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Utility of Social Attention Eye-Tracking Measures as Predictors of Response to Intervention
Thesis (Ph.D.)--University of Washington, 2020Early interventions for children with autism spectrum disorder (ASD) are variability effective, and examination of child characteristics of as predictors of response to intervention have been limited. Based on the social motivation theory, reduced basic visual social attention and joint attention behavior are downstream indicators of reward processing deficits. As such, these measures of social attention may predict child responsiveness to interventions relying heavily on reward learning strategies. Eye-tracking measures of social attention may be particularly useful predictors given their efficiency, high resolution, and ease of administration. However, their properties and construct validity have not been sufficiently investigated. In this study, I examined the properties and construct validity of social attention eye-tracking measures to determine their potential utility as predictors of response to intervention. Differences were not found between ASD and typically developing control groups on percentage of time spent looking at social scenes on a preferential looking eye-tracking task, or on accurate gaze shifts in a response to joint attention eye-tracking task. Age effects may have mitigated group differences. However, participants with ASD had more gaze transitions between face and target object in an initiation of joint attention eye-tracking task. Examination of the eye-tracking measures with more ecological behavioral measures revealed preliminary construct validity for the basic visual social attention eye-tracking task but not for the joint attention eye-tracking tasks. These findings indicate that the eye-tracking measure of basic visual social attention holds promise as a predictor of response to intervention and suggest a need to examine this measure as a pre-test variable in future studies of intervention effectiveness
Development of a turbulent separated flow validation test case: Experimental and computational (RANS) studies
Thesis (Master's)--University of Washington, 2020A new validation test case for CFD of turbulent separated flows is investigated through a combination of experiments and simulations. This work is part of an ongoing collaboration between the University of Washington and Boeing, which aims to contribute to the development of a high-quality validation test case for turbulent separated flows and the improvement of RANS modeling for turbulent separated flows. A three-dimensional speed-bump-like geometry, which causes separation as a result of the surface curvature, was chosen for this study. Tests were conducted to determine the influence of Reynolds number and confinement on the flowfield and to test the ability of common RANS turbulence models to accurately predict the flow. Experimental data was used to formalize the required inflow length so that the bump inflow matched between the simulations and experiments. The parameter used to match the inflows was the Reynolds number based on momentum thickness, , of the incoming boundary layer. The experimental data collected from the incoming boundary layer was also used to prove that the flow upstream of the bump was fully turbulent for all levels of confinement. Five Reynolds numbers were tested in the experiments and the simulations, corresponding to a freestream velocity range of 60 m/s - 20 m/s and four vertical confinement levels were analyzed in the experiments. Six turbulence models were examined: SST, two versions of Spalart-Allmaras (SA and SARC) and three versions of . The geometry was determined to be a challenge to RANS models, which was demonstrated by the pressure coefficient data because the simulations predicted an opposite Reynolds number trend to the experiments in the separated region. Furthermore, the simulations were not able to predict distinctive pressure coefficient profiles seen in the experimental results, such as an inflection point along the streamwise centerline in the separated region and a double-peak in the spanwise direction across the top of the bump. However, the simulations did predict that the flowfield is insensitive to Reynolds number at and above , which is in agreement with the Reynolds number insensitivity determined experimentally. Increasing confinement increased the magnitude of the pressure coefficients over the bump, and the pressure at the peak of the bump went from about -1.2 in the least confined case to about -1.5 in the most confined case. However, there was no change in the shape of the profile. The examination of the various RANS turbulence models concluded that, for this curved geometry, the turbulence models with the curvature correction, SST and SARC, corresponded more closely to the experimental flow than those without a curvature correction. None of the models predicted separation, but SARC, SA and SST all did. It was determined that SARC, SA and SST all displayed