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IntroductionFear of cancer recurrence (FCR) is a common condition among cancer survivors that can lead to significant levels of distress, anxiety and depression. Online mindfulness programmes may provide the mechanism to support cancer survivors manage FCR and distress, and improve people’s well-being over the short, medium and long term. The primary aim of this study is to determine the potential efficacy of MindOnLine, a 9 session mindfulness-based programme for survivors of breast, prostate and colorectal cancer. A formal economic programme will also be conducted.Methods and analysisA single-blind randomised controlled trial to determine the efficacy and cost-efficacy of a MindOnLine programme for cancer survivors. A total of 400 people living with cancer will be recruited via online advertisements on social media platforms, peak consumer advocacy groups or through outpatient services at healthcare providers across Victoria, Australia. People will be randomly allocated to either the MindOnLine programme (n=200) or waitlist control (n=200). Participant assessments will occur at baseline, at 9 weeks and 9-month follow-up. The primary outcome is change in Fear of Recurrence Index Score total score between baseline and 9 weeks; secondary outcomes are changes in depression and anxiety, quality of life and mindfulness. The economic analysis comprises a cost-consequences analysis where all outcomes will be compared with costs.Ethics and disseminationEthics approval was obtained from the Peter MacCallum Cancer Centre (20-53) and Deakin University (2020-284). All participants will be required to provide written informed consent. Findings will be disseminated in peer reviewed journals and among key stakeholder organisations including hospitals, cancer and community organisations and Government. If suc

INTRODUCTION: Fear of cancer recurrence (FCR) is a common condition among cancer survivors that can lead to significant levels of distress, anxiety and depression. Online mindfulness programmes may provide the mechanism to support cancer survivors manage FCR and distress, and improve people's well-being over the short, medium and long term. The primary aim of this study is to determine the potential efficacy of MindOnLine, a 9 session mindfulness-based programme for survivors of breast, prostate and colorectal cancer. A formal economic programme will also be conducted. METHODS AND ANALYSIS: A single-blind randomised controlled trial to determine the efficacy and cost-efficacy of a MindOnLine programme for cancer survivors. A total of 400 people living with cancer will be recruited via online advertisements on social media platforms, peak consumer advocacy groups or through outpatient services at healthcare providers across Victoria, Australia. People will be randomly allocated to either the MindOnLine programme (n=200) or waitlist control (n=200). Participant assessments will occur at baseline, at 9 weeks and 9-month follow-up. The primary outcome is change in Fear of Recurrence Index Score total score between baseline and 9 weeks; secondary outcomes are changes in depression and anxiety, quality of life and mindfulness. The economic analysis comprises a cost-consequences analysis where all outcomes will be compared with costs. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Peter MacCallum Cancer Centre (20-53) and Deakin University (2020-284). All participants will be required to provide written informed consent. Findings will be disseminated in peer reviewed journals and among key stakeholder organisations including hospitals, cancer and community organisations and Government. If successful the project will be rolled out nationally with a formal implementation plan. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (126200

Background: Estimating the parameters that describe the ecology of viruses,particularly those that are novel, can be made possible using metagenomic approaches. However, the best-performing existing methods require databases to first estimate an average genome length of a viral community before being able to estimate other parameters, such as viral richness. Although this approach has been widely used, it can adversely skew results since the majority of viruses are yet to be catalogued in databases. Results: In this paper, we present ENVirT, a method for estimating the richness of novel viral mixtures, and for the first time we also show that it is possible to simultaneously estimate the average genome length without a priori information. This is shown to be a significant improvement over database-dependent methods, since we can now robustly analyze samples that may include novel viral types under-represented in current databases. We demonstrate that the viral richness estimates produced by ENVirT are several orders of magnitude higher in accuracy than the estimates produced by existing methods named PHACCS and CatchAll when benchmarked against simulated data. We repeated the analysis of 20 metavirome samples using ENVirT, which produced results in close agreement with complementary in virto analyses. Conclusions: These insights were previously not captured by existing computational methods. As such, ENVirT is shown to be an essential tool for enhancing our understanding of novel viral populations.

