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    Princesses & Superheroes

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    TSOC 455 The Sociology of GenderAs long as they have been around, princesses and superheroes have been the most prominent figures in children's media. This project focuses on how the gender expectations in this media affects children and how they participate in and see the world

    Patient-reported receipt of goal-concordant care among seriously ill outpatients - prevalence and associated factors

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    Thesis (Master's)--University of Washington, 2020Goal-concordant care is an important indicator of high-quality care in serious illness. We sought to estimate the prevalence of patient-reported receipt of goal-concordant care among seriously ill outpatients and identify factors associated with absence of patient-reported goal-concordance. We analyzed enrollment surveys from a multi-center cluster-randomized trial of outpatients with serious illness. Patients reported their prioritized healthcare goal and the focus of their current medical care; these items were matched to define receipt of goal-concordant care. We found that of 405 patients with a prioritized healthcare goal, 58% reported receipt of goal-concordant care, 17% goal-discordant care, and 25% were uncertain of the focus of their care. Patient-reported receipt of goal-concordance differed by patient goal. For patients who prioritized extending life, 86% reported goal-concordant care, 2% goal-discordant care, and 12% were uncertain of the focus of their care. For patients who prioritized relief of pain and discomfort, 51% reported goal-concordant care, 21% goal-discordant care, and 28% were uncertain of the focus of their care. Patients who prioritized a goal of relief of pain and discomfort were more likely to report goal-discordant care than patients who prioritized a goal of extending life (RRR 22.20; 95%CI 4.59, 107.38). This study found seriously ill outpatients who prioritize a goal of relief of pain and discomfort are less likely to report receipt of goal-concordant care than patients who prioritize extending life. Future interventions designed to improve receipt of goal-concordant care should focus on identifying patients who prioritize relief of pain and discomfort and promoting care aligned with that goal

