When should potentially false research findings be considered acceptable?

Ioannidis estimated that most published research findings are false, but he did not indicate when, if at all, potentially false research results may be considered as acceptable to society. We combined our two previously published models to calculate the probability above which research findings may become acceptable. A new model indicates that the probability above which research results should be accepted depends on the expected payback from the research (the benefits) and the inadvertent consequences (the harms). This probability may dramatically change depending on our willingness to tolerate error in accepting false research findings. Our acceptance of research findings changes as a function of what we call "acceptable regret," i.e., our tolerance of making a wrong decision in accepting the research hypothesis. We illustrate our findings by providing a new framework for early stopping rules in clinical research (i.e., when should we accept early findings from a clinical trial indicating the benefits as true?). Obtaining absolute "truth" in research is impossible, and so society has to decide when less-than-perfect results may become acceptable.     

When should a DDH experiment be mandatory in microbial taxonomy?

DNA–DNA hybridizations (DDH) play a key role in microbial species discrimination in cases when 16S rRNA gene sequence similarities are 97 % or higher. Using real-world 16S rRNA gene sequences and DDH data, we here re-investigate whether or not, and in which situations, this threshold value might be too conservative. Statistical estimates of these thresholds are calculated in general as well as more specifically for a number of phyla that are frequently subjected to DDH. Among several methods to infer 16S gene sequence similarities investigated, most of those routinely applied by taxonomists appear well suited for the task. The effects of using distinct DDH methods also seem to be insignificant. Depending on the investigated taxonomic group, a threshold between 98.2 and 99.0 % appears reasonable. In that way, up to half of the currently conducted DDH experiments could safely be omitted without a significant risk for wrongly differentiated species.     

Can the theory of evolution be falsified?

In this paper we discuss the epistemological positions of evolution theories. A sharp distinction is made between the theory that species evolved from common ancestors along specified lines of descent (here called the theory of common descent), and the theories intended as causal explanations of evolution (e.g. Lamarck's and Darwin's theory). The theory of common descent permits a large number of predictions of new results that would be improbable without evolution. For instance, (a) phylogenetic trees have been validated now; (b) the observed order in fossils of new species discovered since Darwin's time could be predicted from the theory of common descent; (c) owing to the theory of common descent, the degrees of similarity and difference in newly discovered properties of more or less related species could be predicted. Such observations can be regarded as attempts to falsify the theory of common descent. We conclude that the theory of common descent is an easily-falsifiable & often-tested & still-not-falsified theory, which is the strongest predicate a theory in an empirical science can obtain. Theories intended as causal explanations of evolution can be falsified essentially, and Lamarck's theory has been falsified actually. Several elements of Darwin's theory have been modified or falsified: new versions of a theory of evolution by natural selection are now the leading scientific theories on evolution. We have argued that the theory of common descent and Darwinism are ordinary, falsifiable scientific theories.     

When should males lek? Insights from a dynamic state variable model

A central focus in the study of lek evolution is to understandthe clustering of male mating territories. Lekking males typicallydefend small clumped territories and experience intense competitionassociated with dense aggregations. We used dynamic state variablemodeling to evaluate three alternative selective pressures proposedto explain the evolution of lekking. These are female matingbias for large clusters, reduction in predation risk in largeclusters, and male harassment of estrous females. We modeledmale mating decisions during a single breeding season usinga lekking ungulate as a model system. Males could choose fromeight alternative tactics that included a nonreproductive tactic,territorial tactics ranging from low to high clustering, andthe option to join a mixed-sex herd. The model predicted a state-and time-dependent strategy that maximizes mating success overthe course of the season. We then simulated a population of100 males that used the optimal strategy and calculated theproportion of the population that adopted each tactic. Our modelgenerated unique predictions for the three selective pressureswe considered. Female mating bias, when nonlinearly relatedto cluster size, had the greatest potential to generate largeclusters of territorial males, whereas predation risk and harassmentof females typically did not promote male clustering. More generally,our model highlights the conditions that will favor lekking.Lek-like clustering was consistently produced when the benefitsin clustering increased in specific nonlinear ways. Our modelthus emphasizes clarifying the shapes of relationships betweenpotential selective factors and the size of territory clusters.     

What risks should be permissible in controlled human infection model studies?

Controlled human infection model (CHIM) studies involve the intentional exposure of healthy research volunteers to infectious agents. These studies contribute to knowledge about the cause or development of disease and to the advancement of vaccine research. But they also raise ethical questions about the kinds of risks that should be permissible and whether limits should be imposed on research risks in CHIM studies. Two possible risk thresholds have been considered for CHIM studies. The first suggests constraining ethically permissible risks according to a minimal risk threshold and the second endorses a higher risk threshold that excludes irreversible or fatal infections. I argue that neither of these thresholds is persuasive and situate questions about risk thresholds in CHIM studies within a broader debate about permissible risks in research. I argue that risks in CHIM studies should be constrained according to limits on research risks that do not offer corresponding benefits in all studies rather than developing a unique risk threshold for CHIM studies. I then propose five recommendations for the ethical assessment of risk in CHIM studies.     

