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

A Nonlethal Method to Examine Non-Apis Bees for Mark-Capture Research

Studies of bee movement and activities across a landscape are important for developing an understanding of their behavior and their ability to withstand environmental stress. Recent research has shown that proteins, such as egg albumin, are effective for mass-marking bees. However, current protein mass-marking techniques require sacrificing individual bees during the data collection process. A nonlethal sampling method for protein mark-capture research is sorely needed, particularly for vulnerable, sensitive, or economically valuable species. This study describes a nonlethal sampling method, in which three non-Apis bee species (Bombus bifarius Cresson [Hymenoptera: Apidae], Osmia lignaria Say [Hymenoptera: Megachilidae], and Megachile rotundata Fabricius [Hymenoptera: Megachilidae]) were tested for a unique protein marker by immersing them momentarily in saline buffer and releasing them. Results showed that an egg albumin-specific enzyme-linked immunosorbent assay was 100% effective at detecting the protein on bees that were sampled nonlethally. Furthermore, this sampling method did not have an impact on bee survivorship, suggesting that immersing bees in buffer is a reliable and valid surrogate to traditional, destructive sampling methods for mark-capture bee studies

Cataract surgery redesign : meeting increasing demand, training, audit and patient-centered care

Objective: The demand for cataract surgery in Fife (a well-defined region in southeast Scotland) was steadily increasing over 15 years. Cataract surgery was therefore being outsourced to meet demand with consequences on list mix, training needs, patient experience and staff morale. We aimed to redesign our services to meet local demand, retain a patient-centered service and continue to fulfil training needs. Methods: We quantified cataract surgery delivery over an 18-month period: before, during and after redesign of services. We studied numbers of operations, trainee cases and number of outsourced cases. We also considered the economic implications of the redesign. Results: We studied three periods (each of six months duration): before redesign (BR), redesign period (RP) and post-redesign (PR). Data were collected on total operation numbers, number of cases performed by trainees, and numbers performed out with normal working hours (weekend lists) and external providers. An economic analysis examined the cost of outsourcing cataracts during BR and RP and the costs of the redesign, including building, equipment and additional nursing staff. Conclusion: Regional fulfilment of cataract surgery provision remains a continuous challenge within the NHS. We show that with minimal investment, smart redesign process and collaborative working, increased local provision is possible while fulfilling trainee needs and achieving the necessary clinical audits and national standards.Publisher PDFPeer reviewe

Parenting through place-of-care disruptions: a qualitative study of parents' experiences of neonatal care

© 2024 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/hex.13933Introduction: Neonatal care is complex, involving multiple people and technologies within a community of care. When preterm babies are cared for far from home and/or transferred between units, the whole community of care (and particularly parent participation) is disrupted. Although previous studies have captured subjective experiences of parents, there has been little research exploring the material practices undertaken by parents as a consequence of place-of-care decisions, or the social organisation of those practices. Methods: As part of a wider study exploring optimal place-of-care, semistructured interviews were conducted between July 2018 and October 2019 with 48 parents (36 families) with one or more preterm babies (born at 27–31 weeks gestation) cared for in a neonatal unit in the last 12 months. Findings: We highlight parents' labour-intensive and stressful work to: (1) parent in the neonatal care community (an oversight role that goes beyond contemporary notions of ‘involvement’); (2) create continuity amid place-of-care disruptions; and (3) adapt to the managerial logics of neonatal care settings. Our analysis focuses on the work generated by managerial systems that organise place-of-care decision-making and other efficiency-focused practices. Parents are absorbed into negotiating institutional systems and diverted from routine parenting activities. Conclusion: Those involved in the organisation and management of neonatal care should take account of how managerial systems impact parents' workload, ability to participate in their baby's community of care and, ultimately, on the wellbeing and development of babies and their families. Patient or Public Contribution: The OPTI-PREM study embedded parents' experiences of neonatal care into the research, through a discrete workstream that employed qualitative methodology to capture parents' experiences—as reported in this paper. The OPTI-PREM project was also supported by a Bliss volunteer parent panel, which was involved in designing and overseeing the research. Bliss ‘champion[s] the right for every baby born premature or sick to receive the best care by supporting families, campaigning for change and supporting professionals and enabling life-changing research’ (https://www.bliss.org.uk/about-us/about-bliss). A representative of Bliss is a co-author of this manuscript, and a parent representative (named in the Acknowledgements) provided feedback during its preparation.Natalie Armstrong is supported by a Health Foundation Improvement Science Fellowship and also by the National Institute for Health & Care Research (NIHR) Applied Research Collaboration East Midlands (ARC EM).Published versio

