Targeting FGFR signaling to disrupt cellular cross-talk in pancreatic cancer

PhD Thesi

A protocol for co-creating research project lay summaries with stakeholders:Guideline development for Canada's AGE-WELL Network

Background Funding bodies increasingly require researchers to write lay summaries to communicate projects’ real-world relevance to the public in an accessible way. However, research proposals and findings are generally not easily readable or understandable by non-specialist readers. Many researchers find writing lay summaries difficult because they typically write for fellow subject specialists or academics rather than the general public or a non-specialist audience. The primary objective of our project is to develop guidelines for researchers in Canada’s AGE-WELL Network of Centres of Excellence, and ultimately various other disciplines, sectors, and institutions, to co-create lay summaries of research projects with stakeholders. To begin, we produced a protocol for co-creating a lay summary based on workshops we organized and facilitated for an AGE-WELL researcher. This paper presents the lay summary co-creation protocol that AGE-WELL researchers will be invited to use. Methods Eligible participants in this project will be 24 AgeTech project researchers who are funded by the AGE-WELL network in its Core Research Program 2020. If they agree to participate in this project, we will invite them to use our protocol to co-produce a lay summary of their respective projects with stakeholders. The protocol comprises six steps: Investigate principles of writing a good lay summary, identify the target readership, identify stakeholders to collaborate with, recruit the identified stakeholders to work on a lay summary, prepare for workshop sessions, and execute the sessions. To help participants through the process, we will provide them with a guide to developing an accessible, readable research lay summary, help them make decisions, and host, and facilitate if needed, their lay summary co-creation workshops. Discussion Public-facing research outputs, including lay summaries, are increasingly important knowledge translation strategies to promote the impact of research on real-world issues. To produce lay summaries that include information that will interest a non-specialist readership and that are written in accessible language, stakeholder engagement is key. Furthermore, both researchers and stakeholders benefit by participating in the co-creation process. We hope the protocol helps researchers collaborate with stakeholders effectively to co-produce lay summaries that meet the needs of both the public and project funders

Divergent signalling pathways regulate lipopolysaccharide-induced eRNA expression in human monocytic THP1 cells

AbstractRecent studies have indicated that non-coding RNAs transcribed from enhancer regions are important regulators of enhancer function and gene expression. In this report, we have characterised the expression of six enhancer RNAs (eRNAs) induced in human monocytic THP1 cells following activation of the innate immune response by lipopolysaccharide (LPS). Specifically, we have demonstrated that LPS-induced expression of individual eRNAs is mediated through divergent intracellular signalling pathways that includes NF-κB and the mitogen activated protein kinases, extracellular regulated kinase-1/2 and p38

Long Intergenic Noncoding RNAs Mediate the Human Chondrocyte Inflammatory Response and Are Differentially Expressed in Osteoarthritis Cartilage

Objective To identify long noncoding RNAs (lncRNAs), including long intergenic noncoding RNAs (lincRNAs), antisense RNAs, and pseudogenes, associated with the inflammatory response in human primary osteoarthritis (OA) chondrocytes and to explore their expression and function in OA. Methods OA cartilage was obtained from patients with hip or knee OA following joint replacement surgery. Non-OA cartilage was obtained from postmortem donors and patients with fracture of the neck of the femur. Primary OA chondrocytes were isolated by collagenase digestion. LncRNA expression analysis was performed by RNA sequencing (RNAseq) and quantitative reverse transcriptase-polymerase chain reaction. Modulation of lncRNA chondrocyte expression was achieved using LNA longRNA GapmeRs (Exiqon). Cytokine production was measured with Luminex. Results RNAseq identified 983 lncRNAs in primary human hip OA chondrocytes, 183 of which had not previously been identified. Following interleukin-1β (IL-1β) stimulation, we identified 125 lincRNAs that were differentially expressed. The lincRNA p50-associated cyclooxygenase 2-extragenic RNA (PACER) and 2 novel chondrocyte inflammation-associated lincRNAs (CILinc01 and CILinc02) were differentially expressed in both knee and hip OA cartilage compared to non-OA cartilage. In primary OA chondrocytes, these lincRNAs were rapidly and transiently induced in response to multiple proinflammatory cytokines. Knockdown of CILinc01 and CILinc02 expression in human chondrocytes significantly enhanced the IL-1-stimulated secretion of proinflammatory cytokines. Conclusion The inflammatory response in human OA chondrocytes is associated with widespread changes in the profile of lncRNAs, including PACER, CILinc01, and CILinc02. Differential expression of CILinc01 and CIinc02 in hip and knee OA cartilage, and their role in modulating cytokine production during the chondrocyte inflammatory response, suggest that they may play an important role in mediating inflammation-driven cartilage degeneration in OA

