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Human cooperation is often claimed to be special and requiring explanations based on gene–culture coevolution favouring a desire to copy common social behaviours. If this is true, then individuals should be motivated to both observe and copy common social behaviours. Previous economic experiments, using the public goods game, have suggested individuals' desire to sacrifice for the common good and to copy common social behaviours. However, previous experiments have often not shown examples of success. Here we test, on 489 participants, whether individuals are more motivated to learn about, and more likely to copy, either common or successful behaviours. Using the same social dilemma and standard instructions, we find that individuals were primarily motivated to learn from successful rather than common behaviours. Consequently, social learning disfavoured costly cooperation, even when individuals could observe a stable, pro-social level of cooperation. Our results call into question explanations for human cooperation based on cultural evolution and/or a desire to conform with common social behaviours. Instead, our results indicate that participants were motivated by personal gain, but initially confused, despite receiving standard instructions. When individuals could learn from success, they learned to cooperate less, suggesting that human cooperation is maybe not so special after all.

Economic experiments have suggested that cooperative humans will altruistically match local levels of cooperation (conditional cooperation) and pay to punish non-cooperators (altruistic punishment). Evolutionary models have suggested that if altruists punish non-altruists this could favour the evolution of costly helping behaviours (cooperation) among strangers. An often-key requirement is that helping behaviours and punishing behaviours form one single conjoined trait (strong reciprocity). Previous economics experiments have provided support for the hypothesis that punishment and cooperation form one conjoined, altruistically motivated, trait. However, such a conjoined trait may be evolutionarily unstable, and previous experiments have confounded a fear of being punished with being surrounded by cooperators, two factors that could favour cooperation. Here, we experimentally decouple the fear of punishment from a cooperative environment and allow cooperation and punishment behaviour to freely separate (420 participants). We show, that if a minority of individuals is made immune to punishment, they (i) learn to stop cooperating on average despite being surrounded by high levels of cooperation, contradicting the idea of conditional cooperation and (ii) often continue to punish, ‘hypocritically’, showing that cooperation and punishment do not form one, altruistically motivated, linked trait.

Leber congenital amaurosis type 10 is a severe retinal dystrophy caused by mutations in the CEP290 gene1,2. We developed EDIT-101, a candidate genome-editing therapeutic, to remove the aberrant splice donor created by the IVS26 mutation in the CEP290 gene and restore normal CEP290 expression. Key to this therapeutic, we identified a pair of Staphylococcus aureus Cas9 guide RNAs that were highly active and specific to the human CEP290 target sequence. In vitro experiments in human cells and retinal explants demonstrated the molecular mechanism of action and nuclease specificity. Subretinal delivery of EDIT-101 in humanized CEP290 mice showed rapid and sustained CEP290 gene editing. A comparable surrogate non-human primate (NHP) vector also achieved productive editing of the NHP CEP290 gene at levels that met the target therapeutic threshold, and demonstrated the ability of CRISPR/Cas9 to edit somatic primate cells in vivo. These results support further development of EDIT-101 for LCA10 and additional CRISPR-based medicines for other inherited retinal disorders. In human cells, a humanized mouse model and non-human primates, CRISPR/Cas9 corrects the splicing defect in a gene associated with congenital blindness.

BACKGROUND The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN Observational cohort study. SETTING 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS 134��672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE National Institutes of Health.

Background: Previous studies that evaluated the prevalence, awareness and treatment of hypertension in Nigeria were either localized to some specific regions of the country or non-standardized thereby making evaluation of trend in hypertension care difficult.Methods: We used the World Health Organization (WHO) STEPwise approach to chronic disease risk factor surveillance to evaluate in a nationally representative sample of 4192 adult Nigerians selected from a rural and an urban community in one state in each of the six geo-political zones of the country.Results: The overall age-standardized prevalence of hypertension was 38.1% and this varied across the geo-political zones as follows: North-Central, 20.9%; North-East, 27.5%; North-West, 26.8%; South-East, 52.8%; South-South, 44.6%; and South-West, 42.1%. Prevalence rate did not differ significantly (p > 0.05) according to place of residence; 39.2% versus 37.5 %; urban vs rural. Prevalence of hypertension increased from 6.8% among subjects less than 30 years to 63.0% among those aged 70 years and above. Awareness was better (62.2% vs. 56.6%; P = 0.0272); treatment rate significantly higher (40.9 % vs. 30.8%; P < 0.0001) and control similar (14 vs. 10.8%) among urban compared to rural residents. Women were more aware of (63.3% vs. 52.8%; P < 0.0001); had similar (P > 0.05) treatment (36.7 vs. 34.3%) and control (33.9% vs. 35.5%) rates of hypertension compared to men.Conclusion: Our results suggest a large burden of hypertension in Nigeria and a closing up of the rural-urban gap previously reported. This calls for a change in public health policies anchored on a primary health care system to address the emerging disease burden occasioned by hypertension.

