Individualisation of transcranial electric stimulation to improve motor function after stroke:Current challenges and future perspective

Transcranial electric stimulation (tES) is a non-invasive brain stimulation technique that could potentially improve motor rehabilitation after stroke. However, the effects of tES are in general stronger in healthy individuals compared to people with stroke. Interindividual variability in brain structure and function due to stroke potentially explain this difference in effects. This thesis describes the development of methods to facilitate the individualisation of tES in people with stroke and identifies objective neurophysiological correlates of motor learning that could potentially help to monitor the response to tES.In chapter 2, EEG correlates of explicit motor task learning were derived in healthy, young participants. Chapter 3 investigated the effects of 3 different tDCS configurations (sham, targeting contralateral M1 and targeting the full resting motor network) on corticospinal excitability. Both conventional and motor network tDCS did not increase corticospinal excitability relative to sham stimulation. Chapter 4 describes methods to create head models of people with stroke and assesses the effects of stroke lesions on the electric fields within stimulation targets. Chapter 5 describes a method to experimentally determine the electric conductivity of the stroke lesion. Finally, Chapter 6 analyses the electric fields generated by conventional tDCS in people with stroke and age-matched controls. It is shown that the one-size-fits-all approach results in more variable electric fields in people with stroke compared to controls. Optimisation of the electrode positions to maximise the electric field in stimulation targets increases the electric fields in people with stroke to the same level as found in healthy controls.This thesis shows anatomical and motor function variability exists between people with stroke due to differences in lesion characteristics. While there are several opportunities to individualise tES, more research is needed to investigate if this improves the effects of tES. As such, clinical implementation of tES seems unrealistic in the foreseeable future.<br/

Individualisation of transcranial electric stimulation to improve motor function after stroke:Current challenges and future perspective

Transcranial electric stimulation (tES) is a non-invasive brain stimulation technique that could potentially improve motor rehabilitation after stroke. However, the effects of tES are in general stronger in healthy individuals compared to people with stroke. Interindividual variability in brain structure and function due to stroke potentially explain this difference in effects. This thesis describes the development of methods to facilitate the individualisation of tES in people with stroke and identifies objective neurophysiological correlates of motor learning that could potentially help to monitor the response to tES.In chapter 2, EEG correlates of explicit motor task learning were derived in healthy, young participants. Chapter 3 investigated the effects of 3 different tDCS configurations (sham, targeting contralateral M1 and targeting the full resting motor network) on corticospinal excitability. Both conventional and motor network tDCS did not increase corticospinal excitability relative to sham stimulation. Chapter 4 describes methods to create head models of people with stroke and assesses the effects of stroke lesions on the electric fields within stimulation targets. Chapter 5 describes a method to experimentally determine the electric conductivity of the stroke lesion. Finally, Chapter 6 analyses the electric fields generated by conventional tDCS in people with stroke and age-matched controls. It is shown that the one-size-fits-all approach results in more variable electric fields in people with stroke compared to controls. Optimisation of the electrode positions to maximise the electric field in stimulation targets increases the electric fields in people with stroke to the same level as found in healthy controls.This thesis shows anatomical and motor function variability exists between people with stroke due to differences in lesion characteristics. While there are several opportunities to individualise tES, more research is needed to investigate if this improves the effects of tES. As such, clinical implementation of tES seems unrealistic in the foreseeable future.<br/

