Three Pillars of Support for Orphan Drug Programs: Individual Valuations, Societal Valuations, and Anonymous Altruism.

OBJECTIVES: To identify and describe potential societal and individual sources of support for orphan drug programs. METHODS: The Generalized Risk-Adjusted Cost-Effectiveness method shows that acute illness and disability severity increase individuals' willingness to pay for health gains. We develop a social welfare function (SWF) that incorporates individuals' own values, combined with politically or ethically determined weights. We introduce the concept of horizontal equity-that individuals in similar situations should be treated similarly-into the SWF. Finally, we introduce anonymous altruism into individuals' utility functions-the desire to help others, without knowing their identity. RESULTS: Combined with the empirical link between disease severity and rarity, the Generalized Risk-Adjusted Cost-Effectiveness method demonstrates heightened willingness to pay for health gains for people with rare diseases, leading rational individuals to support orphan drug programs, our first pillar of support. Adding horizontal equity to the SWF further increases societal support for orphan drug programs. Anonymous altruism, focusing most strongly on those in the most-dire circumstances, leads to altruistic support for those with severe disorders. Because innovators' economic incentives lead them to focus on larger markets, anonymous altruistic individuals will increasingly prefer public investments into rare diseases over time, as private markets systematically produce gains for common diseases. CONCLUSIONS: We identified 3 supporting pillars for orphan drug programs: (1) individuals' propensity to prefer treatments for severe diseases; (2) the preference for horizontal equity in our social welfare; (3) anonymous altruism, the desire to help strangers, coupled with market incentives that underserve strangers with rare diseases.

The effect of intergroup competition outcome on ingroup cooperation: insights from the male warrior hypothesis.

Introduction: The Male Warrior Hypothesis (MWH) proposes that sex-specific selective pressures have promoted male cooperation with the ingroup members to outcompete rival groups. However, intergroup conflicts do not occur in isolation and the outcomes of previous competitions may influence group cooperativeness. Since this phenomenon is not well understood, we aimed to shed light on the effect of previous competition outcome on later cooperative behavior under intergroup conflicts. Based on the MWH, we hypothesized that repeated contests between groups could enhance ingroup cooperation, regardless of the outcome of the previous contest because status is at risk, but when competition is not present, participants would move to the symmetric equilibria. Methods: To test this hypothesis, we recruited 246 individuals organized in groups of 6 and measured cooperation using a threshold public good game over two rounds, manipulating the outcome in the first round to create groups of winners and losers. Results: Our results show that intergroup conflict scenarios promoted cooperation in both victory and defeat conditions, whereas, in the control scenario only losers increased their cooperation. Discussion: We argue that winners under the presence of an external threat may enhance in-group cooperation in order to assure their status; whereas, losers may be attempting to regain it.

When population growth intensifies intergroup competition, female colobus monkeys free-ride less.

Intergroup aggression often results in the production of public goods, such as a safe and stable social environment and a home range containing the resources required to survive and reproduce. We investigate temporal variation in intergroup aggression in a growing population of colobus monkeys (Colobus vellerosus) to ask a novel question: "Who stepped-up to produce these public goods when doing so became more difficult?". Both whole-group encounters and male incursions occurred more frequently as the population grew. Males and females were both more likely to participate in whole-group encounters when monopolizable food resources were available, indicating both sexes engaged in food defence. However, only females increasingly did so as the population grew, suggesting that it was females who increasingly produced the public good of home range defence as intergroup competition intensified. Females were also more active in male incursions at high population densities, suggesting they increasingly produced the public good of a safe and stable social environment. This is not to say that males were chronic free-riders when it came to maintaining public goods. Males consistently participated in the majority of intergroup interactions throughout the study period, indicating they may have lacked the capacity to invest more time and effort.

Reciprocal sharing of extracellular proteases and extracellular matrix molecules facilitates Bacillus subtilis biofilm formation.

