The Genetic Architecture of Structural Renal and Urinary Tract Malformations

Structural renal and urinary tract malformations are the most common cause of kidney failure in children. These congenital anomalies of the kidneys and urinary tract (CAKUT) are a phenotypically diverse group of malformations that result from defects in embryonic kidney, ureter, and bladder development. A genetic basis for CAKUT has been proposed, with over 50 monogenic causes reported, however, a molecular diagnosis is detected in less than 20% of patients. In this thesis, I used bioinformatics and statistical genetics methodology to investigate the genetic architecture of structural renal and urinary tract malformations using whole-genome sequencing (WGS) data from the 100,000 Genomes Project. Population-based rare and common variant association testing was performed in over 800 cases and 20,000 controls of diverse ancestry seeking enrichment of single-nucleotide/indel and structural variation on a genome-wide, per-gene, and cis-regulatory element basis. Using a sequencing-based genome-wide association study (GWAS) I identified the first robust genetic associations of posterior urethral valves (PUV), the most common cause of kidney failure in boys. Bayesian fine-mapping and functional annotation mapped these two loci to the transcription factor TBX5 and planar cell polarity gene PTK7, with both signals replicated in an independent cohort. Significant enrichment of rare structural variation affecting cis-regulatory elements was also detected providing novel insights into the pathogenesis of this poorly understood disorder. I also demonstrated that the contribution of known monogenic disease to CAKUT has been overestimated and that common and low-frequency variation plays an important role in phenotypic variability. These findings support an omnigenic rather than monogenic model of inheritance for CAKUT and are consistent with the extensive genotypic-phenotypic heterogeneity, variable expressivity, and incomplete penetrance observed in this condition. Finally, this work demonstrates the value of sequencing-based GWAS methodology in rare disease, beyond conventional monogenic gene discovery, and provides strong support for an inclusive diverse-ancestry approach

Allied Health Regional Workforce Analysis: Bay Area Region

Analyzes the racial/ethnic composition of workers in twenty-two health occupations and graduates of healthcare education programs in the Bay Area. Examines disparities by race/ethnicity in the types of occupations held, educational attainment, and wages

Allied Health Regional Workforce Analysis: Central California

Analyzes the racial/ethnic compositions of workers in twenty-two health occupations and graduates of healthcare education programs in the Central Valley. Examines disparities by race/ethnicity in occupations held, educational attainment, and wages

Family Caregivers Resource: A Usability Study

Master's Project paper, TCC 25 Presentation, websiteSelf-care is the active practice of preserving or improving one’s health. Family caregivers, usually informal, non-health care professionals caring for a loved one, often overlook self-care while caregiving. Such oversight potentially leads to exhaustion, stress, burnout, and illness. The purpose of this usability study was to create a resource website to curate existing family caregiver resources relevant to caregivers and supporters of cancer patients. Serving the islands of Maui, Molokai, and Lāna`i, the resource site aimed to facilitate connection to local and online family caregiver resources, and reduce online research time for family caregivers, often overwhelmed with responsibilities. A user-centric (U/X) design approach was utilized to design a site responsive to mobile users. The objective of this usability study was to assess the resource site’s ease-of-use, the perceived value of the site, and to assess the feelings of user self-efficacy after use of the resource site. Twelve participants assessed the navigability of the site and the value of the content. Verbal feedback from participants during the study and data from post-usability surveys indicated that participants found the responsive site moderately easy to navigate, found high value in the content, and expressed high levels of confidence in understanding self-care after completion of the usability study

Perspective : Presuming autistic communication competence and reframing facilitated communication

Debate surrounding the validity of the method of supported typing known as facilitated communication (FC) has been continuous since its inception in the 1990s. Views are polarized on whether FC can be considered an authenticated method for use by people with complex communication needs (CCN) or significant challenges in speech, language, and communication. This perspective article presents an analysis of the research arguing for—and against—the use of FC, combined with the lived experience knowledge of autistic adults who utilize FC, to rehabilitate its current standing as discredited and unevidenced. By considering extant qualitative and quantitative studies, as well as personal accounts of the use of this particular Augmentative and Alternative Communication (AAC) method, the authors argue that the current dismissal of FC is rooted in ableist and outdated approaches. FC research should be reconsidered and reconducted using current best practice autism research approaches, including coproduction and a presumption of autistic communication competence, to assess its validity as a potential AAC method for autistic individuals

"Deaf Learning": Using a Visual Method to Teach Written Language to the Deaf

The majority of deaf people prefer to use the visual channel for communication, choosing a national sign language instead of a spoken language. In many countries, Deaf education is still not bilingual, therefore deaf people frequently have problems with learning and using the written language of their country. The Erasmus+ project "Deaf Learning" addresses the need for a visually-oriented written language course for the levels from A1 to B2. The main target group is that of young deaf adults aged 16 to 25 years. A secondary target group are older deaf people who are interested in improving their written language competence

Allied Health Workforce Analysis: Sacramento-Northern California Region

Analyzes the racial/ethnic compositions of workers in twenty-two health occupations and graduates of healthcare education programs in Sacramento and northern California. Examines racial/ethnic disparities in occupations, educational attainment, and wages

Role of external inputs of nutrients to aquatic ecosystems in determining prevalence of nitrogen vs. phosphorus limitation of net primary productivity

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Howarth, R. W., Chan, F., Swaney, D. P., Marino, R. M., & Hayn, M. Role of external inputs of nutrients to aquatic ecosystems in determining prevalence of nitrogen vs. phosphorus limitation of net primary productivity. Biogeochemistry, (2021), https://doi.org/10.1007/s10533-021-00765-z.Whether net primary productivity in an aquatic ecosystem is limited by nitrogen (N), limited by phosphorus (P), or co-limited by N & P is determined by the relative supply of N and P to phytoplankton compared to their elemental requirements for primary production, often characterized by the “Redfield” ratio. The supply of these essential nutrients is affected by both external inputs and biogeochemical processes within the ecosystem. In this paper, we examine external sources of nutrients to aquatic systems and how the balance of N to P inputs influences nutrient limitation. For ocean subtropical gyres, a relatively balanced input of N and P relative to the Redfield ratio from deep ocean sources often leads to near co-limitation by N and P. For lakes, the external nutrient inputs come largely from watershed sources, and we demonstrate that on average the N:P ratio for these inputs across the United States is well above that needed by phytoplankton, which may contribute to P limitation in those lake that experience this average nutrient loading. Watershed inputs are also important for estuaries and coastal marine ecosystems, but ocean sources of nutrients are also significant contributors to overall nutrient loads. The ocean-nutrient sources of N and P are very often at or below the Redfield ratio of 16:1 molar, and can be substantially so, particularly in areas where the continental shelf is wide. This large input of coastal ocean nutrients with a low N:P ratio is one factor that may make N limitation more likely in many coastal marine ecosystems than in lakes.Preparation of this manuscript was supported by a National Science Foundation Grant # 1654845 from the Long Term Research in Environmental Biology program, a grant from the Atkinson Center for a Sustainable Future at Cornell University, and by an endowment given to Cornell by David R. Atkinson to support a professorship held by RWH