In A Treatise of Human Nature, Hume argues that morality pertains primarily to character, and that actions have moral content only to the extent that they signal good or bad character. I formalize his signalling theory of moral/immoral actions using simple game-theoretic models. Conditions exist under which there is a separating equilibrium in which actions do indeed credibly signal character, but conditions also exist in which there is only a pooling or semi-separating equilibrium. A tradeoff is identified between the signalling value of actions, and the consequentialist goal of incentivizing all character types to choose beneficial actions.

When a measure becomes a target, it ceases to be a good measure. For example, when standardized test scores in education become targets, teachers may start “teaching to the test,” leading to breakdown of the relationship between the measure – test performance – and the underlying goal – quality education. Similar phenomena have been named and described across a broad range of contexts, such as economics, academia, machine learning, and ecology. Yet it remains unclear whether these phenomena bear only superficial similarities, or if they derive from some fundamental unifying mechanism. Here, we propose such a unifying mechanism, which we label proxy failure. We first review illustrative examples and their labels, such as the “cobra effect,” “Goodhart's law,” and “Campbell's law.” Second, we identify central prerequisites and constraints of proxy failure, noting that it is often only a partial failure or divergence. We argue that whenever incentivization or selection is based on an imperfect proxy measure of the underlying goal, a pressure arises that tends to make the proxy a worse approximation of the goal. Third, we develop this perspective for three concrete contexts, namely neuroscience, economics, and ecology, highlighting similarities and differences. Fourth, we outline consequences of proxy failure, suggesting it is key to understanding the structure and evolution of goal-oriented systems. Our account draws on a broad range of disciplines, but we can only scratch the surface within each. We thus hope the present account elicits a collaborative enterprise, entailing both critical discussion as well as extensions in contexts we have missed.

Myhre syndrome is a rare disease secondary to pathogenic variants in SMAD4 gene. It is a multisystem disease characterised by short stature, deafness, joint stiffness, craniofacial dysmorphism, and potential cardiac manifestations. Herein, we report two new paediatric cases of Myhre syndrome who, additionally, presented with mid-aortic syndrome. This confirms and extends the scarce reports describing the association between these two entities.

On 26 March 2020, the leaders of the Group of twenty major economies (G20) convened in an emergency virtual meeting to discuss the extraordinary situation facing the world. Virtual summitry provided a stark visual contrast to the traditional staging of modern multilateral diplomacy – leaders were suddenly responsible for their own staging, leaving them with new opportunities to create a favourable impression of how they, and their respective state, would be seen. Taking the disruption of virtual summitry as a starting point, we focus on the resulting new opportunities for visual diplomacy. We draw on the symbolic interactionism of Erving Goffman and we argue that status signalling in this context was based on a shared understanding of the symbols and resources that have social value in the interaction order of summit diplomacy. Based on a visual analysis of 51 photographs from the G20 video conference, we find that the visual performances during the extraordinary meeting reflected evident, but not necessarily intentional, attempts at status seeking. The article thus contributes to an increased understanding of how visual performances contribute to uphold status distinctions in multilateral diplomacy.

States accused of perpetrating cyber operations typically do not confirm or deny responsibility. They issue ‘non-denial denials’ or refuse to comment on the accusations. These ambiguous signals are prevalent, but they are largely ignored in the existing cyber literature, which tends to treat credit claiming as a binary choice. The ambiguity of non-denial denials and ‘non-comments’ allows states to accomplish two seemingly opposed goals: maintaining crisis stability and leaving open the possibility of their involvement in the attack. By deliberately remaining a suspect, a state can manipulate rivals’ perceptions of its cyber capability and resolve. Refusing to deny responsibility can also shape rivals’ perceptions of allies’ capabilities, enhancing the credibility of deterrence. All of this can be accomplished without the escalatory risks that would come with an explicit admission of responsibility. Where previous research has focused on the dangers of escalation and the limitations of costly signalling with cyber, we show that non-denial denials and non-comments make cyber operations considerably more useful than the literature appreciates.

Audience costs theory posits that domestic audiences punish political leaders who make foreign threats but fail to follow through, and that anticipation of audience costs gives more accountable leaders greater leverage in crisis bargaining. We argue, contrary to the theory, that leaders are often unaware of audience costs and their impact on crisis bargaining. We emphasise the role of domestic opposition in undermining a foreign threat, note that opposition can emerge from policy disagreements within the governing party as well as from partisan oppositions, and argue that the resulting costs differ from audience costs. We argue that a leader's experience of audience costs can trigger learning about audience costs dynamics and alter future behaviour. We demonstrate the plausibility of these arguments through a case study of the 1863–4 Schleswig-Holstein crisis. Prime Minister Palmerston's threat against German intervention in the Danish dispute triggered a major domestic debate, which undercut the credibility of the British threat and contributed to both the failure of deterrence and to subsequent British inaction. Parliament formally censured Palmerston, contributing to a learning-driven reorientation in British foreign policy.

