Marry The Night: Creation of an Illustrated Novel.

The goal of this project was to create an illustrated story. The thesis is combination of research both on narrative theory and the process of storytelling, and different methods of narrative art. The research information obtained was used to create a body of work which was later analyzed on its successfulness at adhering to the ideas presented by the research

Genetic analyses of bovine CARD15, a putative disease resistance gene

Through a binding partner the CARD15 gene activates NF-kB, a molecule with a role in the initiation of the inflammatory immune response. The gene is highly conserved in both structure and function in human and mouse and has recently been implicated as a disease resistance gene in Crohn's disease and Blau Syndrome in human. The gene's relationship to disease and its conservation between species suggests that it may also have a conserved role in bovine disease resistance. To elucidate the potential role of bovine CARD15 in disease resistance, the gene was characterized in cattle. Bovine CARD15 is located 4.2 cR5000 telomeric to ADCY7 on chromosome 18. It spans ~30 kb and is comprised of 12 exons, 11 of which are coding. Bovine CARD15 is expressed in many tissues, but is most abundant in peripheral blood leukocytes. An extensive comparative analysis between the bovine, mouse and human CARD15 genes revealed high levels of inter-species conservation in sequence, genomic structure and protein domains. Conserved putative regulatory motifs were identified in the three species comparison of the 5'UTR, 3'UTR and the intronic sequences flanking exons. Additionally, diverse regulatory motifs were identified in each of the species indicating an evolutionary divergence in the mechanisms of regulation of gene expression. To assess the extent of genetic diversity within bovine CARD15, 41 individuals from nine breeds representing two subspecies were sequenced and screened for polymorphisms. Thirty-six single nucleotide polymorphisms (SNPs) were identified including 26 within the gene transcript. Haplotypes were estimated for each individual and parsimonious SNP sets were identified with which the multi-locus Bos taurus and Bos indicus haplotypes may be reconstructed. There was a significantly higher rate of substitutions within Bos indicus than in Bos taurus. A significantly higher rate of nonsynonymous to synonymous substitutions was found in Bos taurus indicating that positive Darwinian selection is acting on the gene within this subspecies. Association analyses were performed between these SNP loci and haplotypes with Johne's disease. No overwhelming evidence for a simple causal relationship was detected. Assays are provided to screen populations of cattle for variation in the CARD15 gene

“I just wasn’t thinking”: Strategic Ambiguity and women’s accounts of unprotected sex

Heterosexual university students continue to endorse sexual scripts that preference men’s desire and sustain gendered power imbalances in sexual relationships and encounters, leading women to risk pregnancy by engaging in unprotected sex. Because young women also endorse norms encouraging them to protect themselves and their partners from unintended pregnancy, women are caught in a bind between two often competing norms. We conducted semi-structured individual interviews with university women (n=45) to examine how they navigate these competing norms. We found that women explained risky contraceptive decisions by saying they “just weren’t thinking”, thus employing strategic ambiguity, or vague language used to maintain social status, to navigate between competing norms. Our findings suggest that women were actually thinking about risks and making calculated decisions in the moment which often privileged men, putting themselves at risk and sometimes causing distress. To save face, women presented the idea that they “just weren’t thinking” in different ways that conformed to traditional notions of romance and sexuality: being in the moment, love and trust for their partner, and deferring to the perceived or actual wishes of men. We conclude that there is a need to promote and achieve affirmative sexuality which includes women feeling empowered to express their own sexual needs --whether that be consent or refusal, contraception, pleasure, or all of these

Evaluation of an After-School Obesity Prevention Program for Children

Dissemination of obesity prevention programs in different settings is needed. Moreover, new outreach tools to teach parents healthy eating and exercise lessons provided in these programs are important to develop. The pilot studies presented in this paper examined the implementation of the Children's Healthy Eating and Exercise Program in two different after school programs in 2015 and 2016. Participants were elementary school-age children and their parents. Eight lessons were presented at each school. Child perceptions of healthy eating and exercise goals were examined as well as child knowledge retention and perceptions of behavior change. Parent perceptions of the program were analyzed. Results indicated that children reported improved knowledge and behaviors. Parents reported satisfaction with the program, but remained hard to reach. Children recalled key components of the healthy eating lessons at long-term follow-up assessments. In the second pilot study, children served as health coaches for teaching parents about family goals. Children believed they were successful at coaching parents, but they requested help in developing family eating and exercise goals. Improving outreach to parents and involving siblings remains a goal for future studies as does beginning to examine changes in eating and physical activity using food diaries and accelerometry

Complement activation and increased anaphylatoxin receptor expression are associated with cortical grey matter lesions and the compartmentalised inflammatory response of multiple sclerosis

