Epidemic protection zones : centred on cases or based on connectivity?

When an exotic infectious disease invades a susceptible environment, protection zones are enforced. Historically, such zones have been shaped as circles of equal radius (ER), centred on the location of infected premises. Because the ER policy seems to assume that epidemic dissemination is driven by a similar number of secondary cases generated per primary case, it does not consider whether local features, such as connectivity, influence epidemic dispersal. Here we explored the efficacy of ER protection zones. By generating a geographically explicit scenario that mimicked an actual epidemic, we created protection zones of different geometry, comparing the cost-benefit estimates of ER protection zones to a set of alternatives, which considered a pre-existing connecting network (CN) – the road network. The hypothesis of similar number of cases per ER circle was not substantiated: the number of units at risk per circle differed up to four times among ER circles. Findings also showed that even a small area (of <115 km2) revealed network properties. Because the CN policy required 20% less area to be protected than the ER policy, and the CN-based protection zone included a 23.8% greater density of units at risk/km2 than the ER-based alternative, findings supported the view that protection zones are likely to be less costly and more effective if they consider connecting structures, such as road, railroad and/or river networks. The analysis of local geographical factors (contacts, vectors and connectivity) may optimize the efficacy of control measures against epidemics.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1865-1682ab2012ab2013 (Author correction

Intravitreally injected anti-VEGF antibody reduces brown fat in neonatal mice

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondriarelated genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants. Copyright

Connecting network properties of rapidly disseminating epizoonotics

BACKGROUND: To effectively control the geographical dissemination of infectious diseases, their properties need to be determined. To test that rapid microbial dispersal requires not only susceptible hosts but also a pre-existing, connecting network, we explored constructs meant to reveal the network properties associated with disease spread, which included the road structure. METHODS: Using geo-temporal data collected from epizoonotics in which all hosts were susceptible (mammals infected by Foot-and-mouth disease virus, Uruguay, 2001; birds infected by Avian Influenza virus H5N1, Nigeria, 2006), two models were compared: 1) ‘connectivity’, a model that integrated bio-physical concepts (the agent’s transmission cycle, road topology) into indicators designed to measure networks (‘nodes’ or infected sites with short- and long-range links), and 2) ‘contacts’, which focused on infected individuals but did not assess connectivity. RESULTS: The connectivity model showed five network properties: 1) spatial aggregation of cases (disease clusters), 2) links among similar ‘nodes’ (assortativity), 3) simultaneous activation of similar nodes (synchronicity), 4) disease flows moving from highly to poorly connected nodes (directionality), and 5) a few nodes accounting for most cases (a ‘‘20:800 pattern). In both epizoonotics, 1) not all primary cases were connected but at least one primary case was connected, 2) highly connected, small areas (nodes) accounted for most cases, 3) several classes of nodes were distinguished, and 4) the contact model, which assumed all primary cases were identical, captured half the number of cases identified by the connectivity model. When assessed together, the synchronicity and directionality properties explained when and where an infectious disease spreads. CONCLUSIONS: Geo-temporal constructs of Network Theory’s nodes and links were retrospectively validated in rapidly disseminating infectious diseases. They distinguished classes of cases, nodes, and networks, generating information usable to revise theory and optimize control measures. Prospective studies that consider pre-outbreak predictors, such as connecting networks, are recommended.The National Veterinary Research Institute, Vom, Plateau, Nigeria; the Center for Non-Linear Studies of Los Alamos National Laboratory; and partially funded by Defense Threat Reduction Agency (DTRA) Grant CBT-09-IST-05-1-0092 (to JMF).http://www.plosone.orgab2012ab2013 (Author correction

