Contributors:Christian E. Demeure, Anne Derbise, Elisabeth Carniel
Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant strains of Yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. Although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. The vaccine strategy described here is based on an oral vaccination with an attenuated strain of Yersinia pseudotuberculosis. Indeed, this species is genetically almost identical to Y. pestis, but has a much lower pathogenicity and a higher genomic stability. Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953 were performed to generate a safe and immunogenic vaccine. Genes coding for three essential virulence factors were deleted from this strain. To increase cross-species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then generated. For this, the Y. pestis caf operon, which encodes F1, was inserted first on a plasmid, and subsequently into the chromosome. The successive steps achieved to reach maximal vaccine potential are described, and how each step affected bacterial virulence and the development of a protective immune response is discussed. The final version of the vaccine, named VTnF1, provides a highly efficient and long-lasting protection against both bubonic and pneumonic plague after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist or could be engineered, we also analyzed the protection conferred by the vaccine against such strain and found that it also confers full protection against the two forms of plague. Thus, the properties of VTnF1 makes it one of the most efficient candidate vaccine for mass vaccination in tropical endemic areas as well as for populations exposed to bioterrorism.
Contributors:Dahlia D. An, Birgitta Kullgren, Erin E. Jarvis, Rebecca J. Abergel
The potential consequences of a major radiological event are not only large-scale external radiation exposure of the population, but also uncontrolled dissemination of, and internal contamination with, radionuclides. When planning an emergency response to radiological and nuclear incidents, one must consider the need for not only post-exposure treatment for contaminated individuals, but also prophylactic measures to protect the workforce facing contaminated areas and patients in the aftermath of such events. In addition to meeting the desired criteria for post-exposure treatments such as safety, ease of administration, and broad-spectrum efficacy against multiple radionuclides and levels of challenge, ideal prophylactic countermeasures must include rapid onset; induce minimal to no performance-decrementing side effects; be compatible with current military Chemical, Biological, Radiological, Nuclear, and Explosive countermeasures; and require minimal logistical burdens. Hydroxypyridinone-based actinide decorporation agents have shown the most promise as decorporation strategies for various radionuclides of concern, including the actinides plutonium and americium. The studies presented here probe the extent of plutonium decorporation efficacy for two chelating agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), from early pre-exposure time points to a delay of up to 7 days in parenteral or oral treatment administration, i.e., well beyond the initial hours of emergency response. Despite delayed treatment after a contamination event, both ligands clearly enhanced plutonium elimination through the investigated 7-day post-treatment period. In addition, a remarkable prophylactic efficacy was revealed for 3,4,3-LI(1,2-HOPO) with treatment as early as 48 h before the plutonium challenge. This work provides new perspectives in the indication and use of experimental actinide decorporation treatments.
Organophosphorus compounds (OP), which mainly penetrate via the percutaneous pathway, represent a threat for both military and civilians. Body surface decontamination is vital to prevent victims poisoning. The development of a cost-effective formulation, which could be efficient and easy to handle in case of mass contamination, is therefore crucial. Metal oxides nanoparticles, due their large surface areas and the large amount of highly reactive sites, present high reactivity towards OP. First, this study aimed at evaluating the reaction of CeO2 nanoparticles, synthetized by microwave path and calcined at 500 or 600 °C, with Paraoxon (POX) in aqueous solution. Results showed that both nanoparticles degraded 60%–70% of POX. CeO2 calcined at 500 °C, owing to its larger specific area, was the most effective. Moreover, the degradation was significantly increased under Ultra-Violet irradiation (initial degradation rate doubled). Then, skin decontamination was studied in vitro using the Franz cell method with pig-ear skin samples. CeO2 powder and an aqueous suspension of CeO2 (CeO2-W) were applied 1 h after POX exposure. The efficiency of decontamination, including removal and/or degradation of POX, was compared to Fuller's earth (FE) and RSDL lotion which are, currently, the most efficient systems for skin decontamination. CeO2-W and RSDL were the most efficient to remove POX from the skin surface and decrease skin absorption by 6.4 compared to the control not decontaminated. FE reduced significantly (twice) the absorbed fraction of POX, contrarily to CeO2 powder. Considering only the degradation rate of POX, the products ranged in the order CeO2 > RSDL > CeO2-W > FE (no degradation). This study showed that CeO2 nanoparticles are a promising material for skin decontamination of OP if formulated as a dispersion able to remove POX like CeO2-W and to degrade it as CeO2 powder.
Developing countries have urbanized rapidly since 1950. To explain urbanization, standard models emphasize rural–urban migration, focusing on rural push factors (agricultural modernization and rural poverty) and urban pull factors (industrialization and urban-biased policies). Using new historical data on urban birth and death rates for 7 countries from Industrial Europe (1800–1910) and 35 developing countries (1960–2010), we argue that a non-negligible part of developing countries’ rapid urban growth and urbanization may also be linked to demographic factors, i.e. rapid internal urban population growth, or an urban push. High urban natural increase in today’s developing countries follows from lower urban mortality, relative to Industrial Europe, where higher urban deaths offset urban births. This compounds the effects of migration and displays strong associations with urban congestion, providing additional insight into the phenomenon of urbanization without growth.