Purpose: The aims of this study were to describe the demographic characteristics of pediatric dentistry patients undergoing dental rehabilitation under general anesthesia (DRGA) at UNC-Chapel Hill during the last 13 years and identify factors associated with multiple (1 versus 2 or more) DRGA visits during that timeframe. Study design: Administrative claims data were used to identify children and adolescents (age

Purpose: Although high glucocorticoid receptor (GR) expression in early-stage estrogen receptor (ER)-negative breast cancer is associated with shortened relapse-free survival (RFS), how associated GR transcriptional activity contributes to aggressive breast cancer behavior is not well understood. Using potent GR antagonists and primary tumor gene expression data, we sought to identify a tumor-relevant gene signature based on GR activity that would be more predictive than GR expression alone. Experimental Design: Global gene expression and GR ChIP-sequencing were performed to identify GR-regulated genes inhibited by two chemically distinct GR antagonists, mifepristone and CORT108297. Differentially expressed genes from MDA-MB-231 cells were cross-evaluated with significantly expressed genes in GR-high versus GR-low ER-negative primary breast cancers. The resulting subset of GR-targeted genes was analyzed in two independent ER-negative breast cancer cohorts to derive and then validate the GR activity signature (GRsig). Results: Gene expression pathway analysis of glucocorticoid-regulated genes (inhibited by GR antagonism) revealed cell survival and invasion functions. GR ChIP-seq analysis demonstrated that GR antagonists decreased GR chromatin association for a subset of genes. A GRsig that comprised n = 74 GR activation-associated genes (also reversed by GR antagonists) was derived from an adjuvant chemotherapy-treated Discovery cohort and found to predict probability of relapse in a separate Validation cohort (HR = 1.9; P = 0.012). Conclusions: The GRsig discovered herein identifies high-risk ER-negative/GR-positive breast cancers most likely to relapse despite administration of adjuvant chemotherapy. Because GR antagonism can reverse expression of these genes, we propose that addition of a GR antagonist to chemotherapy may improve outcome for these high-risk patients. Clin Cancer Res; 24(14); 3433–46. ©2018 AACR.

Introduction Dismounted military operations often involve prolonged load carriage over complex terrain, which can result in excessive metabolic costs that can directly impair soldiers' performance. Although estimating these demands is a critical interest for mission planning purposes, it is unclear whether existing estimation equations developed from controlled laboratory- and field-based studies accurately account for energy costs of traveling over complex terrain. This study investigated the accuracy of the following equations for military populations when applied to data collected over complex terrain with two different levels of load carriage: American College of Sports Medicine (2002), Givoni and Goldman (1971), Jobe and White (2009), Minetti et al (2002), Pandolf et al (1977), and Santee et al (2003). Materials and methods Nine active duty military personnel (age 21 ± 3 yr; height 1.72 ± 0.07 m; body mass 83.4 ± 12.9 kg; VO2 max 47.8 ± 3.9 mL/kg/min) were monitored during load carriage (with loads equal to 30% and 45% of body mass) over a 10-km mixed terrain course on two separate test days. The course was divided into four 2.5-km laps of 40 segments based on distance, grade, and/or surface factors. Timing gates and radio-frequency identification cards (SportIdent; Scarborough Orienteering, Huntington Beach, CA) were used to record completion times for each course segment. Breath-by-breath measures of energy expenditure were collected using portable oxygen exchange devices (COSMED Sri., Rome, Italy) and compared model estimates. Results The Santee et al equation performed best, demonstrating the smallest estimation bias (-13 ± 87 W) and lowest root mean square error (99 W). Conclusion Current predictive equations underestimate the metabolic cost of load carriage by military personnel over complex terrain. Applying the Santee et al correction factor to the Pandolf et al equation may be the most suitable approach for estimating metabolic demands in these circumstances. However, this work also outlines the need for improvements to these methods, new method development and validation, or the use of a multi-model approach to account for mixed terrain.

