Delivering effective science communication: advice from a professional science communicator.

Science communication is becoming ever more prevalent, with more and more scientists expected to not only communicate their research to a wider public, but to do so in an innovative and engaging manner. Given the other commitments that researchers and academics are required to fulfil as part of their workload models, it is unfair to be expect them to also instantly produce effective science communication events and activities. However, by thinking carefully about what it is that needs to be communicated, and why this is being done, it is possible to develop high-quality activities that are of benefit to both the audience and the communicator(s). In this paper, I present some practical advice for developing, delivering and evaluating effective science communication initiatives, based on over a decade of experience as being a professional science communicator. I provide advice regarding event logistics, suggestions on how to successfully market and advertise your science communication initiatives, and recommendations for establishing effective branding and legacy.

Science communication in the field of fundamental biomedical research (editorial).

The aim of this special issue on science communication is to inspire and help scientists who are taking part or want to take part in science communication and engage with the wider public, clinicians, other scientists or policy makers. For this, some articles provide concise and accessible advice to individual scientists, science networks, or learned societies on how to communicate effectively; others share rationales, objectives and aims, experiences, implementation strategies and resources derived from existing long-term science communication initiatives. Although this issue is primarily addressing scientists working in the field of biomedical research, much of it similarly applies to scientists from other disciplines. Furthermore, we hope that this issue will also be used as a helpful resource by academic science communicators and social scientists, as a collection that highlights some of the major communication challenges that the biomedical sciences face, and which provides interesting case studies of initiatives that use a breadth of strategies to address these challenges. In this editorial, we first discuss why we should communicate our science and contemplate some of the different approaches, aspirations and definitions of science communication. We then address the specific challenges that researchers in the biomedical sciences are faced with when engaging with wider audiences. Finally, we explain the rationales and contents of the different articles in this issue and the various science communication initiatives and strategies discussed in each of them, whilst also providing some information on the wide range of further science communication activities in the biomedical sciences that could not all be covered here.

Polyvalent Diazonium Polymers Provide Efficient Protection of Oncolytic Adenovirus Enadenotucirev from Neutralizing Antibodies while Maintaining Biological Activity In Vitro and In Vivo.

Oncolytic viruses offer many advantages for cancer therapy when administered directly to confined solid tumors. However, the systemic delivery of these viruses is problematic because of the host immune response, undesired interactions with blood components, and inherent targeting to the liver. Efficacy of systemically administered viruses has been improved by masking viral surface proteins with polymeric materials resulting in modulation of viral pharmacokinetic profile and accumulation in tumors in vivo. Here we describe a new class of polyvalent reactive polymer based on poly( N-(2-hydroxypropyl)methacrylamide) (polyHPMA) with diazonium reactive groups and their application in the modification of the chimeric group B oncolytic virus enadenotucirev (EnAd). A series of six copolymers with different chain lengths and density of reactive groups was synthesized and used to coat EnAd. Polymer coating was found to be extremely efficient with concentrations as low as 1 mg/mL resulting in complete (>99%) ablation of neutralizing antibody binding. Coating efficiency was found to be dependent on both chain length and reactive group density. Coated viruses were found to have reduced transfection activity both in vitro and in vivo, with greater protection against neutralizing antibodies resulting in lower transgene production. However, in the presence of neutralizing antibodies, some in vivo transgene expression was maintained for coated virus compared to the uncoated control. The decrease in transgene expression was found not to be solely due to lower cellular uptake but due to reduced unpackaging of the virus within the cells and reduced replication, indicating that the polymer coating does not cause permanent inactivation of the virus. These data suggest that virus activity may be modulated by the appropriate design of coating polymers while retaining protection against neutralizing antibodies.

Developing Reflective Thinking through Poetry Writing: Views from Students and Educators.

