Digital Commons Network^™

New, Potent, Small Molecule Agonists Of Tyrosine Kinase Receptors Attenuate Dry Eye Disease, Zhiyuan Yu, Shaon Joy, Tianxiong Mi, Ghasem Yazdanpanah, Kevin Burgess, Cintia S De Paiva

Faculty, Staff and Students Publications

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin3 (NT-3) bind to tyrosine kinase (Trk) receptors, TrkA, TrkB, and TrkC, respectively. This study investigated the efficacy of novel molecule agonists of Trk receptors in an in vivo model of dry eye disease (DED). Small molecule TrkC agonist (C1) and a pan-Trk agonist (pan) were synthesized for this. C57BL/6J mice were subjected to desiccating stress (DS) and received bilateral eye drops of C1, pan, or vehicle (2x/day). Dry eye signs, inflammation and expression of corneal barrier function, and conjunctival goblet cell (GC) densities were measured as part of the DED …

Targeting Type I Interferons In Systemic Lupus Erythematous, Sebastian Bruera, Thandiwe Chavula, Riya Madan, Sandeep K Agarwal

Faculty, Staff and Students Publications

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with systemic clinical manifestations including, but not limited to, rash, inflammatory arthritis, serositis, glomerulonephritis, and cerebritis. Treatment options for SLE are expanding and the increase in our understanding of the immune pathogenesis is leading to the development of new therapeutics. Autoantibody formation and immune complex formation are important mediators in lupus pathogenesis, but an important role of the type I interferon (IFN) pathway has been identified in SLE patients and mouse models of lupus. These studies have led to the development of therapeutics targeting type I IFN and related pathways for …

Metabolic Targeting, Immunotherapy And Radiation In Locally Advanced Non-Small Cell Lung Cancer: Where Do We Go From Here?, Annika Dhawan, Phillip M Pifer, Vlad C Sandulache, Heath D Skinner

Faculty, Staff and Students Publications

In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with …

Reduced Pro-Inflammatory Dendritic Cell Phenotypes Are A Potential Indicator Of Successful Peanut Oral Immunotherapy, Sara Anvari, Levi B Watkin, Charles G Minard, Kimberly Schuster, Oluwatomi Hassan, Aikaterini Anagnostou, Jordan S Orange, David B Corry, Carla M Davis

Faculty, Staff and Students Publications

Dendritic cells are important mediators in the early presentation of antigen and regulation of the differentiation of T cells. Peanut oral immunotherapy (POIT) results in desensitization in most peanut allergic individuals (responders), but not in others due to allergic reactions (non-responders). Delineation of early immunologic changes contributing to desensitization would help clarify the POIT mechanism of action. We analyzed dendritic cells in 15 pediatric subjects (5-12 years) undergoing a phase 1 single-center POIT study. We examined dendritic cells at baseline, 6-, 12-, 18- and 24-weeks after initiation of POIT and responders of therapy were compared to non-responders and healthy controls. …

Social Disorganisation Theory And Violent Crime: A Spatial-Econometric Analysis Of Chicago And Sydney, Anthony N. Greening

Theses: Doctorates and Masters

The spatialisation of violent crime is explored in two large case studies, Chicago and Sydney, using spatial econometric methods and macro-sociological variables derived from Social Disorganisation Theory.

Social Disorganisation Theory (SDT) is introduced in terms of its formulation in response to highly specific conditions arising in Chicago, as well as its adoption of methodological and theoretical developments from existing traditions. This specificity belies its breadth of application and enduring presence in criminology. With “Social Disorganisation Theory” hosting a wealth of highly nuanced academic dialogue conducted under its banner, current incarnations of SDT appear as branches on an evolutionary tree. This …

A Privacy Preserving Online Learning Framework For Medical Diagnosis Applications, Trang Pham Ngoc Nguyen

Theses: Doctorates and Masters

Electronic Health records are an important part of a digital healthcare system. Due to their significance, electronic health records have become a major target for hackers, and hospitals/clinics prefer to keep the records at local sites protected by adequate security measures. This introduces challenges in sharing health records. Sharing health records however, is critical in building an accurate online diagnosis framework. Most local sites have small data sets, and machine learning models developed locally based on small data sets, do not have knowledge about other data sets and learning models used at other sites.

