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The Influence Of Us Drug Price Dynamics On Cost-Effectiveness Analyses Of Biologics, Stephen Jon Kogut, R. Campbell, Steven D. Pearson

Pharmacy Practice and Clinical Research Faculty Publications

Objectives: This study aimed to evaluate the influence of drug price dynamics in cost-effectiveness analyses.

Methods: We evaluated scenarios involving typical US drug price increases during the exclusivity period and price decreases after the loss of exclusivity (LOE). Worked examples are presented using the Institute for Clinical and Economic Review’s assessments of tezepelumab for the treatment of severe asthma and targeted immune modulators for rheumatoid arthritis.

Results: Tezepelumab case: yearly 2% price increases during the period of exclusivity and a post-LOE price decrease of 25% yielded an incremental cost per quality-adjusted life-year (QALY) gained that increased over the base case …

A Simple And Robust Alternative To Bland-Altman Method Of Assessing Clinical Agreement, Abhaya Indrayan Prof

COBRA Preprint Series

Clinical agreement between two quantitative measurements on a group of subjects is generally assessed with the help of the Bland-Altman (B-A) limits. These limits only describe the dispersion of disagreements in 95% cases and do not measure the degree of agreement. The interpretation regarding the presence or absence of agreement by this method is based on whether B-A limits are within the pre-specified externally determined clinical tolerance limits. Thus, clinical tolerance limits are necessary for this method. We argue in this communication that the direct use of clinical tolerance limits for assessing agreement without the B-A limits is more effective …

Xpo1 As A Therapeutic Target In Gastric Cancer, Rachel Sexton

Wayne State University Dissertations

Gastric cancer is a leading cause of cancer related deaths worldwide. Throughout the world, there is around one million new diagnosed cases per year and only an approximate 25% survival rate. This disease is highly heterogeneous, chemotherapy resistant and deadly. Currently there is no gold standard for care but rather it is physician’s choice. Various chemotherapeutic agents can be used including microtubule inhibitors, DNA damaging agents and anti-metabolite compounds. We have found that nuclear export protein 1 (XPO1) is overexpressed in gastric cancer patients and cell lines compared to normal gastric tissues leading to an aggressive cancerous phenotype that is …

Electrochemistry Of Bubbles: Developing New Sensors, Promoting Gas Evolution Reactions, And Extraction Of Rare Earth Elements, Ruchiranga R. Ranaweera

Wayne State University Dissertations

This dissertation presents new analytical, electrocatalysis, and separation strategies that utilize bubble behaviors in different electrochemical systems. The first part of this dissertation focuses on the method development for PFAS preconcentration and detection. First, we present the bubble-nucleation-based electrochemical method for the selective and sensitive detection of surfactants. Our method utilizes the high surface activity of surfactant analytes to affect the electrochemical bubble nucleation and then transduces the change in nucleation condition to an electrochemical signal for determining the surfactant concentration. Using this method, we demonstrate the quantitation of perfluorinated surfactants in water, a group of emerging environmental contaminants, with …

In The Best Interest Of The Family: The Outcomes Of Children In Foster Care With An Incarcerated Parent And The Adverse Implications Of The Adoptions And Safe Families Act, Tamarie Willis

Wayne State University Dissertations

Approximately 10 million children have experienced parental incarceration at some point in their lives. An estimated 8% of children in foster care were removed because of parental incarceration, with a similar percentage annually for the past five years. Research has shown that 1 in 8 of these cases, incarcerated parents lose their parental rights, regardless of the seriousness of their offenses. The lack of coordination between systems has presented the majority of the barriers to contact between the incarcerated parents and children. And with the passing of the Adoption and Safe Families Act (ASFA) of 1997, this task has become …

Photoacoustic Imaging For Image-Guided Interventions, Samuel John

Wayne State University Dissertations

Image-guided surgeries and therapeutic procedures utilize imaging modalities to enhance the surgeon’s capability of visualizing and guiding the medical instruments within the body. One such application is the endovenous laser ablation (EVLA), which utilizes an ultrasound (US)-guided catheter carrying high power continuous wave (CW) energy for treating varicose veins. Varicose veins, a condition defined by venous insufficiency, affects nearly 40 million people in the United States annually. In EVLA procedures, US limitations including angular dependency, poor contrast-to-noise ratio, poor signal-to-noise ratio, and artifacts limit the ability of the surgeon to detect the catheter tip within the vein. Furthermore, the absence …