Resistance is useless?—Extensions to the game theory of kleptoparasitism

We extend the game theoretic model of kleptoparasitism introduced by Broom and Ruxton (1998, Behav. Ecol. 9, 397–403) in two ways: we allow for asymmetric contests, where the probability α of the challenger winning can take any value from 0 to 1; and we allow the handler to choose not to resist the challenge, but to immediately concede and relinquish its food to the challenger. We find, in general, three possible evolutionarily stable strategies—challenge-and-resist (Hawk), challenge-but-do-not-resist (Marauder) and do-not-challenge-but-resist (Retaliator). When α = 1/2, we find that Hawk and Marauder are the only ESS’s, in contrast to the result of the original model; we also find an overlap region, in parameter space, where two different ESS’s are possible, depending on initial conditions. For general α, we see that all three ESS are possible, depending on different values of the environmental parameters; however, as the average time of a contest over food becomes long, then the Marauder strategy becomes more and more prevalent. The model makes a potentially significant prediction about animal behaviour in the area of kleptoparasitism, that a searcher, when it meets a handler, will only decline to attack that handler when α < 1/2 i.e.when the defender is more likely to win. One possible converse of this statement, that a handler whose probability of success is greater than 1/2 should always resist a challenge, is not true.     

When will rejection of parasite nestlings by hosts of nonevicting avian brood parasites be favored? A misimprinting-equilibrium model

It has been suggested that discrimination and rejection of thenestlings of avian brood parasites are most likely to evolvewhen the parasite nestling is raised alongside the host nestlings,for example, many cowbird-host systems. Under these circumstances,the benefits of discrimination are high because the host parentsmay save most of their brood. However, there is a general absenceof nestling rejection behavior among hosts of nonevicting parasites.In a cost-benefit equilibrium model, based on the premise thathost species learn to recognize their offspring through imprintingon first breeding, we show that nestling recognition can beadaptive for hosts of cowbirds, but only under strict conditions.Namely, when host nestling survival alongside the parasite islow, rates of parasitism are high and the average clutch sizeis large. All of these conditions are seldom simultaneouslyachieved in real systems. Most importantly, the parasite nestling,on average, does not sufficiently depress host nestling survivalto outweigh the costs of nestling recognition and rejectionerrors. Thus, we argue that nestling acceptance behaviors byhosts of nonevicting brood parasites may be explained as anevolutionary equilibrium in which recognition costs act as astabilizing selection pressure against rejection when most ofthe host's offspring survive parasitism.     

When should species richness be energy limited,and how would we know?

Energetic constraints are fundamental to ecology and evolution, and empirical relationships between species richness and estimates of available energy (i.e. resources) have led some to suggest that richness is energetically constrained. However, the mechanism linking energy with richness is rarely specified and predictions of secondary patterns consistent with energy‐constrained richness are lacking. Here, we lay out the necessary and sufficient assumptions of a causal relationship linking energy gradients to richness gradients. We then describe an eco‐evolutionary simulation model that combines spatially explicit diversification with trait evolution, resource availability and assemblage‐level carrying capacities. Our model identified patterns in richness and phylogenetic structure expected when a spatial gradient in energy availability determines the number of individuals supported in a given area. A comparison to patterns under alternative scenarios, in which fundamental assumptions behind energetic explanations were violated, revealed patterns that are useful for evaluating the importance of energetic constraints in empirical systems. We use a data set on rockfish (genus Sebastes) from the northeastern Pacific to show how empirical data can be coupled with model predictions to evaluate the role of energetic constraints in generating observed richness gradients.     

What should the Z-score of native protein structures be?

The Z-score of a protein is defined as the energy separation between the native fold and the average of an ensemble of misfolds in the units of the standard deviation of the ensemble. The Z-score is often used as a way of testing the knowledge-based potentials for their ability to recognize the native fold from other alternatives. However, it is not known what range of values the Z-scores should have if one had a correct potential. Here, we offer an estimate of Z-scores extracted from calorimetric measurements of proteins. The energies obtained from these experimental data are compared with those from computer simulations of a lattice model protein. It is suggested that the Z-scores calculated from different knowledge-based potentials are generally too small in comparison with the experimental values.     

