Innovation under cap-and-trade programs.
Ontology highlight
ABSTRACT:
SUBMITTER: Taylor MR
PROVIDER: S-EPMC3323980 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Understanding the mechanisms governing innovation is a central element of evolutionary theory. Novel traits usually arise through mutations in existing genes, but trade-offs between new and ancestral protein functions are pervasive and constrain the evolution of innovation. Classical models posit that evolutionary innovation circumvents the constraints imposed by trade-offs through genetic amplifications, which provide functional redundancy. Bacterial multicopy plasmids provide a paradigmatic example of genetic amplification, yet their role in evolutionary innovation remains largely unexplored. Here, we reconstructed the evolution of a new trait encoded in a multicopy plasmid using TEM-1 ?-lactamase as a model system. Through a combination of theory and experimentation, we show that multicopy plasmids promote the coexistence of ancestral and novel traits for dozens of generations, allowing bacteria to escape the evolutionary constraints imposed by trade-offs. Our results suggest that multicopy plasmids are excellent platforms for evolutionary innovation, contributing to explain their extreme abundance in bacteria.
| S-EPMC6055991 | biostudies-literature
Project description:ObjectiveThe role of cost-effectiveness analysis (CEA) in incentivizing innovation is controversial. Critics of CEA argue that its use for pricing purposes disregards the 'value of innovation' reflected in new drug development, whereas supporters of CEA highlight that the value of innovation is already accounted for. Our objective in this article is to outline the limitations of the conventional CEA approach, while proposing an alternative method of evaluation that captures the value of innovation more accurately.MethodThe adoption of a new drug benefits present and future patients (with cost implications) for as long as the drug is part of clinical practice. Incidence patients and off-patent prices are identified as two key missing features preventing the conventional CEA approach from capturing 1) benefit to future patients and 2) future savings from off-patent prices. The proposed CEA approach incorporates these two features to derive the total lifetime value of an innovative drug (i.e., the value of innovation).ResultsThe conventional CEA approach tends to underestimate the value of innovative drugs by disregarding the benefit to future patients and savings from off-patent prices. As a result, innovative drugs are underpriced, only allowing manufacturers to capture approximately 15% of the total value of innovation during the patent protection period. In addition to including the incidence population and off-patent price, the alternative approach proposes pricing new drugs by first negotiating the share of value of innovation to be appropriated by the manufacturer (>15%?) and payer (<85%?), in order to then identify the drug price that satisfies this condition.ConclusionWe argue for a modification to the conventional CEA approach that integrates the total lifetime value of innovative drugs into CEA, by taking into account off-patent pricing and future patients. The proposed approach derives a price that allows manufacturers to capture an agreed share of this value, thereby incentivizing innovation, while supporting health-care systems to pursue dynamic allocative efficiency. However, the long-term sustainability of health-care systems must be assessed before this proposal is adopted by policy makers.
| S-EPMC4826462 | biostudies-literature
Project description:Perceptual decision making has been successfully modeled as a process of evidence accumulation up to a threshold. In order to maximize the rewards earned for correct responses in tasks with response deadlines, participants should collapse decision thresholds dynamically during each trial so that a decision is reached before the deadline. This strategy ensures on-time responding, though at the cost of reduced accuracy, since slower decisions are based on lower thresholds and less net evidence later in a trial (compared to a constant threshold). Frazier and Yu (2008) showed that the normative rate of threshold reduction depends on deadline delays and on participants' uncertainty about these delays. Participants should start collapsing decision thresholds earlier when making decisions under shorter deadlines (for a given level of timing uncertainty) or when timing uncertainty is higher (for a given deadline). We tested these predictions using human participants in a random dot motion discrimination task. Each participant was tested in free-response, short deadline (800 ms), and long deadline conditions (1000 ms). Contrary to optimal-performance predictions, the resulting empirical function relating accuracy to response time (RT) in deadline conditions did not decline to chance level near the deadline; nor did the slight decline we typically observed relate to measures of endogenous timing uncertainty. Further, although this function did decline slightly with increasing RT, the decline was explainable by the best-fitting parameterization of Ratcliff's diffusion model (Ratcliff, 1978), whose parameters are constant within trials. Our findings suggest that at the very least, typical decision durations are too short for participants to adapt decision parameters within trials.
