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We previously showed that inhibition of glycolysis in cutaneous squamous cell carcinoma (SCC)-initiating cells had no effect on tumorigenesis, despite the perceived requirement of the Warburg effect, which was thought to drive carcinogenesis. Instead, these SCCs were metabolically flexible and sustained growth through glutaminolysis, another metabolic process frequently implicated to fuel tumorigenesis in various cancers. Here, we focused on glutaminolysis and genetically blocked this process through glutaminase (GLS) deletion in SCC cells of origin. Genetic deletion of GLS had little effect on tumorigenesis due to the up-regulated lactate consumption and utilization for the TCA cycle, providing further evidence of metabolic flexibility. We went on to show that posttranscriptional regulation of nutrient transporters appears to mediate metabolic flexibility in this SCC model. To define the limits of this flexibility, we genetically blocked both glycolysis and glutaminolysis simultaneously and found the abrogation of both of these carbon utilization pathways was enough to prevent both papilloma and frank carcinoma.

Gianpiero Cavalleri is Associate Professor of Human Genetics at the Department of Molecular and Cellular Therapeutics at the Royal College of Surgeons in Ireland and is the lead author of a 2017 study into the genetic structure of the Irish Traveller community. The study provided an estimate of when Irish Travellers split from the ‘settled' population in Ireland. This population-based genetic research project involved researchers from the Royal College of Surgeons in Ireland, University College Dublin, the University of Edinburgh and the Hebrew University of Jerusalem and looked into the history and structure of the Traveller population in the context of ‘settled' Irish as well as neighbouring European and Roma Gypsy groups. A full-text version of the study first published in the journal Scientific Reports can be accessed at https://epubs.rcsi.ie/cgi/viewcontent.cgi?referer=https://www.google.ie/&httpsredir=1&article=1100&context=mctart. This interview took place at RCSI on Tuesday 21st November 2017.

On 9th February 2016 SAH Journal was privileged to host a public interview with arguably Ireland’s most successful filmmaker, Jim Sheridan. Born in 1949, Jim Sheridan grew up in family of social and artistic activists in the Sheriff Street area of Dublin’s inner city. He studied at University College Dublin and worked with an emerging generation of writers, performers and theatre makers. He was instrumental in the establishment of the Project Arts Centre and he occupies a central position among a group of artists who have left an indelible mark on the creative and cultural life of Ireland over the past 40 years. Sheridan left Dublin for Canada and then the United States in the early 1980s and became the artistic director at the Irish Arts Center in New York. Following a course in film production at the NYU Tisch School of the Arts, he returned to Dublin and became quickly involved in the burgeoning Irish film industry. The global impact of his debut feature film My Left Foot (1989) marked the beginning of a uniquely successful career as one of the outstanding Irish filmmakers on the international scene. This impact has continued to the present day with the international release of The Secret Scripture (2016). To coincide with the release of his latest feature film, SAH is delighted to publish an edited transcript of the stimulating conversation held at Dublin’s Filmbase between a number of film lecturers and Jim Sheridan.

On 25th November 2015, Studies in Arts and Humanities (SAH) Journal hosted a public interview with leading Irish film and television producer James Flynn (Octagon Productions) and creator/writer of the groundbreaking Irish television drama Love/Hate Stuart Carolan. The interview was conducted by Conor Murphy (Editor-in-Chief, SAH Journal) at Filmbase Ireland before a live audience comprising students and faculty from the film schools of Dublin Business School, Filmbase and Pulse College. This lively and thought-provoking interview provided key insights into the artistic and production processes behind the making of a successful TV drama. James Flynn gave a detailed overview of the funding and legislative frameworks in which the modern day film producer operates both in Ireland and overseas. He provided a fascinating timeline of developments in the filmmaking industry in Ireland in parallel with his own career over the last twenty years. Stuart Carolan explained how the rich and varied characters that inhabit Love/Hate come into being and offered an insight into the daily writing rituals that shaped the development of character, plot and pace. He also spoke about the significance of casting in Love/Hate on the development of the story. The casting of John Connors, for example, influenced Stuart to develop a traveller theme to a greater extent than initially intended. Stuart’s passion for social justice and equality was evident throughout the interview. The interview is replete with analysis of the process of developing Love/Hate including the logistics of shooting in multiple locations and the tight deadlines under which they operated. In addition, James and Stuart offered focussed, helpful and encouraging advice for emerging screenwriters and filmmakers.

Interest remains robust for investment in the primary care space by private equity sponsors and other strategic partners. The proliferation of medical practice transactions involving a sale, merger, investment or [...]