Humans may cooperate strategically, cooperating at higher levels than expected from their short-term interests, to try and stimulate others to cooperate. To test this hypothesis, we experimentally manipulated the extent an individual's behaviour is known to others, and hence whether or not strategic cooperation is possible. In contrast with many previous studies, we avoided confounding factors by preventing individuals from learning during the game about either pay-offs or about how other individuals behave. We found clear evidence for strategic cooperators—just telling some individuals that their groupmates would be informed about their behaviour led to them tripling their initial level of cooperation, from 17 to 50%. We also found that many individuals play as if they do not understand the game, and their presence obscures the detection of strategic cooperation. Identifying such players allowed us to detect and study strategic motives for cooperation in novel, more powerful, ways.

1. There is limited knowledge regarding the metabolism of megestrol acetate (MA), as it was approved by FDA in 1971, prior to the availability of modern tools for identifying specific drug-metabolizing enzymes. We determined the cytochrome P450s (P450s) and UDP-glucuronosyltransferases (UGTs) that metabolize MA, identified oxidative metabolites and determined pharmacologic activity at the progesterone, androgen and glucocorticoid receptors (PR, AR and GR, respectively). 2. Oxidative metabolites were produced using human liver microsomes (HLMs), and isolated for mass spectral (MS) and nuclear magnetic resonance (NMR) analyses. We screened recombinant P450s using MA at 62 μM (HLM Km for metabolite 1; M1) and 28 μM (HLM Km for metabolite 2; M2). UGT isoforms were simultaneously incubated with UDPGA, nicotinamide adenine dinucleotide phosphate (NADPH), CYP3A4 and MA. Metabolites were evaluated for pharmacologic activity on the PR, AR and GR. CYP3A4 and CYP3A5 are responsible for oxidative metabolism of 62 μM MA. 3. At 28 μM substrate concentration, CYP3A4 was the only contributing enzyme. Mass spectral and NMR data suggest metabolism of MA to two alcohols. After oxidation, MA is converted into two secondary glucuronides by UGT2B17 among other UGTs. MA, M1 and M2 had significant pharmacologic activity on the PR while only MA showed activity on the AR and GR.

OBJECTIVES Whereas paclitaxel treatment is associated with leukopenia, the mechanisms that underlie this effect are not well-characterized. In addition, despite the importance of glucocorticoid signaling in cancer treatment, the genomic effects of glucocorticoid receptor antagonism by mifepristone treatment in primary human cells have never been described. METHODS As part of a randomized phase 1 clinical trial, we used microarrays to profile gene expression in peripheral blood cells sampled from each of four patients at baseline, after placebo/nanoparticle albumin-bound paclitaxel (nab-paclitaxel) treatment (cycle 1), and after mifepristone/nab-paclitaxel treatment (cycle 2). RESULTS We found that 63 genes were differentially expressed following treatment with nab-paclitaxel, including multiple genes in the tubulin pathway. We also found 606 genes that were differentially expressed in response to mifepristone; genes downregulated by mifepristone overlapped significantly with those previously identified as being upregulated by dexamethasone. CONCLUSION These results provide insights into the mechanisms of paclitaxel and glucocorticoid receptor inhibition in peripheral blood cells.

Purpose: Triple-negative breast cancer (TNBC) accounts for 10% to 20% of newly diagnosed invasive breast cancer. Finding effective targets for chemotherapy-resistant TNBC has proven difficult in part because of TNBC's molecular heterogeneity. We have previously reported that likely because of the antiapoptotic activity of glucocorticoid receptor (GR) in estrogen receptor (ER)-negative breast epithelial and cancer cells, high GR expression/activity in early-stage TNBC significantly correlates with chemotherapy resistance and increased recurrence. We hypothesized that pretreatment with mifepristone, a GR antagonist, would potentiate the efficacy of chemotherapy in GR+ TNBCs by inhibiting the antiapoptotic signaling pathways of GR and increasing the cytotoxic efficiency of chemotherapy. Experimental Design: TNBC cell apoptosis was examined in the context of physiologic glucocorticoid concentrations, chemotherapy, and/or pharmacologic concentrations of mifepristone. We used high-throughput live microscopy with continuous recording to measure apoptotic cells stained with a fluorescent dye and Western blot analysis to detect caspase-3 and PARP cleavage. The effect of mifepristone on GR-mediated gene expression was also measured. TNBC xenograft studies were performed in female severe combined immunodeficient (SCID) mice and tumors were measured following treatment with vehicle, paclitaxel, or mifepristone/paclitaxel. Results: We found that although mifepristone treatment alone had no significant effect on TNBC cell viability or clonogenicity in the absence of chemotherapy, the addition of mifepristone to dexamethasone/paclitaxel treatment significantly increased cytotoxicity and caspase-3/PARP cleavage. Mifepristone also antagonized GR-induced SGK1 and MKP1/DUSP1 gene expression while significantly augmenting paclitaxel-induced GR+ MDA-MB-231 xenograft tumor shrinkage in vivo. Conclusions: These results suggest that mifepristone pretreatment could be a useful strategy for increasing tumor cell apoptosis in chemotherapy-resistant GR+ TNBC. Clin Cancer Res; 19(22); 6163–72. ©2013 AACR.

