Potential mental health-related harms associated with the universal screening of anxiety and depressive symptoms in Australian secondary schools.

BACKGROUND: Anxiety and depressive disorders typically emerge in adolescence and can be chronic and disabling if not identified and treated early. School-based universal mental health screening may identify young people in need of mental health support and facilitate access to treatment. However, few studies have assessed the potential harms of this approach. This paper examines some of the potential mental health-related harms associated with the universal screening of anxiety and depression administered in Australian secondary schools. METHODS: A total of 1802 adolescent students from 22 secondary schools in New South Wales, Australia, were cluster randomised (at the school level) to receive either an intensive screening procedure (intervention) or a light touch screening procedure (control). Participants in the intensive screening condition received supervised self-report web-based screening questionnaires for anxiety, depression and suicidality with the follow-up care matched to their symptom severity. Participants in the light touch condition received unsupervised web-based screening for anxiety and depression only, followed by generalised advice on help-seeking. No other care was provided in this condition. Study outcomes included the increased risk of anxiety, depression, psychological distress, decreased risk of help-seeking, increased risk of mental health stigma, determined from measures assessed at baseline, 6 weeks post-baseline, and 12 weeks post-baseline. Differences between groups were analysed using mixed effect models. RESULTS: Participants in the intensive screening group were not adversely affected when compared to the light touch screening condition across a range of potential harms. Rather, participants in the intensive screening group were found to have a decreased risk of inhibited help-seeking behaviour compared to the light touch screening condition. CONCLUSIONS: The intensive screening procedure did not appear to adversely impact adolescents' mental health relative to the light touch procedure. Future studies should examine other school-based approaches that may be more effective and efficient than universal screening for reducing mental health burden among students. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12618001539224) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375821 .

Text mining for contexts and relationships in cancer genomics literature.

MOTIVATION: Scientific advances build on the findings of existing research. The 2001 publication of the human genome has led to the production of huge volumes of literature exploring the context-specific functions and interactions of genes. Technology is needed to perform large-scale text mining of research papers to extract the reported actions of genes in specific experimental contexts and cell states, such as cancer, thereby facilitating the design of new therapeutic strategies. RESULTS: We present a new corpus and Text Mining methodology that can accurately identify and extract the most important details of cancer genomics experiments from biomedical texts. We build a Named Entity Recognition model that accurately extracts relevant experiment details from PubMed abstract text, and a second model that identifies the relationships between them. This system outperforms earlier models and enables the analysis of gene function in diverse and dynamically evolving experimental contexts. AVAILABILITY AND IMPLEMENTATION: Code and data are available here: https://github.com/cambridgeltl/functional-genomics-ie.

How Much Speech Data Is Needed for Tracking Language Change in Alzheimer's Disease? A Comparison of Random Length, 5-Min, and 1-Min Spontaneous Speech Samples.

Introduction: Changes in speech can act as biomarkers of cognitive decline in Alzheimer's disease (AD). While shorter speech samples would promote data collection and analysis, the minimum length of informative speech samples remains debated. This study aims to provide insight into the effect of sample length in analyzing longitudinal recordings of spontaneous speech in AD by comparing the original random length, 5- and 1-minute-long samples. We hope to understand whether capping the audio improves the accuracy of the analysis, and whether an extra 4 min conveys necessary information. Methods: 110 spontaneous speech samples were collected from decades of Youtube videos of 17 public figures, 9 of whom eventually developed AD. 456 language features were extracted and their text-length-sensitivity, comparability, and ability to capture change over time were analyzed across three different sample lengths. Results: Capped audio files had advantages over the random length ones. While most extracted features were statistically comparable or highly correlated across the datasets, potential effects of sample length should be acknowledged for some features. The 5-min dataset presented the highest reliability in tracking the evolution of the disease, suggesting that the 4 extra minutes do convey informative data. Conclusion: Sample length seems to play an important role in extracting the language feature values from speech and tracking disease progress over time. We highlight the importance of further research into optimal sample length and standardization of methods when studying speech in AD.

Developing a Theory of Change for a Digital Youth Mental Health Service (Moderated Online Social Therapy): Mixed Methods Knowledge Synthesis Study.

