Explore the vast range of titles available.

Compared with admissions test scores, why are high school grades better at predicting college graduation? We argue that success in college requires not only cognitive ability but also self-regulatory competencies that are bette indexed by high school grades. In a national sample of 47,303 students who applied to college for the 2009/2010 academic year, Study 1 affirmed that high school grades out-predicted test scores for 4-year college graduation. In a convenience sample of 1,622 high school seniors in the Class of 2013, Study 2 revealed that the incremental predictive validity of high school grades for college graduation was explained by composite measures of self regulation, whereas the incremental predictive validity of test scores was explained by composite measures of cognitive ability.

This dissertation is an exploratory study of the impact on motivation of using autonomy-supportive course design features across a broad range of social science courses at the University of Michigan. The primary goal of this dissertation is to explore how variation in the employment of autonomy-supportive course design features affects the degree to which students internalize their motivation to do well in that course. Broadly, autonomy-supportive course design features are ways that instructors can design a course to give students more ownership over their learning, reduce the cost of failure, provide constructive feedback, and in general allow students’ perspectives to guide the way they interact with the course. The results from this study will ideally inform the way that autonomy-supportive course design is used in gameful courses, but will also be useful for course design in general. By studying autonomy-supportive course design outside of gameful courses I attempt to isolate the effects of autonomy-supportive course design from other features of gameful courses as well as student reactions to the novelty of gameful grading systems. In addition, I consider individual differences as potential moderators of the relationship between autonomy-supportive course design and student autonomous motivation. While there were no main effects of autonomy-supportive course design features on student autonomous motivation, there are significant interactions suggesting that different students react differently to certain autonomy-supportive course design features. Students may not perceive choice in the same way and these perceptions are influenced by student individual differences. Results indicate that higher achieving students were more adept at managing the additional responsibility of choice and thus approached the use of autonomy-supportive course design from a more autonomous perspective than lower achieving students. Students who perceived a low cost of engaging with a course, relative to students who perceived a high cost, tended to also approach autonomy-supportive course design from a more autonomous perspective since they had more time to manage that increased responsibility. One implication of these results for courses that utilize autonomy-supportive course design, including gameful courses, is that instructors should consider providing additional scaffolding to help students adapt to the novel course design elements. The goal of gameful pedagogy is to use the design elements of video games (not the games themselves) to re-design the grading system in a course in order to boost intrinsic motivation. Autonomy-supportive course design is one facet of gameful pedagogy alongside safe failure, and holistic backwards design (Holman, 2018). Self-Determination Theory researchers have found that well-designed video games are intrinsically motivating for players because they satisfy players’ needs for autonomy, competence, and relatedness (Ryan, Rigby, and Przybylski, 2006; Przybylski, Rigby, & Ryan, 2010; Przybylski, Weinstein, Ryan, & Rigby, 2009). The intrinsically motivating nature of well-designed video games is the driver behind the study of the use of game design elements in other contexts, such as education. Limitations of the current study and potential future directions for research are discussed in the final chapter. This exploratory study of autonomy-supportive course design reveals much about the way that different students perceived autonomy-supportive course design features and raises important implications for the use of autonomy-supportive course design in gameful courses.

Background The development of next generation sequencing (NGS) methods led to a rapid rise in the generation of large genomic datasets, but the development of user-friendly tools to analyze and visualize these datasets has not developed at the same pace. This presents a two-fold challenge to biologists; the expertise to select an appropriate data analysis pipeline, and the need for bioinformatics or programming skills to apply this pipeline. The development of graphical user interface (GUI) applications hosted on web-based servers such as Shiny can make complex workflows accessible across operating systems and internet browsers to those without programming knowledge. Results We have developed GENAVi (Gene Expression Normalization Analysis and Visualization) to provide a user-friendly interface for normalization and differential expression analysis (DEA) of human or mouse feature count level RNA-Seq data. GENAVi is a GUI based tool that combines Bioconductor packages in a format for scientists without bioinformatics expertise. We provide a panel of 20 cell lines commonly used for the study of breast and ovarian cancer within GENAVi as a foundation for users to bring their own data to the application. Users can visualize expression across samples, cluster samples based on gene expression or correlation, calculate and plot the results of principal components analysis, perform DEA and gene set enrichment and produce plots for each of these analyses. To allow scalability for large datasets we have provided local install via three methods. We improve on available tools by offering a range of normalization methods and a simple to use interface that provides clear and complete session reporting and for reproducible analysis. Conclusion The development of tools using a GUI makes them practical and accessible to scientists without bioinformatics expertise, or access to a data analyst with relevant skills. While several GUI based tools are currently available for RNA-Seq analysis we improve on these existing tools. This user-friendly application provides a convenient platform for the normalization, analysis and visualization of gene expression data for scientists without bioinformatics expertise.

Septic shock has an unacceptably high mortality rate and unmet need for new therapeutics. Murine models are crucial for research, yet methodologies often differ. This study characterised standard- and high-grade caecal ligation and puncture (CLP) murine models of septic shock by integrating ultraminiature arterial telemetry with comprehensive plasma biomarker analysis. Standard-grade and high-grade CLP was performed in 8–10 week old, male C57BL/6 mice (n = 98), with a subset implanted with arterial telemetry to monitor real-time circulatory function. Plasma markers of inflammation and organ damage were measured at multiple intervals up to 168 h post-CLP. Standard-grade and high-grade CLP showed distinct progressions; episodes of hypotension began 5–6 h after CLP in 30% of standard-grade and all high-grade CLP mice, with respective 168 h mortality of 40% and 71%. Recurrent episodes of hypotension 5–39 h after CLP were universally lethal. The coincidence of hypotension and elevated plasma lactate defined the onset of septic shock after high-grade CLP, which was always lethal. Inflammatory cytokines and markers of liver, renal, and cardiac damage were markedly elevated to 168 h after high-grade CLP, in contrast to standard-grade CLP, which returned to baseline by 48 h. Elevated plasma IL-6, TNFα, and corticosterone, along with reduced albumin, were significantly correlated with mortality. In conclusion, this research refines murine CLP models by providing a precise, dynamic map of the progression to septic shock. The high-grade CLP model consistently models early and late-stage physiological deterioration and serves as a robust model for evaluating the efficacy of novel therapies aimed at human septic shock.

