The logic of failure

Unlike other living creatures, humans can adapt to uncertainty. They can form hypotheses about situations marked by uncertainty and can anticipate their actions by planning. They can expect the unexpected and take precautions against it. In numerous experiments, we have investigated the manner in which humans deal with these demands. In these experiments, we used computer simulated scenarios representing, for example, a small town, ecological or economic systems or political systems such as a Third World country. Within these computer-simulated scenarios, the subjects had to look for information, plan actions, form hypotheses, etc.     

State-dependent decisions cause apparent violations of rationality in animal choice

Normative models of choice in economics and biology usually expect preferences to be consistent across contexts, or “rational” in economic language. Following a large body of literature reporting economically irrational behaviour in humans, breaches of rationality by animals have also been recently described. If proven systematic, these findings would challenge long-standing biological approaches to behavioural theorising, and suggest that cognitive processes similar to those claimed to cause irrationality in humans can also hinder optimality approaches to modelling animal preferences. Critical differences between human and animal experiments have not, however, been sufficiently acknowledged. While humans can be instructed conceptually about the choice problem, animals need to be trained by repeated exposure to all contingencies. This exposure often leads to differences in state between treatments, hence changing choices while preserving rationality. We report experiments with European starlings demonstrating that apparent breaches of rationality can result from state-dependence. We show that adding an inferior alternative to a choice set (a “decoy”) affects choices, an effect previously interpreted as indicating irrationality. However, these effects appear and disappear depending on whether state differences between choice contexts are present or not. These results open the possibility that some expressions of maladaptive behaviour are due to oversights in the migration of ideas between economics and biology, and suggest that key differences between human and nonhuman research must be recognised if ideas are to safely travel between these fields.     

Correlates of cooperation in a one-shot high-stakes televised prisoners' dilemma

Explaining cooperation between non-relatives is a puzzle for both evolutionary biology and the social sciences. In humans, cooperation is often studied in a laboratory setting using economic games such as the prisoners' dilemma. However, such experiments are sometimes criticized for being played for low stakes and by misrepresentative student samples. Golden balls is a televised game show that uses the prisoners' dilemma, with a diverse range of participants, often playing for very large stakes. We use this non-experimental dataset to investigate the factors that influence cooperation when "playing" for considerably larger stakes than found in economic experiments. The game show has earlier stages that allow for an analysis of lying and voting decisions. We found that contestants were sensitive to the stakes involved, cooperating less when the stakes were larger in both absolute and relative terms. We also found that older contestants were more likely to cooperate, that liars received less cooperative behavior, but only if they told a certain type of lie, and that physical contact was associated with reduced cooperation, whereas laughter and promises were reliable signals or cues of cooperation, but were not necessarily detected.     

Emotion, decision making, and the amygdala

Emotion plays a critical role in many contemporary accounts of decision making, but exactly what underlies its influence and how this is mediated in the brain remain far from clear. Here, we review behavioral studies that suggest that Pavlovian processes can exert an important influence over choice and may account for many effects that have traditionally been attributed to emotion. We illustrate how recent experiments cast light on the underlying structure of Pavlovian control and argue that generally this influence makes good computational sense. Corresponding neuroscientific data from both animals and humans implicate a central role for the amygdala through interactions with other brain areas. This yields a neurobiological account of emotion in which it may operate, often covertly, to optimize rather than corrupt economic choice.     

Analysis and evaluation of ecosystem resilience: an economic perspective with an application to the Venice lagoon

This paper focuses on the analysis and evaluation of resilience anchored in an economic perspective. Resilience, as well as most of the benefits provided by ecosystems, is not priced on current markets. However, this does not mean that resilience is of no value for humans. On the contrary, the interest of using an economic perspective, and the respective scientific methodology, will be put forward in terms of resilience relevance for ecosystem functioning, and its impact on human welfare. The economic perspective is anchored in an anthropocentric analysis evaluating resilience in terms of provision of natural capital benefits. These in turn are interpreted as insurance against the risk of ecosystem malfunctioning and the consequent interruption of the provision of goods and services to humans. For this analysis, we make use of a conceptual framework that identifies and describes the different value components of resilience. Finally, we present an illustration that discusses the economic analysis of resilience benefits in the context of the Venice Lagoon.     

