Field evaluation of the efficacy and safety of a combination of spinosad and milbemycin oxime in the treatment and prevention of naturally acquired flea infestations and treatment of intestinal nematode infections in dogs in Europe

AbstractTwo separate randomised, blinded, multicentre field trials were conducted to evaluate the efficacy and safety of a combination of spinosad and milbemycin oxime (MO) (Trifexis®, Elanco Animal Health) in the treatment and prevention of naturally acquired flea infestations and intestinal nematode infections in European dogs. Treatments using Trifexis® and each control veterinary product (CVP) were administered once on Day 0 in both field studies.In the flea field trial, 11 veterinary clinics in France participated in the study. On Day 0, whole body flea comb counts were conducted on all dogs being evaluated for enrolment. Dogs with ≥7 fleas on Day 0 were enrolled, treated once on Day 0 with spinosad/MO or the CVP (Stronghold®; selamectin) and then underwent post-treatment flea counts on Days 14 and 30. There were 150 spinosad/MO treated dogs and 71 CVP treated dogs included in the flea effectiveness population. Effectiveness against fleas (% reduction in geometric means; GM) was 98.97% and 97.37% for the spinosad/MO treated dogs, and 97.43% and 93.96% for the CVP dogs on Days 14 and 30, respectively, compared to the pre-treatment baseline flea counts. Of the spinosad/MO dogs, 89.3% and 80.0% had no live fleas on Days 14 and 30, compared to 77.5% and 70.4% of the CVP dogs, respectively.In the nematode field trial, data from 10 veterinary clinics in France and 19 in Ireland were pooled. Faecal samples from dogs at each clinic were analysed. A positive result at screening (parasite eggs from Toxocara canis, Toxascaris leonina, Trichuris vulpis or Ancylostoma caninum) allowed for enrolment. Dogs were randomised to spinosad/MO or the CVP (Milbemax®; MO/praziquantel). On Day 8, a post-treatment faecal sample was taken and analysed. Of 2333 dogs screened for nematode eggs, 238 dogs were positive with one or more of these nematodes, and 229 were enrolled in the study. Of the 229 dogs, 151 were treated with a single dose of spinosad/MO, and 77 were treated with a single dose of CVP. Post-treatment effectiveness against all nematodes (% reduction GM) was achieved with reductions of 98.57% and 97.57% for the spinosad/MO treated dogs and CVP dogs, respectively, as compared to the pre-treatment baseline faecal egg counts.Trifexis® was shown to be safe and effective against natural infestations of fleas as well as mixed and single intestinal nematode infections in client owned dogs in Europe when administered as a single oral administration at the recommended dose

Axonal growth arrests after an increased accumulation of Schwann cells expressing senescence markers and stromal cells in acellular nerve allografts

Acellular nerve allografts (ANAs) and other nerve constructs do not reliably facilitate axonal regeneration across long defects (>3 cm). Causes for this deficiency are poorly understood. In this study, we determined what cells are present within ANAs before axonal growth arrest in nerve constructs and if these cells express markers of cellular stress and senescence. Using the Thy1-GFP rat and serial imaging, we identified the time and location of axonal growth arrest in long (6 cm) ANAs. Axonal growth halted within long ANAs by 4 weeks, while axons successfully regenerated across short (3 cm) ANAs. Cellular populations and markers of senescence were determined using immunohistochemistry, histology, and senescence-associated β-galactosidase staining. Both short and long ANAs were robustly repopulated with Schwann cells (SCs) and stromal cells by 2 weeks. Schwann cells (S100β(+)) represented the majority of cells repopulating both ANAs. Overall, both ANAs demonstrated similar cellular populations with the exception of increased stromal cells (fibronectin(+)/S100β(−)/CD68(−) cells) in long ANAs. Characterization of ANAs for markers of cellular senescence revealed that long ANAs accumulated much greater levels of senescence markers and a greater percentage of Schwann cells expressing the senescence marker p16 compared to short ANAs. To establish the impact of the long ANA environment on axonal regeneration, short ANAs (2 cm) that would normally support axonal regeneration were generated from long ANAs near the time of axonal growth arrest (“stressed” ANAs). These stressed ANAs contained mainly S100β(+)/p16(+) cells and markedly reduced axonal regeneration. In additional experiments, removal of the distal portion (4 cm) of long ANAs near the time of axonal growth arrest and replacement with long isografts (4 cm) rescued axonal regeneration across the defect. Neuronal culture derived from nerve following axonal growth arrest in long ANAs revealed no deficits in axonal extension. Overall, this evidence demonstrates that long ANAs are repopulated with increased p16(+) Schwann cells and stromal cells compared to short ANAs, suggesting a role for these cells in poor axonal regeneration across nerve constructs

