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IntroductionLarge multicentre studies are key to understanding complex relationships between the gut microbiome and outcomes in IBD. Interrogating the mucosal microbiome may identify biological signals not captured by stool, which mostly reflects distal colon. Gold standard tissue cryopreservation by ‘flash freezing’ is likely to limit large study feasibility. We aimed to compare gold standard and pragmatic mucosal biopsy storage vs stool.MethodsWe collected endoscopic recto-sigmoid biopsies and paired stool (prior to bowel cleansing) from 20 adults with IBD (ethical approval: Wales REC5, ref 21/WA/0228). Biopsy preservation and storage conditions are shown in figure 1. Microbiota was sequenced on the MiSeq (Illumina) platform using the 16S rRNA gene (V4 region). Statistical analyses were performed in R, including decontam package for FFPE analyses.ResultsGut microbiome was consistent between proximal and distal biopsies suggesting any within-patient variation observed would be reflective of storage condition, not location. There was no significant difference in alpha diversity (richness, P=0.99; Shannon index, P=0.99) or microbiota profile (P=1.00; R2=0.01) of reagent-preserved vs gold standard tissue. Whilst FFPE community structure was not significantly different to stool, there was significant dissimilarity vs other tissue (P=0.001, R2 0.23). This was driven by differential relative abundance of obligate gut anaerobes; Faecalibacterium, Anaerostipes and Lachnospiraceae. Despite this, tissue microbiota grouped by participant (P=0.001, R2=0.56) regardless of preservation and storage condition. FFPE richness (P=0.11) and Shannon index (P=0.09) was comparable to other tissue conditions.ConclusionsPreservative reagents are a convenient alternative to flash freezing tissue in large microbiome studies. Whilst less comparable, FFPE specimens provide potential for microbiome studies using historically banked samples. Access to tissue for microbiome and other omic analysis will evolve mechanistic understanding of IBD.Abstract P143 Figure 1Sample preservation and storage.

Atlas‐based autosegmentation is an established tool for segmenting structures for CT‐planned head and neck radiotherapy. MRI is being increasingly integrated into the planning process. The aim of this study is to assess the feasibility of MRI‐based, atlas‐based autosegmentation for organs at risk (OAR) and lymph node levels, and to compare the segmentation accuracy with CT‐based autosegmentation. Fourteen patients with locally advanced head and neck cancer in a prospective imaging study underwent a T1‐weighted MRI and a PET‐CT (with dedicated contrast‐enhanced CT) in an immobilization mask. Organs at risk (orbits, parotids, brainstem, and spinal cord) and the left level II lymph node region were manually delineated on the CT and MRI separately. A ‘leave one out’ approach was used to automatically segment structures onto the remaining images separately for CT and MRI. Contour comparison was performed using multiple positional metrics: Dice index, mean distance to conformity (MDC), sensitivity index (Se Idx), and inclusion index (Incl Idx). Automatic segmentation using MRI of orbits, parotids, brainstem, and lymph node level was acceptable with a DICE coefficient of 0.73−0.91, MDC 2.0−5.1 mm, Se Idx 0.64−0.93, Incl Idx 0.76−0.93. Segmentation of the spinal cord was poor (Dice coefficient 0.37). The process of automatic segmentation was significantly better on MRI compared to CT for orbits, parotid glands, brainstem, and left lymph node level II by multiple positional metrics; spinal cord segmentation based on MRI was inferior compared with CT. Accurate atlas‐based automatic segmentation of OAR and lymph node levels is feasible using T1‐MRI; segmentation of the spinal cord was found to be poor. Comparison with CT‐based automatic segmentation suggests that the process is equally as, or more accurate, using MRI. These results support further translation of MRI‐based segmentation methodology into clinical practice. PACS number(s): 87.55.de

