RESUMEN

One cause of the high rate of COVID-19 cases in the USA is thought to be insufficient prior capital investment in national health programs to preemptively reduce the likelihood of an outbreak and in national capacity to reduce the severity of any outbreak that does occur. We analyze the choice of capital investments (e.g. testing capacity, stockpiles of PPE, and information sharing capacity) and find the economically efficient capital stock associated with mitigating pandemic risk should be dramatically expanded. Policymakers who fail to invest in public health forgo significant expected cost savings from being prepared.

Asunto(s)

RESUMEN

Wildlife diseases pose a substantial threat to the provisioning of ecosystem services. We use a novel modeling approach to study the potential loss of these services through the imminent introduction of chronic wasting disease (CWD) to elk populations in the Greater Yellowstone Ecosystem (GYE). A specific concern is that concentrating elk at feedgrounds may exacerbate the spread of CWD, whereas eliminating feedgrounds may increase the number of elk on private ranchlands and the transmission of a second disease, brucellosis, from elk to cattle. To evaluate the consequences of management strategies given the threat of two concurrent wildlife diseases, we develop a spatiotemporal bioeconomic model. GPS data from elk and landscape attributes are used to predict migratory behavior and population densities with and without supplementary feeding. We use a 4,800 km2 area around Pinedale, Wyoming containing four existing feedgrounds as a case study. For this area, we simulate welfare estimates under a variety of management strategies. Our results indicate that continuing to feed elk could result in substantial welfare losses for the case-study region. Therefore, to maximize the present value of economic net benefits generated by the local elk population upon CWD's arrival in the region, wildlife managers may wish to consider discontinuing elk feedgrounds while simultaneously developing new methods to mitigate the financial impact to ranchers of possible brucellosis transmission to livestock. More generally, our methods can be used to weigh the costs and benefits of human-wildlife interactions in the presence of multiple disease risks.

Asunto(s)

RESUMEN

Infectious livestock disease problems are "biological pollution" problems. Prior work on biological pollution problems generally examines the efficient allocation of prevention and control efforts, but does not identify the specific externalities underpinning the design of efficiency-enhancing policy instruments. Prior analyses also focus on problems where those being damaged do not contribute to externalities. We examine a problem where the initial biological introduction harms the importer and then others are harmed by spread from this importer. Here, the externality is the spread of infection beyond the initial importer. This externality is influenced by the importer's private risk management choices, which provide impure public goods that reduce disease spillovers to others-making disease spread a "filterable externality." We derive efficient policy incentives to internalize filterable disease externalities given uncertainties about introduction and spread. We find efficiency requires incentivizing an importer's trade choices along with self-protection and abatement efforts, in contrast to prior work that targets trade alone. Perhaps surprisingly, we find these incentives increase with importers' private risk management incentives and with their ability to directly protect others. In cases where importers can spread infection to each other, we find filterable externalities may lead to multiple Nash equilibria.

RESUMEN

The rapid urban spread of Ebola virus in West Africa in 2014 and consequent breakdown of control measures led to a significant economic impact as well as the burden on public health and wellbeing. The US government appropriated $5.4 Billion for FY2015 and WHO proposed a $100 Million emergency fund largely to curtail the threat of future outbreaks. Using epidemiological analyses and economic modeling, we propose that the best use of these and similar funds would be to serve as global insurance against the continued threat of emerging infectious diseases. An effective strategy would involve the initial investment in strengthening mobile and adaptable capacity to deal with the threat and reality of disease emergence, coupled with repeated investment to maintain what is effectively a 'national guard' for pandemic prevention and response. This investment would create a capital stock that could also provide access to safe treatment during and between crises in developing countries, lowering risk to developed countries.