It has become an accepted paradigm that humans have “prosocial preferences” that lead to higher levels of cooperation than those that would maximize their personal financial gain. However, the existence of prosocial preferences has been inferred post hoc from the results of economic games, rather than with direct experimental tests. Here, we test how behavior in a public-goods game is influenced by knowledge of the consequences of actions for other players. We found that ( i ) individuals cooperate at similar levels, even when they are not informed that their behavior benefits others; ( ii ) an increased awareness of how cooperation benefits others leads to a reduction, rather than an increase, in the level of cooperation; and ( iii ) cooperation can be either lower or higher than expected, depending on experimental design. Overall, these results contradict the suggested role of the prosocial preferences hypothesis and show how the complexity of human behavior can lead to misleading conclusions from controlled laboratory experiments.

Economic experiments are often used to study if humans altruistically value the welfare of others. A canonical result from public-good games is that humans vary in how they value the welfare of others, dividing into fair-minded conditional cooperators, who match the cooperation of others, and selfish noncooperators. However, an alternative explanation for the data are that individuals vary in their understanding of how to maximize income, with misunderstanding leading to the appearance of cooperation. We show that (i) individuals divide into the same behavioral types when playing with computers, whom they cannot be concerned with the welfare of; (ii) behavior across games with computers and humans is correlated and can be explained by variation in understanding of how to maximize income; (iii) misunderstanding correlates with higher levels of cooperation; and (iv) standard control questions do not guarantee understanding. These results cast doubt on certain experimental methods and demonstrate that a common assumption in behavioral economics experiments, that choices reveal motivations, will not necessarily hold.

SETTING World Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control ("Three I's") for TB prevention and control among persons living with HIV. OBJECTIVE To assess the implementation of the "Three I's" of TB-control at HIV treatment sites in lower income countries. DESIGN Survey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa. RESULTS ICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03). CONCLUSIONS Implementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status.

Mammalian target of rapamycin (mTOR) is an attractive target for cancer treatment. While rapamycin and its derivatives (e.g., everolimus) have been shown to inhibit mTOR signaling and cell proliferation in preclinical models of breast cancer, mTOR inhibition has demonstrated variable clinical efficacy with a trend toward better responses in estrogen receptor alpha positive (ERα+) compared to ERα negative (ERα-) tumors. Recently, serum- and glucocorticoid-regulated kinase 1 (SGK1) was identified as a substrate of mTOR kinase activity. Previous studies have alternatively suggested that either mTORC1 or mTORC2 is exclusively required for SGK1's Ser422 phosphorylation and activation in breast cancer cells. We investigated the effect of rapamycin on the growth of several ERα+ and ERα- breast cancer cell lines and examined differences in the phosphorylation of mTOR substrates (SGK1, p70S6K, and Akt) that might account for the differing sensitivity of these cell lines to rapamycin. We also examined which mTOR complex contributes to SGK1-Ser422 phosphorylation in ERα+ versus ERα- breast cell lines. We then assessed whether inhibiting SGK1 activity added to rapamycin-mediated cell growth inhibition by either using the SGK1 inhibitor GSK650394A or expressing an SGK1 shRNA. We observed sensitivity to rapamycin-mediated growth inhibition and inactivation of insulin-mediated SGK1-Ser422 phosphorylation in ERα+ MCF-7 and T47D cells, but not in ERα- MDA-MB-231 or MCF10A-Myc cells. In addition, either depleting SGK1 with shRNA or inhibiting SGK1 with GSK650394A preferentially sensitized MDA-MB-231 cells to rapamycin. Finally, we found that rapamycin-sensitive SGK1-Ser422 phosphorylation required ERα expression in MCF-7 derived cell lines. Therefore, targeting SGK1 activity may improve the efficacy of rapamycin and its analogs in the treatment of ERα- breast cancer.

