Total neoadjuvant therapy in oesophageal and gastro-oesophageal junctional adenocarcinoma

Adenocarcinoma of the oesophagus and gastro-oesophageal junction represent a large burden of cancer death in the Western World with an increasing incidence. In the past two decades, the overall survival of patients on a potentially curative treatment pathway has more than doubled due to the addition of perioperative oncological therapies to surgery. However, patients often fail to respond to oncological treatment or struggle to complete their treatment after surgery. In this review, we discuss the current evidence for total neoadjuvant therapy and options for assessment of treatment response.</p

PISA 2022. Reporting Australia’s results. Volume II: Student and school characteristics

The Programme for International Student Assessment (PISA) is an international comparative study of student performance directed by the Organisation for Economic Co-operation and Development (OECD). PISA measures the cumulative outcomes of education by assessing how well 15-year-olds, who have nearly completed compulsory schooling in most participating educational systems, are prepared to use their knowledge and skills in particular areas to meet real-world opportunities and challenges. In addition to the cognitive data reported on in Volume I, PISA collected a wealth of student and school contextual data through the background questionnaires. This report focuses on a variety of constructs related to 15-year-old students’ experiences at school, which illustrate student background characteristics and schooling environments, including sense of belonging, student–teacher relationships, disciplinary climate, exposure to bullying, students’ resistance to stress, curiosity, perseverance, shortage of educational staff and shortage of educational material. Volume II of the PISA 2022 national report examines the similarities and differences between a number of participating countries and economies, referred to as comparison countries; the Australian states and territories; and, school sector and different demographic groups for each of the above constructs. The results from PISA, as one of the assessments in the National Assessment Program, allow for nationally comparable reports of student outcomes against the Alice Springs (Mparntwe) Education Declaration (Education Council, 2019)

Performance of charged aerosol detection with hydrophilic interaction chromatography

© 2015 The Authors. The performance of the charged aerosol detector (CAD) was investigated using a diverse set of 29 solutes, including acids, bases and neutrals, over a range of mobile phase compositions, particularly with regard to its suitability for use in hydrophilic interaction chromatography (HILIC). Flow injection analysis was employed as a rapid method to study detector performance. CAD response was 'quasi-universal', strong signals were observed for compounds that have low volatility at typical operating (room) temperature. For relatively involatile solutes, response was reasonably independent of solute chemistry, giving variation of 12-18% RSD from buffered 95% ACN (HILIC) to 10% ACN (RP). Somewhat higher response was obtained for basic compared with neutral solutes. For cationic basic solutes, use of anionic reagents of increasing size in the mobile phase (formic, trifluoroacetic and heptafluorobutyric acid) produced somewhat increased detector response, suggesting that salt formation with these reagents is contributory. However, the increase was not stoichiometric, pointing to a complex mechanism. In general, CAD response increased as the concentration of acetonitrile in the mobile phase was increased from highly aqueous (10% ACN) to values typical in the HILIC range (80-95% ACN), with signal to noise ratios about four times higher than those for the RP range. The response of the CAD is non-linear. Equations describing aerosol formation cannot entirely explain the shape of the plots. Limits of detection (determined with a column for solutes of low k) under HILIC conditions were of the order of 1-3. ng on column, which compares favourably with other universal detectors. CAD response to inorganic anions allows observation of the independent movement through the column of the cationic and anionic constituents of basic drugs, which appear to be accompanied by mobile phase counterions, even at quite high solute concentrations

High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma

Objective: To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy. Design: Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed. Results: A higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity. Conclusion: Resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype

Non-invasive diffusion tensor imaging detects white matter degeneration in the spinal cord of a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Here we examine the ability of magnetic resonance imaging (MRI) to measure axonal degeneration in the lumbar spinal cord of the SOD1 mouse model of ALS. Diffusion tensor imaging (DTI) was successful in detecting axonal spinal cord damage in vivo. Fractional anisotropy (FA) values were reduced exclusively in the ventral white matter tracts of the lumbar spinal cord of ALS-affected SOD1 mice compared to wild-type littermates, with this effect becoming more pronounced with disease progression. The reduced FA values were therefore limited to white matter tracts arising from the motor neurons, whereas sensory white matter fibers were preserved. Significant decreases in water diffusion parallel to the white matter fibers or axial diffusivity were observed in the SOD1 mice, which can be attributed to the axonal degeneration observed by electron microscopy. At the same time, radial diffusivity perpendicular to the spinal column increased in the SOD1 mice, reflecting reduced myelination. These results demonstrate the usefulness of MRI in tracking disease progression in live animals and will aid in the assessment of treatment efficacy. This method could also potentially be adapted to aid the diagnosis and assessment of ALS progression in humans. © 2010 Elsevier Inc. All rights reserved

