Coverage Properties of the Inverse Sinh Transformation and the Adjusted Wald Confidence Intervals for the Odds Ratio and the Relative Risk.

The inverse sinh transformation on the Woolf interval is used to calculate the confidence interval for the odds ratio and the relative risk in a 2 x 2 table. According to Robert Newcombe, the new interval should improve the coverage probabilities and shorten the width of the confidence interval for these ratios, but the new interval requires evaluation of coverage properties. In this thesis, we will evaluate the exact coverage properties of this modified interval in extreme cases. Also, we will compare the coverage properties of this new interval to other widely-used adjusted intervals. Through comparisons of exact coverage probabilities and interval widths, we will discover if Newcombe\u27s inverse sinh transformation provides better coverage properties than the adjusted methods

Residential development choices and consequences: Urban land cover change, perceptions and value of alternative subdivision designs, and the benefits of protected ecosystem services

Municipal officials are often faced with difficult decisions about land uses in and around city boundaries. Urban expansion often causes negative environmental impacts, but there are designs for development which can mitigate some of these effects at the site scale. This dissertation examines urban land cover change in four Iowa cities, examines familiarity with and value for conservation subdivision (CSD) and low-impact design (LID) features, and explores how conservation subdivision design can protect urban ecosystem services. Public datasets and GIS software were used to assess land cover change for four municipalities in Iowa as a framework for predicting land cover change impacts by determining where loss of natural areas has occurred and where future losses are most likely to happen. Urban land cover increased by 28-80% in the four communities examined, primarily involving transitions from grassland and cropland. Losses of mature forest areas occurred (348 to 1335 ha) but were masked by transitions of other lands to early-successional forests. A contingent valuation survey of 777 households and experimental real estate negotiations with 27 participants in Ames, IA assessed residents\u27 familiarity with alternative residential designs and estimated their willingness to pay for CSD and LID features. Most respondents were not familiar with CSD or LID features, but indicated willingness to pay for some of them (52% indicated WTP for buffered streams, 66% for rain gardens), except for clustered housing (only 27%). Negotiation participants indicated added value for homes in neighborhoods with integrated forest (+22% increment) and open spaces (+17%), and streams buffered by forest cover (+13%). A spatial hedonic model estimated effects on housing values and indicated that the presence of neighborhood-owned forest and water features had positive effects on housing prices, both increasing the value of a home by approximately 6%. Surveys and focus groups involving developers and city officials assessed their familiarity with, and interest in, alternative development designs. Developers and planners were more familiar with LID than CSD, but indicated misperceptions about both designs. Both groups also indicated a preference for alternative designs compared to standard designs. Subdivision regulations and perceived lack of demand were identified as barriers to wider implementation of CSD and LID approaches. Alternative designs could provide protection for ecosystem services in urban areas if implementation is goal-oriented, monitored for effectiveness, and when the design is configured to create broad appeal

The trouble with cover crops: Farmers’ experiences with overcoming barriers to adoption

Cover crops are known to promote many aspects of soil and water quality, yet estimates find that in 2012 only 2.3% of the total agricultural lands in the Midwestern USA were using cover crops. Focus groups were conducted across the Corn Belt state of Iowa to better understand how farmers confront barriers to cover crop adoption in highly intensive agricultural production systems. Although much prior research has focused on analyzing factors that help predict cover crop use on farms, there is limited research on how farmers navigate and overcome field-level (e.g. proper planting of a cover crop) and structural barriers (e.g. market forces) associated with the use of cover crops. The results from the analysis of these conversations suggest that there is a complex dialectical relationship between farmers\u27 individual management decisions and the broader agricultural context in the region that constrains their decisions. Farmers in these focus groups shared how they navigate complex management decisions within a generally homogenized agricultural and economic landscape that makes cover crop integration challenging. Many who joined the focus groups have found ways to overcome barriers and successfully integrate cover crops into their cropping systems. This is illustrated through farmers\u27 descriptions of their ‘whole system’ approach to cover crops management, where they described how they prioritize the success of their cover crops by focusing on multiple aspects of management, including changes they have made to nutrient application and modifications to equipment. These producers also engage with farmer networks to gain strategies for overcoming management challenges associated with cover crops. Although many participants had successfully planted cover crops, they tended to believe that greater economic incentives and/or more diverse crop and livestock markets would be needed to spur more widespread adoption of the practice. Our results further illustrate how structural and field-level barriers constrain individual actions, as it is not simply the basic agronomic considerations (such as seeding and terminating cover crops) that pose a challenge to their use, but also the broader economic and market drivers that exist in agriculturally intensive systems. Our study provides evidence that reducing structural barriers to adoption may be necessary to increase the use of this conservation practice to reduce environmental impacts associated with intensive agricultural production

In-Space Structural Assembly: Applications and Technology

As NASA exploration moves beyond earth's orbit, the need exists for long duration space systems that are resilient to events that compromise safety and performance. Fortunately, technology advances in autonomy, robotic manipulators, and modular plug-and-play architectures over the past two decades have made in-space vehicle assembly and servicing possible at acceptable cost and risk. This study evaluates future space systems needed to support scientific observatories and human/robotic Mars exploration to assess key structural design considerations. The impact of in-space assembly is discussed to identify gaps in structural technology and opportunities for new vehicle designs to support NASA's future long duration missions

IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs

The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22–blocking agents in B-cell–mediated autoimmune conditions

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Identification of Novel Single Nucleotide Polymorphisms in Inflammatory Genes as Risk Factors Associated with Trachomatous Trichiasis

infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT). While there are a number of environmental and behavioral risk factors for trachoma, genetic factors that influence inflammation and TT risk remain ill defined. = 0.001] with the combination of TNFA (-308A), LTA (252A), VCAM1 (-1594C), SCYA 11 (23T) minor allele, and the combination of TNFA (-308A), IL9 (113M), IL1B (5′UTR-T), and VCAM1 (-1594C). However, TT risk increased 13.5 times [odds ratio = 13.5 (95% confidence interval 3.3–22), p = 0.001] with the combination of TNFA (-308G), VDR (intron G), IL4R (50V), and ICAM1 (56M) minor allele.Evaluating genetic risk factors for trachoma will advance our understanding of disease pathogenesis, and should be considered in the context of designing global control programs