Intraguild predation is the killing and consuming of a heterospecific competitor that uses similar resources as the prey, and also benefit from preying on each other. We investigated the foraging behaviour of the gallmidge, Aphidoletes aphidimyza, a predator of aphids used for biological control that is also the intraguild prey for most other aphid natural enemies. We focus on how aphid alarm pheromone can alter the behaviour of the gallmidge, and predation by the anthocorid bug Orius laevigatus (O. laevigatus). We hypothesised that gallmidges would respond to the presence of (E)-β-farnesene (EBF) by leaving the host plant. Since feeding by Aphidoletes gallmidge larvae does not induce EBF emission by aphids, this emission indicates the presence of an intraguild predator. We found that gallmidge larvae reduced their foraging activities and left the plant earlier when exposed to EBF, particularly when aphids were also present. Contrastingly, gallmidge females did not change the time visiting plants when exposed to EBF, but lay more eggs on plants that had a higher aphid density. Lastly, EBF reduced the number of attacks of the intraguild predator, O. laevigatus, on gallmidge larvae, potentially because more gallmidges stopped aphid feeding and moved off the plant at which point O. laevigatus predated on aphids. Our work highlights the importance of understanding how intraguild predation can influence the behaviour of potential biological control agents and the impact on pest control services when other natural enemies are also present.

From an evolutionary perspective, art presents many puzzles. Humans invest substantial effort in generating apparently useless displays that include artworks. These vary greatly from ordinary to intricate. From the perspective of signalling theory, these investments in highly complex artistic designs can reflect information about individuals and their social standing. Using a large corpus of kolam art from South India (N = 3139 kolam from 192 women), we test a number of hypotheses about the ways in which social stratification and individual differences affect the complexity of artistic designs. Consistent with evolutionary signalling theories of constrained optimisation, we find that kolam art tends to occupy a ‘sweet spot’ at which artistic complexity, as measured by Shannon information entropy, remains relatively constant from small to large drawings. This stability is maintained through an observable, apparently unconscious trade-off between two standard information-theoretic measures: richness and evenness. Although these drawings arise in a highly stratified, caste-based society, we do not find strong evidence that artistic complexity is influenced by the caste boundaries of Indian society. Rather, the trade-off is likely due to individual-level aesthetic preferences and differences in skill, dedication and time, as well as the fundamental constraints of human cognition and memory.

Ordeals are burdens placed on individuals that yield no benefits to others; hence they represent a dead-weight loss. Ordeals – the most common is waiting time – play a prominent role in rationing health care. The recipients most willing to bear them are those receiving the greatest benefit from scarce health-care resources. Health care is heavily subsidized; hence, moral hazard leads to excess use. Ordeals are intended to discourage expenditures yielding little benefit while simultaneously avoiding the undesired consequences of rationing methods such as quotas or pricing. This analysis diagnoses the economic underpinnings of ordeals. Subsidies for nursing-home care versus home care illustrate.

Religious leaders refrain from sex and food across human societies. Researchers argue that this avoidance influences people's perceptions of leaders’ underlying traits, but few, if any, quantitative data exist testing these claims. Here we show that shamans in a small-scale society observe costly prohibitions and that observers infer cooperativeness, religious belief, difference from normal humans and supernatural power from shamans’ adherence to special taboos. We investigated costly prohibitions on shamanic healers, known as sikerei, among the rainforest horticulturalist Mentawai people of Siberut Island. We found that shamans must observe permanent taboos on various animals, as well as prohibitions on sex and food during initiation and ceremonial healing. Using vignettes, we evaluated Mentawai participants’ inferences about taboo adherence, testing three different but not mutually exclusive hypotheses: cooperative costly signalling, credibility-enhancing displays and supernatural otherness. We found support for all three: Mentawai participants infer self-denying shamans to be (a) cooperative, (b) sincere believers in the religious rules and (c) dissimilar from normal humans and with greater supernatural powers. People's inferences about religious self-denial are multidimensional and consistent with several functional accounts.