Background/Aims: Stress myocardial perfusion imaging (MPI) has established superior sensitivity and specificity to exercise ECG in diagnosing myocardial ischaemia. However, the impact of chest pain or ECG changes during MPI remains unclear. This study aimed to define the relationship between chest pain or ischaemic ECG changes during MPI and the amount of myocardial ischaemia. Method(s): 161 consecutive patients with no cardiac history who presented with chest pain for investigation and underwent exercise stress MPI between July 2014 and March 2015 were analysed retrospectively. The presence of chest pain or ischaemic ECG changes (1 mm or more of ST depression) during the study, as well as the subsequent diagnosis of no, mild, moderate or severe ischaemia was recorded, using visual semiquantitative scoring. Quantitation was by consensus from two experienced readers, blinded to all other information. Result(s): Chest pain during exercise stress testing was significantly associated with severe ischaemia, defined as summed difference score (SDS) > 8 (OR = 14.6, 95%CI = (1.3,169.2), P < 0.05). Whilst a trend was seen for an association between chest pain and moderate ischaemia (SDS = 5- 8) (OR = 3.5, 95%CI = (0.3,39.8), p = 0.34), it is only for severe ischaemia that this association was significant. No association was seen between chest pain and either mild ischaemia (SDS = 2-4), or no ischaemia (SDS < 2) (OR = 0.4, 95%CI = (0.05,2.9), p = 0.47 for mild ischaemia). Conversely, ischaemic ECG changes during exercise stress testing were not associated with severe, moderate, mild or no ischaemia (OR = 4.2, 95%CI = (0.7,26.1), p = 0.13 for severe ischaemia). Conclusion(s): Chest pain occurring during exercise is significantly correlated with ischaemia on MPI, but only when severe, while ischaemic ECG changes during exercise are not. This may assist in the diagnosis of prognostically significant coronary artery disease.

AIM: Precision oncology involves molecularly matching patients to targeted agents usually in early drug development (EDD) programs. Molecular profiling (MP) identifies actionable targets. Comprehensive commercial MP platforms are costly and in resource limited environments, a more practical approach to MP is necessary to support EDD and precision oncology. We adopted a clinician-directed, tailored approach to MP to enrol patients onto molecularly targeted trials. We report the feasibility of this approach. METHODS: All patients referred to the Royal Melbourne Hospital (RMH) EDD between September 2013 and September 2015 were identified in a prospective database. Key captured data included clinicopathological data, MP platform ordered (if any), molecular targets identified and subsequent enrolment onto clinical trials. EDD-clinician decisions to order MP and the platform utilized was guided by patient consultation, tumor type, trial availability and requirement for molecular information. RESULTS: We identified 377 patients referred to RMH EDD. A total of 216 (57%) had MP ordered. The remainder had known actionable targets (19%), or were inappropriate for clinical trials (24%). In those undergoing MP, 187 genetic aberrations were found in 113 patients with 98 considered actionable targets in 86 patients. Ninety-eight (25%) patients were enrolled onto a clinical trial, including 40 (11%) receiving molecularly matched treatments. Median progression-free survival was improved in patients enrolled onto molecularly matched trials compared to those on unmatched trials (3.6 months vs 1.9 months, HR 0.58 [0.38-0.89], P = 0.013). CONCLUSION: A clinician-directed, tailored approach to the use of MP is feasible, resulting in 11% of patients enrolled onto molecularly matched trials.

