Intraplaque angiogenesis and inflammation are key promoters of atherosclerosis and are mediated by the alpha-V beta-3 (α
β
) integrin pathway. We investigated the applicability of the α
β
-integrin ...receptor-selective positron emission tomography (PET) radiotracer 18F-fluciclatide in assessing human aortic atherosclerosis.
Vascular 18F-fluciclatide binding was evaluated using ex vivo analysis of carotid endarterectomy samples with autoradiography and immunohistochemistry, and in vivo kinetic modelling following radiotracer administration. Forty-six subjects with a spectrum of atherosclerotic disease categorised as stable (n=27) or unstable (n=19; recent myocardial infarction) underwent PET and CT imaging of the thorax after administration of 229 (IQR 217-237) MBq 18F-fluciclatide. Thoracic aortic 18F-fluciclatide uptake was quantified on fused PET-CT images and corrected for blood-pool activity using the maximum tissue-to-background ratio (TBR
). Aortic atherosclerotic burden was quantified by CT wall thickness, plaque volume and calcium scoring.
18F-Fluciclatide uptake co-localised with regions of increased α
β
integrin expression, and markers of inflammation and angiogenesis. 18F-Fluciclatide vascular uptake was confirmed in vivo using kinetic modelling, and on static imaging correlated with measures of aortic atherosclerotic burden: wall thickness (r=0.57, p=0.001), total plaque volume (r=0.56, p=0.001) and aortic CT calcium score (r=0.37, p=0.01). Patients with recent myocardial infarction had greater aortic 18F-fluciclatide uptake than those with stable disease (TBR
1.29 vs 1.21, p=0.02).
In vivo expression of α
β
integrin in human aortic atheroma is associated with plaque burden and is increased in patients with recent myocardial infarction. Quantification of α
β
integrin expression with 18F-fluciclatide PET has potential to assess plaque vulnerability and disease activity in atherosclerosis.
Maladaptive repair contributes towards the development of heart failure following myocardial infarction (MI). The α
β
integrin receptor is a key mediator and determinant of cardiac repair. We aimed ...to establish whether α
β
integrin expression determines myocardial recovery following MI.
F-Fluciclatide (a novel α
β
-selective radiotracer) positron emission tomography (PET) and CT imaging and gadolinium-enhanced MRI (CMR) were performed in 21 patients 2 weeks after ST-segment elevation MI (anterior, n=16; lateral, n=4; inferior, n=1). CMR was repeated 9 months after MI. 7 stable patients with chronic total occlusion (CTO) of a major coronary vessel and nine healthy volunteers underwent a single PET/CT and CMR.
F-Fluciclatide uptake was increased at sites of acute infarction compared with remote myocardium (tissue-to-background ratio (TBR
) 1.34±0.22 vs 0.85±0.17; p<0.001) and myocardium of healthy volunteers (TBR
1.34±0.22 vs 0.70±0.03; p<0.001). There was no
F-fluciclatide uptake at sites of established prior infarction in patients with CTO, with activity similar to the myocardium of healthy volunteers (TBR
0.71±0.06 vs 0.70±0.03, p=0.83).
F-Fluciclatide uptake occurred at sites of regional wall hypokinesia (wall motion index≥1 vs 0; TBR
0.93±0.31 vs 0.80±0.26 respectively, p<0.001) and subendocardial infarction. Importantly, although there was no correlation with infarct size (r=0.03, p=0.90) or inflammation (C reactive protein, r=-0.20, p=0.38),
F-fluciclatide uptake was increased in segments displaying functional recovery (TBR
0.95±0.33 vs 0.81±0.27, p=0.002) and associated with increase in probability of regional recovery.
F-Fluciclatide uptake is increased at sites of recent MI acting as a biomarker of cardiac repair and predicting regions of recovery.
NCT01813045; Post-results.
In this paper we empirically explore the ways in which young people were enroled in a multimodal exhibition to creatively produce narratives of their past, presents and futures. We look at the ...different ways this work was framed, and how all memory work and, we argue, future work is relational, interactionally produced and situated in dynamic and unfolding social and political frameworks. We look at the ways young people described the work of producing accounts of their futures within that setting, and the different forms of labour involved in that process. We explore the encounters that fostered local, more humble, acts of care and repair, and how those everyday practices might help build towards reparative futures.
•This paper attends to the practices involved in producing accounts of reparative futures by young people in Uganda.•We look at how a creative, co-produced touring exhibition opened up inclusive encounters that were embedded in broader political and social structures.•We describe the hard work of engaging with different narratives of lived experiences of the past, and how that created space for alternative imaginaries of the future to emerge.•This hard work was a ‘burden’ for the young people, and produced temporal disruptions in their accounts of their past, present and future, which needs to be considered in reparative future work.
Drawing on research in Uganda, we describe our project in which we invited young people to think about their lives in ways that opened up creative and hopeful imaginaries of the future. We understand ...future imaginary work to be a significant part of memory work. An important component in the ways we think about the past is imagining the futures it ties to. We wanted the idea of the future to be something our young participants constructed together, in dialogue and iteratively, so that the project had a sense of collaboration and shared interests. To do so we developed the idea of a touring exhibition through which multiple voices, positions, understandings and values could be accommodated side by side. The article contributes to scholarly and public debates about reparations and memorialisation, particularly by showing the crucial role young people can play in articulating more just futures.
The field of memory studies tends to focus attention on the '3Ms' - museums, monuments, memorials - as sites where memories are constructed, communicated, and contested. Where education is identified ...as a site for memory, the focus is often narrowly on what is or is not communicated within curricula or textbooks, assuming that schools simply pass on messages agreed or struggled over elsewhere. This article explores the possibilities opened when educative processes are not taken as stable and authoritative sites for transmitting historical narratives, but instead as spaces of contestation, negotiation and cultural production. With a focus on 'difficult histories' of recent conflict and historical injustice, we develop a research agenda for education as a site of memory and show how this can illuminate struggles over dominant historical narratives at various scales, highlighting agencies that educational actors bring to making sense of the past.
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