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Abstract Background Accelerated partial breast irradiation (APBI) is an accepted treatment option for early breast cancer. Treatment delivered on the Magnetic Resonance integrated Linear Accelerator (MRL) provides the added assurance of improved soft tissue visibility, important in the delivery of APBI. This technique can be delivered in both the supine and prone positions, however current literature suggests that prone treatment on the MRL is infeasible due to physical limitations with bore size. This study aims to investigate the feasibility of positioning patients on a custom designed prone breast board compared with supine positioning on a personalised vacuum bag. Geometric distortion, the relative position of Organs at Risk (OAR) to the tumour bed and breathing motion (intrafraction motion) will be compared between the supine and prone positions. The study will also investigate the positional impact on dosimetry, patient experience, and position preference. Methods Up to 30 patients will be recruited over a 12-month period for participation in this Human Research Ethics Committee approved exploratory cohort study. Patients will be scanned on the magnetic resonance imaging (MRI) Simulator in both the supine and prone positions as per current standard of care for APBI simulation. Supine and prone positioning comparisons will all be assessed on de-identified MRI image pairs, acquired using appropriate software. Patient experience will be explored through completion of a short, anonymous electronic survey. Descriptive statistics will be used for reporting of results with categorical, parametric/non-parametric tests applied (data format dependent). Survey results will be interpreted by comparison of percentage frequencies across the Likert scales. Thematic content analysis will be used to interpret qualitative data from the open-ended survey questions. Discussion The results of this study will be used to assess the feasibility of treating patients with APBI in the prone position on a custom designed board on the MRL. It may also be used to assist with identification of patients who would benefit from this position over supine without the need to perform both scans. Patient experience and technical considerations will be utilised to develop a tool to assist in this process. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN1262400067583. Registered 28th of May 2024. https://www.anzctr.org.au/ACTRN12624000679583.aspx

Abstract Background Some modifiable risk factors for cancer originate during adolescence. While there is evidence indicating relationships between adverse childhood experiences and health risk behaviours generally, little is known about how childhood adversity influences the engagement of adolescents in cancer risk behaviours. This study aimed to determine the relationship between adverse childhood experiences and adolescent cancer risk behaviours. Methods Data were collected prospectively from birth to age 18 years on children born to mothers enrolled into the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort study. Multivariable linear regression models assessed relationships of a composite exposure measure comprised of adverse childhood experiences (total number of childhood adversities experienced from early infancy until age 9 years) with multiple cancer risk behaviours. The latter was expressed as a single continuous score for tobacco smoking, alcohol consumption, obesity, unsafe sex, and physical inactivity, at ages 11, 14, 16 and 18 years. Analysis was carried out on the complete case and imputation samples of 1,368 and 7,358 participants respectively. Results All adolescent cancer risk behaviours increased in prevalence as the adolescents grew older, except for obesity. Each additional adverse childhood experience was associated with a 0.25 unit increase in adolescent cancer risk behaviour (95% CI 0.16–0.34; p

Background and purposeThis study aimed to investigate the feasibility of safe-dose escalation to dominant intraprostatic lesions (DILs) and assess the clinical impact using dose-volume (DV) and biological metrics in photon and proton therapy. Biological parameters defined as late grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) derived from planned (DP) and accumulated dose (DA) were utilized.Materials and methodsIn total, 10 patients with high-risk prostate cancer with multiparametric MRI-defined DILs were investigated. Each patient had two plans with a focal boost to the DILs using intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT). Plans were optimized to obtain DIL coverage while respecting the mandatory organ-at-risk constraints. For the planning evaluation, DV metrics, tumor control probability (TCP) for the DILs and whole prostate excluding the DILs (prostate-DILs), and normal tissue complication probability (NTCP) for the rectum and bladder were calculated. Wilcoxon signed-rank test was used for analyzing TCP and NTCP data.ResultsIMPT achieved a higher Dmean for the DILs compared to VMAT (IMPT: 68.1 GyRBE vs. VMAT: 66.6 Gy, p < 0.05). Intermediate–high rectal and bladder doses were lower for IMPT (p < 0.05), while the high-dose region (V60 Gy) remained comparable. IMPT-TCP for prostate-DIL were higher compared to VMAT (IMPT: 86%; α/β = 3, 94.3%; α/β = 1.5 vs. VMAT: 84.7%; α/β = 3, 93.9%; α/β = 1.5, p < 0.05). Likewise, IMPT obtained a moderately higher DIL TCP (IMPT: 97%; α/β = 3, 99.3%; α/β = 1.5 vs. VMAT: 95.9%; α/β = 3, 98.9%; α/β = 1.5, p < 0.05). Rectal DA-NTCP displayed the highest GI toxicity risk at 5.6%, and IMPT has a lower GI toxicity risk compared to VMAT-predicted Quantec-NTCP (p < 0.05). Bladder DP-NTCP projected a higher GU toxicity than DA-NTCP, with VMAT having the highest risk (p < 0.05).ConclusionDose escalation using IMPT is able to achieve a high TCP for the DILs, with the lowest rectal and bladder DV doses at the intermediate–high-dose range. The reduction in physical dose was translated into a lower NTCP (p < 0.05) for the bladder, although rectal toxicity remained equivalent.