The prognosis of newly diagnosed and treated epilepsies in adults

The prognosis for seizure control is an important consideration for patients diagnosed with epilepsy. Reversing the social restrictions imposed by seizures and returning to a productive life requires complete and sustained seizure control. The epilepsies are a heterogeneous group of disorders and clinicians discussing the prognosis of epilepsy need to be aware of the natural history of each epilepsy syndrome. Longitudinal follow up studies in newly diagnosed patient populations are required to delineate the natural history of the various syndromes. Previous studies have suggested that the early course of epilepsy is predictive of its longer-term behaviour in the majority of cases. If response to individual antiepileptic drugs (AEDs) in specific epilepsy syndromes can be predicted, prognosis can be assessed more accurately. Genetic influences on response to treatment are probably important in this regard. The completion of the Human Genome Project has opened up the possibility of correlating variations in the human genome with the variability of response to drugs. The discipline of pharmacogenomics, which seeks to study the genetic influence on response to drugs, has the potential to allow drug therapy to be optimised for each patient, maximising the chances of success. Identification of single nucleotide polymorphisms (SNPs) in candidate genes correlating with response to AED treatment can help identify patients at risk of developing drug resistant epilepsy. Epilepsy is associated with an increased mortality risk. The excess risk varies depending on the population studied, and is influenced by patients' clinical and demographic characteristics. Clinicians discussing mortality issues with patients need to be aware of the potential risk in each individual. This is best deduced from studies in representative patient groups. Risks need to be studied separately in patients with newly diagnosed and chronic epilepsy, as the prognoses in these two groups are likely to be different, in terms of both seizure control and survival. Treatment outcomes were analysed in patients newly diagnosed with epilepsy at the Epilepsy Unit, Western Infirmary, Glasgow over a 20-year period by retrospective review of research case notes. Response to treatment was defined as a 12-month seizure free period and those who remained seizure free till the end of follow up were considered to be in remission. A total of 890 patients had been diagnosed with epilepsy. Treatment outcomes were known for 780 who were included in the analysis of treatment outcomes. Four major categories of response to treatment were observed: those who responded rapidly and completely to treatment with the first AED (immediate responders), those who responded with further changes to therapy including combination treatment (delayed responders), those who had an initial period of good control before experiencing seizure recurrence and being subsequently uncontrolled (relapse), and those who never achieved 12 month seizure free period (uncontrolled). Over 90% of those responding to treatment achieved remission. Of those responding to treatment 83% had completed 12 seizure free months by 3 years from starting AEDs. Those failing the first AED had significantly lower likelihood of responding to further pharmacotherapy if the reason for failure was lack of efficacy rather than adverse effects. For patients failing 2 well tolerated antiepileptic drug regimes, the chances of seizure freedom with pharmacotherapy was less than 10% and for those failing 3 such regimes, this figure was only 3%. Alcohol abuse, history of head injury and febrile seizures, psychiatric co-morbidity and family history of epilepsy showed significant univariate association with uncontrolled epilepsy. Voltage gated sodium channels are important in the generation action potentials in the brain and also serve as molecular targets for a range of AEDs. SNPs resulting in altered amino acid sequence in the sodium channel a subunit have the potential to influence the response to AED treatment

Equal access to hospital care for children with learning disabilities and their families : a mixed-methods study

Background To our knowledge, there has yet to be a comprehensive review of how well hospital services are meeting the needs of children and young people (hereafter referred to as children) with learning disability and their families. The extent to which their experiences differ from those of parents of children without learning disability is not known. The views and experiences of children with learning disability are almost non-existent in the literature. Aims To identify the cross-organisational, organisational and individual factors in NHS hospitals that facilitate and prevent children with learning disability and their families receiving equal access to high-quality care and services, and to develop guidance for NHS trusts. Design A four-phase transformative, mixed-methods case study design comparing the experiences of children with and children without learning disability, their parents and health-care staff. Methods Phase 1 comprised interviews with senior managers (n = 65), content analysis of hospital documents and a staff survey (n = 2261) across 24 hospitals in England, including all specialist children’s hospitals. Phases 2–4 involved seven of these hospitals. Phase 2 involved (a) interviews and photography with children and their parents (n = 63), alongside a parent hospital diary and record of safety concerns; (c) hospital staff interviews (n = 98) and community staff survey (n = 429); and (d) retrospective mapping of hospital activity. During phase 3, children (n = 803) and parents (n = 812) completed satisfaction surveys. Phase 4 involved seeking consultation on the findings. Data analysis A model for mixed-methods data analysis and synthesis was used. Qualitative data were managed and analysed thematically, supported with NVivo (QSR International, Warrington, UK). Quantitative data were analysed using parametric and non-parametric descriptive statistics. Results Nationally, there is considerable uncertainty within hospitals and variation between hospitals in terms of the policies, systems and practices in place specifically for children with learning disability. Staff are struggling to individualise care and are being let down by an inadequate system. Attitudes and assumptions can have a lasting impact on parents and children. The findings serve as a useful guide to trusts about how best to meet the Learning Disability Improvement standards that have been set. Conclusions Safety issues and quality of care affect all children in acute hospitals and their parents, but the impact on children with learning disability and their parents is much greater. Individualising care is key. Our findings suggest that staff may need to undertake training and gain experience to build their skills and knowledge about children with learning disability generally, as well as generate knowledge about the individual child through proactively working in partnership with parents before their child’s admission. The findings also suggest that we may need to address the impact of children’s hospitalisation on parents’ health and well-being. Future work The greatest need is for the development and validation of an instrument for the assessment and management of risk in children with learning disability in hospital. Limitations We cannot say with certainty that the sites selected are representative of all services caring for children with learning disability. Study registration The study has been registered on the National Institute for Health and Care Research (NIHR) Clinical Research Network portfolio as 20461 (phase 1) and 31336 (phases 2–4). Funding This project was funded by the NIHR Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 13. See the NIHR Journals Library website for further project information

Work Life 2000 Yearbook 2: 2000

This volume reported the proceedings of a series of international research workshops in 1999, funded by the Swedish National Institute for Working Life, in preparation for the Swedish Presidency of the European Union in 2001

Characterization of an animal model of cognitive impairment associated with schizophrenia. Effets of alpha2-adrenoceptor compounds.