Improvements in feed intake of dairy cows entering the early lactation period potentially decrease the risk of metabolic disorders, but before developing approaches targeting the intake level, mechanisms controlling and dysregulating energy balance and feed intake need to be understood. This review focuses on different inflammatory pathways interfering with the neuroendocrine system regulating feed intake of periparturient dairy cows. Subacute inflammation in various peripheral organs often occurs shortly before or after calving and is associated with increased pro-inflammatory cytokine levels. These cytokines are released into the circulation and sensed by neurons located in the hypothalamus, the key brain region regulating energy balance, to signal reduction in feed intake. Besides these peripheral humoral signals, glia cells in the brain may produce pro-inflammatory cytokines independent of peripheral inflammation. Preliminary results show intensive microglia activation in early lactation, suggesting their involvement in hypothalamic inflammation and the control of feed intake of dairy cows. On the other hand, pro-inflammatory cytokine-induced activation of the vagus nerve transmits signalling to the brain, but this pathway seems not exclusively necessary to signal feed intake reduction. Yet, less studied in dairy cows so far, the endocannabinoid system links inflammation and the hypothalamic control of feed intake. Distinct endocannabinoids exert anti-inflammatory action but also stimulate the posttranslational cleavage of neuronal proopiomelanocortin towards β-endorphin, an orexigen promoting feed intake. Plasma endocannabinoid concentrations and hypothalamic β-endorphin levels increase from late pregnancy to early lactation, but less is known about the regulation of the hypothalamic endocannabinoid system during the periparturient period of dairy cows. Dietary fatty acids may modulate the formation of endocannabinoids, which opens new avenues to improve metabolic health and immune status of dairy cows.

Inositol is a naturally occurring sugar-alcohol present in plants and animals, either in its free form, as a phospholipid component or as inositol phosphate (IP) esters. Dietary inositol is readily absorbed from the intestine via SMIT1 with levels being detectable in the blood as well as in various tissues. Recent studies have revealed a potential link between free inositol content and improved growth response in animals. There is limited data suggesting why an increase in inositol would result in improved growth; however, it would appear that inositol has numerous biological functions within the body. A number of tissues are capable of synthesising this polyol from glucose, although the kidney appears to be the primary site of catabolism. Studies investigating the effect of inositol deficiencies in various animal species have revealed a number of biological processes that are reliant on inositol to function. One of inositol's main functions appears to be its involvement as a phospholipid component of cell membranes and lipoproteins. Cell signalling pathways involving phosphoinositide phospholipids, such as the IP3/DAG and IGF/PIK/Akt pathways, lead to a number of cellular responses that are important for cell survival and growth. On a larger scale, inositol appears to be essential for both prenatal and postnatal development of peripheral nerves, CNS and bone. With regards to a potential growth response, upregulation of specific signalling pathways, such as the IGF/Akt/mTOR pathway, in the skeletal muscle has been shown in response to phytase supplementation and the consequential increase in free inositol. These signalling pathways are responsible for protein synthesis and increased glucose absorption in this tissue. Since inositol has also been shown to be an important regulator of the transport and deposition of fat, it may be possible to use inositol to support the growth of a lean animal.

After controlling a variety of feeder cattle characteristics and market and sale conditions in Iowa feeder auctions, the price premiums for preconditioning claims (vaccinations and minimum 30 days of weaning) with and without third-party certification (TPC) are estimated as $6.12/cwt and $3.35/cwt, respectively. These premiums differ statistically (p < 0.0001), and their difference exceeds the average participation cost of TPC ($l/cwt). This indicates that TPC is valued in the market to credibly signal preconditioning investment under asymmetric information.

The intra-erythrocytic protozoan Babesia bovis is an economically important pathogen that causes an acute and often fatal infection in adult cattle. Babesiosis limitation depends on the early activation of macrophages, essential cells of the host innate immunity, which can generate an inflammatory response mediated by cytokines and nitric oxide (NO). Herein, we demonstrate in bovine macrophages that lipids from B. bovis attenuated R1A strain (LA) produced a stronger NO release, an early TNFα mRNA induction and 2-fold higher IL-12p35 mRNA levels compared to the lipids of virulent S2P strain (LV). Neither LA nor LV induced anti-inflammatory IL-10. Regarding signalling pathways, we here report that LA induced a significant phosphorylation of p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2) whereas LV only induced a reduced activation of ERK1/2. Besides, NF-κB was activated by LA and LV, but LA produced an early degradation of the inhibitor IκB. Interestingly, LV and the majority of its lipid fractions, exerted a significant inhibition of concanavalin A-induced peripheral blood mononuclear cell proliferation with respect to LA and its corresponding lipid fractions. In addition, we determined that animals infected with R1A developed a higher increase in IgM anti-phosphatidylcholine than those inoculated with S2P. Collectively, S2P lipids generated a decreased inflammatory response contributing to the evasion of innate immunity. Moreover, since R1A lipids induced a pro-inflammatory profile, we propose these molecules as good candidates for immunoprophylactic strategies against babesiosis.

