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My thesis offers a detailed textual analysis of Peter Carey's Booker Prize-winning novel True History of the Kelly Gang. Adopting a postcolonial approach, the thesis uses Carey's representation of an iconic Australian hero as a conduit to questions of racial identity in the so-called reconciling nation. Its arguments stem from two major theoretical underpinnings: Alan Lawson's Second World theory, which designates settler nations such as Australia as \suspended between 'mother' and 'other' simultaneously colonized and colonizing\" and Ross Chambers' theory of narrative oppositionality in his book Room For Maneuver: Reading (the) Oppositional (in) Narrative. The thesis argues that Carey's text works hard to affect a change to the white Australian reader's economy of desire and to open up a space for an alternative mode of national belonging ‚ÄövÑvÆ one that replaces the \"sorry\" nation's discourse of atonement with what Ken Gelder and Jane M. Jacobs call a \"mutual (dis)possession\" of its cultural and geographical spaces. The thesis is organised according to what I see as the text's most compelling and potentially subversive oppositional strategies. Chapter One establishes a reading practice that resists the tendency among many Carey critics to too casually engage the terms \"postcolonial\" and \"postmodern.\" Chapter Two uses the trope of the motherland to explore the relationship between racial and sexual identity in Australian settler discourse: as a fiercely contested site of gendered and racial legitimacy the motherland provides a means to imagine a more subversive sexual landscape in which neither mother nor land is virginal. Chapter Three uses True History's intertextual relationship with Shakespeare's Henry Vas a starting point for examining the relationship between theatre and history. It argues that Carey's confusing deployment of theatre as a textual discourse and a narrative practice - and the entanglement of both with questions of historical agency ‚ÄövÑvÆ compels the reader to consider the ideological function of theatre and spectatorship in True History of the Kelly Gang as well as in other kinds of colonial and postcolonial histories. Chapter Four deploys critical discourses of postcolonial melancholia to analyse the text's engagement with convict memory and settler guilt. In this final chapter I consider the uneasy cohabitation between psychoanalysis and postcolonialism as a provocative metaphor for the text's oppositional failures and successes."

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Hip fracture is the most clinically devastating and economically important complication of osteoporosis. Pain, suffering, loss of mobility and independence are some of the devastating consequences of hip fractures. The present study aimed to determine the main characteristics and outcomes of patients with osteoporotic hip fracture and treatment gaps at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. This is a single-center, retrospective cohort study analyzing charts of patients > 45 years who were admitted for hip fracture secondary to low-grade trauma from 2008 to 2012. A total of 264 patients (50.4% males and 49.6% females) were included. The most common fracture types were trochanter (49%) and femoral neck (46%). History of falls was documented in 115 (43.6%) patients. Bone mineral density (BMD) was assessed in only 41 (15.5%) patients. Majority underwent surgery (92%). Surgical complications occurred in 15 (5.7%) patients and medical complications in 21 (7.9%) patients. Vitamin D and calcium were the most common medications, but given only to 45 (17%) patients. Bone mineral density (BMD) assessment was significantly more frequent post-surgery than pre-surgery (p = 0.03). Very few patients received osteoporosis-specific therapy. F ollow-up revealed that 62 (23.5%) patients died 1 year after surgery. These present findings warrant urgent reassessment of clinical care and treatments provided to patients with osteoporotic hip fractures to prevent recurrent fractures. The introduction of Fracture Liaison Service (FLS) in institutions caring for patients with hip fractures as internationally recommended will definitely change the current status of care.

Amyloid β oligomers (Aβo) are the main toxic species in Alzheimer's disease, which have been targeted for single drug treatment with very little success. In this work we report a new approach for identifying functional Aβo binding compounds. A tailored library of 971 fluorine containing compounds was selected by a computational method, developed to generate molecular diversity. These compounds were screened for Aβo binding by a combined 19F and STD NMR technique. Six hits were evaluated in three parallel biochemical and functional assays. Two compounds disrupted Aβo binding to its receptor PrPC in HEK293 cells. They reduced the pFyn levels triggered by Aβo treatment in neuroprogenitor cells derived from human induced pluripotent stem cells (hiPSC). Inhibitory effects on pTau production in cortical neurons derived from hiPSC were also observed. These drug-like compounds connect three of the pillars in Alzheimer's disease pathology, i.e. prion, Aβ and Tau, affecting three different pathways through specific binding to Aβo and are, indeed, promising candidates for further development.

There is a mounting evidence indicated that microRNAs are fundamental elements of almost every biological process. A majority of methodologies have concentrated on detection of mature microRNAs, which execute microRNA-dependent gene silencing. Much less work has been dedicated to microRNA precursors, despite the fact that they are rudiments of microRNA biogenesis and processing. Challenges of microRNA precursor detection are due to their low abundance, necessity of use of a reference transcript, and sequence similarity. We measured 3 different precursors of the same microRNA – miR-9 (pri-miR-9-1, -2 and -3) in primary neuronal cell cultures, to show that these challenges can be easily overcome using QuantStudio™ 3D Digital PCR System, the most recent advancement of technology dedicated to quantification of nucleic acids. This chip-based digital PCR technology employs 20,000 solid partitions and allowed us to performed absolute quantification of each miR-9 precursor, without the use of a reference gene, with very high precision and very good reproducibility between technical and sample replicates. Next, we used short and long alcohol exposure to evoke changes in miR-9 precursors in cultured cells. Again, our measurements were very reproducible with precision overcoming a 1 Ct (a 2-fold change) limit of the real-time PCR. Interestingly, one of miR-9 precursors is a protein-encoding mRNA transcript, while two others are long non-coding transcripts, thus indicating versatility of digital PCR methodology. In summary, the chip-based QuantStudio™ 3D digital PCR technology provides significant improvement in precision and accuracy of measurement of a variety of RNA transcripts existing in a very diversified RNA world.

Vaccination of neonatal calves with Mycobacterium bovis bacillus Calmette-Guerin (BCG) induces a significant degree of protection against infection with virulent M. bovis, the causative agent of bovine tuberculosis (bTB). We compared two strains of BCG, Pasteur and Danish, in order to confirm that the current European human vaccine strain (BCG Danish) induced protective immunity in calves, and we assessed immune responses to determine correlates of protection that could assist future vaccine evaluation in cattle. Both vaccine strains induced antigen (purified protein derivate [PPD])-specific gamma interferon (IFN-gamma) in whole-blood cultures. These responses were not significantly different for BCG Pasteur and BCG Danish and peaked at week 2 to 4 postvaccination. Vaccination with either BCG Danish or BCG Pasteur induced significant protection against bTB, with reductions in both lesion score and bacteriological burden evident in both groups of vaccinated calves compared with nonvaccinated control calves. Measurement of IFN-gamma-expressing T lymphocytes postvaccination and postchallenge revealed both correlates and surrogates of protective efficacy. The frequency of central memory T lymphocytes present at 12 weeks postvaccination (at the time of M. bovis challenge) correlated significantly with protection. Conversely, the number of IFN-gamma-expressing effector T cells present after M. bovis challenge was correlated with disease. These results demonstrate that vaccination of neonatal calves with either BCG Pasteur or BCG Danish induces protective immune responses against TB. In addition, we show that measurement of antigen-specific T lymphocyte populations may provide a reliable means for identifying protective vaccine candidates.