The validation and application of a novel colonic polypectomy trainer. The WIMAT colonoscopy suitcase

Summary Background and Aims The WIMAT colonoscopy suitcase is an ex-vivo, porcine, polypectomy simulator. This has been developed in response to the increasing demand for polypectomy training following the introduction of the National Bowel Cancer Screening Programme. The aims of this thesis are to establish if the simulator is a valid form of polypectomy skills training and to identify if this model can be used to develop objective parameters for polypectomy assessment. Materials and Methods A series of clinical trials were systematically conducted to test the validity of the WIMAT colonoscopy suitcase. This included evaluating its content, construct and concurrent validity and conducting a skills transfer study comparing the WIMAT colonoscopy suitcase with a virtual reality simulator. Objective assessment parameters were examined by measuring the accuracy of self-assessment and using video coding software to analyse the hand movements performed during simulated polypectomy tasks. Results Content validity was demonstrated by experts who scored the model’s anatomical, mechanical and visual realism favourably across multiple parameters (p=0.05). The ratio of rotational hand movements to endoscopic tip angulation (RoTA) was significantly different when comparing novices to experts (p=<0.05). Discussion The WIMAT colonoscopy suitcase is a valid form of polypectomy skills training. The simulator can be used to address the increasing demand for training in this procedure. Further work is needed to assess the reliability of the RoTA score at different stages of the polypectomy procedure before it is used as an assessment tool

Quality assurance of training in diagnostic and therapeutic gastrointestinal endoscopy

Previous evidence has shown that standards of performance in gastrointestinal endoscopy are variable and that there are disparities in training outcomes. Many changes have been made recently to both training and assessment of endoscopy in the UK. However, no prospective methods of evaluating their outcome have been put in place. The aims of this research were to evaluate current and new training processes and assessments in order to quality assure the outcomes and improve the training process. Two audits were undertaken demonstrating improvements in colonoscopy training over 5 years within a single region and in trainee perceptions of their training nationally. Two studies were done investigating a novel computer colonoscopy simulator for assessment of colonoscopic skills, demonstrating excellent construct validity. A multi-centre randomised controlled trial evaluated the use of this simulator in novice training, which was shown to be equivalent to standard bed-side training with a high degree of skills transfer to real-life colonoscopy. Assessment tools for therapeutic endoscopic procedures were developed, validated and used to quality assure a course in therapeutic endoscopy. This course resulted in significant improvements in practical skills for three of the four therapeutic procedures following training. Web-based training and assessment modules for lesion recognition at capsule endoscopy were developed, validated and piloted. This demonstrated the effectiveness of using new training methodologies for skills improvement in this area. A training course for radiographers in virtual colonoscopy was developed and the training evaluated. This demonstrated competence in practical performance and improvements in knowledge and interpretative skill. Finally, two qualitative studies on non-technical skills in endoscopy were undertaken in order to widen the assessment domains from purely knowledge and skill. An interview study provided the basis for development of a nontechnical skills taxonomy and a video-analysis study resulted in production of a marker system for professional behaviour within gastrointestinal endoscopy

Design revolutions: IASDR 2019 Conference Proceedings. Volume 3: People

In September 2019 Manchester School of Art at Manchester Metropolitan University was honoured to host the bi-annual conference of the International Association of Societies of Design Research (IASDR) under the unifying theme of DESIGN REVOLUTIONS. This was the first time the conference had been held in the UK. Through key research themes across nine conference tracks – Change, Learning, Living, Making, People, Technology, Thinking, Value and Voices – the conference opened up compelling, meaningful and radical dialogue of the role of design in addressing societal and organisational challenges. This Volume 3 includes papers from People track of the conference

The HBP1 tumor suppressor is a negative epigenetic regulator of MYCN driven neuroblastoma through interaction with the PRC2 complex

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[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)