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Chemical Analysis of Cells and Tissues with Time-of-Flight Secondary Ion Mass Spectrometry
No full textThesis (Ph.D.)--University of Washington, 2013In this work the chemical analysis of biological cells and tissues with time-of-flight secondary ion mass spectrometry (ToF-SIMS) was explored. ToF-SIMS has the ability to obtain a mass spectrum with submicron spatial resolution for imaging and is extremely surface sensitive. ToF-SIMS for biological sample analysis is still an emerging field, so the development and characterization of novel sample preparation and analysis methods is key to acquiring useable information. In this work, three different methods to prepare NIH/3T3 fibroblasts were investigated: chemically fixed, freeze-dried and frozen-hydrated. Chemical fixation followed by rinsing removed a majority of intracellular Cl-, improving the secondary ion yields of all organic positively charged secondary ions an average of 2.6x. Damage cross sections were reduced during frozen-hydrated analysis, improving the secondary ion yields of higher mass organic fragments. In a separate experiment, accurate 3D reconstructions of NIH/3T3 fibroblasts were produced. A simple z-correction was applied to the data cube, and the biggest assumption for that correction was validated. An intracellular lipid-rich region surrounding the nucleus was visualized. ToF-SIMS applied to two different breast cancer systems. In the first, eight human breast cancer cell lines were distinguished form one another using mass spectra and principal component analysis (PCA). Not only was PCA to distinguish the cell lines form one another, it also highlighted the largest sources of variance between the cells. Phosphocholine, fatty acids, cholesterol and diacylglycerols (DAGs) were identified as key peaks. The identification of these species indicate that differences in lipid metabolism play an important role in separating the cell types from one another. Breast cancer tumor tissues were also investigated. Data from four tumors was collected. PCA applied to the spectra distinguished the four tissues from one another. Imaging PCA determined the largest sources of variance within an analysis area. Structures were identified by PCA that matched structures observed in serial-sectioned, conventionally-stained slices, and other domains that were not visible in the conventionally-stained slices. As with the breast cancer cell lines, phosphocholine, fatty acids, DAGs, cholesterol and vitamin were found to be large sources of variance, indicating lipid metabolism plays in important role in tumor differentiation
Jazz Innovation Series, Part I, May 22, 2013
No full textConcert program for Jazz Innovation Series, Part I, May 22,
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Bariatric Surgery for Severe Obesity: Determinants of Use and Economic Impact
No full textThesis (Ph.D.)--University of Washington, 2013Objectives: Obesity in the U.S. population is a major public health problem with important clinical and economic implications. Bariatric surgery is currently the most effective long-term weight loss treatment for morbid obesity but less than 2% of the potentially eligible population has undergone the procedure. Our aims were to: 1) determine the patient characteristics associated with receiving a bariatric procedure among eligible patients; 2) identify patient characteristics that could be used as predictors of resource use and costs in severely obese patients with and without bariatric surgery; and 3) estimate and project the differences in long-term costs and outcomes across different clinically defined populations undergoing bariatric surgery compared to non-surgical approaches, refining a previously developed cost-effectiveness model. Methods: We used electronic medical records from members of Group Health Cooperative, based in Washington State to identify severely obese individuals, eligible for bariatric surgery, from 2004 to 2010. The probability of undergoing bariatric surgery was assessed using multivariate logistic regression adjusting for demographic and clinical characteristics, as well as patterns of practice. To determine the predictors of costs, we used generalized linear models for both groups with similar adjustment variables. We created a propensity score matched cohort based on specific characteristics previously identified at the date of surgery and the assigned index date for those who did not have surgery. Finally, we used these data to update a previously developed cost-effectiveness model to re-estimate the cost-effectiveness of bariatric surgery compared to non-surgical interventions. Results: A total of 48,166 subjects were identified as eligible for bariatric surgery. Only 1,129 had bariatric surgery. The characteristics associated with having a bariatric procedure were: having insurance coverage for the procedure (OR=5.61; 4.71-6.68), higher body mass index (BMI) (1.10; 1.09-1.11), and older age (1.00; 1.00-1.01). The presence of comorbidities was associated with higher odds of having surgery. Examining comorbidities individually, only coronary heart disease was not associated with the surgery (0.96; 0.74-1.26). These characteristics changed over time, showing time trends towards increasing numbers of older adults and subjects with lower BMI having the procedure in the recent years. For costs, total annual costs were higher prior to surgery in the bariatric surgery group but decreased more (in absolute and relative terms) after the surgery compared to the non-surgical group. The total health care costs post-surgery for both groups were primarily driven by inpatient costs. The presence of comorbid conditions was associated with greater annual total costs in both groups. Major cardiovascular risk factors, such as coronary heart disease, hypertension, diabetes, and a higher comorbidity index, were associated with the highest increase in mean annual total costs. Despite