Aims and Objectives To explore student nurse and educator perspectives on the use of poetry writing as a way to reflect on important nursing practice issues. Background Reflective practice is a well-established method of learning in pre-registration nurse education although student nurses can find reflection a challenging process. Design An exploratory descriptive approach. Methods Data were extracted from unstructured interviews with students and educators (n = 12) from one university in the North-West region of England, United Kingdom (UK). Data were thematically analysed. Results Poetry writing supports a meaningful exploration of events, which have the potential to lead to changes in perspective. Careful planning of the poetry writing process is required, to ensure the potential of this approach is realised. Conclusion Poetry writing is an effective way to reflect on clinical practice. This work has relevance and transferability to a wide range of professional disciplines, where reflective practice is encouraged.

Actin-resistant DNAse I Expression From Oncolytic Adenovirus Enadenotucirev Enhances Its Intratumoral Spread and Reduces Tumor Growth.

Spread of oncolytic viruses through tumor tissue is essential to effective virotherapy. Interstitial matrix is thought to be a significant barrier to virus particle convection between "islands" of tumor cells. One way to address this is to encode matrix-degrading enzymes within oncolytic viruses, for secretion from infected cells. To test the hypothesis that extracellular DNA provides an important barrier, we assessed the ability of DNase to promote virus spread. Nonreplicating Ad5 vectors expressing actin-resistant DNase (aDNAse I), proteinase K (PK), hyaluronidase (rhPH20), and chondroitinase ABC (CABC) were injected into established DLD human colorectal adenocarcinoma xenografts, transcomplemented with a replicating Ad5 virus. Each enzyme improved oncolysis by the replicating adenovirus, with no evidence of tumor cells being shed into the bloodstream. aDNAse I and rhPH20 hyaluronidase were then cloned into conditionally-replicating group B adenovirus, Enadenotucirev (EnAd). EnAd encoding each enzyme showed significantly better antitumor efficacy than the parental virus, with the aDNAse I-expressing virus showing improved spread. Both DNase and hyaluronidase activity was still measurable 32 days postinfection. This is the first time that extracellular DNA has been implicated as a barrier for interstitial virus spread, and suggests that oncolytic viruses expressing aDNAse I may be promising candidates for clinical translation.

Rehearsing empathy: exploring the role of poetry in supporting learning.

Empathy is an important aspect of therapeutic relationships in health and social care settings. Health educators can foster empathy development in learners through creative writing activities. Drawing on the humanities, specifically poetry, this paper offers strategies for educators to support empathy development in learners, with a focus on service user poetry and associated creative writing activities. We discuss how poetry can enable alternative perspectives about care to emerge thereby challenging previously held assumptions about mental and physical states. Using poetry can enable a rehearsal of empathy by bringing experiences to the learner in a safe and facilitated environment. Through creative writing activities, we believe that students can learn to better understand and empathise with others, as well as explore their own feelings and experiences related to caregiving, to support self-care.

Evidence that digital game players neglect age classification systems when deciding which games to play.

This article considers players' experiences seeking out new games to play, and their use of the Australian National Classification Scheme in doing so. The global video game industry is booming, with hundreds of games being released each month across numerous platforms. As a result, players have an unprecedented number of games available when choosing what games to purchase. However, a number of confounding issues around the emergent content of games and the subjective nature of game reviewing makes it difficult to relate what kinds of experiences a given game will facilitate. In this study, we surveyed game players in order to find their game platform and acquisition preferences; strategies and experiences when choosing games; and attitudes towards classification systems. Our findings suggest that players find it difficult to choose what games to purchase, and that existing classification systems are mostly only beneficial when choosing games for minors.

Preclinical Safety Studies of Enadenotucirev, a Chimeric Group B Human-Specific Oncolytic Adenovirus.

Enadenotucirev is an oncolytic group B adenovirus identified by a process of bio-selection for the ability to selectively propagate in and rapidly kill carcinoma cells. It is resistant to inactivation by human blood components, potentially enabling intravenous dosing in patients with metastatic cancer. However, there are no known permissive animal models described for group B adenoviruses that could facilitate a conventional approach to preclinical safety studies. In this manuscript, we describe our tailored preclinical strategy designed to evaluate the key biological properties of enadenotucirev. As enadenotucirev does not replicate in animal cells, a panel of primary human cells was used to evaluate enadenotucirev replication selectivity in vitro, demonstrating that virus genome levels were >100-fold lower in normal cells relative to tumor cells. Acute intravenous tolerability in mice was used to assess virus particle-mediated toxicology and effects on innate immunity. These studies showed that particle toxicity could be ameliorated by dose fractionation, using an initial dose of virus to condition the host such that cytokine responses to subsequent doses were significantly attenuated. This, in turn, supported the initiation of a phase I intravenous clinical trial with a starting dose of 1 × 1010 virus particles given on days 1, 3, and 5.

