Loss Aversion in Cocaine Users: Influence of Risk and Commodity Type

Numerous studies in behavioral economics have demonstrated that individuals are more sensitive to the prospect of a loss than a gain (i.e., loss aversion). Although loss aversion has been well described in healthy populations, little research exists in individuals with substance use disorders. The purpose of this study was to comprehensively evaluate loss aversion in cocaine users. Participants completed measures designed to assess loss aversion for drug and non-drug commodities under varying risk conditions. Cocaine demand was determined using a cocaine purchase task. Cocaine users showed a loss aversion score that was consistent across commodity and risk conditions. Compared to the normative loss aversion coefficient value (i.e., λ = 2) a large effect size decrease in loss aversion was observed in cocaine users. Hypothetical demand for cocaine was well explained by demand models. More intense and inelastic cocaine demand was also associated with greater loss aversion for cocaine. These data represent the first systematic study on loss aversion in cocaine using populations and indicate that reduced loss aversion is associated with cocaine use. Future studies should explore potential behavioral and neurobiological mechanisms to determine the benefit of loss aversion for treatment and intervention development efforts

EXAMINING THE UTILITY OF BEHAVIORAL ECONOMIC DEMAND IN ADDICTION SCIENCE

The marriage of perspectives from behavioral economic theory and learning theory has the potential to advance an understanding of substance use and substance use disorder. Behavioral economic demand is a central concept to this interdisciplinary approach. Evaluating demand in the laboratory and clinic can improve previous research on the relative reinforcing effects of drugs by accounting for the multi-dimensional nature of reinforcement rather than viewing reinforcement as a unitary construct. Recent advances in the commodity purchase task methodology have further simplified the measurement of demand values in human participants. This dissertation project presents a programmatic series of studies designed to demonstrate the utility of using a behavioral economic demand framework and the purchase task methodology for understanding substance use disorder through basic and applied science research. Experiments are presented spanning a continuum from theoretical and methodological development to longitudinal work and clinical application. These experiments demonstrate three key conclusions regarding behavioral economic demand. First, behavioral economic demand provides a reliable and valid measure of drug valuation that is applicable to varied drug types and participant populations. Second, behavioral economic demand is a stimulus-selective measure specifically reflecting valuation for the commodity under study. Third, behavioral economic demand provides incremental information about substance use in the laboratory and clinical setting above and beyond traditional measures of reinforcer valuation and other behavioral economic variables. These findings collectively highlight the benefits of behavioral economic demand and provide an important platform for future work in addiction science

Stimulus-Selectivity of Drug Purchase Tasks: A Preliminary Study Evaluating Alcohol and Cigarette Demand

The use of drug purchase tasks to measure drug demand in human behavioral pharmacology and addiction research has proliferated in recent years. Few studies have systematically evaluated the stimulus selectivity of drug purchase tasks to demonstrate that demand metrics are specific to valuation of or demand for the commodity under study. Stimulus selectivity is broadly defined for this purpose as a condition under which a specific stimulus input or target (e.g., alcohol, cigarettes) is the primary determinant of behavior (e.g., demand). The overall goal of the present study was to evaluate the stimulus selectivity of drug purchase tasks. Participants were sampled from the Amazon.com\u27s crowdsourcing platform Mechanical Turk. Participants completed either alcohol and soda purchase tasks (Experiment 1; N = 139) or cigarette and chocolate purchase tasks (Experiment 2; N = 46), and demand metrics were compared to self-reported use behaviors. Demand metrics for alcohol and soda were closely associated with commodity-similar (e.g., alcohol demand and weekly alcohol use) but not commodity-different (e.g., alcohol demand and weekly soda use) variables. A similar pattern was observed for cigarette and chocolate demand, but selectivity was not as consistent as for alcohol and soda. Collectively, we observed robust selectivity for alcohol and soda purchase tasks and modest selectivity for cigarette and chocolate purchase tasks. These preliminary outcomes suggest that demand metrics adequately reflect the specific commodity under study and support the continued use of purchase tasks in substance use research

A Pilot Study of Loss Aversion for Drug and Non-Drug Commodities in Cocaine Users

Background—Numerous studies in behavioral economics have demonstrated that individuals are more sensitive to the prospect of a loss than a gain (i.e., loss aversion). Although loss aversion has been well described in “healthy” populations, little research exists in individuals with substance use disorders. This gap is notable considering the prominent role that choice and decision-making play in drug use. The purpose of this pilot study was to evaluate loss aversion in active cocaine users. Methods—Current cocaine users (N = 38; 42% female) participated in this within-subjects laboratory pilot study. Subjects completed a battery of tasks designed to assess loss aversion for drug and non-drug commodities under varying risk conditions. Standardized loss aversion coefficients (λ) were compared to theoretically and empirically relevant normative values (i.e., λ = 2). Results—Compared to normative loss aversion coefficient values, a precise and consistent decrease in loss aversion was observed in cocaine users (sample λ ≈ 1). These values were observed across drug and non-drug commodities as well as under certain and risky conditions. Conclusions—These data represent the first systematic study of loss aversion in cocaine-using populations and provide evidence for equal sensitivity to losses and gains or loss equivalence. Futures studies should evaluate the specificity of these effects to a history of cocaine use as well as the impact of manipulations of loss aversion on drug use to determine how this phenomenon may contribute to intervention development efforts

