CD95R-Fc coated Microparticle Delivery to Cancer Cells

PhD thesisTriple-negative breast cancers lack the three main breast cancer biomarkers; oestrogen-, progesterone- or HER2-receptors and chemotherapy is the only established treatment option for patients. Chemotherapies are associated with physically debilitating, off-target toxicities and tumours often develop resistance to cytotoxic compounds. Nanomedicine has the potential to improve chemotherapy efficacy and has enabled the development of small, therapeutic carriers such as microparticles (MPs). These can be made from biodegradable polymers, loaded with (sometimes poorly soluble) chemotherapeutic agents and their surfaces coated in tumour targeting proteins. CD95L has been reported to be upregulated in cancer cells identifying it a promising target. In this study, the CD95 receptor, CD95R, was fused to the Fc region of human IgG1, and baculoviral-mediated expression was optimised in Sf21 and Hi5 insect cells. The protein was purified by affinity chromatography and used to coat microparticles. CD95R-coated MPs improved the uptake into triple-negative, MDA-MB-231 cells, ostensibly via a mechanism involving CD95L. Anti-CD95L antibodies were validated following expression of CD95L-Myc-DDK in otherwise naïve HEK293T cells. The expression of supposed target ligand CD95L was then tested in MDA-MB-231 cells and found to be undetectable. Furthermore, the CD95R-coated particles were efficiently taken up by non-cancerous primary fibroblasts. The reasons for the enhanced uptake of CD95R-coated MPs were explored in MDA-MB-231 cells. Differences in the surface charge of the coated-MPs, characterised by dynamic light scattering (DLS) and electrophoresis, were ruled out as a cause. However, inhibition of the common endocytic pathways did suggest that coated-MP uptake likely occurs via macropino- or phagocytosis. The use of this system for targeted cancer treatment or for wider applications are discussed

The seldom heard-- Using evidence to inform patient feedback programmes

Until recent years many patients have been excluded from research and from service initiatives aimed at understanding and/or improving patients' experiences of care. Often those that go unheard are termed the minority- and /or hard to reach-.- Whsch_nurunpub4831unpu

A discussion of the synergy and divergence between Lean Six Sigma and person-centred improvement sciences

Background: This paper discusses if and how the improvement sciences of Lean Six Sigma and person-centred approaches can be melded or blended in the health care context. The discussion highlights the relationship between each approach to improvement science in terms of their respective purposes, intentions and probable outcomes; positioning these as either synergies or divergences. Comparison of the key theoretical and methodological principles underpinning each approach to improvement is also considered and implications for future practice, policy and research are drawn out. The discussion is informed by part of the findings of a realist review of relevant literature.Conclusions: Lean Six Sigma as a process improvement methodology appeals to a wide range of stakeholders in healthcare internationally. Four key synergies and three key divergences between Lean Six Sigma and person-centred approaches were found. The discussion here highlights the need for further research into Lean Six Sigma implementation and its possible contribution to developing person-centred cultures.Impact: Adoption of Lean Six Sigma in health care by stakeholder groups, external to nursing, has been taking place. At the same time there has been a loss of Lean’s original intention of respect for people in favour of a technical efficiency focus on reducing waste and variation. Our findings of four key synergies and three key divergences between both approaches indicate where synergies can be maximised and divergence narrowed to improve implementation and enhance methodological coherence. Researchers, policy makers and practitioners should be aware that use of Lean Six Sigma alone may have a limited impact on developing personcentred care and culture. Use of Lean combined with person-centred approaches may appeal to a wider range of stakeholders. Yet, their combined use and effectiveness has not as yet been evaluated.This paper was supported by Queen Margaret University Edinburgh and University College Dublinhttps://doi.org/10.3844/ijrnsp.2020.10.2311pubpu

Factors that make a visit to selected Eastern Cape national parks a memorable experience

