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Psychopathology in Functional Neurological and Dissociative Seizure Disorders: using Meta-Analytic and Network Approaches to Gain Insight into Prevalence and Treatment
No full textFunctional Neurological Disorder (FND) is a condition in which people experience
neurological symptoms, such as seizures; movement difficulties; or sensory changes, that are not explained by structural or electrical problems within the brain. One presentation observed in those with FND are Functional Dissociative Seizures (FDS), which resemble epileptic seizures but occur without measurable biological markers. Both conditions significantly impact daily life, are associated with functional disability, and are often linked with psychological disorders.
This thesis explored the relationship between functional conditions and psychological
disorders in two ways. The first study reviewed 34 papers examining how often post-traumatic stress disorder (PTSD) occurs in people with FDS. As individual study results vary, a meta-analysis was conducted; bringing together findings to generate a clearer co-occurrence estimate. Results highlight approximately one third of people with FDS meet the criteria for PTSD, a rate much higher than observed in the general population. Whilst PTSD appears important in the FDS population, it is not universal. This highlights that other biological; psychological; and social factors should be considered as playing a role in the onset and maintenance of the disorder.
The second study conducted network analysis on FND clinical data, gathered from
individuals who attended a neuro-psychotherapy service in England, UK. This allowed exploration of how psychological and functional symptoms relate to each other, in an estimated FND network. Results found PTSD symptoms; low self-efficacy; and difficulties in relationships, were the most connected symptoms within the network, suggesting these areas as potential intervention targets. Together, these studies indicate that trauma-related symptoms; self-perception; and relational functioning are important factors to consider in FND. Clinically, findings support the use of trauma-informed therapies, such as trauma-focused cognitive behavioural therapy (CBT); eye movement desensitisation and reprocessing therapy (EMDR); or interpersonal psychotherapy (IPT), in those with functional neurological and dissociative seizure disorders
Profiling the demands of football Goalkeepers over the competitive week – implications for session design
Get PDFThis thesis aimed to increase the understanding associated with the physical demands and the current in-season practices of professional football Goalkeepers throughout activities indicative of the week-long competitive microcycle (including match-day). Holistically characterising evidence from a range of sources, including desk-based (i.e., literature reviewing), empirical observations (i.e., primary data collection), and from Goalkeeping practitioners (i.e., via survey), has provided an original evaluation of current in-season Goalkeeper practices that has implications for movement solutions and session design.
Using match-play as the main focus, literature review findings (chapter two) summarised the limited availability of works pertaining to the performance responses of football Goalkeepers. Searches were conducted in the PubMed online database during March 2018, (with an updated table included as of January 1st 2025). Keywords relating to the sport (i.e. ‘soccer’, ‘football’) and position (i.e. ‘goalkeeper’, ‘goal keeper’, ‘goal-keeper’, ‘keeper’, ‘goalie’, ‘GK’) were entered in various combinations. Following the removal of duplicates and screening of abstracts, the remaining full-text articles were assessed using a narrative review strategy, with articles retained based on six-stage inclusion criteria.
Although extensive research exists in relation to outfield players, limited studies have investigated the physical demands of football Goalkeepers within match-play. Current research suggests that Goalkeepers cover ~4-6 km on match-day and appear not to experience between-half reductions in physical performance as the match progresses. Whist making saves (preventing a goal) represents the most important phases of play, they occur relatively infrequently during a match (~2-10 #∙match-1), however, should remain a major training focus for football Goalkeepers. Future work should investigate Goalkeepers’ physical responses to particular activities within training and match-play, whilst looking to gain a greater understanding of the current in season Goalkeeping practices and their implications on movement solutions and actions relating to match-play.
Whilst limited research exists to thoroughly compare the match-play performance responses of Goalkeepers and outfield players, literature review findings confirmed the differing physiological profiles between Goalkeepers and outfield players during isolated performance tests, with Goalkeepers generating greater knee flexion and extension peak torque than the majority of outfield players. Most studies involving senior Goalkeepers reported superior jump performance compared with their outfield counterparts. Assessments of linear and multidirectional speed, multi-stage fitness test performance reported some aspect of inferior performance for Goalkeepers when compared to at least one other positional sub-group.