The work in this thesis utilizes …

Russian Logics And The Culture Of Impossible: Part Ii: Reinterpreting Algorithmic Rationality, Ksenia Tatarchenko, Anya Yermakova, Liesbeth De Mol

Research Collection School of Social Sciences

This article reinterprets algorithmic rationality by looking at the interaction between mathematical logic, mechanized reasoning, and, later, computing in the Russian Imperial and Soviet contexts to offer a history of the algorithm as a mathematical object bridging the inner and outer worlds, a humanistic vision that we, following logician Vladimir Uspensky, call the “culture of the impossible.” We unfold the deep roots of this vision as embodied in scientific intelligentsia. In Part I, we examine continuities between the turn-of-the-twentieth-century discussions of poznaniye—an epistemic orientation towards the process of knowledge acquisition—and the postwar rise of the Soviet school of mathematical logic. …

The Lives Of Late Soviet Science, 1945-1991, Grégory Dufaud, Ksenia Tatarchenko

Research Collection College of Integrative Studies

This study explores the multifaceted landscape of Soviet science from the end of World War II to the dissolution of the USSR in 1991. It examines the interplay between scientific innovation and political ideology, highlighting how the state shaped research agendas and scientific practices during a period marked by both significant achievements and profound challenges. Through an analysis of key scientific institutions, prominent figures, and pivotal projects, the study illustrates the tensions between ideological constraints and the pursuit of knowledge. Additionally, it addresses the impacts of international collaboration and competition during the Cold War, revealing how these dynamics influenced scientific …

Interest-Based Incorporation: Statutory Realism Exploring Federalism, Delegation, And Democratic Design, Sheldon Evans

Scholarship@WashULaw

Statutory interpretation is a unique legal field that appreciates fiction as much as fact. For years, judges and scholars have acknowledged that canons of interpretation are often based on erudite assumptions of how Congress drafts federal statutes. But a recent surge in legal realism has shown just how erroneous many of these assumptions are. Scholars have created a robust study of congressional practices that challenge many formalist canons of interpretation that are divorced from how Congress thinks about, drafts, and enacts federal statutes. This conversation, however, has yet to confront statutory incorporation, which describes when Congress incorporates state law into …

International Environmental Law At Its Semicentennial: The Stockholm Legacy, Melissa (M.J.) Durkee

Scholarship@WashULaw

The 1972 United Nations Conference on the Human Environment produced the Stockholm Declaration, an environmental manifesto that forcefully declared a human right to environmental health and birthed the field of modern international environmental law. The historic event powerfully “dramatized . . . the unity and fragility of the biosphere,” sparking a remarkable period of international legal innovation and cooperation on environmental protection in the decades to come.

The Stockholm Declaration can be rightly celebrated for putting environmental issues on the international legal agenda and driving the development of environmental law at the domestic level around the world. At the same …

Standing For Rivers, Mountains - And Trees - In The Anthropocene, David Takacs

Faculty Scholarship

In his well-known article, Should Trees Have Standing?—Toward Legal Rights for Natural Objects, Professor Christopher Stone proposed that courts grant nonhuman entities standing as plaintiffs so their interests may directly represented in court. In this Article, I review Stone’s ideas about standing and our relationship with the natural environment and describe the current, burgeoning, widespread trend toward granting not just standing, but legal rights and legal personhood to rivers, mountains, and other natural entities. I analyze the ways in which courts and legislatures in New Zealand, Australia, Colombia, and elsewhere are addressing concerns similar to Stone’s with expansive, even radical …

The Price Tag Of "Pay-For-Delay", Robin C. Feldman

Faculty Scholarship

In a landmark decision nearly a decade ago, the U.S. Supreme Court opened the door for antitrust suits against brand and generic pharmaceutical companies who engage in collusive settlements to delay the time for the generic to come to market. With these “pay-for-delay” agreements, brand-name companies offer prospective generics some form of compensation in exchange for the generic’s promise not to enter the market until an agreed-upon date. Laying the groundwork for the lawsuit that would eventually lead to the Actavis decision, the Federal Trade Commission (“FTC”) published a study estimating that pay-for-delay agreements cost American consumers $3.5 billion annually, …

Captive Generics: The Wolf In Sheep’S Clothing, Robin C. Feldman

Faculty Scholarship

No abstract provided.