Background: The extent of cortical pathology is an important determinant of multiple sclerosis (MS) severity. Cortical demyelination and neurodegeneration are related to inflammation of the overlying leptomeninges, a more inflammatory CSF milieu and with parenchymal microglia and astroglia activation. These are all components of the compartmentalised inflammatory response. Compartmentalised inflammation is a feature of progressive MS, which is not targeted by disease modifying therapies. Complement is differentially expressed in the MS CSF and complement, and complement receptors, are associated with demyelination and neurodegeneration. Methods: To better understand if complement activation in the leptomeninges is associated with underlying cortical demyelination, inflammation, and microglial activation, we performed a neuropathological study of progressive MS (n = 22, 14 females), neuroinflammatory (n = 8), and non-neurological disease controls (n = 10). We then quantified the relative extent of demyelination, connective tissue inflammation, complement, and complement receptor positive microglia/macrophages. Results: Complement was elevated at the leptomeninges, subpial, and within and around vessels of the cortical grey matter. The extent of complement C1q immunoreactivity correlated with connective tissue infiltrates, whilst activation products C4d, Bb, and C3b associated with grey matter demyelination, and C3a receptor 1+ and C5a receptor 1+ microglia/macrophages closely apposed C3b labelled cells. The density of C3a receptor 1+ and C5a receptor 1+ cells was increased at the expanding edge of subpial and leukocortical lesions. C5a receptor 1+ cells expressed TNFα, iNOS and contained puncta immunoreactive for proteolipid protein, neurofilament and synaptophysin, suggesting their involvement in grey matter lesion expansion. Interpretation: The presence of products of complement activation at the brain surfaces, their association with the extent of underlying pathology and increased complement anaphylatoxin receptor positive microglia/macrophages at expanding cortical grey matter lesions, could represent a target to modify compartmentalised inflammation and cortical demyelination

Digital Pathology Identifies Associations between Tissue Inflammatory Biomarkers and Multiple Sclerosis Outcomes

Background: Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping. Aims: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS. Methods: Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38–98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology. Results: Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death. Conclusion: Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers

The value of targeted biological surveys: an assessment of Australia's Bush Blitz programme

Biodiversity assessment and decisions rely on knowledge of the spatial distribution of species, yet most global biodiversity is inadequately represented by occurrence records. Efforts to improve our knowledge of biodiversity distribution include targeted taxon survey programmes aimed at generating records of new, or previously unrecorded, species. Here, we evaluate nearly 8 years of biodiversity record collection by Bush Blitz, Australia's largest species discovery programme, to test how efficiently knowledge was added through the programme

Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardiomyopathy (ENDEAVOUR)

PURPOSE: The Phase 3 ENDEAVOUR study evaluated revusiran, an investigational RNA interference therapeutic targeting hepatic transthyretin (TTR) production, for treating cardiomyopathy caused by hereditary transthyretin-mediated (hATTR) amyloidosis. / METHODS: Patients with hATTR amyloidosis with cardiomyopathy were randomized 2:1 to receive subcutaneous daily revusiran 500 mg (n = 140) or placebo (n = 66) for 5 days over a week followed by weekly doses. Co-primary endpoints were 6-min walk test distance and serum TTR reduction. / RESULTS: Revusiran treatment was stopped after a median of 6.71 months; the study Sponsor prematurely discontinued dosing due to an observed mortality imbalance between treatment arms. Eighteen (12.9%) patients on revusiran and 2 (3.0%) on placebo died during the on-treatment period. Most deaths in both treatment arms were adjudicated as cardiovascular due to heart failure (HF), consistent with the natural history of the disease. A post hoc safety investigation of patients treated with revusiran found that, at baseline, a greater proportion of those who died were ≥ 75 years and showed clinical evidence of more advanced HF compared with those who were alive throughout treatment. Revusiran pharmacokinetic exposures and TTR lowering did not show meaningful differences between patients who died and who were alive. Revusiran did not deleteriously affect echocardiographic parameters, cardiac biomarkers, or frequency of cardiovascular and HF hospitalization events. / CONCLUSIONS: Causes for the observed mortality imbalance associated with revusiran were thoroughly investigated and no clear causative mechanism could be identified. Although the results suggest similar progression of cardiac parameters in both treatment arms, a role for revusiran cannot be excluded. / CLINICAL TRIAL REGISTRATION: NCT02319005

Period and chemical evolution of SC stars

The SC and CS stars are thermal-pulsing AGB stars with C/O ratio close to unity. Within this small group, the Mira variable BH Cru recently evolved from spectral type SC (showing ZrO bands) to CS (showing weak C2). Wavelet analysis shows that the spectral evolution was accompanied by a dramatic period increase, from 420 to 540 days, indicating an expanding radius. The pulsation amplitude also increased. Old photographic plates are used to establish that the period before 1940 was around 490 days. Chemical models indicate that the spectral changes were caused by a decrease in stellar temperature, related to the increasing radius. There is no evidence for a change in C/O ratio. The evolution in BH Cru is unlikely to be related to an on-going thermal pulse. Periods of the other SC and CS stars, including nine new periods, are determined. A second SC star, LX Cyg, also shows evidence for a large increase in period, and one further star shows a period inconsistent with a previous determination. Mira periods may be intrinsically unstable for C/O ~ 1; possibly because of a feedback between the molecular opacities, pulsation amplitude, and period. LRS spectra of 6 SC stars suggest a feature at wavelength > 15 micron, which resembles one recently attributed to the iron-sulfide troilite. Chemical models predict a large abundance of FeS in SC stars, in agreement with the proposed association.Comment: 14 pages, 20 figures. MNRAS, 2004, accepted for publication. Janet Mattei, one of the authors, died on 22 March, 2004. This paper is dedicated to her memor

The ENCODE Imputation Challenge: a critical assessment of methods for cross-cell type imputation of epigenomic profiles

A promising alternative to comprehensively performing genomics experiments is to, instead, perform a subset of experiments and use computational methods to impute the remainder. However, identifying the best imputation methods and what measures meaningfully evaluate performance are open questions. We address these questions by comprehensively analyzing 23 methods from the ENCODE Imputation Challenge. We find that imputation evaluations are challenging and confounded by distributional shifts from differences in data collection and processing over time, the amount of available data, and redundancy among performance measures. Our analyses suggest simple steps for overcoming these issues and promising directions for more robust research