Pharmacogenomics of GPCR Drug Targets.

Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug- and effector-binding sites in the human population. We experimentally show that certain variants of µ-opioid and Cholecystokinin-A receptors could lead to altered or adverse drug response. By analyzing UK National Health Service drug prescription and sales data, we suggest that characterizing GPCR variants could increase prescription precision, improving patients' quality of life, and relieve the economic and societal burden due to variable drug responsiveness. VIDEO ABSTRACT.

Augmenting the availability of historical GDP per capita estimates through machine learning.

Can we use data on the biographies of historical figures to estimate the GDP per capita of countries and regions? Here, we introduce a machine learning method to estimate the GDP per capita of dozens of countries and hundreds of regions in Europe and North America for the past seven centuries starting from data on the places of birth, death, and occupations of hundreds of thousands of historical figures. We build an elastic net regression model to perform feature selection and generate out-of-sample estimates that explain 90% of the variance in known historical income levels. We use this model to generate GDP per capita estimates for countries, regions, and time periods for which these data are not available and externally validate our estimates by comparing them with four proxies of economic output: urbanization rates in the past 500 y, body height in the 18th century, well-being in 1850, and church building activity in the 14th and 15th century. Additionally, we show our estimates reproduce the well-known reversal of fortune between southwestern and northwestern Europe between 1300 and 1800 and find this is largely driven by countries and regions engaged in Atlantic trade. These findings validate the use of fine-grained biographical data as a method to augment historical GDP per capita estimates. We publish our estimates with CI together with all collected source data in a comprehensive dataset.

Inflation in 2022 did not affect congressional voting, but abortion did.

This study examines voting in the 2022 United States congressional elections, contests that were widely expected to produce a sizable defeat for Democratic candidates for largely economic reasons. Based on a representative national probability sample of voters interviewed in both 2020 and 2022, individuals who changed their vote from one party's congressional candidate to another party's candidate did not do so in response to the salience of inflation or declining economic conditions. Instead, we find strong evidence that views on abortion were central to shifting votes in the midterm elections. Americans who favored (opposed) legal abortions were more likely to shift from voting for Republican (Democratic) candidates in 2020 to Democratic (Republican) candidates in 2022. Since a larger number of Americans supported than opposed legal abortions, the combination of these shifts ultimately improved the electoral prospects of Democratic candidates. New voters were especially likely to weigh abortion views heavily in their vote-shifting calculus. Likewise, those respondents whose confidence in the US Supreme Court declined from 2020 to 2022 were more likely to shift from voting for Republican to Democratic congressional candidates. We provide direct empirical evidence that changes in support for the Supreme Court, a nonpartisan branch of the federal government, are implicated in partisan voting behavior in another branch of government. We explore the implications of these findings for prevalent assumptions about how economic conditions influence voting, as well as for the relationship between the judiciary and electoral politics.

The visual effect of wind turbines on property values is small and diminishing in space and time.

Renewable power generation is the key to decarbonizing the electricity system. Wind power is the fastest-growing renewable source of electricity in the United States. However, expanding wind capacity often faces local opposition, partly due to a perceived visual disamenity from large wind turbines. Here, we provide a US-wide assessment of the externality costs of wind power generation through the visibility impact on property values. To this end, we create a database on wind turbine visibility, combining information on the site and height of each utility-scale turbine having fed power into the U.S. grid, with a high-resolution elevation map to account for the underlying topography of the landscape. Building on hedonic valuation theory, we statistically estimate the impact of wind turbine visibility on home values, informed by data from the majority of home sales in the United States since 1997. We find that on average, wind turbine visibility negatively affects home values in an economically and statistically significant way in close proximity ([Formula: see text]5 miles/8 km). However, the effect diminishes over time and in distance and is indistinguishable from zero for larger distances and toward the end of our sample.

Peer conformity and competition shape how business managers evaluate withdrawals from Russia amid the Ukraine War.