BACKGROUND: Common challenges in the youth mental health system include low access, poor uptake, poor adherence, and limited overall effectiveness. Digital technologies offer promise, yet challenges in real-world integration and uptake persist. Moderated Online Social Therapy (MOST) aims to overcome these problems by integrating a comprehensive digital platform into existing youth mental health services. Theory of change (ToC) frameworks can help articulate how and why complex interventions work and what conditions are required for success. OBJECTIVE: The objective of this study is to create a ToC for MOST to explain how it works, why it works, who benefits and how, and what conditions are required for its success. METHODS: We used a multimethod approach to construct a ToC for MOST. The synthesis aimed to assess the real-world impact of MOST, a digital platform designed to enhance face-to-face youth mental health services, and to guide its iterative refinement. Data were gathered from 2 completed and 4 ongoing randomized controlled trials, 11 pilot studies, and over 1000 co-design sessions using MOST. Additionally, published qualitative findings from diverse clinical contexts and a review of related digital mental health literature were included. The study culminated in an updated ToC framework informed by expert feedback. The final ToC was produced in both narrative and table form and captured components common in program logic and ToC frameworks. RESULTS: The MOST ToC captured several assumptions about digital mental health adoption, including factors such as the readiness of young people and service providers to embrace digital platforms. External considerations included high service demand and a potential lack of infrastructure to support integration. Young people and service providers face several challenges and pain points MOST seeks to address, such as limited accessibility, high demand, poor engagement, and a lack of personalized support. Self-determination theory, transdiagnostic psychological treatment approaches, and evidence-based implementation theories and their associated mechanisms are drawn upon to frame the intervention components that make up the platform. Platform usage data are captured and linked to short-, medium-, and long-term intended outcomes, such as reductions in mental health symptoms, improvements in functioning and quality of life, reductions in hospital visits, and reduced overall mental health care costs. CONCLUSIONS: The MOST ToC serves as a strategic framework for refining MOST over time. The creation of the ToC helped guide the development of therapeutic content personalization, user engagement enhancement, and clinician adoption through specialized implementation frameworks. While powerful, the ToC approach has its limitations, such as a lack of standardized methodology and the amount of resourcing required for its development. Nonetheless, it provides an invaluable roadmap for iterative development, evaluation, and scaling of MOST and offers a replicable model for other digital health interventions aiming for targeted, evidence-based impact.

Examining the impact of a universal positive psychology program on mental health outcomes among Australian secondary students during the COVID-19 pandemic.

BACKGROUND: This study aimed to examine the impact of a web-based positive psychology program delivered universally to secondary school students during school closures caused by the COVID-19 pandemic in New South Wales, Australia. METHODS: Using a quasi-experimental design conducted in 2020, 438 students aged 12-15 years (73% male) from 4 secondary schools were invited to complete the 'Bite Back Mental Fitness Challenge'. This web-based program consisted of 7 self-directed modules that targeted 5 key domains of positive psychology. Self-reported symptoms of anxiety and depression and help-seeking intentions for mental health were assessed at baseline prior to school closures (February to March 2020) and at post-test after the return to school (July to August 2020). At post-test, students also reported on their perceived changes in mental health and help-seeking behavior for mental health during the pandemic. Completion of the program modules was recorded. RESULTS: A total of 445 students consented and 336 (75.5%) completed both assessments. On average, participants completed 2.31 modules (SD: 2.38, range: 0 to 7). There was no change in symptoms of anxiety and depression or help-seeking intentions between baseline and post-test, with no significant effects for gender and history of mental illness. Students who were symptomatic for anxiety and depression at baseline reported lower symptoms at post-test, but this change was not significant. Ninety-seven students (27.5%) reported that their mental health had worsened during the pandemic, and a significant increase in anxiety and depressive symptoms was found in this subsample at post-test. Only 7.7% of students reported a change in their help-seeking behavior, with increased mental health support sought from the Internet, parents, and friends. CONCLUSIONS: The universal delivery of a web-based positive psychology program during school closures did not appear to be associated with improved mental health symptoms; however, completion of the modules was low. Different effects may emerge when selectively delivered to students with mild or greater symptoms. The findings also suggest that broader measures of mental health and wellbeing, including perceived change, are key to the mental health surveillance of students during periods of remote learning.