Albumen was removed from broiler eggs before the start of incubation to induce prenatal protein under-nutrition in chicken embryos. With this method, the direct effect of protein deficiency was investigated, differing from mammalian models manipulating the maternal diet where indirect, hormonal effects can interfere. Based on the estimated albumen/egg weight ratio, 10 % of albumen was removed with an 18G needle, after making a hole at the sharp end of the egg with another 18G needle. Eggs were taped thereafter. The sham group underwent the same procedure, except that no albumen was removed. Control eggs did not receive any treatment. The removal of albumen decreased both embryonic and post-hatch body weight up to day 7 compared with the control group. On embryonic day 18, embryos from the albumen-deprived group had higher plasma uric acid levels compared with the sham (P= 0·016) and control (P= 0·009) groups. Moreover, a lower plasma amino acid concentration was observed at hatch compared with the sham (P= 0·038) and control (P= 0·152) groups. These findings indicate an altered protein metabolism. At hatch, a higher mRNA expression of muscle ring finger-1 (MuRF1), a gene related to proteolysis, was observed in albumen-deprived chicks compared with the control and sham chicks, together with an up-regulated expression of atrogin-1 (another atrogene) at this time point in the male protein-deficient chicks. These findings suggest that muscle proteolysis is transiently increased by the removal of albumen before the start of incubation. No evidence was found for altered protein synthesis capacity and translational efficiency in albumen-deprived chicks.

The rainbow trout (Oncorhynchus mykiss) exhibits high dietary amino acid requirements and an apparent inefficiency to use dietary carbohydrates. Using this species, we investigated the metabolic consequences of long-term high carbohydrates/low protein feeding. Fish were fed two experimental diets containing either 20 % carbohydrates/50 % proteins (C20P50), or high levels of carbohydrates at the expense of proteins (35 % carbohydrates/35 % proteins – C35P35). The expression of genes related to hepatic and muscle glycolysis (glucokinase (GK), pyruvate kinase and hexokinase) illustrates the poor utilisation of carbohydrates irrespective of their dietary levels. The increased postprandial GK activity and the absence of inhibition of the gluconeogenic enzyme glucose-6-phosphatase activity support the hypothesis of the existence of a futile cycle around glucose phosphorylation extending postprandial hyperglycaemia. After 9 weeks of feeding, the C35P35-fed trout displayed lower body weight and feed efficiency and reduced protein and fat gains than those fed C20P50. The reduced activation of eukaryotic translation initiation factor 4-E binding protein 1 (4E-BP1) in the muscle in this C35P35 group suggests a reduction in protein synthesis, possibly contributing to the reduction in N gain. An increase in the dietary carbohydrate:protein ratio decreased the expression of genes involved in amino acid catabolism (serine dehydratase and branched-chain α-keto acid dehydrogenase E1α and E1β), and increased that of carnitine palmitoyltransferase 1, suggesting a higher reliance on lipids as energy source in fish fed high-carbohydrate and low-protein diets. This probably also contributes to the lower fat gain. Together, these results show that different metabolic pathways are affected by a high-carbohydrate/low-protein diet in rainbow trout.

We consider the suggestion that, as a matter of caution, the deliberate broadcast of signals to the cosmos should be proscribed. We explore the likely capabilities of extraterrestrial societies that might conceivably pose a threat to our species and show that this suggestion is without merit because even if followed, it would fail to keep our existence secret. In addition, trying to limit signalling activities would be a burden on our descendants, crippling their own activities for the indefinite future. A corollary to these considerations affects the search for extraterrestrial intelligence (SETI): namely, it seems inarguable that technologically advanced beings will assume that other societies are capable of detecting their leakage. Consequently, the premise that SETI should expect to find deliberate beacons from other worlds may be mistaken.

Protein metabolism is considered to be regulated by amino acids, with major consequences on tissue development. There is evidence that lysine greatly affects carcass composition and muscle growth. In particular, a drastic effect of dietary provision of lysine has been observed on breast muscle development in chickens. Other essential amino acids, such as threonine and valine, do not have as pronounced an effect as lysine on body composition. Increasing lysine can also improve chicken breast muscle quality by increasing its ultimate pH and water holding capacity, but the underlying mechanisms are still unknown. Studies conducted over the last ten years indicate that, in addition to being substrates for protein synthesis, amino acids act as modulators of signal transduction pathways that control metabolism and cell functions. For instance, certain amino acids can modulate the activity of the intracellular protein kinases involved in the control of mRNA translation. Interestingly, enhanced responses to amino acids have been reported during the neonatal period, suggesting that early protein nutrition impacts on the development of broiler chicks. Methionine and cysteine have a very significant place among amino acids because they have several additional roles: they are precursors of essential molecules, for example cysteine is used for the synthesis of the antioxidant glutathione, and thus participates in the control of oxidative status, methionine is a source of the methyl groups needed for all biological methylation reactions, including methylation of DNA and histones, etc. These findings together indicate the importance of optimizing amino acid nutrition and providing a rationale for nutritional advice.