Connecting Network Properties of Rapidly Disseminating Epizoonotics

To effectively control the geographical dissemination of infectious diseases, their properties need to be determined. To test that rapid microbial dispersal requires not only susceptible hosts but also a pre-existing, connecting network, we explored constructs meant to reveal the network properties associated with disease spread, which included the road structure.Using geo-temporal data collected from epizoonotics in which all hosts were susceptible (mammals infected by Foot-and-mouth disease virus, Uruguay, 2001; birds infected by Avian Influenza virus H5N1, Nigeria, 2006), two models were compared: 1) 'connectivity', a model that integrated bio-physical concepts (the agent's transmission cycle, road topology) into indicators designed to measure networks ('nodes' or infected sites with short- and long-range links), and 2) 'contacts', which focused on infected individuals but did not assess connectivity.THE CONNECTIVITY MODEL SHOWED FIVE NETWORK PROPERTIES: 1) spatial aggregation of cases (disease clusters), 2) links among similar 'nodes' (assortativity), 3) simultaneous activation of similar nodes (synchronicity), 4) disease flows moving from highly to poorly connected nodes (directionality), and 5) a few nodes accounting for most cases (a "20:80" pattern). In both epizoonotics, 1) not all primary cases were connected but at least one primary case was connected, 2) highly connected, small areas (nodes) accounted for most cases, 3) several classes of nodes were distinguished, and 4) the contact model, which assumed all primary cases were identical, captured half the number of cases identified by the connectivity model. When assessed together, the synchronicity and directionality properties explained when and where an infectious disease spreads.Geo-temporal constructs of Network Theory's nodes and links were retrospectively validated in rapidly disseminating infectious diseases. They distinguished classes of cases, nodes, and networks, generating information usable to revise theory and optimize control measures. Prospective studies that consider pre-outbreak predictors, such as connecting networks, are recommended

Expectation in Melody: The Influence of Context and Learning

The Implication-Realization (IR) theory (Narmour, 1990) posits two cognitive systems involved in the generation of melodic expectations: The first consists of a limited number of symbolic rules that are held to be innate and universal; the second reflects the top-down influences of acquired stylistic knowledge. Aspects of both systems have been implemented as quantitative models in research which has yielded empirical support for both components of the theory (Cuddy & Lunny, 1995; Krumhansl, 1995a, 1995b; Schellenberg, 1996, 1997). However, there is also evidence that the implemented bottom-up rules constitute too inflexible a model to account for the influence of the musical experience of the listener and the melodic context in which expectations are elicited. A theory is presented, according to which both bottom-up and top-down descriptions of observed patterns of melodic expectation may be accounted for in terms of the induction of statistical regularities in existing musical repertoires. A computational model that embodies this theory is developed and used to reanalyze existing experimental data on melodic expectancy. The results of three experiments with increasingly complex melodic stimuli demonstrate that this model is capable of accounting for listeners’ expectations as well as or better than the two-factor model of Schellenberg (1997)

Clarity of task difficulty moderates the impact of the explicit achievement motive on physical effort in hand grip tasks

Stable personality dispositions, like motives, are often assumed to exert a direct, stable impact on behavior. This also applies to the explicit achievement motive, which is supposed to influence the behavior that individuals select and how strongly they engage in it. Drawing on motivational intensity theory, we demonstrated in two studies that explicit achievement motive strength only predicted exerted force in a hand grip task if task difficulty was unclear. If task difficulty was clear, explicit achievement motive strength did not influence exerted force. Our findings suggest that the availability of information about the difficulty of motive satisfaction moderates the impact of the explicit achievement motive on behavior

Elevated Nitric Oxide Production in Children with Malarial Anemia: Hemozoin-Induced Nitric Oxide Synthase Type 2 Transcripts and Nitric Oxide in Blood Mononuclear Cells

Experiments outlined here investigate the role of nitric oxide (NO) in the pathogenesis of Plasmodium falciparum-induced malarial anemia (MA). The results show that ex vivo and in vitro NO synthase (NOS) activity in peripheral blood mononuclear cells (PBMCs) is significantly elevated in children with MA and inversely associated with hemoglobin levels. Additional experiments using PBMCs from non-malaria-exposed donors demonstrate that physiologic amounts of P. falciparum-derived hemozoin augment NOS type 2 (NOS2) transcripts and NO production. Results of these experiments illustrate that elevated NO production in children with MA is associated with decreased hemoglobin concentrations and that hemozoin can induce NOS2-derived NO formation in cultured blood mononuclear cells