The effect of an internet option and single-sided printing format to increase the response rate to a population-based study : a randomized controlled trial

Acknowledgements We would like to thank the Institute of Applied Health Sciences (IAHS) at the University of Aberdeen for funding the PhD studentship of EF. Furthermore, we would like to thank everyone who was involved in the study, including Professor Sir Lewis Ritchie (Director of Public Health, NHS Grampian), John Lemon (University of Aberdeen), Dr. Fiona Garton (University of Aberdeen) and the Aberdeen Service User Group. Lastly, we would like to acknowledge all data entry clerks (Maxx Livingstone, Rory Macfarlane, Georgia Mannion-Krase and Hazel Reilly) and participants of the study.Peer reviewedPublisher PD

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in three-week-old calves experimentally challenged with BRSV

Bovine respiratory syncytial virus (BRSV) is a widespread cause of lower respiratory tract disease in cattle. Calves less than four months of age are often involved in outbreaks of respiratory disease. We evaluated the efficacy of a single intranasal dose of a bivalent modified live vaccine containing BRSV (Rispoval (R) RS+Pi3 Intranasal, Pfizer Ltd.) in three-week-old calves with and without maternal antibodies to BRSV Two experimental challenge studies were undertaken. In the first study, the time to onset of protection following vaccination was determined in three-week-old colostrum deprived (maternal antibody negative) calves. Calves were challenged at 5, 10 or 21 days after vaccination. Onset of immunity was demonstrated within 5 days after vaccination. After challenge, clinical signs were mostly mild and differences between vaccinated calves and controls were small but the duration of coughing (indicative of upper respiratory tract disease) was significantly shorter in the vaccinates challenged 10 days after vaccination (P = 0.0059) and the duration of hyperpnoea (indicative of lower respiratory tract disease) was significantly shorter in the vaccinates challenged 5 days after vaccination (P = 0.0253). In the second study, the efficacy of the vaccine was assessed in three-week-old calves with maternal antibodies to BRSV Vaccination significantly reduced BRSV nasal shedding after challenge 9 weeks post vaccination and a strong serological booster response was observed in the vaccinated calves following challenge. In addition, clinical signs of respiratory tract disease following challenge were less severe in the vaccinates than the controls with a lower number of mortalities in the vaccinated calves. It is concluded that a single intranasal dose of the bivalent modified live vaccine containing BRSV (Rispoval (R) RS+Pi3 Intranasal, Pfizer Ltd.) provided significant protection against BRSV shedding and disease in young calves both with and without maternal antibodies to BRSV

Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in 3-week-old calves experimentally challenged with BRSV

Two experimental bovine respiratory syncytial virus (BRSV) challenge studies were undertaken to evaluate the efficacy of a single intranasal dose of a bivalent modified live vaccine containing BRSV in 3-week-old calves. In the first study, vaccine efficacy was evaluated in colostrum deprived (maternal antibody negative) calves 5, 10 and 21 days after vaccination. Nasal shedding of BRSV was significantly reduced in vaccinated calves challenged 10 or 21 days after vaccination. Virus excretion titres were also reduced in vaccinates challenged 5 days after vaccination but reduction in duration of shedding and total amount of virus shed were not statistically significant. Clinical disease after challenge in this study was mild. In the second study, vaccine efficacy was assessed in calves with maternal antibodies against BRSV by challenge 66 days post-vaccination. Vaccination significantly reduced nasal shedding after challenge and the severity of clinical disease was also reduce

Neural correlates of noun and verb production

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