being more expensive, bariatric surgery is cost-effective due to the impact on weight loss, which is associated with improved life expectancy and quality of life after the procedure. The incremental cost-effectiveness ratio of the bariatric surgery is sensitive to the presence of multiple comorbidities, mainly due to the reduction in the differences in the lifetime costs between surgical and non-surgical interventions for patients with multiple comorbidities. Conclusions: There are demographic, clinical, and insurance differences among subjects eligible for bariatric surgery that receive and do not receive the surgery. The presence of specific comorbid conditions increases the probability of surgery and is associated with higher total costs in this population. The cost-effectiveness of these procedures also depends on the presence of specific comorbid conditions. Understanding these differences could better inform the decisions that patients, clinicians, payers and policy-makers face in addressing the problem of increasing population obesity
Pangye Surok 磻溪隨錄, Volume 7, Chonje Hurok Kosol Sang 전제 후록 고설(田制後錄攷說) 상(上)
No full textThis chapter relates to the land system as it relates to social organization in China, and the census. Also forestry, taxation, water conservancy, migration, and the relief system. Pan’gye Surok (磻溪隨錄) is Yu Hyŏng-wŏn’s (柳馨遠1622-1673) representative book on a reform for a Korean system of government. It consists of total of 26 volumes. In Pan’gye Surok, Yu extensively elaborates his ideas on reform for governmental organization. The main emphasis of the book is on the idea of land reform, through which the author gives well organized critiques and analysis for remodeling and redistributing wealth. The focus and suggestions for reform, however, also expand to social, military, and financial reforms. He also included a thorough examination of the many Chinese classical and historical texts as well as Korean primary sources and scholarship
Cephalometric Analysis and Long-Term Outcomes of Surgical Jaw Advancement in Obstructive Sleep Apnea
No full textThesis (Master's)--University of Washington, 2013Purpose: To describe the posterior airway space and soft tissue changes in patients who received orthodontics and single or dual surgical jaw advancement and to evaluate if there is a correlation between increasing amounts of advancement and long-term reduction in obstructive sleep apnea. Methods:Records were searched from one oral surgeon and one orthodontist for all patients treated by bilateral sagittal split osteotomy (BSSO) or maxillomandibular advancement (MMA) done in combination with orthodontics. Cephalometric films from pre-treatment, pre-surgery, post-surgery, and final removal of appliances were collected and traced. Pre-surgical and Post-surgical polysomnography results were collected, specifically the apnea-hypopnea indexes (AHI). The patients were recruited to complete a questionnaire and Epworth Sleepiness Scale (ESS) to assess long-term outcomes from treatment. Descriptive statistics were calculated for all cephalometric measurements and the data was analyzed for change from initial to final measurements with significance level set at P Results:Forty-three patients, treated from 1995-2010, were identified for the study. Twenty-nine patients had a complete cephalometric film series. The maxilla and mandible were advanced 5.2 mm and 8.3 mm respectively, with a mean 4 mm increase in posterior airway space. The upper and lower lip protrusion increased by 4.8 mm and 7.6 mm but there was no significant change in relation to the nose-chin line. The soft tissue chin increased by 11.3 mm. Thirty-three patients completed the long-term survey at a mean 6.3 years ± ± 2.6 (range 2-12 years) after removal of appliances. The majority of patients (90%) reported reduction of their OSA symptoms and were pleased with their facial appearance. 79% of patients would recommend the orthodontic and surgical management of OSA to prospective candidates. Twenty-two patients had initial AHI and final ESS values to assess final ESS score as a function of mandibular advancement. The mandibular advancement regression coefficient was -0.03 statistically and clinically insignificant. Twelve patients had initial and final AHI values to assess final AHI value as a function of mandibular advancement. The regression coefficient of mandibular advancement was 0.05, also statistically and clinically insignificant. No correlation could be found due to the lack of variation of mandibular advancement and limited sample size. Conclusions: Soft tissue profile characteristics, AP airway dimensions, and skeletal maxillomandibular advancement were significantly increased after MMA. Soft tissue parameters were considerably protrusive but still demonstrate facial harmony. There was no evidence of a linear relationship between greater amounts of mandibular advancement and improvement of OSA outcomes. An advancement threshold could not be evaluated due to the limited sample size. Patients well below the recommended 10 mm advancement had successful objective short-term and subjective long-term reduction in OSA symptoms. Overall, patients were satisfied with their OSA management, facial aesthetics, and would recommend the treatment to others
The Dilemma of Urban Road Space Reallocation: An Outreach and Engagement Strategy for Bus Rapid Transit on Seattle's Madison Street
