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Characterising Antarctic marine invertebrate microbiomes and their antimicrobial potential
No full textThe West Antarctic Peninsula is experiencing rapid regional warming that will negatively impact endemic marine biodiversity. Antarctic marine invertebrates living in the near-shore are likely to be affected profoundly by warming-related changes, and microbes could help their hosts respond to the demands of environmental change. Moreover, their associated microbiomes may be untapped reservoirs of novel antimicrobial natural products. However, only a handful of the over 17,000 marine invertebrate species in the Southern Ocean have been characterised for the taxonomic identities of their microbiomes, or their antimicrobial potential. Therefore, the research in this doctoral thesis aimed to characterise bacterial diversity in the gut microbiomes of common marine invertebrates using a non-culture dependent method (16S rRNA amplicon sequencing). Furthermore, a culture dependent method was used to produce a bank of diverse host-associated bacteria, which were then assessed for their antimicrobial activity, with whole genomes sequenced from the two most promising candidates. Finally, chemical extracts of two species of Antarctic marine invertebrates were examined for antimicrobial potential, on account of their potential to harbour novel chemical defences. This research provided pilot data that suggested a strong influence of diet on gut microbiome status and revealed the surprisingly high temperature resilience of the culturable gut bacteria. Additionally, the assessment of varied culture conditions led to the successful identification of antimicrobial activity from a potentially novel strain of Psychrobacter and Antarctic strain of Pseudomonas, with in silico genome mining identifying multiple biosynthetic gene clusters. The antimicrobial potential of the chemical extracts harvested from the Antarctic marine invertebrates was also identified, particularly from lipophilic extracts targeted against Gram positive pathogens. Overall, this thesis demonstrated the rich and biodiverse nature of the Antarctic marine invertebrate microbiome and metabolome, both with potential for antimicrobial capacity. Using advanced sequencing methodologies, alongside antimicrobial assays, I was able to demonstrate the untapped potential for the discovery of novel antimicrobials in an extreme and poorly explored environment, whilst providing a first glimpse of a more functional understanding of the ecological and biotechnological significance of the bacterial metabolites, and genes identified
A Conceptual Framework for Improving the Oral Health of Children with Disabilities
No full textAbstractTitle: A Conceptual Framework for Improving the Oral Health of Children with DisabilitiesShiamaa Shihab Al-MashhadaniIntroduction:The effect of good oral health contributes to improving general health, well-being, and quality of life. Children with disabilities are more likely to develop oral diseases than the general population. They are disproportionately affected by dental diseases such as high dental caries, periodontal disease prevalence, missing teeth, and malocclusion. There are many challenges that children with disabilities and their carers experience regarding oral health, including access to dental care, availability of preventive interventions, oral health literacy, and education.This study aims to understand the personal experiences and views of stakeholders involved in the child’s life and/or care, to gain an in-depth understanding of the barriers and enablers of oral health for children with disabilities, and to guide policy by creating a framework for policymakers and stakeholders to address the problems of oral health for children with disabilities.Methods:A systematic review was conducted to understand the existing body of evidence on barriers, facilitators, and the involvement of stakeholders (parents, caregivers, dental and non-dental health providers, health systems, and policies) in the oral healthcare of children with disabilities. This led to the identification of knowledge gaps and provided a clearer understanding of the literature related to the research objectives.A qualitative approach was used, with 31 semi-structured in-depth interviews conducted with parents (using purposive sampling) and dental/non-dental health providers (using snowball sampling). The main findings of the interviews were transcribed and coded using the six steps of thematic analysis, following an inductive approach as outlined by Braun and Clarke. An interpretive approach was adopted to pursue an answer to the research question while considering the primary aims and objectives of the study.ResultsThis study identified five core themes and 29 sub themes of barriers and facilitators shaping oral healthcare for children with disabilities: 1) Infrastructure and health system limitations, 2) Financial barriers, 3) Gaps in