Outcome measures for use in trials of paediatric otorrhoea:A systematic review

Introduction:Paediatric otorrhoea (PO) describes a middle ear infection that results in a perforation of the tympanic membrane and ear discharge, in children and young people (CYP). Prolonged infection may be associated with hearing loss and developmental delay. The current management of paediatric otorrhoea is variable, including non-invasive treatments (conservative, oral antibiotics, topical antibiotics) and surgery, reflecting the lack of a sufficiently strong evidence base. Outcome reporting is fundamental to producing reliable and meaningful evidence to inform best practice.Objectives:Primary objective: to determine which outcome measures are currently used to evaluate treatment success in studies of non-surgical treatments for paediatric otorrhoea. Secondary objectives: to identify outcome measurement instruments used in the literature and assess their applicability for use in clinical trials of PO.Methods:This systematic review was registered with PROSPERO (CRD42023407976). Database searches of EMBASE, MEDLINE and Cochrane was performed on June 6, 2023, covering from Jan 1995 to May 2023. Randomised controlled trials or study protocols involving CYP with PO were included following PRISMA guidelines. Risk of bias was assessed with Cochrane's tool.Results:Of the 377 papers identified, six were included in the systematic review. The primary outcome of five of the studies related to otorrhoea cessation; both time to cessation and proportion recovered at various time points were used as measures. Two measurement instruments were identified: Otitis Media-6 Questionnaire and the Institute for Medical Technology Assessment Productivity Cost Questionnaire. Both were shown to be applicable measurement instruments when used in clinical trials of PO.Conclusions:To promote homogeneity and facilitate meaningful comparison and combination of studies, we propose that time to cessation of otorrhoea from onset of otorrhoea should be used as the primary outcome in future studies. Further research is needed to establish if this is the most important outcome to children and their caregivers

Governance of policing and cultural codes: interpreting and responding to policy directives

In terms of governance, British policing seems to arise from a history of local traditions influenced more recently by centralist managerial demands. A creeping process of privatisation has led social scientists to argue that patterns of governance in British policing are changing in several directions. This has included the way police officers not only are challenged, but also challenge these changing modes of governance in terms of ethical codes of behaviour. There is evidence that police officers, as meaningful actors, have made attempts to diverge from these strictures and have forged their own ways, via their cultural knowledge and practices, to ‘do policing’, rather than relying upon codes of practice or rules and regulations

The Social Care and Support Needs of Adults with Concurrent Dementia and Visual Impairment

Over 100,000 people in the UK have concurrent visual impairment and dementia, resulting in isolation, falls and reduced independence. However, current models of care and support tend to focus on each condition separately, meaning that individual needs are rarely addressed. This can lead to high levels of anxiety and distress as well as placing great demands on carers, highlighting the need for support for informal carers and separate assessment of carer’s needs. This presentation reports on a new study exploring the lived experience of people with both dementia and visual impairment and the views of professionals. The aim was to investigate how best to provide care and support for adults living with both conditions in a range of housing settings, and develop evidence-based practice guidance to improve social care and support. 26 qualitative face-to-face interviews with people with dementia and sight loss, sometimes with their family carers, were conducted. In addition, focus groups were held involving a total of 47 health, social care and housing professionals, using a semi-structured topic guide developed by the project team. Participants were recruited across three sites in England: the North East, the South West and the Midlands. Each interview and focus group was analysed thematically using computer-assisted qualitative data analysis software, with emerging themes being compared and discussed by team members in order to validate the findings. The findings were discussed at a consensus event that included people with dementia and sight loss, family carers and professionals working in housing, health and social care. This led to the development of a set of recommendations for improving social care and support for people with visual impairment and dementia. These include timely diagnosis for both conditions, and a greater focus on holistic care rather than support for one condition over the other

Glass ceilings and stone floors: an intersectional approach to challenges UK geographers face across the career lifecycle

While there has been a steady growth of women working in geography in UK universities since the mid-Twentieth Century, there are continuing challenges in gendered career progression and professional interactions within the contemporary discipline. These range from problems associated with employment precarity and inflexible work practices, life choices and obligations in the domestic arena, discrimination and bullying, to less tangible gendered norms and cultures in the workplace. This paper discusses these challenges and inequalities in the light of a brief overview of sector-wide statistical data on appointments by gender and career-stage and with the analysis of some 250 in-depth responses to a nationwide qualitative survey of gender and career experience in UK universities (Maddrell et al 2016). While the term ‘glass ceiling’ still has significant relevance, findings show a more complicated picture which also includes ‘stone floors’ and stumbling blocks. It also shows how career experience varies by institution and individual: challenges in career progression can be compounded by institutional protocols and intersectional factors, and vary with career stage. The intersection of early-career job precarity, reproductive decisions and associated family responsibilities were particularly highlighted in this study. These ‘pinch points’ in career development disproportionately affect, but are not limited to, female early career scholars. Early career progress may be stalled in mid-career in multi-staged promotional systems such as that in UK universities; some from minorities face compound barriers; men with caring responsibilities may face prejudice. The paper concludes with suggested strategies for change, highlighting the importance of individual university and department protocols and practices; line manager and other senior colleagues’ attitudes and leadership in creating workplaces with an equality-driven ethos and structures that allow individuals to flourish

Doing gender locally: The importance of ‘place’ in understanding marginalised masculinities and young men’s transitions to ‘safe’ and successful futures

Observable anxieties have been developing about the position of boys and young men in contemporary society in recent years. This is expressed as a crisis of masculinity, in which place is often implicitly implicated, but is rarely considered for its role in the shaping of young men’s practices, trajectories and aspirations. Drawing on research conducted with young people who accessed a range of social care support services, this article argues that transition means different things for young men in different locales and that local definitions of masculinity are required to better understand young men’s lives and the opportunities available to them. The authors argue that home life, street life, individual neighbourhoods, regions and nations all shaped the young men’s identities and the practices they (and the staff working with them) drew on in order to create successful futures and ‘safe’ forms of masculinity. It is suggested that this place-based approach has the potential to re-shape the ‘crisis’ discourse surrounding masculinity and the anxieties associated with young men