States have long used economic sanctions in response to violations of international law as a strategy to restore order. Increasingly, firms also reject doing business with violators. In response to the war in Ukraine, hundreds of multinational corporations voluntarily withdrew from Russia, even when policymakers were still debating the extent of sanctions. How did firm managers evaluate whether to withdraw from the Russian market? Using a survey experiment with Japanese firm managers conducted three months after the Russian invasion of Ukraine in 2022, we explore how peer effects-information on what other firms are doing in response to the crisis-influence support for withdrawal of business activity with Russia. Our findings show that information about withdrawal by other firms from a diverse set of countries promotes peer conformity that increases support. In contrast, information about ongoing business with Russia by Chinese firms fosters competition that reduces support. Market exposure moderates these reactions, although the concern about peer behavior does not appear to be driven by a reputation mechanism. Our research provides insight into how business actors perceive the strategic interplay of peer influence and market dynamics in the context of geopolitical conflicts.

Childhood PM2.5 exposure and upward mobility in the United States.

Although it is well documented that exposure to fine particulate matter (PM2.5) increases the risk of several adverse health outcomes, less is known about its relationship with economic opportunity. Previous studies have relied on regression modeling, which implied strict assumptions regarding confounding adjustments and did not explore geographical heterogeneity. We obtained data for 63,165 US census tracts (86% of all census tracts in the United States) on absolute upward mobility (AUM) defined as the mean income rank in adulthood of children born to families in the 25th percentile of the national income distribution. We applied and compared several state-of-the-art confounding adjustment methods to estimate the overall and county-specific associations of childhood exposure to PM2.5 and AUM controlling for many census tract-level confounders. We estimate that census tracts with a 1 µg/m3 higher PM2.5 concentrations in 1982 are associated with a statistically significant 1.146% (95% CI: 0.834, 1.458) lower AUM in 2015, on average. We also showed evidence that this relationship varies spatially between counties, exhibiting a more pronounced negative relationship in the Midwest and the South.

Private management of African protected areas improves wildlife and tourism outcomes but with security concerns in conflict regions.

Protected areas can conserve wildlife and benefit people when managed effectively. African governments increasingly delegate the management of protected areas to private, nongovernmental organizations, hoping that private organizations' significant resources and technical capacities actualize protected areas' potential. Does private sector management improve outcomes compared to a counterfactual of government management? We leverage the transfer of management authority from governments to African Parks (AP)-the largest private manager of protected areas in Africa-to show that private management significantly improves wildlife outcomes via reduced elephant poaching and increased bird abundances. Our results also suggest that AP's management augments tourism, while the effect on rural wealth is inconclusive. However, AP's management increases the risk of armed groups targeting civilians, which could be an unintended outcome of AP's improved monitoring and enforcement systems. These findings reveal an intricate interplay between conservation, economic development, and security under privately managed protected areas in Africa.

Global decarbonization potential of CO2 mineralization in concrete materials.

CO2 mineralization products are often heralded as having outstanding potentials to reduce CO2-eq. emissions. However, these claims are generally undermined by incomplete consideration of the life cycle climate change impacts, material properties, supply and demand constraints, and economic viability of CO2 mineralization products. We investigate these factors in detail for ten concrete-related CO2 mineralization products to quantify their individual and global CO2-eq. emissions reduction potentials. Our results show that in 2020, 3.9 Gt of carbonatable solid materials were generated globally, with the dominant material being end-of-life cement paste in concrete and mortar (1.4 Gt y-1). All ten of the CO2 mineralization technologies investigated here reduce life cycle CO2-eq. emissions when used to substitute comparable conventional products. In 2020, the global CO2-eq. emissions reduction potential of economically competitive CO2 mineralization technologies was 0.39 Gt CO2-eq., i.e., 15% of that from cement production. This level of CO2-eq. emissions reduction is limited by the supply of end-of-life cement paste. The results also show that it is 2 to 5 times cheaper to reduce CO2-eq. emissions by producing cement from carbonated end-of-life cement paste than carbon capture and storage (CCS), demonstrating its superior decarbonization potential. On the other hand, it is currently much more expensive to reduce CO2-eq. emissions using some CO2 mineralization technologies, like carbonated normal weight aggregate production, than CCS. Technologies and policies that increase recovery of end-of-life cement paste from aged infrastructure are key to unlocking the potential of CO2 mineralization in reducing the CO2-eq. footprint of concrete materials.

Expanding economic activity in space may offer a solution to secular stagnation.

In this speculative article, I argue that the expansion of economic activity in space may offer a uniquely promising way to escape indefinitely from what economists call "secular stagnation," a state of self-fulfilling, persistently sluggish economic growth that has increasingly threatened high-income countries. Economists have pointed to both supply-side and demand-side drivers of secular stagnation, and space as a focal point for investment can-at least in principle-address both. On the supply side, space is an unlimited frontier that, as have frontiers in the past, may inspire the individualism, innovation, and world-building needed to sustainably increase productivity and population growth. On the demand side, public investment toward increased economic activity in space could meaningfully add to aggregate demand if it reached historical peak benchmarks in the United States.