AbstractThreshold selection is a fundamental problem in any threshold-based extreme value analysis. While models are asymptotically motivated, selecting an appropriate threshold for finite samples is difficult and highly subjective through standard methods. Inference for high quantiles can also be highly sensitive to the choice of threshold. Too low a threshold choice leads to bias in the fit of the extreme value model, while too high a choice leads to unnecessary additional uncertainty in the estimation of model parameters. We develop a novel methodology for automated threshold selection that directly tackles this bias-variance trade-off. We also develop a method to account for the uncertainty in the threshold estimation and propagate this uncertainty through to high quantile inference. Through a simulation study, we demonstrate the effectiveness of our method for threshold selection and subsequent extreme quantile estimation, relative to the leading existing methods, and show how the method’s effectiveness is not sensitive to the tuning parameters. We apply our method to the well-known, troublesome example of the River Nidd dataset. [ABSTRACT FROM AUTHOR]

Purpose: The posterior orbit is a confined space, harbouring neurovascular structures, frequently distorted by tumours. Image-guided navigation (IGN) has the potential to allow accurate localisation of these lesions and structures, reducing collateral damage whilst achieving surgical objectives. Methods: We assessed the feasibility, effectiveness and safety of using an electromagnetic IGN for posterior orbital tumour surgery via a comparative cohort study. Outcomes from cases performed with IGN were compared with a retrospective cohort of similar cases performed without IGN, presenting a descriptive and statistical comparative analysis. Results: Both groups were similar in mean age, gender and tumour characteristics. IGN set-up and registration were consistently achieved without significant workflow disruption. In the IGN group, fewer lateral orbitotomies (6.7% IGN, 46% non-IGN), and more transcutaneous lid and transconjunctival incisions (93% IGN, 53% non-IGN) were performed (p =.009). The surgical objective was achieved in 100% of IGN cases, with no need for revision surgery (vs 23% revision surgery in non-IGN, p =.005). There was no statistically significant difference in surgical complications. Conclusion: The use of IGN was feasible and integrated into the orbital surgery workflow to achieve surgical objectives more consistently and allowed the use of minimal access approaches. Future multicentre comparative studies are needed to explore the potential of this technology further. [ABSTRACT FROM AUTHOR]

Understanding of past droughts has been mostly shaped by meteorological data, with relatively less known about the human aspects of droughts, their socio‐economic impacts, as well as choices people make in response to droughts in different environmental and socio‐political contexts. The lack of data that systematically record and categorize drought impacts is an important reason for this disparity. In this paper, we present an Irish drought impacts database (IDID) containing 6094 newspaper reports and 11,351 individual impact records for the island of Ireland, covering the period 1733–2019. Relevant articles were identified through systematic searching of the Irish Newspaper Archives, and recorded impacts were categorized using a modified version of the classification scheme employed by the European drought impact inventory (EDII). Drawing on the wealth and diversity of content provided by the newspapers, the IDID database provides information on the documented temporal and geographical extent of drought events, their socio‐economic and political contexts, their consequences, mitigation strategies employed and their change over time. The IDID also facilitates analysis of long‐term patterns in drought incidence, individual impact categories, as well as detailed insight into the impacts of individual drought events over nearly three centuries of Ireland's history. In addition, by allowing an examination of the coherence between meteorological records and identified impacts, it advances our understanding of the influences that contemporary economic, political, environmental and societal events had on the human experience, perception and impact of droughts. This new open‐access database, therefore, provides opportunities for improving understanding of drought vulnerability and is an important step in developing greater capacity to cope with and respond to future droughts on the island of Ireland. [ABSTRACT FROM AUTHOR]

In this case study, Irish academics reflect on our involvement in a project--Transformative Engagement Network (TEN). This project aims to transform the nature of the engagement between the various stakeholders impacted by or concerned with climate change and to insert the voice and concerns of the most vulnerable food producers into climate change debates. Throughout the project, the Maynooth University team has become increasingly aware of the complexities of development and of the practical and intellectual challenges to the assumptions and beliefs that underpin our disciplines.

Purpose: This study aimed to measure student satisfaction with a revised ophthalmology delivery format, which due to the pandemic had previously relied on a remote online flipped classroom (OFC) format compared to a blended learning format. This educational strategy combined online learning with in-person seminars and practical patient centred sessions. Our previous investigations demonstrated a significant lack of student satisfaction with a curriculum solely reliant on a remote OFC, as such we hypothesised that a blended learning approach would result in improved levels of student satisfaction and knowledge gain. Methods: Non-randomised intervention study of two groups; group 1 = OFC group and group 2 = BL group, compared perspectives of 4th year ophthalmology students using a validated course evaluation questionnaire (CEQ). Results: A total of 59 students from the BL group (n = 257; response rate = 23.0%) and 28 from the OFC group agreed to participate in the study (n = 114; response rate = 24.6%). Participants in the BL group felt it was easier to determine the standard of work that was expected (77.42% v 60.71%) and demonstrated significantly increased satisfaction with staff motivation of students (95.16% v 64.29%, p <0.001) and provision of feedback (74.19% v 46.43%, p = 0.004), compared to the OFC group. Furthermore, students in the BL group also felt the course significantly improved their analytical skills (64.52% v 42.85%, p = 0.023) and ability to work as part of team (69.36% v 25%, p <0.001) as well as reporting reduced dissatisfaction with the level of choice afforded in terms of how they would learn (33.88% v 60.71%, p = 0.31) and the how they were assessed (59.68% v 89.28%, p = 0.004). No evidence of a statistical difference in exam score was observed. Conclusions: The COVID-19 pandemic necessitated an unavoidable pivot to online and distance learning, to meet the challenges presented by government mandates and social distancing requirements. Since many of these directives have been reversed, it is important to evaluate the effectiveness and learner perceptions' of the online and distance learning interventions. In this study we demonstrated a significant student preference for BL compared to the OFC approach, with comparable student performances determined by MCQ examinations. Our findings suggest a preference for reintroducing in-person and patient engagement activities in post-pandemic health professions education. [ABSTRACT FROM AUTHOR]

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