South African National Parks (SANParks) manages 19 functional national parks (NPs) and oversees the conservation of South Africa’s (SA’s) biodiversity, landscapes and heritage assets. The organisation plays a significant role in the promotion of SA’s nature-based tourism business which in turn forms part of the nation’s heritage and identity. Tourism to SA’s NPs is significant and interest in visiting these parks continues to increase annually, from both international and domestic markets. Three of these NPs are located in the Eastern Cape province, namely Addo Elephant National Park (AENP), Camdeboo National Park (CNP) and Mountain Zebra National Park (MZNP) and were the focus of this study. The main reason for conducting the current study was to establish what factors make visits to the three aforementioned NPs memorable. The findings of this research could be useful to all NPs and assist them in making decisions regarding the evaluation and creation of product offerings that will enhance experiences and make them memorable for tourists. Based on the findings, and because each NP is unique (for example, the different biodiversity and landscapes), the product offerings can also be made exclusive to each NP and therefore tourists can have the opportunity for different MTEs in each park. Providing product offerings that afford MTE opportunities are particularly important for NPs, as government funding is decreasing and each NP needs to generate its own funds. Tourism is presently the economic lifeline for the parks. If NPs focus on improving current products where necessary and developing new products that provide for MTEs, NPs could increase their competitive advantage. Having a competitive advantage can ensure an increase in tourism numbers and therefore the financial sustainability of the park. Data was collected on site at each of the three NPs selected for the study, using convenience sampling to select respondents. A web-based survey was also posted on the SANParks’ website. Prior to the posting of the web-based survey, SANParks conducted a simple random sampling procedure utilising a sampling frame of tourists who had previously visited the respective NPs. The selected target population emanating from simple random sampling was e-mailed the link to the SANParks website which guided respondents to the online questionnaire if they wished to take part in the survey, hence the response sample was a convenience sample. In total, 463 usable questionnaires were received. Descriptive statistics resulted from the data analysis. A frequency analysis showed the distribution of the results, while an exploratory factors analysis (EFA) was conducted to ascertain any latent factors in the data. The results of the EFA showed the presence of three latent factors which were labelled Pleasure, Social Interaction and Discovery and Enrichment. Firstly, a strong positive correlation was shown between two of the factors, namely Pleasure and Discovery and Enrichment, and secondly, a positive correlation between two other factors, namely Social Interaction and Discovery and Enrichment was indicated. A weak correlation was shown between the factors Pleasure and Social Interaction. This research has contributed to the knowledge base regarding the factors that make a visit to AENP, CNP and MZNP memorable. Future research can make use of these factors for more exhaustive research in a wider range of NPs

Structural insight into the TRIAP1/PRELI-like domain family of mitochondrial phospholipid transfer complexes

The composition of the mitochondrial membrane is important for its architecture and proper function. Mitochondria depend on a tightly regulated supply of phospholipid via intra-mitochondrial synthesis and by direct import from the endoplasmic reticulum. The Ups1/PRELI-like family together with its mitochondrial chaperones (TRIAP1/Mdm35) represent a unique heterodimeric lipid transfer system that is evolutionary conserved from yeast to man. Work presented here provides new atomic resolution insight into the function of a human member of this system. Crystal structures of free TRIAP1 and the TRIAP1–SLMO1 complex reveal how the PRELI domain is chaperoned during import into the intermembrane mitochondrial space. The structural resemblance of PRELI-like domain of SLMO1 with that of mammalian phoshatidylinositol transfer proteins (PITPs) suggest that they share similar lipid transfer mechanisms, in which access to a buried phospholipid-binding cavity is regulated by conformationally adaptable loops

No backstage: the relentless emotional management of acute nursing through the COVID-19 pandemic.

The COVID-19 pandemic disordered the routine delivery of health care. We explored nurses' experiences of working in COVID and non-COVID facing roles, focusing on staff in the acute sector of one Scottish health board. The study covered the period between April and July 2021, and was conducted through twenty in-depth interviews. Interactions between patients, family members and nurses changed due to inflection control measures. Staff experienced a range of conflicting emotions, e.g. fear of infection and transmission but a strong sense professional duty to contribute to the pandemic effort. Nurses were dissatisfied with the care they provided and experienced moral dilemmas, distress and injury from the emotional labour caused not only by working under the infection control measures, but also by the virulence and uncertainty of this new disease. We draw on earlier works - Goffman's (1967) presentation of self, Hochschild's (1983) work on emotional labour, and Bolton and Boyd's (2003) work furthering emotional labour - to illustrate that the usual rules and routines of interaction between patients, family and staff were abandoned. Nurses were able to mask their distress and injury, but were often unable to effectively deliver the correct emotional response due to infection control measures, such as protective clothing (PPE) and social distancing. The 'backstage' spaces, important for dealing with the emotion of front stage performances, were missing for those in COVID-facing roles. The isolating work, and the removal of spaces for the donning and doffing of PPE, resulted in limited or no opportunity for humour and the enacting of collective care. Their private space offered little reprieve with the constant media attention on infection levels, death and nursing 'heroes'