Impact of bioenergy feedstock carbon farming on sustainable aviation fuel viability in the United States.

Biomass-derived sustainable aviation fuel holds significant potential for decarbonizing the aviation sector. Its long-term viability depends on crop choice, longevity of soil organic carbon (SOC) sequestration, and the biomass-to-biojet fuel conversion efficiency. We explored the impact of fuel price and SOC value on viable biojet fuel production scale by integrating an agroecosystem model with a field-to-biojet fuel production process model for 1,4-dimethylcyclooctane (DMCO), a representative high-performance biojet fuel molecule, from Miscanthus, sorghum, and switchgrass. Assigning monetary value to SOC sequestration results in substantially different outcomes than an increased fuel selling price. If SOC accumulation is valued at $185/ton CO2, planting Miscanthus for conversion to DMCO would be economically cost-competitive across 66% of croplands across the continental United States (US) by 2050 if conventional jet fuel remains at $0.74/L (in 2020 US dollars). Cutting the SOC sequestration value in half reduces the viable area to 54% of cropland, and eliminating any payment for SOC shrinks the viable area to 16%. If future biojet fuel prices increase to $1.24/L-Jet A-equivalent, 48 to 58% of the total cultivated land in the United States could support a more diverse set of feedstocks including Miscanthus, sorghum, or switchgrass. Among these options, only 8-14% of the area would be suitable exclusively for Miscanthus cultivation. These findings highlight the intersection of natural solutions for carbon removal and the use of deep-rooted feedstocks for biofuels and biomanufacturing. The results underscore the need to establish clear and consistent values for SOC sequestration to enable the future bioeconomy.

Languages and future-oriented economic behavior-Experimental evidence for causal effects.

Studies have shown that the use of languages which grammatically associate the future and the present tends to correlate with more future-oriented behavior. We take an experimental approach to go beyond correlation. We asked bilingual research participants, people fluent in two languages (12 language pairs) which differ in the way they encode time, to make a set of future-oriented economic decisions. We find that participants addressed in a language in which the present and the future are marked more distinctly tended to value future events less than participants addressed in a language in which the present and the future are similarly marked. In an additional experiment, bilingual research participants (seven language pairs) were asked to choose whether they wish to complete a more enjoyable task first or later (delayed gratification). When addressed in a language in which the present and the future are marked more distinctly, participants tended to prefer immediate gratification more than when addressed in a language in which the present and the future are marked less distinctly. We shed light on the mechanism in a within-person experiment in which bilingual research participants (nine language pairs) were asked to spatially mark the distance between the present and the future. When participants were addressed in a language in which the present and the future are marked more distinctly, they tended to express more precise temporal beliefs compared with when addressed in a language in which the present and the future are marked less distinctly.

Long ties, disruptive life events, and economic prosperity.

Social networks shape and reflect economic life. Prior studies have identified long ties, which connect people who lack mutual contacts, as a correlate of individuals' success within firms and places' economic prosperity. However, we lack population-scale evidence of the individual-level link between long ties and economic prosperity, and why some people have more long ties remains obscure. Here, using a social network constructed from interactions on Facebook, we establish a robust association between long ties and economic outcomes and study disruptive life events hypothesized to cause formation of long ties. Consistent with prior aggregated results, administrative units with a higher fraction of long ties tend to have higher-income and economic mobility. Individuals with more long ties live in higher-income places and have higher values of proxies for economic prosperity (e.g., using more Internet-connected devices and making more donations). Furthermore, having stronger long ties (i.e., with higher intensity of interaction) is associated with better outcomes, consistent with an advantage from the structural diversity constituted by long ties, rather than them being weak ties per se. We then study the role of disruptive life events in the formation of long ties. Individuals who have migrated between US states, have transferred between high schools, or have attended college out-of-state have a higher fraction of long ties among their contacts many years after the event. Overall, these results suggest that long ties are robustly associated with economic prosperity and highlight roles for important life experiences in developing and maintaining long ties.

People are less myopic about future than past collective outcomes.