training and caregiver knowledge, 4) Accessibility and availability of services and 5) Stigma and caregiver perceptions. These empirical findings informed a conceptual framework structured around three interrelated dimensions of socioeconomic and governance, social stigma, and healthcare systems. The framework is underpinned by the social model of disability and the socio-ecological approach, offering both a practical and theoretical tool for system reform.An accompanying implementation tool outlines actionable strategies for health authorities, including stakeholder training, service integration, policy alignment, and inclusive community outreach.ConclusionThis study examined the barriers and facilitators influencing oral healthcare access for children with disabilities in the UAE. Qualitative analysis identified five key themes. These findings informed a conceptual framework that captures the multi-level influences on oral health. The framework supports policy development and service redesign in the UAE. Its utility lies in mapping the interaction between governance, healthcare systems, and lived experience. An implementation tool, developed directly from stakeholder insights, helps stakeholders identify actionable points of intervention. While developed in the UAE context, the framework also offers potential for adaptation and piloting in comparable settings.By anchoring the analysis in stakeholder experiences and drawing on socio-ecological and rights-based perspectives, the study contributes pragmatic, evidence-informed tools for addressing oral health inequities both locally and as a basis for future adaptation and intervention research
Reforming medical training for psychiatry of intellectual disability: from margins to mandate
No full textExploring the Potential use of TEAD Inhibition as Part of a Combination Therapy for NF2-Deficient Schwannoma and Meningioma.
No full textNF2-related Schwannomatosis is a genetic cancer predisposition syndrome, resulting in the development of schwannoma, meningioma and ependymoma tumours. Although surgical resection and adjuvant radiotherapy can be used, new avenues of therapeutic development are essential to target inoperable and recurrent tumours. Previous studies evaluating small molecule TEAD auto-palmitoylation inhibitors have distinguished their anti-proliferative effect in NF2-deficient cancers. Here we aim to identify compounds that could be utilised in conjunction with TEAD inhibition, to target aberrant Hippo signalling and secondary resistance mechanisms. We utilised immortalised and primary cells to evaluate the efficacy and potential synergism of TEAD inhibitors VT3989 and VT107 in combination with brigatinib. Further preclinical in vivo modelling was used, including pre-established intracranial meningioma xenograft implantations and the Postn-Cre;Nf2 fl/fl schwannoma mouse model. These efforts determined that the VT3989/brigatinib combination demonstrates synergistic inhibition of cell viability in meningioma and schwannoma cells, while supressing tumour growth and proliferation of NF2-deficient meningioma xenografts, and the spontaneous schwannoma model. Furthermore, in the absence of ALK, it was determined that the VT3989/brigatinib combination treatment interacts with various tyrosine kinases, alongside a reduction in TEAD driven transcriptional activity to induce its anti-neoplastic effect. Due to the broad inhibitory profile and off target effects of brigatinib, alternative pre-established inhibitors pictilisib and selumetinib were evaluated, reducing proliferation and cell viability of NF2-deficient cells. This thesis had provided evidence that pharmacological disruption of TEAD transcription as part of a combinational strategy demonstrates a major advancement in the development of therapeutics for NF2-related Schwannomatosis
Towards an Evaluation of the Business Value of AI: A System Dynamics Approach
No full textIn the early 2010s, when Artificial Intelligence (AI) emerged from the latest winter of disillusionment, discussions about its use in decision-making tended to be dichotomous: humans or AI. More recently, consensus has shifted toward a complementary humans-and-AI perspective, recognising that augmentation, not substitution, is the more appropriate frame for AI\u27s role in the foreseeable future. This shift foregrounds the challenge of evaluating outcomes in collaborative decision-making contexts.The thesis proposes a simulation-based framework, drawing on system dynamics, to evaluate whether complex, time-varying interactions between humans and AI agents result in collectively rational behaviour. The framework extends the observation of dynamic complexity to settings where algorithmic components handle pattern recognition and prediction while human judgement governs goal-setting, threshold parameters, and cross-process coordination. Two testbeds test the framework\u27s viability: a stylised supply chain model and a bike-share system.In the supply chain