Identification Of Glutathionylated Cysteines Regulating Cell Migration, Dhanushika Kukulage

Wayne State University Dissertations

Cell migration is vital in many physiological processes, such as wound repair and metastasis. Impaired cell migration in wound healing may result in chronic wounds, by which 6.7 million Americans are affected, and they suffer from bacterial infections, amputations, increased mortality, and depression. Reactive oxygen species (ROS) or hydrogen peroxide (H2O2) play an essential role as a second messenger in redox signaling. Evidence has been found that H2O2 takes part in regulating cell migration as well. A primary mechanism of ROS regulating redox signaling is oxidative protein modifications. Protein S-glutathionylation, one of the oxidative modifications, is the conjugation of glutathione …

Microfluidic Thermal Gel Electrophoresis For Native Protein Analysis, Shakila Hasanthika Peli Thanthri

Wayne State University Dissertations

Proteins must be in their native states to carry out their intended biological functions. Native protein structure requires that proteins be folded into the correct conformations and possess the necessary post-translational modifications (PTMs). These higher-order structures are critical to ensuring that proteins are biologically active and properly interact with neighboring molecules. However, assessing folding conformations and modified protein variants is challenging, and routine sample validation techniques like polyacrylamide gel electrophoresis (PAGE) are not capable of analyzing higher-order structures. Gradient PAGE gels can determine the molecular weight of proteins over a wide mass range, but protein separation resolutions are poor because …

The Sweet Smell Of Mystery: The Scent Glands Of Oncopeltus Fasciatus, Despina Tsitlakidou

Wayne State University Theses

Scent glands (ScGs) are defensive glands that are found among a wide variety of insect orders. These glands represent a specialized function of the exocrine system; however, the developmental mechanism remains unclear. Previous functional studies of the endocrine glands revealed that the endocrine and tracheal systems utilize similar genetic regulatory networks which indicate that these systems have common primordia. In Drosophila, sal is localized in the prothoracic gland while in Oncopeltus the gene is localized in the duct cells of the abdominal scent glands (Hanna & Popadić, 2020; Sánchez-Higueras et al., 2014). RNAi mediated knockdown of sal resulted in significant …

The Effects Of Gestational Exposure To Buprenorphine Or Morphine On Offspring Development, Abigail Myers

Wayne State University Theses

The opioid crisis in the United States has grown to epidemic proportions with opioid dependence among pregnant women quadrupling from 1999-2014. Opioid-dependent pregnant women are commonly given opioid maintenance therapies (e.g., buprenorphine), but the developmental and neurological effects of these drugs on offspring development are poorly understood. Our study uses a translational rodent model to characterize the developmental consequences of gestational morphine (“MS”; mimicking opioid use disorder) or buprenorphine (“BUP”; mimicking opioid maintenance therapy) exposure on exposed offspring. Female rats started BUP (1.0 mg/kg) or MS (3-6.0 mg/kg) exposure 7 days before pregnancy to represent an established user and either …

Genetic Analysis Of Vibrio Cholerae During Its Hyperinfectious State In Danio Rerio (Zebrafish), Ravipaul Singh

Wayne State University Theses

ABSTRACTGENETIC ANALYSIS OF VIBRIO CHOLERAE DURING ITS HYPERINFECTIOUS STATE IN DANIO RERIO (ZEBRAFISH) by RAVIPAUL SINGH AUGUST 2022 Advisor: Dr. Jeffrey Withey Major: Biochemistry and Molecular Biology Degree: Master of Science Vibrio cholerae is a gram-negative, comma-shaped, monotrichous bacillus and the causative agent of the diarrheal disease cholera. V. cholerae is a natural resident of aquatic environments such as rivers and estuaries and is a highly motile bacterium. Upon entering the human host, V. cholerae travels to its site of colonization in the small intestine and upregulates its virulence factors. Upon escape from the host, V. cholerae can enter a …