Contributors:Lucio G. Costa, Toby B. Cole, Jacki Coburn, Yu-Chi Chang, Khoi Dao, Pamela J. Roqué
The central nervous system is emerging as an important target for adverse health effects of air pollution, where it may contribute to neurodevelopmental and neurodegenerative disorders. Air pollution comprises several components, including particulate matter (PM) and ultrafine particulate matter (UFPM), gases, organic compounds, and metals. An important source of ambient PM and UFPM is represented by traffic-related air pollution, primarily diesel exhaust (DE). Human epidemiological studies and controlled animal studies have shown that exposure to air pollution, and to traffic-related air pollution or DE in particular, may lead to neurotoxicity. In particular, air pollution is emerging as a possible etiological factor in neurodevelopmental (e.g. autism spectrum disorders) and neurodegenerative (e.g. Alzheimer's disease) disorders. The most prominent effects caused by air pollution in both humans and animals are oxidative stress and neuro-inflammation. Studies in mice acutely exposed to DE (250–300μg/m3 for 6h) have shown microglia activation, increased lipid peroxidation, and neuro-inflammation in various brain regions, particularly the hippocampus and the olfactory bulb. An impairment of adult neurogenesis was also found. In most cases, the effects of DE were more pronounced in male mice, possibly because of lower antioxidant abilities due to lower expression of paraoxonase 2.
This study aims to cluster the world’s top tourist destinations based on the growth of the main tourism indicators over the period between 2000 and 2010. It ranks the destinations with respect to the average growth rate over the sample period. The results find that both China and Turkey are at the top of the rankings of all variables. By assigning a numerical value to each country corresponding to its position, a Spearman’s coefficient is calculated and a negative correlation found between a destination’s dependency on tourism and the profitability of the tourism activity. Finally, several multivariate techniques for dimensionality reduction are used to cluster all destinations according to their positioning. Three groups are obtained: China, Turkey, and the rest of the destinations. These results show that the persistent growth of the tourism industry poses different challenges in different markets regarding destination marketing and management.
Through its role as gatekeeper and filter to the external world, the microbiome affects developmental programming of physiological systems including the immune system. In turn, the immune system must tolerate, personalize, and prune the microbiome. Immune and host barrier status in early life significantly effects everything from embryo viability and pregnancy duration to the likelihood of misregulated inflammation, and risk of noncommunicable diseases (NCDs). Since the programming of and interactions among the microbiome, the host defense barrier, and the immune system can affect inflammation-driven health risks across the lifespan, a systems biology-type understanding of these three biological components may be useful. Here, I consider the potential utility of focusing on programming of a newly-defined systems biology unit termed the “microimmunosome.”
Contributors:Katie R. Thompson, William D. Heyman, S. Hoyt Peckham, Lekelia D. Jenkins
This study examines the key characteristics of successful fisheries learning exchanges (FLEs). FLEs are peer-to-peer gatherings in which fishery stakeholders from different communities freely exchange information and experiences surrounding fisheries challenges and solutions. They are usually organized by fishers, non-governmental organizations and governments and are credited as an integral tool for the diffusion and adoption of fisheries management strategies. Despite their numerous perceived benefits within fisheries conservation and management, little research has been conducted on FLEs. This multiple case study addressed the research question: “What are the key characteristics of successful FLEs?” Success metrics were defined during a workshop on FLEs in 2013. For this study, the authors selected six successful FLEs that were presented during the workshop. Documentation of FLEs and key informant interviews with participants and organizers were used as data. The following key elements of successful FLEs emerged from analyses: (1) a clear guiding purpose and flexible objectives, (2) careful and considered selection of participants with diverse professions and conservation beliefs, (3) a mix of activities including giving presentations, conducting site visits, talking with local fishers, spending time on boats or in the water, and participating in cultural activities, and (4) logistical and financial follow-up support, including information dissemination about what participants learned at the FLE. Based on these results, the authors provide recommendations for conducting successful FLEs.
Contributors:James L. Peugh, Daniel Strotman, Meghan McGrady, Joseph Rausch, Susmita Kashikar-Zuck
Randomized control trials (RCTs) have long been the gold standard for allowing causal inferences to be made regarding the efficacy of a treatment under investigation, but traditional RCT data analysis perspectives do not take into account a common reality: imperfect participant compliance to treatment. Recent advances in both maximum likelihood parameter estimation and mixture modeling methodology have enabled treatment effects to be estimated, in the presence of less than ideal levels of participant compliance, via a Complier Average Causal Effect (CACE) structural equation mixture model. CACE is described in contrast to “intent to treat” (ITT), “per protocol”, and “as treated” RCT data analysis perspectives. CACE model assumptions, specification, estimation, and interpretation will all be demonstrated with simulated data generated from a randomized controlled trial of cognitive-behavioral therapy for Juvenile Fibromyalgia. CACE analysis model figures, linear model equations, and Mplus estimation syntax examples are all provided.
This paper focuses on a perishable product supply chain with a vendor and multiple retailers. These retailers, densely spread in a distribution zone, are sensitive to price, delivery time and product quality. With the aim of optimizing the vendor’s expected long-run average profit during a shipment consolidation cycle, an analytical model is proposed for this problem. According to the upper bound expressions of the expected long-run average profit, the approximate optimal time policy and freshness-keeping cost are given based on a certain range of time parameter. Our theoretical findings are verified through a numerical case. Some useful managerial insights are obtained by analyzing the sensitivity of this model from six perspectives, which are market scenarios, types of perishable products, quality requirements of all retailers, cost parameters, line-haul time and vehicle capacity.