    Investigation of Pertussis Resurgence in King County, Washington

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    Thesis (Ph.D.)--University of Washington, 2020Introduction: Pertussis or “whooping cough” is an infectious disease caused by bacterium Bordetella pertussis. Despite widespread vaccination since the 1950s, it continues to cause epidemics in several countries. In fact, in the last three decades, many countries with high vaccination coverage have reported a resurgence in pertussis activity. Understanding the factors that led to pertussis resurgence and its persistence is important because pertussis remains a leading cause of infant mortality worldwide with close to 100,000 deaths annually (WHO, 2018). This study examines the role of the Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccination coverage and vaccine failure in pertussis resurgence and persistence. Specifically, we described long-term, fine-scale spatio-temporal trends of pertussis incidence and characterized spatial dependence in pertussis cases within King County (Aim 1); estimated the association between pertussis epidemics and area-level vaccination coverage and socio-demographic factors (Aim 2); assessed the role of vaccine schedules and vaccine timeliness on pertussis incidence (Aim 3); estimated the population-level effects of acellular pertussis vaccines (Aim 4); and estimated waning effects of the acellular pertussis vaccine using Schoenfeld residuals (Aim 5) Methods: We obtained pertussis incidence data for all ages for the period between 1999 and 2017 from the Communicable Disease and Immunizations Department within Public Health Seattle and King County. Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccination records, as well as records for all pediatric vaccinations, for all children born or living in King County, WA, between 2008 and 2017 were obtained from the Washington State Immunization Information System (WA-IIS) maintained by the Washington State Department of Health. All five aims use information from either one or both datasets. These datasets were linked using probabilistic linkage methods to obtain DTaP vaccination and pertussis status for the study participants. Information on census-tract level and school-district level socio-demographic factors was obtained from the US Census and the National Historical Geographic Information System (NHGIS) databases. Aim 1 included pertussis incidence data for all ages reported between 1999 and 2017 and used Bayesian hierarchical disease mapping models and the tau statistic to characterize spatio-temporal dependence between pertussis cases. The Kulldorff spatial scan statistic was used to examine location of pertussis clusters and their overlap with clusters of non-medical vaccine exemptions. For aim 2, we used pertussis incidence data for all ages reported between 2010 to 2017 and estimated annual school-district level vaccination coverage as proportion of 19-35 month old children who received ≥4 DTaP doses using immunization data from the WA-IIS. Association between pertussis epidemics and vaccination coverage and other socio-demographic factors was estimated using epidemic-endemic models and the ecological vaccine model. For aims 3, 4, and 5, we used the linked dataset with individual level vaccination and pertussis status for all children born or living in King County between 2008 and 2017. Log binomial models were used to estimate the association between DTaP vaccination schedules and age-specific pertussis incidence. Cox proportional hazards models were used to estimate vaccine direct effects among children older than 3 months and population-level effects among children older than 7 months. Schoenfeld residuals obtained from fitting Cox proportional hazards models were used to estimate waning of vaccine effectiveness among 5-9 year old children. Results: There was no overall increase in pertussis incidence between 1999 and 2017, but we found spatial dependence between pertussis cases at very small spatial scales. Pertussis clusters overlapped with clusters of vaccine refusal suggesting an association between the two. We estimated the vaccine effectiveness of DTaP vaccine to be 83% (95% credible intervals: 63%, 95%) using the ecological vaccine model but found no correlation between the effective reproduction number of pertussis and area-level vaccine coverage. The association between area-level under-vaccination and pertussis epidemics was statistically significant as estimated using the epidemic-endemic models (adjusted Relative Risk, aRR: 2.76; 95% confidence interval: 1.44, 16.6), suggesting areas with low vaccination coverage had higher risk of experiencing pertussis outbreaks. We found significant association between under-vaccination and age-specific pertussis risk, but a short delay of a few weeks in receiving DTaP doses did not significantly alter pertussis risk. Using the Cox proportional hazards models and DTaP vaccine series as a time-dependent exposure, direct vaccine effects were estimated to be 72% (95% CI: 65%, 77%) comparing vaccinated time at risk to under-vaccinated time at risk for the entire cohort. The estimated indirect protection for the 3-dose primary series was 45% (95% CI: 1%, 70%), total protection was 94% (95% CI: 91%, 96%), and overall protection was 42.2% (95% CI: 19%, 60%). We found no evidence of waning of vaccine effectiveness after 5 doses of DTaP among 5-9 year old children. Vaccine effectiveness remained high at 83% (95% CI: 39%, 95%) four years after vaccination with 5th DTaP dose. Conclusion: Our findings show that although pertussis transmission is ongoing in King County, there is no clear evidence for resurgence between 1999 and 2017 as seen in the rest of the country. We found that the current schedule for the 5-dose childhood DTaP vaccine series effectively reduces pertussis risk and adding or delaying booster doses may not be required. We estimated direct vaccine effectiveness (VE) of the acellular pertussis vaccine using different models in this dissertation and found that the estimates were high and consistent across analyses. However, direct VE estimates from the statistical models used in this dissertation do not provide information about mechanism of vaccine failure (i.e.\ leaky vs.\ all-or-none). We found significant vaccine indirect effects for the acellular vaccine suggesting that vaccination with DTaP may contribute to herd effects, although we cannot deduce from these data if the indirect effects are due to decrease in susceptibility to infection or decrease in infectiousness after exposure among vaccinated individuals. We found no evidence of rapid waning of vaccine effects among children who were fully vaccinated with 5 doses of DTaP, suggesting that immediate waning of vaccine effects is likely not the mechanism of vaccine failure for the DTaP vaccine. Understanding the nature of the acellular pertussis vaccine failure in shaping the epidemiology of pertussis is challenging and deserves continued research