Development of a versatile oncolytic virus platform for local intra-tumoural expression of therapeutic transgenes.

Oncolytic viruses which infect and kill tumour cells can also be genetically modified to express therapeutic genes that augment their anti-cancer activities. Modifying oncolytic viruses to produce effective cancer therapies is challenging as encoding transgenes often attenuates virus activity or prevents systemic delivery in patients due to the risk of off-target expression of transgenes in healthy tissues. To overcome these issues we aimed to generate a readily modifiable virus platform using the oncolytic adenovirus, enadenotucirev. Enadenotucirev replicates in human tumour cells but not cells from healthy tissues and can be delivered intravenously because it is stable in human blood. Here, the enadenotucirev genome was used to generate plasmids into which synthesised transgene cassettes could be directly cloned in a single step reaction. The platform enabled generation of panels of reporter viruses to identify cloning sites and transgene cassette designs where transgene expression could be linked to the virus life cycle. It was demonstrated using these viruses that encoded transgene proteins could be successfully expressed in tumour cells in vitro and tumours in vivo. The expression of transgenes did not impact either the oncolytic activity or selective properties of the virus. The effectiveness of this approach as a drug delivery platform for complex therapeutics was demonstrated by inserting multiple genes in the virus genome to encode full length anti-VEGF antibodies. Functional antibody could be synthesised and secreted from infected tumour cells without impacting the activity of the virus particle in terms of oncolytic potency, manufacturing yields or selectivity for tumour cells. In vivo, viral particles could be efficaciously delivered intravenously to disseminated orthotopic tumours.

Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators.

Enadenotucirev (EnAd) is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent. The EnAd death pathway does not involve p53, is predominantly caspase independent, and appears to involve a rapid fall in cellular ATP. Infected cells show early loss of membrane integrity; increased exposure of calreticulin; extracellular release of ATP, HSP70, and HMGB1; and influx of calcium. The virus also causes an obvious single membrane blister reminiscent of ischemic cell death by oncosis. In human tumor biopsies maintained in ex vivo culture, EnAd mediated release of pro-inflammatory mediators such as TNF-α, IL-6, and HMGB1. In accordance with this, EnAd-infected tumor cells showed potent stimulation of dendritic cells and CD4+ T cells in a mixed tumor-leukocyte reaction in vitro. Whereas many viruses have evolved for efficient propagation with minimal inflammation, bioselection of EnAd for rapid killing has yielded a virus with a short life cycle that combines potent cytotoxicity with a proinflammatory mechanism of cell death.

Are scientific abstracts written in poetic verse an effective representation of the underlying research?

The central purpose of science is to explain. However, who is that explanation for, and how is this explanation communicated once it has been deduced? Scientific research is typically communicated via papers in journals, with an abstract presented as a summary of that explanation. However, in many instances they may be written in a manner which is non-communicatory to a lay reader. This study begins to investigate if poetry could be used as an alternative form of communication, by first assessing if poetic verse is an effective form of communication to other scientists. In order to assess this suitability, a survey was conducted in which two different groups of participants were asked questions based on a scientific abstract. One group of participants was given the original scientific abstract, whilst the second group was instead given a poem written about the scientific study. Quantitative analysis found that whilst a scientific audience found a poetic interpretation of a scientific abstract to be no less interesting or inspiring than the original prose, they did find it to be less accessible. However, further qualitative analysis suggested that the poem did a good job in conveying a similar meaning to that presented in the original abstract. The results of this study indicate that whilst for a scientific audience poetry should not replace the prose abstract, it could be used alongside the original format to inspire the reader to find out more about the topic. Further research is needed to investigate the effectiveness of this approach for a general audience.

Aiming for long-term, objective-driven science communication in the UK.

