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Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer
Get PDFFrom Springer Nature via Jisc Publications RouterHistory: received 2020-03-17, rev-recd 2020-05-24, accepted 2020-06-23, registration 2020-06-24, pub-electronic 2020-07-13, online 2020-07-13, pub-print 2020-08-13Publication status: PublishedFunder: Friends of RosieFunder: THRT, Big C, Paget's AssociationAbstract: Metastasis is the leading cause of cancer-related death. This multistage process involves contribution from both tumour cells and the tumour stroma to release metastatic cells into the circulation. Circulating tumour cells (CTCs) survive circulatory cytotoxicity, extravasate and colonise secondary sites effecting metastatic outcome. Reprogramming the transcriptomic landscape is a metastatic hallmark, but detecting underlying master regulators that drive pathological gene expression is a key challenge, especially in childhood cancer. Here we used whole tumour plus single-cell RNA-sequencing in primary bone cancer and CTCs to perform weighted gene co-expression network analysis to systematically detect coordinated changes in metastatic transcript expression. This approach with comparisons applied to data collected from cell line models, clinical samples and xenograft mouse models revealed mitogen-activated protein kinase 7/matrix metallopeptidase 9 (MAPK7/MMP9) signalling as a driver for primary bone cancer metastasis. RNA interference knockdown of MAPK7 reduces proliferation, colony formation, migration, tumour growth, macrophage residency/polarisation and lung metastasis. Parallel to these observations were reduction of activated interleukins IL1B, IL6, IL8 plus mesenchymal markers VIM and VEGF in response to MAPK7 loss. Our results implicate a newly discovered, multidimensional MAPK7/MMP9 signalling hub in primary bone cancer metastasis that is clinically actionable
The bodily-attitudinal theory of emotion
Get PDFFrom Springer Nature via Jisc Publications RouterHistory: accepted 2020-09-30, registration 2020-10-01, online 2020-10-10, pub-electronic 2020-10-10, pub-print 2021-08Publication status: PublishedFunder: British Academy; Grant(s): 180024Funder: University of ManchesterAbstract: This paper provides an assessment of the bodily-attitudinal theory of emotions, according to which emotions are felt bodily attitudes of action readiness. After providing a reconstruction of the view and clarifying its central commitments two objections are considered (absence of bodily phenomenology and what kind of bodily awareness). An alternative object side interpretation of felt action readiness is then provided, which undermines the motivation for the bodily-attitudinal theory and creates problems for its claims concerning the content of emotional experience. The conclusion is that while the bodily-attitudinal theory marks out a distinctive proposal concerning the question of what emotions are, there remain significant issues which need addressing if it is to be a plausible competitor to existing theories of emotion
Risk stratified breast cancer screening: UK healthcare policy decision-making stakeholders’ views on a low-risk breast screening pathway
Get PDFFrom Springer Nature via Jisc Publications RouterHistory: received 2020-05-07, accepted 2020-07-09, registration 2020-07-10, pub-electronic 2020-07-22, online 2020-07-22, collection 2020-12Publication status: PublishedFunder: Manchester Biomedical Research Centre; doi: http://dx.doi.org/10.13039/100014653; Grant(s): IS-BRC-1215-200007Funder: Programme Grants for Applied Research; doi: http://dx.doi.org/10.13039/501100007602; Grant(s): RP-PG-1214-20016Funder: Breast Cancer Now; doi: http://dx.doi.org/10.13039/100009794; Grant(s): 2018RP005Abstract: Background: There is international interest in risk-stratification of breast screening programmes to allow women at higher risk to benefit from more frequent screening and chemoprevention. Risk-stratification also identifies women at low-risk who could be screened less frequently, as the harms of breast screening may outweigh benefits for this group. The present research aimed to elicit the views of national healthcare policy decision-makers regarding implementation of less frequent screening intervals for women at low-risk. Methods: Seventeen professionals were purposively recruited to ensure relevant professional group representation directly or indirectly associated with the UK National Screening Committee and National Institute for Health and Care Excellence (NICE) clinical guidelines. Interviews were analysed using thematic analysis. Results: Three themes are reported: (1) producing the evidence defining low-risk, describing requirements preceding implementation; (2) the impact of risk stratification on women is complicated, focusing on gaining acceptability from women; and (3) practically implementing a low-risk pathway, where feasibility questions are highlighted. Conclusions: Overall, national healthcare policy decision-makers appear to believe that risk-stratified breast screening is acceptable, in principle. It will however be essential to address key obstacles prior to implementation in national programmes
A grounded theory exploration into situational adaptation strategies developed by Paramedics when dealing with mass casualty incidents
Get PDFThe Manchester (U.K.) Arena bombing took place on the 22nd May 2017 at 22:31, when a suicide bomber detonated an improvised explosive device in the foyer of the Manchester Arena, as the crowd was leaving an event. The attack claimed the lives of 22 people, and a further 116 people required medical treatment, mostly for ballistic injuries.