Introduction/backgroundCourse evaluation in health education is a common practice yet few comprehensive evaluations of health education exist that measure the impact and outcomes these programs have on developing health graduate capabilities.Aim/objectivesTo explore how curricula contribute to health graduate capabilities and what factors contribute to the development of these capabilities.MethodsUsing contribution analysis evaluation, a six-step iterative process, key stakeholders in the six selected courses were engaged in an iterative theory-driven evaluation. The researchers collectively developed a postulated theory-of-change. Then evidence from existing relevant documents were extracted using documentary analysis. Collated findings were presented to academic staff, industry representatives and graduates, where additional data was sought through focus group discussions - one for each discipline. The focus group data were used to validate the theory-of-change. Data analysis was conducted iteratively, refining the theory of change from one course to the next.ResultsThe complexity in teaching and learning, contributed by human, organizational and curriculum factors was highlighted. Advances in knowledge, skills, attitudes and graduate capabilities are non-linear and integrated into curriculum. Work integrated learning significantly contributes to knowledge consolidation and forming professional identities for health professional courses. Workplace culture and educators’ passion impact on the quality of teaching and learning yet are rarely considered as evidence of impact.DiscussionCapturing the episodic and contextual learning moments is important to describe success and for reflection for improvement. Evidence of impact of elements of courses on future graduate capabilities was limited with the focus of evaluation data on satisfaction.ConclusionContribution analysis has been a useful evaluation method to explore the complexity of the factors in learning and teaching that influence graduate capabilities in health-related courses.

Creating meaningful assessment for advanced radiation therapy practice training programs is a challenge. This is because it requires a balance of formative and summative assessments, which meet the academic and professional needs of the practitioner, as well as the requirements of local service delivery, educational and professional standards. This paper discusses educational strategies and models used to integrate assessment into theoretical and clinical curricula, allowing practitioners to demonstrate higher order cognitive knowledge, advanced level clinical performance and attitudes/values associated with advanced practice. The discussion draws upon concepts of constructive alignment and programmatic approaches to assessment, which use Bloom’s taxonomy, Benner’s beginner to competent model of skill development, and Miller’s pyramid of clinical competence. These models are analysed with respect to an advanced practice program in adaptive radiation therapy to provide context.

Introduction: Traditionally radiation therapy planning was taught on campus in planning labs, or in the case of fully online programs, during clinical placements. In 2017, an innovative online planning curriculum was developed using a structured, self-directed approach of online learning and assessment, supported by a cloud-based planning system. This study aimed to explore student experiences of learning and practising planning online, and the application of acquired knowledge and skills to clinical practice. Methods: Student experiences were investigated using an interpretive phenomenological method. A purposive sample of under-graduate and graduate entry students was recruited through email and snowballing. A combination of online individual and group interviews were conducted. Two researchers analysed the data, and used reflection, discussion and note taking processes to immerse themselves in the data. Following data collection, the process of organising data for analysis, applying a coding and condensing process to reduce the data into themes and sub-themes was conducted. Results: Seventeen students from three cohorts participated in the interviews. Five key themes were identified: Flexibility, Connectedness, Personal relevance, Professional Experts and Safe environment. Sub-component themes were also identified. Discussion: Student engagement was based on a range of factors that influence the student experience. The planning curriculum allowed students to develop confidence and competence in pre-clinical planning skills prior to placement. Conclusion: Although initial experiences were overwhelming, over time students experienced a sense of engagement with their learning when supported by clinical and academic experts. Students felt more prepared for clinical placement as a result of their experiences.