Chapter three sought to assimilate empirical observations to better understand the physical
demands of professional football Goalkeepers throughout a week-long competitive microcycle. Recruiting eight English Premier League football Goalkeepers, wearing Goalkeeper-specific micromechanical electrical systems (MEMS) devices, all participants completed the demands of each activity and a within-subject design was implemented to allow comparison between the different activities performed throughout a competitive week-long microcycle. It was observed that Goalkeepers did not follow the same pattern as their outfield counterparts relating to match-play loading. Notably, when certain position-specific performance metrics (i.e., dives, jumps, changes of direction, and explosive efforts) were considered, the greatest physical demands occurred during non-match-play activities during the competitive week. Specifically, Goalkeepers performed more dives (~51 vs ~10), high-speed changes of direction (~34 vs ~8), high (~14 vs ~1) and medium (~19 vs ~7) jumps, and explosive efforts (~70 vs ~16) during a ~79-min Goalkeeping-training session when compared with 90-min of match-play. Such findings have likely significant implications for applied practice.
Further empirical evidence was gathered when looking at the transient physical demands that Goalkeepers experienced throughout 90-min of match-play (chapter four) using linear mixed modelling. Similarities between halves were observed in the number of dives performed and high-speed distance covered by Goalkeepers, whilst more explosive efforts and high-speed changes of direction occurred when compared with before half-time. Additionally, Goalkeepers appeared to experience greater physical demands during the final 30-min (i.e., 60-75 and 75-90-min epochs) of a match, when compared with the opening 15-min; possibly indicative of the progressive fatigue experienced by outfield players, or team tactics and state-of-play (or combination thereof) influencing the physical demands of the Goalkeeper that protects their team’s goal and/or quickly re-distributes the ball to team-mates.
With a greater understanding of the physical demands of football Goalkeepers during both training and match-play, a key consideration relating to the degree of synergy between training and competitive demands is the perception of Goalkeeping coaches concerning practice design (including the availability of decision-making and physical movement solutions for the Goalkeeper). Goalkeeping coaches took part in an online survey centred around the ‘practice spectrum’; a scaled session design framework from isolated-technical (announced) to complex (unannounced and live). A mixture of open and closed-ended questions was used, allowing for descriptive statistics to be gained from frequency and thematic analysis (Braun & Clarke, 2006). The study aimed to explore Goalkeeping coaches current planning and delivery strategies of Goalkeeping training sessions, and the effects that this may have on the availability of decision-making and physical movement solutions for the Goalkeeper.
Goalkeeping coaches looked to design sessions in a linear fashion, progressing from isolated-technical (announced) to complex (unannounced and live); announced (part 1 – 84.6%), unannounced (part 2 – 74.7% & 3 – 69.1%) and live (part 4 – 89.5%). Announced session structures (isolated-technical focus and limited in decision making), alongside an increased physical focus were predominantly used at the start of the training week leading into a match. Findings allude to the possibility of coaches purposefully aiming to reduce the cognitive/decision making load during the period soon after a match. Whilst there may be an element of attending to the cognitive needs of the Goalkeeper, the designing of sessions in this manner may lend to repetitive practices of movements and isolated-techniques, designed for Goalkeepers to work on their ‘basics’ in a physical manner far greater and less representative to what would be needed and imparted in a match (as highlighted in chapters three and four). Whilst Goalkeeping sessions were designed in a linear manner from isolated-technical to complex, a desire to implement an environment rich in decision-making for the Goalkeeper and allowing for exploration of movement solutions was observed ‘most of the time’ at an unannounced level. Based on the practice spectrum descriptors of unannounced, the session design structure would positively limit the Goalkeepers’ prior knowledge of the session structure or service type, aiding in the development of their position specific skills.
Whilst Goalkeeping coaches sought to develop Goalkeepers through their session design structures, collaboration was evidenced to take place between Goalkeeping coaches and other staff members, with lesser consultation amongst sports science staff (36.4%), medical team (37.0%) and analysts (29.0%) and greater discussions taking place with the manager (63.6%), other coaches (73.5%), and Goalkeepers (59.9%). Such sentiments may link with the highlighted personal areas of development of Goalkeeping coaches; physical (31.5%) and psychological/social (35.8%) and the primary focus areas of technical (46.3%) and tactical (43.2%) that Goalkeeping coaches attend to within their session design.