A key objective for Ambulance Service Commanders was to establish a casualty management system consisting of clinical triage, treatment, and transport of patients from a Casualty Collection Point into the hospital network. To achieve this, two Hazardous Area Response Teams were deployed alongside Consultant and Advanced Paramedics. The purpose of which was to provide point of injury care within the vicinity of the blast area. Whereas previous studies have identified how individuals react to the biopsychosocial response to traumatic incidents post the event, understanding how Ambulance Service personnel adapt to situations while deploying to, or during mass casualty incidents, remains an area that has received limited research in relation to defining empirical evidence.
This study aimed to identify a process that either supported or inhibited Paramedics in achieving situational adaptability when dealing with a mass casualty situation. Constructivist Grounded Theory was used as the chosen methodology, with fifteen Paramedics volunteering to participate in the research. Analysis identified eleven theoretical categories, which were then divided into four theoretical themes. Combined, these formed the basis for four major theoretical propositions: ‘Training & Education’, appropriate application of ‘Incident Management Frameworks’, established ‘Peer Support Networks’, and individual reaction to ‘Stress stimuli’.
This study makes a novel contribution to the phenomenon of situational adaptively. The significance of the resulting theory is that situational adaptability can be enabled through the application of effective decision making strategies, being able to draw on previous experiences, along with effective scene management. This along with communication strategies, support from peers, the incident commander, and multi-agency partners. Key identified inhibitors are presented as situational stressors, perceptions of threat, risk appetite, and environmental stimuli. Consequently, it is now possible to provide four recommendations for Paramedics preparing to respond to mass casualty incidents
Evaluation of the good night out campaign: a sexual violence bystander training programme for nightlife workers in England
Get PDFThe version of record of this article, first published in [Journal of Public Health], is available online at Publisher’s website: http://dx.doi.org/10.1007/s10389-022-01734-yAbstract
Aim Sexual violence is global public health, human rights and gender equality issue. Sexual violence bystander programmes
for nightlife workers are emerging across a few countries and further examination of such programmes is required. This
exploratory study evaluates the potential effectiveness of the Good Night Out Campaign, a sexual violence bystander programme for nightlife workers.
Subject and methods Two hundred and seven trainees attending the 1.5 hour training programme across two cities in England
were recruited opportunistically, immediately prior to training delivery. Sexual violence myth acceptance and readiness and
confidence to intervene in sexual violence were measured at baseline and post-intervention. Analyses used paired-sample
tests to examine differences in the three measurements pre to post-training and effect sizes were quantified using Cohen’s d.
Results Compared to pre-training, post-training participants were significantly (p<0.001) less likely to agree with sexual
violence myths, and more likely to be confident and ready to intervene in sexual violence or incidents of vulnerability. Erect
sizes were small–medium.