    Genetics, Mammographic Density and Breast Cancer Risk

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    Thesis (Ph.D.)--University of Washington, 2020Mammographic, or breast density, describing breast tissue composition, is one of the strongest risk factors for breast cancer, the most common cancer type among women in the US. In general, women in the highest breast density quartile are estimated to have a three to five-fold higher risk of developing breast cancer, compared to those in the lowest. Despite this strong association, the underlying biological mechanism remains unexplained. The association between mammographic density and breast cancer risk is not homogeneous in the general population. Previous studies suggest that menopausal status and post-menopausal hormone use may interact with high breast density to modify breast cancer risk. To our knowledge, only one previous study in postmenopausal women has focused on the interaction between breast density and other risk factors in relation to breast cancer risk. Further, it is not known whether established risk factors affect breast cancer risk differently by breast density among premenopausal women, or if certain risk factors interplay with breast density to alter the risk of specific breast cancer subtypes with worse prognosis. In addition to being associated with non-genetic factors such as age, parity, body mass index (BMI) and menopausal status, mammographic density is highly heritable, with approximately 60% of the variation attributable to genetics. However, genetic variants identified by previous genome-wide association studies (GWAS) only explain up to 1% of the variation in density. The limited number of identified mammographic density loci is likely a consequence of limited sample sizes. Meanwhile, previous GWAS have focused on genome-wide significant signals, failing to further investigate the potential importance of genetic variants with comparatively weak effects. Estimating the heritability explained by common variants throughout the genome regardless of their marginal association statistics can provide a better understanding of the genetic basis of the traits. In this dissertation, we attempted to extend our knowledge of mammographic density as an intermediate phenotype of breast cancer, from both environmental (Chapter 1) and genetic (Chapter 2) perspectives. The mammographic density traits studied in this work are the area of dense (epithelial, stromal and muscle) tissue, non-dense (adipose) tissue, and percentage of dense tissue, which have all been demonstrated to be significantly associated with breast cancer risk independently. Specifically, we assessed multiplicative interactions between mammographic density and thirteen established breast cancer risk factors, in relation to risk of breast cancer overall and by molecular subtypes, using a case-control population nested under Nurses’ Health Studies I&II (Chapter 1). Although no interaction remained statistically significant after adjusting for number of comparisons, we did observe some noteworthy interactions with nominal significance at p<0.05 level. Next, we performed a meta-analysis of GWAS for mammographic density measures, using genotype and phenotype data collected by the Marker of Density (MODE) consortium and the Breast Cancer Association Consortium (BCAC). We also conducted exploratory bioinformatics analyses, including genetic correlation analyses and a transcriptome-wide association study (TWAS) (Chapter 2). Using data on up to 27,900 women of European ancestry, we identified twenty-eight distinct genome-wide significant loci for mammographic density measures, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2) that have not been reported before. Fourteen loci identified were also observed with significant association with the risk of overall, ER-positive and/or ER-negative breast cancer. Subsequent exploratory analyses improved our understanding of a shared genetic basis between mammographic density and breast cancer. In summary, this work can help understand the underlying mechanisms driving the mammographic density-breast cancer association as well as the genetic architecture of mammographic density. Findings discovered through this dissertation will help to better understand the determinants of breast density, which in turn can help identify strategies that reduce the risk of breast cancer, and ultimately mitigate the burden brought by the disease

    A Framework for Assessing the Equity Impacts of Changing Access Regimes in Fisheries

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    Thesis (Master's)--University of Washington, 2020This thesis outlines historic trends and current policy focus toward privatization in the ocean, provides a basis for assessing how this process is affecting access to fisheries resources, and suggests how considerations of equity should be incorporated into our assessments of such changing access regimes. The current focus on privatization as a means for extracting the most economic benefit from the ocean endangers access to resources that are important for food and livelihood security for a large percentage of the global population. Ultimately, in order to preserve equitable access to fisheries resources and food production in the coastal landscape, we need to develop a system or typology that carefully documents existing access rights and fisheries management regimes, whether reforms are deemed successful, and what their sustainability outcomes are. This documentation is important not only so changes can be measured over time and so we can consider alternatives, but so the voices of those who may be marginalized by large-scale transitions in access can be considered. This thesis provides a brief overview of the history of enclosure of the Commons, drawing parallels between land and sea, before focusing more directly on saving space for food production in the ocean. Next, the access arrangements, governance and management models that are in common use for regulating access to fisheries are introduced before considering how the analysis of fisheries management and governance styles have been approached in the past. Finally, a typology of access arrangements is proposed

