Search

The balance between oxidant production and the antioxidant defence system is essential to brain health. First-episode psychosis (FEP) and schizophrenia (SZ) are psychiatric disorders that affect the patients' contact with reality, with unique presentation of symptoms and experiences. Both FEP and SZ can be characterised by perturbed redox status, notably via antioxidant depletion. Previous research, undertaken in healthy populations, has highlighted the ability of exercise training to regulate redox balance. One particular biomarker of redox status is the antioxidant glutathione (GSH), which has a principal role of removing toxic substances from the cell, especially in the brain. This thesis presents novel data investigating the drawbacks of exercise study design in youth mental health, the efficacy of a training intervention in 'normalising' measures of antioxidant capacity, oxidative stress, inflammation and functionality in FEP. Studies presented go on to interrogate some of the redox-related mechanisms of the neurodevelopmental aspect of psychosis pathophysiology. Assessment of GSH in the brain, blood and in patient-derived cell models offers significant gateways into elucidating the pathological mechanisms of mental ill-health. In order to address some of the principle weaknesses in previous study design which have aimed to provide exercise to a FEP cohort, chapter 2 of this thesis used personalised heart rate zones (50-70% VO2max) to standardise bouts of activity across a range of exercise modalities, in a healthy but sedentary group of young people. The study was successful in provoking a redox response 2 during each acute bout, which typically initiates the stimulation of adaptive processes. This study achieved 100% retention, which also demonstrated that engagement in an exercise intervention is possible in a sedentary group, when choice of activity and variety of exercise mode are offered to the participant. Chapters 3 and 4 highlight the therapeutic benefits of regular exercise training (12 weeks, 3-4 times/week, 40-60 minutes) for FEP patients in a randomised trial. The study highlighted the positive impact of increased physical activity on peripheral and brain indices of GSH, markers of oxidative stress, and patient- centred measures of psychotic symptomology and daily function. In a more in- depth assessment of the GSH cycle and indices of cell damage, chapter 5 describes the characterisation and generation of mature astrocytes and neurons from SZ patient-derived induced pluripotent stem cells (iPSCs), as a model of the neurodevelopmental aspect of disease pathogenesis. It was found that the de-toxifying ability of GSH is impaired in SZ cerebral cells, offering a cogent target for further investigation in this novel approach to assessing the mechanisms of mental ill-health, in the brain.

This Interpretative Phenomenological Analysis study explores how elementary teachers made sense of their experience in the National Writing Project's Summer Institute and how it influenced their teaching of writing. Many elementary teachers have not received writing methods as a stand-alone course during their teacher preparation. Furthermore, the teaching of writing is vast, complex, and rigorous. Complexity Theory in the teaching of writing was framed the study and was used as a lens for understanding. Findings indicated that elementary teachers made sense of their National Writing Project experience in two major ways: as a writer and as a teacher of writing. Findings revealed that teachers understood their experience by grappling with and enduring writing fear, embracing a writer's humanity with structure, and giving themselves permission to make choices. In addition, elementary teachers' enjoyed teaching writing after the Summer Institute and recognized the importance of safeguarding writing time in the classroom. Teachers reworked and recombined their ideas surrounding the purpose of writing and the demands of writing and being a writer. Overall, there were three major understandings that teachers reworked and recombined during the Summer Institute within the Teacher Development as a Complex Adaptive System: (1) organization, (2) choice, and (3) communities of authors. Ingrained within each reworked idea were elements from the first two systems of Complexity Theory in Writing. Revised knowledge from the Summer Institute facilitated ways for teachers to make choices and judgments about teaching writing to students. Implications from the findings include the need to rethink professional development for in-service teachers to follow principles of the National Writing Project, rethinking and disrupting writing and writing instruction paradigms, continue funding for the National Writing Project, and embedding elements of the Summer Institute into pre-service teacher preparation. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

The Gothic in the post-millennial period offers writers an anchoring point, a site of familiarity for the reader, in the midst of an evolving culture of reading. Moving beyond recognising the binary conception of old vs new media, at stake in this thesis is the reader's approach to the text in light of digital developments to reading habits. The evolution of digital technologies that have influenced approaches to reading include our ability to process vast amounts of data in quick succession through hyperlinks, and the capacity to locate relevant data amongst an endless flow in a non-linear, multi-cursal format: recognised as 'browsing or 'surfing' the web. This style of reading is indicative of the pathways through a labyrinth: a key motif for the digital posited by a range of critics included in this thesis such as Pierre Lèvy (1997), Espen J. Aarseth (1997), N. Katherine Hayles (2008) and Marie-Laure Ryan (2015). For the post-millennial novel, it is the changes that have occurred in light of digital reading practices that has led to the re-birth of the reader, not as an individual, but as a collective. Readers of the multimodal novel are driven by the physical responses required of them by the Gothic mode in a moment of boundary transgression of the storyworld and actual world: a Gothic faultline. In the following chapters, I locate the authors' use of familiar Gothic tropes in Mark Z. Danielewski's House of Leaves (2000), Bret Easton Ellis' Lunar Park (2005), JJ Abrams' and Doug Dorst's S. (2013) and Zachary Dodson's Bats of the Republic (2015) as a way of situating the reader in familiar territory. These tropes anchor the reader's navigation through complex narrative structures. It is then possible to identify the moment at which the reader becomes conscious of their direct involvement in the storyworld, an affective and physical experience that can be conceptualised through the Lacanian term extimacy. Spanning both the interior of the print novel and external digital platforms that expand the storyworld, I conceptualise the reader's experience using Garrett Stewart's (1997) 'Gothic of reading' to underpin the process of activation a reader of Gothic fiction experiences. Consequently, I argue that the reader is no longer a mere consumer of entertainment, but an investigator, collaborator, code-breaker, and sometimes even a translator. The Gothic, it seems, is the ideal mode to capture both the anxieties of the digital present whilst harnessing recognisable forms to ease readers into the demands of the multimodal novel.

