Institutions In England Research Articles

Abstract 3098: Epigenetic therapy to target neuroendocrine prostate cancer using precision medicine models

Abstract Background Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer that may either arise de novo or much more commonly after hormonal therapy for prostate adenocarcinoma. Patients diagnosed with NEPC are often treated with platinum chemotherapy able to produce only short duration responses underling the urgent need of identifying novel potential therapeutic targets for this lethal disease. In the context of our Englander Institute for Precision Medicine we developed patient derived 3D NEPC tumor organoids and patient derived PDXs to test specific inhibitors on molecular targets identified by genomic analysis of native tumors. Emerging data from an integrative molecular analysis of metastatic tumors from a large cohort of castration resistant prostate cancer (CRPC) patients, including NEPC, points to a key role of the Polycomb gene EZH2 and the epigenome in the pathogenesis of NEPC. Methods Tumor organoids were developed according to protocols developed by our Englander Institute for Precision Medicine and other Institutes. Briefly the tissue biopsies (liver and bone biopsy) were washed, enzymatically digested and then seeded in a Matrigel (BD) droplet. Organoids were then characterized at both genomic (WES) and protein level (IHC) to confirm the expression of specific markers. Organoids were also subcutaneously injected in NSG mice to generate PDX for drug treatment in vivo. Results Based on the significant EZH2 overexpression in NEPC tumors by RNA-Seq and tissue microarray, we checked the expression of EZH2 and H3K273M, the readout of its activity, in NEPC organoids and we found out that both EZH2 and H3K273M were high expressed in NEPC organoids. Therefore we evaluated the effects of the EZH2 inhibitor, GSK343, in NEPC versus CRPC organoids and in the castration resistant line DU145 versus the NEPC cell line NCI-H660. We found out that GSK343 effectively inhibited H3K27me3 and resulted in a significant reduction of NEPC organoids and H660 viability while DU145 as well as CRPC organoids were insensitive to the drug. We extended our studies generating PDXs by subcutaneously injecting NEPC tumor organoids in NSG mouse. The tumor extracted from the PDXs showed a high proliferative phenotype with molecular features characteristic of NEPC as chromogranin A expression and no androgen receptor expression. NEPC PDXs were treated with the EZH2 inhibitor, GSK126, and we observed a significant reduction of tumor size along with the treatment suggesting that EZH2 is a potential therapeutic target for this highly aggressive disease. Conclusions In the Englander Institute for Precision Medicine we are generating NEPC patient tumor organoids and PDXs to unveil new targets to facilitate therapeutic decision at this late stage disease. Among the possible hits, EZH2 represents a promising drug target and a potential modulator of the NEPC phenotype. Citation Format: Loredana Puca, Wouter R. Karthaus, Dong Gao, John Wongvipat, Andrea Sboner, Marcello Gaudiano, Chantal Pauli, Rema A. Rao, Juan Miguel Mosquera, Joanna Cyrta, Theresa Y. MacDonald, Giorgio Ga Inghirami, Yu Chen, Mark A. Rubin, Himisha Beltran. Epigenetic therapy to target neuroendocrine prostate cancer using precision medicine models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3098.