Extracellular proteases are a class of public good that support growth of Bacillus subtilis when nutrients are in a polymeric form. Bacillus subtilis biofilm matrix molecules are another class of public good that are needed for biofilm formation and are prone to exploitation. In this study, we investigated the role of extracellular proteases in B. subtilis biofilm formation and explored interactions between different public good producer strains across various conditions. We confirmed that extracellular proteases support biofilm formation even when glutamic acid provides a freely available nitrogen source. Removal of AprE from the NCIB 3610 secretome adversely affects colony biofilm architecture, while sole induction of WprA activity into an otherwise extracellular protease-free strain is sufficient to promote wrinkle development within the colony biofilm. We found that changing the nutrient source used to support growth affected B. subtilis biofilm structure, hydrophobicity and architecture. We propose that the different phenotypes observed may be due to increased protease dependency for growth when a polymorphic protein presents the sole nitrogen source. We however cannot exclude that the phenotypic changes are due to alternative matrix molecules being made. Co-culture of biofilm matrix and extracellular protease mutants can rescue biofilm structure, yet reliance on extracellular proteases for growth influences population coexistence dynamics. Our findings highlight the intricate interplay between these two classes of public goods, providing insights into microbial social dynamics during biofilm formation across different ecological niches.

Microbial Primer: Cooperation in bacteria.

The growth and success of many bacteria appear to rely on a stunning range of cooperative behaviours. But what is cooperation and how is it studied?

Efficiency and resilience of cooperation in asymmetric social dilemmas.

Direct reciprocity is a powerful mechanism for cooperation in social dilemmas. The very logic of reciprocity, however, seems to require that individuals are symmetric, and that everyone has the same means to influence each others' payoffs. Yet in many applications, individuals are asymmetric. Herein, we study the effect of asymmetry in linear public good games. Individuals may differ in their endowments (their ability to contribute to a public good) and in their productivities (how effective their contributions are). Given the individuals' productivities, we ask which allocation of endowments is optimal for cooperation. To this end, we consider two notions of optimality. The first notion focuses on the resilience of cooperation. The respective endowment distribution ensures that full cooperation is feasible even under the most adverse conditions. The second notion focuses on efficiency. The corresponding endowment distribution maximizes group welfare. Using analytical methods, we fully characterize these two endowment distributions. This analysis reveals that both optimality notions favor some endowment inequality: More productive players ought to get higher endowments. Yet the two notions disagree on how unequal endowments are supposed to be. A focus on resilience results in less inequality. With additional simulations, we show that the optimal endowment allocation needs to account for both the resilience and the efficiency of cooperation.

Increased privatization of a public resource leads to spread of cooperation in a microbial population.

The phenomenon of cooperation is prevalent at all levels of life. In one such manifestation of cooperation in microbial communities, some cells produce costly extracellular resources that are freely available to others. These resources are referred to as public goods. Saccharomyces cerevisiae secretes invertase (public good) in the periplasm to hydrolyze sucrose into glucose and fructose, which are then imported by the cells. After hydrolysis of sucrose, a cooperator retains only 1% of the monosaccharides, while 99% of the monosaccharides diffuse into the environment and can be utilized by any cell. The non-producers of invertase (cheaters) exploit the invertase-producing cells (cooperators) by utilizing the monosaccharides and not paying the metabolic cost of producing the invertase. In this work, we investigate the evolutionary dynamics of this cheater-cooperator system. In a co-culture, if cheaters are selected for their higher fitness, the population will collapse. On the other hand, for cooperators to survive in the population, a strategy to increase fitness would likely be required. To understand the adaptation of cooperators in sucrose, we performed a coevolution experiment in sucrose. Our results show that cooperators increase in fitness as the experiment progresses. This phenomenon was not observed in environments which involved a non-public good system. Genome sequencing reveals duplication of several HXT transporters in the evolved cooperators. Based on these results, we hypothesize that increased privatization of the monosaccharides is the most likely explanation of spread of cooperators in the population.IMPORTANCEHow is cooperation, as a trait, maintained in a population? In order to answer this question, we perform a coevolution experiment between two strains of yeast-one which produces a public good to release glucose and fructose in the media, thus generating a public resource, and the other which does not produce public resource and merely benefits from the presence of the cooperator strain. What is the outcome of this coevolution experiment? We demonstrate that after ~200 generations of coevolution, cooperators increase in frequency in the co-culture. Remarkably, in all parallel lines of our experiment, this is obtained via duplication of regions which likely allow greater privatization of glucose and fructose. Thus, increased privatization, which is intuitively thought to be a strategy against cooperation, enables spread of cooperation.

