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This paper draws on my experience of organising a photovoice project with asylum seekers to outline the ethical dilemmas and rewards of planning and facilitating a participatory, creative research project with a hard-to-reach, potentially vulnerable population. It offers lessons learnt and useful insights for others considering a similar approach to data collection. The photo project was utilised to explore the impact of involvement with community-based social protection on the self-reported wellbeing of asylum seekers in the United Kingdom. It was also designed to test the efficacy of the photovoice research methodology to produce simple, impactful findings useful for researcher, research participant and policymaker, empowering those who have often had little voice in community development to inform policy discussions. The paper is written from the author’s perspective, adopting a layered approach that utilises fieldnotes, quotes from project participants, and exhibition attendee feedback to provide a rounded description of the project. It pays particular attention to ethical dilemmas concerning project access, recruitment and communication and the complexity of juggling academic ethical rigour with a community-led approach across cultural and linguistic borders. It highlights how power dynamics can be experienced in the research environment entangled with issues of co-researcher dignity, ownership, and vulnerability. It also details the positive outcomes of the photovoice project in relation to collaborative knowledge creation, empathetic understanding, and advocacy opportunities. The author concludes by offering a summary of the key lessons learnt through the project and their implications for future research.

The Sustainable Development Goals 2030 call for an end to poverty in all its forms everywhere through the adoption of integrated social protection policies. However, recent literature suggests an implicit and explicit discrimination towards asylum seekers and refugees (ASRs) in United Kingdom social policy, leading to high rates of destitution, poor health and isolation. Due to the limited nature of UK government support, many ASRs become involved with semi-formal and informal social protection. This systematic literature review synthesizes existing qualitative literature that documents the impact of these interventions on the wellbeing of adult ASRs in the United Kingdom. The literature offers useful insights into asylum seeker and refugee perceptions of wellbeing, agency, and support responsibility, and how their interaction with social protection providers constrains or enables the realization of their fundamental human needs. The findings demonstrate that government support is inadequate to meet the needs of many asylum seekers and refugees, leading to disempowerment, lack of agency and exploitation. Positive wellbeing outcomes are linked to semi-formal and informal interventions, summarized into six categories: the positive impact of volunteering; physical space and intentional gathering; practical and material support; training and skills development; solidarity, inclusion and understanding; and peer support and advice.

Adeno-associated viruses (AAVs) are typically single-stranded deoxyribonucleic acid (ssDNA) encapsulated within 25-nm protein capsids. Recently, tissue-specific AAV capsids (e.g. PHP.eB) have been shown to enhance brain delivery in rodents via the LY6A receptor on brain endothelial cells. Here, we create a non-invasive positron emission tomography (PET) methodology to track viruses. To provide the sensitivity required to track AAVs injected at picomolar levels, a unique multichelator construct labeled with a positron emitter (Cu-64, t 1/2  = 12.7 h) is coupled to the viral capsid. We find that brain accumulation of the PHP.eB capsid 1) exceeds that reported in any previous PET study of brain uptake of targeted therapies and 2) is correlated with optical reporter gene transduction of the brain. The PHP.eB capsid brain endothelial receptor affinity is nearly 20-fold greater than that of AAV9. The results suggest that novel PET imaging techniques can be applied to inform and optimize capsid design. Adeno-associated viruses (AAVs) can be targeted in a tissue-specific manner, but their tissue accumulation cannot be assessed in a non-invasive manner. Here the authors conjugate a multivalent chelator labelled with Cu-64 to the surface of AAVs and image the brain accumulation of the PHB.eB capsid by PET.

The translocator protein (18 kDa) (TSPO), formerly known as the peripheral benzodiazepine receptor, is dramatically upregulated under pathologic conditions. Activated microglia are the main cell type expressing the TSPO at sites of central nervous system pathology. Radioligands for the TSPO can therefore measure active disease in the brain. This article details the synthesis, radiofluorination, and pharmacologic evaluation of a new TSPO-specific pyrazolopyrimidine, DPA-714. The affinity of DPA-714 for the TSPO was measured in rat kidney membranes with (3)H-PK11195. The in vitro functional activity of DPA-714 was measured in a steroidogenic assay in which the ability of DPA-714 to increase pregnenolone synthesis was measured with rat C6 glioma cells. The radiofluorination of DPA-714 was achieved by nucleophilic (18)F-fluoride displacement of the tosylate precursor. (18)F-DPA-714 was assessed in rats harboring unilateral quinolinic acid (QA) lesions. In addition, pretreatment experiments were performed with PK11195 (5 mg/kg), DPA-714 (1 mg/kg), and DPA-713 (1 mg/kg). The in vivo binding and biodistribution of (18)F-DPA-714 were determined in a baboon with PET. Experiments involving presaturation with PK11195 (1.5 mg/kg) and displacement with DPA-714 (1 mg/kg) were conducted to evaluate the specificity of radioligand binding. In vitro binding studies revealed that DPA-714 displayed a high affinity for the TSPO (dissociation constant, 7.0 nM). DPA-714 stimulated pregnenolone synthesis at levels 80% above the baseline. (18)F-DPA-714 was prepared at a 16% radiochemical yield and a specific activity of 270 GBq/mumol. In rats harboring unilateral QA lesions, an 8-fold-higher level of uptake of (18)F-DPA-714 was observed in the ipsilateral striatum than in the contralateral striatum. Uptake in the ipsilateral striatum was shown to be selective because it was inhibited to the level in the contralateral striatum in the presence of PK11195, nonlabeled DPA-714, or DPA-713. PET studies demonstrated rapid penetration and good retention of (18)F-DPA-714 in the baboon brain. Pretreatment with PK11195 effectively inhibited the uptake of (18)F-DPA-714 in the whole brain, indicating its selective binding to the TSPO. The injection of nonlabeled DPA-714 20 min after the injection of (18)F-DPA-714 resulted in radioligand washout, demonstrating the reversibility of (18)F-DPA-714 binding. (18)F-DPA-714 is a specific radioligand for the TSPO, displaying promising in vivo properties and thus warranting further investigation.

