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Barriers to and Enablers of the Transition From Child to Adult Mental Health Services for Autistic Young People and/or Those With Attention Deficit Hyperactivity Disorder: A Scoping Review
No full textBackground: Many autistic young people and/or those with attention deficit hyperactivity disorder (ADHD) have co-occurring mental health conditions. These individuals can experience significant challenges when transitioning from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS). However, barriers and enablers to the transition from CAMHS to AMHS are poorly understood for this population. This scoping review sought to synthesise the available evidence on barriers and enablers to the transition from CAMHS to AMHS for autistic young people and/or those with ADHD. Methods: Arksey and O'Malley's six-step framework for scoping reviews was used to map out the evidence available and report the findings with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines (PRISMA-ScR). Electronic databases of Medline, PsycINFO, CINAHL, Scopus and ProQuest Central were searched for relevant studies published in English with no date limitations. The review included studies that focused on young people with a primary diagnosis of autism spectrum disorder (ASD) and/or ADHD (population) and their care transition barriers and/or enablers (concept) from CAMHS to AMHS (context). A socioecological framework informed data extraction and narrative synthesis of data on barriers and enablers to transition. Results: This review identified 1677 studies, of which 66 proceeded to full-text screening, and 10 were included. Most studies focused on institutional-level transition barriers, including poor communication between CAMHS and AMHS and lack of clarity about their role in the transition process. Involvement of the neurodivergent young person in decision-making processes about their mental health care and clinicians who tailored their approaches to the needs of the neurodivergent young person emerged as key enablers of a positive transition experience. Studies largely failed to examine community and policy-related barriers to mental health care transitions. Most studies examined the perspectives of providers or carers, with only five representing the perspectives of neurodivergent people. Conclusion: Young people who are autistic and/or have ADHD experience many barriers to their transition from CAMHS to AMHS; however, few studies have examined barriers and enablers to the service transition process
Use of lorazepam for analgosedation during mechanical ventilation in pediatric intensive care
No full textIntroduction: Lorazepam has been used off-label for analgosedation in pediatric intensive care units (PICU) as an alternative to midazolam. While its intermediate duration of action makes it suitable for continuous sedation, there is limited evidence to guide dosing in children. This study illustrates how pharmacokinetic modeling and extrapolation principles can be used to (1) identify regimens that maintain the desired analgosedation levels and (2) optimize the design of a prospective protocol in children requiring mechanical ventilation.
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Methods: Pharmacokinetic data and COMFORT-B scores from a preliminary pilot study in six mechanically-ventilated pediatric patients (aged 0.8–4.8 years) were available for the purpose of the current investigation. A previously published population pharmacokinetic model was used to characterize the disposition of lorazepam, accounting for developmental growth and metabolic maturation in children. Parameter distributions were used as priors. Clinical trial simulations (CTS) were subsequently performed in a virtual cohort of 100 children (aged 1.0–12 years) to explore optimized dosing regimens, combining intermittent bolus dosing and continuous infusions over a 72-h period. A target concentration of 500 ng/ml was selected considering the available clinical data and literature evidence on the analgosedative effects and safety profile of lorazepam. Simulation scenarios also explored sample size and sampling time requirements for a prospective clinical trial.
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Results: The pharmacokinetic model adequately described the concentration vs. time profiles, despite appreciable interindividual variability. Population estimates for clearance and volume of distribution were 0.23 L/h/kg and 2.3 L/kg, respectively. Simulation results showed that intermittent bolus dosing every 4 h, followed by continuous infusion allowed for lorazepam steady state concentrations to fluctuate around 500 ng/ml. An initial dose of 0.2 mg/kg given as bolus every 4 h over the first 24 h, followed by a similar regimen with 0.1 mg/kg over the subsequent 24 h and continuous infusion of 0.03 mg/kg/h until the end mechanical ventilation was identified as the recommended regimen to be evaluated in a prospective clinical trial.
