BackgroundThis study was concerned with developing the evidence base for public involvement in research in health and social care. There now is significant support for public involvement within the National Institute for Health Research, and researchers applying for National Institute for Health Research grants are expected to involve the public. Despite this policy commitment, evidence for the benefits of public involvement in research remains limited. This study addressed this need through a realist evaluation.Aim and objectivesThe aim was to identify the contextual factors and mechanisms that are regularly associated with effective public involvement in research. The objectives included identifying a sample of eight research projects and their desired outcomes of public involvement, tracking the impact of public involvement in these case studies, and comparing the associated contextual factors and mechanisms.DesignThe research design was based on the application of realist theory of evaluation, which argues that social programmes are driven by an underlying vision of change – a ‘programme theory’ of how the intervention is supposed to work. The role of the evaluator is to compare theory and practice. Impact can be understood by identifying regularities of context, mechanism and outcome. Thus the key question for the evaluator is ‘What works for whom in what circumstances . . . and why?’ (Pawson R.The Science of Evaluation. London: Sage; 2013). We therefore planned a realist evaluation based on qualitative case studies of public involvement in research.Setting and participantsEight diverse case studies of research projects in health and social care took place over the calendar year 2012 with 88 interviews from 42 participants across the eight studies: researchers, research managers, third-sector partners and research partners (members of the public involved in research).ResultsCase study data supported the importance of some aspects of our theory of public involvement in research and led us to amend other elements. Public involvement was associated with improvements in research design and delivery, particularly recruitment strategies and materials, and data collection tools. This study identified the previously unrecognised importance of principal investigator leadership as a key contextual factor leading to the impact of public involvement; alternatively, public involvement might still be effective without principal investigator leadership where there is a wider culture of involvement. In terms of the mechanisms of involvement, allocating staff time to facilitate involvement appeared more important than formal budgeting. Another important new finding was that many research proposals significantly undercosted public involvement. Nurturing good interpersonal relationships was crucial to effective involvement. Payment for research partner time and formal training appeared more significant for some types of public involvement than others. Feedback to research partners on the value of their contribution was important in maintaining motivation and confidence.ConclusionsA revised theory of public involvement in research was developed and tested, which identifies key regularities of context, mechanism and outcome in how public involvement in research works. Implications for future research include the need to further explore how leadership on public involvement might be facilitated, methodological work on assessing impact and the development of economic analysis of involvement.Funding detailsThe National Institute for Health Research Health Service and Delivery programme.

Phage integrase genes often play a role in the establishment of lysogeny in temperate phage by catalyzing the integration of the phage into one of the host's replicons. To investigate temperate phage gene expression, an induced viral metagenome from Tampa Bay was sequenced by 454/Pyrosequencing. The sequencing yielded 294,068 reads with 6.6% identifiable. One hundred-three sequences had significant similarity to integrases by BLASTX analysis (e≤0.001). Four sequences with strongest amino-acid level similarity to integrases were selected and real-time PCR primers and probes were designed. Initial testing with microbial fraction DNA from Tampa Bay revealed 1.9×107, and 1300 gene copies of Vibrio-like integrase and Oceanicola-like integrase L−1 respectively. The other two integrases were not detected. The integrase assay was then tested on microbial fraction RNA extracted from 200 ml of Tampa Bay water sampled biweekly over a 12 month time series. Vibrio-like integrase gene expression was detected in three samples, with estimated copy numbers of 2.4-1280 L−1. Clostridium-like integrase gene expression was detected in 6 samples, with estimated copy numbers of 37 to 265 L−1. In all cases, detection of integrase gene expression corresponded to the occurrence of lysogeny as detected by prophage induction. Investigation of the environmental distribution of the two expressed integrases in the Global Ocean Survey Database found the Vibrio-like integrase was present in genome equivalents of 3.14% of microbial libraries and all four viral metagenomes. There were two similar genes in the library from British Columbia and one similar gene was detected in both the Gulf of Mexico and Sargasso Sea libraries. In contrast, in the Arctic library eleven similar genes were observed. The Clostridium-like integrase was less prevalent, being found in 0.58% of the microbial and none of the viral libraries. These results underscore the value of metagenomic data in discovering signature genes that play important roles in the environment through their expression, as demonstrated by integrases in lysogeny.

