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Novel stimulation methods are needed to overcome the limitations of contemporary cochlear implants. Optogenetics is a technique that confers light sensitivity to neurons via the genetic introduction of light-sensitive ion channels. By controlling neural activity with light, auditory neurons can be activated with higher spatial precision. Understanding the behaviour of opsins at high stimulation rates is an important step towards their translation. To elucidate this, we compared the temporal characteristics of auditory nerve and inferior colliculus responses to optogenetic, electrical, and combined optogenetic-electrical stimulation in virally transduced mice expressing one of two channelrhodopsins, ChR2-H134R or ChIEF, at stimulation rates up to 400 pulses per second (pps). At 100 pps, optogenetic responses in ChIEF mice demonstrated higher fidelity, less change in latency, and greater response stability compared to responses in ChR2-H134R mice, but not at higher rates. Combined stimulation improved the response characteristics in both cohorts at 400 pps, although there was no consistent facilitation of electrical responses. Despite these results, day-long stimulation (up to 13 h) led to severe and non-recoverable deterioration of the optogenetic responses. The results of this study have significant implications for the translation of optogenetic-only and combined stimulation techniques for hearing loss. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct‐acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2‐year survival for patients receiving HCV DAA therapy. Methods: Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016–2021 were followed up for 2 years. Risky alcohol use was defined by a combination of self‐report (≥40 g/day of ethanol), physician‐reported history of problematic alcohol use, and anti‐craving medication prescription via population‐based database linkage. We examined factors associated with advanced liver fibrosis and survival using multivariable logistic and Cox regression. Results: Among 1634 patients (62.3%) with risky alcohol use, 24.6% reported consuming ≥40 g/day of alcohol, 98.3% physician‐reported problematic alcohol use; only 4.1% were dispensed naltrexone/acamprosate. One hundred and forty‐three patients with cirrhosis reported ≥40 g/day of alcohol, 6 (4.3%) were prescribed naltrexone/acamprosate. Risky alcohol use was associated with advanced fibrosis (adjusted‐odds ratio 1.69, 95% confidence interval 1.32–2.17) and patients were over‐represented for cirrhosis (45.1% vs. 25.6% in no‐risky alcohol use [p < 0.001]) and hepatocellular carcinoma (5.7% vs. 2.5% [p < 0.001]). Sustained viral response (p = 0.319) and 2‐year survival (adjusted‐hazard ratio 1.98, 95% confidence interval 0.84–4.63) after DAA therapy were not associated with risky alcohol use. Discussion and Conclusions: Risky alcohol use in HCV patients was prevalent, but did not reduce HCV cure. Treatment for alcohol dependence was low. Risky alcohol use may be under‐recognised in liver clinics. Better integration of addiction medicine into liver services and increased resourcing and addiction medicine training opportunities for hepatologists may help address this. [ABSTRACT FROM AUTHOR]

In collaboration with end-users and other key stakeholders, this paper describes an innovation process of designing and manufacturing customized assistive technologies for regional and remote communities. The project collaboratively identified the real-world problems of people living with spinal cord injuries, created design solutions to overcome these challenges, and worked with manufacturers to turn these solutions into actual products. The project embodied a co-design method to bring people living with spinal cord injuries, occupational therapists, researchers, designers, and manufacturers together to co-create new solutions to overcome common challenges. Data was collected through the following methods: a desktop study of the literature and the market; an innovation process via 4 x co-design workshops (Ideation, Design and Develop, Pitch and Feedback, Demonstration) from June 2021 to June 2022; a Research through Design methodology to design 3D-printed assistive technologies. Through iterative virtual and physical prototyping, and user testing, the most effective prototypes were refined into the optimal solution. The Project established an innovation process, including online consultation and workshops with end-users, that prioritize 3D printing of assistive technology prototypes; created a demonstrator for allied health engagement and testing; and completed end-user pilot group testing, such as materials, durability, grasping, biomechanical advantage, adaptability, etc. This innovation process produced a minimum viable product (MVP) that has enough features to attract early adopters and provide design validation early in the product development cycle. [ABSTRACT FROM AUTHOR]