Conclusions The study adds to emergent evidence suggesting that sexual violence bystander programmes may be promising
in decreasing sexual violence myths and barriers to bystander intervention, and increasing willingness to intervene amongst
nightlife workers. Findings can support the emergence of sexual violence prevention activities implemented in nightlife
spaces. Further programme implementation and evaluation using experimental designs is needed to explore outcomes in
greater depth, considering the complexity of the nightlife environment
Intellectual capital and new ventures: the entrepreneur's cognizance of company management
No full textThe purpose of this research is to analyse the intellectual capital gauges most often utilized by entrepreneurs in the management of new ventures and to relate the use of these gauges to business performance. On the basis of interview data collected from 103 entrepreneurs, we provide evidence that the use of such measuring techniques impacts positively on overall business performance. Moreover, the results indicate that those entrepreneurs utilizing some form of intellectual capital (IC) measurement have superior results. Consequently, we highlight the importance of detecting, measuring and utilizing IC for new ventures stressing the potential benefits that such analysis can have on the initial steps taken by an entrepreneur in venture formation and business development.The purpose of this research is to analyse the intellectual capital gauges most often utilized by entrepreneurs in the management of new ventures and to relate the use of these gauges to business performance. On the basis of interview data collected from 103 entrepreneurs, we provide evidence that the use of such measuring techniques impacts positively on overall business performance. Moreover, the results indicate that those entrepreneurs utilizing some form of intellectual capital (IC) measurement have superior results. Consequently, we highlight the importance of detecting, measuring and utilizing IC for new ventures stressing the potential benefits that such analysis can have on the initial steps taken by an entrepreneur in venture formation and business development
Playful ambiguity for adaptive capacity
No full textThe need for managers to develop adaptive capacities is now widely documented; it not only enables the potential for organisations to flex in relation to environmental shocks, but it can be a protective factor for stress for the manager and employees more broadly (Ogden et al, 2006; Tökkäri, 2015; Kinder et al, 2019). There are various experiential, simulation, problem based, and live-realtime educational strategies that might promote aspects of adaptive capacity (Hurst et al, 2018; Bosomworth & Gaillard 2019 – in press). For some of these, ambiguity can play a role in navigating or negotiating the task; for example, not knowing how competitors may respond to a strategic move in a simulation task, or not knowing whether or how new group members will deliver their respective tasks for a group task (Wall et al, 2019). Such ambiguities are not necessarily valued or appreciated by students given the potential impact on their individual academic achievement (Wall and Perrin, 2015). Indeed, the "serious play" concept itself is "a practice characterised by the paradox of intentionality" (Statler et al, 2011: 236).
This QIC pushes the intellectual and practical ambition of how far and in what ways ambiguity can feature as an intentional instructional design principle in developing adaptive capacities. For example, whereas many educational approaches may introduce ambiguity in the process of delivering a task (the pedagogic scaffold), many approaches do not introduce it around what the task actually is. Here, 'the task as scaffold' might be replaced by 'serious play as scaffold' whereas a particular mindset or attitudinal frame provides the behavioural coordinates for engagement in educational activity (Spraggon and Bodolica, 2018). This QIC therefore aims to explore playful ambiguity for adaptive capacity, and specifically asks: How can we create the conditions to foster and maintain the paradox of serious play (such as subjectively ‘safe’ spaces), especially set against contexts where learners can be instrumental in their learning? The QIC ultimately aims to pull together examples as well as developing new ideas to be tested in practice.
References
Bosomworth, K. & Gaillard, E. (2019 – in press) Engaging with uncertainty and ambiguity through participatory ‘Adaptive Pathways’ approaches: scoping the literature. Environmental Research Letters. https://doi.org/10.1088/1748-9326/ab3095.
Hurst D., Azevedo A., & Hawranik P. (2018) Building Adaptive Capacity in Online Graduate Management Education. In: Khare A. & Hurst D. (eds) On the Line. Springer, Cham
Kinder, T., Stenvall, J., & Memon, A. (2019). Play at work, learning and innovation. Public Management Review, 21(3), 376-399. doi:10.1080/14719037.2018.1487578
Ogden, P., Minton, K. & Pain, C. (2006). Trauma and the body. New York: W.W.Norton & Company.
Spraggon, M., & Bodolica, V. (2018). A practice-based framework for understanding (informal) play as practice phenomena in organizations. Journal of Management & Organization, 24(6), 846-869. doi:10.1017/jmo.2018.30
Statler, M., Heracleous, L., & Jacobs, C. D. (2011). Serious play as a practice of paradox. The Journal of Applied Behavioral Science, 47(2), 236-256.
Tökkäri, V. (2015). Organizational play: Within and beyond managing. Qualitative Research in Organizations and Management: An International Journal, 10(2), 86-104. doi:10.1108/QROM-11-2013-1181.
Wall, T. & Perrin, D. (2015) Žižek: A Žižekian Gaze at Education, London, Springer.
