Simulation can offer a sustainable contribution to clinical education in osteopathy.

Background: Clinical education forms a substantial component of health professional education. Increased cohorts in Australian osteopathic education have led to consideration of alternatives to traditional placements to ensure adequate clinical exposure and learning opportunities. Simulated learning offers a new avenue for sustainable clinical education. The aim of the study was to explore whether directed observation of simulated scenarios, as part replacement of clinical hours, could provide an equivalent learning experience as measured by performance in an objective structured clinical examination (OSCE). Methods: The year 3 osteopathy cohort were invited to participate in replacement of 50% of their clinical placement hours with online facilitated, video-based simulation exercises (intervention). Competency was assessed by an OSCE at the end of the teaching period. Inferential statistics were used to explore any differences between the control and intervention groups as a post-test control design. Results: The funding model allowed ten learners to participate in the intervention, with sixty-six in the control group. Only one OSCE item was significantly different between groups, that being technique selection (p = 0.038, d = 0.72) in favour of the intervention group, although this may be a type 1 error. Grade point average was moderately positively correlated with the manual therapy technique station total score (r = 0.35, p < 0.01) and a trivial relationship with the treatment reasoning station total score (r = 0.17, p = 0.132). Conclusions: The current study provides support for further investigation into part replacement of clinical placements with directed observation of simulated scenarios in osteopathy

The impact of contact tracing in clustered populations

The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease

Polarimetry and Spectroscopy of the `Oxygen Flaring' DQ Herculis-like nova: V5668 Sagittarii (2015)

Classical novae are eruptions on the surface of a white dwarf in a binary system. The material ejected from the white dwarf surface generally forms an axisymmetric shell of gas and dust around the system. The three-dimensional structure of these shells is difficult to untangle when viewed on the plane of the sky. In this work a geometrical model is developed to explain new observations of the 2015 nova V5668 Sagittarii. To understand the ionisation structure in terms of the nova shell morphology and estimate the emission distribution directly following the light-curve's dust-dip. High-cadence optical polarimetry and spectroscopy observations of a nova are presented. The ejecta is modelled in terms of morpho-kinematics and photoionisation structure. Initially observational results are presented, including broadband polarimetry and spectroscopy of V5668 Sgr nova during eruption. Variability over these observations provides clues towards the evolving structure of the nova shell. The position angle of the shell is derived from polarimetry, which is attributed to scattering from small dust grains. Shocks in the nova outflow are suggested in the photometry and the effect of these on the nova shell are illustrated with various physical diagnostics. Changes in density and temperature as the super soft source phase of the nova began are discussed. Gas densities are found to be of the order of 10$^{9}$ cm$^{-3}$ for the nova in its auroral phase. The blackbody temperature of the central stellar system is estimated to be around $2.2\times10^{5}$ K at times coincident with the super soft source turn-on. It was found that the blend around 4640 $\rm{\AA}$ commonly called `nitrogen flaring' is more naturally explained as flaring of the O~{\sc ii} multiplet (V1) from 4638 - 4696 $\rm{\AA}$, i.e. `oxygen flaring'

Mobile element insertions are frequent in oesophageal adenocarcinomas and can mislead paired-end sequencing analysis.

BACKGROUND: Mobile elements are active in the human genome, both in the germline and cancers, where they can mutate driver genes. RESULTS: While analysing whole genome paired-end sequencing of oesophageal adenocarcinomas to find genomic rearrangements, we identified three ways in which new mobile element insertions appear in the data, resembling translocation or insertion junctions: inserts where unique sequence has been transduced by an L1 (Long interspersed element 1) mobile element; novel inserts that are confidently, but often incorrectly, mapped by alignment software to L1s or polyA tracts in the reference sequence; and a combination of these two ways, where different sequences within one insert are mapped to different loci. We identified nine unique sequences that were transduced by neighbouring L1s, both L1s in the reference genome and L1s not present in the reference. Many of the resulting inserts were small fragments that include little or no recognisable mobile element sequence. We found 6 loci in the reference genome to which sequence reads from inserts were frequently mapped, probably erroneously, by alignment software: these were either L1 sequence or particularly long polyA runs. Inserts identified from such apparent rearrangement junctions averaged 16 inserts/tumour, range 0-153 insertions in 43 tumours. However, many inserts would not be detected by mapping the sequences to the reference genome, because they do not include sufficient mappable sequence. To estimate total somatic inserts we searched for polyA sequences that were not present in the matched normal or other normals from the same tumour batch, and were not associated with known polymorphisms. Samples of these candidate inserts were verified by sequencing across them or manual inspection of surrounding reads: at least 85 % were somatic and resembled L1-mediated events, most including L1Hs sequence. Approximately 100 such inserts were detected per tumour on average (range zero to approximately 700). CONCLUSIONS: Somatic mobile elements insertions are abundant in these tumours, with over 75 % of cases having a number of novel inserts detected. The inserts create a variety of problems for the interpretation of paired-end sequencing data.Funding was primarily from Cancer Research UK program grants to RCF and ST (C14478/A15874 and C14303/A17197), with additional support awarded to RCF from UK Medical Research Council, NHS National Institute for Health Research (NIHR), the Experimental Cancer Medicine Centre Network and the NIHR Cambridge Biomedical Research Centre, and Cancer Research UK Project grant C1023/A14545 to PAWE. JMJW was funded by a Wellcome Trust Translational Medicine and Therapeutics grant