Purpose Cone‐beam CT (CBCT)–based synthetic CT (sCT) dose calculation has the potential to make the adaptive radiotherapy (ART) pathway more efficient while removing subjectivity. This study assessed four sCT generation methods using 15 head‐and‐neck rescanned ART patients. Each patient's planning CT (pCT), rescan CT (rCT), and CBCT post‐rCT was acquired with the CBCT deformably registered to the rCT (dCBCT). Methods The four methods investigated were as follows: method 1—deformably registering the pCT to the dCBCT. Method 2—assigning six mass density values to the dCBCT. Method 3—iteratively removing artifacts and correcting the dCBCT Hounsfield units (HU). Method 4—using a cycle general adversarial network machine learning model (trained with 45 paired pCT and CBCT). Treatment plans were created on the rCT and recalculated on each sCT. Planning target volume (PTV) and organ‐at‐risk (OAR) structures were contoured by clinicians on the rCT (high‐dose PTV, low‐dose PTV, spinal canal, larynx, brainstem, and parotids) to allow the assessment of dose–volume histogram statistics at clinically relevant points. Results The HU mean absolute error (MAE) and minimum dose gamma index pass rate (2%/2 mm) were calculated, and the generation time was measured for 15 patients using the rCT as the comparator. For methods 1–4 the MAE, gamma index analysis, and generation time were as follows: 59.7 HU, 100.0%, and 143 s; 164.2 HU, 95.2%, and 232 s; 75.7 HU, 99.9%, and 153 s; and 79.4 HU, 99.8%, and 112 s, respectively. Dose differences for PTVs and OARs were all <0.3 Gy except for method 2 (<0.5 Gy). Conclusion All methods were considered clinically viable. The machine learning method was found to be most suitable for clinical implementation due to its high dosimetric accuracy and short generation time. Further investigation is required for larger anatomical changes between the CBCT and pCT and for other anatomical sites.

The BQ‐CHECK phantom (PTW Freiburg, Germany) has been designed to be used with a 2D ion chamber array to facilitate the quality assurance (QA) of electron and photon beam qualities (BQ). The BQ‐CHECK phantom has three wedges covering the diagonal axes of the beam: two opposed aluminum wedges used to measure electron energy and a single copper wedge used to measure photon energy. The purpose of this work was to assess the suitability of the BQ‐CHECK phantom for use in a routine QA program. A range of percentage depth dose (PDD) curves for two photon beams and four electron beams were measured using a MP3 plotting tank (PTW Freiburg). These beams were used to irradiate a STARCHECK array (PTW Freiburg) with and without the BQ‐CHECK phantom on top of the array. For photons, the ratio of the signals from two chambers underneath the copper wedge was used as an effective TPR measurement (TPReff) and, for electrons, the full width at half maximum of the profile (EFWHM) underneath the aluminum wedges was used as an electron energy constancy measurement. PDD measurements were compared with TPReff and EFWHM to assess the sensitivity of the BQ‐CHECK phantom. The clinical tolerances of TPReff were determined for 6 MV (0.634–0.649), and 10MV (0.683–0.692). For electrons, the clinical tolerances of EFWHM were determined for 6 MeV (94.8–103.4 mm), 8 MeV (105.5–114.0 mm), 10 MeV (125.4–133.9 mm) and 12 MeV (138.8–147.3 mm). Electron and photon energy metrics are presented which demonstrate that the BQ‐CHECK phantom could be used to form part of an efficient routine monthly QA program. Acceptable beam quality limits for various nominal beam energies were established and at these limits, modified profiles were acquired using the STARCHECK array. From the modified profiles, EFWHM and TPReff were determined for the electron and photon beams, respectively. It was demonstrated that both EFWHM and the TPReff have a linear relationship with conventional beam quality metrics. PACS numbers: 87.56.bd, 87.56.‐v