similar flow features to those observed in the experimental flow visualizations, such as the general shape of the separated region and counter-rotating surface vortices that were symmetric across the streamwise centerline. However, the extent, location and width of the separated region varied. Along with variation in the size of the separation bubble predicted by each turbulence model, they also all predicted different values and profiles for pressure and skin friction coefficient in the separated region. From this experimental and computational analysis, it is clear that this geometry poses a sufficient challenge to current RANS models, due to their inability to accurately predict the location, size and values of pressure coefficients within the separated region. Therefore, is a good choice for a turbulent separated flow validation test. Future work on this project will focus on detailed flowfield comparisons between experiments and simulations
Geographic Variation in the Use of Triptans and Opioids for the Acute Treatment of Migraine Attacks
Thesis (Master's)--University of Washington, 2020BACKGROUND: Clinical guidelines and published literature suggest that opioids should be used sparingly or avoided in patients with acute migraine due to a lack of evidence of their effectiveness, association with disease progression, and risk of dependence. Triptans are the first line option for the acute treatment of moderate to severe migraine attacks. Despite recommendations, published research suggests that opioids are prescribed more frequently than triptans (53% vs 48%) among patients with migraine. Previous studies have been published for other chronic disease states showing that geographic variation plays a role in prescribing patterns in the United States (US). Moreover, 26 states have passed legislation that limit the prescribing or dispensing of opioids for acute pain. Every state in the Northeast has currently implemented these laws. In addition, the Northeast has the greatest number of headache subspecialists and primary care physicians per capita Yet, the level geographic differences in prescribing patterns, among triptan and opioid users for patients with migraine, has not been elucidated. OBJECTIVE: To assess the geographic variations in triptan and opioid prescribing patterns for patients with migraine. METHODS: We conducted a retrospective cohort analysis using claims data from the IBM® MarketScan® Commercial and Medicare Supplemental databases from January 1, 2016 to December 31, 2018. The target population was adults with migraine who had a migraine-related medical encounter in 2017 with a confirmatory encounter taking place between 31 to 365 days after the initial claim. Baseline characteristics were assessed during the 12-month pre-index period. The 12-month follow-up period was used to assess the outcomes of interest, triptan and opioid utilization, stratified by the four Census-Bureau designated regions: Northeast, Midwest, South, and West. State-level descriptive geographic heat maps were created to depict the patterns of triptan and opioid use in the US. Logistic regression models were used to estimate the binary outcomes of any triptan or opioid use in the follow-up period. Zero-truncated Negative binomial regression models were used to estimate the rate of triptan and opioid use among users in the form of incidence rate ratios (IRR). These analyses were adjusted for age, sex, health plan, presence of chronic migraine, and Elixhauser comorbidity scores. RESULTS: A total of 147,700 patients met the study inclusion criteria. The mean age was 45 and 84% of the patients were female. The prevalence of chronic migraine in the study population was 13% and the mean (SD) comorbidity score was 1.5 (1.7). In the follow-up period, the mean (SD) number of triptan claims for the Northeast, Midwest, South, and West regions were 2.36 (4.05), 2.50 (4.15), 2.60 (4.27), and 2.66 (4.32) respectively. The mean (SD) number of opioid claims for the same regions were 1.50 (4.34), 2.20 (5.00), 2.33 (5.13), and 2.35 (5.45), respectively. Compared to the Northeast, a patient with migraine was more likely to be a triptan user in the Midwest (OR: 1.16; 95% CI: 1.12, 1.20), South (OR: 1.17; 95% CI: 1.14, 1.21), and West (OR: 1.21; 95% CI: 1.16, 1.25). However, among triptan users, there were no significant differences in triptan use when compared to the Northeast for the Midwest (IRR: 0.99; 95% CI: 0.96, 1.02), South (IRR: 1.01; 95% CI: 0.98, 1.04), and West (IRR: 0.99; 95% CI: 0.96, 1.02). Compared to the Northeast, a patient with migraine was more likely to be an opioid user in the Midwest (OR: 1.71; 95% CI: 1.65, 1.78), South (OR: 1.91; 95% CI: 1.85, 1.97), and West (OR: 1.71; 95% CI: 1.64, 1.78). Among opioid users, there was also an increase in opioid use when compared to the Northeast for the Midwest (IRR: 1.21; 95% CI: 1.14, 1.29), South (IRR: 1.17; 95% CI: 1.11, 1.24), and West (IRR: 1.41; 95% CI: 1.32, 1.50). CONCLUSION: Results of our study suggest that compared to patients in the Northeast, patients from the other regions of the US were more likely to use triptans and opioids. Among triptan users, the rates of use were similar across all regions. However, among opioid users, the rates of use were lowest in the Northeast, followed by the South, Midwest, and West. Future work should formally evaluate the impact of headache subspecialists and opioid use policies on opioid use across regions
