Cross-reactivity of murine and recently human CD8 + T cells between different viral peptides, i.e., heterologous immunity, has been well characterized. However, the directionality and quality of these cross-reactions is critical in determining their biological importance. Herein we analyzed the response of human CD8 + T cells that recognize both a hepatitis C virus peptide (HCV-NS3) and a peptide derived from the influenza neuraminidase protein (Flu-NA). To detect the cross-reactive CD8 + T cells, we used peptide-MHC class I complexes (pMHCs) containing a new mutant form of MHC class I able to bind CD8 more strongly than normal MHC class I complexes. T cell responses against HCV-NS3 and Flu-NA peptide were undetectable in normal donors. In contrast, some responses against the Flu-NA peptide were identified in HCV + donors who showed strong HCV-NS3-specific reactivity. The Flu-NA peptide was a weak agonist for CD8 + T cells in HCV + individuals on the basis of novel pMHCs and functional assays. These data support the idea of cross-reactivity between the 2 peptides, but indicate that reactivity toward the Flu-NA peptide is highly CD8-dependent and occurs predominantly after priming during HCV infection. Our findings indicate the utility of the novel pMHCs in dissecting cross-reactivity and suggest that cross-reactivity between HCV and influenza is relatively weak. Further studies are needed to relate affinity and functionality of cross-reactive T cells.

No abstract

A total of 5,179 high-risk heifer calves were used to define the potential benefits of delaying the on-arrival respiratory viral vaccine (Pyramid® 5, Boehringer Ingelheim Vetmedica, Inc., St. Joseph, M0] for 30 d with and without the addition of a DNA immunostimulant (Zelnate® DNA Immunostimulant, Bayer Animal Health, Shawnee Mission, KS) at feedlot entry on health, performance, and carcass characteristics. The products were evaluated in a 2 x 2 factorial, randomized complete-block design comparing the following: delayed vaccine (DP), on-arrival vaccine (AP), delayed vaccine plus immunostimulant (DPZ), and on-arrival vaccine plus immunostimulant (APZ) amongst 60 total pens of heifers (15 pens/treatment). Pen-level linear mixed models, including a random effect for allocation block (source), were used for all statistical analyses. There was no P x Z interaction (P > 0.35) for any outcome. At 60 DOF, reimplant (116 d), and close-out, delaying the viral vaccine decreased (P < 0.05) the percent of calves treated twice for bovine respiratory disease (BRD). The inclusion of immunostimulant reduced (P <0.05) BRD mortality and overall mortality at both 60 and 116 DOF. Additionally, the reduction (P = 0.04) in overall mortality and the tendency to lessen BRD mortality (P = 0.06) was maintained through close-out for cattle administered the immunostimulant. No differences in final gain performance, dry matter intake or feed conversion were observed among treatments. There was a tendency for heifers to have heavier finished body weights (P = 0.08) and HCW (P = 0.07) when vaccinated on arrival. No differences in carcass quality or yield grade categories were evident. In conclusion, delaying the viral vaccine and including the immunostimulant both appeared to improve cattle health by significantly reducing BRD retreatment risk and overall mortality, respectively.

Background In-situ simulation is increasingly employed in healthcare settings to support learning and improve patient, staff and organisational outcomes. It can help participants to problem solve within real, dynamic and familiar clinical settings, develop effective multidisciplinary team working and facilitates learning into practice. There is nevertheless a reported lack of a standardised and cohesive approach across healthcare organisations. The aim of this systematic mapping review was to explore and map the current evidence base for in-situ interventions, identify gaps in the literature and inform future research and evaluation questions. Methods A systematic mapping review of published in-situ simulation literature was conducted. Searches were conducted on MEDLINE, EMBASE, AMED, PsycINFO, CINAHL, MIDIRS and ProQuest databases to identify all relevant literature from inception to October 2020. Relevant papers were retrieved, reviewed and extracted data were organised into broad themes. Results Sixty-nine papers were included in the mapping review. In-situ simulation is used 1) as an assessment tool; 2) to assess and promote system readiness and safety cultures; 3) to improve clinical skills and patient outcomes; 4) to improve non-technical skills (NTS), knowledge and confidence. Most studies included were observational and assessed individual, team or departmental performance against clinical standards. There was considerable variation in assessment methods, length of study and the frequency of interventions. Conclusions This mapping highlights various in-situ simulation approaches designed to address a range of objectives in healthcare settings; most studies report in-situ simulation to be feasible and beneficial in addressing various learning and improvement objectives. There is a lack of consensus for implementing and evaluating in-situ simulation and further studies are required to identify potential benefits and impacts on patient outcomes. In-situ simulation studies need to include detailed demographic and contextual data to consider transferability across care settings and teams and to assess possible confounding factors. Valid and reliable data collection tools should be developed to capture the complexity of team and individual performance in real settings. Research should focus on identifying the optimal frequency and length of in-situ simulations to improve outcomes and maximize participant experience.

A total of 2,528 lightweight heifers were used to compare 2 viral-bacterial respiratory vaccine products containing modified-live infectious bovine rhinotracheitis virus, parainfluenza-3 virus, bovine respiratory syncytial virus, bovine viral diarrhea virus types 1 and 2, and a Mannheimia haemolytica bacterial component, on performance, health, and carcass characteristics of cattle in a commercial feedlot setting. The vaccine products compared were Pyramid? 5+Presponse? SQ (PYR PSQ) and Bovi-Shield GOLD? One Shot (BOV ONE). No differences (P?0.68) in gain performance or feed conversion were observed between treatments. Hot-carcass weight tended to be less (P=0.06) in cattle administered PYR PSQ compared to cattle in the BOV ONE treatment group. Percentages of "no roll" and Yield Grade 4 carcasses were higher (P?0.04) for BOV ONE cattle, while the percentage of Yield Grade 1 carcasses was higher (P=0.05) in the PYR PSQ treatment. Neither BRD first treatment morbidity nor retreatment risks were significantly different among treatments (P?0.33), with 13.25% of all cattle receiving treatment for BRD. The incidence of chronics, case fatalities, and mortalities associated with BRD also did not differ (P?0.46) between treatments. Furthermore, the incidence of chronics and mortalities due to all causes did not differ (P?0.62) between treatments. There was little evidence to suggest that administration of these different combination vaccines to lightweight auction-market heifers upon arrival at the feedlot results in important health differences.