Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review

The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies

Heritage, affect and emotion : politics, practices and infrastructures.

Heritage and its economies are driven by affective politics and consolidated through emotions such as pride, awe, joy and pain. In the humanities and social sciences, there is a widespread acknowledgement of the limits not only of language and subjectivity, but also of visuality and representation. Social scientists, particularly within cultural geography and cultural studies, have recently attempted to define and understand that which is more-than-representational, through the development of theories of affect, assemblage, post-humanism and actor network theory, to name a few. While there have been some recent attempts to draw these lines of thinking more forcefully into the field of heritage studies, this book focuses for the first time on relating heritage with the politics of affect. The volume argues that our engagements with heritage are almost entirely figured through the politics of affective registers such as pain, loss, joy, nostalgia, pleasure, belonging or anger. It brings together a number of contributions that collectively - and with critical acuity - question how researchers working in the field of heritage might begin to discover and describe affective experiences, especially those that are shaped and expressed in moments and spaces that can be, at times, intensely personal, intimately shared and ultimately social. It explores current theoretical advances that enable heritage to be affected, released from conventional understandings of both ’heritage-as-objects’ and ’objects-as-representations’ by opening it up to a range of new meanings, emergent and formed in moments of encounter. Whilst representational understandings of heritage are by no means made redundant through this agenda, they are destabilized and can thus be judged anew in light of these developments. Each chapter offers a novel and provocative contribution, provided by an interdisciplinary team of researchers who are thinking theoretically about affect through landscapes, practices of commemoration, visitor experience, site interpretation and other heritage work

Europeanising advisory expertise: The role of 'independent, objective and transparent' scientific advice in agri-biotech regulation

Since various crises of food safety in the European Union (EU), institutional reforms have been designed to regain public confidence in regulatory decisions and their expert basis. By Europeanising advisory expertise, the European Food Safety Authority (EFSA) was also meant to help harmonise 'science-based regulation' and thus facilitate EU decisions. In evaluating agri-biotech products during 2003-2005, however, the EFSA procedure extended previous expert disagreements rather than overcome them. EFSA was designed to demonstrate that expert advice would be 'independent, objective and transparent�; yet tensions arose between expert experience versus independence, between transparency versus objectivity, and between harmonisation versus precaution. These conflicts have been shaped by the dominant problem-diagnosis, which favours a narrow expert consensus within a specific policy view. Alternative problem-diagnoses suggest that expertise should instead be pluralised, so that norms and uncertainties become more explicit. Pressure for EU reform manifests tensions between the dominant and alternative problem-diagnoses

Evaluation of diffusion-weighted MRI and (18F) fluorothymidine-PET biomarkers for early response assessment in patients with operable non-small cell lung cancer treated with neoadjuvant chemotherapy

Objective: To correlate changes in the apparent diffusion coefficient (ADC) from diffusion-weighted (DW)-MRI and standardised uptake value (SUV) from fluorothymidine (18FLT)-PET/CT with histopathological estimates of response in patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant chemotherapy and track longitudinal changes in these biomarkers in a multicentre, multivendor setting. Methods: 14 patients with operable NSCLC recruited to a prospective, multicentre imaging trial (EORTC-1217) were treated with platinum-based neoadjuvant chemotherapy. 13 patients had DW-MRI and FLT-PET/CT at baseline (10 had both), 12 were re-imaged at Day 14 (eight dual-modality) and nine after completing chemotherapy, immediately before surgery (six dual-modality). Surgical specimens (haematoxylin-eosin and Ki67 stained) estimated the percentage of residual viable tumour/necrosis and proliferation index. Results: Despite the small numbers,significant findings were possible. ADCmedian increased (p 30% reduction in unidimensional measurement pre-surgery), showed an increase at Day 14 in ADC75th centile and reduction in total lesion proliferation (SUVmean x proliferative volume) greater than established measurement variability. Change in imaging biomarkers did not correlate with histological response (residual viable tumour, necrosis). Conclusion: Changes in ADC and FLT-SUV following neoadjuvant chemotherapy in NSCLC were measurable by Day 14 and preceded changes in unidimensional size but did not correlate with histopathological response. However, the magnitude of the changes and their utility in predicting (non-) response (tumour size/clinical outcome) remains to be established. Advances in knowledge: During treatment, ADC increase precedes size reductions, but does not reflect histopathological necrosis

Governing policy evaluation? Towards a new typology

As policy evaluation matures, thoughts are turning to its governance. However, few scholars have combined insights from the evaluation and governance literatures to shed new light on this matter. In order to address this important gap, this article develops a new typology of ways to comprehend and perhaps ultimately govern ex-post policy evaluation activities. The article then explores its validity in the context of climate policy evaluation activities, a vibrant policy area in which the demand for and practices of evaluation have grown fast, particularly in Europe. The analysis reveals that the typology usefully guides new thinking, but also highlights important gaps in our empirical knowledge of the various modes of governing policy evaluation. The article identifies a need for a new research agenda that simultaneously develops a fuller understanding of these evaluation practices and the options for governing them