Medical students volunteering in hospital: a novel method of exploring and recording the patient experience

Background: Patient experience is increasingly recognised as an important feature of healthcare quality improvement. However, many of the methods implemented for its collection have significant limitations and reliability issues. This article describes how a UK healthcare organisation worked with medical student volunteers to build capacity for the collection of patient feedback in evidence-informed ways, and summarises student reflections on this process. Aims: To improve the quantity and quality of inpatient feedback, and in doing so provide new learning opportunities for medical students. Conclusions: Patient feedback gathered by volunteers is beneficial to the service and to medical student volunteers. As the feedback gathered is ward-specific, opportunities are created for practice improvements to be identified and acted on. It is feasible for medical students to be trained effectively as volunteers in gathering patient care experiences with adequate support mechanisms in place. Implications for practice: - Healthcare services should consider the use of personnel independent of the care team for thecollection of patient feedback - Patient feedback needs to be shared with practitioners in a timely manner - Medical schools should consider this type of volunteering as a unique opportunity for medicalstudents to improve understanding of patients' experiences of healthcare, and of how care canbe person-centredsch_nurAhmed, F., Burt, J. and Roland, M. (2014) Measuring patient experience: concepts and methods. The Patient. Vol. 7. No. 3. pp 235-241. doi: 10.1007/s40271-014-0060-5. Davies, E. and Cleary, P. (2005) Hearing the patient's voice? Factors affecting the use of patient survey data in quality improvement. Quality and Safety in Health Care. Vol. 14. No. 6. pp 428-432. doi: 10.1136/qshc.2004.012955. Davies, E., Shaller, D., Edgman-Levitan, S., Safran, D., Oftedahl, G., Sakowski, J. and Cleary, P. (2008) Evaluating the use of a modified CAHPS survey to support improvements in patient-centred care: lessons from a quality improvement collaborative. Health Expectations. Vol. 11. No.2. pp 160-176. doi: 10.1111/j.1369-7625.2007.00483.x. De Silva, D. (2013) Measuring Patient Experience. Retrieved from: tinyurl.com/HF-patientexp (Last accessed 12th January 2017). London: The Health Foundation. De Silva, D. (2014) Helping Measure Person-centred Care. Retrieved from: tinyurl.com/HF-personcentred (Last accessed 12th January 2017). London: The Health Foundation. Dewing, J., McCormack, B. and Titchen, T. (2014) Practice Development Workbook for Nursing, Health and Social Care Teams. Oxford: John Wiley and Sons. Doyle, C., Lennox, L. and Bell, D. (2013) A systematic review of evidence on the links between patient experience and clinical safety and effectiveness. BMJ Open. Vol. 3. No. 1. p.e001570. doi: 10.1136/ bmjopen-2012-001570. Edwards, A., Evans, R., White, P. and Elwyn, G. (2011) Experiencing patient-experience surveys: a qualitative study of the accounts of GPs. British Journal of General Practice. Vol. 61. No. 585. pp 157-166. doi: 10.3399/bjgp11X567072. Entwistle, V., Firnigl, D., Ryan, M., Francis, J. and Kinghorn, P. (2012) Which experiences of health care delivery matter to service users and why? A critical interpretive synthesis and conceptual map. Journal of Health Services Research and Policy. Vol. 17. No. 2. pp 70-78. doi: 10.1258/ jhsrp.2011.011029. Framework for Measuring Impact (2012) The Picker Patient Experience Questionnaire (PPE-15). Retrieved from: tinyurl.com/PPE-15. (Last accessed 9th March 2017). Gibbs, G. (1988) Learning by Doing: A Guide to Teaching and Learning Methods. Oxford: Further Education Unit. Jenkinson, C., Coulter, A. and Bruster, S. (2002) The Picker Patient Experience Questionnaire: Development and validation using data from inpatient surveys in five countries. International Journal for Quality in Health Care. Vol. 14. No. 5. pp 353-358. doi: 0.1093/intqhc/14.5.353. The Authors 2017 International Practice Development Journal 7 (1) [9] fons.org/library/journal.aspx 8 Reeves, R. (2008) Better Together: Scotland's Patient Experience Programme. Building on the Experiences of NHS Boards. Retrieved from: tinyurl.com/scot-better (Last accessed 16th March 2017). Edinburgh: Scottish Government Social Research. Reeves, R. and Seccombe, I. (2008) Do patient surveys work? The influence of a national survey programme on local quality-improvement initiatives. Quality and Safety in Health Care. Vol. 17. No. 6. pp 437-441. doi: 10.1136/qshc.2007.022749. Scottish Government (2011) Patient Rights (Scotland) Act 2011, Section 3. Retrieved from: tinyurl. com/scot-patientact (Last accessed 12th January 2017). Skea, Z., Harry, V., Bhattacharya, S., Entwistle, V., Williams, B., MacLennan, G. and Templeton, A. (2004) Women's perceptions of decision-making about hysterectomy. British Journal of Obstetrics and Gynaecology. Vol. 111. No. 2. pp 133-142. doi: 10.1046/j.1471-0528.2003.00027.x. Williams, B., Coyle, J. and Healy, D. (1998) The meaning of patient satisfaction: an explanation of high reported levels. Social Science and Medicine. Vol. 47. No. 9. pp 1351-1359. doi: 10.1016/S0277- 9536(98)00213-5.7pub4769pub