Abstract 619: Personalized models to guide precision medicine

Abstract BACKGROUND Precision oncology is a clinical approach aimed towards tailoring treatment strategies for patients based on the genetic profile of each patient's cancer. Available cell line models alone often do not accurately recapitulate the genetic profile of individual patient tumors and therefore limit preclinical evaluation of newly targeted agents. Furthermore, a high failure rate of drug candidates can be attributed in part to the use of monolayer cultures as the initial screening method that is associated with highly variable responses and does not predict clinically observed chemoresistance. In our Englander Institute for Precision Medicine we developed a program utilizing patient derived tumor organoids, in combination with individualized genomic sequencing, targeted and/or high throughput drug screenings to nominate drug candidates in a precision patient care setting. Drug candidates are further validated with personalized in vivo models. Utilizing these various genomic and biological platforms for pharmacological screenings, we can more closely recapitulate the in vivo tumor of individual patients and can more accurately model personalized therapeutic response and resistance in vitro and in vivo. DESIGN Fresh tissue samples were collected, washed and mechanically or enzymatically dissociated and then plated in a Matrigel (BD) scaffold with primary culture media. Primary spheres were characterized according to our cytology, histology and genomic platforms. Established and characterized tumor organoids were expanded, cryopreserved for banking, used for in vitro studies and implanted in nude mice for patient derived xenografts (PDXs) to further validate potential drug candidates. RESULTS Our success rate in generating patient derived pan-cancer tumor organoids is 30%, depending on specimen quality and tumor type (e.g. endometrial cancer 70%, metastatic prostate cancer 15%). Morphology and molecular profiles show good concordance among tumor organoids and native tumor tissues. The success rate in establishing PDXs from organoid cultures is currently at 70-80%. In vitro and in vivo drug screenings show tumor specific drug sensitivity. CONCLUSION We have developed protocols for the generation and characterization of individual patient-derived tumor organoids. Cytopathology, histopathology and molecular pathology represent important platforms in our Precisicon Medicine Program. Tumor organoid characterization, pharmacological screenings and drug validation in PDX models are effective models which can be used to tailor standard of care treatment, study drug resistance, and nominate novel therapeutic targets unique to the individual genomic landscape and biology of each tumor. Citation Format: Chantal Pauli, Loredana Puca, Brooke M. Emerling, Benjamin Hopkins, Andrea Sboner, Olivier Elemento, Juan Miguel Mosquera, Himisha Beltran, Mark A. Rubin. Personalized models to guide precision medicine. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 619.

An analysis of the stakeholder model of public boards and the case of school governing bodies in England and Wales

This article analyses the stakeholder model of boards that is widely used in public and third sector institutions in England and Wales. The central tenet of this model is that such institutions should be strategically led by individuals who are representative of and from the groups that have an interest in them. The article focuses in particular on the operation of the stakeholder model of governing bodies of schools in England and Wales where a range of stakeholders including teachers, parents and the community are represented. The issues that arise from this stakeholder model of governing are analysed and the alternatives to it are considered. A significant alternative is the skills-based model, where boards are constituted on the basis of their expertise and not their interest in the institution. This skills-based model is becoming more prominent in the way governing bodies of academy schools in England are constituted and this is certainly the direction of travel outlined in the 2015 regulations. The article reviews the stakeholder model for the governance of schools at a time when there is much interest in the skills-based approach. The wider implications of shifting from a stakeholder to a skills-based model of public board membership are considered.

The efficiency of higher education institutions in England revisited: comparing alternative measures

Data envelopment analysis (DEA) has often been used to evaluate efficiency in the context of higher education institutions. Yet there are numerous alternative non-parametric measures of efficiency available. This paper compares efficiency scores obtained for institutions of higher education in England, 2013–2014, using three different methods: the original Charnes et al. method and two slacks-based methods (SBM-Min and SBM-Max) developed by Tone. The findings suggest that results are highly sensitive to methodology chosen. Hence caution is required in applying the results in any policy context.

Troubling ideas for widening participation: how higher education institutions in England engage with research in their access agreements

This article explores how higher education institutions in England engage with research in their access agreements. Through an analysis of access agreements from 2014-15 to 2016-17, a picture of how research is understood, undertaken and documented emerges. A lexical analysis of the texts was used to establish the different ways research is being referred to or funded as part of the access agreement process. The analysis shows a productive relationship between national policy and institutional activity. But there appears to be a lack of infrastructure at an institutional and sector level to join up sustained and rigorous research with widening participation activity and policy. This means that, even after ten years of access agreements, widening participation is not fully embedded into the academic practice of higher education. We argue that research undertaken as part of the access agreement process can provide much needed evidence of impact and situate activity within an institution-wide context. However, we also suggest that widening participation research has the potential to offer productive troubling ideas to dominant rhetoric and, in so doing, shape new ways of thinking about, and doing, widening participation within institutions and across the sector.