Background: Direct‐acting antiviral (DAA) therapies for hepatitis C virus infection (HCV) lead to excellent rates of sustained virological response (SVR). However, loss to follow‐up (LTFU) for SVR testing remains a challenge. We examine factors associated with LTFU in a real‐world setting. Methods: Adults who received DAA therapy for HCV in one of 26 centers across Australia during 2016–2021 were followed up for 2 years. Data sources included the patient medical records and the national Pharmaceutical and Medicare Benefits Schemes. Linkage to Medicare provided utilization data of other health‐care providers and re‐treatment with DAAs. LTFU was defined as no clinic attendance for SVR testing by at least 52 weeks after DAA treatment commencement. Multivariable logistic regression assessed factors associated with LTFU. Results: In 3619 patients included in the study (mean age 52.0 years; SD = 10.5), 33.6% had cirrhosis (69.4% Child–Pugh class B/C), and 19.3% had HCV treatment prior to the DAA era. Five hundred and fifteen patients (14.2%) were LTFU. HCV treatment initiation in 2017 or later (adj‐OR = 2.82, 95% confidence interval [CI] 2.25–3.54), younger age (adj‐OR = 2.63, 95% CI 1.80–3.84), Indigenous identification (adj‐OR = 1.99, 95% CI 1.23–3.21), current injection drug use or opioid replacement therapy (adj‐OR = 1.66, 95% CI 1.25–2.20), depression treatment (adj‐OR = 1.49, 95% CI 1.17–1.90), and male gender (adj‐OR = 1.31, 95% CI 1.04–1.66) were associated with LTFU. Conclusions: These findings stress the importance of strengthening the network of providers caring for patients with HCV. In particular, services targeting vulnerable groups of patients such as First Nations Peoples, youth health, and those with addiction and mental health disorders should be equipped to treat HCV. [ABSTRACT FROM AUTHOR]

Background: School-based universal social and emotional learning (SEL) interventions implemented during the transition to adolescence may be efficacious in preventing the development of mental health difficulties. This protocol describes a two-arm parallel cluster randomised controlled trial to investigate the impact of a universal SEL intervention (Passport, compared to usual provision) on internalising symptoms (primary outcome), emotion regulation, well-being, loneliness, social support, bullying, academic attainment, and health-related quality of life in English primary school pupils aged 9–11 years. A developer-led trial demonstrated the feasibility, acceptability, and utility of Passport; this will be the first independent trial. Methods: Sixty primary schools will be recruited across the Greater Manchester city region and surrounding areas, involving 2400 pupils aged 8–9 at baseline. Schools will be allocated to the intervention arm to implement Passport over 18 weekly sessions or to the control arm to implement the usual school curriculum. Random allocation will be at school level following completion of baseline measures, with minimisation to ensure balance across trial arms in school size and free school meal eligibility. Measures will be collected at baseline, post-intervention (12 months post-baseline), and at 12 months follow-up (24 months post-baseline). The primary outcome analysis (intervention effects on internalising symptoms at post-intervention) will comprise a two-level (school, child) hierarchical linear model, following the intention-to-treat principle. Additional analyses will be undertaken to assess intervention effects on secondary outcomes, maintenance effects for all outcomes, intervention compliance moderator effects, subgroup moderator effects, and mechanisms underpinning intervention effects on the primary outcome. A mixed-methods implementation and process evaluation will examine factors that influence implementation, and a health economic evaluation will assess the cost-effectiveness of the intervention. Discussion: Findings will provide educators with crucial knowledge of whether and how increasing emotion regulation through a universal intervention impacts internalising symptoms and a range of related outcomes. Findings will also inform policy related to the promotion of mental health among children and young people. If the intervention is found to be efficacious in reducing internalising symptoms and is also cost-effective, it may offer high potential as a preventative intervention for widespread implementation. Trial registration: ISRCTN12875599; registered on 24 November 2022 [ABSTRACT FROM AUTHOR]

Soft robotics is becoming a popular choice for end‐effectors. An end‐effector was designed that has various advantages including ease of manufacturing, simplicity and control. This device may have the advantage of enabling probe‐based devices to intraoperatively measure cancer histology, because it can flexibly and gently position a probe perpendicularly over an area of delicate tissue. This is demonstrated in a neurosurgical setting where accurate cancer resection has been limited by lack of accurate visualisation and impaired tumour margin delineation with the need for in‐situ histology. Conventional surgical robotic end‐effectors are unsuitable to accommodate a probe‐based confocal laser endomicroscopy (p‐CLE) probe because of their rigid and non‐deformable properties, which can damage the thin probe. We have therefore designed a new soft robotic platform, which is advantageous by conforming to the probe's shape to avoid damage and to facilitate precision scanning. [ABSTRACT FROM AUTHOR]