This paper considers United Kingdom welfare provision for asylum seekers in the context of social protection scholarship, policy discourse more commonly associated with international development. Social protection definitions are contested, ranging from those focused on state provision to wider interpretations reflecting debates on holistic wellbeing, human rights and self-actualisation. Most recently, the 2030 Agenda for Sustainable Development has called for social protection policies for all citizens to reduce inequality among and within countries. Though there is exigency to reduce the extreme inequality existing between countries, literature is lacking on how social protection can be used to critique inequality within more economically affluent nations. Commentaries on social protection also tend to focus on economic poverty, with less attention given to vulnerabilities such as marginalisation. Literature suggests that UK asylum welfare provision is based on deterrence, control and marginalisation. In response, and to encourage equity in how all countries’ public policy is assessed, this paper utilises an international social protection framework to critique UK asylum welfare provision. It concludes by advocating for transdisciplinary, human-centred and comprehensive social protection policy design, encouraging participation by a wider range of stakeholders and a holistic understanding of wellbeing to meet asylum seekers’ needs effectively and efficiently.

Background B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE). Methods Female C57BL/6 J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG 1–125 ). PET imaging of naïve and EAE mice was performed 19 h after administration of [ 64 Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted. Results Radiolabelling of DOTA-conjugated CD19-mAb with 64 Cu was achieved with a radiochemical purity of 99% and molar activity of 2 GBq/μmol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02 ± 0.092 vs. 1.68 ± 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ± 0.020 vs. 0.12 ± 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry—providing further evidence that [ 64 Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice. Conclusion CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.

The vascular interface of the brain, known as the blood–brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability 1 – 3 . Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins 4 , 5 . Thus, it is unclear whether permeability to individually injected exogenous tracers—as is standard in BBB studies—fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery. Tagging and tracking the blood plasma proteome as a discovery tool reveals widespread endogenous transport of proteins into the healthy brain and the pharmacologically modifiable mechanisms by which the brain endothelium regulates this process with age.

Background The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4 S )-4-(3-[ 18 F]fluoropropyl)- l -glutamate ([ 18 F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. Methods Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG 35–55 ) peptide in complete Freund’s adjuvant (CFA) followed by pertussis toxin. Control mice received CFA emulsion and pertussis toxin without MOG peptide, while a separate cohort of naïve mice received no treatment. PET studies were performed to investigate the kinetics and distribution of [ 18 F]FSPG in naïve, control, pre-symptomatic, and symptomatic EAE mice, compared to 18 F-fluorodeoxyglucose ([ 18 F]FDG). After final PET scans, each mouse was perfused and radioactivity in dissected tissues was measured using a gamma counter. Central nervous system (CNS) tissues were further analyzed using ex vivo autoradiography or western blot. [ 18 F]FSPG uptake in human monocytes, and T cells pre- and post-activation was investigated in vitro. Results [ 18 F]FSPG was found to be more sensitive than [ 18 F]FDG at detecting pathological changes in the spinal cord and brain of EAE mice. Even before clinical signs of disease, a small but significant increase in [ 18 F]FSPG signal was observed in the spinal cord of EAE mice compared to controls. This increase in PET signal became more pronounced in symptomatic EAE mice and was confirmed by ex vivo biodistribution and autoradiography. Likewise, in the brain of symptomatic EAE mice, [ 18 F]FSPG uptake was significantly higher than controls, with the largest changes observed in the cerebellum. Western blot analyses of CNS tissues revealed a significant correlation between light chain of xc- (xCT) protein levels, the subunit of xc- credited with its transporter activity, and [ 18 F]FSPG-PET signal. In vitro [ 18 F]FSPG uptake studies suggest that both activated monocytes and T cells contribute to the observed in vivo PET signal. Conclusion These data highlight the promise of [ 18 F]FSPG-PET as a technique to provide insights into neuroimmune interactions in MS and the in vivo role of xc- in the development and progression of this disease, thus warranting further investigation.

Treatment with plasma of an early developmental stage, human umbilical cord, revitalizes the hippocampus and improves cognitive function in aged mice. Human umbilical cord blood enhances cognition Aging leads to changes in cognitive function that can lead to neurological disorders. Tony Wyss-Coray and colleagues show that human umbilical cord plasma is able to revitalize the hippocampus and improve cognitive function in aged mice. They find that tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor, is enriched in human cord plasma, young mouse plasma and young mouse hippocampi. It enters the brain following systemic administration and is necessary for the cognitive benefits conferred by cord plasma. Systemic TIMP2 is also essential for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, suggesting that TIMP2 has a role in normal hippocampal function. Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation 1 , an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation 2 , 3 , 4 and downregulated in the aged brain 5 , 6 , 7 , 8 . In addition to revitalizing other aged tissues 9 , 10 , 11 , 12 , 13 , exposure to factors in young blood counteracts age-related changes in these central nervous system parameters 14 , 15 , 16 , although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown 17 . We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high translational value for targeting ageing- or disease-associated hippocampal dysfunction.

This meeting report summarizes a Consultants Meeting that was held at International Atomic Energy Agency headquarters in Vienna to provide an update on radionuclide imaging for neuroscience applications.