BACKGROUND: Technology has progressed from single gene panel to large-scale genomic sequencing. This is raising expectations from clinicians and patients alike. The utility and performance of this technology in a clinical setting needs to be evaluated. AIM: This pilot study investigated the feasibility of using exome-scale sequencing (ESS) to identify molecular drivers within cancers in real-time for Precision Oncology in the clinic. METHODS: Between March 2014 and March 2015, the Victorian Comprehensive Cancer Centre Alliance explored the feasibility and utility of ESS in a pilot study. DNA extracted from the tumour specimens underwent both ESS and targeted 'hotspot' sequencing (TS). Blood was taken for germline analysis. A multi-disciplinary molecular tumour board determined the clinical relevance of identified mutations; in particular, whether they were 'actionable' and/or 'druggable'. RESULTS: Of 23 patients screened, 15 (65%) met the tissue requirements for genomic analysis. TS and ESS were successful in all cases. ESS identified pathogenic somatic variants in 73% (11/15 cases) versus 53% (8/15 cases) using TS. Clinically focused ESS identified 63 variants, consisting of 30 somatic variants (including all 13 identified by TS) and 33 germline variants. Overall, there were 48 unique variants. ESS had a clinical impact in 53% (8/15 cases); 47% (7/15 cases) were referred to the familial cancer clinic, and 'druggable' targets were identified in 53% (8/15 cases). CONCLUSION: ESS of tumour DNA impacted clinical decision-making in 53%, with 20% more pathogenic variants identified through ESS than TS. The identification of germline variants in 47% was an unexpected finding.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histological subtypes but also different molecular subtypes. AIM: To describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled in a prospective Thoracic Malignancies Cohort Study between July 2012 and August 2016 were selected. Patients underwent molecular testing for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangements, Kirsten rat sarcoma (KRAS), B-Raf proto-oncogene (BRAF) mutations and ROS1 gene rearrangements. Survival was calculated using the Kaplan-Meier method for groups of interest, and comparisons were made using the log-rank test. RESULTS: A total of 392 patients were included, 43% of whom were female with median age of 64 years (28-92). Of 296 patients tested, 172 patients (58%) were positive for an oncogenic driver: 81 patients (27%) were EGFR positive, 25 patients (9%) were ALK positive, 57 patients (19%) had KRAS mutation and 9 patients (3%) were ROS1 or BRAF positive. Patients with an actionable mutation (EGFR/ALK) had a survival advantage when compared with patients who were mutation negative (hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.33-0.71; P < 0.01). Survival difference between mutation negative and mutation status unknown was not statistically significant when adjusted for confounding factors in a multivariate analysis (HR 1.29; 95% CI 0.97-1.78, P = 0.08). CONCLUSION: In this prospective cohort, the presence of an actionable mutation was the strongest predictor of overall survival. These results confirm the importance of molecular testing and suggest likely survival benefit of identification and treatment of actionable oncogenes.

Freshwater mussels in Australia are rarely studied for their life history and potential as palaeoclimate proxy archives. Therefore, we studied three freshwater mussel species from the Williams River, Hunter Valley, Australia, namely Alathyria profuga, Cucumerunio novaehollandiae and Hyridella drapeta, to identify their potential as new environmental proxy archives from Australian freshwater bodies. Growth analysis revealed that A. profuga and C. novaehollandiae produce distinctive growth lines, which allow the first identification of age and growth structure of these species. The oxygen isotope ratio in A. profuga shells and high-resolution element concentrations in all three species show cyclic, annual variations. A high correlation between growth rates and the combined winter air temperature and annual rainfall, as well as accurate temperature reconstruction using oxygen isotope values in the shells suggest that A. profuga has good potential as an environmental proxy archive. However, the low correlation observed between the Sr : Ca ratio and temperature limited the usefulness of the Sr : Ca ratio in A. profuga shells as a water temperate proxy. In contrast, growth rates and element ratios of C. novaehollandiae do not indicate a significant relationship with environmental variables, suggesting that this species, together with H. drapeta, is probably not suitable for palaeoclimatic studies.

© 2017 The Authors Assessing biodiversity is an important step in the study of microbial ecology associated with a given environment. Multiple indices have been used to quantify species diversity, which is a key biodiversity measure. Measuring species diversity of viruses in different environments remains a challenge relative to measuring the diversity of other microbial communities. Metagenomics has played an important role in elucidating viral diversity by conducting metavirome studies; however, metavirome data are of high complexity requiring robust data preprocessing and analysis methods. In this review, existing bioinformatics methods for measuring species diversity using metavirome data are categorised broadly as either sequence similarity-dependent methods or sequence similarity-independent methods. The former includes a comparison of DNA fragments or assemblies generated in the experiment against reference databases for quantifying species diversity, whereas estimates from the latter are independent of the knowledge of existing sequence data. Current methods and tools are discussed in detail, including their applications and limitations. Drawbacks of the state-of-the-art method are demonstrated through results from a simulation. In addition, alternative approaches are proposed to overcome the challenges in estimating species diversity measures using metavirome data.

