The CRISP colorectal cancer risk prediction tool: an exploratory study using simulated consultations in Australian primary care

BACKGROUND: In Australia, screening for colorectal cancer (CRC) with colonoscopy is meant to be reserved for people at increased risk, however, currently there is a mismatch between individuals' risk of CRC and the type of CRC screening they receive. This paper describes the development and optimisation of a Colorectal cancer RISk Prediction tool ('CRISP') for use in primary care. The aim of the CRISP tool is to increase risk-appropriate CRC screening. METHODS: CRISP development was informed by previous experience with developing risk tools for use in primary care and a systematic review of the evidence. A CRISP prototype was used in simulated consultations by general practitioners (GPs) with actors as patients. GPs were interviewed to explore their experience of using CRISP, and practice nurses (PNs) and practice managers (PMs) were interviewed after a demonstration of CRISP. Transcribed interviews and video footage of the 'consultations' were qualitatively analyzed. Themes arising from the data were mapped onto Normalization Process Theory (NPT). RESULTS: Fourteen GPs, nine PNs and six PMs were recruited from 12 clinics. Results were described using the four constructs of NPT: 1) Coherence: Clinicians understood the rationale behind CRISP, particularly since they were familiar with using risk tools for other conditions; 2) Cognitive participation: GPs welcomed the opportunity CRISP provided to discuss healthy and unhealthy behaviors with their patients, but many GPs challenged the screening recommendation generated by CRISP; 3) Collective Action: CRISP disrupted clinician-patient flow if the GP was less comfortable with computers. GP consultation time was a major implementation barrier and overall consensus was that PNs have more capacity and time to use CRISP effectively; 4) Reflexive monitoring: Limited systematic monitoring of new interventions is a potential barrier to the sustainable embedding of CRISP. CONCLUSIONS: CRISP has the potential to improve risk-appropriate CRC screening in primary care but was considered more likely to be successfully implemented as a nurse-led intervention.This study was funded by a National Health and Medical Research Council (NHMRC) Centre for Research Excellence grant (APP1042021). M Pirotta is supported by an NHMRC Career Development Fellowship. JD Emery is supported by an NHMRC Practitioner Fellowship. FM Walter is supported by a NIHR Clinician Scientist award

Automated analysis of three-dimensional stress echocardiography

Real-time three-dimensional (3D) ultrasound imaging has been proposed as an alternative for two-dimensional stress echocardiography for assessing myocardial dysfunction and underlying coronary artery disease. Analysis of 3D stress echocardiography is no simple task and requires considerable expertise. In this paper, we propose methods for automated analysis, which may provide a more objective and accurate diagnosis. Expert knowledge is incorporated via statistical modelling of patient data. Methods for identifying anatomical views, detecting endocardial borders, and classification of wall motion are described and shown to provide favourable results. We also present software developed especially for analysis of 3D stress echocardiography in clinical practice. Interobserver agreement in wall motion scoring is better using the dedicated software (96%) than commercially available software not dedicated for this purpose (79%). The developed tools may provide useful quantitative and objective parameters to assist the clinical expert in the diagnosis of left ventricular function

Metformin and carotid intima media thickness in never smokers with type 1 diabetes: the REMOVAL trial

Aim: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status. Methods: Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. Results: In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (−0.012 mm, 95% CI −0.021 to −0.002; p = .0137) but not in ever-smokers (0.003 mm, 95% CI −0.008 to 0.014; p = .5767); and similarly in non-current smokers (−0.008 mm, 95% CI −0.015 to −0.00001; p = .0497) but not in current smokers (0.013 mm, 95% CI −0.007 to 0.032; p = .1887). Three-way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p = .0373, prespecified) and non-current versus current smoking (p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (−0.020 mm, 95% CI −0.034 to −0.006; p = .0067) but not in ever-smokers (−0.006 mm, 95% CI −0.020 to 0.008; p = .4067), although this analysis was not supported by a significant three-way interaction term. Conclusions: This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes

Shuttle walk tests in people with COPD who demonstrate exercise-induced oxygen desaturation: An analysis of test repeatability and cardiorespiratory responses