Extracellular transfer of a conserved polymerization factor for multi-flagellin filament assembly in Caulobacter.

Unidirectional growth of filamentous protein assemblies including the bacterial flagellum relies on dedicated polymerization factors (PFs). The molecular determinants and structural transitions imposed by PFs on multi-subunit assembly are poorly understood. Here, we unveil FlaY from the polarized α-proteobacterium Caulobacter crescentus as a defining member of an alternative class of specialized flagellin PFs. Unlike the paradigmatic FliD capping protein, FlaY relies on a funnel-like ß-propeller fold for flagellin polymerization. FlaY binds flagellin and is secreted by the flagellar secretion apparatus, yet it can also promote flagellin polymerization exogenously when donated from flagellin-deficient cells, serving as a transferable, extracellular public good. While the surge in FlaY abundance precedes bulk flagellin synthesis, FlaY-independent filament assembly is enhanced by mutation of a conserved region in multiple flagellin paralogs. We suggest that FlaYs are (multi-)flagellin PFs that evolved convergently to FliDs yet appropriated the versatile ß-propeller fold implicated in human diseases for chaperone-assisted filament assembly.

The Economics of Scientific Publishing.

The peculiar nature of scientific publishing has allowed for a high degree of market concentration and a non-collusive oligopoly. The non-substitutable characteristic of scientific journals has facilitated an environment of market concentration. Acquisition of journals on a capabilities-based approach has seen market concentration increase in favor of a small group of dominant publishers. The digital era of scientific publishing has accelerated concentration. Competition laws have failed to prevent anti-competitive practices. The need for government intervention is debated. The definition of scientific publishing as a public good is evaluated to determine the need for intervention. Policy implications are suggested to increase competitiveness in the short-run and present prestige-maintaining alternatives in the long run. A fundamental change in scientific publishing is required to enable socially efficient and equitable access for wider society's benefit.

The Group Right to Mutual Privacy.

Contemporary privacy challenges go beyond individual interests and result in collective harms. To address these challenges, this article argues for a collective interest in Mutual Privacy which is based on our shared genetic, social, and democratic interests as well as our common vulnerabilities against algorithmic grouping. On the basis of the shared interests and participatory action required for its cumulative protection, Mutual Privacy is then classified as an aggregate shared participatory public good which is protected through the group right to Mutual Privacy.

Utilization of genetic information for medicines development and equitable benefit sharing.

Advances in genomic research have significantly enhanced modern drug development. However, equitable benefit sharing of the results of scientific advancement has not always been achieved. This paper shows how molecular biology has modified medicines development while also leaving open significant challenges for benefit sharing. Presented here is a conceptual modeling describing the processes in genetic-related medicines development and how these are related to specific ethical considerations. The focus is on three important areas: 1) population genetics and the need for discrimination prevention; 2) pharmacogenomics and the need for inclusive governance; and 3) global health to be achieved in open science frameworks. Benefit sharing is taken as the ethical value that underlies all these aspects. The implementation of benefit sharing requires a value shift in which the outcomes of health science are not viewed simply as trade commodities but also as a "global public good". This approach should lead to genetic science to contribute to promoting the fundamental human right to health to all members of the global community.

Bacillus subtilis extracellular protease production incurs a context-dependent cost.

Microbes encounter a wide range of polymeric nutrient sources in various environmental settings, which require processing to facilitate growth. Bacillus subtilis, a bacterium found in the rhizosphere and broader soil environment, is highly adaptable and resilient due to its ability to utilise diverse sources of carbon and nitrogen. Here, we explore the role of extracellular proteases in supporting growth and assess the cost associated with their production. We provide evidence of the essentiality of extracellular proteases when B. subtilis is provided with an abundant, but polymeric nutrient source and demonstrate the extracellular proteases as a shared public good that can operate over a distance. We show that B. subtilis is subjected to a public good dilemma, specifically in the context of growth sustained by the digestion of a polymeric food source. Furthermore, using mathematical simulations, we uncover that this selectively enforced dilemma is driven by the relative cost of producing the public good. Collectively, our findings reveal how bacteria can survive in environments that vary in terms of immediate nutrient accessibility and the consequent impact on the population composition. These findings enhance our fundamental understanding of how bacteria respond to diverse environments, which has importance to contexts ranging from survival in the soil to infection and pathogenesis scenarios.

