Conduct Problems, Callous-Unemotional Traits and Emotion Processing: Adversity and Diversity, a Functional Neuroimaging Study

This thesis focused on youths who present with conduct problems (CP), callous-unemotional traits and functional neuroimaging. PART 1: A narrative review of current neuroimaging literature regarding youths with CP. Firstly, this review outlined general CP related considerations regarding neuroimaging literature and common CP risk factors before summarising structural neuroimaging literature. Functional neuroimaging research was then summarised using neurocognitive domains of functioning: acute threat response, social cognition, cognitive control and reinforcement learning. Findings were discussed with reference to how risk factors and neurocognitive functioning interact to produce behavioural syndromes associated with CP. Future CP related neuroimaging research should focus on domains of functioning and the influence of risk factors on heterogeneity. PART 2: A functional MRI study that used facial expressions (angry/sad/happy) to investigate neural differences in emotion processing amongst boys with CP split between high and low callous-unemotional (CU) traits, compared to matched controls. Findings highlighted perturbations in limbic, frontal, temporal and medial regions for both high and low CU trait boys compared to controls. CP boys demonstrated specific atypical activation in the amygdala, insula and prefrontal cortex when processing negative facial expressions and were associated with more severe pathological parenting practices than controls. Potential explanations and clinical implications were explored. PART 3: A critical appraisal of my learning regarding neuroimaging and youths with CP including my perspective from clinical practice. This appraisal focused on the theoretical, diagnostic, research, clinical and narrative implications of transitioning understandings of neural function from a behavioural, damaged and functionally specialised paradigm toward a dimensional, adapted and interrelated paradigm

Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies

Historical Documents of the Irish Avant-Garde

The contributors who wrote the texts and scores are: John Berndt, Felicity Ford, Panos Ghikas, Paul Gilgunn, Stephen Graham, Majella Munro, Simon O’Connor, Rían O’Rahallaigh, Nick Roth, Benedict Schlepper-Connolly, Jennifer Walshe. Thanks very much to Richard Devine for his recordings which brought Zaftig to life and Jack McMahon for his performance as Ultan O’Farrell, and to Malcolm Tyrrell for his dream of an episode of Hands focussing on Irish performance art.Before you begin reading the articles in this book and listening to the recordings on the Aisteach Foundation’s website, I have a confession to make – all of the composers and artists are fictional. The Aisteach Foundation and the Historical Documents of the Irish Avant-Garde are a communal thought experiment, a revisionist exercise in “what if?”, a huge effort by many people to create an alternative history of avant-garde music in Ireland, to write our ancestors into being and shape their stories with care. We played fast and loose with history and the truth and we like to think Flann O’Brien would have approved. I am extremely grateful to the Arts Council of Ireland for funding this project and allowing me to collaborate with the contributors listed below. If you feel there’s something we missed, something you want to have happened and would like to bring into being, please let us know. This project is dedicated with love to Bob Gilmore. Dr. Jennifer Walshe, President, Aisteach FoundationArts Council of Irelandhttp://www.lulu.com/shop/http://www.lulu.com/shop/jennifer-walshe/historical-documents-of-the-irish-avant-garde/paperback/product-22906851.html#productDetail

Predictions for the future of kallikrein-related peptidases in molecular diagnostics

Kallikrein-related peptidases (KLKs) form a cancer-related ensemble of serine proteases. This multigene family hosts the most widely used cancer biomarker that is PSA-KLK3, with millions of tests performed annually worldwide. The present report provides an overview of the biomarker potential of the extended KLK family (KLK1-KLK15) in various disease settings and envisages approaches that could lead to additional KLK-driven applications in future molecular diagnostics. Particular focus is given on the inclusion of KLKs into multifaceted cancer biomarker panels that provide enhanced diagnostic, prognostic and/or predictive accuracy in several human malignancies. Such panels have been described so far for prostate, ovarian, lung and colorectal cancers. The role of KLKs as biomarkers in non-malignant disease settings, such as Alzheimer’s disease and multiple sclerosis, is also commented upon. Predictions are given on the challenges and future directions regarding clinically oriented KLK research

