Buy Time Research Articles

Normobaric hyperoxia-based neuroprotective therapies in ischemic stroke

Stroke is a leading cause of death and disability due to disturbance of blood supply to the brain. As brain is highly sensitive to hypoxia, insufficient oxygen supply is a critical event contributing to ischemic brain injury. Normobaric hyperoxia (NBO) that aims to enhance oxygen delivery to hypoxic tissues has long been considered as a logical neuroprotective therapy for ischemic stroke. To date, many possible mechanisms have been reported to elucidate NBO’s neuroprotection, such as improving tissue oxygenation, increasing cerebral blood flow, reducing oxidative stress and protecting the blood brain barrier. As ischemic stroke triggers a battery of damaging events, combining NBO with other agents or treatments that target multiple mechanisms of injury may achieve better outcome than individual treatment alone. More importantly, time loss is brain loss in acute cerebral ischemia. NBO can be a rapid therapy to attenuate or slow down the evolution of ischemic tissues towards necrosis and therefore “buy time” for reperfusion therapies. This article summarizes the current literatures on NBO as a simple, widely accessible, and potentially cost-effective therapeutic strategy for treatment of acute ischemic stroke.

Avoiding debt traps

In this article we develop a simple and stylised analytical framework, which is both tractable and feasible to estimate, capturing several key dimensions of the sovereign debt crisis in Europe. We use it to examine if and how a combination of fiscal consolidation, structural reform and financial backstops can help countries, notably the southern euro-area countries, to escape from the debt trap. Our analysis confirms that the loss of fiscal policy space in countries trapped in bad dynamics inevitably requires that fiscal action be directed towards consolidation despite some output loss in the short run. In particular, reducing debt levels breeds stronger growth and results in lower sovereign risk premia. We identify also a very important role for structural reform to help countries escape from bad dynamics. Last but not least, we find that financial backstops are helpful, but only to “buy time”. This additional time must be used productively, for fiscal consolidation and structural reforms to bear fruit as well as to make progress with institutional reforms of the European monetary union.

Inhaled Nitric Oxide and Cerebral Malaria

There are approximately 225-600 million new malaria infections worldwide annually, with severe and cerebral malaria representing major causes of death internationally. The role of nitric oxide (NO) in the host response in cerebral malaria continues to be elucidated, with numerous known functions relating to the cytokine, endovascular and cellular responses to infection with Plasmodium falciparum. Evidence from diverse modes of inquiry suggests NO to be critical in modulating the immune response and promoting survival in patients with cerebral malaria. This line of investigation has culminated in the approval of 2 phase II randomized prospective clinical trials in Uganda studying the use of inhaled NO as adjuvant therapy in children with severe malaria. The strategy underlying both trials is to use the sytemic antiinflammatory properties of inhaled NO to "buy time" for chemical antiparasite therapy to lower the parasite load. This article reviews the nexus of malaria and NO biology with a primary focus on cerebral malaria in humans.

Live virus-free or die: coupling of antivirus immunity and programmed suicide or dormancy in prokaryotes

BackgroundThe virus-host arms race is a major theater for evolutionary innovation. Archaea and bacteria have evolved diverse, elaborate antivirus defense systems that function on two general principles: i) immune systems that discriminate self DNA from nonself DNA and specifically destroy the foreign, in particular viral, genomes, whereas the host genome is protected, or ii) programmed cell suicide or dormancy induced by infection.Presentation of the hypothesisAlmost all genomic loci encoding immunity systems such as CRISPR-Cas, restriction-modification and DNA phosphorothioation also encompass suicide genes, in particular those encoding known and predicted toxin nucleases, which do not appear to be directly involved in immunity. In contrast, the immunity systems do not appear to encode antitoxins found in typical toxin-antitoxin systems. This raises the possibility that components of the immunity system themselves act as reversible inhibitors of the associated toxin proteins or domains as has been demonstrated for the Escherichia coli anticodon nuclease PrrC that interacts with the PrrI restriction-modification system. We hypothesize that coupling of diverse immunity and suicide/dormancy systems in prokaryotes evolved under selective pressure to provide robustness to the antivirus response. We further propose that the involvement of suicide/dormancy systems in the coupled antivirus response could take two distinct forms:1) induction of a dormancy-like state in the infected cell to ‘buy time’ for activation of adaptive immunity; 2) suicide or dormancy as the final recourse to prevent viral spread triggered by the failure of immunity.Testing the hypothesisThis hypothesis entails many experimentally testable predictions. Specifically, we predict that Cas2 protein present in all cas operons is a mRNA-cleaving nuclease (interferase) that might be activated at an early stage of virus infection to enable incorporation of virus-specific spacers into the CRISPR locus or to trigger cell suicide when the immune function of CRISPR-Cas systems fails. Similarly, toxin-like activity is predicted for components of numerous other defense loci.Implications of the hypothesisThe hypothesis implies that antivirus response in prokaryotes involves key decision-making steps at which the cell chooses the path to follow by sensing the course of virus infection.ReviewersThis article was reviewed by Arcady Mushegian, Etienne Joly and Nick Grishin. For complete reviews, go to the Reviewers’ reports section.

