Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

Newsprint coverage of smoking in cars carrying children : a case study of public and scientific opinion driving the policy debate

Acknowledgements Date of Acceptance:17/10/2014 Acknowledgements: This project was funded by Cancer Research UK (MC_U130085862) and the Scottish School of Public Health Research. Cancer Research UK and the Scottish School of Public Health Research was not involved in the collection, analysis, and interpretation of data, writing of the manuscript or the decision to submit the manuscript for publication. Shona Hilton, Karen Wood, Josh Bain and Chris Patterson are funded by the UK Medical Research Council as part of the Understandings and Uses of Public Health Research programme (MC_UU_12017/6) at the MRC/CSO Social and Public Health Sciences Unit, University of Glasgow. We thank Alan Pollock who provided assistance with coding.Peer reviewedPublisher PD

Refining the role of laparoscopy and laparoscopic ultrasound in the staging of presumed pancreatic head and ampullary tumours

Laparoscopy and laparoscopic ultrasound have been validated previously as staging tools for pancreatic cancer. The aim of this study was to identify if assessment of vascular involvement with abdominal computed tomography (CT) would allow refinement of the selection criteria for laparoscopy and laparoscopic ultrasound (LUS). The details of patients staged with LUS and abdominal CT were obtained from the unit's pancreatic cancer database. A CT grade (O, A-F) of vascular involvement was recorded by a single radiologist. Of 152 patients, who underwent a LUS, 56 (37%) had unresectable disease. Three of 26 (12%) patients with CT grade O, 27 of 88 (31%) patients with CT grade A to D, 17 of 29 (59%) patients with CT grade E and all nine patients with CT grade F were found to have unresectable disease. In all, 24% of patients with tumours <3 cm were found to have unresectable disease. In those patients with tumours considered unresectable, local vascular involvement was found in 56% of patients and vascular involvement with metastatic disease in 17%, while 20% of patients had liver metastases alone and 5% had isolated peritoneal metastases. The remaining patient was deemed unfit for resection. Selective use of laparoscopic ultrasound is indicated in the staging of periampullary tumours with CT grades A to D

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

On the Coupling Time of the Heat-Bath Process for the Fortuin–Kasteleyn Random–Cluster Model

We consider the coupling from the past implementation of the random-cluster heat-bath process, and study its random running time, or coupling time. We focus on hypercubic lattices embedded on tori, in dimensions one to three, with cluster fugacity at least one. We make a number of conjectures regarding the asymptotic behaviour of the coupling time, motivated by rigorous results in one dimension and Monte Carlo simulations in dimensions two and three. Amongst our findings, we observe that, for generic parameter values, the distribution of the appropriately standardized coupling time converges to a Gumbel distribution, and that the standard deviation of the coupling time is asymptotic to an explicit universal constant multiple of the relaxation time. Perhaps surprisingly, we observe these results to hold both off criticality, where the coupling time closely mimics the coupon collector's problem, and also at the critical point, provided the cluster fugacity is below the value at which the transition becomes discontinuous. Finally, we consider analogous questions for the single-spin Ising heat-bath process

The effect of weight loss on lameness in obese dogs with osteoarthritis

This paper describes the effect of weight loss on lameness in obese dogs with osteoarthritis (OA). Fourteen obese client-owned dogs with clinical and radiographic signs of OA participated in an open prospective clinical trial. After a screening visit and a visit for collection of baseline data, the dogs were fed a restricted-calorie diet over a study period of 16 weeks that incorporated six follow-up visits. At each visit, body weight and pelvic circumference were measured and severity of lameness was assessed using a numeric rating scale (NRS), a visual analogue scale (VAS) and kinetic gait analysis. This is the first study to assess both subjectively and objectively, the effect of weight loss alone on lameness in obese dogs with OA. The results indicate that body weight reduction causes a significant decrease in lameness from a weight loss of 6.10% onwards. Kinetic gait analysis supported the results from a body weight reduction of 8.85% onwards. These results confirm that weight loss should be presented as an important treatment modality to owners of obese dogs with OA and that noticeable improvement may be seen after modest weight loss in the region of 6.10 – 8.85% body weight

Quantification of Circadian Rhythms in Single Cells

Bioluminescence techniques allow accurate monitoring of the circadian clock in single cells. We have analyzed bioluminescence data of Per gene expression in mouse SCN neurons and fibroblasts. From these data, we extracted parameters such as damping rate and noise intensity using two simple mathematical models, one describing a damped oscillator driven by noise, and one describing a self-sustained noisy oscillator. Both models describe the data well and enabled us to quantitatively characterize both wild-type cells and several mutants. It has been suggested that the circadian clock is self-sustained at the single cell level, but we conclude that present data are not sufficient to determine whether the circadian clock of single SCN neurons and fibroblasts is a damped or a self-sustained oscillator. We show how to settle this question, however, by testing the models' predictions of different phases and amplitudes in response to a periodic entrainment signal (zeitgeber)

Contributions to the Content Analysis of Gender Roles: An Introduction to a Special Issue

This special issue on gender-related content analysis is the second of two parts (see Rudy et al. 2010b). The current special issue is more diverse than was the first in the number of countries that are represented and in the variety of media genres and content types that are included. The primary aim of this paper is to outline some of the contributions of the individual papers in this second special issue. Some of these advancements and innovations include (a) examining underresearched measures, countries, time spans, sexual orientations, and individual media programs; (b) addressing both international and intranational differences in gender-role portrayals; (c) comparing multiple content formats within the same media unit; (d) updating past findings to take into consideration the current media landscape; (e) employing established measures in novel ways and novel contexts; (f) uncovering limitations in established intercultural measures and media-effects theories; (g) suggesting variables that could predict additional differences in gender-role portrayals; (h) adopting virtually identical methods and measures across distinct content categories in order to facilitate comparisons; (i) conducting multiple tests of a given hypothesis; (j) examining, from multiple perspectives, the implications of racial differences in gender portrayals; and (k) examining the implications of underrepresentation of women and the perspectives that women hold. In addition to the original content-analytical research presented in this special issue, two reviews, one methodological and the other analytical, offer recommendations of procedures and perspectives to be implemented in future research

Effects of bursty protein production on the noisy oscillatory properties of downstream pathways

Experiments show that proteins are translated in sharp bursts; similar bursty phenomena have been observed for protein import into compartments. Here we investigate the effect of burstiness in protein expression and import on the stochastic properties of downstream pathways. We consider two identical pathways with equal mean input rates, except in one pathway proteins are input one at a time and in the other proteins are input in bursts. Deterministically the dynamics of these two pathways are indistinguishable. However the stochastic behavior falls in three categories: (i) both pathways display or do not display noise-induced oscillations; (ii) the non-bursty input pathway displays noise-induced oscillations whereas the bursty one does not; (iii) the reverse of (ii). We derive necessary conditions for these three cases to classify systems involving autocatalysis, trimerization and genetic feedback loops. Our results suggest that single cell rhythms can be controlled by regulation of burstiness in protein production