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Modeling and Miniaturization of a Centrifugal Bioreactor with Applications in Cancer Immunotherapy and Chemical Engineering Education

Modeling and Miniaturization of a Centrifugal Bioreactor with Applications in Cancer Immunotherapy and Chemical Engineering Education

Primary author: Kitana Kaiphanliam
Co-author(s): Brenden Fraser-Hevlin, Bernard Van Wie
Faculty sponsor: Bernard J. Van Wie

Primary college/unit: Voiland College of Engineering and Architecture
Campus: Pullman

Abstract:

A centrifugal bioreactor (CBR) system has been designed and studied in Professor Bernard Van Wie’s laboratory with applications ranging from tissue engineering for arthritis to T cell biomanufacturing for cancer therapies. A major issue in using the CBR for T cell expansion is the numerous sources for potential contamination, as half of the system is exposed outside of a biosafety cabinet. If the current system were implemented in hospitals, it would require a cleanroom costing up to $3 million; however, if the CBR was downsized to fit in a biosafety cabinet, containment costs would be reduced to $15,000, at most. By reducing the size of the CBR to fit in a biosafety cabinet and assuming proper aseptic technique is followed, we will nearly eliminate contamination sources, making the system more affordable and accessible for cancer immunotherapy applications. Current efforts in the downsizing process include drafting and modeling of a prototype scalable to that of a compact disc (CD). Additionally, the CBR can be further miniaturized as a hands-on learning module for classroom use. The physics principles that define the CBR can be used to introduce separations to chemical engineering undergraduate students, as well as expose them to applications in the biomedical field. We hypothesize that these CBR-like fidget spinner modules will increase motivation and retention amongst female students in a freshman-level chemical engineering course. Prototypes for the hands-on learning modules have been manufactured, and we will be implementing them along with motivational assessments in the spring CHE 110 class.

Development of a Functional Maternity Hospital Gown Through User-Centered Design

Development of a Functional Maternity Hospital Gown Through User-Centered Design

Primary author: Chanmi Hwang
Co-author(s): Lindsay McCoy

Primary college/unit: Agricultural, Human and Natural Resource Sciences
Campus: Pullman

Abstract:

Maternity hospital gowns are usually made according to a one-size-fits-all standard with full back openings which are physically and emotionally uncomfortable, not functional, and revealing. The purpose of this research was to understand the design requirements of patients and practitioners in order to develop a functional and sustainable maternity hospital gown design. The researchers applied user-centered design (UCD) methods to develop a new design based on data from market research (23 birthing institutions and 25 leading retailers) and focus group interviews (15 postpartum women). The researchers created a two-piece stretchy gown with an adjustable waist and a washable nursing breast pad insert system which contributed to the gowns overall fit, mobility, closure access, modesty, and tactile comfort. Through wear trials (5 women) and an online survey (501 women and 42 practitioners), participants found the prototype to be successful in enhancing physical and psychological comfort throughout different stages of labor and postpartum, resulting in a novel maternity gowns concept that address many needs of both patients and practitioners. The resulting technical package includes the order of operations, bill of materials, marker layout, and cost analysis for the new design which can be tested for mass production. Future research may explore partnering with a manufacturing company such as Medline, the largest manufacturer and distributor of medical supplies, to conduct a patient satisfaction survey after implementing the new design.

Youth’s Proximity to Marijuana Retailers and Advertisements: Factors Associated with Washington State Adolescents’ Intentions to Use Marijuana

Youth’s Proximity to Marijuana Retailers and Advertisements: Factors Associated with Washington State Adolescents’ Intentions to Use Marijuana

Primary author: Stacey Hust
Co-author(s): Jessica Willoughby; Leticia Couto; Jiayu Li

Primary college/unit: Edward R. Murrow College of Communication
Campus: Pullman

Abstract:

The current study explored the influences of advertising exposure, numbers of marijuana retailers, distance to retailers, and constructs from the Integrative Model of Behavioral Prediction, including outcome beliefs, perceived norms, and efficacy, on youth’s intentions to use marijuana in a state in which the use of recreational marijuana is legal. A state-wide online cross-sectional survey of 350 adolescents ages 13-17, residing in Washington state, was conducted in June 2018. The results of the regression analysis suggest that exposure to marijuana advertising, positive and negative outcome beliefs, and perceived peer norms were associated with intention to use marijuana. Distances to retailers moderated the relationships between exposure to advertising and intentions as well as between positive outcome beliefs and intentions. States that have legalized recreational marijuana may want to consider the location of retailers in relation to neighborhoods and advertising regulations to reduce appeal to youth. Additionally, prevention efforts could aim to influence outcome beliefs and norms in an attempt to reduce adolescents’ intentions to use recreational marijuana.