Buspirone Maintenance Does Not Alter the Reinforcing, Subjective, and Cardiovascular Effects of Intranasal Methamphetamine

Background—Medications development efforts for methamphetamine-use disorder have targeted central monoamines because these systems are directly involved in the effects of methamphetamine. Buspirone is a dopamine autoreceptor and D3 receptor antagonist and partial agonist at serotonin 1A receptors, making it a logical candidate medication for methamphetamine-use disorder. Buspirone effects on abuse-related behaviors of methamphetamine have been mixed in clinical and preclinical studies. Experimental research using maintenance dosing, which models therapeutic use, is limited. This study evaluated the influence of buspirone maintenance on the reinforcing effects of methamphetamine using a self-administration procedure, which has predictive validity for clinical efficacy. The impact of buspirone maintenance on the subjective and cardiovascular response to methamphetamine was also determined. Methods—Eight research participants (1 female) reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind protocol in which the pharmacodynamic effects of intranasal methamphetamine (0, 15, and 30 mg) were assessed after at least 6 days of buspirone (0 and 45 mg/day) maintenance. Results—Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like subjective (e.g., increased ratings of Good Effects and Like Drug) and cardiovascular (e.g., elevated blood pressure) effects. These effects of methamphetamine were similar under buspirone and placebo maintenance conditions. Maintenance on buspirone was well tolerated and devoid of effects when administered alone. Conclusions—These data suggest that buspirone is unlikely to be an effective pharmacotherapy for methamphetamine-use disorder. Given the central role of monoamines in methamphetamine-use disorder, it is reasonable for future studies to continue to target these systems

Pharmacokinetic-based failure of a detergent virucidal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) nasal infections: A preclinical study and randomized controlled trial

BACKGROUND: The nose is the portal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, suggesting the nose as a target for topical antiviral therapies. The purpose of this study was to assess both the in vivo and in vitro efficacy of a detergent-based virucidal agent, Johnson and Johnson's Baby Shampoo (J&J), in SARS-CoV-2-infected subjects. METHODS: Subjects were randomized into three treatment groups: (1) twice daily nasal irrigation with J&J in hypertonic saline, (2) hypertonic saline alone, and (3) no intervention. Complementary in vitro experiments were performed in cultured human nasal epithelia. The primary outcome measure in the clinical trial was change in SARS-CoV-2 viral load over 21 days. Secondary outcomes included symptom scores and change in daily temperature. Outcome measures for in vitro studies included change in viral titers. RESULTS: Seventy-two subjects completed the clinical study (n = 24 per group). Despite demonstrated safety and robust efficacy in in vitro virucidal assays, J&J irrigations had no impact on viral titers or symptom scores in treated subjects relative to controls. Similar findings were observed administering J&J to infected cultured human airway epithelia using protocols mimicking the clinical trial regimen. Additional studies of cultured human nasal epithelia demonstrated that lack of efficacy reflected pharmacokinetic failure, with the most virucidal J&J detergent components rapidly absorbed from nasal surfaces. CONCLUSION: In this randomized clinical trial of subjects with SARS-CoV-2 infection, a topical detergent-based virucidal agent had no effect on viral load or symptom scores. Complementary in vitro studies confirmed a lack of efficacy, reflective of pharmacokinetic failure and rapid absorption from nasal surfaces

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

Evaluating Strategies for Sustainable Intensification of US Agriculture Through the Long-Term Agroecosystem Research Network

Sustainable intensification is an emerging model for agriculture designed to reconcile accelerating global demand for agricultural products with long-term environmental stewardship. Defined here as increasing agricultural production while maintaining or improving environmental quality, sustainable intensification hinges upon decision-making by agricultural producers, consumers, and policy-makers. The Long-Term Agroecosystem Research (LTAR) network was established to inform these decisions. Here we introduce the LTAR Common Experiment, through which scientists and partnering producers in US croplands, rangelands, and pasturelands are conducting 21 independent but coordinated experiments. Each local effort compares the outcomes of a predominant, conventional production system in the region (\u27business as usual\u27) with a system hypothesized to advance sustainable intensification (\u27aspirational\u27). Following the logic of a conceptual model of interactions between agriculture, economics, society, and the environment, we identified commonalities among the 21 experiments in terms of (a) concerns about business-as-usual production, (b) \u27aspirational outcomes\u27 motivating research into alternatives, (c) strategies for achieving the outcomes, (d) practices that support the strategies, and (e) relationships between practice outreach and adoption. Network-wide, concerns about business as usual include the costs of inputs, opportunities lost to uniform management approaches, and vulnerability to accelerating environmental changes. Motivated by environmental, economic, and societal outcomes, scientists and partnering producers are investigating 15 practices in aspirational treatments to sustainably intensify agriculture, from crop diversification to ecological restoration. Collectively, the aspirational treatments reveal four general strategies for sustainable intensification: (1) reducing reliance on inputs through ecological intensification, (2) diversifying management to match land and economic potential, (3) building adaptive capacity to accelerating environmental changes, and (4) managing agricultural landscapes for multiple ecosystem services. Key to understanding the potential of these practices and strategies are informational, economic, and social factors—and trade-offs among them—that limit their adoption. LTAR is evaluating several actions for overcoming these barriers, including finding financial mechanisms to make aspirational production systems more profitable, resolving uncertainties about trade-offs, and building collaborative capacity among agricultural producers, stakeholders, and scientists from a broad range of disciplines