Asunto(s)

RESUMEN

An individual's infectious disease risks, and hence the individual's incentives for risk mitigation, may be influenced by others' risk management choices. If so, then there will be strategic interactions among individuals, whereby each makes his or her own risk management decisions based, at least in part, on the expected decisions of others. Prior work has shown that multiple equilibria could arise in this setting, with one equilibrium being a coordination failure in which individuals make too few investments in protection. However, these results are largely based on simplified models involving a single management choice and fixed prices that may influence risk management incentives. Relaxing these assumptions, we find strategic interactions influence, and are influenced by, choices involving multiple management options and market price effects. In particular, we find these features can reduce or eliminate concerns about multiple equilibria and coordination failure. This has important policy implications relative to simpler models.

Asunto(s)

RESUMEN

Most models designed to understand how to manage infected wildlife systems with bioeconomic multi-stability take the initial conditions as given, thereby treating pathogen invasion as unanticipated. We examine how ex ante management is an opportunity to influence the ex post conditions, which in turn affect the ex post optimal outcome. To capture these ex ante management choices, we extend the Poisson "collapse" model of Reed and Heras (Bull Math Biol 54:185-207, 1992) to allow for endogenous initial conditions and ex post multi-stability. We account for two uncertain processes: the introduction and establishment of the pathogen. Introduction is conditional on anthropogenic investments in prevention, and both random processes are conditional on how we manage the native population to provide natural prevention of invasion and natural insurance against establishment placing the system in an undesirable basin of attraction. We find that both multi-stability of the invaded system and these uncertainty processes can create economic non-convexities that yield multiple candidate solutions to the ex ante optimization problem. Additionally, we illustrate how the nature of natural protection against introduction and establishment risks can play an important role in the allocation of anthropogenic investments.

RESUMEN

Alkynyl sulfonamides undergo sequential 1,4- then 1,2-addition/rearrangement with lithium acetylides to yield enediynes in the absence of any promoters or catalysts. Mechanistic investigations suggest that the reaction proceeds via 1,4-conjugate addition of the nucleophile to the unsaturated system to give a key alkenyl lithium species which is stabilised by an intramolecular coordination effect by a sulfonamide oxygen atom. This species can be considered a vinylidene carbenoid given the carbon atom bears both an anion (as a vinyllithium) and a leaving group (the sulfonamide). The intramolecular coordination effect serves to stabilise the vinyllithium but activates the sulfonamide motif towards nucleophilic attack by a second mole of acetylide. The resulting species can then undergo rearrangement to yield the enediyne framework in a single operation with concomitant loss of aminosulfinate.

RESUMEN

A fundamental mechanistic study of the s-BuLi/chiral diamine-mediated lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine is reported. We show that lithiated thiopivalamides are configurationally unstable at -78 °C. Reaction then proceeds via a dynamic resolution of diastereomeric lithiated intermediates and this accounts for the variable sense and degree of asymmetric induction observed compared to N-Boc heterocycles.

RESUMEN

We develop a multi-group epidemic framework via virtual dispersal where the risk of infection is a function of the residence time and local environmental risk. This novel approach eliminates the need to define and measure contact rates that are used in the traditional multi-group epidemic models with heterogeneous mixing. We apply this approach to a general n-patch SIS model whose basic reproduction number [Formula: see text] is computed as a function of a patch residence-time matrix [Formula: see text]. Our analysis implies that the resulting n-patch SIS model has robust dynamics when patches are strongly connected: There is a unique globally stable endemic equilibrium when [Formula: see text], while the disease-free equilibrium is globally stable when [Formula: see text]. Our further analysis indicates that the dispersal behavior described by the residence-time matrix [Formula: see text] has profound effects on the disease dynamics at the single patch level with consequences that proper dispersal behavior along with the local environmental risk can either promote or eliminate the endemic in particular patches. Our work highlights the impact of residence-time matrix if the patches are not strongly connected. Our framework can be generalized in other endemic and disease outbreak models. As an illustration, we apply our framework to a two-patch SIR single-outbreak epidemic model where the process of disease invasion is connected to the final epidemic size relationship. We also explore the impact of disease-prevalence-driven decision using a phenomenological modeling approach in order to contrast the role of constant versus state-dependent [Formula: see text] on disease dynamics.