Profiting from business model innovation: Evidence from Pay-As-You-Drive auto insurance

The emergent business model literature, revolving mainly around the mechanisms through which new business models create and deliver value, has left the value capture challenge under-explored. This paper examines how an incumbent firm profits from business model innovation through the study of Pay-As-You-Drive auto insurance. Although business models do not warrant formal intellectual property (IP) protection, their constituent components (e.g. business methods and brands) often do. Drawing on the profiting-from-innovation framework, we find that formal and strategic IP protection methods play complementary roles. Initially, formal IP rights are used primarily as a defensive strategy, as vehicles for packaging and trading know-how, and most importantly as a means of “buying time” to build specialised complementary assets. Long-term competitiveness, however, depends on whether the innovator builds a strong position in specialised complementary assets and is capable of reconfiguring them over time in line with changes in the market environment. Thus, we explicate the complex mechanism and dynamic capability for capturing value from business model innovation.

The Limits to Sustainability Science: Ecological Constraints or Endless Innovation?

The Limits to Sustainability Science: Ecological Constraints or Endless Innovation?

Pre-hospital thrombolysis: end of an era?

For much of the last 20 years thrombolysis has been the preferred initial treatment for ST segment elevation myocardial infarction (STEMI). This treatment was originally given in hospital but was later used extensively and successfully before hospital admission. Primary percutaneous coronary intervention (PPCI) has proved itself to be more efficacious than thrombolysis, if it can be delivered within two hours, despite the extra time it takes to take patients to a Heart Attack Centre. Giving thrombolysis prior to the PPCI does not buy time safely. Prehospital thrombolysis still has a role when events long journies prevent timely access to the catheter laboratory.

An Effective Stock Portfolio Trading Strategy using Genetic Algorithms and Weighted Fuzzy Time Series

Investments in a stock market may incur risk. To reduce the risk of an investment, many portfolio selection methods have been proposed. By buying several stocks together, a portfolio selection method aims at maximizing the return of an investment given a predefined risk level. To build an optimal stock portfolio, one needs to select stocks and decide the proportion of the capital on each stock. Also, it is very important to decide when to buy or sell a stock portfolio. In this paper, we present a genetic algorithm to build stock portfolios. The proposed method comprises a genetic algorithm and a weighted fuzzy time series. The genetic algorithm is used to construct an optimal portfolio while the weighted fuzzy time series is used to predict the return of the portfolio which in turn is used to formulate the fitness function of the genetic algorithm. Furthermore, we propose the periodically checking and stop-loss point policies to decide selling and buying time points of the stock portfolio. The experiments on the stocks of Taiwan 50 show that the proposed method outperforms the Taiwan 50 index and the TAIEX index in terms of the 7-year average return rate.

Bought by Chance? Understand Why!

This research has the aim of identifying previous variants to impulsivity at the time of buying and as well as to verify the relationship between the tendency to buy things by impulse and human values. To achieve this goal a survey was carried out through an orkut profile account, where the students were invited to take part in a survey answering to an on line questionnaire available. Five instruments were applied: 1) Scale of shopping activity; 2) scale of circulation in the stores 3) Scale of Basic Human Values; 4) Social-Demographic Questionnaire; and, 5) Questionnaire about consumption habits. 154 students have taken part in this survey. (77 men and 77 women) currently registered at Universidade Federal da Paraiba, between 18 to 25 years of age (average=21; DP=2). We have calculated the distribution of the social demographic frequencies and the spending habits amongst the participants; the Alfa of Cronbach to the facts of the scales; and the analyze multiple linear regression to each block of questions as dependent variant (DV) having the impulsivity as the independent variant (IV); The variants which have showed predicted power to impulse shopping were the values of “Pleasure” and “Personal Stability”, the value System “Existence”, the circulation in the stores, the frequent usage of credit cards on shoppings, the hobby of going to shopping mall, and social-demographic variant such as sex, age and family’s wage. Key words: Human values. Impulsivity on buying. Consumption habits. Youngsters. Undergraduate students.