Introduction: Clear, timely communication between practitioners and patients is key in ensuring equitable access to health services and optimal care. Australia’s linguistically diverse population adds complexity to healthcare provision. This paper describes a validation study to assess clinical suitability of a language translation device, intended for use with Mandarin speaking patients undergoing radiotherapy (RT). Materials and methods: After a comprehensive device selection process, common phrases used in RT practice were curated within one clinical center and translated by interpreters. Phrases were categorized by conversation type and readability (according to Flesch-Kincaid and FORCAST scores). Validation of device performance was undertaken by purposely selected radiation therapists (RTTs) who tested and evaluated the device using a survey with 5-point Likert scale responses. Statistical analysis was undertaken on Excel using Pearson’s chi-square, z-test, interrater reliability/agreement and linear regression analyses. Results: Six RTTs and two interpreters volunteered to participate in this study. 188 common phrases were spoken verbatim into the device and scored on a 5-point Likert scale, yielding an overall output accuracy of 66%. A z-test confirmed significance against prior comparative research and Linear regression analysis observed improved output between consecutive participants. 62.7% of interpreter scores were identical; a further 29.1% constituted a single point scoring variation. Poorer outcomes were observed with colloquial English and lower readability. Conclusions: This study found the device produced suitable translation accuracy and identified language styles that should be avoided with use. Further research could consider clinical application, expanded languages and/or health disciplines, and development of a national RTT phrase list.

Background and purpose: Significant dose deviations have been reported between planned (DP) and accumulated (DA) dose in prostate radiotherapy. This study aimed to develop multivariate analysis (MVA) models associating Grade 1 and 2 gastrointestinal (GI) toxicity with clinical and DP or DA dosimetric variables separately. Materials and methods: Dose volume (DV) metrics were compared between DA and DP for 150 high-risk prostate cancer patients. MV models were generated from significant clinical and dosimetric variables (p

Background and purpose: Significant deviations between bladder dose planned (DP) and dose accumulated (DA) have been reported in patients receiving radiotherapy for prostate cancer. This study aimed to construct multivariate analysis (MVA) models to predict the risk of late genitourinary (GU) toxicity with clinical and DP or DA as dose-volume (DV) variables. Materials and methods: Bladder DA obtained from 150 patients were compared with DP. MVA models were built from significant clinical and DV variables (p 0.6. Prostate volume (OR: 0.87, p: 0.01) was significant in predicting Grade 2 GU toxicity with a high AUC of 0.81. Conclusions: Higher DA (V30-65 Gy) received by the bladder were not translated to higher late GU toxicity. DB-ROIs demonstrated higher predictive power than standard DV metrics in associating Grade ≥ 1 toxicity. Smaller prostate volumes have a minor protective effect on late Grade 2 GU toxicity.

