Many studies show that time preference data from experiments and surveys are related to field behavior. Time preference measures in these studies typically depend simultaneously on utility curvature, ...the level of impatience, and the change in the level of impatience. Thus, these studies do not allow one to establish which of these three components drive(s) the field behavior of interest. Of these components, the change in the level of impatience is theoretically thought to be the main driver of time inconsistencies and self-control problems. To test this theoretical presumption, one has to measure the change in the level of impatience independently from utilities and levels of impatience. This paper introduces a measure of the degree of decreasing impatience, the DI-index. It measures the change of impatience independently from the level of impatience and independently from utility. It can also be used to test various discounting models. An experiment finds no correlation between the degree of decreasing impatience and self-reported self-control problems in daily life, suggesting that changing impatience is not the sole driver of self-control problems.
Data and the supplementary material are available at
https://doi.org/10.1287/mnsc.2017.3015
.
This paper was accepted by Manel Baucells, decision analysis.
Risk attitudes in a social context Rohde, Ingrid M. T.; Rohde, Kirsten I. M.
Journal of risk and uncertainty,
12/2011, Letnik:
43, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Many experiments have demonstrated that when evaluating payoffs, people take not only their own payoffs into account, but also the payoffs of others in their social environment. Most of this evidence ...is found in settings where payoffs are riskless. It is plausible that if people care about the payoffs of others, they do so not only in a riskless context, but also in a risky one. This suggests that an individual's decision making under risk depends on the risks others in his or her environment face. This paper is the first to test whether individuals' risk attitudes are affected by the risks others face. The results show that risk attitudes appear to be less affected by others' risks than expected, even though the same subjects do show concerns for inequality in a riskless setting. Interestingly, we find that people prefer risks to be independent across individuals in society rather than correlated.
Groundwater is a vital water supply worldwide for people and nature. However, species and ecosystems that depend on groundwater for some or all of their water needs, known as groundwater dependent ...ecosystems (GDEs), are increasingly becoming threatened worldwide due to growing human water demands. Over the past two decades, the protection and management of GDEs have been incorporated into several water management policy initiatives worldwide including jurisdictions within Australia, the European Union, South Africa, and the United States. Among these, Australia has implemented the most comprehensive framework to manage and protect GDEs through its water policy initiatives. Using a science‐based approach, Australia has made good progress at reducing uncertainty when selecting management thresholds for GDEs in their water management plans. This has been achieved by incorporating appropriate metrics for GDEs into water monitoring programs so that information gathered over time can inform management decisions. This adaptive management approach is also accompanied by the application of the “Precautionary Principle” in cases where insufficient information on GDEs exist. Additionally, the integration of risk assessment into Australia's approach has enabled water managers to prioritize the most valuable and vulnerable ecologic assets necessary to manage GDEs under Australia's national sustainable water management legislation. The purpose of this paper is to: (1) compare existing global policy initiatives for the protection and management of GDEs; (2) synthesize Australia's adaptive management approach of GDEs in their state water plans; and (3) highlight opportunities and challenges of applying Australia's approach for managing GDEs under other water management policies worldwide.
Article Impact Statement: Global synthesis of opportunities and challenges for managing groundwater dependent ecosystems under sustainable water management policies.
As societies are increasingly concerned with risks, it is important to evaluate risks not only from an individual but also from a societal perspective. Two essential dimensions of public or social ...risks are the inequality concerning the distribution of risks over various groups and members of society and the level of risk faced by individuals and by the society as a whole. This paper disentangles these two essential dimensions and studies people's preferences concerning different types of allocations of risks over groups of people. We do so in a laboratory experiment with real incentives, where subjects are placed in the role of a social planner and choose between different types of allocations of risks over 10 other participants. The allocations differ only in terms of dispersion, i.e. they differ only in terms of inequality and risk. The majority of our subjects exhibit clear preferences over different types of allocations consistent with ex ante inequality and individual risk aversion, and ex post inequality and collective risk seeking behavior. These results are consistent with the literature on public risk and can be reconciled with responsibility aversion.
Precisely how silver nanoparticles (AgNPs) kill mammalian cells still is not fully understood. It is not clear if AgNP-induced damage differs from silver cation (Ag
), nor is it known how AgNP damage ...is transmitted from cell membranes, including endosomes, to other organelles. Cells can differ in relative sensitivity to AgNPs or Ag
, which adds another layer of complexity to identifying specific mechanisms of action. Therefore, we determined if there were specific effects of AgNPs that differed from Ag
in cells with high or low sensitivity to either toxicant.