© 2017, © The Author(s) 2017. Exercise-induced oxygen desaturation (EID) is prevalent in people with chronic obstructive pulmonary disease (COPD). This article reports a sub-analysis from a randomized controlled trial (RCT) in people with COPD and EID (COPD/EID). The primary aim, in people with COPD/ EID, was to determine the repeatability of the distance and time walked in the incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT), respectively. A secondary aim was to determine whether any participant characteristics predicted those who did not demonstrate improvements on a repeat ISWT or ESWT. Participants with nadir oxygen saturation (SpO2) < 90% on the 6-minute walk test were recruited to the RCT. Two ISWTs and two ESWTs were then performed as part of the baseline assessments, and participants were included in this sub-analysis if their nadir SpO2was <90% during the better of two ISWTs. Repeatability of the tests was analysed using Bland–Altman plots and paired t-tests. Participant characteristics of age, lung function, level of nadir SpO2and end-test dyspnoea were used to predict those who were not likely to demonstrate improvements on a repeat test using receiver operating curves. Eighty-seven participants (mean age (standard deviation, SD) 70 (7) years; forced expiratory volume in one second (FEV1) 47 (17)% predicted) were included. The mean differences (coefficient of repeatability) for the ISWTs and ESWTs were 9 m (55 m) and 19 seconds (142 seconds) respectively (p < 0.05). No participant characteristic predicted the absence of improvement on the second ISWT (area under the curve (AUC) ranged from 0.49 to 0.58, all p > 0.2) or the second ESWT (AUC ranged from 0.43 to 0.52, all p > 0.3). Although repeating the tests showed only small improvements in distance (ISWT) and time (ESWT) walked in people with COPD/EID, the variability was large making definite conclusions about test repeatability in these individuals difficult

The Malthusian Paradox: performance in an alternate reality game

The Malthusian Paradox is a transmedia alternate reality game (ARG) created by artists Dominic Shaw and Adam Sporne played by 300 participants over three months. We explore the design of the game, which cast players as agents of a radical organisation attempting to uncover the truth behind a kidnapping and a sinister biotech corporation, and highlight how it redefined performative frames by blurring conventional performer and spectator roles in sometimes discomforting ways. Players participated in the game via a broad spectrum of interaction channels, including performative group spectacles and 1-to-1 engagements with game characters in public settings, making use of low- and high-tech physical and online artefacts including bespoke and third party websites. Players and game characters communicated via telephony and social media in both a designed and an ad-hoc manner. We reflect on the production and orchestration of the game, including the dynamic nature of the strong episodic narrative driven by professionally produced short films that attempted to respond to the actions of players; and the difficulty of designing for engagement across hybrid and temporally expansive performance space. We suggest that an ARG whose boundaries are necessarily unclear affords rich and emergent, but potentially unsanctioned and uncontrolled, opportunities for interactive performance, which raises significant challenges for design

Should I Take Aspirin? (SITA): RCT of a decision aid for cancer chemoprevention.

Background Australian guidelines recommend that all people aged 50-70 years old consider taking low-dose aspirin to reduce the risk of colorectal cancer (CRC). Aim To determine the effect of a consultation with a researcher in general practice using a decision aid about taking low-dose aspirin to prevent CRC on informed decision-making and low-dose aspirin uptake compared to a general CRC prevention brochure. Design and Setting Individually randomised controlled trial in six general practices in Victoria, Australia, from October 2020 to March 2021. Method Patients aged 50-70 years attending a general practitioner (GP) were recruited consecutively. The intervention was a consultation using a decision aid to discuss taking aspirin to reduce CRC risk; control consultations discussed reducing CRC risk generally. The self-reported co-primary outcomes were informed choices about taking aspirin at one month and low-dose aspirin uptake at six months. Results 261 participants (86% of eligible patients) were randomised into trial arms (129 intervention, 132 control). 17.7% (20/113) of intervention and 7.6% (9/118) control participants reported making an informed choice at one month, an estimated 9.1% (95% CI 0.29% to 18.5) between-arm difference in proportions [odds ratio (OR) 2.47 (97.5% CI:0.94 to 6.52) p=0.074]. The proportions of individuals who reported using aspirin at six months were: 10.2% (12/118) intervention vs 13.8% (16/116) control (estimated between-arm difference: -4.0% (95% CI: -13.5 to 5.5); [OR= 0.68 (97.5% CI:0.27 to 1.70), p= 0.692]. Conclusion The decision aid improved informed decision-making; but has little effect on long-term regular use of aspirin to reduce CRC risk

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

On thermodynamic modeling and the role of the second law of thermodynamics in geophysics

The article contains a brief review of elements of thermodynamic modeling in theoretical geophysics. We motivate the existence of the second law of thermodynamics in macroscopic theoretical physics and demonstrate its evaluation. In particular we show its consequences in the construction of constitutive laws for a two-component poroelastic medium. This construction is also related to microstructural properties verified by means of the second law

Genome landscapes and bacteriophage codon usage

Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.Comment: 9 Color Figures, 5 Tables, 53 Reference