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Lysogeny has been documented as a fundamental process occurring in natural marine communities of heterotrophic and autotrophic bacteria. Prophage induction has been observed to be prevalent during conditions of low host abundance, but factors controlling the process are poorly understood. A research cruise was undertaken to the Gulf of Mexico during July 2005 to explore environmental factors associated with lysogeny. Ambient physical and microbial parameters were measured and prophage induction experiments were performed in contrasting oligotrophic Gulf and eutrophic Mississippi plume areas. Three of 11 prophage induction experiments in heterotrophic bacteria (27%) demonstrated significant induction in response to Mitomycin C. In contrast, there was significant Synechococcus cyanophage induction in seven of nine experiments (77.8%). A strong negative correlation was observed between lysogeny and log-transformed activity measurements for both heterotrophic and autotrophic populations (r ¼ À0.876, P ¼ 0.002 and r ¼ À0.815, P ¼ 0.025, respectively), indicating that bacterioplankton with low host growth favor lysogeny. Multivariate statistical analyses indicated that ambient level of viral abundance and productivity were inversely related to heterotrophic prophage induction and both factors combined were most predictive of lysogeny (q ¼ 0.899, P ¼ 0.001). For Synechococcus, low ambient cyanophage abundance was most predictive of lysogeny (q ¼ 0.862, P ¼ 0.005). Abundance and productivity of heterotrophic bacteria was strongly inversely correlated with salinity, while Synechococcus was not. This indicated that heterotrophic bacterial populations were well adapted to the river plume environments, thus providing a possible explanation for differences in prevalence of lysogeny observed between the two populations.

The genome for the marine pseudotemperate member of the Siphoviridae HSIC has been sequenced using a combination of linker amplification library construction, restriction digest library construction, and primer walking. HSIC enters into a pseudolysogenic relationship with its host, Listonella pelagia, characterized by sigmoidal growth curves producing >10 9 cells/ml and >10 11 phage/ml. The genome (37,966 bp; G؉C content, 44%) contained 47 putative open reading frames (ORFs), 17 of which had significant BLASTP hits in GenBank, including a ␤ subunit of DNA polymerase III, a helicase, a helicase-like subunit of a resolvasome complex, a terminase, a tail tape measure protein, several phage-like structural proteins, and 1 ORF that may assist in host pathogenicity (an ADP ribosyltransferase). The genome was circularly permuted, with no physical ends detected by sequencing or restriction enzyme digestion analysis, and lacked a cos site. This evidence is consistent with a headful packaging mechanism similar to that of Salmonella phage P22 and Shigella phage Sf6. Because none of the phage-like ORFs were closely related to any existing phage sequences in GenBank (i.e., none more than 62% identical and most <25% identical at the amino acid level), HSIC is unique among phages that have been sequenced to date. These results further emphasize the need to sequence phages from the marine environment, perhaps the largest reservoir of untapped genetic information.

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While co‐infections are common in both wild and cultured fish, knowledge of the interactive effects of multiple pathogens on host physiology, gene expression and immune response is limited. To evaluate the impact of co‐infection on host survival, physiology and gene expression, sockeye salmon Oncorhynchus nerka smolts were infected with the salmon louse Lepeophtheirus salmonis (V−/SL+), infectious hematopoietic necrosis virus (IHNV; V+/SL−), both (V+/SL+), or neither (V−/SL−). Survival in the V+/SL+ group was significantly lower than the V−/SL− and V−/SL+ groups (p = 0.024). Co‐infected salmon had elevated osmoregulatory indicators and lowered haematocrit values as compared to the uninfected control. Expression of 12 genes associated with the host immune response was analysed in anterior kidney and skin. The only evidence of L. salmonis‐induced modulation of the host antiviral response was down‐regulation of mhc I although the possibility of modulation cannot be ruled out for mx‐1 and rsad2. Co‐infection did not influence the expression of genes associated with the host response to L. salmonis. Therefore, we conclude that the reduced survival in co‐infected sockeye salmon resulted from the osmoregulatory consequences of the sea lice infections which were amplified due to infection with IHNV.