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Conclusion: Our study underscores the importance of model-based approaches to identify suitable dosing regimens to be used in children when limited pharmacokinetic and pharmacodynamic data are available. The proposed dosing regimen balances efficacy and safety data, thereby offering the foundation for the repurposing of lorazepam as an alternative, second line option for analgosedation of mechanically ventilated subjects in a pediatric intensive care unit setting
Population attributable fractions of a wide range of peripheral diseases for the burden of dementia
No full textGrowing evidence suggests that peripheral diseases serve as risk factors for dementia, but the population-level burden of dementia associated with various peripheral diseases has remained unknown. Here, by conducting a systematic review and Bayesian meta-analyses to estimate the relative risks of 26 peripheral diseases across 9 systems with dementia, including 202 articles searched from the PubMed until 6 September 2024, we identified 16 peripheral diseases as associated with increased risk of dementia. With the relative risks estimated from meta-analyses, prevalences extracted from the Global Burden of Disease Study, and communalities among these 16 peripheral diseases derived from the UK Biobank, we analysed the population attributable fractions (PAFs) of these 16 peripheral diseases for dementia, stratified by sex, age, sociodemographic index level, world region and country, and trends from 1990 to 2021. Globally, these peripheral diseases collectively were related to a combined PAF of 33.18% (95% confidence interval (CI) 16.80-48.43) of dementia burden, corresponding to 18.8 million prevalent cases. The leading ten PAF contributors were periodontal diseases (6.10%, 95% CI 0.95-10.28), cirrhosis and other chronic liver diseases (5.51%, 95% CI 1.77-8.86), age-related and other hearing loss (4.70%, 95% CI 3.51-6.06), blindness and vision loss (4.30%, 95% CI 3.43-5.05), type 2 diabetes mellitus (3.80%, 95% CI 3.06-4.53), chronic kidney disease (2.74%, 95% CI 1.53-4.02), osteoarthritis (2.26%, 95% CI 0.41-4.12), stroke (1.01%, 95% CI 0.86-1.17), ischaemic heart disease (0.97%, 95% CI 0.69-1.29) and chronic obstructive pulmonary disease (0.92%, 95% CI 0.34-1.54). This study revealed that a series of peripheral diseases were associated with increased risk of dementia and collectively were related to about one-third of the global dementia burden, highlighting the need for targeted public health strategies
Catch Me If You Can: The Dynamic Nature of Bias in Machine Learning Applications
No full textBias in machine learning (ML) applications represents systematic differences between expected and actual values of the predicted outputs, such that certain individuals or groups are systematically and disproportionately (dis)advantaged. This paper investigates the dynamic nature of bias in ML applications. We conducted an empirical study of bias in the context of an ML application that assesses applicants' competencies for a given job based on their job interviews. We analysed primary data (27 interviews with 21 members from six departments) and secondary data (e.g., company reports, webinars, and software demonstrations) from the organisation that develops and deploys the application. Drawing on the concept of reflexivity in digitised processes and associated notions of drift and control, we theorise the emergence and evolvement of bias as constituting dynamic relationships among sources of bias and associated effects of drift, and actions of bias mitigation and associated effects of control. We further demonstrate how actions aimed at mitigating bias, while weakening some sources of bias, also create additional sources through unintended side effects. We explain how sources of bias and bias mitigation actions continually (re)shape each other through dynamic and reflexive effects. For HR practitioners and policymakers, we provide actionable insights into bias detection and mitigation in ML-based job competency assessment
Mitochondria and Lipids in Cellular Signaling of the Brain: from Physiology to Neurodegeneration
No full textThe brain is one of the most lipid-rich organs, reflecting the critical role of lipid metabolism in neuronal and glial cell function. While mitochondria are central to energy metabolism, calcium signaling, and cell death, they do not utilize lipid oxidation for energy but rely on lipids for membrane integrity and intracellular communication. Here we review the interactions between lipids and mitochondria in intracellular signaling within brain cells, examining their roles in normal physiology and the mechanisms underlying major neurodegenerative diseases. Alterations in lipid homeostasis and mitochondrial metabolism are implicated in neurodegeneration, highlighting the importance of lipid-mediated mitochondrial signaling pathways. Understanding these interactions provides insights into cellular dysfunction in neurodegenerative disorders and may inform future therapeutic strategies targeting lipid and mitochondrial pathways
Disrupted hippocampal replay is associated with reduced offline map stabilization in an Alzheimer’s mouse model