    Interprofessional perceptions of dental providers’ engagement in childhood obesity prevention

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    Thesis (Master's)--University of Washington, 2020Pediatric dental professionals offer basic dietary guidance on the prevention of dental caries; however, there has been a public health call to action for further engagement in childhood obesity prevention. This cross-sectional study explored how registered dietitian nutritionists (RDNs) and primary care providers (PCPs) perceive the initiation of weight-, nutrition-, and health-related conversations in a pediatric dental setting using an online survey and mixed methods analysis. Survey respondents were eligible for study inclusion by self-identification as an RDN or PCP (medical doctor, physician assistant, nurse practitioner). One hundred and twenty RDNs and PCPs were recruited by clinicians practicing in the Puget Sound region of Washington State through relevant electronic listservs. Beliefs about the extent to which pediatric dental health providers should engage in childhood obesity prevention varied. Seventy two percent of participants felt comfortable with pediatric dental health providers addressing nutrition topics that relate to oral health, whereas 25% of participants felt comfortable with them offering broader nutrition recommendations. Qualitative analysis revealed three themes and nine subthemes detailing areas of concern about dental engagement in childhood obesity prevention, suggestions for appropriate engagement, and opportunities for interprofessional collaboration. Concern over pediatric dental health providers discussing child weight was highly prevalent, though PCPs displayed a greater openness to this and other forms of dental engagement overall. Interprofessional education, training, and collaboration are needed to understand appropriate forms of childhood obesity prevention across different settings of care. Dental professionals seeking to engage in preventive efforts should continue to recommend avoidance of cariogenic foods/beverages, though further research is needed to understand their role in broader forms of dietary guidance and health conversations with families

    Antioxidant-loaded nanoparticles for the treatment of excitotoxicity in neurological disease

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    Thesis (Ph.D.)--University of Washington, 2020In the United States alone, neurological diseases affect tens of millions of people, costing $800 billion annually. In acute neurological injury, a process known as excitotoxicity manifests from energy failure or direct trauma, causing overexcitation of neurons that leads to neuronal toxicity. Following neuronal death, toxic metabolites and cellular debris accumulate in the brain, perpetuating excitotoxicity to neighboring neurons. Despite the heavy social and economic toll and extensive research into neurotherapeutic development, there are currently no approved therapeutics for targeting excitotoxicity after acute neurological injury. The difficulty in clinical translation is largely attributed to several barriers intrinsic to the brain, including traversing the blood-brain barrier (BBB) and diffusion through the brain parenchyma. Therefore, in addition to understanding the biological complexity of the brain, developing effective therapeutics is a drug delivery problem. To expedite the pre-clinical research process, we have developed a tailorable organotypic whole hemisphere (OWH) brain slice model, capable of mimicking in vivo processes including excitotoxity and neuroinflammation. Using OWH models, we can systematically study disease processes and screen therapeutics in a high-throughput fashion, bypassing delivery obstacles. To improve therapeutic enzyme delivery, we have developed brain-penetrating antioxidant enzyme-loaded polymeric nanoparticles that inhibit enzymatic degradation. Furthermore, via nanoparticle screening on the OWH model, we have elucidated the toxicity of a common polymeric nanoparticle formulation involving poly(ethylene glycol) (PEG) and sonication, and developed alternative biocompatible nanoparticle formulations. Finally, the OWH model has enabled detailed observation of disease-dependent nanoparticle-microglia interactions that can better inform drug delivery strategies. Throughout these studies, we have implemented a transdisciplinary approach that emphasizes thorough understanding of the neurobiology of disease and leverages chemical engineering fundamentals, to ultimately advance neurotherapeutic development