Effect Of Allosteric Site Binding On Smyd2 Conformational Ensemble, Jacob Daniel Sobota

Wayne State University Theses

Molecular dynamics simulation allows for the simulation of proteins with precise control over what ligands are present at what sites. The conformational ensemble of a protein can be obtained from MD simulation with and without binding at an allosteric site and compared between to gain insight at what effects binding at an allosteric site has on a protein’s structure. SMYD2, a critical regulator of cellular processes, was recently found to have a novel secondary binding site with allosteric effects on its activity. The discovery of an allosteric site has implications for drug design in the inhibition of SMYD2 to treat …

Prescience, Mustafa Yasar Ii

LMU Theses and Dissertations

In a society where one percent of the population can see into the future, a stubborn man who drinks alcohol to suppress his psychic powers is compelled to use his foresight when his brother disappears.

Attic Salt, 2022, Loyola Marymount University, The Honors Program

Attic Salt

No abstract provided.

A Rib Construct For Severe Spinal Deformity: Clinical, Biomechanical, Animal Studies, And Commercialization, Daniel James Bonthius

MUSC Theses and Dissertations

Introduction: Current treatments for early-onset spinal deformity (EOSD) have high complication rates and limited effectiveness. The rib construct (RC) is a novel technique for correcting early-onset spinal deformity. A series of hooks are used on the proximal superior ribs for proximal fixation to contour the thorax, with traditional fixation distally. Methods: The performance of the rib construct was evaluated in ex vivo biomechanical testing, an in vivo animal model, and a clinical study. An R-FIX (Rib-FIXation) System was developed based on these studies for optimization of the technique. Results: Ex vivo biomechanical testing showed that porcine spines instrumented with the …

Understanding The Role Of Brain Insulin Levels And Signaling In Post Stroke Cognitive Impairment, Crystal Smith

MUSC Theses and Dissertations

Stroke is the leading cause of long term disability and has the potential to impact a person’s activities of daily life on a physical and cognitive level. Insulin resistance has been linked to increased risk of stroke recurrence, death, and poor outcome following stroke. Insulin resistance leads to decreased insulin transport into the brain. Insulin was thought to be primarily important for peripheral bodily function, however brain insulin has proven to improve memory and cognition as well as having neuroprotective properties. Brain insulin levels and increasing insulin in the brain has not been examined as a therapeutic model for improving …

Elucidating The Effects Of Erα: Isoform Expression And Differential Receptor Localization In Immune Function, Cameron Leyers

MUSC Theses and Dissertations

Estrogen can be anti- or pro-inflammatory depending on milieu and has a role in increased incidence of lupus in reproductive age women versus men. Estrogen’s pleiotropic effects are in part due to Estrogen receptorα (ERα) and its variants that localize to cytoplasmic pools, nuclear regions and to the membrane. To understand the role of sex hormone receptors in immune responses, we investigated the effects of altered ERα isoform overexpression in dendritic and B cells. Toll like receptor 7 (TLR7) stimulated endpoints, often dysregulated in lupus were also investigated. Genetically modified MOER (membrane-only ERα) and NOER (nuclear-only ERα) mice were used …

Vaccinia Virus Dna Metabolism: The Contributions Of The Cellular Milieu And Novel Roles Of The Viral Dna Replication Machinery Following Exogenous Dna Damage, Conor W. Templeton

MUSC Theses and Dissertations

Poxviruses are large dsDNA viruses, unique in their cytoplasmic replication. This autonomy from the host nucleus poses novel challenges to genome replication, recombination and repair. Biochemical and genetic studies have confirmed that the viral genome encodes a repertoire of replication components (polymerase, processivity factor, single-strand DNA binding protein, primase/helicase, DNA ligase, scaffold protein). However, our knowledge of the mechanism of viral DNA replication remains incomplete, as is our understanding of which, if any, cellular proteins participate. We have shown that infection does not induce or dampen the cellular DNA damage response, but that a key component of this response, the …