Loss of SRY-box2 (SOX2) expression and its impact on survival of patients with oesophageal adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma (OAC) is a highly aggressive malignancy with poor survival, which is highly variable amongst patients with comparable conventional prognosticators. Therefore molecular biomarkers are urgently needed to improve the prediction of survival in these patients. SRY (sex determining region Y)-box 2, also known as SOX2, is a transcription factor involved in embryonal development of the gastrointestinal tract as well as in carcinogenesis. The purpose of this study was to see whether SOX2 expression is associated with survival in patients with OAC. METHODS: SOX2 was studied by immunohistochemistry in patients who had undergone potentially curative oesophagectomy for adenocarcinoma. Protein expression of SOX2 was evaluated using tissue microarrays from resection specimens, and results were analysed in relation to the clinical data by Cox regression analysis. SOX2 was evaluated in two independent OAC cohorts (Rotterdam cohort and a multicentre UK cohort). RESULTS: Loss of SOX2 expression was independently predictive of adverse overall survival in the multivariable analysis, adjusted for known factors influencing survival, in both cohorts (Rotterdam cohort: hazard ratio (HR) 1·42, 95 per cent c.i. 1·07 to 1·89, P = 0·016; UK cohort: HR 1·54, 1·08 to 2·19, P = 0·017). When combined with clinicopathological staging, loss of SOX2 showed an increased effect in patients with pT1-2 tumours (P = 0·010) and node-negative OAC (P = 0·038), with an incrementally adverse effect on overall survival for stage I OAC with SOX2 loss (HR 3·18, 1·18 to 8·56; P = 0·022). CONCLUSION: SOX2 is an independent prognostic factor for long-term survival in OAC, especially in patients with stage I OAC

New insights into organ-specific oxidative stress mechanisms using a novel biosensor zebrafish

This is the final version. Available from Elsevier via the DOI in this record. Background: Reactive oxygen species (ROS) arise as a result from, and are essential in, numerous cellular processes. ROS, however, are highly reactive and if left unneutralised by endogenous antioxidant systems, can result in extensive cellular damage and/or pathogenesis. In addition, exposure to a wide range of environmental stressors can also result in surplus ROS production leading to oxidative stress (OS) and downstream tissue toxicity. Objectives: Our aim was to produce a stable transgenic zebrafish line, unrestricted by tissue-specific gene regulation, which was capable of providing a whole organismal, real-time read-out of tissue-specific OS following exposure to a wide range of OS-inducing environmental contaminants and conditions. This model could, therefore, serve as a sensitive and specific mechanistic in vivo biomarker for all environmental conditions that result in OS. Methods: To achieve this aim, we exploited the pivotal role of the electrophile response element (EpRE) as a globally-acting master regulator of the cellular response to OS. To test tissue specificity and quantitative capacity, we selected a range of chemical contaminants known to induce OS in specific organs or tissues, and assessed dose-responsiveness in each using microscopic measures of mCherry fluorescence intensity. Results: We produced the first stable transgenic zebrafish line Tg (3EpRE:hsp70:mCherry) with high sensitivity for the detection of cellular RedOx imbalances, in vivo in near-real time. We applied this new model to quantify OS after exposure to a range of environmental conditions with high resolution and provided quantification both of compound- and tissue-specific ROS-induced toxicity. Discussion: Our model has an extremely diverse range of potential applications not only for biomonitoring of toxicants in aqueous environments, but also in biomedicine for identifying ROS-mediated mechanisms involved in the progression of a number of important human diseases, including cancer.Natural Environmental Research CouncilEuropean Unio

Two New Nova Shells associated with V4362 Sagittarii and DO Aquilae

A classical nova is an eruption on the surface of a white dwarf in an accreting binary system. The material ejected from the white dwarf surface generally forms an axisymmetric shell. The shaping mechanisms of nova shells are probes of the processes that take place at energy scales between planetary nebulae and supernova remnants. We report on the discovery of nova shells surrounding the post-nova systems V4362 Sagittarii (1994) and more limited observations of DO Aquilae (1925). Distance measurements of 0.5p/m1.4 kpc for V4362 Sgr and 6.7 p/m 3.5 kpc -0.2 for DO Aql are found based on the expansion parallax method. The growth rates are measured to be 0.07``/year for DO Aql and 0.32``/year for V4362 Sgr. A preliminary investigation into the ionisation structure of the nova shell associated with V4362 Sgr is presented. The observed ionisation structure of nova shells depends strongly on their morphology and the orientation of the central component towards the observer. X-ray, IR and UV observations as well as optical integral field unit spectroscopy are required to better understand these interesting objects