    Jane Porter in the Margins: Paratext in the Romantic National Novel

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    Thesis (Ph.D.)--University of Washington, 2020“Jane Porter in the Margins: Paratext in the Romantic National Novel” argues that Romantic novelist Jane Porter uses paratext in her national novels to accomplish bold political and personal goals. I examine her most famous novel The Scottish Chiefs (1810) as a case study of Romantic female authorship in which Porter asserts women’s power to shape conceptions of national identity. Often studied as an imitator of Walter Scott, Porter published two historical novels before Waverley (1814) and claimed her innovative precedence in multiple prefaces and footnotes to her novels. While Porter presented a modest feminine authorial persona to her public, my archival and bibliographical study reveals a politically engaged woman writer seeking to serve her nation from the margins. Each of the three chapters traces a paratextual element across multiple editions (1. Title page; 2. Footnotes and prefaces; and 3. Illustrations and bindings) to reveal how it facilitates Porter’s fervent support of British unity and women’s patriotic service. This dissertation studies the paratext of The Scottish Chiefs to help restore Porter’s reputation as a political writer and reveal her contributions to the nineteenth-century novel and women’s authorship. Beyond Porter, I seek wider acknowledgement of paratext’s crucial role beside the text within a book, particularly how it shapes the legacy of both book and author

    Computational Guidance and Control for Aerospace Systems

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    Thesis (Ph.D.)--University of Washington, 2020The objective of this dissertation is to develop new techniques that advance the state of the art in optimization-based trajectory generation. Two complementary techniques are studied. First, explicit trajectory generation computes a single path that connects two boundary conditions. For a general optimal control problem, sequential convex programming is used to design iterative algorithms that solve challenging aerospace problems. The limited power available on a spacecraft has long been at odds with the computationally demanding algorithms required to solve such problems, and so specialized techniques for developing real-time capable implementations of these algorithms are presented. Runtime analysis offers initial evidence that it is possible to solve explicit trajectory optimization problems reliably and fast enough to be considered a viable technology. As an alternative approach, implicit trajectory generation computes a set of functions that implicitly define an entire set of trajectories. By carrying out more extensive offline computations, it is shown that a feasible trajectory can be obtained from a wide array of initial conditions by using numerical integration. Consequently, the required real-time computations are significantly reduced compared to explicit trajectory optimization algorithms. Implicit trajectory generation methods can also offer a stronger theoretical, and offline-certifiable, guarantee that a feasible trajectory will be available for a prescribed set of vehicle conditions. Examples in powered descent and satellite attitude control are used to demonstrate each method

    Prevalence and Risk Factors of Hypertension Stratified by HIV Status in Western Kenya

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    Thesis (Master's)--University of Washington, 2020Introduction The burden of cardiovascular disease (CVD) is increasing in sub-Saharan Africa (SSA) and untreated hypertension is a major contributing factor. The prevalence and risk factors associated with hypertension among PLWHV who are on long-term ART are not well studied and we determined these in a cohort of PLWHV and HIV negative individuals in Kisumu, Kenya. Methods In this cross-sectional study, we enrolled 300 PLWHV on long-term ART (≥6 months) and 298 HIV-negative adults seeking routine services at the Kisumu County hospital between 2017-2018. We diagnosed participants with hypertension (defined as blood pressure of ≥140/90mmHg) and used multivariate regression to evaluate the association between hypertension, HIV, other sociodemographic, and CVD risk factors. Results The overall prevalence of hypertension was 25% and PLWHV had a lower prevalence of hypertension than HIV- negative persons (18% vs 33% respectively; p51 years had a 4.66-fold higher hypertension risk (95% CI 2.62-8.29) compared to individuals 30 kg/m2 had a 2.65 fold-greater risk of hypertension (95% CI 1.55-4.50) compared to those with BMI in the normal range (18-25 kg/m2). Conclusion We found a high prevalence of hypertension overall, and this was associated with advancing age and higher BMI. PLWHV on stable ART had a lower prevalence compared to HIV-negative individuals

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