The Generalizability of Longitudinal Changes in Speech Before Alzheimer's Disease Diagnosis.

BACKGROUND: Language impairment in Alzheimer's disease (AD) has been widely studied but due to limited data availability, relatively few studies have focused on the longitudinal change in language in the individuals who later develop AD. Significant differences in speech have previously been found by comparing the press conference transcripts of President Bush and President Reagan, who was later diagnosed with AD. OBJECTIVE: In the current study, we explored whether the patterns previously established in the single AD-healthy control (HC) participant pair apply to a larger group of individuals who later receive AD diagnosis. METHODS: We replicated previous methods on two larger corpora of longitudinal spontaneous speech samples of public figures, consisting of 10 and 9 AD-HC participant pairs. As we failed to find generalizable patterns of language change using previous methodology, we proposed alternative methods for data analysis, investigating the benefits of using different language features and their change with age, and compiling the single features into aggregate scores. RESULTS: The single features that showed the strongest results were moving average type:token ratio (MATTR) and pronoun-related features. The aggregate scores performed better than the single features, with lexical diversity capturing a similar change in two-thirds of the participants. CONCLUSION: Capturing universal patterns of language change prior to AD can be challenging, but the decline in lexical diversity and changes in MATTR and pronoun-related features act as promising measures that reflect the cognitive changes in many participants.

Virtual Clinics: A Student-Led, Problem-Based Learning Approach to Supplement Veterinary Clinical Experiences.

The COVID-19 pandemic created an abrupt need for effective remote clinical experiences for senior clinical veterinary students. Subsequently, the authors created virtual clinics. This activity was derived from a problem-based learning (PBL) model wherein students designed clinical cases and participated through virtual role play as clients and clinicians. The purpose of this article is to describe virtual clinics and to report data from focus groups of participating students and faculty facilitators from two institutions regarding the positive and negative aspects of the shift in practice. A few common emerging themes included that case rounds were fun and engaging, students could learn at their own pace, and peer-to-peer learning opportunities had perceived value. Themes are reflected against the pedagogical literature to draw out areas that resonated. Students felt this activity was more engaging than listening to a discussion of a case they had no ownership of, and facilitators agreed that the peer-to-peer interactions added to student engagement. Additionally, students developed deeper knowledge about the underlying disease process and clinical presentation of their case, which required independent and self-directed learning, enabling students to think about a case from a client's perspective. By participating in these activities, students developed skills of classroom-to-clinic transitional value. While virtual clinics should not replace in-person clinical experiences, this activity might be useful to facilitate students' transition from a structured classroom setting to a less-structured clinical experience.

Students Satisfaction with the Use of PlayDoh® as a Tool to Actively Learn 3D Veterinary Anatomy More Accurately.

Understanding veterinary anatomy is an essential skill for the study of veterinary medicine as well as for diagnostic imaging and therapy. Dissection facilities are increasingly limited in some schools and its alternatives have often focussed on using two-dimensional images. However, the study of veterinary anatomy is mainly concerned with identifying structures and spatial relationships between them within a 3D space, and the use of 2D teaching approaches does not provide accurate information. We tested whether PlayDoh® student-built models could be an inexpensive potential tool beneficial to veterinary students learning anatomy in three distinct scenarios: (1) during a lecture, introducing a new concept; (2) during a flipped classroom approach where a video-podcast lecture was to be watched by the students prior to the lecture and (3) as a revision session where students brought their own questions and created, under supervision, their own models to respond to them. PlayDoh® sessions benefitted 172 first-year Veterinary Medicine and Animal Science students. The most accurate visualisation of anatomical structures in 3D was the principal benefit mentioned by the learners (35%). In addition, the learners noted that the technique would help with 'retention' (18%). According to the students' preferences, it was possible to create four groups: A, B, C and D. Group A encompassed the methodologies most liked by students and consisted of lectures, dissection and demonstrations. Group B included demonstrations and 3D modelling using PlayDoh®. Group C consisted of 3D modelling using PlayDoh®, books and online and, finally, group D included the methodologies least preferred by students, i.e. online and PBL. Our findings suggest that using 3D PlayDoh® modelling has potential as a method to enhance the learning of veterinary anatomy and may be most valuable to those students learning more complex subject areas that require a 3D teaching approach in practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01892-y.

