Protective Efficacy of Centralized and Polyvalent Envelope Immunogens in an Attenuated Equine Lentivirus Vaccine

Lentiviral Envelope (Env) antigenic variation and related immune evasion present major hurdles to effective vaccine development. Centralized Env immunogens that minimize the genetic distance between vaccine proteins and circulating viral isolates are an area of increasing study in HIV vaccinology. To date, the efficacy of centralized immunogens has not been evaluated in the context of an animal model that could provide both immunogenicity and protective efficacy data. We previously reported on a live-attenuated (attenuated) equine infectious anemia (EIAV) virus vaccine, which provides 100% protection from disease after virulent, homologous, virus challenge. Further, protective efficacy demonstrated a significant, inverse, linear relationship between EIAV Env divergence and protection from disease when vaccinates were challenged with viral strains of increasing Env divergence from the vaccine strain Env. Here, we sought to comprehensively examine the protective efficacy of centralized immunogens in our attenuated vaccine platform. We developed, constructed, and extensively tested a consensus Env, which in a virulent proviral backbone generated a fully replication-competent pathogenic virus, and compared this consensus Env to an ancestral Env in our attenuated proviral backbone. A polyvalent attenuated vaccine was established for comparison to the centralized vaccines. Additionally, an engineered quasispecies challenge model was created for rigorous assessment of protective efficacy. Twenty-four EIAV-naïve animals were vaccinated and challenged along with six-control animals six months post-second inoculation. Pre-challenge data indicated the consensus Env was more broadly immunogenic than the Env of the other attenuated vaccines. However, challenge data demonstrated a significant increase in protective efficacy of the polyvalent vaccine. These findings reveal, for the first time, a consensus Env immunogen that generated a fully-functional, replication-competent lentivirus, which when experimentally evaluated, demonstrated broader immunogenicity that does not equate to higher protective efficacy

The connection between galaxy environment and the luminosity function slopes of star-forming regions

We present the first study of GALEX far ultra-violet (FUV) luminosity functions of individual star-forming regions within a sample of 258 nearby galaxies spanning a large range in total stellar mass and star formation properties. We identify ~65,000 star-forming regions (i.e., FUV sources), measure each galaxy's luminosity function, and characterize the relationships between the luminosity function slope (alpha) and several global galaxy properties. A final sample of 82 galaxies with reliable luminosity functions are used to define these relationships and represent the largest sample of galaxies with the largest range of galaxy properties used to study the connection between luminosity function properties and galaxy environment. We find that alpha correlates with global star formation properties, where galaxies with higher star formation rates and star formation rate densities (Sigma_SFR) tend to have flatter luminosity function slopes. In addition, we find that neither stochastic sampling of the luminosity function in galaxies with low-number statistics nor the effects of blending due to distance can fully account for these trends. We hypothesize that the flatter slopes in high Sigma_SFR galaxies is due to higher gas densities and higher star formation efficiencies which result in proportionally greater numbers of bright star-forming regions. Finally, we create a composite luminosity function composed of star-forming regions from many galaxies and find a break in the luminosity function at brighter luminosities. However, we find that this break is an artifact of varying detection limits for galaxies at different distances.Science and Technology Facilities CouncilThis is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw169

Measuring Metacognition in Cancer: Validation of the Metacognitions Questionnaire 30 (MCQ-30)

Objective The Metacognitions Questionnaire 30 assesses metacognitive beliefs and processes which are central to the metacognitive model of emotional disorder. As recent studies have begun to explore the utility of this model for understanding emotional distress after cancer diagnosis, it is important also to assess the validity of the Metacognitions Questionnaire 30 for use in cancer populations. Methods 229 patients with primary breast or prostate cancer completed the Metacognitions Questionnaire 30 and the Hospital Anxiety and Depression Scale pre-treatment and again 12 months later. The structure and validity of the Metacognitions Questionnaire 30 were assessed using factor analyses and structural equation modelling. Results Confirmatory and exploratory factor analyses provided evidence supporting the validity of the previously published 5-factor structure of the Metacognitions Questionnaire 30. Specifically, both pre-treatment and 12 months later, this solution provided the best fit to the data and all items loaded on their expected factors. Structural equation modelling indicated that two dimensions of metacognition (positive and negative beliefs about worry) were significantly associated with anxiety and depression as predicted, providing further evidence of validity. Conclusions These findings provide initial evidence that the Metacognitions Questionnaire 30 is a valid measure for use in cancer populations

Neutron Stars in Teleparallel Gravity

In this paper we deal with neutron stars, which are described by a perfect fluid model, in the context of the teleparallel equivalent of general relativity. We use numerical simulations to find the relationship between the angular momentum of the field and the angular momentum of the source. Such a relation was established for each stable star reached by the numerical simulation once the code is fed with an equation of state, the central energy density and the ratio between polar and equatorial radii. We also find a regime where linear relation between gravitational angular momentum and moment of inertia (as well as angular velocity of the fluid) is valid. We give the spatial distribution of the gravitational energy and show that it has a linear dependence with the squared angular velocity of the source.Comment: 19 pages, 14 figures. arXiv admin note: text overlap with arXiv:1206.331

A pilot telephone intervention to increase uptake of breast cancer screening in socially deprived areas in Scotland (TELBRECS):study protocol for a randomised controlled trial