When should a female avoid adding eggs to the clutch of another female? A simultaneous oviposition and sex allocation game

Summary Avoidance of double oviposition (ADO) is the strategy not to oviposit on food patches where another female has oviposited before. If two females oviposit on the same patch, competitive and mating interactions within and between broods may lead to both a clutch size game and a sex allocation game between the two visitors. Though the two games interact, they are usually considered separately. Here, the ESS conditions for ADO are investigated in an analysis that combines the two games into one. The analysis strengthens the notion that it is really ADO that needs to be explained, because role-dependent net pay-off from an additional egg is most likely to favour double oviposition (DO). To a first female, the net payoff includes the effect on the eggs already present, whereas to a second female only the egg's gross pay-off matters. ADO is the evolutionary stable strategy (ESS) if there are enough patches still without eggs and either (1) the fitness of an additional egg is so low that the first female would not lay it even in the absence of detrimental effects on earlier offspring, so neither would a second female, or (2) differences in either the survival probability of the offspring or their reproductive success are sufficient to counterbalance the differential interest in the eggs already present. The first condition requires that eggs are relatively large, because then the decrease in pay-off between two successive eggs can be large. The second condition may be met when there is a time interval between ovipositions of subsequent females. The resulting developmental lag of the second clutch will (1) diminish its ability to compete for food and (2) lower its reproductive success when there is local mate competition and sons are too late to mate with daughters of the first female. If sons of first and second females compete on equal terms, however, ADO is unlikely. Male migration between patches reduces the influence of sex allocation strategies on clutch size decisions; the same holds for small clutch sizes. To illustrate the importance of considering sex allocation and clutch size decisions in an integrated way, oviposition strategies of plant-inhabiting predatory mites (Acari: Phytoseiidae) are discussed.     

When do mixotrophs specialize? Adaptive dynamics theory applied to a dynamic energy budget model

In evolutionary history, several events have occurred at which mixotrophs specialized into pure autotrophs and heterotrophs. We studied the conditions under which such events take place, using the Dynamic Energy Budget (DEB) theory for physiological rules of the organisms' metabolism and Adaptive Dynamics (AD) theory for evolutionary behavior of parameter values. We modeled a population of mixotrophs that can take up dissolved inorganic nutrients by autotrophic assimilation and detritus by heterotrophic assimilation. The organisms have a certain affinity for both pathways; mutations that occur in the affinities enable the population to evolve. One of the possible evolutionary outcomes is a branching point which provides an opportunity for the mixotrophic population to split up and specialize into separate autotrophs and heterotrophs. Evolutionary branching is not a common feature of the studied system, but is found to occur only under specific conditions. These conditions depend on intrinsic properties such as the cost function, the level of the costs and the boundaries of the trait space: only at intermediate cost levels and when an explicit advantage exists to pure strategies over mixed ones may evolutionary branching occur. Usually, such an advantage (and hence evolutionary branching) can be induced by interference between the two affinities, but this result changes due to the constraints on the affinities. Now, only some of the more complicated cost functions give rise to a branching point. In contrast to the intrinsic properties, extrinsic properties such as the total nutrient content or light intensity were found to have no effect on the evolutionary outcomes at all.     

When can the cause of a population decline be determined?

Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time.     

Commercialisation of entomopathogenic nematodes: should import regulations be revised?

Entomopathogenic nematodes (EPNs) in the families Steinernematidae and Heterorhabditidae are obligate insect pathogens. Their favourable characteristics as biocontrol agents have resulted in some species of EPNs being released globally and widely used for the control of diverse insect pests. In this review, we consider the occurrence of currently described EPN species, including those that have been released globally for commercial purposes. We also discuss the contribution of regulation policies to the global distribution of these species and issues that influence import regulations. Possible non-target effects, the use of commercial versus native EPNs and the possible interaction between these species are considered. Finally, we provide a view as to whether existing policies adequately deal with the risks associated with the global movement of EPNs and we suggest future directions that should be considered for the use of EPNs as biological control agents.     

How rational should bioethics be? The value of empirical approaches

Rational justification of claims with empirical content calls for empirical and not only normative philosophical investigation. Empirical approaches to bioethics are epistemically valuable, i.e., such methods may be necessary in providing and verifying basic knowledge about cultural values and norms. Our assumptions in moral reasoning can be verified or corrected using these methods. Moral arguments can be initiated or adjudicated by data drawn from empirical investigation. One may argue that individualistic informed consent, for example, is not compatible with the Asian communitarian orientation. But this normative claim uses an empirical assumption that may be contrary to the fact that some Asians do value and argue for informed consent. Is it necessary and factual to neatly characterize some cultures as individualistic and some as communitarian? Empirical investigation can provide a reasonable way to inform such generalizations. In a multi-cultural context, such as in the Philippines, there is a need to investigate the nature of the local ethos before making any appeal to authenticity. Otherwise we may succumb to the same ethical imperialism we are trying hard to resist. Normative claims that involve empirical premises cannot be reasonable verified or evaluated without utilizing empirical methods along with philosophical reflection. The integration of empirical methods to the standard normative approach to moral reasoning should be reasonably guided by the epistemic demands of claims arising from cross-cultural discourse in bioethics.