The economic approach to 'theory of mind'

Theory of mind (ToM) is a great evolutionary achievement. It is a special intelligence that can assess not only one's own desires and beliefs, but also those of others. Whether it is uniquely human or not is controversial, but it is clear that humans are, at least, significantly better at ToM than any other animal. Economists and game theorists have developed sophisticated and powerful models of ToM and we provide a detailed summary of this here. This economic ToM entails a hierarchy of beliefs. I know my preferences, and I have beliefs (a probabilistic distribution) about your preferences, beliefs about your beliefs about my preferences, and so on. We then contrast this economic ToM with the theoretical approaches of neuroscience and with empirical data in general. Although this economic view provides a benchmark and makes useful suggestions about empirical tendencies, it does not always generate a close fit with the data. This provides an opportunity for a synergistic interdisciplinary production of a falsifiable theory of bounded rationality. In particular, a ToM that is founded on evolutionary biology might well be sufficiently structured to have predictive power, while remaining quite general. We sketch two papers that represent preliminary steps in this direction.     

Is dietary restriction beneficial for human health, such as for immune function?

PURPOSE OF REVIEW: The impact of dietary restriction on physiologic function in humans is now beginning to be examined. The clinical trials are fueled by decades of animal experiments showing that dietary restriction delays the aging process and decreases the incidence of many age-associated diseases. The critical issue addressed in this article is whether or not dietary restriction long term is feasible or beneficial in humans. RECENT FINDINGS: Short-term dietary restriction in humans does appear to have beneficial effects at lowering metabolism, especially when examining carbohydrates and weight loss. Dietary restriction long term does, however, have detrimental psychological effects in humans, making its feasibility questionable. Even short-term dietary restriction can negatively impact physical activity and potentially some aspects of immunity. The best avenue for humans to benefit from dietary restriction would be for pharmacological or bioactive food ingredient mimetics to be developed which would be more applicable for long-term use. SUMMARY: Dietary restriction per se is unlikely to emerge as a feasible long-term strategy to improve human health. Developing dietary restriction mimetics targeting energy metabolism may prove beneficial, not only in aging, but also in diabetes and obesity.     

Field studies of cytotoxic T lymphocytes in malaria infections: implications for malaria vaccine development

The search for a cytotoxic T lymphocyte (CTL)-inducing malaria vaccine has moved forward from epitope identification to planning stages of safety and immunogenicity trials of candidate vaccines. Development of CTL-inducing vaccine candidates has taken center stage based on the observation that CTL-mediated protection might be the dominant mechanism by which sterile immunity is achieved in irradiated sporozoite immunization experiments in humans and laboratory animals. However, studies in naturally infected individuals living in endemic areas, as reviewed here by Michael Aidoo and Venkatachalam Udhayakumar, have revealed that CTL induction might be influenced by factors such as parasite variants, host genes, other infections and transmission patterns. The influence of these factors on CTL induction has been demonstrated individually and in various combinations in controlled animal experiments. However, in naturally infected humans, they are presented in a complex host-parasite-environment interaction, in a manner that is not easily achieved in laboratory-based experiments. Understanding these interactions is crucial for the development and testing of CTL-inducing vaccines for humans.     

Endangered fishes and economics: intergenerational obligations

Synopsis The diversity of fishes is declining worldwide, largely as the result of habitat alterations created by decisions that foster short-term economic gain. While the best arguments for preserving endangered fishes and ecosystems are non-economic arguments, they have been relatively ineffective. Therefore, it is necessary to provide economic arguments as well. Fish in general have high market values and are a vital source of protein for humans but these values have contributed more to their decline than to their conservation. Fish also have high value as indicators of the health of ecosystems which provide many services to humans, such as clean water. This has not prevented the degradation of aquatic ecosystems, although the value of fisheries has occasionally justified ecosystem protection. Existence values have been developed as a way of putting an economic value on some of the less tangible aspects of fish and ecosystems but they also make it possible to justify extinctions. If the continuous increase in the number of endangered fishes and aquatic ecosystems is to be halted, then the economic costs of environmental degradation to future generations must be included as part of the cost of doing business today (intergenerational value). Political action is needed to protect fishes and aquatic habitats against the day when more benign economic and philosophical systems become predominant.Invited essay     

Low fertility in humans as the evolutionary outcome of snowballing resource games

For decades, evolutionary biologists and anthropologists havepuzzled over the negative relationship that exists between wealthand fertility in humans. Particularly mystifying have been that(1) humans do not appear to translate their reproductive resourcesinto additional offspring, and (2) attempts to model naturalselection resulting in a negative relationship between amountof economic resources and fertility have all predicted the oppositerelationship. In this article, we use game theory to derivethe evolutionarily stable ratio of offspring investment versusresource generation when the continuing survival of offspringlineages is strongly affected by long-term resource accumulation.The model generates the prediction that fertility should belower when there are more resources available and when moreintensive investment in resource generation has the potentialto acutely increase the survival probability of descendant offspringlineages. This prediction provides a simple and general evolutionaryexplanation for why fertility negatively correlates with wealthboth within and between human populations. Indeed, this mayprovide a new understanding of low fertility in contemporaryhuman groups in addition to furthering our understanding thedemographic transition in general.     