No full textThesis (Master's)--University of Washington, 2013The 2012 Seattle Transit Master Plan recommends bus rapid transit (BRT) for a new high capacity transit line on Madison Street. In the most recent budget, the City approved $1 million to study and develop a BRT concept for the corridor. In order to build full-fledged BRT, as opposed to enhanced bus service or "BRT Lite," the City must reallocate road space to create a dedicated right of way, high quality stations and transit priority treatments. While there is an extensive body of literature covering the technical challenges to implementing BRT in a dense, urban environment, the political challenges have received far less attention. This thesis examines key American BRT implementation cases, stakeholder engagement research, and a careful analysis of Madison Street's unique opportunities and constraints in order to craft a strategy that will lead to successful implementation of true BRT. The resulting strategy, dubbed "BRT+," builds on the success of Cleveland's Healthline BRT and other cases, bringing diverse stakeholders together to develop a vision for the corridor that includes non-transit investments such as station area plans, pedestrian improvements, and other stakeholder generated priorities. In order to craft a BRT plan and complimentary non-transit improvements, the strategy relies on a multi-layered outreach and engagement effort that combines civic leadership, robust stakeholder involvement and effective broad based communications
Challenges and Opportunities for the Development of a Sustainable Forest Sector in the Russian Far East
No full textThesis (Master's)--University of Washington, 2013Twenty-three percent of global forests are contained within the Russian Federation's nine time zones, which is more than the combined forest area of Canada and Brazil. Despite the fact that Russia contains the largest area of natural forests in the world, its current share in the trade of world forest products is below 4 percent. Russia's forest sector is known for high transportation costs, aging infrastructure, and high instances of bribery and corruption, issues that have had widespread impacts. In 2006, Russia's easternmost region, the Far East, had the ability to process only two percent of its regional timber harvest. While the Far East's processing capacity was particularly low, the situation for most other regions of Russia was little better. With such a low capacity to process timber, Russia increasingly became an exporter of roundwood logs; between 2003 and 2005, Russia exported more roundwood than any other country. Beginning in 2007, the Russian government implemented a series of policies, including export tariffs on roundwood, in order to develop a more competitive timber-processing sector and increase the production and exports of value-added forest products. Yet, in 2009, 96% of the forest product exports from the Far East were in the form of unprocessed roundwood logs. Thus, the efficacy of these national forest policies in the Far East has been unclear in the short-term. Additionally, Russia's World Trade Organization (WTO) accession in August 2012 is expected to alter many aspects of Russia's forest sector development and exports. Through semi-structured interviews with people involved in the forest sector, this research investigates the most recent challenges facing the development of a sustainable forest sector in the Russian Far East
Walls of Indifference: Arizona and the Ecology of Militarization
No full textThesis (Ph.D.)--University of Washington, 2013This ethnography documents and explores the social, political, and material consequences of militarization in the borderlands of Arizona. Basing my conclusions on two years of fieldwork in Phoenix, Tucson, and along the US-Mexico border, I identify militarization as a social and political phenomenon that gradually reconfigures both individuals and communities. What is most striking about the process of militarization is its instrumentalization. Although fieldwork participants use the tropes of immigration and race as central points for discussion, I observed that these discourses point to a much broader trend of social, psychological, and political transformation connected to the proliferation of vigilantism, gated communities, and detention centers. Most recently, this transformation is embodied and articulated through the experiences of border crossers. Border crossers are migrants who enter the United States without authorization due to multiple factors, including socioeconomic constraints, and they include women, children, and men. Many cross the border hoping to reunite with family members who work in the United States and who can no longer risk returning to Mexico or other parts of Latin America. Each dissertation chapter is an examination of the extravagant devices that assist in the reconfiguration of the social, political, and psychological landscape and allow for the emergence of militarization within the context of the immigration debate. In chapter 1, I provide a basic overview of three main threads of Arizona history from which the current social and political climate of Arizona emerged. Chapter 2 charts out how the language of war functions as an instrument of governance. Through ethnographic instances, I explore how the vocabularies of race, nationalism, and patriotism actually decrease political engagement. The third chapter examines how, when local authorities govern through crime, individuals learn how to identify criminals and ethnoracial others as enemies of the state. In Chapter 4 I analyze how the borderland areas of Arizona are contested terrains and geographies of anguish. I examine the experiences of the now infamous Arizona residents Jared Lee Loughner and Shawna Forde to demonstrate that these geographies of anguish are testaments to the continuing deleterious effects of imperialism on both persons and places. In Chapter 5, I explore the effects of what is known as statecraft and examine its social, physical, and psychological consequences. I argue that physical encampments and social exclusion allow for a psychic landscape where subjects assist in the social and physical death of others. Finally, chapter 6 is a visual ethnography: I use photographs to chronicle the harsh realms that border crossers traverse, including both the hostile physical landscape and the inflammatory social and political debates. The photographs examine narratives of race, crime, migrancy, indigeneity, and the continuing deleterious effects of