Effect of Total Sleep Deprivation on Word Recognition of Previously Studied Words with Different Emotional Valence

Effect of Total Sleep Deprivation on Word Recognition of Previously Studied Words with Different Emotional Valence

Primary author: Amanda Hudson
Co-author(s): Paul Whitney; John Hinson; Devon Hansen; Hans Van Dongen; Kimberly Honn
Faculty sponsor: Kimberly Honn

Primary college/unit: Arts and Sciences
Campus: Spokane

Abstract:

Stimuli with an emotional valence tend to produce better recognition from memory than neutral stimuli. Sleep loss is believed to increase reactivity to negative stimuli, compared to positive stimuli, which may comparatively enhance subsequent recognition from memory for negative stimuli. We investigated the impact of total sleep deprivation (TSD) on recognition accuracy for words with different emotional valence using the Affective Item Source Memory Task (AISM).

Fourteen adults (ages 21-39; 7 females) completed a 4-day/3-night laboratory study with a baseline sleep opportunity, 39h acute TSD, and recovery sleep. The AISM was administered at 16:30 during baseline and after 34h TSD. During a study phase, participants heard a list, twice, of positive, negative, and neutral words spoken with a male or female voice. During an immediately subsequent recognition phase, participants heard and judged whether words were previously presented (item memory). For words judged to have been presented previously, participants indicated whether those were presented by a female or male speaker (source memory).

We found session (p<0.001) and valence (p<0.001) effects on item memory, but no interaction. At baseline, accuracy was higher for neutral and positive words than negative words. During TSD, accuracy declined for all valences as expected. However, there was no comparatively greater impact on item or source memory for negative words nor any differential effect of TSD for different valences. Whether our results would hold with longer time intervals between task phases or an intervening sleep period remains to be determined. This research was supported by Jazz Pharmaceuticals.

Letting Go and Staying Connected: A theoretically guided, developmentally targeted, and empirically supported intervention for parents of students transitioning to college

Letting Go and Staying Connected: A theoretically guided, developmentally targeted, and empirically supported intervention for parents of students transitioning to college

Primary author: Laura Hill
Co-author(s): Brittany Cooper; Matt Bumpus; Kevin Haggerty; Richard Catalano; Martie Skinner

Primary college/unit: Agricultural, Human and Natural Resource Sciences
Campus: Pullman

Abstract:

Early adulthood is a critical developmental period when many youth transition from living at home with parents to the relative autonomy of college. This transition results in increased opportunity both for positive growth and identity development as well as increased risky substance use and sexual behaviors. This developmental transition also presents opportunities for prevention. Research shows that parents continue to influence young adult behavior even at a distance; however, few studies have tested parent-college student interventions. We created a parent-student handbook intervention that provides parents with tools designed to help them support their students as they transition to living away from home, by providing encouragement, communicating clear expectations, and supporting growth in students’ autonomy.

Data for the present study come from the efficacy trial of the self-directed handbook for parents of first-year college students. In the summer before college, parent-student dyads were randomly assigned to one of three conditions: control (N=313), parent handbook (N=278), or parent handbook plus booster texts (N=323). We collected data on substance use early in the students’ first fall semester at WSU.

Among students who reported substance use in high school, students in the handbook condition reported significantly lower increases in frequency of 30-day alcohol use, binge drinking, marijuana, and co-use once they came to college. Students who had reported no previous use were significantly less likely to report initiation of alcohol, marijuana, or co-use of both once they came to college. Results suggest that this low-cost intervention significantly reduces new students’ risk behaviors.

