Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier

Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even though expression of interferon-stimulated genes was induced. We observed no differences in West Nile virus burden between wild-type and Ifnlr1-/- mice in the draining lymph nodes, spleen, or blood. We detected increased West Nile virus infection in the brain and spinal cord of Ifnlr1-/- mice, yet this was not associated with a direct antiviral effect in mouse neurons. Instead, we observed an increase in blood-brain barrier permeability in Ifnlr1-/- mice. Treatment of mice with pegylated interferon-λ2 resulted in decreased blood-brain barrier permeability, reduced West Nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge. An in vitro model of the blood-brain barrier showed that interferon-λ signaling in mouse brain microvascular endothelial cells increased transendothelial electrical resistance, decreased virus movement across the barrier, and modulated tight junction protein localization in a protein synthesis- and signal transducer and activator of transcription 1 (STAT1)-independent manner. Our data establish an indirect antiviral function of interferon-λ in which noncanonical signaling through IFNLR1 tightens the blood-brain barrier and restricts viral neuroinvasion and pathogenesis

Purpose and enactment in job design: An empirical examination of the processes through which job characteristics have their effects

Job characteristics are linked with health, safety, well-being and other performance outcomes. Job characteristics are usually assessed by their presence or absence, which gives no indication of the specific purposes for which workers might use some job characteristics. We focused on job control and social support as two job characteristics embedded in the well-known Demand-Control-Support model (Karasek & Theorell, 1990). In Study 1, using an experience sampling methodology (N = 67) and a cross-sectional survey methodology (N = 299), we found that relationships between the execution of job control or the elicitation of social support and a range of other variables depended on the purposes for which job control was executed or social support elicited. In Study 2 (N = 28), we found that it may be feasible to improve aspects of well-being and performance through training workers on how to use job control or social support for specific purposes

Relationship between advanced maternal age and timing of first developmental evaluation in children with autism

Objective: Mothers of advanced maternal age (AMA) at childbirth (age ‡35 years) may have different perceptions of autism spectrum disorder (ASD) risk, independent of sociodemographic factors, that may affect ASD identification. We aimed to estimate associations between AMA and both age of a child's first evaluation noting developmental concerns and time from first evaluation to first ASD diagnosis. Methods: We used data for 8-year-olds identified with ASD in the 2008 to 2012 Autism and Developmental Disabilities Monitoring Network. We estimated differences in age at first evaluation noting developmental concerns and time to first ASD diagnosis by AMA using quantile and Cox regression. Results: Of 10,358 children with ASD, 19.7% had mothers of AMA. AMA was associated with higher educational attainment and previous live births compared with younger mothers. In unadjusted analyses, AMA was associated with earlier first evaluation noting developmental concerns (median 37 vs 40 mo) and patterns in time to first evaluation (hazard ratio: 1.12, 95% confidence interval: 1.06-1.18). Associations between AMA and evaluation timing diminished and were no longer significant after adjustment for socioeconomic and demographic characteristics. Children's intellectual disability did not modify associations between AMA and timing of evaluations. Conclusion: Advanced maternal age is a sociodemographic factor associated with younger age of first evaluation noting developmental concerns in children with ASD, but AMA was not independently associated likely, because it is a consequence or cofactor of maternal education and other sociodemographic characteristics. AMA may be a demographic factor to consider when aiming to screen and evaluate children at risk for ASD

Oseltamivir-resistant influenza A(H1N1)pdm09 virus in Dutch travellers returning from Spain, August 2012

Two Dutch travellers were infected with oseltamivirresistant influenza A(H1N1)pdm09 viruses with an H275Y neuraminidase substitution in early August 2012. Both cases were probably infected during separate holidays at the Catalonian coast (Spain). No epidemiological connection between the two cases was found, and neither of them was treated with oseltamivir before specimen collection. Genetic analysis of the neuraminidase gene revealed the presence of previously described permissive mutations that may increase the likelihood of such strains emerging and spreading widely

Defining simple and comprehensive assessment units for CO2 storage in saline formations beneath the UK North Sea and continental shelf

In the UK, by far the largest CO2 storage opportunities lie offshore. The North Sea in particular has a long and complex geological history, with potential reservoirs geographically widespread and occurring at multiple stratigraphic levels. Diverse storage estimates have been made, using a range of working methods, and yielding different values, e.g. SCCS (2009); Bentham (2006). Consequently the UK Storage Appraisal Project (UKSAP), commissioned and funded by the Energy Technologies Institute (ETI), is undertaking the most comprehensive assessment to date, using abundant legacy seismic and borehole data. This study has a remit to use best current practice, consistent between locations, to calculate the CO2 storage capacity of the entire UK Continental Shelf (UKCS) within saline aquifers and hydrocarbon fields. The potential storage formations have been subdivided into units for assessment, and filtered to remove units with only a small estimated storage capacity to concentrate resources on more viable units. The size of potential storage units approximate to a power law distribution, similar to that of hydrocarbon fields, with a large number of small units and a small number of large units

Prevalence of intellectual disability among eight-year-old children from selected communities in the United States, 2014

Background: Children with intellectual disability (ID), characterized by impairments in intellectual functioning and adaptive behavior, benefit from early identification and access to services. Previous U.S. estimates used administrative data or parent report with limited information for demographic subgroups. Objective: Using empiric measures we examined ID characteristics among 8-year-old children and estimated prevalence by sex, race/ethnicity, geographic area and socioeconomic status (SES) area indicators. Methods: We analyzed data for 8-year-old children in 9 geographic areas participating in the 2014 Autism and Developmental Disabilities Monitoring Network. Children with ID were identified through record review of IQ test data. Census and American Community Survey data were used to estimate the denominator. Results: Overall, 11.8 per 1,000 (1.2%) had ID (IQ ≤ 70), of whom 39% (n = 998) also had autism spectrum disorder. Among children with ID, 1,823 had adaptive behavior test scores for which 64% were characterized as impaired. ID prevalence per 1,000 was 15.8 (95% confidence interval [95% CI], 15.0–16.5) among males and 7.7 (95% CI, 7.2–8.2) among females. ID prevalence was 17.7 (95% CI, 16.6–18.9) among children who were non-Hispanic black; 12.0 (95% CI, 11.1–13.0), among Hispanic; 8.6 (95% CI, 7.1–10.4), among non-Hispanic Asian; and 8.0 (95% CI, 7.5–8.6), among non-Hispanic white. Prevalence varied across geographic areas and was inversely associated with SES. Conclusions: ID prevalence varied substantively among racial, ethnic, geographic, and SES groups. Results can inform strategies to enhance identification and improve access to services particularly for children who are minorities or living in areas with lower SES

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

The International Pulsar Timing Array: First data release

International audienceThe highly stable spin of neutron stars can be exploited for a variety of (astro)physical investigations. In particular, arrays of pulsars with rotational periods of the order of milliseconds can be used to detect correlated signals such as those caused by gravitational waves. Three such 'pulsar timing arrays' (PTAs) have been set up around the world over the past decades and collectively form the 'International' PTA (IPTA). In this paper, we describe the first joint analysis of the data from the three regional PTAs, i.e. of the first IPTA data set. We describe the available PTA data, the approach presently followed for its combination and suggest improvements for future PTA research. Particular attention is paid to subtle details (such as underestimation of measurement uncertainty and long-period noise) that have often been ignored but which become important in this unprecedentedly large and inhomogeneous data set. We identify and describe in detail several factors that complicate IPTA research and provide recommendations for future pulsar timing efforts. The first IPTA data release presented here (and available on-line) is used to demonstrate the IPTA's potential of improving upon gravitational-wave limit