BACKGROUND: In metagenomics, the separation of nucleotide sequences belonging to an individual or closely matched populations is termed binning. Binning helps the evaluation of underlying microbial population structure as well as the recovery of individual genomes from a sample of uncultivable microbial organisms. Both supervised and unsupervised learning methods have been employed in binning; however, characterizing a metagenomic sample containing multiple strains remains a significant challenge. In this study, we designed and implemented a new workflow, Coverage and composition based binning of Metagenomes (CoMet), for binning contigs in a single metagenomic sample. CoMet utilizes coverage values and the compositional features of metagenomic contigs. The binning strategy in CoMet includes the initial grouping of contigs in guanine-cytosine (GC) content-coverage space and refinement of bins in tetranucleotide frequencies space in a purely unsupervised manner. With CoMet, the clustering algorithm DBSCAN is employed for binning contigs. The performances of CoMet were compared against four existing approaches for binning a single metagenomic sample, including MaxBin, Metawatt, MyCC (default) and MyCC (coverage) using multiple datasets including a sample comprised of multiple strains. RESULTS: Binning methods based on both compositional features and coverages of contigs had higher performances than the method which is based only on compositional features of contigs. CoMet yielded higher or comparable precision in comparison to the existing binning methods on benchmark datasets of varying complexities. MyCC (coverage) had the highest ranking score in F1-score. However, the performances of CoMet were higher than MyCC (coverage) on the dataset containing multiple strains. Furthermore, CoMet recovered contigs of more species and was 18 - 39% higher in precision than the compared existing methods in discriminating species from the sample of multiple strains. CoMet resulted

Despite known limitations of positron emission tomography (PET) for mediastinal staging of non-small cell lung cancer (NSCLC), radiation treatment fields are generally based on PET-identified disease extent. However, no studies have examined the accuracy of FDG-PET/CT on a per-node basis in patients being considered for curative-intent radiotherapy in NSCLC. In a prospective trial, patients with NSCLC being considered for definitive thoracic radiotherapy ( systemic chemotherapy) underwent minimally invasive systematic mediastinal evaluation with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) following noninvasive staging with integrated PET-CT. Thirty patients underwent EBUS-TBNA, with TBNA performed from a mean 2.5 lymph node (LN) stations per patient (median 3, range 1-5). Discordant findings between PET-CT and EBUS-TBNA were observed in 10 patients (33%, 95% CI 19%-51%). PET-occult LN metastases were demonstrated by EBUS in 4 patients, whereas a lesser extent of mediastinal involvement, compared with FDG-PET, was demonstrated by EBUS in 6 patients, incluDing 2 patients downstaged from cN3 to pN2. LNs upstaged by EBUS were significantly smaller than nodes downstaged by EBUS, 7.5mm (range 7-9) versus 12mm (range 6-21), P=0.005. A significant proportion of patients considered for definitive radiotherapy (/-chemotherapy) undergoing systematic mediastinal evaluation with EBUS-TBNA in this study have an extent of mediastinal NSCLC involvement discordant with that indicated by PET-CT. Systematic EBUS-TBNA may aid in defining the extent of mediastinal involvement in NSCLC patients undergoing radiotherapy. Systematic EBUS-TBNA has the potential to contribute significantly to radiotherapy planning and delivery, by either identifying occult nodal metastases, or demonstrating FDG-avid LNs to be disease-free.Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

This chapter examines the potentials arising from the embodiment of Machine Performers. Thru an analysis of a robotic reappropriation of the early 20th century dance ensemble named The Tiller Girls, I argue that alternate views of the body further the concept of embodiment as currently seen by artificial intelligence. The chapter first compares embodiment from the biological to the social and cultural. Second, it analyses the passage of a walking robot, nicknamed Stumpy, from the AI lab to the stage. It describes how the historical body of the Tiller Girls shifts the perception of audiences and how such inherited competence contributes to the interpretive skills of a machine. I discuss on intrinsic characteristics that make them perform as opposed to solely function. Finally, by shifting this scientific investigation on gaits towards the perception and reception of robot movements, I am exploring audience mechanisms of empathy and identification towards those non-human performers.

