Simulation as a Disruptive Innovation in Advanced Practice Nursing Programs: A Report from a Qualitative Examination

Simulation as a pedagogy is used extensively to educate healthcare professionals in both academic and clinical arenas with the intent to improve the delivery of care and patient outcomes. Advanced practice nursing (APN) programs use simulation as a pedagogy even though APN accreditation and certification organizations prohibit substituting simulation hours for the minimum 500 clinical hours. The purpose of this qualitative study was to explore faculty perceptions of educating APN students using simulation. Focus groups were conducted with a convenience sample of APN simulation faculty. Disruptive innovation theory was used by the researchers to guide the data analysis. Themes emerging during analysis included: 1) extrinsic tension and pressure in the midst of chaos, 2) internal vulnerability, and 3) passion and tenacity to remain resilient. The study results provide clarity to understand integration of APN simulation in the current environment, and introduce the impact of simulation as a disruptive innovation

Placenta Imaging Workshop 2018 report:Multiscale and multimodal approaches

The Centre for Medical Image Computing (CMIC) at University College London (UCL) hosted a two-day workshop on placenta imaging on April 12th and 13th 2018. The workshop consisted of 10 invited talks, 3 contributed talks, a poster session, a public interaction session and a panel discussion about the future direction of placental imaging. With approximately 50 placental researchers in attendance, the workshop was a platform for engineers, clinicians and medical experts in the field to network and exchange ideas. Attendees had the chance to explore over 20 posters with subjects ranging from the movement of blood within the placenta to the efficient segmentation of fetal MRI using deep learning tools. UCL public engagement specialists also presented a poster, encouraging attendees to learn more about how to engage patients and the public with their research, creating spaces for mutual learning and dialogue

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

The Use of Simulation In Advanced Practice Nursing Programs: A North American Perspective

Simulation is an effective pedagogy used extensively in prelicensure nursing education. Advanced practice nursing (APN) programs use simulation even though APN accreditation and certification organizations do not allow substitution of simulation hours for the minimum 500 clinical hours. There is a lack of rigorous research supporting the benefits or describing the outcomes of using simulation in APN programs. This presentation will present the results of a descriptive survey on the current use of simulation in APN programs. A descriptive survey was sent to all APN program Directors in the United States and Canada. Data obtained from the survey provide a baseline for current simulation use, as well as data on the use of International Nursing Association for Clinical Simulation and Learning (INACSL) Standards of Best Practice as an organizing framework for the implementation of simulations in APN programs. Data on the barriers and resources required to support the provision of simulation in APN programs will also be provided. The information obtained will inform the stakeholders in APN education on current use of simulation, general information on adherence to INACSL’s Standards, perceptions of the value of simulation, and barriers and resources to conducting quality simulations in APN education. The results from this study can provide a base to build further rigorous research on how simulation can enhance the education of APN students, improve knowledge transfer, impact behaviors, and improve outcomes. In addition, the outcomes of this study may help educators develop training and support systems that can enhance quality APN simulations

Simulation in Advanced Practice Nursing Programs: A North American Study

Simulation is an effective pedagogy and is used extensively in prelicensure nursing education. Advanced practice nursing (APN) programs also use simulation as a component of their curriculum even though APN accreditation and certification organizations do not allow students to substitute simulation hours for the minimum 500 clinical hours. There is a lack of rigorous research studies supporting the benefits or describing the outcomes of using simulation in APN programs. This article presents the results of a descriptive survey on the use of simulation in APN programs in the United States and Canada. Data obtained from the survey provide a base for current simulation use, so do data on the use of the International Nursing Association for Clinical Simulation and Learning Standards of Best Practice as an organizing framework for the implementation of simulations in APN programs. The results of the survey include courses in which simulation is used, modalities of simulation used, purposes for simulation use, and the number of hours of simulation. Data on barriers to simulation use and faculty educational needs are provided. Key findings include the following: 98% of respondents report using simulation in their APN programs, and 77% of respondents support the replacement of a percentage of clinical hours with simulation. The results from this study provide a base to build further rigorous research on how simulation can enhance the education of APN students, improve knowledge transfer, impact behaviors, and improve outcomes. In addition, the outcomes of this study may help educators develop training and support systems that can enhance the quality of APN simulations