| 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. |
- Austin, K., et al.
(author)
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Serum neurofilament light concentration does not increase following exposure to low velocity football heading
- 2021
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In: Science and Medicine in Football. - : Informa UK Limited. - 2473-3938 .- 2473-4446. ; 5:3, s. 188-194
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Journal article (peer-reviewed)abstract
- Objectives: To investigate if heading frequency and impact biomechanics in a single session influence the concentration of serum neurofilament light (NF-L), a sensitive biomarker for axonal damage, up to 7 days after heading incident at ball velocities reflecting basic training drills. Methods: Forty-four males were randomized into either control (n = 8), 10 header (n = 12), 20 header (n = 12) or 40 header (n = 12) groups. Linear and angular head accelerations were quantified during heading. Venous blood samples were taken at baseline, 6 h, 24 h and 7 days after heading. Serum NF-L was quantified using Quanterix NF-L assay kit on the Simoa HD-1 Platform. Results: Serum NF-L did not alter over time (p = 0.44) and was not influenced by number of headers [p = 0.47; mean (95% CI) concentrations at baseline 6.00 pg center dot ml(-) (1) (5.00-7.00 pg center dot ml(-) (1)); 6 h post 6.50 pg center dot ml(-1) (5.70-7.29 pg center dot ml(-1)); 24 h post 6.07 pg center dot ml(-1) (5.14-7.01 pg center dot ml(-) (1)); and 7 days post 6.46 pg center dot ml(-1) (5.45-7.46 pg center dot ml(-1))]. There was no relationship between percentage change in NF-L and summed session linear and angular head accelerations. Conclusion: In adult men, heading frequency or impact biomechanics did not affect NF-L response during a single session of headers at ball velocities reflective of basic training tasks.
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| 3. |
- Garland, Patrick, et al.
(author)
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Neurofilament light predicts neurological outcome after subarachnoid haemorrhage.
- 2021
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 144:3, s. 761-768
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Journal article (peer-reviewed)abstract
- To improve outcome prediction following subarachnoid haemorrhage (SAH), we sought a biomarker integrating early brain injury and multiple secondary pathological processes in a prospective study of 42 non-traumatic SAH patients and 19 control individuals. Neurofilament light (NF-L) was elevated in CSF and serum following SAH. CSF and serum NF-L on Days 1-3 post-SAH strongly predicted modified Rankin score at 6 months, independent of World Federation of Neurosurgical Societies (WFNS) score. NF-L from Day 4 onwards also had a profound impact on outcome. To link NF-L to a SAH-specific pathological process, we investigated NF-L's relationship with extracellular haemoglobin. Most CSF haemoglobin was not complexed with haptoglobin, yet was able to be bound by exogenous haptoglobin i.e. haemoglobin was scavengeable. CSF scavengeable haemoglobin was strongly predictive of subsequent CSF NF-L. Next, we investigated NF-L efflux from the brain after SAH. Serum and CSF NF-L correlated positively. The serum/CSF NF-L ratio was lower in SAH versus control subjects, in keeping with glymphatic efflux dysfunction after SAH. CSF/serum albumin ratio was increased following SAH versus controls. The serum/CSF NF-L ratio correlated negatively with the CSF/serum albumin ratio, indicating that transfer of the two proteins across the blood-brain interface is dissociated. In summary, NF-L is a strong predictive marker for SAH clinical outcome, adding value to the WFNS score, and is a promising surrogate end point in clinical trials.
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| 4. |
- Karusala, N., et al.
(author)
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The Future of Care Work : Towards a Radical Politics of Care in CSCW Research and Practice
- 2021
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In: Proceedings of the ACM Conference on Computer Supported Cooperative Work, CSCW 2021. - New York, NY, USA : Association for Computing Machinery (ACM). ; , s. 338-342
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Conference paper (peer-reviewed)abstract
- Computer-Supported Cooperative Work (CSCW) and Human- Computer Interaction (HCI) have long studied how technology can support material and relational aspects of care work, typically in clinical healthcare settings. More recently, we see increasing recognition of care work such as informal healthcare provision, child and elderly care, organizing and advocacy, domestic work, and service work. However, the COVID-19 pandemic has underscored long-present tensions between the deep necessity and simultaneous devaluation of our care infrastructures. This highlights the need to attend to the broader social, political, and economic systems that shape care work and the emerging technologies being used in care work. This leads us to ask several critical questions: What counts as care work and why? How is care work (de)valued, (un)supported, or coerced under capitalism and to what end? What narratives drive the push for technology in care work and whom does it benefit? How does care work resist or build resilience against and within oppressive systems? And how can we as researchers advocate for and with care and caregivers? In this one-day workshop, we will bring together researchers from academia, industry, and community-based organizations to reflect on these questions and extend conversations on the future of technology for care work.
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| 5. |
- Toombs, J., et al.
(author)
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Untangling the tau microtubule-binding region
- 2021
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 144:2, s. 359-362
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Journal article (peer-reviewed)abstract
- This scientific commentary refers to ‘CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer’s disease’, by Horie et al. (doi:10.1093/brain/awaa373).
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