The effect of subliminal priming on team trust: The mediating role of perceived trustworthiness.

The present study aimed to explore the effect of subliminal priming on team trust and the mechanism through the mediating role of perceived trustworthiness. A total of 144 participants were asked to complete a lexical decision task that was embedded with the "trust" or "suspicion" Chinese words as the subliminal stimuli. Then, they played a public good game and evaluated the perceived trustworthiness of the team. The results of the study showed that subliminal stimuli had a significant effect on team trust [ß = -0.99, 95% CI = (-1.64, -0.33)]. Perceived trustworthiness was found to have a significant mediating effect between the priming condition and team trust [ß = -0.35, 95% CI = (-0.72, -0.02)]. The current study revealed the underlying mechanism through which subliminal priming techniques influence team trust and informed efforts by altering perceived trustworthiness.

Like parent, like offspring: Intergenerational association of parental scarcity mindset with offspring's cooperative behaviors.

A sense of resource availability creates a scarcity mindset, leading people to behave in a more competitive way instead of in a collaborative way. This study aims to examine the relationship between scarcity mindset and cooperative behaviors among parents and offspring, and to explore whether parents' scarcity mindset is related to their offspring's scarcity mindset and cooperative behaviors. We collected 239 parent-offspring pairs from several universities in northwest China. They completed the scarcity mindset scale and a one-shot public good game (PGG). A path model analysis was conducted to examine the relationship between scarcity mindset and cooperative behaviors for offspring and their parents, respectively. The relationship between parental scarcity mindset and offspring's cooperative behaviors was also examined. The results showed that there was a high correlation of scarcity mindset between parents and their offspring. Scarcity mindset was negatively related to cooperative behaviors among both parents and offspring. In addition, both parents' cooperative behaviors and offspring's scarcity mindset mediated the relationship between the parental scarcity mindset and offspring's cooperative behaviors. Our results supported the idea that scarcity mindset triggers competitive rather than cooperative orientation. The present findings reveal an intergenerational relationship between scarcity mindset and cooperative behaviors by highlighting the impacts of parental scarcity mindset on that of their offspring's and its additional effects on offspring's cooperative behaviors.

Digital health technology used in emergency large-scale vaccination campaigns in low- and middle-income countries: a narrative review for improved pandemic preparedness.

INTRODUCTION: Large-scale vaccination campaigns can benefit from using digital health tools, particularly in low- and middle-income countries (LMICs). Selecting the best tool to fit into a pre-existing digital landscape can be challenging. AREAS COVERED: We conducted a narrative review in PubMed and the grey literature for data available within 5 years to provide an overview of digital health tools used in large-scale vaccination campaigns for outbreak response in LMICs. We discuss tools used along the typical steps of a vaccination process. Digital tool functionalities and technical specifications, open-source options, data privacy and security concerns, and lessons learned from the use of these tools are discussed. EXPERT OPINION: The landscape of digital health tools for large-scale vaccination processes in LMICs is growing. For efficient implementation, countries should prioritize the appropriate tool(s) depending on their needs and available resources, develop a robust framework around data privacy and security, and select sustainable features. Improving internet connectivity and digital literacy in LMICs will facilitate adoption. This review may aid LMICs still needing to prepare large-scale vaccination campaigns in the selection of supporting digital health tools. Further research on impact and cost-effectiveness is needed.

Construing Climate Change Adaptation as Global Public Good Under International Law: Problems and Prospects.

Article 7 of the Paris Agreement recognizes that adaptation is a 'global challenge faced by all with local, regional and international dimensions.' It further establishes the 'global goal on adaptation focusing on enhancing adaptive capacity, strengthening resilience and reducing vulnerability to climate change, with a view to contributing to sustainable development.' However, the lack of international cooperation between the global north and global south challenge the formulation and implementation of climate change adaptation strategies. This paper brings in the concept of global public goods (GPGs) to the lexicon of climate adaptation and highlights that adverse impacts of climate change such as climate-induced global migration are global public bad. Hence, the measures taken to respond to such impacts, which consequently enhance the resilience of affected countries, make them more adaptive to those adverse impacts, and deliver common values of universal character, should be construed as the global public good. The paper argues that that the idea of GPGs with its universality offers a normative and practical foundation for understanding, addressing, and strengthening the international community's climate adaptation actions and cooperation.