| S-EPMC4133757 | biostudies-literature
Project description:Centromeres are essential genetic elements that enable spindle microtubule attachment for chromosome segregation during mitosis and meiosis. While this function is preserved across species, centromeres display an array of dynamic features, including: (1) rapidly evolving DNA; (2) wide evolutionary diversity in size, shape and organization; (3) evidence of mutational processes to generate homogenized repetitive arrays that characterize centromeres in several species; (4) tolerance to changes in position, as in the case of neocentromeres; and (5) intrinsic fragility derived by sequence composition and secondary DNA structures. Centromere drive underlies rapid centromere DNA evolution due to the "selfish" pursuit to bias meiotic transmission and promote the propagation of stronger centromeres. Yet, the origins of other dynamic features of centromeres remain unclear. Here, we review our current understanding of centromere evolution and plasticity. We also detail the mutagenic processes proposed to shape the divergent genetic nature of centromeres. Changes to centromeres are not simply evolutionary relics, but ongoing shifts that on one side promote centromere flexibility, but on the other can undermine centromere integrity and function with potential pathological implications such as genome instability.
| S-EPMC7463522 | biostudies-literature
Project description:BackgroundFollowing the September 11, 2001, attacks on the World Trade Center (WTC), thousands of workers were exposed to an array of toxins known to cause adverse health effects, including cancer. This study evaluates cancer incidence in the WTC Health Program General Responder Cohort occurring within 12 years post exposure.MethodsThe study population consisted of 28 729 members of the General Responder Cohort enrolled from cohort inception, July 2002 to December 31, 2013. Standardized incidence ratios (SIRs) were calculated with cancer case inclusion and follow-up starting post September 11, 2001 (unrestricted) and, alternatively, to account for selection bias, with case inclusion and follow-up starting 6 months after enrollment in the WTC Health Program (restricted). Case ascertainment was based on linkage with six state cancer registries. Under the restricted criterion, hazard ratios were estimated using multivariable Cox proportional hazards models for all cancer sites combined and for prostate cancer.ResultsRestricted analyses identified 1072 cancers in 999 responders, with elevations in cancer incidence for all cancer sites combined (SIR = 1.09, 95% confidence interval [CI] = 1.02 to 1.16), prostate cancer (SIR = 1.25, 95% CI = 1.11 to 1.40), thyroid cancer (SIR = 2.19, 95% CI = 1.71 to 2.75), and leukemia (SIR = 1.41, 95% CI = 1.01 to 1.92). Cancer incidence was not associated with any WTC exposure index (composite or individual) for all cancer sites combined or for prostate cancer.ConclusionOur analyses show statistically significant elevations in cancer incidence for all cancer sites combined and for prostate and thyroid cancers and leukemia. Multivariable analyses show no association with magnitude or type of exposure.
| S-EPMC7050150 | biostudies-literature
Project description:BackgroundPolicies to mitigate climate change by reducing greenhouse gas (GHG) emissions can yield public health benefits by also reducing emissions of hazardous co-pollutants, such as air toxics and particulate matter. Socioeconomically disadvantaged communities are typically disproportionately exposed to air pollutants, and therefore climate policy could also potentially reduce these environmental inequities. We sought to explore potential social disparities in GHG and co-pollutant emissions under an existing carbon trading program-the dominant approach to GHG regulation in the US and globally.Methods and findingsWe examined the relationship between multiple measures of neighborhood disadvantage and the location of GHG and co-pollutant emissions from facilities regulated under California's cap-and-trade program-the world's fourth largest operational carbon trading program. We examined temporal patterns in annual average emissions of GHGs, particulate matter (PM2.5), nitrogen oxides, sulfur oxides, volatile organic compounds, and air toxics before (January 1, 2011-December 31, 2012) and after (January 1, 2013-December 31, 2015) the initiation of carbon trading. We found that facilities regulated under California's cap-and-trade program are disproportionately located in economically disadvantaged neighborhoods with higher proportions of residents of color, and that the quantities of co-pollutant emissions from these facilities were correlated with GHG emissions through time. Moreover, the majority (52%) of regulated facilities reported higher annual average local (in-state) GHG emissions since the initiation of trading. Neighborhoods that experienced increases in annual average GHG and co-pollutant emissions from regulated facilities nearby after trading began had higher proportions of people of color and poor, less educated, and linguistically isolated residents, compared to neighborhoods that experienced decreases in GHGs. These study results reflect preliminary emissions and social equity patterns of the first 3 years of California's cap-and-trade program for which data are available. Due to data limitations, this analysis did not assess the emissions and equity implications of GHG reductions from transportation-related emission sources. Future emission patterns may shift, due to changes in industrial production decisions and policy initiatives that further incentivize local GHG and co-pollutant reductions in disadvantaged communities.ConclusionsTo our knowledge, this is the first study to examine social disparities in GHG and co-pollutant emissions under an existing carbon trading program. Our results indicate that, thus far, California's cap-and-trade program has not yielded improvements in environmental equity with respect to health-damaging co-pollutant emissions. This could change, however, as the cap on GHG emissions is gradually lowered in the future. The incorporation of additional policy and regulatory elements that incentivize more local emission reductions in disadvantaged communities could enhance the local air quality and environmental equity benefits of California's climate change mitigation efforts.
