Efficient inference and identifiability analysis for differential equation models with random parameters.

Heterogeneity is a dominant factor in the behaviour of many biological processes. Despite this, it is common for mathematical and statistical analyses to ignore biological heterogeneity as a source of variability in experimental data. Therefore, methods for exploring the identifiability of models that explicitly incorporate heterogeneity through variability in model parameters are relatively underdeveloped. We develop a new likelihood-based framework, based on moment matching, for inference and identifiability analysis of differential equation models that capture biological heterogeneity through parameters that vary according to probability distributions. As our novel method is based on an approximate likelihood function, it is highly flexible; we demonstrate identifiability analysis using both a frequentist approach based on profile likelihood, and a Bayesian approach based on Markov-chain Monte Carlo. Through three case studies, we demonstrate our method by providing a didactic guide to inference and identifiability analysis of hyperparameters that relate to the statistical moments of model parameters from independent observed data. Our approach has a computational cost comparable to analysis of models that neglect heterogeneity, a significant improvement over many existing alternatives. We demonstrate how analysis of random parameter models can aid better understanding of the sources of heterogeneity from biological data.

Homogenisation for the monodomain model in the presence of microscopic fibrotic structures.

Computational models in cardiac electrophysiology are notorious for long runtimes, restricting the numbers of nodes and mesh elements in the numerical discretisations used for their solution. This makes it particularly challenging to incorporate structural heterogeneities on small spatial scales, preventing a full understanding of the critical arrhythmogenic effects of conditions such as cardiac fibrosis. In this work, we explore the technique of homogenisation by volume averaging for the inclusion of non-conductive micro-structures into larger-scale cardiac meshes with minor computational overhead. Importantly, our approach is not restricted to periodic patterns, enabling homogenised models to represent, for example, the intricate patterns of collagen deposition present in different types of fibrosis. We first highlight the importance of appropriate boundary condition choice for the closure problems that define the parameters of homogenised models. Then, we demonstrate the technique's ability to correctly upscale the effects of fibrotic patterns with a spatial resolution of 10 µm into much larger numerical mesh sizes of 100- 250 µm . The homogenised models using these coarser meshes correctly predict critical pro-arrhythmic effects of fibrosis, including slowed conduction, source/sink mismatch, and stabilisation of re-entrant activation patterns. As such, this approach to homogenisation represents a significant step towards whole organ simulations that unravel the effects of microscopic cardiac tissue heterogeneities.

A nuclear phylogenomic study of the angiosperm order Myrtales, exploring the potential and limitations of the universal Angiosperms353 probe set.

PREMISE: To further advance the understanding of the species-rich, economically and ecologically important angiosperm order Myrtales in the rosid clade, comprising nine families, approximately 400 genera and almost 14,000 species occurring on all continents (except Antarctica), we tested the Angiosperms353 probe kit. METHODS: We combined high-throughput sequencing and target enrichment with the Angiosperms353 probe kit to evaluate a sample of 485 species across 305 genera (76% of all genera in the order). RESULTS: Results provide the most comprehensive phylogenetic hypothesis for the order to date. Relationships at all ranks, such as the relationship of the early-diverging families, often reflect previous studies, but gene conflict is evident, and relationships previously found to be uncertain often remain so. Technical considerations for processing HTS data are also discussed. CONCLUSIONS: High-throughput sequencing and the Angiosperms353 probe kit are powerful tools for phylogenomic analysis, but better understanding of the genetic data available is required to identify genes and gene trees that account for likely incomplete lineage sorting and/or hybridization events.

Exposing latent fingermarks on problematic metal surfaces using time of flight secondary ion mass spectroscopy.