IntroductionReduced bone mineral density (BMD) and muscle dysfunction are complications of Crohn’s Disease (CD). This study evaluates the effect of exercise on BMD and muscular function in adults with CD.MethodsThis was a randomised, parallel-group and assessor-blind trial (Trial registration: ISRCTRN11470370). Adults (>16 years) in clinical remission or with a mildly active CD (Crohn’s Disease Activity Index <220; Faecal Calprotectin <250 mcg/g) were recruited from The Newcastle Upon Tyne Hospitals NHS Foundation Trust, UK. Eligible patients were randomly allocated (1:1) to receive either a 60-minute, thrice-weekly, 6-month progressive impact and resistance training programme with usual care or usual care only, stratified by gender and disease activity using a computer based programme . Primary outcomes were BMD, (lumbar spine (L2-L4), femoral neck, greater trochanter) and muscle function parameters at 6 months in the intention-to-treat population, with analyses adjusted for baseline values, gender and disease status.ResultsBetween February 2018 and March 2019, 76 patients were assessed for eligibility, of whom 47 patients were recruited and randomised (68% female; mean age 49.3 [SD 13.0] years) to the exercise intervention (n= 23) or control (n=24). 6-month follow up data were recorded for 43 (91%) of 47 participants. At 6 months, BMD values were superior in the exercise group at the lumbar spine (adjusted mean difference 0.036 g/cm2, 95% CI 0.024 to 0.048; p<0.001) and femoral neck (0.018 g/cm2, 0.001 to 0.035; p=0.039), but not at the greater trochanter (0.013 g/cm2, -0.019 to 0.045; p=0.415). Muscular function parameters were also superior in the exercise group: grip strength (8.3 kg, 6.2 to 10.5; p <0.001), 30-seconds bicep curl test (7 reps, 5 to 8; p<0.001), 30-seconds chair stand test (4 reps, 3 to 6; p<0.001), isokinetic knee extension strength at angular velocities of 60°/s and 180°/s and isokinetic elbow flexion strength at angular velocities of 60°/s and 120°/s (all p<0.001). Three exercise-related adverse events were recorded: light-headedness (n=2) and nausea (n=1).ConclusionsProgressive impact and resistance training is a safe and effective method to enhance BMD and muscular function in adults with CD and should be considered as a therapeutic option for the preservation of bone and muscle parameters. Due to the small sample size, further larger-scale studies are warranted.

Background and purpose:This project developed and validated an automated pipeline for prostate treatments to accurately determine which patients could benefit from adaptive radiotherapy (ART) using synthetic CTs (sCTs) generated from on-treatment cone-beam CT (CBCT) images.Materials and methods:The automated pipeline converted CBCTs to sCTs utilising deep-learning, for accurate dose recalculation. Deformable image registration mapped contours from the planning CT to the sCT, with the treatment plan recalculated. A pass/fail assessment used relevant clinical goals. A fail threshold indicated ART was required. All acquired CBCTs (230 sCTs) for 31 patients (6 who had ART) were assessed for pipeline accuracy and clinical viability, comparing clinical outcomes to pipeline outcomes.Results:The pipeline distinguished patients requiring ART; 74·4% of sCTs for ART patients were red (failure) results, compared to 6·4% of non-ART sCTs. The receiver operator characteristic area under curve was 0·98, demonstrating high performance. The automated pipeline was statistically significantly (p < 0·05) quicker than the current clinical assessment methods (182·5s and 556·4s, respectively), and deformed contour accuracy was acceptable, with 96·6% of deformed clinical target volumes (CTVs) clinically acceptable.Conclusion:The automated pipeline identified patients who required ART with high accuracy while reducing time and resource requirements. This could reduce departmental workload and increase efficiency and personalisation of patient treatments. Further work aims to apply the pipeline to other treatment sites and investigate its potential for taking into account dose accumulation.

