Background: There is increasing recognition of the need for service development for patients in the advanced stages of neurological conditions. This study explores the palliative care needs of people with advanced amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s disease and related disorders, and assesses the impact of a new specialist palliative care service (SPCS) Methods:. A mixed methods approach was adopted: • a qualitative needs assessment using in-depth interviews with patients and their family carers and focus groups of professionals involved in the care of this population. • a quantitative pilot-explorative randomized and controlled trial (RCT) to assess the impact of a new SPCS designed to meet the palliative care needs of the study population – using a waiting list methodology comparing the immediate provision of SPCS with standard care . Results: • Qualitative study: 22 patients, 21 family carers and 11 professionals participated to the needs assessment. The content analysis showed a high prevalence of problems. Professionals confirmed the high burden of problems, were positive about the creation of a new SPCS and their knowledge of specific palliative care topics seemed lacking. • Quantitative study: 50 patients, with 45 carers, participated in the explorative RCT. The comparison between the groups (FT-ST) after 16 weeks revealed significant improvement for the SPCS group for quality of life and in four physical symptoms - pain, breathlessness, sleep disturbance and intestinal symptoms Conclusions: This research confirms the high prevalence of physical symptoms, psychosocial issues and spiritual themes for people severely affected by advanced neurodegenerative disorders and that these can be helped by specialist palliative care. The input of a SPCS caused a significant improvement of the individual quality of life of the patients and improved symptom control for pain, breathlessness, quality of sleep and intestinal symptoms compared to standard best care alone.

This current PhD Thesis in Neuropathology focuses on the development and assessment of in vitro simulation approaches to intracerebral haemorrhage. The PhD Thesis provides a clinical and experimental neuropathological overview of intracerebral haemorrhage as well as an account of the in vitro simulation approaches to the disease, before proceeding to the presentation of the experimental work designed and performed by the author. The development of the herein presented in vitro simulation approaches to intracerebral haemorrhage was based on the use of an immortalized embryonic murine hippocampal cell-line (mHippoE-14) and its response to oligomycin-A and ferrum or haemin under appropriately selected conditions (aiming to simulate the natural history of the disease in a more reliable manner). The PhD Thesis provides a characterization of the mHippoE-14 cell-line (through a real-time cellular response analysis and a cytomorphological characterization), before proceeding to the actual experimental justification of the conditions chosen for the development of the herein presented in vitro simulation approaches to intracerebral haemorrhage, and their assessment. The latter was performed through the undertaking of: (a) real-time cellular response analysis, (b) cytomorphological assessment, (c) profiling of neuronal markers’ expression, (d) neurochemical assessment, and (e) proteomic profiling. All experiments were performed at the University of Glasgow. The current PhD Thesis also provides a critical appraisal of: (a) the utility, novelty and limitations of the developed in vitro simulation approaches, and (b) the positioning of the developed in vitro simulation approaches within the neuropathopoietic context.

One new treatment strategy for children with hemiplegic cerebral palsy (CP) is constraint-induced movement therapy (CIMT). CIMT combines restraint of the less affected upper extremity and intensive exercise with the affected limb. CIMT has been shown to be effective in adults following stroke but it is not clear whether or not CIMT can readily be incorporated into clinical practice either with adults or children. An intervention that may be more practical involves the restraint element of CIMT without additional exercise (Forced use therapy-FUT). FUT has been only sparsely investigated, especially in children with CP. Different versions of CIMT protocols have been suggested as being „child-friendly‟ but identifying a practical and effective protocol remains challenging. Part of a child-friendly protocol includes identification of the most appropriate type of constraint, as different splints have been used for different populations without justification of their selection. In this project, the aim was to identify the most appropriate splint from children‟s and parents‟ perspective as reflected by effectiveness and adherence to home-based FUT (feasibility study) and to investigate the functional effects of a modified version of CIMT (mCIMT) (effectiveness study) that was designed based on the findings of the feasibility study. A further aim of the study was to compare the effect of additional functional activities and feedback with constraint alone. Two questions emerged as being important during the course of the project; the first addressed poor recruitment to the effectiveness study and explored parents and therapist‟ views on the practicality and effectiveness of both the classic paediatric protocol and the one suggested by the present study. The second was to provide insight into the physiological effects of CIMT or other treatments that might explain variations in response. In this study a test using the lateralised readiness potential (LRP) component of the EEG that was appropriate for young children was developed and evaluated with a small sample of unimpaired children and children with CP.