colonialism. I conclude that the social suffering that my research illuminates is the social and material consequence of statecraft. Both residents and those who travel through the borderlands live along the fault lines of the nation-state and are habituated to conflict through the militarization of their communities. I end by examining militarization as a socioecological process, arguing that militarization reconfigures an individual's sense of self. This ethnography is significant not only to anthropology, but also to interdisciplinary research collaborations that focuses on environmental psychology, trauma, conflict resolution, and the effects of war and militarization on communities. Rather than examining the social and political environment as a problem of the border or immigration, I argue that such perspectives need to be decentered and critically examined. My aim is to offer a critical and holistic perspective that looks beyond these normalized tropes. I hope that this investigation will be of interest to a wide variety of academics, civilians, students, and grassroots organizations
Stress Physiology and Post-traumatic Stress Symptoms in Children Exposed to Intimate Partner Violence
No full textThesis (Ph.D.)--University of Washington, 2013Intimate partner violence (IPV) is a prevalent problem in families with many children exposed to the violence each year. IPV has been associated with negative outcomes in children including trauma symptoms. A potential avenue to explore to determine which IPV-exposed children are at greatest risk for trauma symptom development is physiological functioning both at baseline and in response to stress. Previous research has demonstrated that trauma exposed children may display atypical physiological functioning of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS). Additionally, atypical physiological functioning has also been associated with maladjustment in children. However, much of this work has focused on the independent effects of the HPA axis and SNS and results have been inconsistent with some finding increased activation, decreased activation or normative functioning associated with poor child outcomes. Bauer and colleagues (2002) argued that these physiological systems need to be examined concurrently to understand which children are at highest risk for maladjustment. Additionally, they put forth two competing models, the interactive (asymmetrical activation is associated with increased risk) and additive (symmetrical functioning is associated with increased risk) models, to describe how the HPA axis and SNS may interact. The present study examined whether the inclusion of both systems best predicts trauma symptoms in IPV-exposed children over the individual effects of each system. Furthermore, it investigates which model, the additive or interactive, best describe the interaction of the two physiological systems. Thirty-five mother-child dyads (children aged 6-12 years) with a history of IPV exposure were included in the study. Children completed a parent-child interaction and mental arithmetic task with saliva samples collected five times over the course of the session. Hierarchical linear regression analyses were conducted to assess whether the interaction between both baseline levels and reactivity levels of cortisol and alpha amylase best predicted child trauma symptoms. Significant interactions were plotted per Aiken and West (1991). Findings supported Bauer et al.'s (2002) suggestion of using a multi-system approach and there was support for both the additive and interactive models. Future directions for research are also discussed
New technologies for sequencing and interpreting genomes
No full textThesis (Ph.D.)--University of Washington, 2013A central goal of biomedical research is to catalog genetic variation and uncover its causal relationship to phenotype. As humans are diploid organisms with two copies of each chromosome (except for the sex chromosomes in males), a critical aspect of each individual's genetic variation is not only the full list of alleles he or she carries, but additionally the arrangement of those alleles (termed haplotypes) along each of the inherited chromosomes. Although current strategies for genome sequencing are highly effective at cataloging allelic variation, they are largely unable to link consecutive variant alleles onto longer haplotypes. This limitation arises from mechanical or enzymatic shearing used as one of the first steps by every sequencing technology in current use. By shearing input material into fragments much shorter than the average distance between adjacent heterozygous variants, the contiguity information encoded by the pairing of adjacent variants is lost. In this dissertation, I describe techniques that I developed to recover this contiguity information by preserving long fragments for several additional steps prior to sequencing. In a proof-of-concept, I show for an individual human genome that this approach can resolve haplotype phase with substantial completeness (94% of detected heterozygous variants) and across long physical spans (50% of the genome in blocks of ≥386 kbp). The ability to obtain haplotype-resolved genome sequences enables numerous important applications, of which I demonstrate several here. I show how this approach can be used to uncover novel aspects of genome structure, from genotyping variation in structurally complex, duplicated portions of the genome, to mapping positions of sequence not present in the human genome. Finally, to demonstrate the translational value of this information, I combined haplotype-resolved sequences of parental genomes with maternal plasma DNA sequencing in order to non-invasively predict the genome sequence of a human fetus in the second trimester. As sequencing technology continues to expand in scale, quality, and its scope of application, continued development of techniques to preserve contiguity information will remain an important area of focus