Background This study aimed to quantify the variation in oropharyngeal squamous cell carcinoma gross tumour volume (GTV) delineation between CT, MR and FDG PET-CT imaging. Methods A prospective, single centre, pilot study was undertaken where 11 patients with locally advanced oropharyngeal cancers (2 tonsil, 9 base of tongue primaries) underwent pre-treatment, contrast enhanced, FDG PET-CT and MR imaging, all performed in a radiotherapy treatment mask. CT, MR and CT-MR GTVs were contoured by 5 clinicians (2 radiologists and 3 radiation oncologists). A semi-automated segmentation algorithm was used to contour PET GTVs. Volume and positional analyses were undertaken, accounting for inter-observer variation, using linear mixed effects models and contour comparison metrics respectively. Results Significant differences in mean GTV volume were found between CT (11.9 cm 3 ) and CT-MR (14.1 cm 3 ), p  < 0.006, CT-MR and PET (9.5 cm 3 ), p  < 0.0009, and MR (12.7 cm 3 ) and PET, p  < 0.016. Substantial differences in GTV position were found between all modalities with the exception of CT-MR and MR GTVs. A mean of 64 %, 74 % and 77 % of the PET GTVs were included within the CT, MR and CT-MR GTVs respectively. A mean of 57 % of the MR GTVs were included within the CT GTV; conversely a mean of 63 % of the CT GTVs were included within the MR GTV. CT inter-observer variability was found to be significantly higher in terms of position and/or volume than both MR and CT-MR ( p  < 0.05). Significant differences in GTV volume were found between GTV volumes delineated by radiologists (9.7 cm 3 ) and oncologists (14.6 cm 3 ) for all modalities ( p  = 0.001). Conclusions The use of different imaging modalities produced significantly different GTVs, with no single imaging technique encompassing all potential GTV regions. The use of MR reduced inter-observer variability. These data suggest delineation based on multimodality imaging has the potential to improve accuracy of GTV definition. Trial registration ISRCTN Registry: ISRCTN34165059 . Registered 2nd February 2015.

III-Nitride materials-based visible emission LEDs have emerged as a disruptive technology in the fields of lighting, communications and displays. Shorter wavelength LEDs in the DUV spectral region (210nm – 360nm) with ultra-wide bandgap (UWBG) AlxGa1-xN active layers are now poised to displace toxic Mercury-based light sources. Over the past decade AlGaN LEDs operating in the deep ultra-violet (DUV) spectral region (200 nm < λemission < 300 nm) have been deployed in novel applications including autonomous drone-based sterilization and sanitization systems, point-of-use water purification systems, photo-therapeutics, gas sensors, and non-line-of-sight (NLOS) communications. Similarly, DUV light detectors using ultra-wide bandgap (UWBG) AlxGa1-xN hetero-junctions have also been reported by several research groups. Currently, several DOD early threat warning systems employ such solar-blind DUV photodiodes. These detectors have also garnered attention for environmental safety applications in flame and radiation monitoring systems. Furthermore, ultra-wide Bandgap (UWBG) AlGaN materials-based devices are robust to the harsh conditions of outer space. Hence, the integration of UWBG (> 4 eV) AlGaN-based DUV optoelectronics and electronic devices is of great interest for future miniaturized system-on-chip (SOC) applications. Unlike visible emission materials platforms, at the onset of this work, there were no reports of high brightness DUV emitters, DUV Photonic Integrated Circuits (PIC), nor deeply-scaled DUV micro-LEDs. In this work, we designed and characterized the world’s first monolithically integrated DUV PICs comprised of AlGaN MQW-based light emitters and detectors and an AlGaN waveguide, demonstrated sub-20 µm sized DUV micro-LEDs (also referred to as micropixels) with record kW/cm2 class brightness, and integrated these ultra-bright emitters into a modularly interconnected array architecture with excellent power and area scalability. This work is divided into two sections with the first focused on providing proof-of-concept and experimental characterizations of DUV PICs. The second revolves around the development and characterization of deeply-scaled sub-20 um diameter DUV emitters with aim to improve the electrical, optical, and thermal performance of the devices in addition to opening the door to future applications where traditional large-area DUV LEDs are unsuited such as high speed data transfer and direct write lithography.In our pioneering work on DUV PICs, we first qualified MQW AlGaN LED epitaxial layers for use as both an emitter and detector. We next established the suitability of the n-AlGaN