Background and purposeNormal tissue complication probability (NTCP) parameters derived from traditional 3D plans may not be ideal in defining toxicity outcomes for modern radiotherapy techniques. This study aimed to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively scored clinical data for late gastrointestinal (GI) and genitourinary (GU) toxicities for high-risk prostate cancer patients treated using volumetric-modulated-arc-therapy (VMAT). Dose-volume-histograms (DVH) extracted from planned (DP) and accumulated dose (DA) were used.Material and methodsDP and DA obtained from the DVH of 150 prostate cancer patients with pelvic-lymph-nodes irradiation treated using VMAT were used to generate LKB-NTCP parameters using maximum likelihood estimations. Defined GI and GU toxicities were recorded up to 3-years post RT follow-up. Model performance was measured using Hosmer-Lemeshow goodness of fit test and the mean area under the receiver operating characteristics curve (AUC). Bootstrapping method was used for internal validation.ResultsFor mild-severe (Grade ≥1) GI toxicity, the model generated similar parameters based on DA and DP DVH data (DA-D50:71.6 Gy vs DP-D50:73.4; DA-m:0.17 vs DP-m:0.19 and DA/P-n 0.04). The 95% CI for DA-D50 was narrower and achieved an AUC of >0.6. For moderate-severe (Grade ≥2) GI toxicity, DA-D50 parameter was higher and had a narrower 95% CI (DA-D50:77.9 Gy, 95% CI:76.4-79.6 Gy vs DP-D50:74.6, 95% CI:69.1-85.4 Gy) with good model performance (AUC>0.7). For Grade ≥1 late GU toxicity, D50 and n parameters for DA and DP were similar (DA-D50: 58.8 Gy vs DP-D50: 59.5 Gy; DA-n: 0.21 vs DP-n: 0.19) with a low AUC of0.6.ConclusionsThe achieved NTCP parameters using modern RT techniques and accounting for organ motion differs from QUANTEC reported parameters. DA-D50 of 77.9 Gy for GI and DA/DP-D50 of 81.7-81.9 Gy for GU demonstrated good predictability in determining the risk of Grade ≥2 toxicities especially for GI derived D50 and are recommended to incorporate as part of the DV planning constraints to guide dose escalation strategies while minimising the risk of toxicity.

Abstract Background Adolescent multiple risk behaviour (MRB) is associated with negative outcomes such as police arrests, unemployment and premature mortality and morbidity. What is unknown is whether MRB is associated with socioeconomic status (SES) in adulthood. We test whether adolescent MRB is associated with socioeconomic status (SES) in young adulthood and whether it is moderated by early life SES variables. Methods Prospective cohort studies; British Cohort Study 1970 (BCS70) and Avon Longitudinal Study of Parents and Children (ALSPAC), born in 1991–1992, were used and two comparable MRB variables were derived. Logistic regression was used to determine the association between MRB and young adult SES. The moderating effect of three early life SES variables was assessed using logistic regression models with and without interaction parameters. Evidence to support the presence of moderation was determined by likelihood ratio tests ≤p = 0.05. Multiple imputation was used to account for missing data. Results Adolescents had a median of two risk behaviours in BCS70 and three in ALSPAC. Adolescent MRB was negatively associated with young adult SES (university degree attainment) in BCS70 (OR 0.81, 95% CI: 0.76, 0.86) and ALSPAC (OR 0.85, 95% CI: 0.82, 0.88). There was a dose response relationship, with each additional risk behaviour resulting in reduced odds of university degree attainment. MRB was associated occupational status at age 34 in BCS70 (OR 0.86 95% CI: 0.82, 0.90). In BCS70, there was evidence that maternal education (p = 0.03), parental occupational status (p = 0.009) and household income (p = 0.03) moderated the effect of adolescent MRB on young adult SES in that the negative effect of MRB is stronger for those with low socioeconomic backgrounds. No evidence of moderation was found in the ALSPAC cohort. Conclusions Adolescence appears to be a critical time in the life course to address risk behaviours, due to the likelihood that behaviours established here may have effects in adulthood. Intervening on adolescent MRB could improve later SES outcomes and thus affect health outcomes later in life. Evidence for a moderation effect in the BCS70 but not ALSPAC suggests that more detailed measures should be investigated to capture the nuance of contemporary young adult SES.

Background This study examined whether exposure to misinformation found on Twitter about e-cigarette harms leads to inaccurate knowledge and misperceptions of harms of e-cigarette use among cigarette smokers. Methods We conducted an online randomized controlled experiment in November 2019 among an online sample of 2400 adult US and UK cigarette smokers who did not currently use e-cigarettes. Participants viewed four tweets in one of four conditions: 1) e-cigarettes are as or more harmful than smoking, 2) e-cigarettes are completely harmless, 3) e-cigarette harms are uncertain and 4) control (physical activity). Outcomes were knowledge about e-cigarettes and harm perceptions of e-cigarette use for five diseases. We conducted multiple logistic and linear regressions to analyze the effect of experimental conditions on outcomes, controlling for baseline knowledge and perceived harms. Findings Participants in the ‘as or more harmful’ condition (vs. control group) had higher odds of accurate knowledge about e-cigarettes containing toxic chemicals ( p

