Purpose Epstein-Barr virus (EBV) is associated with several cancers in which the tumour cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumour antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses. Experimental Design Sixteen patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma (NPC), received three intradermal vaccinations of MVA-EL at 3-weekly intervals at dose levels between 5×107 and 5×108 plaque forming units (pfu). Blood samples were taken at screening, after each vaccine cycle and during the post-vaccination period. T-cell responses were measured using IFNγ ELISpot assays with overlapping EBNA1/LMP2 peptide mixes or HLA-matched epitope peptides. Polychromatic flow cytometry was used to characterize functionally responsive T-cell populations. Results Vaccination was generally well-tolerated. Immunity increased after vaccination to at least one antigen in 8/14 patients (7/14, EBNA1; 6/14, LMP2), including recognition of epitopes that vary between EBV strains associated with different ethnic groups. Immunophenotypic analysis revealed that vaccination induced differentiation and functional diversification of responsive T-cell populations specific for EBNA1 and LMP2 within the CD4 and CD8 compartments respectively. Conclusions MVA-EL is safe and immunogenic across diverse ethnicities and thus suitable for use in trials against different EBV-positive cancers globally as well as in South East Asia where NPC is most common. The highest dose (5×108 pfu) is recommended for investigation in current phase IB and II trials.

Summary The likelihood of finding evidence of inflammation in 551 tracheal washes collected endoscopically from 278 Thoroughbred racehorses increased with the number of bacterial colony forming units (cfu) per ml of wash (P<0.00l). The aerobic bacteria Streptococcus zooepidemicus, Pasteurella/Actinobacillus‐like species and Streptococcus pneumoniae were significantly associated with lower airway inflammation whereas coagulase‐negative Staphylococcus spp., α‐haemolytic Streptococcus spp., Acinetobacter spp., Bacillus spp., Escherichia coli, Pseudomonas aeruginosa, non‐haemolytic Streptococcus spp. and Enterobacteriaceae were not; Bordetella bronchiseptica was not isolated. Lower airway inflammation was particularly associated with bacteria in horses ≤3 years of age. S. zooepidemicus, S. pneumoniae and Pasteurella/Actinobacillus‐like species were isolated from 167 of 551 washes, either alone or in combination.

Structured risk assessment should guide clinical risk management, but it is uncertain which instrument has the highest predictive accuracy among men and women. In the present study, the authors compared the Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991, 2003); the Historical, Clinical, Risk Management-20 (HCR-20; C. D. Webster, K. S. Douglas, D. Eaves, & S. D. Hart, 1997); the Risk Matrix 2000-Violence (RM2000[V]; D. Thornton et al., 2003); the Violence Risk Appraisal Guide (VRAG; V. L. Quinsey, G. T. Harris, M. E. Rice, & C. A. Cormier, 1998); the Offenders Group Reconviction Scale (OGRS; J. B. Copas & P. Marshall, 1998; R. Taylor, 1999); and the total previous convictions among prisoners, prospectively assessed prerelease. The authors compared predischarge measures with subsequent offending and instruments ranked using multivariate regression. Most instruments demonstrated significant but moderate predictive ability. The OGRS ranked highest for violence among men, and the PCL-R and HCR-20 H subscale ranked highest for violence among women. The OGRS and total previous acquisitive convictions demonstrated greatest accuracy in predicting acquisitive offending among men and women. Actuarial instruments requiring no training to administer performed as well as personality assessment and structured risk assessment and were superior among men for violence.

Summary To investigate whether horses were able to acclimate to conditions of high temperature and humidity, 5 horses of different breeds were trained for 80 min on 15 consecutive days on a treadmill at 30°C and 80% RH. Training consisted of a combination of long duration low‐intensity exercise, medium duration medium intensity exercise and short duration high intensity exercise. Between training sessions the horses were maintained at 11 ± 3°C and 74 ± 2% RH. Before (PRE‐ACC) and after acclimation (POST‐ACC) the horses undertook a simulated Competition Exercise Test (CET), designed to represent the Speed and Endurance Test of a 3‐day event, at 30°C/80% RH. Maximal oxygen uptake (VO2PEAK) was not changed following acclimation (PRE‐ACC 141 ± 8 ml/min/kg bwt vs. POST‐ACC 145 ± 9 ml/min/kg bwt [STPD], P>0.05). Following acclimation, 4 of the 5 horses were able to complete a significantly greater amount of Phase D in the CET (PRE‐ACC 6.3 ± 0.3 min vs. POST‐ACC 7.3 ± 0.3 min, P<0.05; target time = 8 min). Resting body temperatures (pulmonary artery [TPA], rectal [TREC] and tail‐skin [TTSK] temperatures) were all significantly lower following acclimation. During exercise, metabolic heat production (M) and heat dissipation (HD), for the same exercise duration, were both significantly lower following acclimation (P<0.05), although heat storage (HS) was significantly higher (P<0.05). The higher heat storage following acclimation was associated with a lower TTSK for a given TPA and a decreased total fluid loss (% bodyweight, P<0.05). Plasma volume was not changed following acclimation. The relationship of sweating rate (SR) to TPA or TTSK on either the neck or the gluteal region was not significantly altered by acclimation, although the onset of sweating occurred at a lower TPA or TTSK following acclimation (P<0.05). The horses in the present study showed a number of physiological adaptations to a period of 15 days of exposure to high heat and humidity consistent with a humid heat acclimation response. These changes were mostly similar to those reported to occur in man and other species and were consistent with thermal acclimation and an increased thermotolerance, leading to an improved exercise tolerance. It is concluded that a 15 day period of acclimation is beneficial for horses from cooler and or drier climates, that have to compete in hot humid conditions and that this may redress, to some extent, the decrement in exercise tolerance seen in nonacclimated horses and reduce the risk of heat related disorders, such as heat exhaustion.