Feasibility Of A School-Based Mental Health Program Implementation To Improve The Status Of Depression And Quality Of Life Of Mothers Of Children With Autism Spectrum Disorders In Urban Bangladesh: Menthol Study, Aliya Naheed, Saimul Islam, Meredith B. Brooks, Mary C. Smith Fawzi, Mir Nabila Ashraf, Helal Uddin Ahmed, M. M. Jalal Uddin, Kamrun Nahar Koly, Jerome T. Galea, Shaheen Akhter, Charles Nelson, Saima Wazed Hossain, Kerim M. Munir

Social Work Faculty Publications

Background: We assessed the feasibility of implementing psychological counseling services (PCS) for mothers of children with autism spectrum disorders (ASD) integrated within special education settings in urban Bangladesh. Method: In two special education schools for ASD in Dhaka City, trained female psychologists screened mothers using the Patient Health Questionnaire (PHQ-9). PCS was administered to all the mothers irrespective of a diagnosis of depression. Mothers with a PHQ-9 score >4 who met criteria for a major depressive episode (MDE) based on the DSM-IV Structured Interview Axis I Disorders (SCID-I) were also administered skill-building training through monthly home visits to support ASD …

The Role Od Daf-12/ Nhr In Regulating C. Elegans Environment Sensing Through Osm-9/Trpv, Mary Ross

Renée Crown University Honors Thesis Projects - All

No abstract provided.

Cognitive Biases Incidence In College Students Of A Midwestern Institution, Camilo A. Castelblanco Riveros

Modern Psychological Studies

Cognitive biases, including the misinformation effect, cognitive dissonance, and confirmation bias, are misleading ways of reasoning that can alter our perception of reality. Using questionnaires, this study investigated the extent to which these biases are present in the student community of a Midwestern University. It was hypothesized that a moderate proportion of individuals would show cognitive biases based on the literature and previous experiments. Furthermore, it was expected that participants would employ multiple strategies to justify their behavior and thought processes. With a qualitative design, 81 undergraduate students participated in the study. The research design was observational and statistical analysis …

Covid, Inequalities And Health: A Sociological Analysis About The Resilience Found In Unique Student Life Experiences, Sarah Da Silva

Electronic Theses and Dissertations, 2020-2023

This study demonstrates how adversity during the covid pandemic has impacted the lives of diverse college students. Specifically, this study analyzes students' perspectives on how they respond through resilience to daily academic, financial, and social stressors impacting their health during the pandemic. For this study, the research questions are: 1) what themes and forms of coping emerge among marginalized racially, ethnically diverse U.S. college students about their mental health and daily life experiences exacerbated by the covid pandemic? 2) And to what do experiences with stressors in combination with the covid pandemic reveal about the mental health of marginalized groups …

Changes In Bark Properties And Hydrology Following Prescribed Fire, Courtney Siegert, Anna Ilek, Adam Wade

CFR Publications

No abstract provided.

Evaluating Novel Combinations Of Polyamine Targeting Therapeutics In Pancreatic Ductal Adenocarcinoma, Sai Preethi Nakkina

Electronic Theses and Dissertations, 2020-2023

Pancreatic cancer overall has a poor five-year survival rate of less than 8%. Well-tolerated regimens and immune cell infiltration to promote anti-cancer treatments are major challenges. Studies described herein leveraged testing different combinations/doses of polyamine targeting inhibitors to further understand the impact of targeting key polyamine pathway mediators in pancreatic ductal adenocarcinoma (PDAC). Placebo controls were compared to groups treated with difluoromethylornithine (DFMO, a polyamine biosynthesis inhibitor of ornithine decarboxylase), different polyamine transport inhibitors, and compound combinations in strategies for polyamine blockage therapy (PBT). Informatic analyses showed that the dysregulation of key polyamine pathway mediators are associated with poor patient …

Mathematical Model For Giraffe Population Dynamics, Huntir Bass

Electronic Theses and Dissertations, 2020-2023

Since the 1980s the overall giraffe population has dropped at least 40% causing some researchers to label this rapid decline as the "Silent Extinction." Due to this plummet, understanding the behaviors of the giraffe population is absolutely necessary before they are on the brink of extinction. Through the usage of mathematical modeling methodologies, a general model is created to illustrate the relationship between juvenile and adult female giraffes through numerous interaction parameters. Variations on specific variables generate different simulations, which allows more biological accuracy. With each variation having an established coexistence equilibrium between the juvenile and adult female populations, the …