Asunto(s)

RESUMEN

There is growing concern that trade, by connecting geographically isolated regions, unintentionally facilitates the spread of invasive pathogens and pests - forms of biological pollution that pose significant risks to ecosystem and human health. We use a bioeconomic framework to examine whether trade always increases private risks, focusing specifically on pathogen risks from live animal trade. When the pathogens have already established and traders bear some private risk, we find two results that run counter to the conventional wisdom on trade. First, uncertainty about the disease status of individual animals held in inventory may increase the incentives to trade relative to the disease-free case. Second, trade may facilitate reduced long-run disease prevalence among buyers. These results arise because disease risks are endogenous due to dynamic feedback processes involving valuable inventories, and markets facilitate the management of private risks that producers face with or without trade.

RESUMEN

There is a growing concern that risks of disease outbreak and pandemics are increasing over time. We consider optimal investments in prevention before an outbreak using an endogenous risk approach within an optimal control setting. Using the threat of pandemic influenza as an illustrative example, we demonstrate that prevention expenditures are relatively small in comparison to the potential losses facing the USA, and these expenditures need to be flexible and responsive to changes in background risk. Failure to adjust these expenditures to changes in background risk poses a significant threat to social welfare into the future.

RESUMEN

Mathematical epidemiology, one of the oldest and richest areas in mathematical biology, has significantly enhanced our understanding of how pathogens emerge, evolve, and spread. Classical epidemiological models, the standard for predicting and managing the spread of infectious disease, assume that contacts between susceptible and infectious individuals depend on their relative frequency in the population. The behavioral factors that underpin contact rates are not generally addressed. There is, however, an emerging a class of models that addresses the feedbacks between infectious disease dynamics and the behavioral decisions driving host contact. Referred to as "economic epidemiology" or "epidemiological economics," the approach explores the determinants of decisions about the number and type of contacts made by individuals, using insights and methods from economics. We show how the approach has the potential both to improve predictions of the course of infectious disease, and to support development of novel approaches to infectious disease management.

Asunto(s)

RESUMEN

A synthetic study on the preparation of N-Boc α-amino sulfoxides has revealed an unexpected instability which is believed to be due to α-elimination of the sulfoxide to give an iminium ion. Full synthetic details are reported on two main synthetic routes: lithiation and sulfinate trapping of N-Boc heterocycles and oxidation of N-Boc α-amino sulfides. Six novel α-amino sulfoxides were successfully prepared and isolated. It is speculated that four other α-amino sulfoxides were synthesised but could not be isolated due to their propensity to α-eliminate the sulfoxide. Ultimately, a stable, cyclic N-Boc α-amino sulfoxide was prepared and this successful synthesis relied on the α-amino sulfoxide being part of a bicyclic [3.1.0] fused ring system that could not undergo α-elimination of the sulfoxide.

Asunto(s)

RESUMEN

A strategy for the generation of enantiomerically pure α-functionalized chiral Grignard reagents is presented. The approach involves the synthesis of α-alkoxy and α-amino sulfoxides in ≥99:1 dr and ≥99:1 er via asymmetric deprotonation (s-BuLi/chiral diamine) and trapping with Andersen's sulfinate (menthol derived). Subsequent sulfoxide → Mg exchange (room temperature, 1 min) and electrophilic trapping delivers a range of enantiomerically pure α-alkoxy and α-amino substituted products. Using this approach, either enantiomer of products can be accessed in 99:1 er from asymmetric deprotonation protocols without the use of (-)-sparteine as the chiral ligand. Two additional discoveries are noteworthy: (i) for the deprotonation and trapping with Andersen's sulfinate, there is a lack of stereospecificity at sulfur due to attack of a lithiated intermediate onto the α-alkoxy and α-amino sulfoxides as they form, and (ii) the α-alkoxy-substituted Grignard reagent is configurationally stable at room temperature for 30 min.

