Virulence characterization of Rift Valley fever virus strains and efficacy of glycoprotein subunit vaccines in mice

Master of ScienceDepartment of Diagnostic Medicine/PathobiologyJuergen A. RichtRift Valley fever virus (RVFV) is a vector-borne zoonotic pathogen endemic to sub-Saharan Africa and the Arabian Peninsula that causes severe disease in ruminants and humans. RVFV is a significant threat to US livestock and public health due to a lack of licensed, efficacious vaccines and its ability to become established in non-endemic areas. Subunit vaccine candidates based on RVFV N- and C-terminal glycoproteins (Gn and Gc) are a viable option for use in ruminants due to their ease of production, safety, and ability to induce immune responses that offer differentiation between infected and vaccinated animals (DIVA). Importantly, subunit Gn+Gc vaccine candidates have demonstrated efficacy in sheep. However, despite the efficacy of a dual glycoprotein vaccine, no studies have directly compared protective efficacies of the individual glycoproteins. Furthermore, although RVFV demonstrates 2.1% maximum pairwise amino acid strain divergence within Gn/Gc ectodomains, it remains unclear how this may affect cross-protective vaccine efficacy. In this study, we used a BALB/c mouse model to determine the median lethal dose (LD₅₀) of 3 wildtype RVFV strains and used this information to standardize challenge doses in subsequent vaccine efficacy studies using baculovirus-expressed Gn/Gc antigens derived from RVFV strain Zagazig Hostpital 1977 (ZH548). Strains Kenya 2006 (Ken06) and Saudi Arabia 2001 (SA01) demonstrated equally high virulence (LD₅₀= 7.9pfu), while recombinant strain South Africa 1951 (rSA51) was less virulent (LD₅₀=150pfu). Following prime-boost vaccination, 100% (10/10) of the Gn+Gc vaccinated mice survived challenge with x1000 LD₅₀ Ken06 and SA01, while only 50% (5/10) of Gn+Gc vaccinated mice survived challenge with rSA51. Additionally, 90% (9/10) of Gn-only vaccinated and 40% (4/10) of Gc-only vaccinated mice survived challenge with Ken06. These data suggest that a Gn-only subunit vaccine is an efficacious alternative to dual glycoprotein vaccine candidates and that our ZH548-derived Gn+Gc vaccine has the potential to cross-protect against divergent RVFV strains. Results from this study can be used to optimize current vaccine formulations and inform future vaccine efficacy and licensure studies in ruminants

Unique deformation mechanisms of an ultra-high strength NiTiHf alloy

Ultra-high strength and energy storage has been observed of a nickel-rich (54-at. %), hafnium-lean (1-at. %), balance titanium alloy. Specifically, full recovery of 4.5% strain upon release of 2.3 GPa uniaxial stress is realized during compressive loading. Furthermore, in cyclic loading, accumulation of permanent set is not observed after the first cycle. Robustness to permanent set is attributed to precipitation of a relatively high volume fraction of fine Ni4Ti3 precipitates, which is the expected result. It was also anticipated that the ability to recover large strains would arise from superelasticity via martensitic transformation. However, in-situ diffraction experimentation revealed a different result. Martensitic (or any other) phase transformation was not observed. Instead, line profile analysis of the diffraction patterns shows the formation of ~25 nm subdomains of B2 structure within the ~5 µm parent grains, accompanied by heterogeneous deformation among similarly orientated diffracting domains. The subdomains fully revert upon unload. In this presentation, the in-situ diffraction characterization of this phenomenal deformation mechanism will be reviewed and conclusions will be supported with in-situ electron microscopy and macroscopic characterization data

Initial mass function variability from the integrated light of diverse stellar systems