The thesis purposefully aimed to assess the current literature of the unique and specialised position of the football Goalkeeper, whilst providing original insights into the physical demands and the present in-season Goalkeeping practices throughout a week-long competitive microcycle (including match-day). Evidence was found to support the importance of understanding activity-type demands that professional Goalkeepers are placed under and the effects that such activities may have on future training designs and recovery methods. Further insight attended to the knowledge of the fluctuating demands within 90-minutes of match-play and the implications for the Goalkeeper, and team (physically and tactically). A greater awareness was gained into the current planning and delivery strategies of Goalkeeping coaches in relation to the practice spectrum, thus allowing for an appreciation of the training methodologies employed and the availability of decision-making and physical movement solutions for the Goalkeeper
Continuous Separation of Biotransformation Products
Get PDFIn the last decade the continuous flow synthesis of fine chemicals and active
pharmaceutical ingredients (APIs) for drug production has become increasingly
widespread. Continuous flow systems offer a pathway to improved mass transfer,
thermal control, in-line purification and mixing, indicating a beneficial alternative
to batch systems. A major challenge for industry is the application of continuous
flow technology to relevant biotransformation processes. There has been little
research into the combination of biocatalysis with continuous flow chemistry, due
to the complexity of extraction techniques for the removal of biotransformation
products from complex reaction mixtures, and the need for cofactor regeneration.
These difficulties associated with biocatalysis reported in literature could be
overcome with the combination of efficient continuous separation techniques and
enzyme solubilisation. This report aims to explore the integration of biocatalytic
transformations in continuous flow with emphasis on separation techniques,
enzymes, whole cells, and co-factor recycling. This report also includes an outline
of the future objectives and directions of this project
Development of Hydrodynamic Downforce for Locomotion of In-Pipe Robots in Active Water Pipes
No full textNon-Planar Aromatic Diimide-Based Organic Light Emitters
No full textThe development of photoluminescent aromatic diimides (ADIs) remains an ongoing point of interest for research because of their potential to benefit our realisation of more advanced chemosensing, (bio)chemical diagnostics, functional nanomaterials and organic display technologies. With the exception of intrinsically emissive perylene diimides, smaller and more energy-dense ADIs such as benzene and naphthalene diimides are not naturally emissive and have traditionally required installation of electron-rich donor substituents on their aromatic cores to induce favourable charge distributions to “turn on” and “tune” photoluminescent properties. Other strategies to overcome this fundamental challenge have explored the embedding of electronegative (i.e., lone-pair possessing) heteroatoms to achieve light-emitting properties, as well as manipulating the degree of π-conjugation within ADI systems to tune their donor–acceptor charge-transfer and excited states.