Fingermarks are a key form of physical evidence for identifying persons of interest and linking them to the scene of a crime. Visualising latent (hidden) fingermarks can be difficult and the correct choice of techniques is essential to develop and preserve any fingermarks or other (e.g. DNA) evidence that might be present. Metal surfaces (stainless steel in particular) have proven to be challenging substrates from which to reliably obtain fingermarks. This is a great cause for concern among police forces around the globe as many of the firearms, knives and other metal weapons used in violent crime are potentially valuable sources of fingermark evidence. In this study, a highly sensitive and non-destructive surface science technique called time of flight secondary ion mass spectroscopy (ToF-SIMS) was used to image fingermarks on metal surfaces. This technique was compared to a conventional superglue based fuming technique that was accompanied by a series of contrast enhancing dyes (basic yellow 40 (BY40), crystal violet (CV) and sudan black (SB)) on three different metal surfaces. The conventional techniques showed little to no evidence of fingermarks being present on the metal surfaces after a few days. However, ToF-SIMS revealed fingermarks on the same and similar substrates with an exceptional level of detail. The ToF-SIMS images demonstrated clear ridge definition as well as detail about sweat pore position and shape. All structures were found to persist for over 26 days after deposition when the samples were stored under ambient conditions.

Feasibility evaluation of a pilot scribe-training program in an Australian emergency department.

Objective Medical scribes have an emerging and expanding role in health, particularly in Emergency Medicine in the US. Scribes assist physicians with documentation and clerical tasks at the bedside while the physician consults with his or her patient. Scribes increase medical productivity. The aim of the present study was to examine the feasibility of a pilot hospital-administered scribe-training program in Australia and to evaluate the ability of an American training course (Medical Scribe Training Systems) to prepare trainee scribes for clinical training in an emergency department in Australia. Methods The present study was a pilot, prospective, observational cohort study from September 2015 to February 2016 at Cabrini Emergency Department, Melbourne. Scribe trainees were enrolled in the pre-work course and then trained clinically. Feasibility of training scribes and limited efficacy testing of the course was undertaken. Results The course was acceptable to users and demand for training exists. There were many implementation tasks and issues experienced and resources were required to prepare the site for scribe implementation. Ten trainees were enrolled for preclinical training. Six candidates undertook clinical training, five achieved competency (required seven to 16 clinical shifts after the preclinical course). The training course was helpful and provided a good introduction to the scribe role. The course required adaptation to a non-US setting and the specific hospital setting. In addition, it needed more detail in some common emergency department topics. Conclusion Training scribes at a hospital in Australia is feasible. The US training course used can assist with preclinical training. Course modification is required. What is known about the topic? Scribes increase emergency physician productivity in Australia. There is no previous work on how to train scribes in Australia. What does this paper add? We show that implementing a scribe-training program is feasible and that a training package can be purchased from the US to train scribes in Australia and that it is useful. We also show the adaptation that the course may require to meet Australian emergency department needs. What are the implications for practitioners? Scribes could become an additional member of the emergency department team in Australia and can be trained locally.

A linear sequence to facilitate curation of herbarium specimens of Annonaceae.

This paper provides a linear sequence of four subfamilies, 15 tribes and 106 genera of the magnoliid family Annonaceae, based on state-of-the-art and stable phylogenetic relationships. The linear sequence facilitates the organisation of Annonaceae herbarium specimens.

Characterization of anomalous relaxation using the time-fractional Bloch equation and multiple echo T2 *-weighted magnetic resonance imaging at 7 T.

PURPOSE: To study the utility of fractional calculus in modeling gradient-recalled echo MRI signal decay in the normal human brain. METHODS: We solved analytically the extended time-fractional Bloch equations resulting in five model parameters, namely, the amplitude, relaxation rate, order of the time-fractional derivative, frequency shift, and constant offset. Voxel-level temporal fitting of the MRI signal was performed using the classical monoexponential model, a previously developed anomalous relaxation model, and using our extended time-fractional relaxation model. Nine brain regions segmented from multiple echo gradient-recalled echo 7 Tesla MRI data acquired from five participants were then used to investigate the characteristics of the extended time-fractional model parameters. RESULTS: We found that the extended time-fractional model is able to fit the experimental data with smaller mean squared error than the classical monoexponential relaxation model and the anomalous relaxation model, which do not account for frequency shift. CONCLUSIONS: We were able to fit multiple echo time MRI data with high accuracy using the developed model. Parameters of the model likely capture information on microstructural and susceptibility-induced changes in the human brain. Magn Reson Med 77:1485-1494, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

An economic evaluation of the costs of training a medical scribe to work in Emergency Medicine.