Promoting blood donation through social media: Evidence from Brazil, India and the USA.

Social media has the potential to encourage prosocial behaviors at scale, yet very little causal evidence exists on the impact of related efforts. Blood donation is a particularly difficult, but essential prosocial behavior that is often critically undersupplied. We examine the effect of Facebook's blood donation tool on voluntary blood donation. We partnered with four major blood banks in the United States covering 363 collection facilities in 46 states and Washington, D.C. We tracked the tool's impact on blood donations during its staggered rollout on a sample of more than 47,000 facility-date observations from March 2019 to September 2019. The tool caused an increase of 0.55 total donations per facility per day (+4.0% [95% CI: 0.04%-8.0%]), and an increase of 0.15 donations from first-time donors per facility per day (+18.9% [95% CI: 4.7%-33.1%]). Longitudinal evidence from Brazil and India suggests the share of donors who both received a message from the tool and stated they were influenced by Facebook to donate increased from 0% to 14.1% [95% CI: 12.1%-16.2%] in the first year of the tool's deployment (i.e., September 2018 to August 2019). These meaningful increases, especially from first-time donors, demonstrate that social media platforms can play an important role in fostering offline prosocial behaviors that benefit the health and well-being of societies around the world.

From public health to public good: Toward universal wellbeing.

We aim to consolidate recent trends in public health into a reconceptualization of the field as public good. We build on several strands of theory, research and action to formulate a more impactful future for the field. Our argument comprises three main parts. In the first part, we describe the central components of the proposed public good: conditions of justice, experiences of mattering, and outcomes of subjective and objective wellbeing. In the second section, we identify continua of practices that paint a trajectory from traditional public health to ecological and participatory public health, to universal wellbeing framed as a public good. The continua are defined in terms of assumptions, practices and roles. Among others, these continua pertain to capabilities, scope of the field, ecological focus, timing of intervention, role of citizen, role of professional, role of settings and role of government. Finally, the third section introduces a series of strategies and recommendations to make the narrative of universal wellbeing as public good a reality.

Acceptance or rejection of welfare migration-an experimental investigation.

We study decisions on welcoming or opposing welfare migration in a laboratory setting with two societies in which one subject can migrate from the poorer to the richer society, provided a majority in the richer society votes to allow that. In each society, subjects indicate their preference for a percentage contribution to a public pool. The median of these rates sets the contributions paid by everybody; a feature that results in high contribution rates with an average of 90%. Varying the multiplier with which contributions are magnified before redistribution to society members, and thus the expected gain/loss associated with migration, we find that subjects overwhelmingly welcome migrants if they expect an economic benefit, while most participants oppose migration if they would be negatively affected by it. Regarding participants' attitudes, we find that more altruistic people are more in favor of migration than more selfish people and that center right-wing oriented subjects propose lower contribution levels than center left-wing oriented subjects. We conclude that economic motives are a crucial factor for accepting or rejecting welfare migration. Therefore, a key to promoting acceptance of new migrants is to ensure and then communicate that their net effect on growth, society, and the public purse is positive. Supplementary Information: The online version contains supplementary material available at 10.1007/s43546-022-00356-6.

Competition among public good providers for donor rewards.

We present experimental evidence for decision settings where public good providers compete for endogenous rewards which are donations (transfers) offered by outside donors. Donors receive benefits from public good provision but cannot provide the good themselves. The performance of three competition mechanisms is examined in relation to the level of public good provision and transfers offered by donors. In addition to a contest where transfers received by public good providers are proportional to effort, we study two contests with exclusion from transfers, namely a winner-takes-all and a loser-gets-nothing. We compare behavior in these three decision settings to the default setting of no-contest (no-transfers). Results for this novel decision environment with endogenous transfers show that donors offer transfers (contest prizes) at similar levels across contests and contributions to the public good are not significantly different in the three contests settings, but are consistently and significantly higher in all contests compared to the setting with no-transfers. Initially, the winner-takes-all setting leads to a significantly higher increase in public good contributions compared to the other two contests; but this difference diminishes across decision rounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s10683-022-09766-7.