Senior management perspectives of mathematics and statistics support in higher education: moving to an ‘ecological’ approach

ABSTRACTThis article explores the perspectives of three senior managers in higher education institutions in England regarding their mathematics and statistics support provision. It does so by means of a qualitative case study that draws upon the writing of Ronald Barnett about the identity of an ‘ecological’ university, along with metaphors associated with the notion of organisations as living ‘organisms’, suggested by Gareth Morgan. Using these ideas as a heuristic sheds light upon the view that whilst outwardly universities appear to represent a uniform landscape, mathematics and statistics support alternatively, can be seen as different ‘species’ within the higher education system. The study illustrates how three universities occupying contrasting ecological ‘niches’ are responding to the challenges they face by providing and planning different forms of learning support for mathematics and statistics. In conclusion, it is recommended that senior managers reflect upon the possibilities offered by the idea of ‘ecological’ identities in order to explore how they might respond strategically to a rapidly changing environment. This includes adapting various solutions and the further development of innovative ways of supporting students’ transitions throughout the academic lifecycle. In addition, an ecological approach could also aid the formation of the co-creational relationships and networks required for the future success of those developments.

Should students have to borrow?

Since autumn 2012, higher education institutions in England have been able to charge undergraduate students up to £9,000 a year in tuition fees. Full‐time students are expected to take out loans large enough to cover their tuition fees and living costs for the duration of their studies. They must start repaying these loans if and when their earnings reach £21,000 a year.In this bold and timely pamphlet, Christopher Martin argues that forcing students to borrow is a serious mistake. He contends that higher education is a welfare good on a par with basic schooling and health care. To flourish in liberal democratic societies, citizens must be personally autonomous, and the educational demands of personal autonomy are too heavy to be met by compulsory schooling alone. To lead autonomous lives, adult citizens need ongoing educational support, support that the liberal democratic state has an obligation to provide. Higher education should therefore be a universal entitlement and free at the point of use.The global debate about who should pay for higher education is by no means settled. As England shifted the financial burden from taxpayers to students, Germany moved in the opposite direction: all German universities have offered free tuition since 2014. Christopher Martin's distinctive contribution to the debate is to lay out a principled argument, based on a plausible assessment of the purpose of higher education, for the view that students should not have to pay for their education. His argument is controversial, to be sure, but it represents a serious and considered attempt to set the question of higher education funding on sure normative foundations.

Data and performance: can education and health learn from each other?

At a time when all public sector institutions in England are under increasing pressure to do more with less1 and are often judged on simple numerical scores reflecting aspects of performance, now may be a good time for different sectors to work together to understand the benefits and challenges of collecting and publishing data. In both health and education, data are collected and published about a multitude of inputs and outcomes, and are frequently used to understand performance, inform policy and practice, as well as to judge and rank institutions and, sometimes, individuals. I have worked in primary and secondary education for 20 years and am now involved in analysing health data. I have been intrigued by some of the differences in the approach to data in these two important public sector areas and this article highlights two areas which may be of particular interest to people working in general practice, focusing on school settings and general practices in England. Staff in English schools know who they are teaching to an amazing level of detail. They know about pupils’ progress, achievement, and attendance, but also about the interventions they have received and their participation in extra-curricular activities. Pupils are tracked in terms of national and local targets as well as school-based targets. This is known for individual children and year groups. Schools also know this in terms of groups of pupils; for example, whether pupils in receipt of the pupil premium, (extra funding given to schools for children from socioeconomically disadvantaged backgrounds) are making as much progress as pupils who aren’t. In addition, they know about the progress of sub-groups; for example, whether girls in receipt of the pupil premium and who have English as an additional language are making good progress in comparison to their peers. This information …

Institutional adaptive capacities to promote Ecosystem-based Adaptation (EbA) to flooding in England

Purpose – The purpose of this paper is to assess the inherent adaptive capacities of multilevel flood management institutions in England that are necessary to espouse the concept of Ecosystem-based Adaptation (EbA). Design/methodology/approach – This paper is based on an extensive assessment of flood management literature including European and English flood management policies, strategies, regulations and reports. First, an assessment protocol was developed from systematic literature search and, second, multilevel flood management policies and organizations were evaluated. A qualitative scoring method was applied at the assessment stage. Findings – The protocol included 18 major assessment criteria under seven EbA principles. Application of the protocol showed that English national flood policies showed comparatively greater adaptive capacities than European- and local-level policies and local organizations. Specialized flood management policies such as Catchment Flood Management Policies at the local level and European Policies such as flood directives are among the lowest-scoring policy institutions. It was also identified that there is an emerging trend of stakeholder participation, catchment-based approach and knowledge-based adaptation planning at the national level which potentially can be the entry points of wider-scale EbA implementation. This paper recommends proactive roles of local executive organizations through improving institutional communication, consideration of catchment-scale planning with clear adaptation goals and valuing local knowledge base. Originality/value – The research is important to identify the institutional aspects of adaptive capacity that require attention for promoting alternative adaptation measures such as EbA.