OBJECTIVE: To undertake a cost analysis of training medical scribes in an ED. METHODS: This was a pilot, observational, single-centre study at Cabrini ED, Melbourne, Australia, studying the costs of initiating a scribe programme from the perspective of the hospital and Australian Health sector. Recruitment and training occurred between August 2015 and February 2016 and comprised of a prework course (1 month), prework training sessions and clinical training shifts for scribe trainees (2-4 months, one shift per week) who were trained by emergency physicians. Costs of start-up, recruitment, administration, preclinical training, clinical training shifts and productivity changes for trainers were calculated. RESULTS: 10 trainees were recruited to the prework course, 9 finished, 6 were offered clinical training after simulation assessment, 5 achieved competency. Scribes required clinical training ranging from 68 to 118 hours to become competent after initial classroom training. Medical students (2) required 7 shifts to become competent, premedical students (3) 8-16 shifts, while a trainee from an alternative background did not achieve competency. Based on a scribe salary of US$15.91/hour (including 25% on-costs) plus shift loadings, costs were: recruitment and start-up US$3111, education US$1257, administration US$866 and clinical shift costs US$1137 (overall cost US$6317 per competent scribe). Physicians who trained the clinical trainee scribes during shifts did not lose productivity. CONCLUSIONS: Training scribes outside the USA is feasible using an on-line training course and local physicians. It makes economic sense to hire individuals who can work over a long period of time to recoup training costs. TRIAL REGISTRATION NUMBER: ACTRN12615000607572.

Knowledge and predictors of dysplasia surveillance performance in inflammatory bowel diseases in Australia.

BACKGROUND: Dysplasia surveillance is recognized as an integral component in the management of inflammatory bowel diseases (IBDs). The adherence to surveillance guidelines is variable, and understanding of quality indicators and predictors of behavior is currently limited. OBJECTIVE: To perform a nationwide evaluation of the quality of IBD surveillance practiced by Australian endoscopists and to determine the predictors of quality practice. DESIGN: Cross-sectional nationwide survey. SETTING: Survey distributed through the gastroenterology and colorectal surgery societies covering knowledge and practice of IBD surveillance. MAIN OUTCOME MEASUREMENTS: Adherence to indicators of high-quality surveillance and median score of IBD surveillance guideline knowledge. RESULTS: A total of 264 responses were received, comprising 240 respondents who perform surveillance screening (218 gastroenterologists, 46 colorectal surgeons). Gastroenterologists were significantly more likely to undertake surveillance (P < .001), adhere to guidelines (P = .02), use advanced imaging modalities (P = .04), and have greater surveillance knowledge than colorectal surgeons (P < .001). Knowledge score and gastroenterologists were independent predictors of dysplasia screening (odds ratio [OR] 1.66; 95% confidence interval [CI], 1.41-1.96 and OR 11.2; 95% CI, 4.53-27.87), guideline adherence (OR 1.15; 95% CI, 1.01-1.31 and OR 2.42; 95% CI, 1.11-5.30), and advanced endoscopic imaging technique use (OR 1.19; 95% CI, 1.05-1.35 and OR 2.2; 95% CI, 1.02-4.74). LIMITATIONS: Potential responder bias results appear, however, aligned with those of previous studies. CONCLUSIONS: IBD dysplasia surveillance in Australia is being performed at a high standard. Gastroenterology specialization and knowledge score have been demonstrated to be strong predictors of high-quality surveillance practice. This is the first study to determine predictors of screening behavior and quantify surveillance quality. These results further emphasize that gastroenterologists should play a key role in IBD surveillance.

A systematic review of potential productivity, egg quality, and animal welfare implications of extended lay cycles in commercial laying hens in Canada.