Communicating science to wider lay audiences is of increasing importance and is becoming an ever larger part of a scientist's remit which also offers important opportunities. We discuss here the current state of science communication in the field of the natural sciences in the UK, and the enormous improvements that could be achieved through putting more weight on objective-driven long-term initiatives, ideally in the form of interdisciplinary networks, to achieve higher impact. We describe the barriers that stand in the way of such developments and make a number of suggestions how funding organisations in particular could play a major role in overcoming these barriers.

What does the UK public want from academic science communication?

The overall aim of public academic science communication is to engage a non-scientist with a particular field of science and/or research topic, often driven by the expertise of the academic. An e-survey was designed to provide insight into respondent's current and future engagement with science communication activities. Respondents provided a wide range of ideas and concerns as to the 'common practice' of academic science communication, and whilst they support some of these popular approaches (such as open-door events and science festivals), there are alternatives that may enable wider engagement. Suggestions of internet-based approaches and digital media were strongly encouraged, and although respondents found merits in methods such as science festivals, limitations such as geography, time and topic of interest were a barrier to engagement for some. Academics and scientists need to think carefully about how they plan their science communication activities and carry out evaluations, including considering the point of view of the public, as although defaulting to hands-on open door events at their university may seem like the expected standard, it may not be the best way to reach the intended audience.

What's in a Name? Exploring the Nomenclature of Science Communication in the UK.

This study, via a consideration of the literature, and a survey of science communicators, presents concise and workable definitions for science outreach, public engagement, widening participation, and knowledge exchange, in a UK context.   Sixty-six per cent of participants agreed that their definitions of outreach, public engagement, and widening participation aligned with those of their colleagues, whilst 64% felt that their personal definitions matched those of their institute. However, closer inspection of the open-ended questions found the respondents often differed in the use of the nomenclature. In particular, the respondents found it difficult to define knowledge exchange in this context.

Tropism ablation and stealthing of oncolytic adenovirus enhances systemic delivery to tumors and improves virotherapy of cancer.

Intravenous delivery of therapeutic virus particles remains a major goal for virotherapy of metastatic cancer. Avoiding phagocytic capture and unwanted infection of nontarget cells is essential for extended plasma particle kinetics, and simply ablating one or the other does not give extended plasma circulation. Here we show that polymer coating of adenovirus type 5 (Ad5) can combine with predosing strategies or Kupffer cell ablation to achieve systemic kinetics with a half-life >60 min, allowing ready access to peripheral tumors. Accumulation of virus particles within tumor nodules is proportional to the area under the plasma concentration/time curve. Polymer coating wild-type Ad5 in this way is known to decrease hepatic toxicity, increasing the dose of virus particles that can be safely administered. Using polymer-coating technology to deliver a replicating Ad5 systemically, virus replication and transgene expression was almost totally confined to tumor tissues, giving a much improved therapeutic index compared with uncoated virus, and complete control of human HepG2 tumor xenografts.

Tumour necrosis factor-alpha increases extravasation of virus particles into tumour tissue by activating the Rho A/Rho kinase pathway.

Tumour Necrosis Factor alpha (TNF) is a pleiotropic pro-inflammatory cytokine with known vascular permeabilising activity. It is employed during isolated limb perfusion to enhance delivery of chemotherapeutic drugs into tumour tissue. The use of conditionally-replicating lytic viruses, so called 'oncolytic virotherapy', provides a new approach to cancer treatment that is currently limited by the low efficiency of extravasation of viral particles into tumours. We report here evidence that TNF significantly enhances the delivery of virus particles through the endothelial layer to allow access to tumour cells both in vitro and in vivo. Intravenous administration of TNF resulted in a 3- to 6-fold increase in EL4 tumour uptake of Evans Blue/Albumin, adenovirus and long-circulating polymer coated adenovirus. Interestingly, endothelial permeabilisation could be suppressed in vitro and in vivo by Y-27632, a Rho kinase inhibitor, without inhibiting viral infection. These data indicate that TNF can enhance the delivery of virus particles into tumours through a Rho A/Rho kinase dependent mechanism and may be a valuable strategy for increasing the delivery of oncolytic viruses and other therapeutic agents.