Anticipating the species jump: surveillance for emerging viral threats.

Zoonotic disease surveillance is typically triggered after animal pathogens have already infected humans. Are there ways to identify high-risk viruses before they emerge in humans? If so, then how and where can identifications be made and by what methods? These were the fundamental questions driving a workshop to examine the future of predictive surveillance for viruses that might jump from animals to infect humans. Virologists, ecologists and computational biologists from academia, federal government and non-governmental organizations discussed opportunities as well as obstacles to the prediction of species jumps using genetic and ecological data from viruses and their hosts, vectors and reservoirs. This workshop marked an important first step towards envisioning both scientific and organizational frameworks for this future capability. Canine parvoviruses as well as seasonal H3N2 and pandemic H1N1 influenza viruses are discussed as exemplars that suggest what to look for in anticipating species jumps. To answer the question of where to look, prospects for discovering emerging viruses among wildlife, bats, rodents, arthropod vectors and occupationally exposed humans are discussed. Finally, opportunities and obstacles are identified and accompanied by suggestions for how to look for species jumps. Taken together, these findings constitute the beginnings of a conceptual framework for achieving a virus surveillance capability that could predict future species jumps

Mechanical measurements of heterogeneity and length scale effects in PEG-based hydrogels.

Colloidal-probe spherical indentation load-relaxation experiments with a probe radius of 3 μm are conducted on poly(ethylene glycol) (PEG) hydrogel materials to quantify their steady-state mechanical properties and time-dependent transport properties via a single experiment. PEG-based hydrogels are shown to be heterogeneous in both morphology and mechanical stiffness at this scale; a linear-harmonic interpolation of hyperelastic Mooney-Rivlin and Boussinesq flat-punch indentation models was used to describe the steady-state response of the hydrogels and determine upper and lower bounds for indentation moduli. Analysis of the transient load-relaxation response during displacement-controlled hold periods provides a means of extracting two time constants τ1 and τ2, where τ1 and τ2 are assigned to the viscoelastic and poroelastic properties, respectively. Large τ2 values at small indentation depths provide evidence of a non-equilibrium state characterized by a phenomenon that restricts poroelastic fluid flow through the material; for larger indentations, the variability in τ2 values decreases and pore sizes estimated from τ2via indentation approach those measured via macroscopic swelling experiments. The contact probe methodology developed here provides a means of assessing hydrogel heterogeneity, including time-dependent mechanical and transport properties, and has potential implications in hydrogel biomedical and engineering applications.The authors would like to acknowledge funding from the National Institutes of Health.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5SM01210

Functional diversity of marine ecosystems after the Late Permian mass extinction event

Article can be accessed from http://www.nature.com/ngeo/journal/v7/n3/full/ngeo2079.htmlThe Late Permian mass extinction event was the most severe such crisis of the past 500 million years and occurred during an episode of global warming. It is assumed to have had significant ecological impact, but its effects on marine ecosystem functioning are unknown and the patterns of marine recovery are debated. We analysed the fossil occurrences of all known Permian-Triassic benthic marine genera and assigned each to a functional group based on their inferred life habit. We show that despite the selective extinction of 62-74% of marine genera there was no significant loss of functional diversity at the global scale, and only one novel mode of life originated in the extinction aftermath. Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed, which explains the absence of a Cambrian-style Triassic radiation in higher taxa. Functional diversity was, however, significantly reduced in particular regions and habitats, such as tropical reefs, and at these scales recovery varied spatially and temporally, probably driven by migration of surviving groups. Marine ecosystems did not return to their pre-extinction state, however, and radiation of previously subordinate groups such as motile, epifaunal grazers led to greater functional evenness by the Middle Triassic

Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

Sporormiella as a tool for detecting the presence of large herbivores in the Neotropics

The reliability of using the abundance of Sporormiella spores as a proxy for the presence and abundance of megaherbivores was tested in southern Brazil. Mud-water interface samples from nine lakes, in which cattle-use was categorized as high, medium, or low, were assayed for Sporormiella representation. The sampling design allowed an analysis of both the influence of the number of animals using the shoreline and the distance of the sampling site from the nearest shoreline. Sporormiella was found to be a reliable proxy for the presence of large livestock. The concentration and abundance of spores declined from the edge of the lake toward the center, with the strongest response being in sites with high livestock use. Consistent with prior studies in temperate regions, we find that Sporormiella spores are a useful proxy to study the extinction of Pleistocene megafauna or the arrival of European livestock in Neotropical landscapes

Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis

Background: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth. Methods: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic. Results: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65). Conclusion: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users

A Survey on Continuous Time Computations

We provide an overview of theories of continuous time computation. These theories allow us to understand both the hardness of questions related to continuous time dynamical systems and the computational power of continuous time analog models. We survey the existing models, summarizing results, and point to relevant references in the literature

Effects of strategies to promote children\u27s physical activity on potential mediators

The aim of this paper is to review evidence of the effectiveness of interventions that present physical activity outcomes and potential mediators of behavioural change among 4&ndash;12-year-old children. A systematic search of electronic databases for original research articles published in peer-review journals between January 1985 and the end of June 2006 was carried out. A total of 19 studies that reported intervention effects on physical activity and mediators of behavioural change were identified. The most common mediators reported included physical activity knowledge or beliefs (11 studies); self-efficacy (8 studies); and enjoyment or preference for physical activity (6 studies). Less frequently reported mediators included attitudes, behavioural capability, intentions, outcome expectancies, social norms, social support and self-concept. Seven of the 11 interventions that reported intervention effects on knowledge/beliefs stated positive changes in this mediator. Four of the eight studies that reported intervention effects on self-efficacy had significant improvements; however, only two out of six interventions reported significant improvements in physical activity enjoyment or preference. None of the studies reviewed reported whether changes in these constructs mediated changes in children\u27s physical activity behaviours. Although more than half of the studies reviewed reported a positive intervention effect on children\u27s physical activity, no study carried out a mediating analysis to attempt to identify the mechanisms of change. Future research should more clearly identify the mediators of behavioural change that are being targeted and whether this explains intervention effects.<br /

Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner

Objective: Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs). Methods: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. Results: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. Significance: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma

Sympatric Speciation: When Is It Possible in Bacteria?

This study investigated a potential auditory illusion in duration perception induced by rhythmic temporal contexts. Listeners with or without musical training performed a duration discrimination task for a silent period in a rhythmic auditory sequence. The critical temporal interval was presented either within a perceptual group or between two perceptual groups. We report the just-noticeable difference (difference limen, DL) for temporal intervals and the point of subjective equality (PSE) derived from individual psychometric functions based on performance of a two-alternative forced choice task. In musically untrained individuals, equal temporal intervals were perceived as significantly longer when presented between perceptual groups than within a perceptual group (109.25% versus 102.5% of the standard duration). Only the perceived duration of the between-group interval was significantly longer than its objective duration. Musically trained individuals did not show this effect. However, in both musically trained and untrained individuals, the relative difference limens for discriminating the comparison interval from the standard interval were larger in the between-groups condition than in the within-group condition (7.3% vs. 5.6% of the standard duration). Thus, rhythmic grouping affected sensitivity to duration changes in all listeners, with duration differences being harder to detect at boundaries of rhythm groups than within rhythm groups. Our results show for the first time that temporal Gestalt induces auditory duration illusions in typical listeners, but that musical experts are not susceptible to this effect of rhythmic grouping.Ellison Medical FoundationSwiss National Science Foundation (PA00P1_131448/1