Cells were exposed to intact AgNPs, Ag
, or defined mixtures of AgNPs with Ag
, and viability was assessed. The level of dissolved Ag
in AgNP suspensions was determined using inductively coupled plasma mass spectrometry. Changes in reactive oxygen species following AgNP or Ag
exposure were quantified, and treatment with catalase, an enzyme that catalyzes the decomposition of H
O
to water and oxygen, was used to determine selectively the contribution of H
O
to AgNP and Ag
induced cell death. Lipid peroxides, formation of 4-hydroxynonenol protein adducts, protein thiol oxidation, protein aggregation, and activation of the integrated stress response after AgNP or Ag
exposure were quantified. Lastly, cell membrane integrity and indications of apoptosis or necrosis in AgNP and Ag
treated cells were examined by flow cytometry.
We identified AgNPs with negligible Ag
contamination. We found that SUM159 cells, which are a triple-negative breast cancer cell line, were more sensitive to AgNP exposure less sensitive to Ag
compared to iMECs, an immortalized, breast epithelial cell line. This indicates that high sensitivity to AgNPs was not predictive of similar sensitivity to Ag
. Exposure to AgNPs increased protein thiol oxidation, misfolded proteins, and activation of the integrated stress response in AgNP sensitive SUM159 cells but not in iMEC cells. In contrast, Ag
cause similar damage in Ag
sensitive iMEC cells but not in SUM159 cells. Both Ag
and AgNP exposure increased H
O
levels; however, treatment with catalase rescued cells from Ag
cytotoxicity but not from AgNPs. Instead, our data support a mechanism by which damage from AgNP exposure propagates through cells by generation of lipid peroxides, subsequent lipid peroxide mediated oxidation of proteins, and via generation of 4-hydroxynonenal (4-HNE) protein adducts.
There are distinct differences in the responses of cells to AgNPs and Ag
. Specifically, AgNPs drive cell death through lipid peroxidation leading to proteotoxicity and necrotic cell death, whereas Ag
increases H
O
, which drives oxidative stress and apoptotic cell death. This work identifies a previously unknown mechanism by which AgNPs kill mammalian cells that is not dependent upon the contribution of Ag
released in extracellular media. Understanding precisely which factors drive the toxicity of AgNPs is essential for biomedical applications such as cancer therapy, and of importance to identifying consequences of unintended exposures.
Situations where independent agents need to align their activities to achieve individually and socially beneficial outcomes are abundant, reaching from everyday situations like fixing a time for a ...meeting to global problems like climate change agreements. Often such situations can be described as stag-hunt games, where coordinating on the socially efficient outcome is individually optimal but also entails a risk of losing out. Previous work has shown that in fixed interaction neighborhoods agents' behavior mostly converges to the collectively inefficient outcome. However, in the field, interaction neighborhoods often can be self-determined. Theoretical work investigating such circumstances is ambiguous in whether the efficient or inefficient outcome will prevail. We performed an experiment with human subjects exploring how free neighborhood choice affects coordination. In a fixed interaction treatment, a vast majority of subjects quickly coordinates on the inefficient outcome. In a treatment with neighborhood choice, the outcome is dramatically different: behavior quickly converges to the socially desirable outcome leading to welfare gains 2.5 times higher than in the environment without neighborhood choice. Participants playing efficiently exclude those playing inefficiently who in response change their behavior and are subsequently included again. Importantly, this mechanism is effective despite that only few exclusions actually occur.