Recommendation to Implement an Alliance-wide Alternative to the LCSH “Illegal Aliens” Subject Terminology
Toward an improved method for the interpolation and differentiation of particle tracking velocimetry data
Thesis (Master's)--University of Washington, 2020An approach is presented in two and three dimensions for the employment of natural-neighbor techniques to improve the efficiency of interpolating scattered PTV data. Velocity and vorticity were interpolated for an artificial Lamb-Oseen vortex in two dimensions and an artificial Burgers vortex in three dimensions. Gradient calculations were performed using finite differences on the generated interpolants in two and three dimensions; additionally, the natural-neighbor shape functions were differentiated to compute gradients directly in two dimensions. Natural-neighbor interpolation was found to offer a significant savings in both setup and computational time when compared to RBF interpolation. Both methods offered low average relative error across the domains, with the relative accuracy between methods dependent on the problem. Neither technique was found to significantly amplify or filter noise in the data. Further investigation is necessary to refine the use of natural-neighbor methods for PTV, but such algorithms offer a promising direction for accurate rapid interpolation and differentiation of sparse and dense flow information
Sedimentary and hydrodynamic measurements in the Ayeyarwady River Delta from 2017-01-01 to 2019-10-31
The data falls into four categories:
Fixed Instrumentation:
- Instruments that were installed in a single location for the entire sampling period.
- The variables measured include water turbidity, water temperature, water salinity, water pressure, air temperature, air pressure, wind speed and direction, Photosynthetically available radiation, humidity, and rainfall collected at 10 minute intervals semi-continuously in 2017-2019.
- All of the data is available as both csv and raw instrument files.
Surveying Data:
- Data collected during boat-based surveys periodically throughout the study period.
- The variables measured include water turbidity, temperature, salinity, pressure, and velocity. Data was collected during daylight hours transiting either along a river or across a single transect of a river.
- All of the data is available as both csv and raw instrument files.
Samples processed in the laboratory:
- Data produced by laboratory analysis of physical samples collected periodically during boat-based surveys.
- The variables measured are sediment grain size and suspended-sediment concentration.
GPS and Logbooks:
- Field notes and GPS points created during the study period which support the above data.
The file naming convention for instrument data is as follows:
InstrumentManufacturer_DataType_River_DownloadDateAsddmmyyyyHHMM_DataVersion
e.g. onset_salinitytemp_bogale_010320180000_rawoutput.csv
The file naming convention for laboratory samples is as follows:
e.g. ls13320_bedgrainsize_bogale_304_rawoutput.csvThe data to be archived was collected for the project "Understanding sediment dynamics in the estuarine reach of the Ayeyarwady Delta", ONR Contract Number: N000141712350. It consists of in-situ hydrodynamic, meteorological, and geological measurements from the Pathein, Bogale, and Yangon distributaries of the Ayeyarwady River, Myanmar in 2017-2019. None of the data to be archived has been altered since collection
Elucidating the role of unique structural features of the α1D-adrenergic receptor: A tale of two tails
Thesis (Ph.D.)--University of Washington, 2020G protein-coupled receptors (GPCRs) are seven transmembrane domain proteins accounting for ~4% of the human genome, and the predicted target of ~30% FDA approved therapeutics. Often, drugs compete with endogenous ligands for orthosteric binding sites, giving rise to off-target interactions and deleterious side-effects – thus there is a need to identify novel potential ligand binding sites with increased specificity. Recent advances in the field suggest that targeting protein:protein interaction networks, or post-translational modifications that regulate GPCR expression, trafficking, and/or function, may be the key to improving ligand selectivity and decreasing unwanted toxicities. To this end, I devoted my Ph.D. studies to studying two unique structural features that regulate the function of the α1D-adrenergic receptor (α1D-AR) – a GPCR vital for myriad peripheral and central nervous processes which has been implicated in the development and maintenance of hypertension, benign prostate hypertrophy, schizophrenia, and post-traumatic stress disorder – a distal