Wall, T., Clough, D., Österlind, E., & Hindley, A. (2019) Conjuring a ‘Spirit’ for Sustainability: A Review of the Socio-Materialist Effects of Provocative Pedagogies. In: Leal Filho W., Consorte McCrea A. (eds) Sustainability and the Humanities. Springer, Cham
Appetitive augmental functions and common physical properties in a pain-tolerance metaphor: An extended replication
Get PDFRelational frame theory claims that the tacit understanding of metaphorical language rests upon our ability to derive relations based on relevant contextual cues; with metaphor aptness being a function of learning history and the number and nature of contextual cues presented. Recent experimental research has explored whether metaphor aptness plays a role in changing behaviour. Sierra, Ruiz, Flórez, Riaño Hernández, and Luciano (2016) demonstrated that the presence of common physical properties (herein common properties; “cold”) within a perseverance metaphor increased pain tolerance to the cold pressor task. When the metaphor also specified appetitive augmental functions (herein augmentals; “something important to you”), pain tolerance also increased. We tested the replicability of these findings under more stringent conditions, using a stratified (by sex) double-blind randomised-controlled experimental design. Eighty-nine participants completed baseline measures of psychological flexibility, cognitive fusion, generalised pliance, and analogical reasoning ability. Participants were then allocated to a pre-recorded audio-delivered metaphor exercise containing either: (i) common properties; (ii) augmentals; (iii) both; or (iv) neither (control condition). Participants completed the cold pressor task before and after intervention. We found no change in pain tolerance following intervention in any condition. Given potential implications for apt metaphor use for changing behaviour, further work is required to establish why the original study's findings were not replicated, to identify boundary conditions for the putative effect, and test metaphor use in ecologically valid settings
Barth and Hans W. Frei
No full textIn this chapter, I will summarise the development of Hans Frei’s reading of Karl Barth in order to contextualise his own Christology as an attempt to learn from Barth yet think beyond him on the locus central to all his theology. While we can trace significant lines of continuity between Frei’s Identity of Jesus Christ and Karl Barth as Frei understood him, we can also see it as a bold, risky essay in pursuit of an even more focused attention to the concreteness of God’s presence in Jesus Christ given us in the text of Scripture
Managing Degree Apprenticeships through a Work-Based Learning Framework: Opportunities and Challenges
No full textThe Higher Education Institute (HEI) employer interface has attracted much attention in recent years, particularly in light of current dissatisfaction with graduate work-readiness. Concurrently, pressure upon new entrants to the workplace is accelerating through an unprecedented pace of change in technology, requiring currency of employability skills and resilience for individuals to adapt, thrive and perform effectively in an increasingly unpredictable global environment. In 2014 a new form of apprenticeship was proposed in England to simultaneously address these skills shortages whilst offering a genuine alternative to undergraduate degree programmes. Hailed as “the greatest opportunity ever seen for anyone concerned with skills and employment” (Jeffrey 2016, p.1) early HEI adopters have already successfully collaborated with employers to launch business management degree apprenticeships with initial cohorts nearing completion of their first year.
The chapter proposed here is therefore highly significant for two reasons. The first is to inform HEI practice and pedagogic development, particularly in terms of work-based learning degree apprenticeship design and delivery within the new political apprenticeship reforms, which are attracting renewed interest across the globe. This is one of the first evaluations to be published upon this type of programme, affording a unique opportunity to explore how pedagogic approaches to building graduate employability can be improved.
Secondly it considers the effectiveness of the emerging generation of work-based business degree apprentices in terms of performance, retention and engagement as a result of well-developed employability skills. This degree apprenticeship challenges academically led, full time provision with a 20% off the job learning model. An explicit employer led focus cumulates in a separate synoptic end point assessment, altering the fundamentally traditional approach to embedding employability skills into something far more tacit in nature, through negotiated projects, reflective learning and employer mentoring.
In order to examine the effectiveness of this new pedagogic approach, the chapter focuses upon the design and development of a business management degree apprenticeship. It explores current literature concerning work-based learning pedagogy and reflective practice, the role of the employer as a mentor and the development of employability skills. It incorporates an exploratory case study based upon one of the earliest cohorts in England, collectively identifying a complex range of themes and issues for each stakeholder in designing and developing degree apprenticeships.
The chapter concludes with recommendations for HEIs who wish to take advantage of this new and fast changing political agenda through their own development of similar, highly innovative and lucrative initiatives
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