Inter-species differences in drug properties

There has been a clear trend towards decreased reliance upon animal studies and increased emphasis upon experiments with human-derived tissues. Nonetheless, we continue to need investigations of interspecies differences for two principal reasons: (1) to prospectively design experiments so that the animal species most similar to humans can be chosen, on a case-by-case basis, for each drug; (2) to properly evaluate and interpret data obtained from the experiments ("risk assessment"). Four core examples derived from the work in our FDA laboratory are used to illustrate these points. For paclitaxel, different metabolites were formed in humans and rats, which makes metabolic drug-drug interaction studies in rats irrelevant. For zidovudine (AZT), rapid glucuronidation in humans produced a much shorter half-life than expected from studies in animals, which have negligible glucuronidation. The toxicology and efficacy of both parent drug and metabolite need to be assessed in cases such as iododeoxydoxorubicin, in which the parent molecule is the dominant circulating species in mice, but patients have more than 10-fold greater exposure to the metabolite compared with the parent. While rats have highly-active arylamine N-acetyltransferases, dogs totally lack this enzyme family, and humans have intermediate amounts. For some situations, we've suggested that it can be desirable to inhibit NAT to make the human exposure more similar to dogs. In conclusion, although the ratio of animal:human data is decreasing, our ability to use animal data effectively for drug development has actually increased. Continued focus should be placed upon the application of comparative interspecies data for prospective design of animal experiments and retrospective interpretation of animal findings in terms of the potential for human risk and benefit.     

A Model of Human Cooperation in Social Dilemmas

Social dilemmas are situations in which collective interests are at odds with private interests: pollution, depletion of natural resources, and intergroup conflicts, are at their core social dilemmas. Because of their multidisciplinarity and their importance, social dilemmas have been studied by economists, biologists, psychologists, sociologists, and political scientists. These studies typically explain tendency to cooperation by dividing people in proself and prosocial types, or appealing to forms of external control or, in iterated social dilemmas, to long-term strategies. But recent experiments have shown that cooperation is possible even in one-shot social dilemmas without forms of external control and the rate of cooperation typically depends on the payoffs. This makes impossible a predictive division between proself and prosocial people and proves that people have attitude to cooperation by nature. The key innovation of this article is in fact to postulate that humans have attitude to cooperation by nature and consequently they do not act a priori as single agents, as assumed by standard economic models, but they forecast how a social dilemma would evolve if they formed coalitions and then they act according to their most optimistic forecast. Formalizing this idea we propose the first predictive model of human cooperation able to organize a number of different experimental findings that are not explained by the standard model. We show also that the model makes satisfactorily accurate quantitative predictions of population average behavior in one-shot social dilemmas.     

Caspase-2 is not required for thymocyte or neuronal apoptosis even though cleavage of caspase-2 is dependent on both Apaf-1 and caspase-9

We have generated rat monoclonal antibodies that specifically recognise caspase-2 from many species, including mouse, rat and humans. Using these antibodies, we have investigated caspase-2 expression, subcellular localisation and processing. We demonstrate that caspase-2 is expressed in most tissues and cell types. Cell fractionation and immunohistochemistry experiments show that caspase-2 is found in the nuclear and cytosolic fractions, including a significant portion present in the Golgi complex. We found that caspase-2 is processed in response to many apoptotic stimuli but experiments with caspase-2 deficient mice demonstrated that it is not required for apoptosis of thymocytes or dorsal root ganglia (DRG) neurons in response to a variety of cytotoxic stimuli. Caspase-2 processing does not occur in thymocytes lacking Apaf-1 or caspase-9, suggesting that in this cell type, activation of caspase-2 occurs downstream of apoptosome formation.     

Influenza: lessons from past pandemics, warnings from current incidents

Recent outbreaks of highly pathogenic avian influenza A virus infections (H5 and H7 subtypes) in poultry and in humans (through direct contact with infected birds) have had important economic repercussions and have raised concerns that a new influenza pandemic will occur in the near future. The eradication of pathogenic avian influenza viruses seems to be the most effective way to prevent influenza pandemics, although this strategy has not proven successful so far. Here, we review the molecular factors that contribute to the emergence of pandemic strains.     

Metabolic State Alters Economic Decision Making under Risk in Humans

Background

Animals'' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans.

Methodology/Principal Findings

We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects'' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual''s baseline leptin and changes in acyl-ghrelin levels respectively.

Conclusions/Significance

We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity.     