Loss of function mutations in Kelch-like ECH Associated Protein 1 (KEAP1), or gain-of-function mutations in nuclear factor erythroid 2-related factor 2 (NRF2), are common in non-small cell lung ...cancer (NSCLC) and associated with therapeutic resistance. To discover novel NRF2 inhibitors for targeted therapy, we conducted a quantitative high-throughput screen using a diverse set of ∼400 000 small molecules (Molecular Libraries Small Molecule Repository Library, MLSMR) at the National Center for Advancing Translational Sciences. We identified ML385 as a probe molecule that binds to NRF2 and inhibits its downstream target gene expression. Specifically, ML385 binds to Neh1, the Cap ‘N’ Collar Basic Leucine Zipper (CNC-bZIP) domain of NRF2, and interferes with the binding of the V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homologue G (MAFG)-NRF2 protein complex to regulatory DNA binding sequences. In clonogenic assays, when used in combination with platinum-based drugs, doxorubicin or taxol, ML385 substantially enhances cytotoxicity in NSCLC cells, as compared to single agents. ML385 shows specificity and selectivity for NSCLC cells with KEAP1 mutation, leading to gain of NRF2 function. In preclinical models of NSCLC with gain of NRF2 function, ML385 in combination with carboplatin showed significant antitumor activity. We demonstrate the discovery and validation of ML385 as a novel and specific NRF2 inhibitor and conclude that targeting NRF2 may represent a promising strategy for the treatment of advanced NSCLC.
The development and regulatory review of BNT162b2, a COVID-19 vaccine, and PaxlovidTM (nirmatrelvir tablets/ritonavir tablets), a COVID-19 therapeutic, are benchmarks for accelerated innovation ...during a global pandemic. Rapid choice of the SARS-CoV-2 spike protein and main protease (Mpro) as targets for the vaccine and therapeutic, respectively, leveraged the available knowledge of the biology of SARS-CoV-2 and related viruses. The nonclinical immunogenicity and safety of BNT162b2 was rigorously assessed. Likewise, a comprehensive nonclinical safety assessment was conducted for the therapeutic candidates, lufotrelvir (PF-07304814) and nirmatrelvir (PF-07321332). The development and regulatory review of BNT162b2 and Paxlovid was enabled through close collaboration of the pharmaceutical industry with regulatory agencies and public health organizations. This experience highlights approaches that could be adopted for pandemic preparedness including risk-based investment strategies, conduct of activities in parallel that normally are conducted sequentially, quick kill decisions, simultaneous evaluation of multiple candidates, and use of flexible, established vaccine platforms.
Background The first wave of the COVID-19 pandemic overwhelmed healthcare systems in many countries, and the rapid spread of the virus and the acute course of the disease resulted in a shortage of ...intensive care unit (ICU) beds. We studied preferences of the public in the Netherlands regarding the allocation of ICU beds during a health crisis. Methods We distributed a cross-sectional online survey at the end of March 2020 to a representative sample of the adult population in the Netherlands. We collected preferences regarding the allocation of ICU beds, both in terms of who should be involved in the decision-making and which rationing criteria should be considered. We conducted Probit regression analyses to investigate associations between these preferences and several characteristics and opinions of the respondents. Results A total of 1,019 respondents returned a completed survey. The majority favored having physicians (55%) and/or expert committees (51%) play a role in the allocation of ICU beds and approximately one-fifth did not favor any of the proposed decision-makers. Respondents preferred to assign higher priority to vulnerable patients and patients who have the best prospect of full recovery. They also preferred that personal characteristics, including age, play no role. Conclusion "Our findings show that current guidelines for allocating ICU beds that include age as an independent criterion may not be consistent with societal preferences. Age may only play a role indirectly, in relation to the vulnerability of patients and their prospect of full recovery. Allocation of ICU beds during a health crisis requires a multivalue ethical framework."
We conduct a laboratory experiment among male participants to investigate whether rewarding schemes that depend on work performance—in particular, tournament incentives—induce more stress than ...schemes that are independent of performance—fixed payment scheme. Stress is measured over the entire course of the experiment at both the hormonal and psychological level. Hormonal stress responses are captured by measuring salivary cortisol levels. Psychological stress responses are measured by self-reported feelings of stress and primary appraisals. We find that tournament incentives induce a stress response whereas a fixed payment does not induce stress. This stress response does not differ significantly across situations in which winners and losers of the tournament are publically announced and situations in which this information remains private. Biological and psychological stress measures are positively correlated, i.e. increased levels of cortisol are associated with stronger feelings of stress. Nevertheless, neither perceived psychological stress nor elevated cortisol levels in a previous tournament predict a subsequent choice between tournaments and fixed payment schemes, indicating that stress induced by incentives schemes is not a relevant criterion for sorting decisions in our experiment. Finally, we find that cortisol levels are severely elevated at the beginning of the experiment, suggesting that participants experience stress in anticipation of the experiment per se, potentially due to uncertainties associated with the unknown lab situation. We call this the novelty effect.
PDF