Haiti in the Context of the Current Global Cholera Pandemic

Haiti in the Context of the Current Global Cholera Pandemic

Buying Support and Buying Time: The Effect of Regime Consolidation on Public Goods Provision1

History provides many examples of benevolent dictators who become increasingly repressive and new democracies that take years to improve public welfare. I account for this temporal variation in public goods provision by considering how regime consolidation changes leaders’ incentives to provide public goods. To stay in office, all leaders must maintain a sufficient level of support from those possessing the power to replace the leader via institutional processes. Leaders of unconsolidated regimes face additional threats posed by viable extra-institutional challengers, such as coup plotters and revolutionaries. Tests on public goods spanning political freedoms, government expenditures, education, and health generally suggest leaders’ incentives for public goods provision change as regime consolidation insulates leaders from these extra-institutional threats to power. Regimes with inclusive institutions spend more on public goods as they consolidate and become less vulnerable to elite demands. Exclusive regimes spend more on public goods when they are vulnerable to the excluded masses, but become increasingly repressive as they become insulated from popular uprisings. Consequently, consolidation magnifies the positive effect of democracy on public goods provision. These findings have important implications for the literatures on public goods provision and regime survival.

Life at the Frontier

Life at the Frontier

Early-stage transformation of coastal marine governance in Vietnam?

This paper examines an apparent ‘early stage’ governance transformation in the Tam Giang Lagoon, Vietnam. In this context, the role of key policy windows for innovative governance practice is assessed (e.g., changes to Land and Fisheries Laws). Also examined is the emergence of recent initiatives to catalyze a wider shift in governance practice in the region, including the formation of co-management institutional networks that contribute to trust building and learning, and the allocation of collective territorial use rights for fisheries. While these changes are consistent with experiences in other coastal marine contexts, the paper shows that place-based and longitudinal research is necessary to explain and predict the conditions and incentives that catalyze governance shifts. Differences between a governance change and more fundamental transformation are difficult to discern using point-in-time analysis. Moreover, the results show that current declines in ecological conditions in the lagoon may not be reversed by changes to access rights or the emergence of co-management. Rather, these governance changes may simply help to stabilize the situation and buy time until other livelihood opportunities arise. Assessments of governance transformation thus need to be linked to ecological outcomes (i.e., reversing degradation of coastal marine systems, avoiding biophysical tipping points) which may not be easily identified in the short-term. Despite uncertainty, the emergence of policy windows, evidence of institutional innovation, and small-scale rights allocation experiments, all suggest important shifts in the trajectory of governance are underway in the Tam Giang Lagoon.

Company duplication – plain fraud or a ‘poor man's’ bankruptcy? A case study in the financial distress of small businesses