BACKGROUND Breast cancer accounts for almost 30% of all cancers and is the second leading cause of cancer deaths in women in Scotland. Screening is key to early detection. The Scottish Breast Screening Programme is a nationwide, free at point of delivery screening service, to which all women aged between 50 and 70 years are invited to attend every 3 years. Currently over three-quarters of invited women regularly attend screening. However, women from more deprived areas are much less likely to attend: for example in the 3 years from 2010-2012 only 63% of women in the most deprived area attended the East of Scotland Breast Screening programme versus 81% in the least deprived. Research has suggested that reminders (telephone or letter) and brief, personalised interventions addressing barriers to attendance may be helpful in increasing uptake in low-income women. METHODS/DESIGN We will employ a brief telephone reminder and support intervention, whose purpose is to elicit and address any mistaken beliefs women have about breast screening, with the aim that the perceived benefits of screening come to outweigh any perceived barriers for individuals. We will test whether this intervention, plus a simple anticipated regret manipulation, will lead to an increase in the uptake of breast cancer screening amongst low-income women who have failed to attend a first appointment, in a randomised controlled trial with 600 women. Participants will be randomly allocated to one of four treatment arms i.e. 1) Letter reminder (i.e. Treatment as usual: CONTROL); 2) Telephone reminder (TEL), 3) Telephone reminder plus telephone support (TEL-SUPP) and 4) Telephone reminder plus support plus AR (TEL-SUPP-AR). The primary outcome will be attendance at breast screening within 3 months of the reminder letter. DISCUSSION If this simple telephone support intervention (with or without AR intervention) leads to a significant increase in breast screening attendance, this would represent a rare example of a theoretically-driven, relatively simple psychological intervention that could result in earlier detection of breast cancer amongst an under-served group of lower socio-economic women. TRIAL REGISTRATION Current Controlled trials: ISRCTN06039270. Registered 16th January 2014

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Measuring hearing in wild beluga whales

Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in "The Effects of Noise on Aquatic Life II," edited by Arthur N. Popper, Anthony Hawkins, 729-735. New York, NY: Springer, 2016. doi: 10.1007/978-1-4939-2981-8_88.We measured the hearing abilities of seven wild beluga whales (Delphinapterus leucas) during a collection-and-release experiment in Bristol Bay, AK, USA. Here we summarize the methods and initial data from one animal, discussing the implications of this experiment. Audiograms were collected from 4-150 kHz. The animal with the lowest threshold heard best at 80 kHz and demonstrated overall good hearing from 22-110 kHz. The robustness of the methodology and data suggest AEP audiograms can be incorporated into future collection-and-release health assessments. Such methods may provide high-quality results for multiple animals facilitating population-level audiograms and hearing measures in new species.Project funding and field support provided by Georgia Aquarium and the National Marine Mammal Laboratory of the Alaska Fisheries Science Center (NMML/AFSC). Field work also supported by National Marine Fisheries Service Alaska Regional Office (NMFS AKR), WHOI Arctic Research Initiative, WHOI Ocean Life Institute, U.S. Fish and Wildlife Service, Bristol Bay Native Association, Alaska SeaLife Center, Shedd Aquarium and Mystic Aquarium. Audiogram analyses were funded by the Office of Naval Research award number N000141210203 (from Michael Weise)

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Peer reviewedPublisher PD

Optimization of the design of ducted-fan hovering micro air vehicles using finite element simulation and orthogonal design

The structural design and flight stability characteristics of micro air vehicles have received much attention due to its low Reynolds number. Compared with fixed-wing aircraft, hovering ducted-fan micro air vehicles with vertical takeoff and landing and hovering capabilities have promising prospect. In this article, a flexible membrane and inflatable structure has been used as the aerodynamic shape of an aircraft model. Its advantages have been analyzed and verified by fluid-structure interaction based on finite element method. The flight stability of hovering micro air vehicles has also been investigated based on the theory of motion of structure. In order to improve the flight stability of the designed hovering micro air vehicle model, the effects of geometrical parameters and materials have been analyzed through an orthogonal experimental design. Based on the optimized results, the aircraft prototype has been manufactured for experimental test. The elastic deformation produced on its flexible membrane structure is obtained by stroboscopic stereo imaging method and a purpose-built experimental environment. The numerical simulation results indicated that the thickness of membrane and material of vertical duct have significant effects on the micro air vehicle flight stability and disturbance resistance ability. The results have confirmed that the flexible aerodynamic mechanisms produced by the aeroelastic deformation of spherical membrane can enhance the micro air vehicle stability.This work was financially supported by Support Program of National Ministry of Education of China (No. 625010110), National Natural Science Foundation of China (No. 61179043), and Specialized Research Fund for the Doctoral Program (SRFDP) of Higher Education (No. 20070056085)

Flood fragility analysis for bridges with multiple failure modes

Bridges are one of the most important infrastructure systems that provide public and economic bases for humankind. It is also widely known that bridges are exposed to a variety of flood-related risk factors such as bridge scour, structural deterioration, and debris accumulation, which can cause structural damage and even failure of bridges through a variety of failure modes. However, flood fragility has not received as much attention as seismic fragility despite the significant amount of damage and costs resulting from flood hazards. There have been few research efforts to estimate the flood fragility of bridges considering various flood-related factors and the corresponding failure modes. Therefore, this study proposes a new approach for bridge flood fragility analysis. To obtain accurate flood fragility estimates, reliability analysis is performed in conjunction with finite element analysis, which can sophisticatedly simulate the structural response of a bridge under a flood by accounting for flood-related risk factors. The proposed approach is applied to a numerical example of an actual bridge in Korea. Flood fragility curves accounting for multiple failure modes, including lack of pier ductility or pile ductility, pier rebar rupture, pile rupture, and deck loss, are derived and presented in this study.ope