Collective Cognitive Capital, Emily R. Murphy

Faculty Scholarship

This Article calls for a new project for law and neuroscience. It outlines a structural, not individual, application of brain and behavioral science that is aligned with the general goal of basic science research: improving the lives of citizens with a better un- derstanding of the human experience. It asks brain and behavioral science to move explicitly into public policy territory, and specifically onto ground more traditionally occupied by economists—but in ways the project of “behavioral economics” has not yet ventured. Put sim- ply, policy analysts should focus on brains—“collective cognitive capital”—with the same intensity with which they focus on …

Challenges With Defining Pharmaceutical Markets And Potential Remedies To Screen For Industry Consolidation, Robin Feldman, Brent D. Fulton, Jamie R. Godwin, Richard M. Scheffler

Faculty Scholarship

Context: Dramatic increases in pharmaceutical merger and acquisition (M&A) activity since 2010 suggest we are in the midst of a third wave of industry consolidation. Methods: The authors reviewed 168 economic, legal, medical, industry, and government sources to examine the effects of consolidation on competition and innovation and to explore how industry attributes complicate M&A regulation in a pharmaceutical context. Findings: The authors find that, in spite of certain metrics that might argue otherwise, con- solidation consistently reduces innovation and harms the public good. They also find that several factors within the pharmaceutical industry impede proper evaluation of proposed mergers. …

Brains Without Money: Poverty As Disabling, Emily R. Murphy

Faculty Scholarship

e United States has long treated poverty and disability as separate legal and social categories, a division grounded in widespread assumptions about the “deserving” and “undeserving” poor. In the case of disability, individuals generally are not thought to be morally responsible for their disadvantage, whereas in the case of poverty, individuals are assumed to be at fault for their disadvantage and are therefore less deserving of aid. This Article argues that recent advances in brain and behavioral science undermine the factual basis for those assumptions. Poverty inhibits brain development during childhood and, later in life, adversely affects cognitive capacities that …

Egg-Freezing, Uterine Transplants, And In Vitro Gametogenesis: Disruptive Or Normalizing Reproductive Technologies?, Radhika Rao

Faculty Scholarship

In the last year, headlines have heralded the introduction of several radical new technologies that promise to revolutionize procreation and transform our understanding of reproduction. In March 2021, for example, scientists revealed that mouse embryos had been grown in" artificial wombs" for 11 days, roughly half the animal's natural gestation period. According to Jacob Hanna, the biologist at the Weizmann Institute of Science in Israel who led the research team: "This sets the stage for other species. I hope that it will allow scientists to grow human embryos until week five." At the same time, two groups of researchers reported …

Advertising Medicine: Selling The Cure, Robin Feldman

Faculty Scholarship

Although most countries forbid advertising medicine to patients, “direct-to- consumer advertising” has flourished in the United States over the past century. Research shows that the practice prompts inappropriate prescriptions and disadvantages generic competitors, leading to adverse drug reactions and increased prescription drug spending. Nevertheless, a comprehensive regulatory system for direct-to-consumer advertising continues to escape the grasp of policymakers. Regulatory authority has bounced between the Federal Trade Commission (FTC) and the Food and Drug Administration (FDA), where primary jurisdiction now resides. Since the FDA assumed responsibility, the agency’s only major regulatory initiative has been to minimize disclosure requirements for advertisements. Enforcement …

Trade Secrets In Biologic Medicine: The Boundary With Patents, Robin Feldman

Faculty Scholarship

Can something be both open and secret? That is the conundrum facing society as trade secret rights chafe against patent rights in cutting-edge, biologic medicine. The conflict is unsurprising. Trade secret has emerged as a relatively late bloomer among the family of intellectual property rights and only recently has begun to establish the boundaries of its own space, a process in which it will inevitably knock against other intellectual property doctrines already occupying their own domains. Nor is it surprising that the clash would arise in a fast-moving area of medical science. From insulin products, to cancer treatments, to mRNA …