Parenting through place‐of‐care disruptions: A qualitative study of parents' experiences of neonatal care

Introduction: Neonatal care is complex, involving multiple people and technologies within a community of care. When preterm babies are cared for far from home and/or transferred between units, the whole community of care (and particularly parent participation) is disrupted. Although previous studies have captured subjective experiences of parents, there has been little research exploring the material practices undertaken by parents as a consequence of place‐of‐care decisions, or the social organisation of those practices. Methods: As part of a wider study exploring optimal place‐of‐care, semistructured interviews were conducted between July 2018 and October 2019 with 48 parents (36 families) with one or more preterm babies (born at 27–31 weeks gestation) cared for in a neonatal unit in the last 12 months. Findings: We highlight parents' labour‐intensive and stressful work to: (1) parent in the neonatal care community (an oversight role that goes beyond contemporary notions of ‘involvement’); (2) create continuity amid place‐of‐care disruptions; and (3) adapt to the managerial logics of neonatal care settings. Our analysis focuses on the work generated by managerial systems that organise place‐of‐care decision‐making and other efficiency‐focused practices. Parents are absorbed into negotiating institutional systems and diverted from routine parenting activities. Conclusion: Those involved in the organisation and management of neonatal care should take account of how managerial systems impact parents' workload, ability to participate in their baby's community of care and, ultimately, on the wellbeing and development of babies and their families. Patient or Public Contribution: The OPTI‐PREM study embedded parents' experiences of neonatal care into the research, through a discrete workstream that employed qualitative methodology to capture parents' experiences—as reported in this paper. The OPTI‐PREM project was also supported by a Bliss volunteer parent panel, which was involved in designing and overseeing the research. Bliss ‘champion[s] the right for every baby born premature or sick to receive the best care by supporting families, campaigning for change and supporting professionals and enabling life‐changing research’ (https://www.bliss.org.uk/about-us/about-bliss). A representative of Bliss is a co‐author of this manuscript, and a parent representative (named in the Acknowledgements) provided feedback during its preparation

In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications

The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-existing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile—remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications

Inhibition of lipid oxidation increases glucose metabolism and enhances 2-deoxy-2-[¹⁸F]fluoro-D-glucose uptake in prostate cancer mouse xenografts

Includes bibliographic references.PURPOSE: Prostate cancer (PCa) is the second most common cause of cancer-related death among men in the United States. Due to the lipid-driven metabolic phenotype of Pca, imaging with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) is suboptimal, since tumors tend to have low avidity for glucose. PROCEDURES: We have used the fat oxidation inhibitor etomoxir (2-[6-(4-chlorophenoxy)-hexyl]oxirane-2-carboxylate) that targets carnitine-palmitoyl-transferase-1 (CPT-1) to increase glucose uptake in PCa cell lines. Small hairpin RNA specific for CPT1A was used to confirm the glycolytic switch induced by etomoxir in vitro. Systemic etomoxir treatment was used to enhance [¹⁸F]FDG-positron emission tomography ([¹⁸F]FDG-PET) imaging in PCa xenograft mouse models in 24 h. RESULTS: PCa cells significantly oxidize more of circulating fatty acids than benign cells via CPT-1 enzyme, and blocking this lipid oxidation resulted in activation of the Warburg effect and enhanced [¹⁸F]FDG signal in PCa mouse models. CONCLUSIONS: Inhibition of lipid oxidation plays a major role in elevating glucose metabolism of PCa cells, with potential for imaging enhancement that could also be extended to other cancers

Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery

BACKGROUND: Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified. RESULTS: To search for such proteins twenty three nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells. CONCLUSIONS: The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.Publisher PDFPeer reviewe