Bioculture Journal
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Super-resolution Reconstruction of Orientation Distribution Function from Motion Scattered Diffusion Weighted Image Slices and its Application to Fetal Brain Connectivity Study
No full textThesis (Master's)--University of Washington, 2015Diffusion-weighted MRI brings new and complimentary information about the development of the brain. It is also actively investigated how diffusion contrast properties correlates with brain diseases. Though promising, this technique faces a number of technical challenges, especially in fetal imaging, where unrestricted movement occurs. Despite the usage of fast imaging sequences, the acquired images are still corrupted by motion artifacts, making them hardly ready to use by doctors or researchers. Therefore, post image processing methods are in great need to estimate the movement of the subject and to reconstruct high quality diffusion volumes for both clinical and research purposes, e.g., the study of fetal brain connectivity. This thesis firstly gives a background of diffusion and its mathematical models, diffusion inside the brain and diffusion-weighted MRI. Then it introduces the source of the motion artifacts in fetal MRI, and presents the current state-of-the-art method for its removal. After that, a novel super-resolution reconstruction framework for recovering a higher order ODF volume from motion scattered DWI image slices is proposed and experimentally compared to the methods reported in the literature. Both human adult data and macaque fetal data are used for evaluation. Finally, a structural connectivity study of the developing macaque fetal brains is carried out using unbiased template free brain parcellation schemes and graph theory based analysis
Genetic testing for Autism Spectrum Disorder (ASD): evaluating the challenges of genomic translation
No full textThesis (Ph.D.)--University of Washington, 2015Genetic testing for ASD is a new, complex and evolving aspect of healthcare, occurring in the setting of substantial challenges to the diagnosis and treatment of this group of conditions (Jeste & Geschwind, 2014). To date there has been little focused research examining what families experience through the genetic testing process and what they see as the benefits and or harms of genetic testing for ASD. There also has not been any research exploring health care provider views about genetic testing for ASD. My research focuses on three aspects of genetic testing for ASD: guidelines, parent’s experiences, and provider and parent perspectives. In Chapter 2, a guideline review tool was used to analyze five professional guidelines, identifying similarities and differences both in their content and in the process used to develop them to determine where there is and is not consensus in regard to genetic testing for individuals with ASD and to evaluate the guideline creation process. Chapter 3 examines, through qualitative interviews and exploration of diagnostic services for ASD, what genetic testing is being offered to families with ASD and what the path from a clinical ASD diagnosis to genetic testing looks like. Currently the pathway from an ASD diagnosis to genetic testing is messy, expensive, sometimes random and, the interviews in this study suggest, often puzzling or dissatisfying to both patients and providers so efforts to create a clearer and more transparent approach would benefit all involved. Chapter 4 examines provider and parent attitudes about genetic testing for ASD, identifying their concerns and motivations to obtain testing and their thoughts on the benefits and barriers to testing. There is variability in provider attitude and practices toward genetic testing for ASD, as well as parent uncertainty about the value of testing. When providers recommend testing, parents generally follow their advice but they do so primarily to ensure that they are providing all recommended care. In conclusion, there is a broad range of opinion in the medical community when it comes to offering genetic testing for individuals with ASD and these divergent perspectives extend to the clinical guidelines. As a result, offering genetic testing to individuals with ASD is disorganized and as a result, confusing for parents. Finding a way to make the process understandable and easy for families to navigate would be most beneficial to parents. Providers involved in the diagnosis, treatment, and care of individuals with ASD should focus on transparency for families, more research on benefits and outcomes of genetic testing related to ASD, and movement towards clinician consensus on testing recommendations
An Architecture of Fire: Restoring the former Denny-Renton Clay and Coal Co. site in Renton
No full textThesis (Master's)--University of Washington, 2015-12Since the early nineteenth century, the manufacturing of clay products in the United State has produced a wide variety of building materials. Products like face brick, clay veneers and sewer pipe have greatly contributed to the growth of American cities. But, with the declined of demand and the rise of the use of modern building materials like steel, concrete and glass, many of these factories have closed. Little traces of this once thriving industry have been left on the landscape. Today, for the communities that now occupy these sites, the history of clay products is largely forgotten. The abandoned sites of the manufacturing of building materials are unique in the wasted landscapes they have left behind. The extractive industries they once housed have often left only the debris of built form that has been overtaken by natural growth. Brick making, in particular, relied on a process of extraction, reshaping and firing that literally re-shaped the land around it. This thesis proposes that these scarred landscapes have the potential to be re-activated in a way that recall their former use but looks forward to their future. It argues for the role of architecture as fire, a transformative process that consumes resources as it builds
What are the critical indicators of effectiveness of a VGAL? An evaluation of the Snohomish County Volunteer Guardian Ad Litem Program