Positron emission tomography (PET) is a non-invasive medical imaging technique that allows visualisation and quantification of biochemical, physiological and pharmacological processes in living subjects. This is achieved through application of radiotracers – compounds labelled with positron emitting radionuclides. Neurodegeneration is the progressive loss of neurons resulting in impairment of brain function leading to cognitive decline and can affect movement. The underlying pathology of many neurodegenerative diseases is misfolding of proteins such as α-synuclein, the key pathological hallmark of Parkinson’s disease. Also implicated in the processes of neurodegeneration is neuroinflammation, which is observed by the activation of microglia – the immune cells of the brain. Activation of microglia is associated with the upregulation of the 18 kDa mitochondrial translocator protein (TSPO). This work has involved the synthesis and characterisation of novel compounds that have the potential for being applied as radiotracers for imaging α-synuclein fibrils (project 1), or TSPO (project 2) via PET. Over the course of project 1 a library of compounds was synthesised based upon structural modifications of a lead structure identified from the literature. These compounds then underwent screening via biophysical methodologies in order to determine their affinity to α-synuclein fibrils. This stage of the work involved the development of a novel biophysical technique – microscale thermophoresis (MST). A general automated radiosynthetic method to afford the [18F]fluoro-derivatives of these compounds has also been developed, and preliminary in vitro autoradiography studies and an in vivo microPET scan has been performed. For project 2, an automated radiosynthetic method was developed to produce [18F]GE387, a lead compound identified through collaboration with GE Healthcare. This radiotracer has then been applied to preliminary in vitro autoradiography and an in vivo microPET study using rats with induced neuroinflammation alongside control rats.

Background:Total joint replacement (TJR) is one of the most frequently performed surgeries in the United States. Many hospitals offer "joint classes"; to prepare patients for TJR procedures. No recent synthesis of evidence of the effectiveness of these classes in promoting postoperative outcomes has been published. With such a large number of people having this procedure, a synthesis of evidence of outcomes of TJR classes is needed. Objectives: The purpose of this evidence-based literature review is to synthesize available evidence to address the following PICO question: (P) In preoperative patients undergoing total joint replacement surgery (I) what effect do preoperative educational classes have on (O) postoperative patient outcomes? Search strategy: Key words derived from the PICO question were used for free text searching in several databases including CINAHL, EMBASE, PubMed, Cochrane Collaboration Products, PsycINFO, and ProQuest Dissertations. Selection criteria: Randomized controlled trials and quasi-experimental studies comparing educational class interventions given preoperatively to patients undergoing total hip or total knee replacement surgery were included in the review. Any study not reporting measured outcomes (qualitative), including a postoperative intervention, not published in English, or not published in the past 10 years were excluded from the review.Main results: Significant results were found concerning anxiety, patient satisfaction, patient knowledge, and empowerment (Johansson, K., Salantera, S., & Katajisto, J., 2005; Sjoling, Slover, J. D., Rubash, H. E., Malchau, H., & Bosco, J. A., 2003; Thomas & Sethares, 2008). These results fall within the psychological realm, whereas the results that fell within the physiological realm—pain and falls—and healthcare associated realm—postop rehab utilization and medication utilization—were found to be insignificant. Physical function and length of stay provided contradictory results (Beaupre, L. A., Lier, D., Davies, D. M., & Johnston, D. 2005; Clarke, H. D., Timm, V. L., Goldberg, B. R., & Hattrup, S. J., 2012; Giraudet-Le Quintrec et al., 2003; Johansson et al., 2007; Jones et al., 2011; Sjoling et al., 2003; Thomas & Sethares, 2008; Yoon et al., 2010).Conclusions: There is insufficient evidence for or against the use of preoperative educational classes to improve postoperative outcomes with regards to physical recovery or healthcare associated outcomes. There is support for the use of preoperative educational classes in psychological outcomes including anxiety, patient satisfaction, patient knowledge and empowerment based upon several studies that measured these two outcomes.

Interpersonal contact with members of different groups can reduce prejudice and encourage people to see members of other social categories as part of their own ingroups. This research examines a quality of the social environment that might facilitate this type of contact: social capital, or the norms about trust and reciprocity within a social network. People who believe that their communities have high levels of social capital may be likely to have positive contact with members of other social groups. This positive contact could then lead these people to focus on their shared identity as members of that community. Both of these processes could lead to improved attitudes about other groups. Two studies are conducted to test these relationships. Study 1 surveys students about their perceptions of social capital levels within their university community as well as their experiences with students of other races and their attitudes about racial groups. This study provides cross-sectional evidence that social capital relates to contact quality, social categorization and racial attitudes. Study 2 extends this theory by investigating how these variables affect each other over time. Panel data support the claim that social capital is an antecedent of intergroup contact and categorization. These two studies provide novel evidence that qualities of the social environment can influence individual-level experiences and intergroup attitudes.