An Open Trial Of Acceptance And Commitment Therapy With Exposure And Response Prevention In An Intensive Outpatient Setting For Adults With Ocd, L. K. Capel, P. Zurita-Ona, C. Muller, Michael P. Twohig

Psychology Faculty Publications

Intensive outpatient (IOP) treatment settings for adults with obsessive-compulsive disorder (OCD) are common, but data on their effectiveness is limited. The effectiveness of IOP treatment for adults with OCD using combined Acceptance and Commitment Therapy (ACT) and Exposure and Response Prevention (ERP) was studied with eight adults. The intervention was 15 hours per week for three weeks. Measures were collected at pre-treatment, one-week, two-weeks, post-treatment, and at one-month follow-up. At the end of treatment, all participants were in the mild range of OCD symptom severity with a mean symptom decrease of 58%. Psychological inflexibility, depression, anxiety and stress significantly decreased …

The Experiences Of The Elderly Transitioning From Home To The Nursing Home Setting, Brent James Munson

Theses and Dissertations

Elderly persons transitioning from home to a nursing home setting may struggle with unaddressed mental health issues. The problem addressed in this study involved a lack of evidence regarding how elderly individuals experience these transitions in living from their own perspectives. The purpose of this study was to better understand the lived experiences of elderly people who are making the transition from home to a nursing home setting.

The qualitative design utilized in the research was phenomenology. Fourteen participants were interviewed to ascertain their experiences in the transition from home to a nursing home setting. Follow-up questions were formulated and …

A Comparative Evaluation Of The Effects Of Social Skills Group Training And Computer- Based Social Skills Training, Indira Hightower

Theses and Dissertations

This applied dissertation was designed to evaluate the effects of social skills training programs as a method to improve social skills in children diagnosed with autism spectrum disorder. The study sought to advance the social skills training options for children with autism spectrum disorder by comparing various evidence-based social skills training programs in hope to provide meaningful, significant, and sustainable social-emotional changes that are explicitly taught and later generalized across individuals, settings, and environments. The researcher specifically evaluated the effects of social skills group training and computer-based social skills training among the three study participants with autism spectrum disorder.

The …

Teacher Perceptions Of Classroom Management Programs To Improve Whole-School Measures Of Attendance, Disruptive Classroom Behaviors, And Academic Outcomes, Charles E. Natt, Jr

Theses and Dissertations

This qualitative case study explored how the implementation of Capturing Kids’ Hearts (CKH) and Multi-Tiered System of Supports (MTSS) classroom management programs when implemented together affected students and teachers of a Louisiana K-12 school compared with using the Positive Behavior Interventions and Supports (PBIS) program alone. Teachers at the school who had used the PBIS alone and then also used the newly implanted CKH and MTSS programs participated in in-depth interviews to examine the practical effectiveness of both program implementations upon students and classroom learning effectiveness. Teacher perceptions were also compared with ex post facto data for the school from …

Discovery Of Inhibitors Of Peptidoglycan O-Acetyltransferase B (Patb) From Neisseria Gonorrhoeae, A New Potential Antibacterial Target, Stefen Stangherlin

Theses and Dissertations (Comprehensive)

Experts project that by 2050, 10 million lives will be lost annually as a result of antimicrobial resistant infections, surpassing all current leading causes of death, and costing the global economy $100 trillion USD on healthcare efforts. To promote research and development of novel antibiotics, the World Health Organization and Centers for Disease Control and Prevention released a list of priority pathogens regarded as serious or urgent threats of antimicrobial resistance. Many pathogenic bacteria, including several priority pathogens, produce O-acetylated peptidoglycan to establish infection and avoid host immune responses. Consequently, the enzymes responsible for producing O-acetylated peptidoglycan in Gram-negative pathogenic …

Changing Snowmelt Conditions In The Western Canadian Arctic, Matthew Y. T. Tsui

Theses and Dissertations (Comprehensive)