Abstract An automated dose accumulation and contour propagation workflow using daily cone beam computed tomography (CBCTs) images for prostate cases that require pelvic lymph nodes irradiation (PLNs) was developed. This workflow was constructed using MIM® software with the intention to provide accurate dose transformations for plans with two different isocentres, whereby two sequential treatment phases were prescribed. The pre‐processing steps for data extractions from treatment plans, CBCTs, determination of couch shift information and management of missing CBCTs are described. To ensure that the imported translational couch shifts were in the correct orientation and readable in MIM, phantom commissioning was performed. For dose transformation, rigid registration with corrected setup shifts and scaled fractional dose was performed for pCT to daily CBCTs, which were then deformed onto CBCT1. Fractional dose summation resulted in the final accumulated dose for the patient allowing differences in dosimetry between the planned and accumulated dose to be analysed. Contour propagations of the prostate, bladder and rectum were performed within the same workflow. Transformed contours were then deformed onto daily CBCTs to generate trending reports for analysis, including Dice Similarity Coefficient (DSC) and Mean Distance to Agreement (MDA). Results obtained from phantom commissioning (DSC = 0.96, MDA = 0.89 mm) and geometrical analysis of the propagated contours for twenty patients; prostate (DSC: 0.9 ± 0.0, MDA: 1.0 ± 0.3 mm), rectum (DSC: 0.8 ± 0.1, mm, MDA: 1.7 ± 0.6 mm) and bladder (DSC: 0.8 ± 0.1, MDA: 2.8 ± 1.0 mm) were within clinically accepted tolerances for both DSC (>0.8) and MDA (< 0.3 mm). The developed workflow is being performed on a larger patient cohort for predictive model building, with the goal of correlating observed toxicity with the actual accumulated dose received by the patient.

Non-coding regions of viral RNA (vRNA) genomes are critically important in the regulation of gene expression. In particular, pseudoknot (PK) structures, which are present in a wide range of RNA molecules, have a variety of roles. The 5' untranslated region (5' UTR) of foot-and-mouth disease virus (FMDV) vRNA is considerably longer than in other viruses from the picornavirus family and consists of a number of distinctive structural motifs that includes multiple (2, 3 or 4 depending on the virus strain) putative PKs linked in tandem. The role(s) of the PKs in the FMDV infection are not fully understood. Here, using bioinformatics, sub-genomic replicons and recombinant viruses we have investigated the structural conservation and importance of the PKs in the FMDV lifecycle. Our results show that despite the conservation of two or more PKs across all FMDVs, a replicon lacking PKs was replication competent, albeit at reduced levels. Furthermore, in competition experiments, GFP FMDV replicons with less than two (0 or 1) PK structures were outcompeted by a mCherry FMDV wt replicon that had 4 PKs, whereas GFP replicons with 2 or 4 PKs were not. This apparent replicative advantage offered by the additional PKs correlates with the maintenance of at least two PKs in the genomes of FMDV field isolates. Despite a replicon lacking any PKs retaining the ability to replicate, viruses completely lacking PK were not viable and at least one PK was essential for recovery of infections virus, suggesting a role for the PKs in virion assembly. Thus, our study points to roles for the PKs in both vRNA replication and virion assembly, thereby improving understanding the molecular biology of FMDV replication and the wider roles of PK in RNA functions.

