| 1. |
- Alagaratnam, J., et al.
(author)
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No evidence of neuronal damage as measured by neurofilament light chain in a HIV cure study utilising a kick-and-kill approach
- 2021
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In: Journal of Virus Eradication. - : Elsevier BV. - 2055-6640. ; 7:3
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Journal article (peer-reviewed)abstract
- Objective: HIV-remission strategies including kick-and-kill could induce viral transcription and immune activation in the central nervous system, potentially causing neuronal injury. We investigated the impact of kick-and-kill on plasma neurofilament light (NfL), a marker of neuro-axonal injury, in RIVER trial participants commencing antiretroviral treatment (ART) during primary infection and randomly allocated to ART-alone or kick-and-kill (ART + vaccination + vorinostat (ART + V + V)). Design: Sub-study measuring serial plasma NfL concentrations. Methods: Plasma NfL (using Simoa digital immunoassay), plasma HIV-1 RNA (using single-copy assay) and total HIV-1 DNA (using quantitative polymerase chain reaction in peripheral CD4(+) T-cells) were measured at randomisation (following >= 22 weeks ART), week 12 (on final intervention day in ART + V + V) and week 18 post randomisation. HIV-specific T-cells were quantified by intracellular cytokine staining at randomisation and week 12. Differences in plasma NfL longitudinally and by study arm were analysed using mixed models and Student's t-test. Associations with plasma NfL were assessed using linear regression and rank statistics. Results: At randomisation, 58 male participants had median age 32 years and CD4(+) count 696 cells/mu L. No significant difference in plasma NfL was seen longitudinally and by study arm, with median plasma NfL (pg/mL) in ART-only vs ART + V + V: 7.4 vs 6.4, p = 0.16 (randomisation), 8.0 vs 6.9, p = 0.22 (week 12) and 7.1 vs 6.8, p = 0.74 (week 18). Plasma NfL did not significantly correlate with plasma HIV-1 RNA and total HIV-1 DNA concentration in peripheral CD4(+) T-cells at any timepoint. While higher HIV-specific T-cell responses were seen at week 12 in ART + V + V, there were no significant correlations with plasma NfL. In multivariate analysis, higher plasma NfL was associated with older age, higher CD8(+) count and lower body mass index. Conclusions: Despite evidence of vaccine-induced HIV-specific T-cell responses, we observed no evidence of increased neuro-axonal injury using plasma NfL as a biomarker up to 18 weeks following kick-and-kill, compared with ART-only.
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| 2. |
- Garland, P., et al.
(author)
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Haemoglobin causes neuronal damage in vivo which is preventable by haptoglobin
- 2020
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In: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 2:1
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Journal article (peer-reviewed)abstract
- After subarachnoid haemorrhage, prolonged exposure to toxic extracellular haemoglobin occurs in the brain. Here, we investigate the role of haemoglobin neurotoxicity in vivo and its prevention. In humans after subarachnoid haemorrhage, haemoglobin in cerebrospinal fluid was associated with neurofilament light chain, a marker of neuronal damage. Most haemoglobin was not complexed with haptoglobin, an endogenous haemoglobin scavenger present at very low concentration in the brain. Exogenously added haptoglobin bound most uncomplexed haemoglobin, in the first 2 weeks after human subarachnoid haemorrhage, indicating a wide therapeutic window. In mice, the behavioural, vascular, cellular and molecular changes seen after human subarachnoid haemorrhage were recapitulated by modelling a single aspect of subarachnoid haemorrhage: prolonged intrathecal exposure to haemoglobin. Haemoglobin-induced behavioural deficits and astrocytic, microglial and synaptic changes were attenuated by haptoglobin. Haptoglobin treatment did not attenuate large-vessel vasospasm, yet improved clinical outcome by restricting diffusion of haemoglobin into the parenchyma and reducing small-vessel vasospasm. In summary, haemoglobin toxicity is of clinical importance and preventable by haptoglobin, independent of large-vessel vasospasm.
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| 3. |
- Talhouk, R., et al.
(author)
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Involving syrian refugees in design research : Lessons learnt from the field
- 2019
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In: DIS 2019 - Proceedings of the 2019 ACM Designing Interactive Systems Conference. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450358507 ; , s. 1583-1594
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Conference paper (peer-reviewed)abstract
- With the Syrian crisis entering its 8th year, refugees have become the focus of research across multiple disciplines, including design and HCI research. While some researchers have reflected upon designing with refugees, these accounts have been limited to conducting design workshops in formal spaces. Through reflecting on our experiences of conducting design research in informal refugee settlements in Lebanon we unpack lessons learnt, design practices and research approaches that facilitate design engagements with refugees. We highlight the value in participants configuring the design space, using a dialogical approach as well as creating a safe space for both participants and the researcher. We also reflect on the roles that researchers may take on when conducting similar research. By doing so we contribute specific design practices that may be transferrable to other similar contexts.
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| 4. |
- Toombs, A. L., et al.
(author)
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Supporting the complex social lives of new parents
- 2018
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In: CHI '18 Proceedings of the 2018 CHI Conference on Human Factors in Computing Systems. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450356206 - 9781450356213
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Conference paper (peer-reviewed)abstract
- One of the many challenges of becoming a parent is the shift in one's social life. As HCI researchers have begun to investigate the intersection of sociotechnical system design and parenthood, they have also sought to understand how parents' social lives can be best supported. We build on these strands of research through a qualitative study with new parents regarding the role of digital technologies in their social lives as they transition to parenthood. We demonstrate how sociotechnical systems are entangled in the ways new parents manage their relationships, build (or resist building) new friendships and ad hoc support systems, and navigate the vulnerabilities of parenthood. We discuss how systems designed for new parents can better support the vulnerabilities they internalize, the diverse friendships they desire, and the logistical challenges they experience. We conclude with recommendations for future design and research in this area.
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