| S-EPMC6038989 | biostudies-literature
Project description: Not available
| S-EPMC8015769 | biostudies-literature
Project description:Covid-19 has rapidly redefined the agenda of technological research and development both for academics and practitioners. If the medical scientific publication system has promptly reacted to this new situation, other domains, particularly in new technologies, struggle to map what is happening in their contexts. The pandemic has created the need for a rapid detection of technological convergence phenomena, but at the same time it has made clear that this task is impossible on the basis of traditional patent and publication indicators. This paper presents a novel methodology to perform a rapid detection of the fast technological convergence phenomenon that is occurring under the pressure of the Covid-19 pandemic. The fast detection has been performed thanks to the use of a novel source: the online blogging platform Medium. We demonstrate that the hybrid structure of this social journalism platform allows a rapid detection of innovation phenomena, unlike other traditional sources. The technological convergence phenomenon has been modelled through a network-based approach, analysing the differences of networks computed during two time periods (pre and post COVID-19). The results led us to discuss the repurposing of technologies regarding "Remote Control", "Remote Working", "Health" and "Remote Learning".
| S-EPMC7774967 | biostudies-literature
Project description:Appropriate choice about delayed reward is fundamental to the survival of animals. Although animals tend to prefer immediate reward, delaying gratification is often advantageous. The dorsal raphe (DR) serotonergic neurons have long been implicated in the processing of delayed reward, but it has been unclear whether or when their activity causally directs choice. Here, we transiently augmented or reduced the activity of DR serotonergic neurons, while mice decided between differently delayed rewards as they performed a novel odor-guided intertemporal choice task. We found that these manipulations, precisely targeted at the decision point, were sufficient to bidirectionally influence impulsive choice. The manipulation specifically affected choices with more difficult trade-off. Similar effects were observed when we manipulated the serotonergic projections to the nucleus accumbens (NAc). We propose that DR serotonergic neurons preempt reward delays at the decision point and play a critical role in suppressing impulsive choice by regulating decision trade-off.
| S-EPMC5691357 | biostudies-literature
Project description:Climate change could either directly or indirectly cause population declines via altered temperature, rainfall regimes, food availability or phenological responses. However few studies have focused on allocation trade-offs between growth and reproduction under marginal resources, such as food scarce that may be caused by climate warming. Such critical changes may have an unpredicted impact on amphibian life-history parameters and even population dynamics. Here, we report an allocation strategy of adult anuran individuals involving a reproductive stage under experimental warming. Using outdoor mesocosm experiments we simulated a warming scenario likely to occur at the end of this century. We examined the effects of temperature (ambient vs. pre-/post-hibernation warming) and food availability (normal vs. low) on reproduction and growth parameters of pond frogs (Pelophylax nigromaculatus). We found that temperature was the major factor influencing reproductive time of female pond frogs, which showed a significant advancing under post-hibernation warming treatment. While feeding rate was the major factor influencing reproductive status of females, clutch size, and variation of body size for females, showed significant positive correlations between feeding rate and reproductive status, clutch size, or variation of body size. Our results suggested that reproduction and body size of amphibians might be modulated by climate warming or food availability variation. We believe this study provides some new evidence on allocation strategies suggesting that amphibians could adjust their reproductive output to cope with climate warming.
| S-EPMC4614843 | biostudies-literature