We propose to change the default P-value threshold for statistical significance from 0.05 to 0.005 for claims of new discoveries. T he lack of reproducibility of scientific studies has caused growing concern over the credibility of claims of new discoveries based on 'statistically significant' findings. There has been much progress toward documenting and addressing several causes of this lack of reproducibility (for example, multiple testing, P-hacking, publication bias and under-powered studies). However, we believe that a leading cause of non-reproducibility has not yet been adequately addressed: statistical standards of evidence for claiming new discoveries in many fields of science are simply too low. Associating statistically significant findings with P < 0.05 results in a high rate of false positives even in the absence of other experimental, procedural and reporting problems.For fields where the threshold for defining statistical significance for new discoveries is P < 0.05, we propose a change to P < 0.005. This simple step would immediately improve the reproducibility of scientific research in many fields. Results that would currently be called significant but do not meet the new threshold should instead be called suggestive. While statisticians have known the relative weakness of using P ≈ 0.05 as a threshold for discovery and the proposal to lower it to 0.005 is not new 1,2 , a critical mass of researchers now endorse this change.We restrict our recommendation to claims of discovery of new effects. We do not address the appropriate threshold for confirmatory or contradictory replications of existing claims. We also do not advocate changes to discovery thresholds in fields that have already adopted more stringent standards (for example, genomics and high-energy physics research; see the 'Potential objections' section below).We also restrict our recommendation to studies that conduct null hypothesis significance tests. We have diverse views about how best to improve reproducibility, and many of us believe that other ways of summarizing the data, such as Bayes factors or other posterior summaries based on clearly articulated model assumptions, are preferable to P values. However, changing the P value threshold is simple, aligns with the training undertaken by many researchers, and might quickly achieve broad acceptance.
Most researchers acknowledge an intrinsic hierarchy in the scholarly journals (“journal rank”) that they submit their work to, and adjust not only their submission but also their reading strategies accordingly. On the other hand, much has been written about the negative effects of institutionalizing journal rank as an impact measure. So far, contributions to the debate concerning the limitations of journal rank as a scientific impact assessment tool have either lacked data, or relied on only a few studies. In this review, we present the most recent and pertinent data on the consequences of our current scholarly communication system with respect to various measures of scientific quality (such as utility/citations, methodological soundness, expert ratings or retractions). These data corroborate previous hypotheses: using journal rank as an assessment tool is bad scientific practice. Moreover, the data lead us to argue that any journal rank (not only the currently-favored Impact Factor) would have this negative impact. Therefore, we suggest that abandoning journals altogether, in favor of a library-based scholarly communication system, will ultimately be necessary. This new system will use modern information technology to vastly improve the filter, sort and discovery functions of the current journal system.
Operant conditioning is a form of associative learning through which an animal learns about the consequences of its behavior. Here, we report an appetitive operant conditioning procedure in Aplysia that induces long-term memory. Biophysical changes that accompanied the memory were found in an identified neuron (cell B51) that is considered critical for the expression of behavior that was rewarded. Similar cellular changes in B51 were produced by contingent reinforcement of B51 with dopamine in a single-cell analog of the operant procedure. These findings allow for the detailed analysis of the cellular and molecular processes underlying operant conditioning.
Brains are usually described as input/output systems: they transform sensory input into motor output. However, the motor output of brains (behavior) is notoriously variable, even under identical sensory conditions. The question of whether this behavioral variability merely reflects residual deviations due to extrinsic random noise in such otherwise deterministic systems or an intrinsic, adaptive indeterminacy trait is central for the basic understanding of brain function. Instead of random noise, we find a fractal order (resembling Lévy flights) in the temporal structure of spontaneous flight maneuvers in tethered Drosophila fruit flies. Lévy-like probabilistic behavior patterns are evolutionarily conserved, suggesting a general neural mechanism underlying spontaneous behavior. Drosophila can produce these patterns endogenously, without any external cues. The fly's behavior is controlled by brain circuits which operate as a nonlinear system with unstable dynamics far from equilibrium. These findings suggest that both general models of brain function and autonomous agents ought to include biologically relevant nonlinear, endogenous behavior-initiating mechanisms if they strive to realistically simulate biological brains or out-compete other agents.
To understand how transposon landscapes (TLs) vary across animal genomes, we describe a new method called the Transposon Insertion and Depletion AnaLyzer (TIDAL) and a database of >300 TLs in Drosophila melanogaster (TIDAL-Fly). Our analysis reveals pervasive TL diversity across cell lines and fly strains, even for identically named sub-strains from different laboratories such as the ISO1 strain used for the reference genome sequence. On average, >500 novel insertions exist in every lab strain, inbred strains of the Drosophila Genetic Reference Panel (DGRP), and fly isolates in the Drosophila Genome Nexus (DGN). A minority (<25%) of transposon families comprise the majority (>70%) of TL diversity across fly strains. A sharp contrast between insertion and depletion patterns indicates that many transposons are unique to the ISO1 reference genome sequence. Although TL diversity from fly strains reaches asymptotic limits with increasing sequencing depth, rampant TL diversity causes unsaturated detection of TLs in pools of flies. Finally, we show novel transposon insertions negatively correlate with Piwi-interacting RNA (piRNA) levels for most transposon families, except for the highly-abundant roo retrotransposon. Our study provides a useful resource for Drosophila geneticists to understand how transposons create extensive genomic diversity in fly cell lines and strains.
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