114 research outputs found

    Effective, Robust Design of Community Mitigation for Pandemic Influenza: A Systematic Examination of Proposed US Guidance

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    BACKGROUND: The US government proposes pandemic influenza mitigation guidance that includes isolation and antiviral treatment of ill persons, voluntary household member quarantine and antiviral prophylaxis, social distancing of individuals, school closure, reduction of contacts at work, and prioritized vaccination. Is this the best strategy combination? Is choice of this strategy robust to pandemic uncertainties? What are critical enablers of community resilience? METHODS AND FINDINGS: We systematically simulate a broad range of pandemic scenarios and mitigation strategies using a networked, agent-based model of a community of explicit, multiply-overlapping social contact networks. We evaluate illness and societal burden for alterations in social networks, illness parameters, or intervention implementation. For a 1918-like pandemic, the best strategy minimizes illness to <1% of the population and combines network-based (e.g. school closure, social distancing of all with adults' contacts at work reduced), and case-based measures (e.g. antiviral treatment of the ill and prophylaxis of household members). We find choice of this best strategy robust to removal of enhanced transmission by the young, additional complexity in contact networks, and altered influenza natural history including extended viral shedding. Administration of age-group or randomly targeted 50% effective pre-pandemic vaccine with 7% population coverage (current US H5N1 vaccine stockpile) had minimal effect on outcomes. In order, mitigation success depends on rapid strategy implementation, high compliance, regional mitigation, and rigorous rescinding criteria; these are the critical enablers for community resilience. CONCLUSIONS: Systematic evaluation of feasible, recommended pandemic influenza interventions generally confirms the US community mitigation guidance yields best strategy choices for pandemic planning that are robust to a wide range of uncertainty. The best strategy combines network- and case-based interventions; network-based interventions are paramount. Because strategies must be applied rapidly, regionally, and stringently for greatest benefit, preparation and public education is required for long-lasting, high community compliance during a pandemic

    The Decline of Remarriage: Evidence From German Village Populations in the Eighteenth and Nineteenth Centuries

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    Family reconstitution data for fourteen German village populations permit the examination of remarriage during the eighteenth and nineteenth cen turies. The results provide compelling evidence for a secular decline in the tenden cy to remarry. Pronounced age and sex differentials in the likelihood of remar riage were evident: widows were far less likely to remarry than widowers, and the probability of remarriage declined rapidly with age, particularly for women. The probability of remarriage was also inversely associated with the number and age of children. There were, however, no clear differences in either the probability of remarriage or its tendency to decline over time among major occupational groups. The decline in remarriage probabilities was caused in part by declines in adult mortality, which gradually raised the ages of surviving spouses to levels at which remarriage has historically been rather unlikely. However, age-specific marriage probabilities also declined, affecting both men and women and all oc cupational groups, suggesting the presence of a social change of wide scope. Some comments on possible factors contributing to the decline of remarriage are presented. The need for a comprehensive explanation of remarriage trends and differentials remains an important challenge for family historians.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68212/2/10.1177_036319908501000103.pd

    Natural Host Genetic Resistance to Lentiviral CNS Disease: A Neuroprotective MHC Class I Allele in SIV-Infected Macaques

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    Human immunodeficiency virus (HIV) infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS) have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS) disease using a well-characterized simian immunodeficiency (SIV)/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis) was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5). Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001). Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease

    Autoantibodies to Agrin in Myasthenia Gravis Patients

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    To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ

    Phoenix : Complex Adaptive System of Systems (CASoS) engineering version 1.0.

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    Complex Adaptive Systems of Systems, or CASoS, are vastly complex ecological, sociological, economic and/or technical systems which we must understand to design a secure future for the nation and the world. Perturbations/disruptions in CASoS have the potential for far-reaching effects due to pervasive interdependencies and attendant vulnerabilities to cascades in associated systems. Phoenix was initiated to address this high-impact problem space as engineers. Our overarching goals are maximizing security, maximizing health, and minimizing risk. We design interventions, or problem solutions, that influence CASoS to achieve specific aspirations. Through application to real-world problems, Phoenix is evolving the principles and discipline of CASoS Engineering while growing a community of practice and the CASoS engineers to populate it. Both grounded in reality and working to extend our understanding and control of that reality, Phoenix is at the same time a solution within a CASoS and a CASoS itself

    High-Yield Hydrogen Production from Starch and Water by a Synthetic Enzymatic Pathway