Glycosylation is an androgen-regulated process essential for prostate cancer cell viability

Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer. Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer. Amongst 700 genes displaying reciprocal expression patterns we observed a significant enrichment in the cellular process glycosylation. Of 31 reciprocally-regulated glycosylation enzymes, a set of 8 (GALNT7, ST6GalNAc1, GCNT, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3) were significantly up-regulated in clinical prostate carcinoma. Androgen exposure stimulated synthesis of glycan structures downstream of this core set of regulated enzymes including sialyl-Tn (sTn), sialyl LewisX (SLeX), O-GlcNAc and chondroitin sulphate, suggesting androgen regulation of the core set of enzymes controls key steps in glycan synthesis. Expression of each of these enzymes also contributed to prostate cancer cell viability. This study identifies glycosylation as a global target for androgen control, and suggests loss of specific glycosylation enzymes might contribute to tumour regression following androgen depletion therapy.This article is freely available via Open Access. Click on the link above to access the full-text via the publisher's site.This work was funded by Prostate Cancer UK (PG12-34), The J. G. W Patterson Foundation, The Wellcome Trust (grant numbers WT080368MA and WT089225/Z/09/Z), BBSRC (grant BB/1006923/1 and BB/J007293/1) and Breast Cancer Now (grant number 2014NovPR355)Published (Open Access

“Living the dream”: the dialectics of being a Canadian student athlete in the United States

Many young Canadian athletes seek athletic scholarships from universities and colleges in the United States that will enable them to become student athletes. Among parents, coaches, and children who are involved in Canadian youth sports, a commonly encountered discourse characterizes athletic scholarships as offering beneficial opportunities, including playing American intercollegiate sports, earning an education, and living abroad. From a young age, Canadian athletes witness this discourse and it becomes a part of their lived experiences, especially should they attain “the dream” of winning an athletic scholarship and going to the U.S. as a student athlete. Drawing on original ethnographic research conducted in Boston, MA and the surrounding area, this thesis critically examines what “living the dream” involves for some student athletes and considers the dialectical relationship between their actual experiences and the popular discourse that both shapes and is sometimes contradicted by the realities of these young Canadians’ lives

Distillation and Synthesis: Aesthetics and Practice in Rhys Chatham's Music for Electric Guitar

This is a critical study of music for electric guitars by composer-performer Rhys Chatham (b. 1952), work that distils and synthesises elements from various genres, primarily, minimalism and rock. I investigate the development, realisation, and import of these works, created between 1977 and 2006, in an analytical, biographical, and cultural account that examines unpublished performance directions, scores, and original interviews with this significant, yet under-explored artist and his collaborators. An immanent sublime aesthetic characterises Chatham’s formative experiences in downtown music, and I explain how this informs his composition, performance, and listening practices (including attendant issues of entrainment, frisson, and perceptualization). This reading is situated within major music traditions of the later twentieth century and at the forefront of a nexus of postmodern radical pluralism, operating across the borderline of the avant-garde and the popular. I use a range of research methods: aesthetics, cultural theory, interviews, musical analysis, music theory, and my own experience of performing several of these works. Part One maps Chatham’s development as a composer and performer through his engagement with modernist, serialist, electronic, minimalist, improvised, North Indian classical, popular, and rock music between 1952 to 1978, to interpret how he distilled key components of these experiences. Part Two outlines how he synthesised these elements in several non-notated works for the electric guitar, from 1977 to 1982, using idiosyncratic and inventive approaches to composition and performance. Part Three provides in-depth analyses of Chatham’s notated music for increasingly large ensembles of electric guitars from 1984 to 2006, to outline the development of his post-Cagean musical language, and interpret the wider import of these works. I argue that the interpenetration and reciprocity of musical elements in these works expand, and implode, pre-established forms of art and rock music. While this eludes ‘either/or’ classifications, per se, this is a particular kind of post-minimalism, with significant components of popular music, identifiable as part of a post-1945 culture that was distinguished by immanence, participation, and subjectivity