Multidecadal Changes in Spring Snowmelt in the Western Canadian Arctic

This study investigates the changes in key aspects of snowmelt in the western Canadian Arctic. Specifically, we will look at changes in the onset of snowmelt and the duration of snowmelt between 1999 and 2019, and extended air temperature between 1957 and 2019. In addition, we will look at changes in eight meteorological variables during the melt period. It was found that the onset of snowmelt occurred 14 days earlier, while the melt period ends 20 days earlier than 20 years ago. As a result, the duration of melt period …

Exploring The Relationship Between Drought And Population Change On The North American Great Plains, 1970-2010, George Heath

Theses and Dissertations (Comprehensive)

Through the second half of the 20th century, the North American Great Plains saw widespread rural out-migration, a continuation of trends that began with the Dust Bowl crisis during the Great Depression of the 1930s. As part of a wider academic focus on the roles climate and environmental changes have on migration, this research project sought to understand the relationship between drought conditions and rural population decline on the Great Plains. In this explorative research, census population data for Canada and the US from 1970-2010 were analyzed along with temperature, precipitation, and Palmer Drought Severity Index data for the same …

Imagining White Victims And Punishing Black Trauma: Whiteness, Anti-Blackness, Trauma, And Social Work In Canadian K-12 Schools, Christine Mayor

Theses and Dissertations (Comprehensive)

This study critically examined how whiteness and anti-Blackness structure Canadian school social workers’ understanding and responses to students’ expressions of trauma in K-12 schools. Very few studies have previously explored the damage that increasingly popular trauma-engaged school programs may be doing, particularly to Black students. Therefore, this study addressed the role that school social workers play in reproducing harm for racialized, and especially Black, students when implementing trauma-engaged practices.

This critical qualitative study used an innovative methodology combining fictional vignettes and semi-structured interview questions with Ontario school social workers (n=19). Data were analyzed using critical whiteness, anti-Blackness, and critical trauma …

Influence Of Dissolved Organic Matter On Phosphate Interactions With Hydrous Ferric Oxides, Alaa Hasan Alsherbi

Theses and Dissertations (Comprehensive)

Phosphorus, iron oxides, and dissolved organic matter (DOM) are components present in all aquatic systems. Excess amounts of phosphorus in aquatic systems have the potential for toxic effects, in particular, contributing to eutrophication. Most of the previous studies performed looked at the surface complexation of inorganic phosphate anions (P) to mineral surfaces such as hydrous ferric oxide (HFO). However, the role of DOM on the interactions between HFO and P is unknown. This study investigates the influence of DOM on the surface complexation of P onto HFO surfaces. Moreover, this study looks at the possibility of cation bridging formation (Ca …

Exploring Visitor Perceptions And Behaviours Related To Ticks And Lyme Disease Risk In An Ontario Protected Area, Ryan Brady

Theses and Dissertations (Comprehensive)

Lyme disease is the most common vector-borne zoonosis in North America and over the past decade, reported cases of the disease have been rapidly increasing in many regions throughout Canada. The relative novelty of this public health threat presents nature-based tourism and recreation organizations with a range of policy and management challenges. Currently, there is a limited understanding of public perceptions and behaviours associated with tick and Lyme disease risk, especially within a Canadian parks and protected areas visitation and visitor experience context. To address this practical and scholarly knowledge gap, this study utilized in-situ surveys to explore visitor perceptions, …

The Untended Garden: How Adoptees Navigate Relationships With First Family Members, Dawn Michele Mccormick Tracz

Theses and Dissertations (Comprehensive)

This research explores how people who were adopted over the age of 6 years old in open adoption arrangements navigate ongoing relationships with first family members. It explores perceptions of how a connection with both adoptive and first family members impacts self-concept. Using an interpretivist-constructivist lens, the narratives of four women are presented and analyzed. In addition to qualitative interviews, each participant was invited to create images that represented relationships with significant family members. The narratives are re-presented in detail adhering closely to the teller’s organization and emphases. In the analysis, themes related to relationships with first family members and …