382 p.Schizophrenia is a multi multifaceted, heterogeneous, chronic and debilitating disorder triggered by a series of interacting genetic, developmental and environmental factors. Cognitive impairment is considered a core feature of this disorder and highly dependent on the correct functioning of the prefrontal cortex, however, current antipsychotics lack efficacy for treating this condition. Prenatal exposure to infection is contemplated as one the most significant environmental risk factors for developing schizophrenia in the offspring. In this context, maternal immune activation animal models produce neurochemical and behavioral alterations considered relevant for the study of schizophrenia dysfunctions.The first part of this thesis consists of a neurochemical and behavioral characterization of an animal model of cognitive impairment associated with schizophrenia by the administration of the immunostimulant agent Poly (I:C). The second part involves the study of the effects of ¿2-adrenoceptor compounds on cognitive performance in the offspring. Finally, selective targeting of the locus coeruleus-prefrontal cortex circuit by different optogenetic approaches was performed.The Poly (I:C) animal model shows a catecholaminergic hypofunction in the prefrontal cortex with marked cognitive deficits, which are reversed by the administration of 2A-adrenoceptor agonist guanfacine and the 2C-adrenoceptor antagonist MK-912.These results support the important role of the noradrenergic system in the prefrontal cortex-dependent cognitive functions and the Poly (I:C) animal model as a promising translational model of cognitive impairment associated with schizophrenia

Feature Papers "Age-Friendly Cities & Communities: State of the Art and Future Perspectives"

The "Age-Friendly Cities & Communities: States of the Art and Future Perspectives" publication presents contemporary, innovative, and insightful narratives, debates, and frameworks based on an international collection of papers from scholars spanning the fields of gerontology, social sciences, architecture, computer science, and gerontechnology. This extensive collection of papers aims to move the narrative and debates forward in this interdisciplinary field of age-friendly cities and communities

Epidemiology of Injury in English Women's Super league Football: A Cohort Study

INTRODUCTION: The epidemiology of injury in male professional football has been well documented (Ekstrand, Hägglund, & Waldén, 2011) and used as a basis to understand injury trends for a number of years. The prevalence and incidence of injuries occurring in womens super league football is unknown. The aim of this study is to estimate the prevalence and incidence of injury in an English Super League Women’s Football squad. METHODS: Following ethical approval from Leeds Beckett University, players (n = 25) signed to a Women’s Super League Football club provided written informed consent to complete a self-administered injury survey. Measures of exposure, injury and performance over a 12-month period was gathered. Participants were classified as injured if they reported a football injury that required medical attention or withdrawal from participation for one day or more. Injuries were categorised as either traumatic or overuse and whether the injury was a new injury and/or re-injury of the same anatomical site RESULTS: 43 injuries, including re-injury were reported by the 25 participants providing a clinical incidence of 1.72 injuries per player. Total incidence of injury was 10.8/1000 h (95% CI: 7.5 to 14.03). Participants were at higher risk of injury during a match compared with training (32.4 (95% CI: 15.6 to 48.4) vs 8.0 (95% CI: 5.0 to 10.85)/1000 hours, p 28 days) of which there were three non-contact anterior cruciate ligament (ACL) injuries. The epidemiological incidence proportion was 0.80 (95% CI: 0.64 to 0.95) and the average probability that any player on this team will sustain at least one injury was 80.0% (95% CI: 64.3% to 95.6%) CONCLUSION: This is the first report capturing exposure and injury incidence by anatomical site from a cohort of English players and is comparable to that found in Europe (6.3/1000 h (95% CI 5.4 to 7.36) Larruskain et al 2017). The number of ACL injuries highlights a potential injury burden for a squad of this size. Multi-site prospective investigations into the incidence and prevalence of injury in women’s football are require

Design revolutions: IASDR 2019 Conference Proceedings. Volume 2: Living, Making, Value

In September 2019 Manchester School of Art at Manchester Metropolitan University was honoured to host the bi-annual conference of the International Association of Societies of Design Research (IASDR) under the unifying theme of DESIGN REVOLUTIONS. This was the first time the conference had been held in the UK. Through key research themes across nine conference tracks – Change, Learning, Living, Making, People, Technology, Thinking, Value and Voices – the conference opened up compelling, meaningful and radical dialogue of the role of design in addressing societal and organisational challenges. This Volume 2 includes papers from Living, Making and Value tracks of the conference