Background Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). Methods We performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with stage III/IV HGSOC, of which 11 patients carried germline, pathogenic BRCA1 and/or BRCA2 mutations. Results Landscapes of genome-wide methylation (on average 24.2 million CpGs per tumor) and transcriptomes in primary and recurrent tumors showed extensive heterogeneity between patients but were highly preserved in tumors from the same patient. We identified significant differences in the burden of differentially methylated regions (DMRs) in tumors from BRCA1/2 compared to non- BRCA1/2 carriers (mean 659 DMRs and 388 DMRs in paired comparisons respectively). We identified overexpression of immune pathways in BRCA1/2 carriers compared to non-carriers, implicating an increased immune response in improved survival ( P  = 0.006) in these BRCA1/2 carriers. Conclusion These findings indicate methylome and gene expression programs established in the primary tumor are conserved throughout disease progression, even after extensive chemotherapy treatment, and that changes in methylation and gene expression are unlikely to serve as drivers for chemoresistance in HGSOC.

Many hope that ocean waves will be a source for clean, safe, reliable and affordable energy, yet wave energy conversion facilities may affect marine ecosystems through a variety of mechanisms, including competition with other human uses. We developed a decision-support tool to assist siting wave energy facilities, which allows the user to balance the need for profitability of the facilities with the need to minimize conflicts with other ocean uses. Our wave energy model quantifies harvestable wave energy and evaluates the net present value (NPV) of a wave energy facility based on a capital investment analysis. The model has a flexible framework and can be easily applied to wave energy projects at local, regional, and global scales. We applied the model and compatibility analysis on the west coast of Vancouver Island, British Columbia, Canada to provide information for ongoing marine spatial planning, including potential wave energy projects. In particular, we conducted a spatial overlap analysis with a variety of existing uses and ecological characteristics, and a quantitative compatibility analysis with commercial fisheries data. We found that wave power and harvestable wave energy gradually increase offshore as wave conditions intensify. However, areas with high economic potential for wave energy facilities were closer to cable landing points because of the cost of bringing energy ashore and thus in nearshore areas that support a number of different human uses. We show that the maximum combined economic benefit from wave energy and other uses is likely to be realized if wave energy facilities are sited in areas that maximize wave energy NPV and minimize conflict with existing ocean uses. Our tools will help decision-makers explore alternative locations for wave energy facilities by mapping expected wave energy NPV and helping to identify sites that provide maximal returns yet avoid spatial competition with existing ocean uses.

Medullary carcinoma (MC) is a rare subtype of colorectal cancer, which presents with poorly differentiated histology and is often confused with conventional adenocarcinoma of the colon. While this form of colorectal cancer is rare, it often does not meet the high-risk criteria to qualify for adjuvant chemotherapy even with a favorable prognosis. Diagnosis of MC is a proven difficulty because of the lack of immunohistochemical stains on pathology seen in adenocarcinoma of the colon. Unlike adenocarcinoma of the colon, distant metastasis is rare. Patients diagnosed with MC have one- and two-year survival rates of 93% and 74%, respectively. The patient was a 75-year-old female diagnosed with MC of the sigmoid colon and a large uterine fibroid. In this case report, we discuss the high-risk indications of colorectal cancer and the recommended treatment of patients with stage II MC of the colon.

Michael Talkowski, David FitzPatrick, Erica Davis and colleagues report rare inherited or de novo missense variants in SMCHD1 in arhinia patients. Some of the same mutations in SMCHD1 are known to cause a phenotypically distinct muscular dystrophy disorder, FSHD2, and the distinct clinical features of the two disorders suggests that additional genes interact with SMCHD1 to cause arhinia. Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans -acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes.

Mantle cell lymphoma (MCL) is a type of non-Hodgkin (B-cell) lymphoma (NHL) with manifestations ranging from indolent to aggressive disease. This type of NHL is predominately found in western countries and affects men more often than women (M:F 2:1). The median age of diagnosis with the disease is around 60 years of age. In this report, the patient is a 68-year-old female who had an atraumatic splenic rupture with no past medical history of trauma. She presented to the emergency department with severe abdominal pain in her left upper quadrant. An emergency splenectomy was executed successfully, and the patient was stabilized. In this case report, we will discuss the pathogenesis, clinical presentation, known clinical treatment, diagnostic testing, and atraumatic splenic rupture.

Large bowel obstruction (LBO) accounts for nearly 25% of all bowel occlusions. LBO is managed as a surgical emergency due to its increased risk of bowel perforation. Nearly, 2% to 4% of all surgical admissions are a result of LBO. The most common pathological development of LBO remains colonic malignancy, representing approximately 60% of cases. Other etiology includes abdominal adhesions, diverticulosis, hernia, inflammatory bowel disease (IBD), and in rare cases endometriosis. In this report, the patient is a 36-year-old female with an LBO, originally thought to be a complication of diverticulitis. However, it was confirmed that the obstruction was a result of endometriosis tissue adherence to the colonic wall narrowing the intestinal lumen. The patient presented to the emergency department (ED) with nausea, vomiting, and abdominal pain that started six weeks prior. In this case report, we will discuss the rare complication of endometriosis causing LBO, clinical presentation, diagnosis, and management.