Targeting of widening participation measures by elite institutions: widening access or simply aiding recruitment?

ABSTRACTThe impact of widening participation policy and how it is enacted institutionally is a central concern to Higher Education. It is not simply about the admission of students from disadvantaged backgrounds, but also ensuring that these students complete their courses successfully. This work therefore goes far beyond those departments tasked with access and outreach and has implications for staff across all academic and support service areas. The way in which national policy is interpreted and translated into local policy can therefore affect the whole institution. To bring a spotlight on these issues, this paper will focus on a case study of a single elite institution in England. Focusing primarily on selection of students, it will examine how selection measures can in fact reproduce inequalities. It will therefore demonstrate how this programme may not improve access to Higher Education but instead focuses on ensuring that students already on a path to Higher Education choose this institution in preference to others.

The eco-club: a place for the becoming active citizen?

This paper makes a twofold contribution. Firstly it presents a typology of eco-clubs that can be used to contextualise eco-club observations by researchers and can support management of eco-clubs by practitioners. Secondly it explains how participation in eco-clubs provides a space for a child to both enact and develop as a citizen, a place for being-as-becoming. It shows how children navigate adult behaviours in these settings and how these experiences afford opportunities for the development of attributes including critical and analytical thinking that are commonly associated with citizenship education in England. In conclusion the paper makes links between these unintended outcomes and the liberal underpinnings of educational institutions in England.

The student-as-consumer approach in higher education and its effects on academic performance

Students studying at universities in England have been defined as customers by the government since the introduction of student tuition fees. Although this approach has been rejected by educators, there is a lack of empirical evidence about the extent to which students express a consumer orientation and its effects on academic performance. These issues were examined in the current study by surveying 608 undergraduates at higher education institutions in England about their consumer attitudes and behaviours in relation to their higher education, learner identity, and academic performance. The analysis revealed that consumer orientation mediated traditional relationships between learner identity, grade goal and academic performance, and found that a higher consumer orientation was associated with lower academic performance. Furthermore, responsibility for paying tuition fees and studying a Science, Technology, Engineering and Mathematics subject were associated with a higher consumer orientation and subsequently lower academic performance. Implications for academic performance are discussed.

Towards a Theology of Competition: The Case of Anglican Theological Institutions in England

Beginning with the current state of competition in English Theological Education Institutes (TEIs), which is mirrored on both sides of the Atlantic, this multidisciplinary article introduces an initial theological reflection into competition by considering history, social theory and theology and by looking through the lenses of sport, schools and business. The competitive climate that has emerged within Anglican TEIs over the last few centuries is observed by considering an historical overview. That climate is then discussed in terms of social theory using Michael Porter's Competitive Strategy and then with the insights of theology. The way forward is discussed with awareness of how a Christian theology of theological education must include a theology of competition. The aim is to open a discussion rather than to answer the question, though various theological leads are suggested.

Discussion Paper: The Changing Face of the HE student

This discussion paper explores the current drivers of change in Higher Education institutions in England. It presents models of students and asks you to consider your own institution and student engagement within it. It will then offer detail of a current research project that Newman University have begun.

An emerging role for cytopathology in precision oncology.

Precision medicine is an emerging field in medicine for disease prevention and treatment that takes into account the individual variability in genes, environment, and lifestyle for each individual patient. The authors have developed a special program as part of the Englander Institute for Precision Medicine to grow patient-derived, 3-dimensional tumor organoids for tumor-specific drug testing, tailoring treatment strategies, and as models for studying drug resistance. Routine cytology preparations represent a cost-effective and powerful tool to aid in performing molecular testing in the age of personalized medicine. In this commentary, the platforms used for the characterization and validation of patient-derived, 3-dimensional tumor organoids are outlined and discussed, and the role of cytology as a cost-effective and powerful quality-control measure is illustrated.