Psychological and Genetic Predictors of Pain Tolerance

Previous studies have shown associations between genetic polymorphisms and pain tolerance, but psychological evaluations are seldom measured. The objective of this study was to determine the independent effects of demographic, psychological, and genetic predictors of cold noxious pain tolerance. Healthy subjects (n = 89) completed the Pain Catastrophizing Scale (PCS) and Fear of Pain Questionnaire (FPQ-III), underwent genotyping for candidate single nucleotide polymorphisms (SNPs), and completed a cold-pressor test in a 1-2 degrees C water bath for a maximum of 3 minutes. The primary outcome measure was pain tolerance, defined as the maximum duration of time subjects left their nondominant hand in the cold-water bath. Cox proportional hazards regression indicated that female sex, Asian race, and increasing PCS and FPQ-III scores were associated with lower pain tolerance. No candidate SNP was significantly associated with pain tolerance. Future genetic studies should include demographic and psychological variables as confounders in experimental pain models.Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Ion Propulsion System for the Solar Electric Propulsion Technology Demonstration Mission

The Asteroid Redirect Robotic Mission is a candidate Solar Electric Propulsion Technology Demonstration Mission whose main objectives are to develop and demonstrate a high-power solar electric propulsion capability for the Agency and return an asteroidal mass for rendezvous and characterization in a companion human-crewed mission. The ion propulsion system must be capable of operating over an 8-year time period and processing up to 10,000 kg of xenon propellant. This high-power solar electric propulsion capability, or an extensible derivative of it, has been identified as a critical part of an affordable, beyond-low-Earth-orbit, manned-exploration architecture. Under the NASA Space Technology Mission Directorate the critical electric propulsion and solar array technologies are being developed. The ion propulsion system being co-developed by the NASA Glenn Research Center and the Jet Propulsion Laboratory for the Asteroid Redirect Vehicle is based on the NASA-developed 12.5 kW Hall Effect Rocket with Magnetic Shielding (HERMeS0 thruster and power processing technologies. This paper presents the conceptual design for the ion propulsion system, the status of the NASA in-house thruster and power processing activity, and an update on flight hardware

Beyond Spheroids and Discs: Classifications of CANDELS Galaxy Structure at 1.4 < z < 2 via Principal Component Analysis

Important but rare and subtle processes driving galaxy morphology and star-formation may be missed by traditional spiral, elliptical, irregular or S\'ersic bulge/disk classifications. To overcome this limitation, we use a principal component analysis of non-parametric morphological indicators (concentration, asymmetry, Gini coefficient, $M_{20}$, multi-mode, intensity and deviation) measured at rest-frame $B$-band (corresponding to HST/WFC3 F125W at 1.4 $10^{10} M_{\odot}$) galaxy morphologies. Principal component analysis (PCA) quantifies the correlations between these morphological indicators and determines the relative importance of each. The first three principal components (PCs) capture $\sim$75 per cent of the variance inherent to our sample. We interpret the first principal component (PC) as bulge strength, the second PC as dominated by concentration and the third PC as dominated by asymmetry. Both PC1 and PC2 correlate with the visual appearance of a central bulge and predict galaxy quiescence. PC1 is a better predictor of quenching than stellar mass, as as good as other structural indicators (S\'ersic-n or compactness). We divide the PCA results into groups using an agglomerative hierarchical clustering method. Unlike S\'ersic, this classification scheme separates compact galaxies from larger, smooth proto-elliptical systems, and star-forming disk-dominated clumpy galaxies from star-forming bulge-dominated asymmetric galaxies. Distinguishing between these galaxy structural types in a quantitative manner is an important step towards understanding the connections between morphology, galaxy assembly and star-formation.Comment: 31 pages, 24 figures, accepted for publication in MNRA