PERMANENT GENETIC RESOURCES: Development of polymorphic microsatellite loci for the common vampire bat, Desmodus rotundus (Chiroptera: Phylostomidae)

The common vampire bat (Desmodus rotundus) is one of three haematophagous species of bats and the only species in this genus. These New World bats prey on mammals and create significant economic impacts through transmission of rabies in areas where livestock are prevalent. Furthermore, in some portions of their range, it is not uncommon for them to prey upon humans. It is critical to the management of this species and for understanding the spread of bat rabies that detailed studies of D. rotundus population structure be conducted. To further such studies, we have characterized 12 microsatellite loci for this species.     

Economic behaviours among non-human primates

Do we have any valid reasons to affirm that non-human primates display economic behaviour in a sufficiently rich and precise sense of the phrase? To address this question, we have to develop a set of criteria to assess the vast array of experimental studies and field observations on individual cognitive and behavioural competences as well as the collective organization of non-human primates. We review a sample of these studies and assess how they answer to the following four main challenges. (i) Do we see any economic organization or institutions emerge among groups of non-human primates? (ii) Are the cognitive abilities, and often biases, that have been evidenced as underlying typical economic decision-making among humans, also present among non-human primates? (iii) Can we draw positive lessons from performance comparisons among primate species, humans and non-humans but also across non-human primate species, as elicited by canonical game-theoretical experimental paradigms, especially as far as economic cooperation and coordination are concerned? And (iv) in which way should we improve models and paradigms to obtain more ecological data and conclusions? Articles discussed in this paper most often bring about positive answers and promising perspectives to support the existence and prevalence of economic behaviours among non-human primates.This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.     

Harmful fungi in both agriculture and medicine

Most fungi are saprophytic and not pathogenic to plants, animals and humans. However, a relative few fungal species are phytopathogenic, cause disease (e.g., infections, allergies) in man, and produce toxins that affect plants, animals and humans. Among such fungi are members of the Aspergillus and Fusarium genera as well as other genera (e.g., Alternaria, Mucor) comprising the emerging pathogen group in humans. These fungi present a common threat to both agricultural production and the health of healthy and immunocompromised individuals. Taken together, these relative few fungi can cause huge economic losses to agriculture, loss of food for consumption, and serious, often fatal diseases in humans and animals. Plants may be a source of antifungal compounds since they have had to develop compounds to resist infections by fungi present in their environment.     

The economic approach to ‘theory of mind’

Theory of mind (ToM) is a great evolutionary achievement. It is a special intelligence that can assess not only one''s own desires and beliefs, but also those of others. Whether it is uniquely human or not is controversial, but it is clear that humans are, at least, significantly better at ToM than any other animal. Economists and game theorists have developed sophisticated and powerful models of ToM and we provide a detailed summary of this here. This economic ToM entails a hierarchy of beliefs. I know my preferences, and I have beliefs (a probabilistic distribution) about your preferences, beliefs about your beliefs about my preferences, and so on. We then contrast this economic ToM with the theoretical approaches of neuroscience and with empirical data in general. Although this economic view provides a benchmark and makes useful suggestions about empirical tendencies, it does not always generate a close fit with the data. This provides an opportunity for a synergistic interdisciplinary production of a falsifiable theory of bounded rationality. In particular, a ToM that is founded on evolutionary biology might well be sufficiently structured to have predictive power, while remaining quite general. We sketch two papers that represent preliminary steps in this direction.     

In silico model as a tool for interpretation of intestinal infection studies

In nutrition research the number of human in vivo experiments is limited because of the many restrictions and the high costs of testing in humans. Up to now predictive computer models aiming to enhance research have been rare or too complex, with many nonmeasurable adjustable parameters. This study aimed to develop a basic physicochemical computer model for a first quantitative interpretation of results obtained from in vivo intestinal experiments with bacteria. This new modeling approach is validated with results obtained from gut infection studies in vivo. The design of the model is described, and its ability to reproduce experimental data is evaluated. The model predictions are compared with new experimental data. The phenomena that take place in the gastrointestinal tract are summarized by model constants for growth, adherence, and release of bacteria. Although the model is far from describing all details and many processes in the intestine are combined, the model calculation results lead to reasonable conclusions and interesting hypotheses. One of these hypotheses concluded from the model outcomes is that Escherichia coli bacteria have a much lower intestinal growth rate in humans than in rats. Extra laboratory validation experiments proved the reliability of this hypothesis predicted by the model. In addition, the known protective effect of dietary calcium and detrimental effect of clindamycin on the growth and adherence of Salmonella bacteria could be quantified. From these results it is clear that the model enhances the interpretation of in vivo gastrointestinal experiments and will facilitate research trajectories towards new functional foods that improve resistance to pathogenic bacteria in humans.