Despite known limitations of positron emission tomography (PET) for mediastinal staging of non-small cell lung cancer (NSCLC), radiation treatment fields are generally based on PET-identified disease extent. However, no studies have examined the accuracy of FDG-PET/CT on a per-node basis in patients being considered for curative-intent radiotherapy in NSCLC.In a prospective trial, patients with NSCLC being considered for definitive thoracic radiotherapy (± systemic chemotherapy) underwent minimally invasive systematic mediastinal evaluation with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) following noninvasive staging with integrated PET-CT.Thirty patients underwent EBUS-TBNA, with TBNA performed from a mean 2.5 lymph node (LN) stations per patient (median 3, range 1-5). Discordant findings between PET-CT and EBUS-TBNA were observed in 10 patients (33%, 95% CI 19%-51%). PET-occult LN metastases were demonstrated by EBUS in 4 patients, whereas a lesser extent of mediastinal involvement, compared with FDG-PET, was demonstrated by EBUS in 6 patients, including 2 patients downstaged from cN3 to pN2. LNs upstaged by EBUS were significantly smaller than nodes downstaged by EBUS, 7.5 mm (range 7-9) versus 12 mm (range 6-21), P = 0.005.A significant proportion of patients considered for definitive radiotherapy (+/-chemotherapy) undergoing systematic mediastinal evaluation with EBUS-TBNA in this study have an extent of mediastinal NSCLC involvement discordant with that indicated by PET-CT. Systematic EBUS-TBNA may aid in defining the extent of mediastinal involvement in NSCLC patients undergoing radiotherapy. Systematic EBUS-TBNA has the potential to contribute significantly to radiotherapy planning and delivery, by either identifying occult nodal metastases, or demonstrating FDG-avid LNs to be disease-free.

Social cues facilitate engagement between interaction participants, whether they be two (or more) humans or a human and an artificial agent such as a robot. Previous work specific to human–agent/robot interaction has demonstrated the efficacy of implemented social behaviours, such as eye-gaze or facial gestures, for demonstrating the illusion of engagement and positively impacting interaction with a human. We describe the implementation of THAMBS, The Thinking Head Attention Model and Behavioural System, which is used to model attention controlling how a virtual agent reacts to external audio and visual stimuli within the context of an interaction with a human user. We evaluate the efficacy of THAMBS for a virtual agent mounted on a robotic platform in a controlled experimental setting, and collect both task- and behavioural-performance variables, along with self-reported ratings of engagement. Our results show that human subjects noticeably engaged more often, and in more interesting ways, with the robotic agent when THAMBS was activated, indicating that even a rudimentary display of attention by the robot elicits significantly increased attention by the human. Back-channelling had less of an effect on user behaviour. THAMBS and back-channelling did not interact and neither had an effect on self-report ratings. Our results concerning THAMBS hold implications for the design of successful human–robot interactive behaviours.

In this study participants judged on the relationship between two interacting robots, one of them a mobile robot, the other one a stationary, robot arm-based artistic installation with a high flexibility in orienting its anthropomorphic face. The robots’ behaviour was either (1) weakly correlated through a loose tracking function, (2) independently random, or (3) independently random, but constrained to the same closely limited area. It was found that the true degree of coupling was reflected on average in the rating responses but that pseudo-random behaviour of one of the robots was judged less random if a relationship between the two robots was present. We argue that such robot-robot interaction experiments hold great value for social robotics as the interaction parameters are under complete control of the researchers.