Asunto(s)

RESUMEN

Agricultural nonpoint source water pollution has long been recognized as an important contributor to U.S. water quality problems and the subject of an array of local, state, and federal initiatives to reduce the problem. A "pay-the-polluter" approach to getting farmers to adopt best management practices has not succeeded in improving water quality in many impaired watersheds. With the prospects of reduced funding for the types of financial and technical assistance programs that have been the mainstay of agricultural water quality policy, alternative approaches need to be considered. Some changes to the way current conservation programs are implemented could increase their efficiency, but there are limits to how effective a purely voluntary approach can be. An alternative paradigm is the "polluter pays" approach, which has been successfully employed to reduce point source pollution. A wholesale implementation of the polluter-pays approach to agriculture is likely infeasible, but elements of the polluter-pays approach could be incorporated into agricultural water quality policy.

Asunto(s)

RESUMEN

Many ecosystems appear subject to regime shifts--abrupt changes from one state to another after crossing a threshold or tipping point. Thresholds and their associated stability landscapes are determined within a coupled socioeconomic-ecological system (SES) where human choices, including those of managers, are feedback responses. Prior work has made one of two assumptions about managers: that they face no institutional constraints, in which case the SES may be managed to be fairly robust to shocks and tipping points are of little importance, or that managers are rigidly constrained with no flexibility to adapt, in which case the inferred thresholds may poorly reflect actual managerial flexibility. We model a multidimensional SES to investigate how alternative institutions affect SES stability landscapes and alter tipping points. With institutionally dependent human feedbacks, the stability landscape depends on institutional arrangements. Strong institutions that account for feedback responses create the possibility for desirable states of the world and can cause undesirable states to cease to exist. Intermediate institutions interact with ecological relationships to determine the existence and nature of tipping points. Finally, weak institutions can eliminate tipping points so that only undesirable states of the world remain.

Asunto(s)

RESUMEN

The science and management of infectious disease are entering a new stage. Increasingly public policy to manage epidemics focuses on motivating people, through social distancing policies, to alter their behavior to reduce contacts and reduce public disease risk. Person-to-person contacts drive human disease dynamics. People value such contacts and are willing to accept some disease risk to gain contact-related benefits. The cost-benefit trade-offs that shape contact behavior, and hence the course of epidemics, are often only implicitly incorporated in epidemiological models. This approach creates difficulty in parsing out the effects of adaptive behavior. We use an epidemiological-economic model of disease dynamics to explicitly model the trade-offs that drive person-to-person contact decisions. Results indicate that including adaptive human behavior significantly changes the predicted course of epidemics and that this inclusion has implications for parameter estimation and interpretation and for the development of social distancing policies. Acknowledging adaptive behavior requires a shift in thinking about epidemiological processes and parameters.

Asunto(s)

RESUMEN

The primary goal of disease ecology is to understand disease systems and then use this information to inform management. The purpose of this paper is to show that conventional disease ecology models are limited in their ability to inform management of systems that are already infected, and to show how such models can be integrated with economic decision models to improve upon management recommendations. Management strategies based solely on disease ecology entail managing infected host populations or reservoir populations below a threshold value based on R0, the basic reproductive ratio of the pathogen, or a multiple-host version of this metric. These metrics measure a pathogen's ability to invade uninfected systems and do not account for postinfection dynamics. Once a pathogen has invaded a population, alternative management criteria are needed. Bioeconomic modeling offers a useful alternative approach to developing management criteria and facilitates the consideration of ecological-economic trade-offs so that diseases are managed in a cost-effective manner. The threshold concept takes on a more profound role under a bioeconomic paradigm: rather than unilaterally determining disease control choices, thresholds inform control choices and are influenced by them.

Asunto(s)

RESUMEN

The bengazoles are a family of marine natural products that display potent antifungal activity and a unique structure, containing two oxazole rings flanking a single carbon atom. Total syntheses of bengazole A and B are described, which contain a sensitive stereogenic centre at this position between the two oxazoles. Additionally, the synthesis of 10-epi-bengazole A is reported. Two parallel synthetic routes were investigated, relying on construction of the 2,4-disubstituted oxazole under mild conditions and a diastereoselective 1,3-dipolar cycloaddition. Our successful route is high yielding, provides rapid access to single stereoisomers of the complex natural products and allows the synthesis of analogues for biological evaluation.

Asunto(s)