This Thesis investigates similar π-donor conjugation approaches to induce and control the photoluminescence properties in two novel class of ADI-based redox-active molecules: (i) non-linear heteroaromatic diimides referred to as isoindole diimides (IDIs) and (ii) donor-functionalised [5]helical non-planar aromatic diimides (H). In Chapter 2, IDIs are established as a new class of inherently emissive aromatic diimides with PLQYs up to 0.93, that are further explored for their optical tunability via core functionalisation with substituents of different nature including aliphatic and aromatic moieties, polar groups to induce intramolecular interactions, and ultimately, development of dyads with electron-rich chromophores to discern their photoluminescence mechanism. Experimental and theoretical studies revealed IDIs to switch between locally-excited (LE) and charge transfer (CT) characteristic-S1 state depending on the core substituent with pathologically low T1 state for all, affording fluorescence via aggregation or intramolecular charge transfer (ICT). In the latter Chapters, ADI-based helicenes are functionalised with pyrene (Chapter 3) and pyridine (Chapter 4) to explore the influence of π-conjugation and heteroatom incorporation, respectively, towards “switching on” and in turn, accessing energy-efficient photoluminescence via intra/inter-molecular (excimeric) interactions and/or charge transfer in the excited states. Notably, upon pyridine substitution, not only are the helicenes found to be emissive, but also stimuli-responsive to produce white-tunable emission, which remains a current challenge for single-molecule organic light emitters. These advances in ADI chemistry enables access to a wide range of functional organic molecules in addition to offering a deeper understanding of the fundamental molecular interactions at play in affording energy-efficient photoluminescent properties that can be applied towards the development of advanced light-emitting technologies paving the way to a brighter, more sustainable future
Estimating the clinical effectiveness of virtual fractional flow reserve (vFFR) and its potential impact upon the quality of life and costs of treatment in coronary artery disease
Get PDFBackground:
Invasive (measured) fractional flow reserve (mFFR) is a pivotal tool for evaluating and directing management strategies for moderate coronary artery disease (CAD); however, its utilisation in clinical practice is limited due to its invasive nature, expense, and time constraints. Virtual FFR (vFFR) computed from the coronary angiogram (CAG) can be performed without needing a pressure wire or hyperaemia induction. Whilst vFFR is gaining clinical effectiveness data, little is known about its cost-effectiveness and implications for quality of life (QOL). In the VIRTU-4 study, patients with acute and chronic coronary syndromes underwent CAG and vFFR assessment. Their management plan was made on the basis of the CAG, and any potential (virtual) change after vFFR was documented.
Hypothesis:
Management plans based upon vFFR will lead to important potential changes in cost-effectiveness and QOL compared to those based upon coronary angiograms only at 12 months.
Methods:
Patients in VIRTU-4 were contacted at one year for clinical endpoints, including all-cause mortality, myocardial infarction, stroke, hospital re-admissions, repeat revascularisations, outpatient attendances and cardiac rehabilitation. Data on quality of life (EQ-VAS and EQ-indexed scores), NYHA and CCS classes at one-year follow-up were gathered. Total costs incurred were calculated. Patients who experienced a virtual change in management plan following vFFR disclosure underwent review in two independent expert MDTs to predict virtual changes in the actual outcomes if vFFR-based plans had been followed. The clinical and economic implications of these changes were estimated, guided by available literature.
Results:
Of 308 patients in VIRTU-4, 266 were contactable at one year. There were seven deaths, five MIs, and three strokes. In the ACS cohort, there were 32 cardiac re-admissions and five repeat revascularisations, and in the CCS cohort, 25 cardiac re-admissions and seven revascularisations. There was no statistically significant difference in patients' QOL at 12 months compared to baseline. However, QOL parameters demonstrated improvement after excluding non-cardiac factors. 65/266 patients (24.4%) had a virtual change in management plan after vFFR disclosure. vFFR-based treatment decisions would have saved 26 invasive pressure wire assessments. Within the ACS group, 17/39 patients (43.5%) treated with PCI would have received conservative treatment, whereas in the CCS group, 13/26 patients (50%) who received conservative treatment would have undergone PCI. vFFR-guided plans would have resulted in an average virtual increase in the cost of £60 per patient in the virtual change subset (n=65), comprising a saving of £163 per patient in the ACS group and an extra spend of £395 per patient in the CCS group. vFFR guidance could have led to a virtual increase in QOL scores for ACS patients by 0.3% in EQ-VAS (p=0.96) and 0.1% in EQ-indexed scores (p=0.96). For CCS patients, vFFR could have resulted in a virtual increase of 6.7% in EQ-VAS (p=0.02) and 5% in EQ-indexed scores (p=0.03). When factoring in the cost of a vFFR licence to the total annual costs, the ICER remained well below the willingness-to-pay (WTP) threshold for the UK, demonstrating the cost-effectiveness of vFFR+CAG compared to CAG-only. The ICERs were £2803, £4077, and £6626 per QALY for voucher-based licence costs of £50, £100, and £200 per patient, respectively. Similarly, with an institutional license, the ICERs were £4077, £5352, and £7901 per QALY for annual license tariffs of £20,000, £30,000, and £50,000, respectively.