A modified Delphi process to establish future research priorities in malignant oesophagogastric surgery

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this frecordBackground: With rapid advancement in the genomics of oesophagogastric (OG) cancer and raised expectations in clinical outcomes from patients and clinicians alike there is a clear need to determine the current research priorities in OG cancer surgery. The aim of our study was to use a modified Delphi process to determine the research priorities among OG cancer surgeons in the United Kingdom. Methods: Delphi methodology may be utilised to develop consensus opinion amongst a group of experts. Members of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland were invited to submit individual research questions via an online survey (phase I). Two rounds of prioritisation by multidisciplinary expert healthcare professionals (phase II and III) were completed to determine a final list of high priority research questions. All questions submitted and subsequently ranked were analysed on an anonymised basis. Results: In total, 427 questions were submitted in phase I and 75 with an OG cancer focus were taken forward for prioritisation in phase II. Phase III produced a final list of 12 high priority questions with an emphasis on tailored or personalised treatment strategies in OG cancer surgery. Conclusion: A modified Delphi process produced a list of 12 high priority research questions in OG cancer surgery. Future studies and awards from funding bodies should reflect this consensus list of prioritised questions in the interest of improving patient care and encouraging collaborative research across multiple centres

Developing a business case for greening hard coastal and estuarine infrastructure: preliminary results

This paper presents a new framework of critical success factors (CSF) that is being developed to aid approval of ecological enhancements and green engineering options in cities, historic conservation areas, estuaries and at the coast. This is intended to support asset managers, engineers, conservation and biodiversity teams, decision-makers, and other end-users. The CSF framework is outlined and demonstrated by assessing the engineering performance and ecosystem services benefits of ecological enhancements used in specific operational scale case studies. Where data availability permits, the costs and benefits of different greening approaches compared to ‘business as usual’ are assessed. Three coastal and estuarine case studies are presented to demonstrate how the framework can be applied to compare traditional engineering solutions to green-grey options. Results show that simple, inexpensive ecological enhancement and green engineering solutions can deliver more multifunctional benefits than business as usual solutions for similar or reduced costs. They also demonstrate that the CSF framework will be a powerful tool that can aid practitioners in evaluating green engineering solutions compared with business as usual

Optimising care transitions for people with multiple long-term conditions::learning from a stakeholder engagement workshop

This briefing paper reports on the findings from a stakeholder engagement workshop undertaken in collaboration with the Digital Health and Care Innovation Centre (DHI). This work is part of the Systems Engineering and Thinking to Transform Transitions (SET4) of Health and Social Care study. The stakeholder engagement workshop included a diverse group of individuals from various sectors, including those directly involved in providing health and care services, as well as representatives from universities, industry, policy-making bodies, and other representative organisations

Association of Upper Gastrointestinal Surgery of Great Britain and Ireland (AUGIS)/Perioperative Quality Initiative (POQI) consensus statement on intraoperative and postoperative interventions to reduce pulmonary complications after oesophagectomy

BACKGROUND: Pulmonary complications are the most common morbidity after oesophagectomy, contributing to mortality and prolonged postoperative recovery, and have a negative impact on health-related quality of life. A variety of single or bundled interventions in the perioperative setting have been developed to reduce the incidence of pulmonary complications. Significant variation in practice exists across the UK. The aim of this modified Delphi consensus was to deliver clear evidence-based consensus recommendations regarding intraoperative and postoperative care that may reduce pulmonary complications after oesophagectomy. METHODS: With input from a multidisciplinary group of 23 experts in the perioperative management of patients undergoing surgery for oesophageal cancer, a modified Delphi method was employed. Following an initial systematic review of relevant literature, a range of anaesthetic, surgical, and postoperative care interventions were identified. These were then discussed during a two-part virtual conference. Recommendation statements were drafted, refined, and agreed by all attendees. The level of evidence supporting each statement was considered. RESULTS: Consensus was reached on 12 statements on topics including operative approach, pyloric drainage strategies, intraoperative fluid and ventilation strategies, perioperative analgesia, postoperative feeding plans, and physiotherapy interventions. Seven additional questions concerning the perioperative management of patients undergoing oesophagectomy were highlighted to guide future research. CONCLUSION: Clear consensus recommendations regarding intraoperative and postoperative interventions that may reduce pulmonary complications after oesophagectomy are presented