Myopia involves giving disproportionate weight to outcomes that occur close to the present. Myopia in people's evaluations of political outcomes and proposals threatens effective policymaking. It can lead to inefficient spending just before elections, cause inaction on important future policy challenges, and create incentives for government interventions aimed at boosting short-term performance at the expense of long-term welfare. But, are people generally myopic? Existing evidence comes mostly from studies that disregard either the future or collective outcomes. Political science characterizes people as myopic based on how they retrospectively evaluate collective outcomes, such as the state of the economy. Behavioral economics and psychology find that people make myopic choices involving future individual outcomes, such as money or personal health. To characterize myopia more generally, we offer two innovations: First, we adapt measurement approaches from behavioral economics and psychology to precisely gauge myopia over politically relevant collective outcomes. Second, we estimate myopia using the same approach for collective political outcomes in both past and future. We conduct two surveys on three different samples (including a large probability-based sample) asking respondents to evaluate national conditions randomly described as past or future while holding constant the domain, information about conditions, and the elicitation method. Results show that prospective evaluations are significantly less myopic than retrospective evaluations. People are often not myopic at all when looking to the future. This surprising pattern calls for more research to probe its robustness and spell out how low prospective myopia might lead to forward-looking policy.

The emergence of economic rationality of GPT.

As large language models (LLMs) like GPT become increasingly prevalent, it is essential that we assess their capabilities beyond language processing. This paper examines the economic rationality of GPT by instructing it to make budgetary decisions in four domains: risk, time, social, and food preferences. We measure economic rationality by assessing the consistency of GPT's decisions with utility maximization in classic revealed preference theory. We find that GPT's decisions are largely rational in each domain and demonstrate higher rationality score than those of human subjects in a parallel experiment and in the literature. Moreover, the estimated preference parameters of GPT are slightly different from human subjects and exhibit a lower degree of heterogeneity. We also find that the rationality scores are robust to the degree of randomness and demographic settings such as age and gender but are sensitive to contexts based on the language frames of the choice situations. These results suggest the potential of LLMs to make good decisions and the need to further understand their capabilities, limitations, and underlying mechanisms.

Global patterns of migration of scholars with economic development.

We leverage metadata on over 36 million journal articles and reviews indexed by Scopus in order to estimate migration of scholars based on information on changes in their institutional affiliations over time. We produce a database of yearly international migration flows of scholars, for all countries from 1998 to 2017. We use the open-access database to provide descriptive evidence on the relationship between economic development and the emigration propensity of scholars. Statistical analysis using generalized additive mixed models reveals that emigration rates initially decrease as GDP per capita increases. Then, starting from around 25,000 dollars (2017 constant international dollars at purchasing power parity), the trend reverses and emigration propensity increases as countries get richer. This U-shaped pattern contrasts with what has been found in the literature for emigration rates for the general population and calls for theoretical frameworks to understand the heterogeneous responses of migration to development.

The Economic Iceberg of Celiac Disease: More Than the Cost of Gluten-Free Food.

Celiac disease (CeD) is a chronic autoimmune disorder of global relevance, with the potential for acute and long-term complications. However, the economic burden of CeD is rarely considered and largely thought of as limited to the cost of gluten-free food. Fortunately, recent research has shed light on the various societal costs of CeD across the health care continuum. This article summarizes the current evidence on the economic impacts of CeD, which suggest that the societal economic burden of CeD stretches beyond the cost of gluten-free food. This review provides ample evidence of larger but hidden costs related to excess health care use for complications and comorbidities, as well as reduced productivity. Although significant advances are expected in the management of CeD, their effect on the economic burden of CeD remain uncertain. The aim of this review was to inform stakeholders across society and contribute to improved policies to support patients with CeD.

Continuous decision to wait for a future reward is guided by fronto-hippocampal anticipatory dynamics.

Deciding whether to wait for a future reward is crucial for surviving in an uncertain world. While seeking rewards, agents anticipate a reward in the present environment and constantly face a trade-off between staying in their environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here, we show that anticipatory activity in the anterior prefrontal cortex, ventrolateral prefrontal cortex, and hippocampus underpins continuous stay-leave decision-making. Participants awaited real liquid rewards available after tens of seconds, and their continuous decision was tracked by dynamic brain activity associated with the anticipation of a reward. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When the dynamic anticipatory brain activity was enhanced in the anterior prefrontal cortex, participants remained in their current environment, but when this activity diminished, they left the environment. Moreover, while experiencing a delayed reward in a novel environment, the ventrolateral prefrontal cortex and hippocampus showed anticipatory activity. Finally, the activity in the anterior prefrontal cortex and ventrolateral prefrontal cortex was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced hippocampal activity. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision-making while anticipating a future reward.