We present a uniform analysis of the stellar initial mass function (IMF) from integrated light spectroscopy of 15 compact stellar systems (11 globular clusters in M31 and 4 ultra compact dwarfs in the Virgo cluster, UCDs) and two brightest Coma cluster galaxies (BCGs), covering a wide range of metallicities ($-$1.7 $<$ [Fe/H] $<$ 0.01) and velocity dispersions (7.4 km~s$^{-1}$ $< \sigma <$ 275 km~s$^{-1}$). The S/N $\sim 100$ \AA$^{-1}$ Keck LRIS spectra are fitted over the range 4000<\lambda/\mbox{\AA}<10,000 with flexible, full-spectrum stellar population synthesis models. We use the models to fit simultaneously for ages, metallicities, and individual elemental abundances of the population, allowing us to decouple abundance variations from variations in IMF slope. We show that compact stellar systems do not follow the same trends with physical parameters that have been found for early-type galaxies. Most globular clusters in our sample have an IMF consistent with that of the Milky Way, over a wide range of [Fe/H] and [Mg/Fe]. There is more diversity among the UCDs, with some showing evidence for a bottom-heavy IMF, but with no clear correlation with metallicity, abundance, or velocity dispersion. The two Coma BCGs have similar velocity dispersion and metallicity, but we find the IMF of NGC~4874 is consistent with that of the Milky Way while NGC~4889 presents evidence for a significantly bottom-heavy IMF. For this sample, the IMF appears to vary between objects in a way that is not explained by a single metallicity-dependent prescription.Comment: Accepted for publication in MNRA

Still at Odds with Conventional Galaxy Evolution: The Star Formation History of Ultra-Diffuse Galaxy Dragonfly 44

We study the star formation history (SFH) of the ultra-diffuse galaxy (UDG) Dragonfly 44 (DF44) based on the simultaneous fit to near-ultraviolet to near-infrared photometry and high signal-to-noise optical spectroscopy. In fitting the observations we adopt an advanced physical model with a flexible SFH, and we discuss the results in the context of the degeneracies between stellar population parameters. Through reconstructing the mass-assembly history with a prior for extended star formation (akin to methods in the literature) we find that DF44 formed 90 per cent of its stellar mass by $z\sim 0.9$ ($\sim 7.2$ Gyr ago). In comparison, using a prior that prefers concentrated star formation (as informed by previous studies of DF44's stellar populations) suggests that DF44 formed as early as $z\sim 8$ ($\sim 12.9$ Gyr ago). Regardless of whether DF44 is old or very old, the SFHs imply early star formation and rapid quenching. This result, together with DF44's large size and evidence that it is on its first infall into the Coma cluster, challenges UDG formation scenarios from simulations that treat all UDGs as contiguous with the canonical dwarf population. While our results cannot confirm any particular formation scenario, we can conclude from this that DF44 experienced a rare quenching event.Comment: 25 pages, 15 figures. Accepted for publication in MNRA

The Variation of the Galaxy Luminosity Function with Group Properties

We explore the shape of the galaxy luminosity function (LF) in groups of different mass by creating composite LFs over large numbers of groups. Following previous work using total group luminosity as the mass indicator, here we split our groups by multiplicity and by estimated virial (group halo) mass, and consider red (passive) and blue (star forming) galaxies separately. In addition we utilise two different group catalogues (2PIGG and Yang et al.) in order to ascertain the impact of the specific grouping algorithm and further investigate the environmental effects via variations in the LF with position in groups. Our main results are that LFs show a steepening faint end for early type galaxies as a function of group mass/ multiplicity, with a much suppressed trend (evident only in high mass groups) for late type galaxies. Variations between LFs as a function of group mass are robust irrespective of which grouping catalogue is used, and broadly speaking what method for determining group `mass' is used. We find in particular that there is a significant deficit of low-mass passive galaxies in low multiplicity groups, as seen in high redshift clusters. Further to this, the variation in the LF appears to only occur in the central regions of systems, and in fact seems to be most strongly dependent on the position in the group relative to the virial radius. Finally, distance-rank magnitude relations were considered. Only the Yang groups demonstrated any evidence of a correlation between a galaxy's position relative to the brightest group member and its luminosity. 2PIGG possessed no such gradient, the conclusion being the FOF algorithm suppresses the signal for weak luminosity--position trends and the Yang grouping algorithm naturally enhances it.Comment: 20 pages, 29 figures, accepted for submission to MNRA