No full textAlzheimer’s disease is characterized by progressive memory decline associated with hippocampal degeneration. However, the specific physiological mechanisms underlying hippocampal dysfunction in the disease remain poorly understood—improved knowledge may aid diagnosis and identify new avenues for therapeutic intervention. We investigated how disruptions in hippocampal reactivations relate to place cell stability and spatial memory deficits in an Alzheimer’s mouse model. Using the App knockin mouse model NL-G-F, we conducted simultaneous behavioral and electrophysiological recordings in a radial arm maze. NL-G-F mice exhibited significant impairments in memory performance, demonstrated by an increased propensity to revisit arms, compared with wild-type controls. These memory deficits were associated with reduced stability of hippocampal place cells, which was particularly pronounced following rest periods. Crucially, although wild-type mice showed enhanced place cell stability after quiescence, NL-G-F mice failed to exhibit this consolidation. Although the rate of hippocampal reactivation events during rest remained unchanged, analysis of replay content revealed significantly degraded replay quality in NL-G-F mice. This degradation manifested as disrupted cell recruitment and reduced co-firing structure within reactivation events, both of which predicted the failure of offline place cell stabilization. Together, these findings suggest that compromised reactivation quality may underlie disruptions in offline consolidation processes, offering a potential mechanism for memory dysfunction in Alzheimer's disease
Why we need to teach everyone about reproductive health
No full textReproductive health is a topic that concerns everyone but its coverage in schools worldwide is patchy. Given current falls in total fertility rate and rises in the age at which women have their first child, there is an urgent need to ensure that teenagers and young adults understand fertility and reproductive health. This would help them to make informed choices about family building. Recent research has shown that even in England, one of the few countries that explicitly incorporates reproductive health education into its school curriculum, teenagers report being taught little about reproductive health and fertility. We conclude that there is an urgent need to improve the quality of the education that school students receive about reproductive health
Microstructural Financial Modelling: Point Processes and Reinforcement Learning
No full textThis thesis explores the intersection of high-frequency market microstructure mod-
elling, stochastic optimal control and reinforcement learning (RL) for optimal
decision making in electronic trading. Specifically, it focuses on developing realistic,
data-driven models of Limit Order Book (LOB) dynamics using point processes,
mathematically formulating impulse control settings for algorithmic trading tasks
in a pure jump-driven market, and designing RL algorithms capable of learning
robust strategies within such stochastic and reactive environments. The research
addresses the challenge of building adaptive trading agents in low signal-to-noise ratio
(SNR) settings—where traditional RL methods often exhibit poor sample efficiency,
convergence to local minima, and limited generalizability.
Conducted in collaboration with JP Morgan Chase & Co., this work investigates
how realistic jump-driven microstructure modelling and impulse control formulations
can bridge the gap between theoretical stochastic control and practical algorithmic-
trading. Among the various LOB modelling philosophies in the literature explored in
this thesis, we especially focus on and make use of the Hawkes process methodology.
This is due to the memoryfulness, high adaptivity and mathematical tractability of
this class of LOB models. One of the core tenets of this thesis is to rely on minimal
assumptions on the nature of financial markets, perform scientifically rigorous studies
in a data-driven way, and to be cognizant of the practical applicability of the trading
strategies developed during the course of this research
Development of Undergraduate Student Research Capability in Sociology: A Comparative Study between China, the UK and US
No full textThis Ph.D. research explores the development of Chinese undergraduates’ research capability in Sociology across China, the UK, and the US through a comparative lens. While research-integrated education has been widely adopted for fostering graduate attributes, employability, and academic talent, existing studies predominantly focus on STEM disciplines and postgraduate contexts, leaving undergraduate social science research under-explored. Disparities in conceptualising and cultivating research capabilities between China and Anglo-Saxon contexts, represented by the UK and US, further highlight the need for cross-national investigation. Drawing on Healey and Jenkins’ research capability model, alongside frameworks of epistemic culture, performativity, socio-materiality, and relational pedagogies, this study employs a qualitative case study approach. One university with a leading Sociology department from each country was selected, with data collected through document analysis and semi-structured interviews with Chinese undergraduates and academics. The focus on Chinese students was a result of the participant recruitment process where all volunteers were Chinese, possibly due to the researcher’s positionality. Findings reveal that core research capabilities, such as criticality, methodology, and collaboration, are universally valued, but their enactment is shaped by socio-material, political, and cultural contexts. Notably, performativity manifests differently across settings. Students in China navigate ambiguous curricula by pursuing extracurricular research aligned with national agendas, while students in the UK and US face pressures to perform verbally in collaborative spaces, often marginalizing alternative learning approaches. Materiality also influences research experiences, with criticality being welcomed in classrooms but suppressed in informal settings. Online and campus environments further mediate research engagement, underscoring its fluid, embodied nature. This study contributes by providing an alternative lens to examine undergraduates’ knowledge and practice of research in Sociology. Challenging existing perspectives that frame research capabilities as parallel or supplementary to generic abilities and employability, this study repositions it as a nuanced process shaped by interpersonal, institutional, and material relations