Management of Complicated Crown Fractures in Vital Immature Incisors

Introduction: Dental trauma is one of the most serious oral conditions especially among children. It frequently occurs in children from 6 to 13 years old, often involving teeth with incomplete root formation. The most common dental injury at this age is crown fracture. Arguments: To provide this clinical guide, Pubmed and Scopus were searched using the following keywords: Immature, Incisor and Pulpotomy. More importantly, the latest clinical guidelines provided by the International Association for Dental Traumatology, British Society of Paediatric Dentistry, and the Royal College of Surgeons of England and National Institute for Health and Care Excellence were studied and incorporated into this paper (Grade 1 evidence). Conclusions: Management of a young patient who has sustained such trauma includes a wide range of options based on the clinical and radiographic findings. Here we explain in detail the latter as well as covering available literature and guidelines.

Self-care project for faculty and staff of future health care professionals: Case report.

Self-care among health care providers is an important component of their ability to provide quality health care to patients. Health care institutions have programs in place for students that emphasize health and wellness, but few programs are available for faculty and staff. To address this gap and facilitate modeling health and wellness strategies for students, a New England institution that educates health care practitioners began a pilot self-care project for faculty and staff. Both quantitative and qualitative data were collected. The template used for this project could be used as a stepping-stone for future wellness self-care program in higher education for faculty, staff, and students.

Reconciling Carboniferous Accretions: A Performative Script

Reconciling Carboniferous Accretions: A Performance Script is a spatial writing text that sets the scene for a site-specific performance at The North of England Institute of Mining and Mechanical Engineers (NEIMME) in Newcastle upon Tyne, UK. Like any script, the text anticipates the possibility of multiple performances, and yet when augmented visually by sketches, photographs and dialogue, the script recalls one version of what did happen at its only performance to date as part of the Architecture and Humanities Research Association’s (AHRA) Industries of Architecture conference in November 2014. The artwork advocates for coal as a live material caught up amongst material–corporeal relations, an approach that emerges from of the philosophies of Luce Irigaray, Donna Haraway, Jane Bennett and Elizabeth Grosz. The performance proceeds as a love poem to coal, a recitation that poses a radical encounter with geological processes, opencast mining practices and a red-carpeted room in NEIMME set aside for coalmining conciliations and Freemason meetings.

Who governs Britain - Democracy in action? Directly Elected Mayors in England

Over the past decade and a half in Britain, citizens have been consulted by referenda on questions of devolution, the office of Mayor of London (1997), directly elected mayors (2002-2012) and, more recently, the voting system (2012). The office of Mayor has a long-standing history in Britain. What is new is the manner in which some are now elected and the significance this office has taken on with the changes in their electoral legitimacy. This paper examines the debates about the advantages and disadvantages of directly electing mayors and on the nature of democracy and the reliability of democratic institutions in Britain. It also analyses reasons for the relative successes and failures of the changes introduced, looking in particular at the scale at which direct democracy can operate.

Succumbing, surviving, succeeding? Women managers in academia

Purpose– The purpose of this paper is to address an under-explored and under-theorised aspect of gender work in UK academia in that it looks at the professional lives of middle and senior women managers and leaders who are responsible for initial teacher training in their institutions. As Maguire (2002) and Murray (2002, 2006) point out, within academia, teacher trainers occupy a particularly under-researched space despite some recent interest (Korthagen and Vasalos, 2005; Thompson, 2007).Design/methodology/approach– This research draws on a larger study which explored how 22 middle and senior managers and leaders in ten institutions in England try to come to terms with carrying out their roles in the education marketplace. In-depth semi-structured interviews were carried out with these women and data were also collected from field notes from participant observation undertaken at three of the institutions.Findings– Whereas some women are moving into positions of authority in the education marketplace, some existing women managers are being marginalised within new internally differentiated layers of managerial structures. Simultaneously, many women who manage teacher training are engaged in a struggle for survival individually and professionally. Those who succeed have managed to re-invent themselves to endorse neo-liberal discourses.Originality/value– Original empirical research which sheds new light on previous discourses related to women managers in neo-liberal academia.