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Quasi-experimental designs are gaining popularity in epidemiology and health systems research—in particular for the evaluation of health care practice, programs, and policy—because they allow strong causal inferences without randomized controlled experiments. We describe the concepts underlying five important quasi-experimental designs: Instrumental Variables, Regression Discontinuity, Interrupted Time Series, Fixed Effects, and Difference-in-Differences designs. We illustrate each of the designs with an example from health research. We then describe the assumptions required for each of the designs to ensure valid causal inference and discuss the tests available to examine the assumptions.

The purpose of this research was to develop an algorithm that could predict ramp meter wait time at metered freeway on-ramps throughout the state of Utah using existing loop detector systems on the ramps. The loop detectors provided data in 60-second increments that include volume, occupancy, and the metering rate. Using these data sources, several ramp meter queue length algorithms were applied; these predicted queue lengths were then converted into wait times by using the metering rate provided by the detector data. A conservation model and several variations of a Kalman filter model generated predicted queue lengths and wait times that were compared to the observed queue lengths. The Vigos model—the model that yielded the best results—provided wait time estimates that were generally within approximately 45 seconds of the observed wait time. This model is simple to implement and can be automated for the Utah Department of Transportation (UDOT) to provide wait time estimates at any metered on-ramp throughout the state.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. It is an aggressive cancer, with 50–70% of patients diagnosed at an advanced stage and 30–50% of patients not cured by chemoimmunotherapy. DLBCL is almost always caused by genetic damage sustained during the germinal center (GC) reaction. The mechanisms that govern the GC reaction bear a striking resemblance to those that drive DLBCL. Genomic studies have shown that some of its most common mutations occur in genes that encode epigenetic modifiers, including the lysine (histone) acetyltransferases CREBBP and p300. These mutations prevent the acetylation of multiple histone residues, including H3K27Ac (activating) along the enhancers of genes whose expression is required for essential functions like GC exit and differentiation. CBP/p300 mutations also prevent the acetylation of p53 (activating) and BCL6 (inhibiting). In light of recent evidence that ω-3 fatty acids (ω-3 FA) can influence histone acetylation in cancer, we tested the ability of the ω-3 FA docosahexaenoic acid (DHA) to restore levels of histone and p53 acetylation in three DLBCL cell lines (with different CREBBP/EP300 mutational statuses) and one line of normal B-cells. After exposure to DHA at clinically attainable doses, we observed significant changes in the genome-wide levels of histone post-translational modifications (PTMs) (including acetylated residues H3K9Ac, H4K5Ac, H4K8Ac, H4K12Ac, H4K16Ac) in a cell-line and dose-dependent manner. Histone acetylation did not uniformly increase as expected, but levels of p53 acetylation did. We also observed significant changes in the expression of relevant genes, such as increased expression of CREBBP and PRDM1; the latter is required for the differentiation of GC B-cells into plasma cells or memory B-cells. Overall, we have performed (to our knowledge) the first characterization of the epigenetic effects of ω-3 FA in DLBCL. Our results highlight their therapeutic potential and emphasize the need for further investigation.

This thesis focuses on the behaviour of defects and polarons in TiO2, which is a model catalyst widely used due to its low cost, versatility and stability. TiO2 exists as two main polymorphs, anatase and rutile. Although these polymorphs have the same chemical structure, the manner in which defects exist and behave is distinctly different. Photoemission spectroscopies are suitable techniques for studying polarons. In the first results chapter, bulk defects in rutile TiO2 are investigated with two-photon photoemission and supported with density functional theory. It is found that bulk polarons are less bound than their surface analogues and create an alternative photoexcitation vector. The second results chapter describes the effect of formic and acetic acid adsorption on polaron behaviour in rutile TiO2. Carboxylic acids alter the local crystal field of polarons. Two-photon photoemission spectroscopy is used to demonstrate how this leads to adsorbate specific transitions which is dictated by the electronegativity of the adsorbate. Lastly, in the final results chapter, formic acid adsorption is also considered on the anatase surface. The valence band structure is studied with ultraviolet photoemission spectroscopy to show that oxygen vacancies migrate to the surface upon dissociative adsorption, leading to the stabilisation and diffusion of the associated polarons.

Statement of Purpose The purpose of this study was twofold: 1) to compare the ACT examination results of Canadian students with their American counterparts to see if the ACT is biased against Canadian students; and 2) to compare Canadian and American students' academic achievement while the students are in their first year at Brigham Young University as a way of determining if high school grades of Canadian students were being undervalued in the admissions process at BYU. [...]there is the problem of selectivity of those things that will be compared. The assumption was that if the admissions selection criteria being used by the BYU Admissions Committee incorrectly under-valued the academic preparation of Canadian students, that under-valuing would be demonstrated by their superior first year university grade performance when compared to the first year university grade performance of U.S. students with whom they were matched. [...]the difference between a 2.83 and a 2.96 grade point average is statistically validated because the difference would continue to appear if the same research procedures were followed a second or third time.

Ad26.COV2.S vaccine is a replication-incompetent human adenovirus type 26 vector containing the gene sequence that produces SARS-CoV-2 spike protein in a prefusion-stabilized conformation. In a randomized trial involving nearly 40,000 persons, vaccine efficacy was 66% against moderate to severe–critical Covid-19 and 85% against severe–critical Covid-19. Efficacy against the variant first identified in South Africa was 64% against moderate disease and 82% against severe–critical disease.

Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches. A streamlined sequencing process enables identification of disease-causing variants in the clinic within 8 hours.

Because a genetic diagnosis can guide clinical management and improve prognosis in critically ill patients, much effort has gone into developing methods that result in rapid, reliable results. The authors describe extremely rapid sequencing and analysis of the genomes of 12 patients, 5 of whom received a diagnosis.

Renewable energy development is an arena where ecological, political, and socioeconomic values collide. Advances in renewable energy will incur steep environmental costs to landscapes in which facilities are constructed and operated. Scientists – including those from academia, industry, and government agencies – have only recently begun to quantify trade-offs in this arena, often using ground-mounted, utility-scale solar energy facilities (USSE, ≥1 megawatt) as a model. Here, we discuss five critical ecological concepts applicable to the development of more sustainable USSE with benefits over fossil-fuel-generated energy: (1) more sustainable USSE development requires careful evaluation of trade-offs between land, energy, and ecology; (2) species responses to habitat modification by USSE vary; (3) cumulative and large-scale ecological impacts are complex and challenging to mitigate; (4) USSE development affects different types of ecosystems and requires customized design and management strategies; and (5) long-term ecological consequences associated with USSE sites must be carefully considered. These critical concepts provide a framework for reducing adverse environmental impacts, informing policy to establish and address conservation priorities, and improving energy production sustainability.