Conclusions:
Incorporating vFFR into revascularisation plans for coronary artery disease (CAD) not only resulted in a change of management plans in one-fifth of cases but could also offer potential clinical and economic benefits over conventional CAG, with trivial additional net costs
Engineering Functional Partial Joint Replacements: A Soft Solution To A Hard Problem
Get PDFArthritis often leads to joint replacement, where metal and plastic or ceramic components are used to restore function. While effective, these replacements can fail over time, leading to complex and unpredictable revision surgeries. In many cases, arthritis affects only one side of the joint, making partial joint replacement (hemiarthroplasty or focal cartilage repair) a less invasive alternative. However, replacing soft cartilage with hard metallic surfaces in current hemiarthroplasty devices often results in poor outcomes, as the stiff implants reduce contact area and increase stress on the remaining cartilage, potentially causing further degeneration.
This thesis explores the use of polyelectrolyte functionalised biomaterials as cartilage interfacing surfaces, focusing on SPMK-g-PEEK — a biomimetic interface composed of 3-sulfopropyl methacrylate potassium salt (SPMK) tethered to a polyetheretherketone (PEEK) substrate, inspired by the natural biopolyelectrolytes in synovial fluid. SPMK-g-PEEK surfaces form a highly hydrated, compliant layer (~ 5 μm thick) due to their dense coverage of hydrophilic sulphonic acid groups, which supports aqueous boundary lubrication and promotes cartilage interstitial fluid recovery.
Under aqueous conditions, SPMK-g-PEEK exhibits ultra-low friction coefficients (μ < 0.02), consistent across physiologically relevant speeds (0.1 – 200 mm/s) and contact pressures (0.25 – 2 MPa), mimicking the tribological properties of natural cartilage. Additionally, these surfaces facilitate a novel mechanism of polyelectrolyte-enhanced tribological rehydration (PETR), promoting cartilage interstitial fluid recovery even in static contact areas. This mechanism supports continuous lubrication and contrasts with conventional theories that attribute cartilage rehydration to hydrodynamic fluid entrainment facilitated by convergent cartilage contact geometries. PETR is attributed to the combined effects of fluid confinement within the contact gap and the enhanced elastohydrodynamic behaviour of surface tethered polyelectrolytes.
This work not only enhances the understanding of cartilage tribology but also offers a promising strategy for developing joint replacement materials that more effectively replicate the natural function of cartilage. The implications extend to advancing the design of next-generation implants for focal cartilage repair, offering new potential for improved patient outcomes in orthopaedic applications
Vessel Tree Segmentation and Modality Agnostic Aneurysm Detection
Get PDFSegmentation of cerebral vessels and aneurysms is vital for diagnosing cerebrovascular conditions, developing treatment plans, and supporting in silico trials.
The intricate nature of cerebrovascular anatomy and the small and irregular characteristics of aneurysms pose significant challenges for obtaining high-precision segmentation, which is vital for accurate clinical evaluations and planning of interventions.
The motivation stems from the necessity to address several critical challenges that compromise the efficiency of existing segmentation models. These challenges include class imbalance, where smaller structures, like aneurysms, are often under-represented in datasets, leading to suboptimal segmentation performance. Moreover, the insufficiency of labelled data constrains the potential of fully supervised models. In addition, the issue of domain shifts across various imaging modalities and patient populations can cause models trained on one dataset to perform inadequately on another. Finally, there is a need for models that can generalise effectively across diverse datasets from various clinical data sources, ensuring consistent performance regardless of the data source.
In response to these challenges, this thesis presents several novel contributions. It introduces a 3D patch-based multi-class model that effectively manages class imbalance and inter-class interference in vessel and aneurysm segmentation, employing advanced network elements and paired preprocessing and postprocessing techniques to enhance accuracy. A semi-supervised learning approach is also developed to leverage both labelled and unlabelled data, significantly improving segmentation consistency and continuity, particularly in scenarios with limited annotations. Furthermore, the thesis proposes a transwarp contrastive learning framework for unsupervised domain adaptation, allowing the model to handle domain shifts and perform robustly across different data modalities. Finally, a gradient-based domain generalisation method is introduced to ensure that segmentation models can generalise well across various imaging conditions, overcoming the challenges posed by data source variability
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