testbed, forecasting product returns is handled by machine learning, while human judgement determines how forecasts translate into capacity and inventory decisions. A partial model tests local rationality, while a fuller model places forecasting in a broader operational context to assess holistic rationality. In the bike-share case, inventory balancing relies on crowdsourcing, where incentivised users take action. Using open data from New York\u27s Citi Bike, the study highlights misalignments between incentives and system needs, underscoring the complexity of user behaviour mediated by bike availability.The findings confirm that AI models evaluated in isolation may deliver disappointing results when task performance is considered holistically. These cases demonstrate the central contribution: a simulation-based framework for assessing the joint performance of human and AI decision-makers, supported by a simulation workbench that enables systematic exploration of alternative policies
Prioritising follow-up for people with suspected epilepsy using a digital EEG biomarker
No full textLengthy waits for follow-up testing are common for people with suspected epilepsy. This delays diagnosis, prolongs uncertainty and increases seizure risk. Initial EEGs are frequently inconclusive, yet follow-ups are often dictated by referral date, and there is no established method for risk-based prioritisation. Here, we tested whether an established digital EEG biomarker could help prioritise those most likely to have epilepsy for expedited follow-up EEG testing. We analysed 196 normal non-contributory (non-diagnostic) initial EEGs collected from six National Health Service (NHS) sites in England. From these recordings, we extracted eight previously validated computational features that quantify the likelihood that the EEG was recorded from someone with active epilepsy. We then used this information to reorder follow-up lists and compared outcomes against standard referral-based scheduling.We found that ordering for follow-up testing based upon the digital biomarker consistently prioritised people subsequently diagnosed with epilepsy; for a waitlist of 40 patients, the median number of follow-up EEGs needed to see 50% of true epilepsy patients was decreased by 6 (95% CI 4–7). The EEG diagnostic yield for epilepsy of follow-ups was increased relative to orderings based on time of referral (median increase in yield for epilepsy at 50% follow-up EEGs was 5%; 95 CI 4.9%-10%). Our study indicates that a routine EEG may furnish an objective risk metric that could accelerate second-line investigations and so reduce diagnostic delay whilst improving resource allocation in clinical practice
The academic lives of commuter students: examining the use of the physical and digital spaces within the contemporary university
No full textIt is estimated that 40% of UK undergraduates commute to study, travelling varying distances, and often daily. Although commuting can be challenging, many learners see it as a way to access university, whilst maintaining existing commitments and support networks, and offsetting growing costs of higher education (HE). This study employed a novel participatory mapping technique to stimulate focus groups of second- and third-year undergraduates who commute. We explored participants’ engagement with their institution’s campus, and online/digital spaces. Our findings show commuters have nuanced and intentional interactions with the University’s physical and digital landscape. We consider how these interactions may be mediated by distances commuters travel, their motivations for commuting, and the extent to which they seek wider university experiences. Participants reported shortcomings in provision of essential information at key moments (e.g., induction), which impacted their sense of belonging to the campus. They also queried the relevance of some services commonly perceived as important to the university experience (e.g. students union). Our findings indicate limited visibility of the sizeable commuter population within institutional practices and illustrate the heterogeneity of their university spatial experiences. We discuss implications for the widening access agenda and democratic functioning of universities, Finally, we consider how to optimise spatial engagement of commuters, to enhance their sense of belonging, engagement, and retention
Devaluation insensitivity of event related potentials associated with food cues
No full textEating in the absence of hunger represents a failure of homeostatic mechanisms responsible for energy balance and is a cause of obesity. The pervasive presence of food cues in the modern environment may play a role in this phenomenon. The present study used the technique of satiety-specific selective devaluation to investigate eating in the absence of hunger in the context of a reinforcement learning task. While participants’ performance on the task suggested that food on which they had sated no longer held value for them, event related potentials following images of the food were unaffected by the devaluation. Food cues may thus serve as an entry point for over-eating in otherwise healthy individuals
