Best Practices for Creating Replicable Research

Author(s):  
Aaron M. Ellison

This chapter suggests a series of best practices for creating replicable research that cross disciplinary boundaries. First, the observational or experimental design should account for variation within and among sites, whether in the field or in the laboratory. Second, the acceptable levels of Type I and Type II statistical errors should be set before the project begins. Third, investigators should carefully and quantitatively review the literature and/or do a pilot study to determine the expected effect size (e.g., the expected relationship(s) between two or more variables of interest or the difference in outcome between experimental treatments and controls) and its variance. Finally, there should be a clear assessment of resources available.

1999 ◽  
Vol 82 (5) ◽  
pp. 2092-2107 ◽  
Author(s):  
Harumitsu Hirata ◽  
James W. Hu ◽  
David A. Bereiter

Corneal-responsive neurons were recorded extracellularly in two regions of the spinal trigeminal nucleus, subnucleus interpolaris/caudalis (Vi/Vc) and subnucleus caudalis/upper cervical cord (Vc/C1) transition regions, from methohexital-anesthetized male rats. Thirty-nine Vi/Vc and 26 Vc/C1 neurons that responded to mechanical and electrical stimulation of the cornea were examined for convergent cutaneous receptive fields, responses to natural stimulation of the corneal surface by CO2 pulses (0, 30, 60, 80, and 95%), effects of morphine, and projections to the contralateral thalamus. Forty-six percent of mechanically sensitive Vi/Vc neurons and 58% of Vc/C1 neurons were excited by CO2 stimulation. The evoked activity of most cells occurred at 60% CO2 after a delay of 7–22 s. At the Vi/Vc transition three response patterns were seen. Type I cells ( n = 11) displayed an increase in activity with increasing CO2 concentration. Type II cells ( n = 7) displayed a biphasic response, an initial inhibition followed by excitation in which the magnitude of the excitatory phase was dependent on CO2 concentration. A third category of Vi/Vc cells (type III, n = 3) responded to CO2 pulses only after morphine administration (>1.0 mg/kg). At the Vc/C1 transition, all CO2-responsive cells ( n = 15) displayed an increase in firing rates with greater CO2 concentration, similar to the pattern of type I Vi/Vc cells. Comparisons of the effects of CO2 pulses on Vi/Vc type I units, Vi/Vc type II units, and Vc/C1 corneal units revealed no significant differences in threshold intensity, stimulus encoding, or latency to sustained firing. Morphine (0.5–3.5 mg/kg iv) enhanced the CO2-evoked activity of 50% of Vi/Vc neurons tested, whereas all Vc/C1 cells were inhibited in a dose-dependent, naloxone-reversible manner. Stimulation of the contralateral posterior thalamic nucleus antidromically activated 37% of Vc/C1 corneal units; however, no effective sites were found within the ventral posteromedial thalamic nucleus or nucleus submedius. None of the Vi/Vc corneal units tested were antidromically activated from sites within these thalamic regions. Corneal-responsive neurons in the Vi/Vc and Vc/C1 regions likely serve different functions in ocular nociception, a conclusion reflected more by the difference in sensitivity to analgesic drugs and efferent projection targets than by the CO2 stimulus intensity encoding functions. Collectively, the properties of Vc/C1 corneal neurons were consistent with a role in the sensory-discriminative aspects of ocular pain due to chemical irritation. The unique and heterogeneous properties of Vi/Vc corneal neurons suggested involvement in more specialized ocular functions such as reflex control of tear formation or eye blinks or recruitment of antinociceptive control pathways.


2021 ◽  
Author(s):  
Mutsuaki Edama ◽  
Tomoya Takabayashi ◽  
Hirotake Yokota ◽  
Ryo Hirabayashi ◽  
Chie Sekine ◽  
...  

Abstract Background For the anterior talofibular ligament (ATFL), a three-fiber bundle has recently been suggested to be weaker than a single or double fiber bundle in terms of ankle plantarflexion and inversion braking function. However, the studies leading to those results all used elderly specimens. Whether the difference in fiber bundles is a congenital or an acquired morphology is important when considering methods to prevent ATFL damage. The purpose of this study was to classify the number of fiber bundles in the ATFL of fetuses. Methods This study was conducted using 30 legs from 15 Japanese fetuses (mean weight, 1764.6 ± 616.9 g; mean crown-rump length, 283.5 ± 38.7 mm; 8 males, 7 females). The ATFL was then classified by the number of fiber bundles: Type I, one fiber bundle; Type II, two fiber bundles; and Type III, three fiber bundles. Results Ligament type was Type I in 5 legs (16.7%), Type II in 21 legs (70%), and Type III in 4 legs (13.3%). Conclusions The present results suggest that the three fiber bundles of the structure of the ATFL may be an innate structure.


Author(s):  
XU Chuang ◽  
Shen Tai-yu ◽  
YAO Yuan ◽  
Yu Hong-jiang ◽  
XIA Cheng ◽  
...  