Abstract Background An estimated 40% of cancer cases in the UK in 2015 were attributable to cancer risk behaviours. Tobacco smoking, alcohol consumption, obesity, and unprotected sexual intercourse are known causes of cancer and there is strong evidence that physical inactivity is associated with cancer. These cancer risk behaviours co-occur however little is known about how they pattern longitudinally across adolescence and early adulthood. Using data from ALSPAC, a prospective population-based UK birth cohort study, we explored patterns of adolescent cancer risk behaviours and their associations with cancer risk behaviours in early adulthood. Methods Six thousand three hundred fifty-one people (46.0% of ALSPAC participants) provided data on all cancer risk behaviours at one time during adolescence, 1951 provided data on all cancer risk behaviours at all time points. Our exposure measure was quartiles of a continuous score summarising cumulative exposure to cancer risk behaviours and longitudinal latent classes summarising distinct categories of adolescents exhibiting similar patterns of behaviours, between age 11 and 18 years. Using both exposure measures, odds of harmful drinking (Alcohol Use Disorders Identification Test-C ≥ 8),daily tobacco smoking, nicotine dependence (Fagerström test ≥4), obesity (BMI ≥30), high waist circumference (females: ≥80 cm and males: ≥94 cm, and high waist-hip ratio (females: ≥0.85 and males: ≥1.00) at age 24 were estimated using logistic regression analysis. Results We found distinct groups of adolescents characterised by consistently high and consistently low engagement in cancer risk behaviours. After adjustment, adolescents in the top quartile had greater odds of all outcomes in early adulthood: nicotine dependency (odds ratio, OR = 5.37, 95% confidence interval, CI = 3.64–7.93); daily smoking (OR = 5.10, 95% CI =3.19–8.17); obesity (OR = 4.84, 95% CI = 3.33–7.03); high waist circumference (OR = 2.48, 95% CI = 1.94–3.16); harmful drinking (OR = 2.04, 95% CI = 1.57–2.65); and high waist-hip ratio (OR = 1.88, 95% CI = 1.30–2.71), compared to the bottom quartile. In latent class analysis, adolescents characterised by consistently high-risk behaviours throughout adolescence were at higher risk of all cancer risk behaviours at age 24, except harmful drinking. Conclusions Exposure to adolescent cancer risk behaviours greatly increased the odds of cancer risk behaviours in early adulthood. Interventions to reduce these behaviours should target multiple rather than single risk behaviours and should focus on adolescence.

Abstract Background Radiation therapy to upper abdominal sites is technically challenging due to motion of tumors and surrounding organs resulting from normal respiration. Breath-hold, using an Active Breathing Coordinator is one strategy used to reduce motion in these tumor sites. Though widely used, no studies have prospectively compared the different breath-hold techniques (inspiration, deep-inspiration and expiration) using ABC in the same patient cohort. Methods Patients planned for radiation therapy to upper abdominal tumors are invited to participate in this prospective study. Participants attempt three breath hold techniques: inspiration, deep-inspiration and expiration breath-hold, in random order. kV fluoroscopy images of the dome of diaphragm are taken of five consecutive breath-holds in each technique. Reproducibility and stability of tumour position are measured, and used to select the technique with which to proceed to planning and treatment. Reproducibility at planning and each treatment fraction is measured, along with breath hold time, treatment efficiency and patient experience. Discussion The screening method was validated after the first three participants. This screening process may be able to select the best breath-hold technique for an individual, which may lead to improved reproducibility. The screening process is being piloted as a prospective clinical trial. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): 12618001691235. Registered 12th October 2018. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376109&isReview=true .

Abstract Background Experimentation with new behaviours during adolescence is normal. However, engagement in two or more risk behaviours, termed multiple risk behaviours is associated with socioeconomic disadvantage and poor health and social outcomes. Evidence of how adolescents cluster based on their risk behaviours is mixed. Methods Latent Class Analysis was used to study patterns of engagement in 10 self-reported risk behaviours (including substance use, self-harm and sexual health) from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort at ages 15–16 years. Data was available for 6556 adolescents. Associations between risk profile and sex were explored. Results A 3-class model for both females and males was deemed to have acceptable fit. Whilst we found evidence of a sex difference in the risk behaviours reported within each class, the sex-specific results were very similar in many respects. For instance, the prevalence of membership of the high-risk class was 8.5% for males and 8.7% for females and both groups had an average of 5.9 behaviours. However, the classes were both statistically dubious, with class separation (entropy) being poor as well as conceptually problematic, because the resulting classes did not provide distinct profiles and varied only by quantity of risk-behaviours. Conclusion Clusters of adolescents were not characterised by distinct risk behaviour profiles, and provide no additional insight for intervention strategies. Given this is a more complicated, software-specific method, we conclude that an equally effective, but more readily replicable approach is to use a count of the number of risk behaviours.