C-terminal Type I PDZ (PSD95/Dlg/ZO-1) ligand and an unusual N-terminal domain. Using yeast two-hybrid and tandem affinity MS/MS assays, the Hague lab previously identified that the α1D-AR C-terminal PDZ ligand is responsible for the formation of obligate, cell-type specific, macromolecular protein complexes containing syntrophin, utrophin, α-dystrobrevin, α-catulin, liprin, phospholipase-Cβ2, and scribble. These complexes enhance receptor cell surface expression and function both in vitro and in vivo. Furthermore, a screen of 23 GPCRs containing Type I PDZ ligands revealed that these interacting partners are unique to α1D-AR. Thus, these protein:protein interaction networks represent an opportunity to develop novel medications with increased specificity for α1D-AR than currently available drugs. However, before this can come to fruition, a more thorough understanding of how these complexes are organized is necessary. Towards mapping α1D-AR complex architecture, biolayer interferometry revealed that scribble displays >8x binding affinity compared to other known α1D-AR interactors. Complementary in situ and in vitro interaction assays revealed that scribble PDZ domains 1 and 4 are high affinity α1D-AR PDZ ligand interaction sites. The development of a novel SNAP-GST pull-down assay found that scribble is able to bind multiple α1D-AR C-terminal PDZ ligands via a cooperative mechanism. Structure-function analyses identified R1110PDZ4 as a unique, critical residue dictating the α1D-AR:PDZ4 interaction. A crystal structure of a non-binding mutant, PDZ4 R1110G, predicts a spatial shift of the carboxylate-binding loop prevents docking of the C-terminal PDZ ligand. Thus, these findings identify scribble PDZ1 and 4 as high affinity α1D-AR interaction sites, and potential targets to treat diseases associated with aberrant α1D-AR function. Additionally, α1D-ARs contain two putative N-glycosylation sites within the large N-terminal domain at N65 and N82. However, determining the glycosylation state of this receptor has proven challenging. Towards understanding the role of these putative glycosylation sites, site-directed mutagenesis and lectin affinity purification identified N65 and N82 as bona fide acceptors for N-glycans. Surprisingly, it was revealed that simultaneously mutating N65 and N82 causes early termination of α1D-AR between transmembrane domain 2 and 3. Label-free dynamic mass redistribution and cell surface trafficking assays revealed that single and double glycosylation-deficient mutants display limited function with impaired plasma membrane expression. Confocal microscopy imaging analysis and SNAP-tag sucrose density fractionation assays revealed the dual glycosylation mutant α1D-AR is widely distributed throughout the cytosol and nucleus. Based on these novel findings, I propose α1D-AR transmembrane domain 2 acts as an ER localization signal during active protein biogenesis, and that α1D-AR N-terminal glycosylation is required for complete translation of nascent, functional receptor. Taken together, the results from these studies identify two promising mechanisms for the development of targeted therapeutics to treat diseases and disorders associated with α1D-AR dysfunction
Withering Syndrome Disease Dynamics in Wild and Cultured Northeastern Pacific Abalones
Thesis (Ph.D.)--University of Washington, 2020Withering syndrome (WS) is a chronic bacterial disease of abalones, Haliotis spp., caused by a Rickettsia-like organism (WS-RLO). The etiological agent, Candidatus Xenohaliotis californiensis, occurs along the eastern Pacific margin of North America in California, US and Baja California, Mexico. However, as infected abalones have been transported to Chile, China, Taiwan, Iceland, Ireland, Israel, Spain, Thailand, and Japan, the geographic range of the bacterium is likely broad especially where California red abalone (Haliotis rufescens) are cultured or in areas where native species have been exposed to red abalone. Disease susceptibility varies among abalones with up to 99% losses of black abalone (H. cracherodii) in lab and field studies in the US, to no losses among the small abalone (H. diversicolor supertexta) in Thailand. Some abalone populations that have suffered severe WS mortality events have developed resistance to the disease. In addition, a newly identified phage hyperparasite of the WS-RLO may reduce pathogenicity and dampen associated losses. Proper diagnosis of WS requires the identification of infection with the pathogen (WS-RLO detected via in situ hybridization or histology coupled with PCR and sequence analysis) accompanied by morphological changes that characterize this disease (e.g. digestive gland metaplasia and pedal atrophy). A quantitative PCR (qPCR) assay was recently developed and validated for the detection of WS-RLO DNA in abalone tissues, feces, and seawater. While confirmation of infection cannot be done by PCR-based assays alone, they can be used as proxies for infection in areas where the WS-RLO is established and are recommended for inclusion in all