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Publications by theme

Recent publications
Deaf awareness strategies in healthcare
Hough K, Tsimpida D, Boswell S, Satchwell C, Smith S, Dhuria P, Newberry E, Impey B, Hudson M and Newman T
Longitudinal urinary neopterin is associated with hearing threshold change over time in independent older adults
Kidd RL, Agyemang-Prempeh A, Sanderson A, Stuart C, Mahajan S, Verschuur CA and Newman TA
Longitudinal urinary neopterin is associated with hearing threshold change over time in independent older adults
Kidd RL, Agyemang-Prempeh A, Sanderson A, Stuart C, Mahajan S, Verschuur CA and Newman TA
Low-grade chronic inflammation is associated with many age-related conditions. Non-invasive methods to monitor low-grade chronic inflammation may improve the management of older people at risk of poorer outcomes. This longitudinal cohort study has determined baseline inflammation using neopterin volatility in monthly urine samples of 45 independent older adults (aged 65-75 years). Measurement of neopterin, an inflammatory metabolite, enabled stratification of individuals into risk categories based on how often in a 12-month period their neopterin level was raised. Hearing was measured (pure-tone audiometry) at baseline, 1 year and 3 years of the study. Results show that those in the highest risk category (neopterin raised greater than 50% of the time) saw greater deterioration, particularly in high-frequency, hearing. A one-way Welch's ANOVA showed a significant difference between the risk categories for change in high-frequency hearing (W (3, 19.6) = 9.164, p = 0.0005). Despite the study size and duration individuals in the highest risk category were more than twice as likely to have an additional age-related morbidity than those in the lowest risk category. We conclude that volatility of neopterin in urine may enable stratification of those at greatest risk of progression of hearing loss.
Patient and public involvement and engagement (PPIE): how valuable and how hard? An evaluation of ALL_EARS@UoS PPIE group, 18 months on
Hough K, Grasmeder M, Parsons H, Jones WB, Smith S, Satchwell C, Hobday I, Taylor S and Newman T
Patient and public involvement and engagement (PPIE): how valuable and how hard? An evaluation of ALL_EARS@UoS PPIE group, 18 months on
Hough K, Grasmeder M, Parsons H, Jones WB, Smith S, Satchwell C, Hobday I, Taylor S and Newman T
ALL_EARS@UoS is a patient and public involvement and engagement (PPIE) group for people with lived experience of hearing loss. The purpose of the group is to share experiences of hearing loss and hearing healthcare, inform research and improve services for patients at University of Southampton Auditory Implant Service. A year after inception, we wanted to critically reflect on the value and challenges of the group. Four members of ALL_EARS@UoS were recruited to an evaluation steering group. This paper reports the evaluation of the group using the UK Standards for Public Involvement.
Leveraging real-world data to improve cochlear implant outcomes: Is the data available?
Findlay C, Edwards M, Hough K, Grasmeder M and Newman TA
Leveraging real-world data to improve cochlear implant outcomes: Is the data available?
Findlay C, Edwards M, Hough K, Grasmeder M and Newman TA
A small but persistent proportion of individuals do not gain the expected benefit from cochlear implants(CI). A step-change in the understanding of factors affecting outcomes could come through data science. This study evaluates clinical data capture to assess the quality and utility of CI user's health records for data science, by assessing the recording of otitis media. Otitis media was selected as it is associated with the development of sensorineural hearing loss and may affect cochlear implant outcomes.
Tau-mediated axonal degeneration is prevented by activation of the Wld pathway
Stubbs K, Batchelor B, Sivanantharajah L, Sealey M, Ramirez-Moreno M, Ruiz E, Richardson B, Perry VH, Newman TA and Mudher A
Tau-mediated axonal degeneration is prevented by activation of the Wld pathway
Stubbs K, Batchelor B, Sivanantharajah L, Sealey M, Ramirez-Moreno M, Ruiz E, Richardson B, Perry VH, Newman TA and Mudher A
Tauopathy is characterized by neuronal dysfunction and degeneration occurring as a result of changes to the microtubule-associated protein tau. The neuronal changes evident in tauopathy bear striking morphological resemblance to those reported in models of Wallerian degeneration. The mechanisms underpinning Wallerian degeneration are not fully understood although it can be delayed by the expression of the slow Wallerian degeneration (Wld) protein, which has also been demonstrated to delay axonal degeneration in some models of neurodegenerative disease. Given the morphological similarities between tauopathy and Wallerian degeneration, this study investigated whether tau-mediated phenotypes can be modulated by co-expression of Wld. In a model of tauopathy in which expression of human 0N3R tau protein leads to progressive age-dependent phenotypes, Wld was expressed with and without activation of the downstream pathway. The olfactory receptor neuron circuit was used for these studies in adults, and the larval motor neuron system was employed in larvae. Tau phenotypes studied included neurodegeneration, axonal transport, synaptic deficits and locomotor behaviour. Impact on total tau was ascertained by assessing total, phosphorylated and misfolded tau levels by immunohistochemistry. Activation of the pathway downstream of Wld completely suppressed tau-mediated degeneration. This protective effect was evident even if the pathway downstream of Wld was activated several weeks after tau-mediated degeneration had become established. Though total tau levels were not altered, the protected neurons displayed significantly reduced MC1 immunoreactivity suggestive of clearance of misfolded tau, as well as a trend for a decline in tau species phosphorylated at the AT8 and PHF1 epitopes. In contrast, Wld expression without activation of the downstream protective pathway did not rescue tau-mediated degeneration in adults or improve tau-mediated neuronal dysfunction including deficits in axonal transport, synaptic alterations and locomotor behaviour in tau-expressing larvae. This collectively implies that the pathway mediating the protective effect of Wld intersects with the mechanism(s) of degeneration initiated by tau and can effectively halt tau-mediated degeneration at both early and late stages. Understanding the mechanisms underpinning this protection could identify much-needed disease-modifying targets for tauopathies.