The purpose was to determine the difference of blood clinicopathological changes between type I and type II ketosis in dairy cow. Fifty-eight cows, from dairy cattle farm in Heilongjiang of China, were included. An ELISA test was used to evaluate the blood indicators. The plasma concentrations of beta-hydroxybutyric acid (BHBA) and insulin sensitivity decreased, and the plasma concentration of glucose (Glc), non-esterified fatty acid (NEFA) and bilirubin content increased in type II ketosis group compared with the type I ketosis group. These results showed that there was a difference in etiology between type II ketosis and type I ketosis. Type II ketosis was not only associated with energy metabolism and insulin resistance, but also with oxidative stress and liver function. It laid the foundation for further investigate the mechanism and prevention of type II ketosis in the future.


2002 ◽  
Vol 28 (4) ◽  
pp. 515-530 ◽  
Author(s):  
Rachel A. Smith ◽  
Timothy R. Levine ◽  
Kenneth A. Lachlan ◽  
Thomas A. Fediuk

2021 ◽  
Vol 81 (5) ◽  
Author(s):  
Fabrizio Canfora ◽  
Seung Hun Oh

AbstractTwo analytic examples of globally regular non-Abelian gravitating solitons in the Einstein–Yang–Mills–Higgs theory in (3 + 1)-dimensions are presented. In both cases, the space-time geometries are of the Nariai type and the Yang–Mills field is completely regular and of meron type (namely, proportional to a pure gauge). However, while in the first family (type I) $$X_{0} = 1/2$$ X 0 = 1 / 2 (as in all the known examples of merons available so far) and the Higgs field is trivial, in the second family (type II) $$X_{0} = 1/2$$ X 0 = 1 / 2 is not 1/2 and the Higgs field is non-trivial. We compare the entropies of type I and type II families determining when type II solitons are favored over type I solitons: the VEV of the Higgs field plays a crucial role in determining the phases of the system. The Klein–Gordon equation for test scalar fields coupled to the non-Abelian fields of the gravitating solitons can be written as the sum of a two-dimensional D’Alembert operator plus a Hamiltonian which has been proposed in the literature to describe the four-dimensional Quantum Hall Effect (QHE): the difference between type I and type II solutions manifests itself in a difference between the degeneracies of the corresponding energy levels.


Development ◽  
1997 ◽  
Vol 124 (14) ◽  
pp. 2819-2828 ◽  
Author(s):  
M. Vervoort ◽  
D.J. Merritt ◽  
A. Ghysen ◽  
C. Dambly-Chaudiere

The embryonic peripheral nervous system of Drosophila contains two main types of sensory neurons: type I neurons, which innervate external sense organs and chordotonal organs, and type II multidendritic neurons. Here, we analyse the origin of the difference between type I and type II in the case of the neurons that depend on the proneural genes of the achaete-scute complex (ASC). We show that, in Notch- embryos, the type I neurons are missing while type II neurons are produced in excess, indicating that the type I/type II choice relies on Notch-mediated cell communication. In contrast, both type I and type II neurons are absent in numb- embryos and after ubiquitous expression of tramtrack, indicating that the activity of numb and the absence of tramtrack are required to produce both external sense organ and multidendritic neural fates. The analysis of string- embryos reveals that when the precursors are unable to divide they differentiate mostly into type II neurons, indicating that the type II is the default neuronal fate. We also report a new mutant phenotype where the ASC-dependent neurons are converted into type II neurons, providing evidence for the existence of one or more genes required for maintaining the alternative (type I) fate. Our results suggest that the same mechanism of type I/type II specification may operate at a late step of the ASC-dependent lineages, when multidendritic neurons arise as siblings of the external sense organ neurons and, at an early step, when other multidendritic neurons precursors arise as siblings of external sense organ precursors.