Investigation of Exoskeletal Engine Propulsion System Concept

An innovative approach to gas turbine design involves mounting compressor and turbine blades to an outer rotating shell. Designated the exoskeletal engine, compression (preferable to tension for high-temperature ceramic materials, generally) becomes the dominant blade force. Exoskeletal engine feasibility lies in the structural and mechanical design (as opposed to cycle or aerothermodynamic design), so this study focused on the development and assessment of a structural-mechanical exoskeletal concept using the Rolls-Royce AE3007 regional airliner all-axial turbofan as a baseline. The effort was further limited to the definition of an exoskeletal high-pressure spool concept, where the major structural and thermal challenges are represented. The mass of the high-pressure spool was calculated and compared with the mass of AE3007 engine components. It was found that the exoskeletal engine rotating components can be significantly lighter than the rotating components of a conventional engine. However, bearing technology development is required, since the mass of existing bearing systems would exceed rotating machinery mass savings. It is recommended that once bearing technology is sufficiently advanced, a "clean sheet" preliminary design of an exoskeletal system be accomplished to better quantify the potential for the exoskeletal concept to deliver benefits in mass, structural efficiency, and cycle design flexibility

Overview of the Development and Mission Application of the Advanced Electric Propulsion System (AEPS)

NASA remains committed to the development and demonstration of a high-power solar electric propulsion capability for the Agency. NASA is continuing to develop the 14 kilowatt Advanced Electric Propulsion System (AEPS), which has recently completed an Early Integrated System Test and System Preliminary Design Review. NASA continues to pursue Solar Electric Propulsion (SEP) Technology Demonstration Mission partners and mature high-power SEP mission concepts. The recent announcement of the development of a Power and Propulsion Element (PPE) as the first element of an evolvable human architecture to Mars has replaced the Asteroid Redirect Robotic Mission as the most probable first application of the AEPS Hall thruster system. This high-power SEP capability, or an extensible derivative of it, has been identified as a critical part of an affordable, beyond-low-Earth-orbit, manned-exploration architecture. This paper presents the status of the combined NASA and Aerojet AEPS development activities and updated mission concept for implementation of the AEPS hardware as part of the ion propulsion system for a PPE

Basins of attraction on random topography

We investigate the consequences of fluid flowing on a continuous surface upon the geometric and statistical distribution of the flow. We find that the ability of a surface to collect water by its mere geometrical shape is proportional to the curvature of the contour line divided by the local slope. Consequently, rivers tend to lie in locations of high curvature and flat slopes. Gaussian surfaces are introduced as a model of random topography. For Gaussian surfaces the relation between convergence and slope is obtained analytically. The convergence of flow lines correlates positively with drainage area, so that lower slopes are associated with larger basins. As a consequence, we explain the observed relation between the local slope of a landscape and the area of the drainage basin geometrically. To some extent, the slope-area relation comes about not because of fluvial erosion of the landscape, but because of the way rivers choose their path. Our results are supported by numerically generated surfaces as well as by real landscapes

On plane wave and vortex-like solutions of noncommutative Maxwell-Chern-Simons theory

We investigate the spectrum of the gauge theory with Chern-Simons term on the noncommutative plane, a modification of the description of the Quantum Hall fluid recently proposed by Susskind. We find a series of the noncommutative massive ``plane wave'' solutions with polarization dependent on the magnitude of the wave-vector. The mass of each branch is fixed by the quantization condition imposed on the coefficient of the noncommutative Chern-Simons term. For the radially symmetric ansatz a vortex-like solution is found and investigated. We derive a nonlinear difference equation describing these solutions and we find their asymptotic form. These excitations should be relevant in describing the Quantum Hall transitions between plateaus and the end transition to the Hall Insulator.Comment: 17 pages, LaTeX (JHEP), 1 figure, added references, version accepted to JHE