Only One Percent of Important Shark and Ray Areas in the Western Indian Ocean Are Fully Protected From Fishing Pressure
No full textThe Western Indian Ocean (WIO) is known for its high diversity of chondrichthyans (sharks, rays, and chimaeras). However, intense fishing pressure has led to severe population declines and local extinctions of several species. The Important Shark and Ray Area (ISRA) process is a collaborative, evidence-based approach used to identify critical habitat for chondrichthyans. We analysed ISRAs across the WIO to quantify the diversity of research methods used to identify them, evaluate spatial overlap with designated marine protected areas (MPAs), model the influence of several species- and jurisdiction-specific variables on ISRA delineation, and explore the importance of incorporating unpublished data into the delineation process. In total, 125 ISRAs (covering \u3e 2.8 million km2; ~10% of total regional surface area) were identified within the WIO from surface waters to ~2000 m depth. These ISRAs contain over one-third (n = 104, 39%) of the 270 chondrichthyan species reported from the region, with 76% being threatened with extinction according to the IUCN Red List of Threatened Species. The underlying evidence supporting ISRA identification was primarily drawn from relatively inexpensive research methods, such as visual census (25%) or fish-market/landing site surveys (22.6%), as well as citizen science (9.5%). Incorporating unpublished records substantially increased the frequency of ISRA delineation, leading to expanded taxonomic and geographic coverage. Still, the full dataset was influenced by the same biases as the published record, tending to favour large-bodied, wide-ranging, and shallow-dwelling species. Only 7.1% of ISRAs are within designated MPAs, with just 1.2% in fully protected no-take areas. The highest no-take overlap occurs in the Seychelles and Chagos Archipelago. These findings highlight the shortfalls in spatial protection of chondrichthyan habitats, but also present a strategic opportunity for policy-makers and resource managers to improve current MPA coverage and meet their commitments under international agreements, such as the Global Biodiversity Framework
The impact of skin tone on performance of pulse oximeters used by NHS England COVID Oximetry @home scheme: measurement and diagnostic accuracy study
No full textOBJECTIVES: To assess the impact of skin tone on the measurement and diagnostic accuracy of five fingertip pulse oximeters used by patients in the NHS (National Health Service) England COVID Oximetry @home scheme.
DESIGN: Measurement and diagnostic accuracy study (exploring pulse oximeter accuracy across skin tones-EXAKT).
SETTING: Twenty four intensive care units in England between June 2022 and August 2024.
PARTICIPANTS: 903 critically ill adults admitted to intensive care units screened for or enrolled into a trial evaluating different approaches to oxygen therapy.
INTERVENTIONS: Pulse oximetry derived peripheral oxygen saturation (SpO2) measurements were compared with paired arterial oxygen saturation (SaO2) measurements from arterial blood analysed by co-oximetry (gold standard). Skin tone (individual typology angle) was objectively measured using a handheld spectrophotometer.
MAIN OUTCOME MEASURES: Pulse oximeter measurement accuracy was assessed for bias, precision, and overall accuracy. Diagnostic accuracy for identifying SaO2 ≤92% was assessed by false negative and false positive rates for SpO2 using thresholds of ≤92% and ≤94%, and the area under the receiver operating characteristic curve, and by the presence of occult hypoxaemia (SaO2 \u3c88% with SpO2 \u3e92%).
RESULTS: 11 018 paired SpO2-SaO2 measurements were analysed. All tested pulse oximeters overestimated at lower values and underestimated at higher values of SaO2. On average, SpO2 readings were 0.6-1.5 percentage points higher for patients with darker skin tone (individual typology angle -44°) than for those with lighter skin tone (46°). At both SpO2 thresholds assessed, false negative rates increased with darker skin tones; the proportion of SpO2 measurements \u3e94% despite a paired SaO2 ≤92% ranged from 5.3 to 35.3 percentage points higher for patients with darker skin tones than for those with lighter skin tones (7.6-62.2% v 1.2-26.9%, rate ratio 2.3-7.1). By contrast, false positive rates decreased with darker skin tones.
CONCLUSIONS: Five pulse oximeters provided by the NHS England COVID Oximetry @home scheme yielded higher SpO2 measurements for patients with darker skin tones compared with those with lighter skin tones, which could translate into potentially clinically important differences in false negative and false positive rates for detecting hypoxaemia.
TRIAL REGISTRATION: ClinicalTrials.gov NCT05481515