The links between physical activity and prosocial behavior: an fNIRS hyperscanning study.

The prevalence of physically inactive lifestyles in modern society raises concerns about the potential association with poor brain health, particularly in the lateral prefrontal cortex, which is crucial for human prosocial behavior. Here, we explored the relationship between physical activity and prosocial behavior, focusing on potential neural markers, including intra-brain functional connectivity and inter-brain synchrony in the lateral prefrontal cortex. Forty participants, each paired with a stranger, completed two experimental conditions in a randomized order: (i) face-to-face and (ii) face stimulus (eye-to-eye contact with a face stimulus of a fictitious person displayed on the screen). Following each condition, participants played economic games with either their partner or an assumed person displayed on the screen. Neural activity in the lateral prefrontal cortex was recorded by functional near-infrared spectroscopy hyperscanning. Sparse multiset canonical correlation analysis showed that a physically inactive lifestyle was covaried with poorer reciprocity, greater trust, shorter decision-making time, and weaker intra-brain connectivity in the dorsal lateral prefrontal cortex and poorer inter-brain synchrony in the ventral lateral prefrontal cortex. These associations were observed exclusively in the face-to-face condition. Our findings suggest that a physically inactive lifestyle may alter human prosocial behavior by impairing adaptable prosocial decision-making in response to social factors through altered intra-brain functional connectivity and inter-brain synchrony.

Epigenetic mechanisms linking early-life adversities and mental health.

Early-life adversities, whether prenatal or postnatal exposure, have been linked to adverse mental health outcomes later in life increasing the risk of several psychiatric disorders. Research on its neurobiological consequences demonstrated an association between exposure to adversities and persistent alterations in the structure, function, and connectivity of the brain. Consistent evidence supports the idea that regulation of gene expression through epigenetic mechanisms are involved in embedding the impact of early-life experiences in the genome and mediate between social environments and later behavioral phenotypes. In addition, studies from rodent models and humans suggest that these experiences and the acquired risk factors can be transmitted through epigenetic mechanisms to offspring and the following generations potentially contributing to a cycle of disease or disease risk. However, one of the important aspects of epigenetic mechanisms, unlike genetic sequences that are fixed and unchangeable, is that although the epigenetic markings are long-lasting, they are nevertheless potentially reversible. In this review, we summarize our current understanding of the epigenetic mechanisms involved in the mental health consequences derived from early-life exposure to malnutrition, maltreatment and poverty, adversities with huge and pervasive impact on mental health. We also discuss the evidence about transgenerational epigenetic inheritance in mammals and experimental data suggesting that suitable social and pharmacological interventions could reverse adverse epigenetic modifications induced by early-life negative social experiences. In this regard, these studies must be accompanied by efforts to determine the causes that promote these adversities and that result in health inequity in the population.

Interacting pest control and pollination services in coffee systems.

Biodiversity-mediated ecosystem services (ES) support human well-being, but their values are typically estimated individually. Although ES are part of complex socioecological systems, we know surprisingly little about how multiple ES interact ecologically and economically. Interactions could be positive (synergy), negative (trade-offs), or absent (additive effects), with strong implications for management and valuation. Here, we evaluate the interactions of two ES, pollination and pest control, via a factorial field experiment in 30 Costa Rican coffee farms. We found synergistic interactions between these two critical ES to crop production. The combined positive effects of birds and bees on fruit set, fruit weight, and fruit weight uniformity were greater than their individual effects. This represents experimental evidence at realistic farm scales of positive interactions among ES in agricultural systems. These synergies suggest that assessments of individual ES may underestimate the benefits biodiversity provides to agriculture and human well-being. Using our experimental results, we demonstrate that bird pest control and bee pollination services translate directly into monetary benefits to coffee farmers. Excluding both birds and bees resulted in an average yield reduction of 24.7% (equivalent to losing US$1,066.00/ha). These findings highlight that habitat enhancements to support native biodiversity can have multiple benefits for coffee, a valuable crop that supports rural livelihoods worldwide. Accounting for potential interactions among ES is essential to quantifying their combined ecological and economic value.