AbstractTwo possible solutions to corporate financial distress are traditionally considered: commencing a formal bankruptcy proceeding or arranging an out‐of‐court capital restructuring. Corporate bankruptcy scholarship has largely ignored a third solution occasionally undertaken by small businesses, that is, resorting to self‐help measures. The purpose of this paper is to start filling the gap using a unique case study. The paper describes and analyses an existing phenomenon among small firms in Israel experiencing financial distress – company duplication. A typical scenario unfolds as follows. An entrepreneur who controls the financially distressed Company A registers a new Company B in an attempt to avoid a complete shutdown of her creditors' disturbed business. The assets of Company A are transferred to Company B in what appears to be fraudulent conveyance. Company B serves as a vehicle through which the original business is kept running. If necessary, the entrepreneur will also register Company C and repeat the process. Israeli law regulates company duplication in an ambivalent manner. On the one hand, conventional wisdom considers company duplication to be tantamount to fraud against Company A's unaware creditors. Accordingly, company duplication has been recently denounced by the Israeli Supreme Court as an illegitimate way of conducting business. The Court held that notwithstanding the principle of limited liability, an entrepreneur resorting to company duplication is personally liable to pay any debt of Company A that was not serviced by it. On the other hand, company duplicators do not face criminal charges. To the extent that company duplication is practiced by insolvent entrepreneurs, deterrence is therefore suboptimal, as insolvent duplicators are not sanctioned at all. Against this backdrop, this paper advances two normative arguments. First, a more sympathetic explanation should be considered to account for company duplication. An entrepreneur resorting to company duplication might actually be arranging for a ‘home‐made’ bankruptcy proceeding (i.e. buying time which could help the business establish its viability and regenerate). According to this narrative, the duplication mimics the role of a formal bankruptcy stay on unsecured creditors' collection efforts, thus suggesting that company duplication serves as ‘a poor man's’ bankruptcy proceeding. Second, this new explanation of company duplication, combined with the current level of suboptimal deterrence, mandates a re‐evaluation of this business pattern to assess its relative efficacy. I argue that at least in the Israeli context because of its special features, company duplication should be tolerated with regard to small businesses, assuming that the entrepreneur is not defrauding creditors or attempting to rescue a business that has failed due to economic rather than merely financial factors. To that end, company duplicators should be held personally liable to debts of the duplicated companies and be pursued with criminal sanctions only selectively, as explained in the paper. Copyright © 2011 John Wiley & Sons, Ltd.

Mitigation Strategies for Pandemic Influenza A: Balancing Conflicting Policy Objectives

Mitigation of a severe influenza pandemic can be achieved using a range of interventions to reduce transmission. Interventions can reduce the impact of an outbreak and buy time until vaccines are developed, but they may have high social and economic costs. The non-linear effect on the epidemic dynamics means that suitable strategies crucially depend on the precise aim of the intervention. National pandemic influenza plans rarely contain clear statements of policy objectives or prioritization of potentially conflicting aims, such as minimizing mortality (depending on the severity of a pandemic) or peak prevalence or limiting the socio-economic burden of contact-reducing interventions. We use epidemiological models of influenza A to investigate how contact-reducing interventions and availability of antiviral drugs or pre-pandemic vaccines contribute to achieving particular policy objectives. Our analyses show that the ideal strategy depends on the aim of an intervention and that the achievement of one policy objective may preclude success with others, e.g., constraining peak demand for public health resources may lengthen the duration of the epidemic and hence its economic and social impact. Constraining total case numbers can be achieved by a range of strategies, whereas strategies which additionally constrain peak demand for services require a more sophisticated intervention. If, for example, there are multiple objectives which must be achieved prior to the availability of a pandemic vaccine (i.e., a time-limited intervention), our analysis shows that interventions should be implemented several weeks into the epidemic, not at the very start. This observation is shown to be robust across a range of constraints and for uncertainty in estimates of both R0 and the timing of vaccine availability. These analyses highlight the need for more precise statements of policy objectives and their assumed consequences when planning and implementing strategies to mitigate the impact of an influenza pandemic.

How much time can herbivore protection buy for coral reefs under realistic regimes of hurricanes and coral bleaching?

Coral reefs have been more severely impacted by recent climate instability than any other ecosystem on Earth. Corals tolerate a narrow range of physical environmental stress, and increases in sea temperature of just 1 °C over several weeks can result in mass coral mortality, often exceeding 95% of individuals over hundreds of square kilometres. Even conservative climate models predict that mass coral bleaching events could occur annually by 2050. Unfortunately, managers of coral-reef resources have few options available to meet this challenge. Here, we investigate the role that fisheries conservation tools, including the designation of marine reserves, can play in altering future trajectories of Caribbean coral reefs. We use an individual-based model of the ecological dynamics to test the influence of spatially realistic regimes of disturbance on coral populations. Two major sources of disturbance, hurricanes and coral bleaching, are simulated in contrasting regions of the Caribbean: Belize, Bonaire, and the Bahamas. Simulations are extended to 2099 using the HadGEM1 climate model. We find that coral populations can maintain themselves under all levels of hurricane disturbance providing that grazing levels are high. Regional differences in hurricane frequency are found to cause strikingly different spatial patterns of reef health with greater patchiness occurring in Belize, which has less frequent disturbance, than the Bahamas. The addition of coral bleaching led to a much more homogenous reef state over the seascape. Moreover, in the presence of bleaching, all reefs exhibited a decline in health over time, though with substantial variation among regions. Although the protection of herbivores does not prevent reef degradation it does delay rates of coral loss even under the most severe thermal and hurricane regimes. Thus, we can estimate the degree to which local conservation can help buy time for reefs with values ranging between 18 years in the Bahamas and over 50 years in Bonaire, compared with heavily fished systems. Ultimately, we demonstrate that local conservation measures can benefit reef ecosystem services but that their impact will vary spatially and temporally. Recognizing where such management interventions will either help or fail is an important step towards both achieving sustainable use of coral-reef resources and maximizing resource management investments.