Lay cycle lengths in the Canadian egg industry are currently 50 to 52 wk (68-70 wk of age). In light of increased productivity in commercial laying hens over the last few decades, the much longer lay cycle lengths already implemented in other countries, extending lay cycle lengths in Canada, should be considered with careful attention to potential environmental, economic, and animal welfare implications. However, there is a lack of information in the public domain that provides robust evidence of performance levels and potential trade-offs to support comprehensive consideration of the desirability of extending lay cycles beyond current Canadian norms. Hence, a systematic literature review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was undertaken. Data collection focused primarily on information related to feed-, flock management-, and hen genetics/physiology-related interventions that were studied in literature to support extension of lay cycles (review objective 1), and compiling and analyzing productivity, egg quality, and animal welfare outcomes reported at 70 wk of age or beyond (review objective 2). Several feed-related interventions such as high-protein diets, and probiotics supplements, and flock management interventions such split-feeding were found to potentially improve productivity, and especially egg quality, outcomes in the late laying phase. More studies with bigger flock sizes and in commercial lay facilities need to be undertaken before any of these interventions can be definitively recommended for commercial egg production. Under objective 2, productivity was found to be at acceptable levels well beyond 70 wk of age. Performance on most egg quality traits and animal welfare indicators were also at acceptable levels past 70 wk of age but increased variability was observed beyond ∼80 wk of age. There were also inconclusive indications on how hens in caged housing and white laying hens fare relative to hens in noncaged housing and brown-type layers during the late laying phase. Economic data were limited but suggested that lay cycle lengths beyond 90 wk might not generated net economic benefits.

An obscure cause of gastrointestinal bleeding: Recurrent duodenal variceal hemorrhage treated with intramuscular octreotide in the absence of portal hypertension.

Duodenal varices (DVs) are ectopic gastrointestinal varices (ECVs) associated with portal hypertension (PH). We present the case of an 82-year-old woman who presented with symptomatic anemia secondary to DV hemorrhage diagnosed on oesophagogastroduodenoscopy. This lesion was treated with endoscopic adrenaline injection and clip application. The patient re-presented on multiple occasions with bleeding recurrence localized to the duodenum, which was managed with intramuscular octreotide and oral beta-blockade resulting in sustained remission of bleeding. This case highlights a rare cause of upper gastrointestinal hemorrhage and highlights the value of somatostatin analogues for conservative treatment of DVs.

Self-identification of electronically scanned signatures (ESS) and digitally constructed signatures (DCS).

The use of electronic signatures as a form of identification is increasingly common, yet they have been shown to lack the dynamic features found in online signatures. In this study, handwritten signatures were scanned to produce electronically scanned signatures (ESS) which were then digitally altered to produce digitally constructed signatures (DCS). The ESS and DCS were presented back to participants to identify which were genuine. Only 1% of participants correctly identified all signatures, with a mean score of 57.6% identifications. The lack of self-recognition of ESS raises questions on their reliability and usefulness as means of personal identification.

Role-play Games (RPGs) for Mental Health (Why Not?): Roll for Initiative.

COVID-19 has impacted the mental health of the general public negatively, associated with preventative measures, restricting life activities. These restrictions, such as the stay-at-home strategy, resulted in heightened stress, depression, loneliness, substance abuse, and domestic violence, violating people's occupational and personal lives. During the pandemic, the demands for role-play games (RPGs) have increased: for example, the sales of "Dungeons & Dragons" tripled, underscoring the potential mental health benefits of such games. However, research into the mental health benefits of such games remains under-developed, needing more scientific attention. Accordingly, this commentary paper reviews the existing literature, and suggests areas for application and research about RPGs and mental health including psychotherapy, career guidance, education, and people with disabilities. Insights offered can help practitioners and researchers in RPGs and mental health conduct empirical research and develop alternative approaches for mental health in stressful times.

RemoteForensicCSI: Enriching teaching, training and learning through networking and timely CPD.