Seizure onset prediction in epilepsy is a challenge which is under investigation using many and varied signal processing techniques, across the world. This research thesis contributes to the advancement of digital signal analysis of neurophysiological signals of epileptic patients. It has been studied especially in the context of epileptic seizure onset prediction, with a motivation to help epileptic patients by advancing the knowledge on the possibilities of seizure prediction and inching towards a clinically viable seizure predictor. In this work, a synchrony based multi-stage system is analyzed that brings to bear the advantages of many techniques in each substage. The 1st stage of the system unmixes and de-noises continuous long-term (2-4 days) multichannel scalp Electroencephalograms using spatially constrained Independent Component Analysis. The 2d stage estimates the long term significant phase synchrony dynamics of narrowband (2-8 Hz and 8-14 Hz) seizure components. The synchrony dynamics are assessed with a novel statistic, the PLV-d, analyzing the joint synchrony in two frequency bands of interest. The 3rd stage creates multidimensional features of these synchrony dynamics for two classes (‘seizure free’ and ‘seizure predictive’) which are then projected onto a 2-dimensional map using a supervised Neuroscale, a topographic projection scheme based on a Radial Basis Neural Network. The 4th stage evaluates the probability of occurrence of predictive events using Gaussian Mixture Models used in supervised and semi-supervised forms. Preliminary analysis is performed on shorter data segments and the final system is based on nine patient’s long term (2-4 days each) continuous data. The training and testing for feature extraction analysis is performed on five patient datasets. The features extracted and the parameters ascertained with this analysis are then applied on the remaining four long-term datasets as a test of performance. The analysis is tested against random predictors as well. We show the possibility of seizure onset prediction (performing better than a random predictor) within a prediction window of 35-65 minutes with a sensitivity of 65-100% and specificity of 60-100% across the epileptic patients.

Government policies currently emphasise the need to support those with dementia at home, and family carers are increasingly advised to engage their relative in daily activities. Knowledge about family carers involvement in the activity needs of individuals living with dementia is fragmented. This study explored carers' decision making related to their engagement with their relative in everyday activities at home. Following research governance and ethical approval, 30 in-depth interviews (initial and follow-up) were carried out with 15 resident-carers who were recruited via local community mental health teams. Then five focus groups were conducted through carer support groups. The majority of carers were spouses, three were daughters and one a female friend. Both the interviews and focus groups explored the experiences of involving relatives in daily activities and highlighted the carers' strategies, feelings and reflections. Themes were identified which formed a temporal model consisting of five activity patterns. These were the usual, recognisable, illogical, irresponsible and dispossessed patterns. The model illustrated the complexity and long-term nature of family carers activity-related decisions. Over the passage of time carers attempted to recapture the past self of their relative through engaging them in beneficial activity. The findings provided deeper insight in the understanding of the processes by which carers negotiated strategies; and how such processes challenged the carers' own sense of self. The model offers a new approach for occupational therapists and other healthcare professionals to guide home-based activity programmes in which carers' perspectives are taken into account. Practitioners could gain a more complete understanding of the caregiving situation, so that they can, more effectively, support the family member and hence the person with dementia more effectively. Further research will focus on developing a toolkit to enable practitioners to recognise the complexities, uncertainties and conflicting values which confront carers in their decision-making and so enhance partnership working.