The Twinning Of Crisis: Intimate Partner Violence, State-Level Policy, And Female-Headed Family Poverty Across The United States, Julio Montanez

Electronic Theses and Dissertations, 2020-2023

Intimate partner violence (IPV) and poverty plague populations as twin social crises. Just as IPV has implications in terms of gender, race, magnitude, and deleteriousness—so does poverty. IPV cuts across demography but has concentrated burden for certain groups. In addition to the many dimensions of violence survivors may face, survivors may face economic abuse, as well as difficulty working or attaining an education. Poverty, measured in relative and absolute terms, is stratified by various demographic categories (e.g., disability, ethnicity, gender), with certain groups facing an enhanced prevalence of the issue. With these demographic disparities working in the background of the …

Paleoethnobotany And Starch Grain Residue Analysis Of Pottery From Site 8br85, Cape Canaveral, Florida, Hanna Park

Electronic Theses and Dissertations, 2020-2023

Located on Cape Canaveral within the Indian River region of Central Florida, the Burns Site (8BR85) reveals important information about the Ais, a mobile fisher-gatherer group who occupied the area during the Malabar II Period (A.D.1000 – 1600). As a bridging region between the two largest cultures in Florida (Timucua to the North and Calusa to the South), Central Florida and the Ais, in general, are under-studied concerning paleoethnobotanical research. The research presented here investigated starch residues of ceramic vessel sherds from the Burns Site which were identified through a comparative catalog which was built-in part of this research project. …

Combinatorial Optimization With Photonics-Inspired Clock Models, Mostafa Honari-Latifpour, Matthew S. Mills, Mohammad-Ali Miri

Publications and Research

NP-hard combinatorial optimization problems are in general hard problems that their computational complexity grows faster than polynomial scaling with the size of the problem. Thus, over the years there has been a great interest in developing unconventional methods and algorithms for solving such problems. Here, inspired by the nonlinear optical process of q-photon down-conversion, in which a photon is converted into q degenerate lower energy photons, we introduce a nonlinear dynamical model that builds on coupled single-variable phase oscillators and allows for efficiently approximating the ground state of the classical q-state planar Potts Hamiltonian. This reduces the exhaustive search in …

Prenatal Exposure To A Natural Disaster And Early Development Of Psychiatric Disorders During The Preschool Years: Stress In Pregnancy Study, Yoko Nomura, Jeffrey H. Newcorn, Christine Ginalis, Catherine Heitz, Jeenia Zaki, Farzana Khan, Mardia Nasrin, Kathryn Sie, Donato Deingeniis, Yasmin L. Hurd

Publications and Research

Background: Growing evidence shows an association between in utero exposure to natural disasters and child behavioral problems, but we still know little about the development of specific psychopathology in preschool-aged children. Methods: Preschool children (n = 163, mean age = 3.19, 85.5% racial and ethnic minorities) and their parents (n = 151) were evaluated annually at ages 2–5 to assess the emergence of psychopathology using the Preschool Age Psychopathological Assessment (PAPA), a parent-report structured diagnostic interview developed for preschool-age children. Sixty-six (40.5%) children were exposed to Sandy Storm (SS) in utero and 97 (59.5%) were not. Survival analysis evaluated patterns …

The Interaction Of Children Living In Single-Parent Households With Healthcare In Tennessee, Molly Balcer

Scholarship in Medicine - All Papers

The objective of this paper is to examine how a child living in a single-parent home is able to interact with healthcare in the state of Tennessee in 2020. Family structure in the United States trends away from the nuclear family, with 32% of households containing children headed by single-parents in 2018 as recorded by the United States Census Bureau. Given the knowledge that children in single-parent families are at higher risk for unmet healthcare needs, it is prudent to determine whether these trends are mirrored in Tennessee. Tests of statistical analysis were conducted on publicly available data collected from …