The COVID-19 pandemic brought about rapid, transformational change to pedagogic practice on a global scale. During this time, educators across all levels needed to significantly broaden and upskill their digital skills and competence to instantaneously turn face-2-face content into remote, online provision, particularly during periods of national lockdown. Whilst there was significant e-content available in some subject domains, there were limited e-resources available to those working within the criminal justice sector. The #RemoteForensicCSI network was established in attempts to fill this gap and support both practitioner and learner transition within further and higher education and industry. This article evaluates the value and impact that the #RemoteForensicCSI initiative had on the personal development of network participants, their peers and learners, whilst considering, reflecting on and recommending how remote delivery may influence the future of teaching, training and learning within education and the wider criminal justice sector.

An unusual atrial tachycardia in a patient with Friedreich ataxia.

We present the unusual association of an atrial tachycardia with Friedreich ataxia. The arrhythmia was initially suspected to be focal in origin; however, use of a three-dimensional mapping system demonstrated that the tachycardia was macro-reentrant. This was subsequently treated successfully by linear ablation.

Trends in presentations to a private emergency department during the first and second waves of the COVID-19 pandemic in Australia.

Objective The COVID-19 pandemic in Australia coincided with an early trend of reduced visits to the emergency department (ED), but to determine which patients presented less requires closer evaluation. Identifying which patient groups are presenting less frequently will provide a better understanding of health care utilisation behaviours during a pandemic and inform healthcare providers of the potential challenges in managing these groups. Methods This single-centre retrospective study examined trends in presentations in 2020 to a private, mixed paediatric and adult ED in an inner city suburb within the state of Victoria that treats both COVID-19 and non-COVID-19 patients. The 2019 dataset was used as a reference baseline for comparison. All analyses were performed using baseline characteristics and triage data. Results The total number of visits to the ED dropped from 24 775 in 2019 to 22 754 in 2020, representing an overall reduction of 8%. Significant reductions in daily presentations and admissions from the ED were observed in the months immediately following the peak of the two COVID-19 waves in the state of Victoria. Visits by those in the 0- to 17-year age group, triage categories 4 and 5 and musculoskeletal presentations were also reduced for most of 2020. Gastrointestinal/abdominal and urological/renal presentations were reduced immediately after the first COVID-19 wave, whereas infectious diseases visits were reduced during and after the second COVID-19 wave. Conclusions These findings add to the growing body of evidence regarding emergency care underutilisation during the COVID-19 pandemic. Reduced private ED presentations were observed overall and in paediatric patients, lower acuity triage categories, musculoskeletal, abdominal/gastrointestinal and urological/renal presentations during the first wave, whereas infectious disease cases were reduced during the second wave. What is known about the topic? During the first and second waves of COVID-19 in Victoria, ED visits were reduced in the public sector across all diagnostic categories and all triage categories. The effect of the COVID-19 pandemic on private ED attendance is less well known. What does this paper add? Total visits to the private ED during the first and second waves of COVID-19 were reduced across all major diagnostic categories except cardiac presentations. During this same period, visits for triage categories 4 and 5 were significantly reduced. What are the implications for practitioners? ED underutilisation during the initial two waves of the COVID-19 pandemic is apparent in both the private and public sector. Patients should be encouraged not to delay seeking urgent medical care during the pandemic.

High-resolution, large-scale laboratory measurements of a sandy beach and dynamic cobble berm revetment.

High quality laboratory measurements of nearshore waves and morphology change at, or near prototype-scale are essential to support new understanding of coastal processes and enable the development and validation of predictive models. The DynaRev experiment was completed at the GWK large wave flume over 8 weeks during 2017 to investigate the response of a sandy beach to water level rise and varying wave conditions with and without a dynamic cobble berm revetment, as well as the resilience of the revetment itself. A large array of instrumentation was used throughout the experiment to capture: (1) wave transformation from intermediate water depths to the runup limit at high spatio-temporal resolution, (2) beach profile change including wave-by-wave changes in the swash zone, (3) detailed hydro and morphodynamic measurements around a developing and a translating sandbar.

A three species model to simulate application of Hyperbaric Oxygen Therapy to chronic wounds.

Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy.

Not weather beaten.

On behalf of the Registered Nursing Home Association, we should like to express our sincere thanks to nursing home staff throughout the UK for maintaining vital services to patients during the extremely difficult weather conditions that have prevailed over recent weeks.