“Growing foods from home”: food production, migrants and the changing cultural landscapes of gardens and allotments

The paper arises out of research that explored how migrant identities are constructed in relation to food practices in a Northern city. Using narrative accounts and participant observation collected through a small scale qualitative study we examine how, in using gardens and allotments to “grow foods from home” alongside locally established fruit and vegetables, a landscape approach allows us to see how migrant gardeners are re-shaping existing cultural landscapes and constructing places of belonging. Whilst these landscapes can be viewed visually as representations of both traditional and hybrid practices, the paper draws on non-representational theories in landscape to explore emotions, embodiment, performance and practice. Such an approach uncovers some of the differences in the meaning of food production for diasporic and non-diasporic migrant gardeners

The heritage of slavery in British jazz festivals

This article explores site-specific heritage questions of the contemporary cultural practice of festivals of jazz – a key transatlantic music form – by bringing together three areas for discussion and development: questions of slavery heritage and legacy; the location, built environment and (touristic) offer of the historic city; and the contemporary British jazz festival, its programme and the senses or silences of (historical) situatedness in the festival package. Other artistic forms, cultural practices and festivals are involved in self-reflexive efforts to confront their own pasts; such are discussed as varying processes of the decolonisation of knowledge and culture. This provides the critical and cultural context for consideration of the jazz festival in the Georgian urban centre. Preliminary analysis of relevant jazz festivals’ programmes, commissions and concerts leads to interrogating the relationship – of silence, of place – between jazz in Britain, historic or heritage locations and venues, and the degree or lack of understanding of the transatlantic slave trade. The heritage centres clearly associated with the slave trade that also have significant (jazz) festivals referred to include Bristol, Cheltenham, Edinburgh, Glasgow, Hull, Lancaster, Liverpool, London, and Manchester

Steps on the Path to Clinical Translation: A workshop by the British and Irish Chapter of the ISMRM

The British and Irish Chapter of the International Society for Magnetic Resonance in Medicine (BIC-ISMRM) held a workshop entitled "Steps on the path to clinical translation" in Cardiff, UK, on 7th September 2022. The aim of the workshop was to promote discussion within the MR community about the problems and potential solutions for translating quantitative MR (qMR) imaging and spectroscopic biomarkers into clinical application and drug studies. Invited speakers presented the perspectives of radiologists, radiographers, clinical physicists, vendors, imaging Contract/Clinical Research Organizations (CROs), open science networks, metrologists, imaging networks, and those developing consensus methods. A round-table discussion was held in which workshop participants discussed a range of questions pertinent to clinical translation of qMR imaging and spectroscopic biomarkers. Each group summarized their findings via three main conclusions and three further questions. These questions were used as the basis of an online survey of the broader UK MR community

Memorials to the victims of Nazism: the impact on tourists in Berlin

This qualitative study explores tourist responses to memorials to the victims of Nazism in Berlin and the impact they have on the tourist experience. The findings are located in the field of study known as dark tourism, of which visiting memorials is a part. The analysis shows that tourists increased their knowledge of the crimes committed by the Nazis, thus fulfilling the educational function of memorials. Tourists were also overwhelmed by their experience; they attested to feelings of sadness, shock, anger, despair and incomprehension. These feelings made it hard for them to resume the role of tourist after their exposure to a memorial. There was acknowledgement of the extent of commemoration practised in Germany

Ghosts in the Garden: locative gameplay and historical interpretation from below

© 2017 Steve Poole. Published with licence by Informa UK Limited, trading as Taylor & Francis Group. The heritage industry now makes extensive use of digital audioguides and similar interpretation tools to reach new audiences but many remain rooted in authoritative and didactic conservatism. This paper critically evaluates the state of play in the field, from downloadable audio tours and apps, through more complex engagements with theatrically enhanced and affective simulation, to attempts at fuller dialogic visitor participation and the use of gps or RFID-triggered game mechanics. While ‘armchair’ and home screen-based game and interpretation models are addressed, particular attention is paid to the use of mobile and locative design, where embodiment in place is privileged over less associative or remote experience. The paper takes a research project led by the author as a case study. Ghosts in the Garden was conceived in collaboration with a museum and an experience design SME to test the potential of immersive, affective real world games on public understandings of history. It sought to engage visitors with researched history from below by using a pervasive media soundscape, the ‘ghosts’ of past visitors and a ‘choose-your-own-adventure’ game mechanic in which outcomes are variable, visitor agency is retained and a more radical model of historical knowledge suggested