Developing new methods for person-centred approaches to adjudicate context−mechanism−outcome configurations in realist evaluation

From MDPI via Jisc Publications RouterRealist evaluation provides a general method of evaluating the application of interventions including policy, legislation, projects, and new processes in social settings such as law enforcement, healthcare and education. Realist evaluation focuses on what about interventions works, for whom, and in what circumstances, and there is a growing body of work using realist evaluation to analyse interventions in healthcare organizations, including those using Lean Six Sigma improvement methodologies. Whilst realist evaluation facilitates the analysis of interventions using both qualitative and quantitative research, there is little guidance given on methods of data collection and analysis. The purpose of this study is to address this lack of guidance through detailing the use of innovative person-centred methods of data collection and analysis in a realist evaluation that enabled us to understand the contribution of Lean Six Sigma to person-centred care and cultures. This use of person-centred principles in the adjudication of identified program theories has informed novel methods of collecting and analysing data in realist evaluation that facilitate a person-centred approach to working with research participants and a way of making the implicit explicit when adjudicating program theory.19pubpub

A realist inquiry to identify the contribution of Lean Six Sigma to person-centred care and cultures

From MDPI via Jisc Publications RouterA lack of fidelity to Lean Six Sigma’s (LSS) philosophical roots can create division between person-centred approaches to transforming care experiences and services, and system wide quality improvement methods focused solely on efficiency and clinical outcomes. There is little research into, and a poor understanding of, the mechanisms and processes through which LSS education influences healthcare staffs’ person-centred practice. This realist inquiry asks ‘whether, to what extent and in what ways, LSS in healthcare contributes to person-centred care and cultures’. Realist review identified three potential Context, Mechanism, Outcome configurations (CMOcs) explaining how LSS influenced practice, relating to staff, patients, and organisational influences. Realist evaluation was used to explore the CMOc relating to staff, showing how they interacted with a LSS education Programme (the intervention) with CMOc adjudication by the research team and study participants to determine whether, to what extent, and in what ways it influenced person-centred cultures. Three more focused CMOcs emerged from the adjudication of the CMOc relating to staff, and these were aligned to previously identified synergies and divergences between participants’ LSS practice and person-centred cultures. This enabled us to understand the contribution of LSS to person-centred care and cultures that contribute to the evidence base on the study of quality improvement beyond intervention effectiveness alone.https://doi.org/10.3390/ijerph18191042718pubpub1