abalone health examinations. Avoidance of WS is best accomplished by the establishment of a health history, good husbandry practices, and multiple health examinations prior to the movement of animals. Population declines in wild and cultured abalones due to WS have been well documented along the northeastern Pacific Ocean. However, observed differences in species susceptibility to the disease are not well understood. The first objective of my dissertation was to examine the susceptibility of three temperate abalone species, the cool water (4-14°C) pinto or northern abalone (H. kamtschatkana), the intermediate water (8-18°C) red abalone, and the warm water (12-23°C) pink abalone (H. corrugata), to experimental WS infection at temperatures facilitating disease proliferation. Mortality data paired with histological and molecular detection of the WS pathogen confirmed that these abalone species exhibit different levels of susceptibility to infection and resistance to WS development ranging from high susceptibility and low resistance in pinto abalone to moderate/low susceptibility and resistance in red and pink abalones. The temperature associated with WS induced mortalities also varied among species: pinto abalone died at the lowest experimental temperature (17.32 ± 0.09°C), while red abalone died at an intermediate temperature (17.96 ± 0.16°C), and pink abalone required the highest temperature (18.84 ± 0.16°C). When data from the current and previous studies were examined, susceptibility to WS was inversely related to phylogenetic distance from white abalone (H. sorenseni), which had the highest susceptibility and lowest resistance of all abalone species tested prior to the current study. These results provide further evidence that an abalone’s thermal optima and phylogenetic relationship can determine its susceptibility to WS; species with cool water evolutionary histories are most susceptible to WS and the most susceptible species appear to be closely related. Differences among the thermal ranges of abalone species have broad implications for WS disease dynamics and highlight the importance of understanding the mechanisms governing the abalone-WS relationship in order to properly manage declining abalone populations. My second dissertation objective was to elucidate important epidemiological information on the WS-RLO. The bacterium remains unculturable thereby limiting our understanding of WS disease dynamics. My goals were to: (1) determine the temporal stability of WS-RLO DNA outside of its abalone host in 14°C and 18°C seawater, (2) develop a standardized protocol for exposing abalones to known concentrations of WS-RLO DNA and (3) calculate the dose of WS-RLO DNA required to generate 50% infection prevalence (ID50) in the highly cultured red abalone. WS-RLO stability trials were conducted in October 2016, February 2017, and June 2017 during which qPCR analysis was used to quantify bacterial DNA for 7 days in seawater collected at an abalone farm in southern California where the pathogen is endemic. For all trials and temperature treatments, WS-RLO DNA was not stable in seawater longer than 2 days. To determine an ID50, groups of uninfected juvenile red abalone were subjected to 3-hour bath exposures of WS-RLO at four concentrations: 0, 103, 104, and 105 DNA copies/mL. Abalone feces were monitored bi-weekly for the presence of WS-RLO DNA and abalone tissues were sampled 9 weeks after dosing for histology and qPCR examination. Results from the ID50 indicated that our protocol was successful in generating WS-RLO infections and a pathogen dose of 2.3 x 103 DNA copies/mL was required to generate 50% infection prevalence in the tissue of red abalone as assessed by qPCR. The WS-RLO is considered an established bacterial pathogen in coastal CA seawaters and is of great concern to coastal managers and local abalone aquaculture facilities (AFs) conducting open or flow-through seawater culture methods. California AFs are at high risk for spillback (wild to farm) and spillover (farm to wild) disease transmission due to high abalone host densities and the use and release of coastal seawater that may contain the WS-RLO and its associated novel phage. To address these concerns, my third and final dissertation objective was to sample nearshore surface seawater from nine established wild black abalone sites and four red abalone AFs from Bodega Bay, Sonoma County, CA, US to Ventura County, CA, US including the Channel Islands over two consecutive summers to determine the presence and amount of WS-RLO and phage DNA via qPCR. In July 2010, WS-RLO DNA was detected as far north as Andrew Molera State Park, Big Sur, CA and as far south as San Nicolas Island (SNI). Phage DNA was detected from Monterey Bay, CA to SNI. In July 2011, WS-RLO DNA was detected as far north as Davenport, CA and as far south as SNI. The phage DNA detection range remained the same as the 2010 survey. Phage DNA loads did not vary by year at AF or wild sites. However, WS-RLO DNA loads were greater in 2011 than 2010 at wild sites, while those