Coccydynia is a form of back pain and occurs more commonly in women than in men, and is a particular clinical problem seen in Taiwan. Understanding of the condition is limited and it cannot be isolated from other dysfunctions in the lumbopelvic region. It is proposed that neuromuscular alterations that occur in low back pain (LBP) could also occur in coccydynia and forms the topic of this thesis. The aims of this study were to explore neuromuscular and musculoskeletal changes in Taiwanese women with coccydynia. A total of 55 Taiwanese women, aged 23-65 years were studied in three groups: healthy young participants in Southampton (n=18, aged 23-35 years); patients with coccydynia in Taiwan (n=20 aged 23-65 years) and healthy older women in Taiwan (n=17, aged 35-65 years). Three techniques were used to investigate musculoskeletal changes in coccydynia: rehabilitative ultrasound imaging (RUSI), 3-dimensional motion analysis (using the VICON system) and surface electromyography (sEMG).The reliability of the developed experimental protocols was first established at the University of Southampton and then the protocols were replicated for he main study in Taiwan. Patients had thicker resting transversus abdominis (TrA) muscles than healthy participants but showed less thickness change during a functional task, indicating reduced ability to contract the muscle. Differences between patients and healthy groups from motion analysis and EMG studies were found and indicate that neuromuscular alterations occur in coccydynia. In six case studies, a six week intervention using a pelvic belt, patients reported improvements in symptoms and function but there were no changes in the objective tests of musculoskeletal function. The contributions of this preliminary work to knowledge include: (1) provision of normal reference data of muscle morphology in Taiwanese women of different ages; (2) a possible effect of age on muscle contractile ability; (3) objective evidence of changes in musculoskeletal function in patients with coccydynia, specifically muscle morphology, motor control and biomechanical changes; (4) evidence of the feasibility of using RUSI as an appropriate tool to detect differences in the lumbopelvic muscles between patients with coccydynia and healthy participants; (5) Reliability of inter-recti distance measurement on RUSI at rest and during contractions in patients with coccydynia and healthy participants; (6) the pelvic belt may be a potentially effective intervention in the management of pain in coccydynia.

The vision for maternity services focuses on women-centred care with choice, control and promoting normality at its centre, thus emphasising the need to empower women to make choices and decisions regarding their care in labour and birth. Some women will choose the medical model of care, however others prefer to be in control and choose to use non-pharmacological alternatives for pain control in labour such as Transcutaneous Electrical Nerve Stimulation (TENS). TENS has enabled the provision of non-invasive, mobile, self-controlled pain relief for women in labour and is used extensively by women in the UK who, when asked, assess it favourably and say they would use it again. Currently the available literature on TENS fails to consider individual women’s experiences of using TENS for labour and birth, this study therefore seeks to redress this balance. Set in the south of England, the study uses Interpretative Phenomenological Analysis (IPA) in order to explore the experiences of twenty purposively selected women, who were interviewed to expose their in-depth experiences of using TENS for pain control in labour and birth. The analysis of the verbatim transcripts revealed comprehensive findings ensuring an idiographic focus along with making claims for the larger group of women. In this study women used TENS as part of a combination of more natural pain control or as a ‘sole’ form of pain control for labour and birth. TENS was recognised as being part of a wider strategy for the maintenance of control in labour and normal birth for women. A super-ordinate theme of ‘control’ emerged from the data particularly relating to ‘internal control of self’, ‘external control of others’ and ‘control of the TENS machine’. Women’s positive experiences were enhanced by remaining mobile, using drug free pain control, being knowledgeable, having partners’ and midwives’ support, being distracted from their pain and trusting in TENS. By uncovering a group of women’s in-depth experiences of using TENS for pain control in labour and birth this study has filled a “gap” in the knowledge base. In addition, the findings suggest that TENS was identified as an ‘enabling mechanism’ for the women in order to be in control of a normalised birth. Women were able to maintain their independence, make decisions and actively take part in their pain control using TENS.