OPTIMAL STOCK SELLING/BUYING STRATEGY WITH REFERENCE TO THE ULTIMATE AVERAGE

We are concerned with the optimal decision to sell or buy a stock in a given period with reference to the ultimate average of the stock price. More precisely, we aim to determine an optimal selling (buying) time to maximize (minimize) the expectation of the ratio of the selling (buying) price to the ultimate average price over the period. This is an optimal stopping time problem which can be formulated as a variational inequality problem. The problem gives rise to a free boundary that corresponds to the optimal selling (buying) strategy. We provide a partial differential equation approach to characterize the free boundary (or equivalently, the optimal selling (buying) region). It turns out that the optimal selling strategy is bang‐bang, which is the same as that obtained by Shiryaev, Xu, and Zhou taking the ultimate maximum of the stock price as benchmark, whereas the optimal buying strategy can be a feedback one subject to the type of averaging and parameter values. Moreover, by a thorough characterization of free boundary, we reveal that the bang‐bang optimal selling strategy heavily depends on the assumption that no time‐vesting restrictions are imposed. If a time‐vested stock is considered, then the optimal selling strategy can also be a feedback one. In terms of a similar analysis developed by the present paper, the same phenomenon can be proved when taking the ultimate maximum as benchmark.

Review article: the current management of acute liver failure

Acute liver failure is a devastating clinical syndrome with a persistently high mortality rate despite critical care advances. Orthotopic liver transplantation (OLT) is a life-saving treatment in selected cases, but effective use of this limited resource requires accurate prognostication because of surgical risks and the requirement for subsequent life-long immunosuppression. To review the aetiology of acute liver failure, discuss the evidence behind critical care management strategies and examine potential treatment alternatives to OLT. Literature review using Ovid, PubMed and recent conference abstracts. Paracetamol remains the most common aetiology of acute liver failure in developed countries, whereas acute viral aetiologies predominate elsewhere. Cerebral oedema is a major cause of death, and its prevention and prompt recognition are vital components of critical care support, which strives to provide multiorgan support and 'buy time' to permit either organ regeneration or psychological and physical assessment prior to acquisition of a donor organ. Artificial liver support systems do not improve mortality in acute liver failure, whilst most other interventions have limited evidence bases to support their use. Acute liver failure remains a truly challenging condition to manage, and requires early recognition and transfer of patients to specialist centres providing intensive, multidisciplinary input and, in some cases, OLT.

Hotelling Competition with Multi-Purchasing: Time Magazine, Newsweek, or Both?

Equilibrium prices behave quite differently if consumers single-purchase (buy either Time Magazine or Newsweek) or if some consumers multi-purchase (buy both). Prices are strategic complements under single-purchase, and increase with magazine quality. In a multi-purchase regime prices are strategically independent because firms then act monopolistically by pricing the incremental benefit to marginal consumers. Furthermore, prices can decrease with magazine quality due to overlapping content. Higher preference heterogeneity increases prices and profits in equilibrium with single-purchase, but decreases them with multi-purchase. We determine when each regime holds, and present a detailed reaction function analysis which applies more generally to duopoly pricing.

Time to Buy or Just Buying Time? The Market Reaction to Bank Rescue Packages

This paper reviews the market reaction to bank rescue packages announced in six countries between October 2008 and January 2009. The study distinguishes the impact on creditors as seen in the change of CDS spreads from the impact on shareholders as seen in the movement of bank stock prices. Government interventions benefited creditors at the expense of shareholders, with bank CDS spreads narrowing around the announcements in all cases. Despite a brief positive reaction, bank stock prices continued to underperform in all countries except the United States where the favourable terms of the government support allowed bank stocks to outperform.