at AFs did not vary by year. In October 2013, surface seawater surveys were conducted at the two southern-most AFs in Cayucos and Goleta, CA to assess fine-scale WS-RLO DNA dilution potential from a point-source discharge. In the 2013 samples, WS-RLO DNA loads in seawater directly adjacent to the AFs were less than the mean levels detected at all wild black abalone sites previously surveyed within 50 to 500 m of the AFs effluent outfalls. While these findings present management concerns for both wild and cultured California abalones, it is important to acknowledge that PCR-based assays do not indicate the presence of viable pathogen or active infection and serve as a proxy for WS exposure. In order to fully assess the potential for wild and cultured abalone disease interactions, additional experiments should be conducted to determine the longevity and infectivity of the WS-RLO and novel phage in seawater. Collectively, these findings are critical components of disease dynamics that will help assess WS transmission risk within and among abalone populations and facilitate appropriate management and restoration strategies for both wild and cultured abalone species in WS-endemic areas
Data-Driven Assessment of Disaster Damage and Recovery Time
Thesis (Ph.D.)--University of Washington, 2020Although natural hazards may sometimes be predictable, their occurrence is not preventable, especially in low-frequency-yet-high-impact events such as earthquakes and hurricanes. The catastrophic effects of natural hazards can vary vastly from year to year, depending on the seasons, locations, demographics, or resilience of the affected areas. Therefore, improving response system and recovery time is one of the most efficient ways to limit fatality and economic loss from a hazard event. Unfortunately, without being able to gain adequate situation awareness about the damage extent and the potential recovery, we cannot effectively improve these processes. This dissertation provides a suite of methodological frameworks utilizing statistical tools to aid in the damage assessment and estimation of various infrastructures' recovery to provide emergency managers and stakeholders with timely and extensive situation awareness after a hazard event. The initial step is to assess the actual damage extent immediately after a hazard event so that adequate planning and resources can be allocated. The first methodological framework aims to speed up the post-event damage assessment process. Instead of the more time-consuming and labor-intensive windshield survey method, machine learning algorithms are applied to automatically annotate the damaged and/or flooded buildings on satellite imagery. The annotation results can be used as a proxy for assessing how badly an area is affected. The machine learning algorithms require much less time and resources while still yielding results with reasonable accuracy. Secondly, to improve generalizability and accuracy of the previous damage assessment framework, a mixed data approach is adopted to combine satellite imagery and other geolocation features such as each building's elevation and proximity to water bodies. Finally, a recovery trajectory estimation framework is introduced to aid in recovery planning for critical infrastructures. The estimation will provide infrastructure management agencies with an idea of the most likely recovery pattern of various critical infrastructures (such as electricity, water, and gas), given different hazard scenarios. This will give them a quantitative assessment of how resilient their infrastructure systems are so that resources can be allocated and necessary investment can be informed effectively. Besides extensive results from numerical studies and empirical data, this dissertation research also contributes two curated datasets to open-access repositories so that others can reproduce and improve the proposed framework
(investigator formerly known as architect): an architectural thesis disguised as a murder investigation
Thesis (Master's)--University of Washington, 2020When architecture student, Alexander Barr, is murdered inside of a mysterious room in an undisclosed location, (investigator formerly known as architect) is hired by an unknown suspect in order to solve the crime. To find the murderer, (investigator formerly known as architect) must find new ways of doing architecture before time runs out; however, nothing here is quite as it seems. in this darkened landscape, tangled duplicity, time loops, and unlikely clues challenge one’s understanding of spatiality and identity. As evidence reveals itself, an unlikely character might be the prime suspect of his Alexander Barr’s murder... What happens when the architect’s dedication to solve the climate crisis becomes a pawn in the game of binary thinking? When do dreamscapes end and investigations begin? How do we find other ways of doing architecture? Which parts of us must die so others may live? ...Who murdered Alexander Barr? ...why was he the central target of the crime?...and what did he know