J. Fairchild ◽  
Dexin Shi ◽  
Rosemarie M. Booze ◽  
Charles F. Mactutus
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Experimental Design ◽  
Simulation Study ◽  
Fixed Effects ◽  
Interactive Effects ◽  
Multilevel Data ◽  
Preclinical Research ◽  
Culture Dish ◽  
Monte Carlo Simulation Study

AbstractThe translation of preclinical studies to human applications is associated with a high failure rate, which may be exacerbated by limited training in experimental design and statistical analysis. Nested experimental designs, which occur when data have a multilevel structure (e.g., in vitro: cells within a culture dish; in vivo: rats within a litter), often violate the independent observation assumption underlying many traditional statistical techniques. Although previous studies have empirically evaluated the analytic challenges associated with multilevel data, existing work has not focused on key parameters and design components typically observed in preclinical research. To address this knowledge gap, a Monte Carlo simulation study was conducted to systematically assess the effects of inappropriately modeling multilevel data via a fixed effects ANOVA in studies with sparse observations, no between group comparison within a single cluster, and interactive effects. Simulation results revealed a dramatic increase in the probability of type 1 error and relative bias of the standard error as the number of level-1 (e.g., cells; rats) units per cell increased in the fixed effects ANOVA; these effects were largely attenuated when the nesting was appropriately accounted for via a random effects ANOVA. Thus, failure to account for a nested experimental design may lead to reproducibility challenges and inaccurate conclusions. Appropriately accounting for multilevel data, however, may enhance statistical reliability, thereby leading to improvements in translatability. Valid analytic strategies are provided for a variety of design scenarios.

scholarly journals Germline Engineering and Human Rights

AJIL Unbound ◽  
2018 ◽  
Vol 112 ◽  
pp. 344-349 ◽  
Author(s):  
R. Alta Charo
Keyword(s):  
Human Rights ◽  
Genome Editing ◽  
Genetic Manipulation ◽  
Preclinical Research ◽  
Subject Recruitment ◽  
Decision Points ◽  
Medical Need ◽  
New Gene ◽  
International Summit ◽  
Germline Engineering

With the ever-increasing range of medical technologies at our disposal to mediate the processes of life, from conception to death, comes an ever-increasing number of decision points about human control of fate. And as we debate altering our fate—whether dictated by a deity or by chance—the discussion frequently devolves into a question of whether we may alter not only our own fate, but also that of our children. The advent of genome editing, whether by older methods or the newer, often more easily used methods employing CRISPR, has only made debating the controversial possibility of heritable “germline” editing more urgent. The advent of genome editing, whether by older methods or the newer, often more easily used methods employing CRISPR, has only made debating the controversial possibility of heritable “germline” editing more urgent. On the eve of the Second International Summit on Human Genome Editing, held at the end of November 2018 in Hong Kong, a startling and disturbing story began circulating - a Chinese researcher announced the first births of children whose genomes had been edited at the embryonic stage. The work (assuming the claim can be verified) suffered from myriad problems, beginning with the lack of a compelling medical need, and including inadequate preclinical research, lack of peer review, flawed subject recruitment and consent procedures, and an apparent disregard for both formal and informal rules governing genetic manipulation of embryos. The summit's organizing committee issued a statement, distinguishing this experiment from what would be a responsible translational pathway forward. But not surprisingly, others around the world immediately called for a global, enforceable prohibition on such genetic engineering. On the occasion of the Universal Declaration on Human Rights (UDHR)’s seventieth anniversary, this essay argues that the current human rights law on germline editing misunderstands both the mechanisms of genetics and the moral basis for human rights, suggesting a more nuanced approach as we move forward and keep pace with new gene-editing technologies.

scholarly journals Translational Intracerebral Hemorrhage Research: Has Current Neuroprotection Research ARRIVEd at a Standard for Experimental Design and Reporting?

2020 ◽  
Vol 11 (6) ◽  
pp. 1203-1213 ◽  
Author(s):  
Lane J. Liddle ◽  
Shivani Ralhan ◽  
Daniel L. Ward ◽  
Frederick Colbourne
Keyword(s):  
Experimental Design ◽  
Intracerebral Hemorrhage ◽  
Animal Studies ◽  
Effect Sizes ◽  
Healthy Male ◽  
Preclinical Research ◽  
Exclusion Criteria ◽  
Current Review ◽  
Pubmed Database ◽  
Design Characteristics

Abstract One major aim of preclinical intracerebral hemorrhage (ICH) research is to develop and test potential neuroprotectants. Published guidelines for experimental design and reporting stress the importance of clearly and completely reporting results and methodological details to ensure reproducibility and maximize information availability. The current review has two objectives: first, to characterize current ICH neuroprotection research and, second, to analyze aspects of translational design in preclinical ICH studies. Translational design is the adoption and reporting of experimental design characteristics that are thought to be clinically relevant and critical to reproducibility in animal studies (e.g., conducting and reporting experiments according to the STAIR and ARRIVE guidelines, respectively). Given that ICH has no current neuroprotective treatments and an ongoing reproducibility crisis in preclinical research, translational design should be considered by investigators. We conducted a systematic review of ICH research from 2015 to 2019 using the PubMed database. Our search returned 281 published manuscripts studying putative neuroprotectants in animal models. Contemporary ICH research predominantly uses young, healthy male rodents. The collagenase model is the most commonly used. Reporting of group sizes, blinding, and randomization are almost unanimous, but group size calculations, mortality and exclusion criteria, and animal model characteristics are infrequently reported. Overall, current ICH neuroprotection research somewhat aligns with experimental design and reporting guidelines. However, there are areas for improvement. Because failure to consider translational design is associated with inflation of effect sizes (and possibly hindered reproducibility), we suggest that researchers, editors, and publishers collaboratively consider enhanced adherence to published guidelines.

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