Tidal range electricity generation: A comparison between estuarine barrages and coastal lagoons.

The potential power from coastal tidal range is becoming better appreciated due to the need to mitigate global warming. Great Britain (GB) is ideally situated to exploit tidal power but currently has no operational systems. Historically, estuaries have been proposed as sites for barrages, but more recently coastal lagoons are favoured due to a lower environment impact. To contrast the differences between barrages and lagoons two potential schemes are analysed using the Lancaster 0-D Tidal Range Model. Both schemes were analysed with a range of turbine numbers and generator ratings. The schemes are compared in terms of energy generation, flood protection, navigation, and selected environmental impacts. The analysis indicates that the schemes are not categorically different, characterised by the shape and alignment of the impoundment. Barrages impoundments across estuaries are generally shorter than lagoons impounding similar volumes, with lower civil engineering costs. Whilst estuaries tend to have slightly higher tidal ranges, they also create unique ecological conditions with diverse natural ecosystems that are increasingly valued. The analysis shows that 2-way generation and pumping can match the full tidal range and help preserve inter-tidal areas.

The Urothelial Transcriptomic Response to Interferon Gamma: Implications for Bladder Cancer Prognosis and Immunotherapy.

Interferon gamma (IFNγ) is central to the inflammatory immune response, such as that entrained by BCG immunotherapy for bladder cancer. However, immune-mediated tumour cell killing is subject to modulation by immunoinhibitory "checkpoint" receptors such as PD-L1. We investigated the effects of IFNγ on barrier-forming in vitro-differentiated normal human urothelium using mRNA-sequencing, and showed canonical upregulation of MHC class I/II and de novo expression of the T cell tropic CXCL9-11 chemokines. Normal urothelium constitutively expressed immunoinhibitory B7 family member VSIR (VISTA), while CD274 (PD-L1) expression was induced/upregulated by IFNγ. We generated a urothelial IFNγ response gene signature. When applied to the unsupervised clustering of non-muscle-invasive bladder cancers, the IFNγ-signature predicted longer recurrence-free survival. In muscle-invasive cancers, the IFNγ-signature split the basal/squamous consensus subtype, with significantly worse overall survival when weak or absent. This study offers novel insights into strategies to enhance immunotherapy via the IFNγ and VISTA/PD-L1 nexus.

LPCAT4 Knockdown Alters Barrier Integrity and Cellular Bioenergetics in Human Urothelium.

Urothelium is a transitional, stratified epithelium that lines the lower urinary tract, providing a tight barrier to urine whilst retaining the capacity to stretch and rapidly resolve damage. The role of glycerophospholipids in urothelial barrier function is largely unknown, despite their importance in membrane structural integrity, protein complex assembly, and the master regulatory role of PPARγ in urothelial differentiation. We performed lipidomic and transcriptomic characterisation of urothelial differentiation, revealing a metabolic switch signature from fatty acid synthesis to lipid remodelling, including 5-fold upregulation of LPCAT4. LPCAT4 knockdown urothelial cultures exhibited an impaired proliferation rate but developed elevated trans-epithelial electrical resistances upon differentiation, associated with a reduced and delayed capacity to restitute barrier function after wounding. Specific reduction in 18:1 PC fatty acyl chains upon knockdown was consistent with LPCAT4 specificity, but was unlikely to elicit broad barrier function changes. However, transcriptomic analysis of LPCAT4 knockdown supported an LPC-induced reduction in DAG availability, predicted to limit PKC activity, and TSPO abundance, predicted to limit endogenous ATP. These phenotypes were confirmed by PKC and TSPO inhibition. Together, these data suggest an integral role for lipid mediators in urothelial barrier function and highlight the strength of combined lipidomic and transcriptomic analyses for characterising tissue homeostasis.