contact layer for waveguiding DUV radiation. Using a symmetric array of micro-LEDs with a pixel size of 30 µm, we determined the directional dependence of DUV radiation within the AlGaN waveguide layer. Then, using a neighboring emitter and detector, we etched a trench between the devices down to the sapphire substrate and measured the photocurrent after each etching iteration to determine the distribution of guided light among the epilayers. We next fabricated DUV PICs with different emitter-detector spacings and extracted the optical losses for both planar and ridge waveguides. In those studies, successful detection of DUV emission at waveguide channel lengths up to 3 mm was realized for the first time. With continued development, such next-generation AlGaN materials-based PICs will have profound impacts in the fields of DUV-based gas and bio-chemical sensing as well as covert and quantum communications.To realize high brightness DUV emitters with theorized high modulation bandwidths, AlGaN-based micro-LEDs (micropixel LEDs) were designed and fabricated with sub-20 µm mesa diameters, slanted sidewalls, and a monolithically integrated heat-spreader. Despite the reduced emission area for these AlGaN-based micro-LEDs, the brightness (W/cm2) is remarkably enhanced due to their efficient light generation at kA/cm2-level current densities enabled by a superior uniformity of current injection and removal of the self-generated heat from the device active region. At these levels of injection current density, the dynamic carrier lifetimes, which chiefly dictate the maximum modulation bandwidth in the case of visible emission micro-LEDs, is significantly reduced. Further tailoring of our micro-sized devices for applications requiring a high dose of UVC radiation, we developed a novel device layout architecture for large arrays via a hierarchically interconnected micropixel geometry which we showed to decrease the series resistance and thermal impedance of the devices while increasing the EQE, maximum LOP, and peak brightness compared to a single macro-LED with an equal emission area. The first-generation 5 um micropixel of this work, with vertical sidewalls, had a record-setting brightness of 291 W/cm2 at a current density of 10.2 kA/cm2 under continuous wave (CW) operation. Second generation micro-LEDs with slanted sidewalls and an optimized fabrication procedure yielded a CW brightness of up to 600 W/cm2 at 15 kA/cm2 and a pulsed-mode brightness as high as 10.2 kW/cm2 at a current density of 50 kA/cm2 without flip-chip packaging nor encapsulation. This kW/cm2-class performance is an order of magnitude brighter than some of the most luminescent blue LEDs found in the literature, the current benchmark. To date, these are the smallest and brightest DUV LEDs globally. This technology, when further matured, will be particularly useful in the areas of DUV direct-write lithography, time-resolved fluorescence, optically pumped polymer-based lasers, charge control systems like envisaged in the evolved Laser Interferometer Space Antenna (eLISA) mission, and optical communications. Future development of selective area growth (SAG) techniques to marry electronic control and read-out devices with DUV micro-LED-based PIC technology is expected to lead to demonstrations of high-bandwidth multi-functional UWBG AlGaN-based SOCs.

Aim:The patient experience of radiotherapy magnetic resonance (MR) simulation is unknown. This study aims to evaluate the patient experience of MR simulation in comparison to computed tomography (CT) simulation, identifying the quality of patient experience and pathway changes which could improve patient experience outcomes.Materials and Methods:MR simulation was acquired for 46 anal and rectal cancer patients. Patient experience questionnaires were provided directly after MR simulation. Questionnaire responses were assessed after 33 patients (cohort one). Changes to the scanning pathway were identified and implemented. The impact of changes was assessed by cohort two (13 patients).Results:Response rates were 85% (cohort one) and 54% (cohort two). 75% of cohort one respondents found the magnetic resonance imaging (MRI) experience to be better or similar to their CT experience. Implemented changes included routine use of blankets, earplugs and headphones, music and feet-first positioning and further MRI protocol optimisation. All cohort two respondents found the MRI experience to be better or similar to the CT experience.Findings:MR simulation can be a comfortable and positive experience that is comparable to that of standard radiotherapy CT simulation. Special attention is required due to the fundamental differences between CT and MRI scanning.