No full textThe child welfare system in the United States is experiencing an increasing number of cases of abused and neglected children and a lack of Volunteers Guardian Ad Litem (VGALs) available for each case. A VGAL is a court-appointed special advocate who represents a child’s best interests in dependency cases. The purpose of this study is to address a gap in literature that explores the effectiveness of VGALs by gathering data from the volunteers themselves instead of case outcomes. This study interviews ten VGALs in Snohomish County with the intent to produce a more in depth picture of what indicators of effectiveness were common to successful volunteers. The potential factors of effectiveness identified in this study are personal development, belief in program, support systems, balance and objectivity, and personal identity. A better understanding of what makes a VGAL effective could lay the groundwork for future quantitative studies, as well as be used to identify areas of strength or weakness for future program improvement and policy
Electro-Optic Material Design Criteria Derived from Condensed Matter Simulations Using the Level-of-Detail Coarse-Graining Approach
No full textThesis (Ph.D.)--University of Washington, 2015Electro-optic materials enable a wide variety of photonics applications such as micro-scale optical sensors, terahertz spectroscopy, photonic computing, quantum key distribution, and high speed data transmission for computing as well as global telecommunications. Organic 2nd-order non-linear optical (ONLO) materials offer several key advantages for photonic devices such as intrinsically higher bandwidth on the order of THz, lower power consumption, and smaller device structures compared to currently used inorganic materials such as lithium niobate. ONLO materials consist of electro-optic chromophores arranged such that overall, acentric dipole order is present in the material. Crucial insight into the acentric ordering of an ensemble of electro-optic chromophores can be provided by computational modeling. Presented in this dissertation is a coarse-graining (CG) Monte Carlo approach, the Level-of-Detail (LoD) method, enabling the systematic determination of CG model parameters with no adjustable parameters from ab initio quantum mechanical calculations and fully-atomistic force fields. The LoD method’s ability to correctly represent all-atom behavior is demonstrated on a diverse range of condensed molecular systems relevant to different aspects of the simulation of electro-optic materials such as the accurate simulation of π-π interactions, the incorporation of flexible molecular linkers, and the prediction of dielectric behavior. Details of molecular interactions that determine the extent of acentric order are investigated and the observations and conclusions derived in this thesis culminate in a set of design criteria for construction of future molecules by experimentalists
Adherence to Adjuvant Endocrine Therapy among Women Diagnosed with Early Breast Cancer
No full textThesis (Ph.D.)--University of Washington, 2015Estrogen receptor-positive (ER+) breast cancer is diagnosed in two-thirds of breast cancer cases in the US. Treatment with adjuvant endocrine therapy (AET) is recommended for five years for women with ER+ breast cancer. Despite the effectiveness of AET to improve survival and decrease cancer recurrence, adherence to recommended treatment is suboptimal. Understanding the factors that are associated with adherence to AET could improve overall breast cancer survival. Therefore, the goal of this dissertation is to identify target areas that are amenable for interventions in order to improve adherence to AET. The objective is threefold: 1) determine the association between combined out-of-pocket costs for AET medication and adherence; 2) examine how factors affect adherence to AET medication among women with very low adherence, moderately low adherence, and high adherence; and 3) understand, from the patient’s perspective, how their physicians communicate with them about AET treatment. For objective 1 and 2 we conducted a retrospective cohort study using longitudinal medical and pharmacy claims data from the MarketScan Database from 2007-2011. We included women who were recently diagnosed and surgically treated for breast cancer and who filled at least one prescription for AET. For objective 3, we conducted semi structured in-depth interviews with breast cancer survivors taking AET. We found that high out-of-pocket costs for AET medication put patients at an increased risk of non-adherence. Factors associated with adherence to AET differed across the distribution of adherence and the use of mail-order pharmacies had the greatest influence on adherence. Physician-patient communication played an important role in both the initiation and management of AET. We found that women continue to take AET medication because their physician communicated key aspects of AET treatment in a way that they understood. Women also trusted and had confidence in their physicians. In summary, organizational-level interventions have the potential to improve adherence to AET. The use of mail-order pharmacies as well as lowering out-of-pocket costs may have the greatest influence on improving adherence. Women may also be more likely to continue AET treatment if physicians communicate the benefits of AET and actively engage patients in follow-up care to manage potential side effects
Parent Preferences for Dental Preparatory Aids for Children with Autism Spectrum Disorders