BackgroundInformation and misinformation on the internet about e-cigarette harms may increase smokers’ misperceptions of e-cigarettes. There is limited research on smokers’ engagement with information and misinformation about e-cigarettes on social media. ObjectiveThis study assessed smokers’ likelihood to engage with—defined as replying, retweeting, liking, and sharing—tweets that contain information and misinformation and uncertainty about the harms of e-cigarettes. MethodsWe conducted a web-based randomized controlled trial among 2400 UK and US adult smokers who did not vape in the past 30 days. Participants were randomly assigned to view four tweets in one of four conditions: (1) e-cigarettes are as harmful or more harmful than smoking, (2) e-cigarettes are completely harmless, (3) uncertainty about e-cigarette harms, or (4) control (physical activity). The outcome measure was participants’ likelihood of engaging with tweets, which comprised the sum of whether they would reply, retweet, like, and share each tweet. We fitted Poisson regression models to predict the likelihood of engagement with tweets among 974 Twitter users and 1287 non-Twitter social media users, adjusting for covariates and stratified by UK and US participants. ResultsAmong Twitter users, participants were more likely to engage with tweets in condition 1 (e-cigarettes are as harmful or more harmful than smoking) than in condition 2 (e-cigarettes are completely harmless). Among other social media users, participants were more likely to likely to engage with tweets in condition 1 than in conditions 2 and 3 (e-cigarettes are completely harmless and uncertainty about e-cigarette harms). ConclusionsTweets stating information and misinformation that e-cigarettes were as harmful or more harmful than smoking regular cigarettes may receive higher engagement than tweets indicating e-cigarettes were completely harmless. Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN) 16082420; https://doi.org/10.1186/ISRCTN16082420

Abstract The Australian radiotherapy profession is challenged by job dissatisfaction, stress, burnout and unfavourable attrition. This paper will use psychological models to discuss the confluence of job demands, resources and personal characteristics that contribute to these challenges. Factors contributing to burnout and attrition amongst Australian Radiation Therapists will be explored, and a number of leadership strategies will be introduced to improve workplace culture. These strategies – aligned with positive psychology – seek to address staff engagement, emotional needs, and job stressors.

Abstract Background Surgeons use the Internet and social media to provide health information, promote their clinical practice, network with clinicians and researchers, and engage with journal clubs and online campaigns. While surgical patients are increasingly Internet-literate, the prevalence and purpose of searching for online health information vary among patient populations. We aimed to characterise patient and colorectal surgeon (CRS) use of the Internet and social media to seek health information. Methods Members of the Colorectal Society of Australia and New Zealand and patients under the care of CRS at the Royal Prince Alfred Hospital, Sydney, were surveyed. Questions pertained to the types of information sought from the Internet, the platforms used to seek it, and the perceived utility of this information. Results Most CRS spent 2–6 h per week using the Internet for clinical purposes and an additional 2–6 h per week for research. 79% preferred literature databases as an information source. CRS most commonly directed patients to professional healthcare body websites. 59% of CRS use social media, mainly for socialising or networking. Nine percent of surgeons spent > 1 h per week on social media for clinical or research purposes. 72% of surgeons have a surgical practice website. 43% of patients searched the Internet for information on their doctor, and 75% of patients sought information on their symptoms or condition. However, 25% used health-specific websites, and 14% used professional healthcare body websites. Around 84% of patients found the information helpful, and 8% found it difficult to find information on the Internet. 12% of patients used social media to seek health information. Conclusions Colorectal surgery patients commonly find health information on the Internet but social media is not a prominent source of health information for patients or CRS.

Background Chronic cough is a distressing symptom for many people with pulmonary sarcoidosis. Continuous treatment with a macrolide antibiotic may improve cough. We aimed to assess the potential efficacy of azithromycin in patients with sarcoidosis and self-reported cough. Methods We conducted a noncontrolled, open-label clinical trial of azithromycin 250 mg once daily for 3 months in patients with pulmonary sarcoidosis who reported a chronic cough. The primary outcome was number of coughs in 24 h. Secondary outcomes were cough visual analogue scales and quality of life measured using the Leicester Cough Questionnaire and King's Sarcoidosis Questionnaire. Safety outcomes included QTc interval on ECG. Measurements were made at baseline and after 1 and 3 months of treatment. Results All 21 patients were white, median age 57 years, 9 males, 12 females, median 3 years since diagnosis. Five were taking oral corticosteroids and none were taking other immunosuppressants. Twenty patients completed the trial. The median (range) number of coughs in 24 h was 228 (43–1950) at baseline, 122 (20–704) at 1 month, and 81 (16–414) at 3 months (p=0.002, Friedman's test). The median reduction in cough count at 3 months was 49.6%. There were improvements in all patient-reported outcomes. Azithromycin was well tolerated. Conclusion In a noncontrolled open-label trial in people with sarcoidosis who reported a chronic cough, 3 months of treatment with azithromycin led to improvements in a range of cough metrics. Azithromycin should be tested as a treatment for sarcoidosis cough in a randomised placebo-controlled trial.