This research uses the records of the Hampshire County Asylum (HCA) between its opening in 1852 and the end of the nineteenth century to offer a different perspective on asylum history. Though it discusses the asylum in legal, medical and social welfare contexts it focuses on the experience of individuals and their families and the part played by the HCA in their lives. The perspective and methodology of the research reflect the recognition of the importance of individual experience in the construction of historical exposition. In the course of the research a database of patients' personal information was constructed from asylum records. The resulting analysis of individual experience of admission to the HCA suggests that, for many patients, admission was short-term and temporary, caused by a combination of symptoms and events that erupted into crisis. For others the HCA provided a level of care that could not be sustained at home and for some an asylum admission was only part of a wider and continuing strategy of care which enabled troubled families to continue to function. The thesis concludes that, although the county asylum was a potent symbol of many aspects of Victorian society, it should be seen, not as defining those who encountered it, but as a part, sometimes essential but often small, of their personal and family narratives.

An inability to perform tasks involving reaching is a common problem following stroke. Evidence supports the use of robotic therapy and electrical stimulation (ES) to reduce upper limb impairments following stroke, but current systems may not encourage maximal voluntary contribution from the participant. This study developed and tested iterative learning control (ILC) algorithms mediated by ES, using a purpose designed robotic workstation, for upper limb rehabilitation post stroke. Surface electromyography (EMG) which may be related to impaired performance and function was used to investigate seven shoulder and elbow muscle activation patterns in eight neurologically intact and five chronic stroke participants during nine tracking tasks. The participants’ forearm was supported using a hinged arm-holder, which constrained their hand to move in a two dimensional horizontal plane. Outcome measures taken prior to and after an intervention consisted of the Fugl- Meyer Assessment (FMA) and the Action Research Arm Test (ARAT), isometric force and error tracking. The intervention for stroke participants consisted of eighteen sessions in which a similar range of tracking tasks were performed with the addition of responsive electrical stimulation to their triceps muscle. A question set was developed to understand participants’ perceptions of the ILC system. Statistically significant improvements were measured (p≤0.05) in: FMA motor score, unassisted tracking, and in isometric force. Statistically significant differences in muscle activation patterns were observed between stroke and neurologically intact participants for timing, amplitude and coactivation patterns. After the intervention significant changes were observed in many of these towards neurologically intact ranges. The robot–assisted therapy was well accepted and tolerated by the stroke participants. This study has demonstrated the feasibility of using ILC mediated by ES for upper limb stroke rehabilitation in the treatment of stroke patients with upper limb hemiplegia.

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common psychiatric disorder of childhood and manifests as symptoms of developmentally inappropriate inattention, impulsivity and hyperactivity. Although numerous deficits have been identified in ADHD, one of the most consistent findings is that patients with ADHD are more variable in the speed of their reaction time (RT) responses on neuropsychological tasks than control children. In 2008, the default-mode interference hypothesis of ADHD was introduced by Sonuga-Barke and Castellanos as a biologically plausible account of this increased within-subject variability in ADHD. This hypothesis suggests that some patients with ADHD might not effectively attenuate low frequency resting brain activity from rest to task and that these low frequency oscillations may then intrude onto task performance and cause periodic attention lapses. These periodic attention lapses would manifest as increased variability in RT data. The present thesis provided the first test of this hypothesis using DC-EEG. We assessed the power in very low frequency EEG bands (< .1 Hz) during rest and during goal-directed task performance in two samples. First was a sample of adults who self-reported either high- or low-ADHD scores, and second was a clinic referred sample of adolescent boys with ADHD and age- and gender-matched controls. We found that in both samples, low frequency EEG was generally attenuated from rest to task, but the degree of this attenuation was lower in ADHD or inattentive participants compared to controls. We also found that periodicity was evident in RT data, and that there was synchrony between low frequency fluctuations in RT data and low frequency EEG. These findings provide some initial support for the default mode interference hypothesis. The findings also highlight the potential involvement of low frequency electrodynamics in attentional processes and in the pathophysiology of ADHD.