No full textThesis (Master's)--University of Washington, 2015Purpose: To investigate caregivers’ preference regarding the use of storyboard preparatory aids to prepare children with Autism Spectrum Disorders (ASD) for dental visits. Methods: Caregivers of new patients with ASD were given a survey regarding demographics, behavioral and medical characteristics, and media preferences. They were then shown dental preparatory aids available via different media (print or digital) and image types (photographs, drawings, or videos). Caregivers were invited to use these preparatory aids and complete a follow-up survey. Fisher’s exact tests were used to determine associations between predictive factors and media preferences. Results: Forty initial and 16 (40%) follow up surveys were completed. Subjects were male (85%) and white (48%). Mean child age was 6.7 years (SD =2.9 years). Nine (64%) caregivers found the aid useful for themselves and their child. Two (14%) caregivers found the aid helpful for themselves but not their child. Preferred media type was associated with language understanding (P=.038) and home media preference (P=.002). Prior use of preparatory aids (P=.043), media type (P=.009), and image type (P <.001) of aids the child had used in the past were associated with child preferences. Preferred dental aid image type was significantly associated with the image type used in prior aids (P=.013) Conclusions: Practitioners should consider using visual aids to help prepare children for dental visits. Individual preferences for media and image types vary, asking parents which types of media their child has been responsive to in the past may aid in selecting preparatory aids that are effective
Reading the Household: Towards an Economic and Textual Understanding of Early English Drama
No full textThesis (Ph.D.)--University of Washington, 2015This dissertation examines the domestic household's relationship to early English dramatic narratives from the fourteenth century to the start of the professional London stage. During this period the English household--understood as the basic unit of economic production in society--was both a source of public fascination and an active site of cultural and political meaning. Early English drama repeatedly dramatized household tensions, articulating the complicated social and economic arrangements found within contemporary households. This dissertation studies the English domestic household as a playing space and a dramatic subject while tracing the household's shaping influence on a wide range of early dramatic texts. Attending not only to household players and spectators, the project also traces the history of dramatic "book use": how plays were physically used, read, and altered by household readers. Using economic history, the dissertation examines the domestic household's material and ideological engagement with dramatic narratives while making a contribution to current research in the fields of early English drama and book history
DGCR8 Phosphorylation is Required for the Repair of UV-induced DNA Lesions Independently of MicroRNA Processing
No full textThesis (Ph.D.)--University of Washington, 2015Ultraviolet (UV) radiation generates toxic and mutagenic DNA lesions such as cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidone photoproducts (6-4PPs) and is a carcinogen. MicroRNAs have been implicated in cellular response to UV. However, mechanisms connecting the microRNA biogenesis machinery and UV response are unknown. Here we show a critical role of DGCR8, an RNA binding protein in the microRNA processing Drosha-DGCR8 complex, in repair of UV-induced DNA lesions. Treatment with UV (UV-C and UV-B) induced phosphorylation on Serine 153 (S153) of DGCR8 in human cells. DGCR8-deficient cells were hypersensitive to UV and deficient in removal of UV-induced CPDs and 6-4PPs. Phosphorylation of S153 was critical for removing CPDs and 6-4PPs and cellular resistance to UV, but not for microRNA expression. In contrast, the RNA-binding and the Drosha-binding activities of DGCR8 were not critical for UV resistance. DGCR8 depletion did not sensitize cells deficient in CSA, CSB or XPA, the genes involved in transcription-coupled nucleotide excision repair (TC-NER), to UV, while it sensitized wild-type or XPC-deficient cells to UV. DGCR8-depleted cells and S153A DGCR8 mutant cells showed delayed recovery of RNA synthesis after UV exposure, further suggesting that phosphorylation of S153 is involved in TC-NER. Interestingly, Drosha-depleted cells were UV sensitive, but proficient in repairing UV-induced DNA lesions. Thus, UV-inducible phosphorylation on S153 of DGCR8 mediates TC-NER of UV-induced DNA lesions in a manner independent of microRNA processing and Drosha. Our study revealed an unexpected role of DGCR8 in TC-NER and establishes a novel UV-response signaling pathway (the DGCR8-mediated UV response pathway) that connects the microRNA biogenesis machinery and DNA repair of UV-induced DNA damage. Since both the microRNA biogenesis machinery and DNA repair have been implicated in human diseases including cancer, these findings provide novel insights into our understanding of such diseases
On numerics and inverse problems
No full textThesis (Ph.D.)--University of Washington, 2015In this thesis, two projects in inverse problems are described. The first concerns a simple mathematical model of synthetic aperture radar with undirected beam, modeled as a 2D circular Radon transform with centers restricted to a plane curve \gamma. From the work of Stefanov and Uhlmann (2013), it is known that this operator is microlocally non-injective locally, but microlocally injective globally if \gamma is closed. The problem for non-closed \gamma is examined; it is shown that the Radon transform R_\gamma is microlocally non-injective to leading order if a certain geometric condition is satisfied. Known examples where this condition holds are given. Numerical simulations demonstrate R_\gamma's microlocal non-injectivity for a single curve, and for a four-curve setup satisfying the geometric condition. The second project involves the implementation of an algorithm by de Hoop, Uhlmann, Vasy, and Wendt (2013), with refinements, for computing generic Fourier integral operators (FIOs) associated with canonical graphs, possibly involving caustics. The algorithm can be divided into two parts: a local component that approximately evaluates an FIO A: C^\infty_0(X)\to \mathcal D'(Y) expressed in the oscillatory integral form Af(y)=\int e^{i\phi(y,\xi)} a(y,\xi)\,\hat f(\xi)\,d\xi, modulo an error operator of order 1/2 less than the order of A, and a global component that expresses an arbitrary FIO associated with a canonical graph as a finite sum of these local oscillatory integrals composed with appropriate coordinate changes. A numerical implementation of their algorithm is demonstrated and successfully applied to a variety of FIOs associated with canonical graphs. This algorithm is designed to be easy-to-use for future researchers and the code is freely available from the author