Objectives To test the hypothesis that glucocorticoid receptor (GR) activation increases resistance to chemotherapy in high-grade serous ovarian cancer (HGS-OvCa) and that treatment with a GR antagonist will improve sensitivity to chemotherapy. Methods GR expression was assessed in OvCa cell lines by qRT-PCR and Western blot analysis and in xenografts and primary human tumors using immunohistochemistry (IHC). We also examined the effect of GR activation versus inhibition on chemotherapy-induced cytotoxicity in OvCa cell lines and in a xenograft model. Results With the exception of IGROV-1 cells, all OvCa cell lines tested had detectable GR expression by Western blot and qRT-PCR analysis. Twenty-five out of the 27 human primary HGS-OvCas examined expressed GR by IHC. No cell line expressed detectable progesterone receptor (PR) or androgen receptor (AR) by Western blot analysis. In vitro assays showed that in GR-positive HeyA8 and SKOV3 cells, dexamethasone (100nM) treatment upregulated the pro-survival genes SGK1 and MKP1/DUSP1 and inhibited carboplatin/gemcitabine-induced cell death. Concurrent treatment with two GR antagonists, either mifepristone (100nM) or CORT125134 (100nM), partially reversed these effects. There was no anti-apoptotic effect of dexamethasone on chemotherapy-induced cell death in IGROV-1 cells, which did not have detectable GR protein. Mifepristone treatment alone was not cytotoxic in any cell line. HeyA8 OvCa xenograft studies demonstrated that adding mifepristone to carboplatin/gemcitabine increased tumor shrinkage by 48% compared to carboplatin/gemcitabine treatment alone (P=0.0004). Conclusions These results suggest that GR antagonism sensitizes GR+ OvCa to chemotherapy-induced cell death through inhibition of GR-mediated cell survival pathways.

Humans are an intensely social species, frequently performing costly behaviors that benefit others. Efforts to solve the evolutionary puzzle of altruism have a lengthy history, and recent years have seen many important advances across a range of disciplines. Here we bring together this interdisciplinary body of research and review the main theories that have been proposed to explain human prosociality, with an emphasis on kinship, reciprocity, indirect reciprocity, punishment, and morality. We highlight recent methodological advances that are stimulating research and point to some areas that either remain controversial or merit more attention.

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.

The results of numerous economic games suggest that humans behave more cooperatively than would be expected if they were maximizing selfish interests. It has been argued that this is because individuals gain satisfaction from the success of others, and that such prosocial preferences require a novel evolutionary explanation. However, in previous games, imperfect behavior would automatically lead to an increase in cooperation, making it impossible to decouple any form of mistake or error from prosocial cooperative decisions. Here we empirically test between these alternatives by decoupling imperfect behavior from prosocial preferences in modified versions of the public goods game, in which individuals would maximize their selfish gain by completely (100%) cooperating. We found that, although this led to higher levels of cooperation, it did not lead to full cooperation, and individuals still perceived their group mates as competitors. This is inconsistent with either selfish or prosocial preferences, suggesting that the most parsimonious explanation is imperfect behavior triggered by psychological drives that can prevent both complete defection and complete cooperation. More generally, our results illustrate the caution that must be exercised when interpreting the evolutionary implications of economic experiments, especially the absolute level of cooperation in a particular treatment.

Geographic patterns and time trends for breast cancer suggest there are preventable causes that may include environmental factors. This article describes the development of new methods used in the Cape Cod Breast Cancer and Environment Study to investigate whether synthetic chemicals in the environment contribute to breast cancer risk.

Therapeutic camping for the mentally ill may provide an opportunity for remotivating chronic hospital patients. Two camping sessions initiated by the Maryland Department of Mental Hygiene were attended by 90 state hospital patients, each of whom had been hospitalized for at least two years and appeared to be making no progress in the hospital. Responses of patients to the camping experience were varied; no correlation between diagnosis and the patient's reaction to camping was apparent. However, within three months following the camp sessions, 41 patients were able to be discharged from the hospital.

What motivates human behaviour in social dilemmas? The results of public goods games are commonly interpreted as showing that humans are altruistically motivated to benefit others. However, there is a competing ‘confused learners’ hypothesis: that individuals start the game either uncertain or mistaken (confused) and then learn from experience how to improve their payoff (payoff-based learning). Here we (1) show that these competing hypotheses can be differentiated by how they predict contributions should decline over time; and (2) use metadata from 237 published public goods games to test between these competing hypotheses. We found, as predicted by the confused learners hypothesis, that contributions declined faster when individuals had more influence over their own payoffs. This predicted relationship arises because more influence leads to a greater correlation between contributions and payoffs, facilitating learning. Our results suggest that humans, in general, are not altruistically motivated to benefit others but instead learn to help themselves. Why does cooperation decline? Burton-Chellew and West compare data from 237 public goods games and find that cooperation declines faster when learning is easier.