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease that causes breathlessness and cough that worsen over time, limiting daily activities and negatively impacting quality of life. Although treatments are now available that slow the rate of lung function decline, trials of these treatments have failed to show improvement in symptoms or quality of life. There is an immediate unmet need for evidenced-based interventions that improve patients' symptom burden and make a difference to everyday living. This study aims to assess the feasibility of conducting a definitive randomised controlled trial of a holistic, complex breathlessness intervention in people with IPF. Methods and analysis The trial is a two-centre, randomised controlled feasibility trial of a complex breathlessness intervention compared with usual care in patients with IPF. 50 participants will be recruited from secondary care IPF clinics and randomised 1:1 to either start the intervention within 1 week of randomisation (fast-track group) or to receive usual care for 8 weeks before receiving the intervention (wait-list group). Participants will remain in the study for a total of 16 weeks. Outcome measures will be feasibility outcomes, including recruitment, retention, acceptability and fidelity of the intervention. Clinical outcomes will be measured to inform outcome selection and sample size calculation for a definitive trial. Ethics and dissemination Yorkshire and The Humber – Bradford Leeds Research Ethics Committee approved the study protocol (REC 18/YH/0147). Results of the main trial and all secondary end-points will be submitted for publication in a peer-reviewed journal.

The RNA genomes of picornaviruses are translated into single polyproteins which are subsequently cleaved into structural and non-structural protein products. For genetic economy, proteins and processing intermediates have evolved to perform distinct functions. The picornavirus precursor protein, P3, is cleaved to produce membrane-associated 3A, primer peptide 3B, protease 3Cpro and polymerase 3Dpol. Uniquely, foot-and-mouth disease virus (FMDV) encodes three similar copies of 3B (3B1-3), thus providing a convenient natural system to explore the role(s) of 3B in the processing cascade. Using a replicon system, we confirmed by genetic deletion or functional inactivation that each copy of 3B appears to function independently to prime FMDV RNA replication. However, we also show that deletion of 3B3 prevents replication and that this could be reversed by introducing mutations at the C-terminus of 3B2 that restored the natural sequence at the 3B3-3C cleavage site. In vitro translation studies showed that precursors with 3B3 deleted were rapidly cleaved to produce 3CD but that no polymerase, 3Dpol, was detected. Complementation assays, using distinguishable replicons bearing different inactivating mutations, showed that replicons with mutations within 3Dpol could be recovered by 3Dpol derived from "helper" replicons (incorporating inactivation mutations in all three copies of 3B). However, complementation was not observed when the natural 3B-3C cleavage site was altered in the "helper" replicon, again suggesting that a processing abnormality at this position prevented the production of 3Dpol. When mutations affecting polyprotein processing were introduced into an infectious clone, viable viruses were recovered but these had acquired compensatory mutations in the 3B-3C cleavage site. These mutations were shown to restore the wild-type processing characteristics when analysed in an in vitro processing assay. Overall, this study demonstrates a dual functional role of the small primer peptide 3B3, further highlighting how picornaviruses increase genetic economy.

The accumulation of mutations in RNA viruses is thought to facilitate rapid adaptation to changes in the environment. However, most mutations have deleterious effects on fitness, especially for viruses. Thus, tolerance to mutations should determine the nature and extent of genetic diversity that can be maintained in the population. Here, we combine population genetics theory, computer simulation, and experimental evolution to examine the advantages and disadvantages of tolerance to mutations, also known as mutational robustness. We find that mutational robustness increases neutral diversity and, as expected, can facilitate adaptation to a new environment. Surprisingly, under certain conditions, robustness may also be an impediment for viral adaptation, if a highly diverse population contains a large proportion of previously neutral mutations that are deleterious in the new environment. These findings may inform therapeutic strategies that cause extinction of otherwise robust viral populations.