Experimental infection of calves by two genetically-distinct strains of rift valley fever virus

Citation: Wilson, W. C., Davis, A. S., Gaudreault, N. N., Faburay, B., Trujillo, J. D., Shivanna, V., . . . Richt, J. A. (2016). Experimental infection of calves by two genetically-distinct strains of rift valley fever virus. Viruses, 8(5). doi:10.3390/v8050145Additional Authors: McVey, D. S.Recent outbreaks of Rift Valley fever in ruminant livestock, characterized by mass abortion and high mortality rates in neonates, have raised international interest in improving vaccine control strategies. Previously, we developed a reliable challenge model for sheep that improves the evaluation of existing and novel vaccines in sheep. This sheep model demonstrated differences in the pathogenesis of Rift Valley fever virus (RVFV) infection between two genetically-distinct wild-type strains of the virus, Saudi Arabia 2001 (SA01) and Kenya 2006 (Ken06). Here, we evaluated the pathogenicity of these two RVFV strains in mixed breed beef calves. There was a transient increase in rectal temperatures with both virus strains, but this clinical sign was less consistent than previously reported with sheep. Three of the five Ken06-infected animals had an early-onset viremia, one day post-infection (dpi), with viremia lasting at least three days. The same number of SA01-infected animals developed viremia at 2 dpi, but it only persisted through 3 dpi in one animal. The average virus titer for the SA01-infected calves was 1.6 logs less than for the Ken06-infected calves. Calves, inoculated with either strain, seroconverted by 5 dpi and showed time-dependent increases in their virus-neutralizing antibody titers. Consistent with the results obtained in the previous sheep study, elevated liver enzyme levels, more severe liver pathology and higher virus titers occurred with the Ken06 strain as compared to the SA01 strain. These results demonstrate the establishment of a virulent challenge model for vaccine evaluation in calves. © 2016 by the authors; licensee MDPI, Basel, Switzerland

State-of-the-Art Sensor Technology in Spain: Invasive and Non-Invasive Techniques for Monitoring Respiratory Variables

The interest in measuring physiological parameters (especially arterial blood gases) has grown progressively in parallel to the development of new technologies. Physiological parameters were first measured invasively and at discrete time points; however, it was clearly desirable to measure them continuously and non-invasively. The development of intensive care units promoted the use of ventilators via oral intubation ventilators via oral intubation and mechanical respiratory variables were progressively studied. Later, the knowledge gained in the hospital was applied to out-of-hospital management. In the present paper we review the invasive and non-invasive techniques for monitoring respiratory variables

Measures of Galaxy Environment - I. What is "Environment"?

The influence of a galaxy's environment on its evolution has been studied and compared extensively in the literature, although differing techniques are often used to define environment. Most methods fall into two broad groups: those that use nearest neighbours to probe the underlying density field and those that use fixed apertures. The differences between the two inhibit a clean comparison between analyses and leave open the possibility that, even with the same data, different properties are actually being measured. In this work we apply twenty published environment definitions to a common mock galaxy catalogue constrained to look like the local Universe. We find that nearest neighbour-based measures best probe the internal densities of high-mass haloes, while at low masses the inter-halo separation dominates and acts to smooth out local density variations. The resulting correlation also shows that nearest neighbour galaxy environment is largely independent of dark matter halo mass. Conversely, aperture-based methods that probe super-halo scales accurately identify high-density regions corresponding to high mass haloes. Both methods show how galaxies in dense environments tend to be redder, with the exception of the largest apertures, but these are the strongest at recovering the background dark matter environment. We also warn against using photometric redshifts to define environment in all but the densest regions. When considering environment there are two regimes: the 'local environment' internal to a halo best measured with nearest neighbour and 'large-scale environment' external to a halo best measured with apertures. This leads to the conclusion that there is no universal environment measure and the most suitable method depends on the scale being probed.Comment: 14 pages, 9 figures, 1 table, published in MNRA

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely