Digital Commons Network^™

Longitudinal Natural History Studies Based On Real-World Data In Rare Diseases: Opportunity And A Novel Approach, Laura Ann Adang, Anjana Sevagamoorthy, Omar Sherbini, Jamie L Fraser, Joshua L Bonkowsky, Francesco Gavazzi, Russel D'Aiello, Nicholson B Modesti, Emily Yu, Sylvia Mutua, Emma Kotes, Justine Shults, Ariel Vincent, Lisa T Emrick, Stephanie Keller, Keith P Van Haren, Sarah Woidill, Isabella Barcelos, Amy Pizzino, Johanna L Schmidt, Florian Eichler, Ali Fatemi, Adeline Vanderver

Faculty, Staff and Students Publications

Growing interest in therapeutic development for rare diseases necessitate a systematic approach to the collection and curation of natural history data that can be applied consistently across this group of heterogenous rare diseases. In this study, we discuss the challenges facing natural history studies for leukodystrophies and detail a novel standardized approach to creating a longitudinal natural history study using existing medical records.

Prospective studies are uniquely challenging for rare diseases. Delays in diagnosis and overall rarity limit the timely collection of natural history data. When feasible, prospective studies are often cross-sectional rather than longitudinal and are unlikely to capture …

The Evidence Is Mounting: Insurance Coverage Disruptions Lead To Worse Outcomes Among Children Diagnosed With Cancer, Philip J Lupo, Christina L Magyar

Faculty, Staff and Students Publications

No abstract provided.

Validation Of Single-Nucleotide Mosaic Variants Through Droplet Digital Pcr, Christopher M Grochowski, Richard A Gibbs, Harsha Doddapaneni

Faculty, Staff and Students Publications

The detection, validation, and subsequent interpretation of potentially mosaic single-nucleotide variants (SNV) within next-generation sequencing data remains a challenge in both research and clinical laboratory settings. The ability to identify mosaic variants in high genome coverage sequencing data at levels of 1% or lower underscores the necessity for developing guidelines and best practices to verify these variants orthogonally. Droplet digital PCR (ddPCR) has proven to be a powerful and precise method that allows for the determination of low-level variant fractions within a given sample. Herein we describe two precise ddPCR methods using either a fluorescent TaqMan hydrolysis probe approach or …

Single-Tube Four-Target Lateral Flow Assay Detects Human Papillomavirus Types Associated With Majority Of Cervical Cancers, Maria Barra, Megan Chang, Mila P Salcedo, Kathleen Schmeler, Michael Scheurer, Mauricio Maza, Leticia Lopez, Karla Alfaro, Rebecca Richards-Kortum

Faculty, Staff and Students Publications

Isothermal nucleic acid amplification methods have many advantages for use at the point of care. However, there is a lack of multiplexed isothermal amplification tests to detect multiple targets in a single reaction, which would be valuable for many diseases, such as infection with high-risk human papillomavirus (hrHPV). In this study, we developed a multiplexed loop-mediated isothermal amplification (LAMP) reaction to detect the three most common hrHPV types that cause cervical cancer (HPV16, HPV18, and HPV45) and a cellular control for sample adequacy. First, we characterized the assay limit of detection (LOD) in a real-time reaction with fluorescence readout; after …

Substance Misuse In Adults: A Primary Care Approach, Alicia Kowalchuk, Sandra J Gonzalez, Roger J Zoorob

Faculty, Staff and Students Publications

Substance misuse and substance use disorder continue to be major causes of morbidity and mortality, and family physicians are well positioned to provide evidence-based prevention and management for these conditions. Of people 12 years and older, 13% reported using a nonprescribed controlled substance in the past month, and 24% had at least one episode of binge drinking of alcohol, defined as five or more drinks for men and four or more drinks for women on one occasion. Benzodiazepines are used by 12% of the U.S. population. Clinicians should incorporate standardized screening and brief intervention for use of alcohol and other …

Age-Related Differences In The Mouse Corneal Epithelial Transcriptome And Their Impact On Corneal Wound Healing, Anmar Abu-Romman, Kaitlin K Scholand, Gowthaman Govindarajan, Zhiyuan Yu, Sonali Pal-Ghosh, Mary A Stepp, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: Aging is a risk factor for dry eye. We sought to identify changes in the aged mouse corneal epithelial transcriptome and determine how age affects corneal sensitivity, re-epithelialization, and barrier reformation after corneal debridement.

METHODS: Corneal epithelium of female C57BL/6J (B6) mice of different ages (2, 12, 18, and 24 months) was collected, RNA extracted, and bulk RNA sequencing performed. Cornea sensitivity was measured with an esthesiometer in 2- to 3-month-old, 12- to 13-month-old, 18- to 19-month-old, and 22- to 25-month-old female and male mice. The 2-month-old and 18-month-old female and male mice underwent unilateral corneal debridement using a …

Piezo1 Regulates Meningeal Lymphatic Vessel Drainage And Alleviates Excessive Csf Accumulation, Dongwon Choi, Eunkyung Park, Joshua Choi, Renhao Lu, Jin Suh Yu, Chiyoon Kim, Luping Zhao, James Yu, Brandon Nakashima, Sunju Lee, Dhruv Singhal, Joshua P Scallan, Bin Zhou, Chester J Koh, Esak Lee, Young-Kwon Hong

Faculty, Staff and Students Publications

Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of …

A Biophysically Constrained Brain Connectivity Model Based On Stimulation-Evoked Potentials, William Schmid, Isabel A Danstrom, Maria Crespo Echevarria, Joshua Adkinson, Layth Mattar, Garrett P Banks, Sameer A Sheth, Andrew J Watrous, Sarah R Heilbronner, Kelly R Bijanki, Alessandro Alabastri, Eleonora Bartoli

Faculty, Staff and Students Publications

BACKGROUND: Single-pulse electrical stimulation (SPES) is an established technique used to map functional effective connectivity networks in treatment-refractory epilepsy patients undergoing intracranial-electroencephalography monitoring. While the connectivity path between stimulation and recording sites has been explored through the integration of structural connectivity, there are substantial gaps, such that new modeling approaches may advance our understanding of connectivity derived from SPES studies.

NEW METHOD: Using intracranial electrophysiology data recorded from a single patient undergoing stereo-electroencephalography (sEEG) evaluation, we employ an automated detection method to identify early response components, C1, from pulse-evoked potentials (PEPs) induced by SPES. C1 components were utilized for a …

How Hydrophobicity, Side Chains, And Salt Affect The Dimensions Of Disordered Proteins, Michael C Baxa, Xiaoxuan Lin, Cedrick D Mukinay, Srinivas Chakravarthy, Joseph R Sachleben, Sarah Antilla, Nina Hartrampf, Joshua A Riback, Isabelle A Gagnon, Bradley L Pentelute, Patricia L Clark, Tobin R Sosnick

Faculty, Staff and Students Publications

Despite the generally accepted role of the hydrophobic effect as the driving force for folding, many intrinsically disordered proteins (IDPs), including those with hydrophobic content typical of foldable proteins, behave nearly as self-avoiding random walks (SARWs) under physiological conditions. Here, we tested how temperature and ionic conditions influence the dimensions of the N-terminal domain of pertactin (PNt), an IDP with an amino acid composition typical of folded proteins. While PNt contracts somewhat with temperature, it nevertheless remains expanded over 10-58°C, with a Flory exponent, ν, >0.50. Both low and high ionic strength also produce contraction in PNt, but this contraction …

Evaluating Distributed Software Design Conformance Through Trace Comparison, Reid Barry Anderson

Theses and Dissertations

The design of a system and its implementation are two tasks often carried out by different individuals on a development team and can occur weeks or months apart. This creates a potential for divergence between real behavior and the designed model that the implementation is intended to match. Particularly as time passes and individuals that were present for the original conception of the design leave, a system can begin to lose coherence and drift apart from intended design principles. Even with a robust and high-quality design for a software system, more is needed to guarantee that the key details of …

Advancing Bridge Hydraulic Assessment With Hec-Ras 2d And Bathymetry Modeling In Arcgis Pro Using Hycat Asv Data, Daniel Iancu

Theses and Dissertations

This research centers on verifying an accurate and reliable method in deriving river bathymetry near bridge sites, which leads to critical enhancement of bridge scour analysis. The structural integrity of bridges is paramount, and accurate scour analysis is a cornerstone in civil engineering and public safety. Existing methods, though reliable and very well cemented in practice, may be improved with more precise water velocity estimates, which is essential for thorough bridge scour evaluations. Bridge assessments utilize bathymetry measurements in significant spots and or map out the continuous surface at the bottom of the river. This study seeks to validate if …

A Qualitative Case Study Of Students' Of Color Perceptions And Experiences Of Academic Success In College Algebra At Snow College, Melanie Larsen Jenkins

Theses and Dissertations

This qualitative case study explored perceptions of learning support and student success, particularly for students of color who had enrolled in a college algebra course. The purpose of this study was primarily to include student voices in the conversations about student success. The study uses a qualitative case study approach in two ways: 1) to interview nine students who found success and students who did not find success in College Algebra to glean information about their personal experiences and perceptions of learning and 2) to interview three professors of College Algebra to understand their pedagogical strategies that are designed to …

Exploring Ambiguous Asteroid Taxonomic Classification, Tyler Linder

Theses and Dissertations

The Sloan Digital Sky Survey (SDSS) Moving Object Catalog (MOC) shows color variations between asteroid observations, which were observed multiple times. This is a surprising result that was not identified in the literature. Therefore, a data processing pipeline was built to extract the asteroid observations to analyze new data collected with the SMARTS 1.0m and 4m Blanco with DECam. The results appear to confirm the color variations on short timescales. However, there is still a long series of steps required before such a result can be proven, such as ensuring the level of photometric accuracy in the processing is smaller …

Metamemory And Disconfirming Feedback: An Evaluation Of The Blank Lineup Procedure, James Robert Owens

Theses and Dissertations

Evaluating an eyewitness for their efficacy is a difficult endeavor. Traditionally, scientists have used post-identification confidence to gauge the accuracy of an eyewitness. Recently, other methods are being explored to evaluate the efficacy of an eyewitness, such as, using blank lineups, measures of metamemory, and pre-identification confidence. The present study evaluated a blank lineup procedure where participants were given disconfirming feedback when they made an incorrect decision on an initial blank lineup. Participants then moved to a target present or target absent final lineup. I sought to evaluate the potential effects of disconfirming feedback using the Eyewitness Metamemory Scale (EMS) …

Using An Airship Design To Extend A Small Uncrewed Aircraft Flight Endurance, Joseph Reilly

Theses and Dissertations

One limitation of uncrewed aircraft is being unable to fly as long as needed for some operations, such as linear inspection. This research explores the flight endurance of an uncrewed aircraft using airship design. It investigates the benefits of using an airship design to increase the efficiency and extension of the flight of a small, uncrewed aerial system (sUAS). Thus, it is crucial to find ways to augment flight endurance. Two different airframes were built, and flight tested using a lifting gas to provide the lifting force and vectored thrust needed to move. Flight testing captured time in the air …

Parent’S Perspectives On The Impact Of Recurrent Otitis Media On Speech And Language Development, Andrea Rose Wilson

Theses and Dissertations

The purpose of this study is to investigate the parent’s perspective on whether otitis media delayed their child’s speech and language development. It also focuses on intervention options and the parent’s relationship with their medical providers regarding intervention options for otitis media. Research has shown the importance of early intervention; however, when it comes to recurrent otitis media, many physicians require patients to express symptoms for extended periods before surgical solutions are considered (Granath, 2021). An electronic survey was distributed to parents and caregivers on various parenting Facebook pages. The study was open for one month before the research was …

Plastic Alternatives And Substitutes In The Packaging Sector – A Uk Consumer Perspective, Sohvi Nuojua, Sabine Pahl, Richard C. Thompson

School of Biological and Marine Sciences

Alternative and substitute materials to conventional plastic packaging offer a range of potential opportunities to help reduce the environmental impacts of single-use plastic. Policymakers and industry stakeholders are currently debating measures to address the plastic pollution crisis globally, but successful implementation of new policies or packaging technologies will require understanding of consumer perspectives and consumer acceptability. The present study aimed to examine consumer perceptions around plastic alternatives and substitutes by employing a life cycle approach. The Kano model of consumer satisfaction was used to investigate how UK consumers (n = 1177) responded to a variety of environmentally relevant attributes and …

Classifying Forecasts, Michael S. Drake, James R. Moon Jr., James D. Warren

Faculty Publications

We employ a novel machine learning technique to classify analysts’ forecast revisions into five types based on how the revision weighs publicly available signals. We label these forecast types as quant, sundry, contrarian, herder, and independent forecasts. Our tests reveal that a greater diversity of forecast types within the consensus is associated with increased consensus dispersion and improved consensus accuracy. Additionally, consensus diversity is associated with an improved information environment for firms, as reflected in reduced earnings announcement information asymmetry and volatility, higher earnings response coefficients, and faster price formation. Our study sheds light on how analysts revise their forecasts …

Advances In Smoke Retrievals Using Lidar: Techniques And Applications, Natalie Midzak

Theses and Dissertations

Smoke aerosols arise from a variety of regional sources and fuel types dependent on the properties of the fire, leading to spatial variability in smoke composition and optical properties. After emission, these aerosols age and mix in the atmosphere with other aerosol species, such as sulfates, altering the optical and microphysical properties of the smoke aerosols over time. Further, smoke particles originating from biomass burning events are typically assumed to be spherical, yet non-spherical smoke particles are also reported from in situ observations. Thus, lidar ratio (extinction to backscatter ratio) and depolarization ratio exhibit spatiotemporal variability for smoke. In this …

Vehicle Crashes In Minnesota: Spatial And Temporal Patterns And Contributing Factors To Crash Severity, Bastien Koralalage Pavithra Navodi Rodrigo

Theses and Dissertations

Vehicle crashes represent a critical global issue, resulting in numerous fatalities, injuries, and significant economic and societal impacts. In response, government officials worldwide are developing strategies and policies to enhance road safety and promote sustainable transportation systems, aiming for zero fatalities and injuries. Understanding the causes of crashes is essential for these efforts. This study focuses on identifying spatial and temporal patterns and contributing factors for the crash severity of vehicle crashes in Minnesota. Spatial distribution of crash hotspots is identified and visualized using spatial autocorrelation (global Moran I), hotspot analysis (Getis–Ord Gi*), and kernel density estimation in ArcGIS Pro. …

Effect Of The Age Of Garments Used Under Real-Life Conditions On Microfibre Release From Polyester And Cotton Clothing, Andreia N. Fernandes, Larissa Z. Lara, Francesca De Falco, Andrew Turner, Richard C. Thompson

School of Geography, Earth and Environmental Sciences

The release of microfibres from fabrics during laundering represents an important source of plastic and natural microfibres to aquatic environments. Garment age - how long the garment has been used - could be a key factor influencing the rate of release, yet most studies of microfibre shedding have only assessed newly manufactured products. To this end, we quantified microfibre release during laundering in domestic washing machines from polyester (PES) and cotton garments (n = 38) used in real-life conditions for periods between 1 and 31 years with different use intensities. In addition, to better understand the factors involved in microfibre …

Big Capital & The Carceral State, Laura I. Appleman

UC Law Journal

Who is accountable for the imposition of punishment in our carceral system? The answer used to be much simpler, as we held local, state, and federal government actors responsible. In recent decades, however, our correctional system has become increasingly privatized, with deeply troubling results. All aspects of the carceral state—whether prisons, jails, juvenile detention, rehabilitation, forensic hospitals, bail, or electronic monitoring—have dramatically increased their use of privatized correctional services.

With this new world of privatized corrections, we frequently don’t know whom can be held accountable when wrongdoing occurs. The bulk of our correctional services are now provided by complicated web …

Proton Therapy Mediates Dose Reductions To Brain Structures Associated With Cognition In Children With Medulloblastoma, Julianna Sienna, Lisa S Kahalley, Donald Mabbott, David Grosshans, Anna Theresa Santiago, Arnold Dela Cruz Paulino, Thomas E Merchant, Gohar S Manzar, Hitesh Dama, David C Hodgson, Murali Chintagumpala, Mehmet Fatih Okcu, William E Whitehead, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Uri Tabori, Julie M Bennett, Anirban Das, Tim Craig, Derek S Tsang

Faculty, Staff and Student Publications

Purpose: Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy.

Methods and materials: In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed. Doses to brain structures were compared between treatment modalities. Linear mixed-effects models were used to create models of global IQ and cognitive domain scores.

Results: The mean dose and dose to …

Circulating Immune Signatures In Chronic Pancreatitis With And Without Preceding Acute Pancreatitis: A Pilot Study, Rasmus Hagn-Meincke, Dhiraj Yadav, Dana K Andersen, Santhi Swaroop Vege, Evan L Fogel, Jose Serrano, Melena D Bellin, Mark D Topazian, Darwin L Conwell, Liang Li, Stephen K Van Den Eeden, Asbjørn M Drewes, Stephen J Pandol, Chris E Forsmark, William E Fisher, Phil A Hart, Søren S Olesen, Walter G Park, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Objective: To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP).

Methods: We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons …

Family Accommodation In Children And Adolescents With Misophonia, Eric A Storch, Andrew G Guzick, Johann D'Souza, Jane Clinger, Daphne Ayton, Minjee Kook, Conor Rork, Eleanor E Smith, Isabel A Draper, Nasim Khalfe, Catherine E Rast, Nicholas Murphy, Marijn Lijfijjt, Wayne K Goodman, Matti Cervin

Center for Medical Ethics and Health Policy Staff Publications

Family accommodation (e.g., reassurance, modifying routines, assisting avoidance) has not been explored among youth with misophonia but may have important clinical and intervention implications. We examined family accommodation in 102 children and adolescents with interview-confirmed misophonia and compared its frequency and content to family accommodation in 95 children and adolescents with anxiety disorders. Findings showed that family accommodation was ubiquitous in pediatric misophonia and may be even more frequent than in youth with anxiety disorders. Assisting the child, participating in misophonia-related behaviors, and modifying family routines were endorsed by more than 70% of parents of children with misophonia. Further, compared …

Public Attitudes, Interests, And Concerns Regarding Polygenic Embryo Screening, Rémy A Furrer, Dorit Barlevy, Stacey Pereira, Shai Carmi, Todd Lencz, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Importance: Polygenic embryo screening (PES) is a novel technology that estimates the likelihood of developing future conditions (eg, diabetes or depression) and traits (eg, height or cognitive ability) in human embryos, with the goal of selecting which embryos to use. Given its commercial availability and concerns raised by researchers, clinicians, bioethicists, and professional organizations, it is essential to inform key stakeholders and relevant policymakers about the public's perspectives on this technology.

Objective: To survey US adults to examine general attitudes, interests, and concerns regarding PES use.

Design, setting, and participants: For this survey study, data were collected from 1 stratified …

Ethical Concerns For Remote Computer Perception In Cardiology: New Stages For Digital Health Technologies, Artificial Intelligence, And Machine Learning, Kristin Kostick-Quenet, Jerry Estep, Jennifer S Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Igwas: Image-Based Genome-Wide Association Of Self-Supervised Deep Phenotyping Of Retina Fundus Images, Ziqian Xie, Tao Zhang, Sangbae Kim, Jiaxiong Lu, Wanheng Zhang, Cheng-Hui Lin, Man-Ru Wu, Alexander Davis, Roomasa Channa, Luca Giancardo, Han Chen, Sui Wang, Rui Chen, Degui Zhi

Faculty, Staff and Student Publications

Existing imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on these phenotypes …

Targeted Accurate Rna Consensus Sequencing (Tarc-Seq) Reveals Mechanisms Of Replication Error Affecting Sars-Cov-2 Divergence, Catherine C Bradley, Chen Wang, Alasdair J E Gordon, Alice X Wen, Pamela N Luna, Matthew B Cooke, Brendan F Kohrn, Scott R Kennedy, Vasanthi Avadhanula, Pedro A Piedra, Olivier Lichtarge, Chad A Shaw, Shannon E Ronca, Christophe Herman

Duncan NRI Faculty and Staff Publications

RNA viruses, like SARS-CoV-2, depend on their RNA-dependent RNA polymerases (RdRp) for replication, which is error-prone. Monitoring replication errors is crucial for understanding the virus’s evolution. Current methods lack the precision to detect rare de novo RNA mutations, particularly in low-input samples such as those from patients. Here, we introduce a new targeted Accurate RNA Consensus sequencing method (tARC-seq) to accurately determine the mutation frequency and types in SARS-CoV-2, both in cell culture and clinical samples. Our findings show an average of 2.68×10−5 new errors per cycle with a C>T bias that cannot be solely attributed to APOBEC …

Single-Nucleotide Variant Calling In Single-Cell Sequencing Data With Monopogen, Jinzhuang Dou, Yukun Tan, Kian Hong Kock, Jun Wang, Xuesen Cheng, Le Min Tan, Kyung Yeon Han, Chung-Chau Hon, Woong-Yang Park, Jay W Shin, Haijing Jin, Yujia Wang, Han Chen, Li Ding, Shyam Prabhakar, Nicholas Navin, Rui Chen, Ken Chen

Faculty, Staff and Student Publications

Single-cell omics technologies enable molecular characterization of diverse cell types and states, but how the resulting transcriptional and epigenetic profiles depend on the cell's genetic background remains understudied. We describe Monopogen, a computational tool to detect single-nucleotide variants (SNVs) from single-cell sequencing data. Monopogen leverages linkage disequilibrium from external reference panels to identify germline SNVs and detects putative somatic SNVs using allele cosegregating patterns at the cell population level. It can identify 100 K to 3 M germline SNVs achieving a genotyping accuracy of 95%, together with hundreds of putative somatic SNVs. Monopogen-derived genotypes enable global and local ancestry inference …