Author(s):  
Rand R. Wilcox

Hypothesis testing is an approach to statistical inference that is routinely taught and used. It is based on a simple idea: develop some relevant speculation about the population of individuals or things under study and determine whether data provide reasonably strong empirical evidence that the hypothesis is wrong. Consider, for example, two approaches to advertising a product. A study might be conducted to determine whether it is reasonable to assume that both approaches are equally effective. A Type I error is rejecting this speculation when in fact it is true. A Type II error is failing to reject when the speculation is false. A common practice is to test hypotheses with the type I error probability set to 0.05 and to declare that there is a statistically significant result if the hypothesis is rejected. There are various concerns about, limitations to, and criticisms of this approach. One criticism is the use of the term significant. Consider the goal of comparing the means of two populations of individuals. Saying that a result is significant suggests that the difference between the means is large and important. But in the context of hypothesis testing it merely means that there is empirical evidence that the means are not equal. Situations can and do arise where a result is declared significant, but the difference between the means is trivial and unimportant. Indeed, the goal of testing the hypothesis that two means are equal has been criticized based on the argument that surely the means differ at some decimal place. A simple way of dealing with this issue is to reformulate the goal. Rather than testing for equality, determine whether it is reasonable to make a decision about which group has the larger mean. The components of hypothesis-testing techniques can be used to address this issue with the understanding that the goal of testing some hypothesis has been replaced by the goal of determining whether a decision can be made about which group has the larger mean. Another aspect of hypothesis testing that has seen considerable criticism is the notion of a p-value. Suppose some hypothesis is rejected with the Type I error probability set to 0.05. This leaves open the issue of whether the hypothesis would be rejected with Type I error probability set to 0.025 or 0.01. A p-value is the smallest Type I error probability for which the hypothesis is rejected. When comparing means, a p-value reflects the strength of the empirical evidence that a decision can be made about which has the larger mean. A concern about p-values is that they are often misinterpreted. For example, a small p-value does not necessarily mean that a large or important difference exists. Another common mistake is to conclude that if the p-value is close to zero, there is a high probability of rejecting the hypothesis again if the study is replicated. The probability of rejecting again is a function of the extent that the hypothesis is not true, among other things. Because a p-value does not directly reflect the extent the hypothesis is false, it does not provide a good indication of whether a second study will provide evidence to reject it. Confidence intervals are closely related to hypothesis-testing methods. Basically, they are intervals that contain unknown quantities with some specified probability. For example, a goal might be to compute an interval that contains the difference between two population means with probability 0.95. Confidence intervals can be used to determine whether some hypothesis should be rejected. Clearly, confidence intervals provide useful information not provided by testing hypotheses and computing a p-value. But an argument for a p-value is that it provides a perspective on the strength of the empirical evidence that a decision can be made about the relative magnitude of the parameters of interest. For example, to what extent is it reasonable to decide whether the first of two groups has the larger mean? Even if a compelling argument can be made that p-values should be completely abandoned in favor of confidence intervals, there are situations where p-values provide a convenient way of developing reasonably accurate confidence intervals. Another argument against p-values is that because they are misinterpreted by some, they should not be used. But if this argument is accepted, it follows that confidence intervals should be abandoned because they are often misinterpreted as well. Classic hypothesis-testing methods for comparing means and studying associations assume sampling is from a normal distribution. A fundamental issue is whether nonnormality can be a source of practical concern. Based on hundreds of papers published during the last 50 years, the answer is an unequivocal Yes. Granted, there are situations where nonnormality is not a practical concern, but nonnormality can have a substantial negative impact on both Type I and Type II errors. Fortunately, there is a vast literature describing how to deal with known concerns. Results based solely on some hypothesis-testing approach have clear implications about methods aimed at computing confidence intervals. Nonnormal distributions that tend to generate outliers are one source for concern. There are effective methods for dealing with outliers, but technically sound techniques are not obvious based on standard training. Skewed distributions are another concern. The combination of what are called bootstrap methods and robust estimators provides techniques that are particularly effective for dealing with nonnormality and outliers. Classic methods for comparing means and studying associations also assume homoscedasticity. When comparing means, this means that groups are assumed to have the same amount of variance even when the means of the groups differ. Violating this assumption can have serious negative consequences in terms of both Type I and Type II errors, particularly when the normality assumption is violated as well. There is vast literature describing how to deal with this issue in a technically sound manner.


2018 ◽  
Vol 108 (1) ◽  
pp. 15-22 ◽  
Author(s):  
David H. Gent ◽  
Paul D. Esker ◽  
Alissa B. Kriss

In null hypothesis testing, failure to reject a null hypothesis may have two potential interpretations. One interpretation is that the treatments being evaluated do not have a significant effect, and a correct conclusion was reached in the analysis. Alternatively, a treatment effect may have existed but the conclusion of the study was that there was none. This is termed a Type II error, which is most likely to occur when studies lack sufficient statistical power to detect a treatment effect. In basic terms, the power of a study is the ability to identify a true effect through a statistical test. The power of a statistical test is 1 – (the probability of Type II errors), and depends on the size of treatment effect (termed the effect size), variance, sample size, and significance criterion (the probability of a Type I error, α). Low statistical power is prevalent in scientific literature in general, including plant pathology. However, power is rarely reported, creating uncertainty in the interpretation of nonsignificant results and potentially underestimating small, yet biologically significant relationships. The appropriate level of power for a study depends on the impact of Type I versus Type II errors and no single level of power is acceptable for all purposes. Nonetheless, by convention 0.8 is often considered an acceptable threshold and studies with power less than 0.5 generally should not be conducted if the results are to be conclusive. The emphasis on power analysis should be in the planning stages of an experiment. Commonly employed strategies to increase power include increasing sample sizes, selecting a less stringent threshold probability for Type I errors, increasing the hypothesized or detectable effect size, including as few treatment groups as possible, reducing measurement variability, and including relevant covariates in analyses. Power analysis will lead to more efficient use of resources and more precisely structured hypotheses, and may even indicate some studies should not be undertaken. However, the conclusions of adequately powered studies are less prone to erroneous conclusions and inflated estimates of treatment effectiveness, especially when effect sizes are small.


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