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    BACKGROUND: The future hydrogen economy offers a compelling energy vision, but there are four main obstacles: hydrogen production, storage, and distribution, as well as fuel cells. Hydrogen production from inexpensive abundant renewable biomass can produce cheaper hydrogen, decrease reliance on fossil fuels, and achieve zero net greenhouse gas emissions, but current chemical and biological means suffer from low hydrogen yields and/or severe reaction conditions. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate a synthetic enzymatic pathway consisting of 13 enzymes for producing hydrogen from starch and water. The stoichiometric reaction is C(6)H(10)O(5) (l)+7 H(2)O (l)→12 H(2) (g)+6 CO(2) (g). The overall process is spontaneous and unidirectional because of a negative Gibbs free energy and separation of the gaseous products with the aqueous reactants. CONCLUSIONS: Enzymatic hydrogen production from starch and water mediated by 13 enzymes occurred at 30°C as expected, and the hydrogen yields were much higher than the theoretical limit (4 H(2)/glucose) of anaerobic fermentations. SIGNIFICANCE: The unique features, such as mild reaction conditions (30°C and atmospheric pressure), high hydrogen yields, likely low production costs ($∼2/kg H(2)), and a high energy-density carrier starch (14.8 H(2)-based mass%), provide great potential for mobile applications. With technology improvements and integration with fuel cells, this technology also solves the challenges associated with hydrogen storage, distribution, and infrastructure in the hydrogen economy

    Worm Burden-Dependent Disruption of the Porcine Colon Microbiota by Trichuris suis Infection

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    Helminth infection in pigs serves as an excellent model for the study of the interaction between human malnutrition and parasitic infection and could have important implications in human health. We had observed that pigs infected with Trichuris suis for 21 days showed significant changes in the proximal colon microbiota. In this study, interactions between worm burden and severity of disruptions to the microbial composition and metabolic potentials in the porcine proximal colon microbiota were investigated using metagenomic tools. Pigs were infected by a single dose of T. suis eggs for 53 days. Among infected pigs, two cohorts were differentiated that either had adult worms or were worm-free. Infection resulted in a significant change in the abundance of approximately 13% of genera detected in the proximal colon microbiota regardless of worm status, suggesting a relatively persistent change over time in the microbiota due to the initial infection. A significant reduction in the abundance of Fibrobacter and Ruminococcus indicated a change in the fibrolytic capacity of the colon microbiota in T. suis infected pigs. In addition, ∼10% of identified KEGG pathways were affected by infection, including ABC transporters, peptidoglycan biosynthesis, and lipopolysaccharide biosynthesis as well as α-linolenic acid metabolism. Trichuris suis infection modulated host immunity to Campylobacter because there was a 3-fold increase in the relative abundance in the colon microbiota of infected pigs with worms compared to naïve controls, but a 3-fold reduction in worm-free infected pigs compared to controls. The level of pathology observed in infected pigs with worms compared to worm-free infected pigs may relate to the local host response because expression of several Th2-related genes were enhanced in infected pigs with worms versus those worm-free. Our findings provided insight into the dynamics of the proximal colon microbiota in pigs in response to T. suis infection

    The Formation of Collective Silk Balls in the Spider Mite Tetranychus urticae Koch

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    Tetranychus urticae is a phytophagous mite that forms colonies of several thousand individuals. These mites construct a common web to protect the colony. When plants become overcrowded and food resources become scarce, individuals gather at the plant apex to form a ball composed of mites and their silk threads. This ball is a structure facilitating group dispersal by wind or animal transport. Until now, no quantitative study had been done on this collective form of migration. This is the first attempt to understand the mechanisms that underlie the emergence and growth of the ball. We studied this collective behaviour under laboratory conditions on standardized infested plants. Our results show that the collective displacement and the formation of balls result from a recruitment process: by depositing silk threads on their way up to the plant apex, mites favour and amplify the recruitment toward the balls. A critical threshold (quorum response) in the cumulative flow of mites must be reached to observe the emergence of a ball. At the beginning of the balls formation, mites form an aggregate. After 24 hours, the aggregated mites are trapped inside the silk balls by the complex network of silk threads and finally die, except for recently arrived individuals. The balls are mainly composed of immature stages. Our study reconstructs the key events that lead to the formation of silk balls. They suggest that the interplay between mites' density, plant morphology and plant density lead to different modes of dispersions (individual or collective) and under what conditions populations might adopt a collective strategy rather than one that is individually oriented. Moreover, our results lead to discuss two aspects of the cooperation and altruism: the importance of Allee effects during colonization of new plants and the importance of the size of a founding group
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