Natural Genetic Variation in the Drosophila Genetic Reference Panel Reveals Genes Associated with Susceptibility or Tolerance to Coxiella burnetii Infection

Natural Genetic Variation in the Drosophila Genetic Reference Panel Reveals Genes Associated with Susceptibility or Tolerance to Coxiella burnetii Infection

Primary author: Rosa Guzman
Faculty sponsor: Alan Goodman

Primary college/unit: College of Veterinary Medicine
Campus: Pullman

Abstract:

The Gram-negative bacterium Coxiella burnetii (C. burnetii) is the causative agent of Query (Q) fever in humans and coxiellosis in livestock. Association between host genetic background and C. burnetii pathogenesis has been demonstrated both in humans and animals; however, specific genes associated with severity of infection remain unknown. Our lab has shown that the Drosophila melanogaster model is suitable for studying host-pathogen interactions during C. burnetii infection. In this study, we employed the Drosophila Genetics Reference Panel (DGRP), a library of 209 inbred wild-type fly lines, to identify host genetic variants that affect susceptibility or tolerance to C. burnetii infection. We infected each DGRP line, monitored survival, and calculated a hazard ratio for each line to perform a genome-wide association study (GWAS). We tested 25 GWAS candidate genes by infecting flies carrying a null mutation or RNAi knockdown of each gene and monitoring survival. Of these 25 genes, 6 validated in null mutants only, 5 in RNAi knockdown only, and 4 in both null mutants and RNAi. One gene that validated in both null mutants and RNAi knockdown flies was taranis, which is essential for regeneration and JNK signaling. The human ortholog of taranis is SERTAD1, which has been recently linked to immunity. Our results demonstrate that from genes identified and validated in our genetic screen, mechanism of action studies should be performed to determine the genes’ role in the host immune response to infection.

Treatment for Injuries Among Washington State Adults: Differences by Rurality

Treatment for Injuries among Washington State Adults: Differences by Rurality

Primary author: Janessa Graves
Co-author(s): Demetrius Abshire

Primary college/unit: College of Nursing
Campus: Spokane

Abstract:

Statement of Purpose: Rural residents face significant barriers in accessing trauma care, with access becoming more challenging in highly rural areas. We examined differences in injury-related medical care among Washington State residents across the rural-urban continuum.

Methods/Approach: Stratified random sampling was used to select 2575 adults from small rural, large rural, suburban, and urban areas who were invited to complete a survey on factors affecting health. Data were obtained from 616 adults (278 from small rural, 100 from large rural, 98 from suburban, and 140 from urban areas). Respondents reported past-year injury experience and barriers to access for medical care. We examined variation in access by rurality using chi-squared and modified Poisson regression models.

Results: Fewer than half (45.1%) of respondents reported any activity-restricting injury in the last year and 32.4% reported seeking care. Injuries were often treated by a primary care provider (59.7%) or walk-in clinic (21.9%) with no significant difference in care location by rurality. Overall, 20.2% of small rural residents sought medical care >30 minutes away, compared to 3.9% of urban, 8.0% of suburban, and 12.1% of large rural residents (p30 minutes away from home (adjusted IRR, p<0.01).

Conclusions: Washington residents face differential access to medical care for injuries across levels of rurality, with small rural residents reporting the most substantial access-related concerns. Health systems and policies must address inequities in access to care for residents along the rural-urban gradient.

Evidence and Use of the Washington Assessment of Risk and Needs

Evidence and Use of the Washington Assessment of Risk and Needs

Primary author: Brian French
Co-author(s): Bruce Austin; Thao Vo; Cihan Demir; Paul Strand

Primary college/unit: Arts and Sciences
Campus: Pullman

Abstract:

The Washington Assessment of Risk and Needs (WARNS) is widely used in over 100 districts in the State of Washington. School districts and court entities rely on scores from the WARNS to inform conversations with youth and families about adolescent behaviors related to chronic school absences, or truancy. WARNS assesses six domains including peer deviance, aggression and defiance, substance abuse, depression and anxiety, school engagement, and family environment. With Washington having one of the highest rates of truancy in the United States, WARNS plays a critical role in understanding such factors. We present work in three areas to highlight support for the WARNS. First, our research highlights how we account for a students’ contextual environments when examining WARNS items for fairness, ensuring scores carry equal meaning across ethnic groups. Second, we highlight the development of a computerized adaptive test (CAT) that provides users with a time-efficient and short form of the WARNS, reducing assessment fatigue without degrading score accuracy. Third, we highlight the WARNS models of use from large to small districts around the State, and new developments including a Spanish version. The evidence and use of the WARNS help to bring student voices back into the truancy conversation in the State. Our work has resulted in increased use of the WARNS and decreases in student truancy and negative behavioral trajectories, and have led to distal outcomes of student success.

Modeling Growth Kinetics of Cytotoxic T Lymphocytes for Cancer Immunotherapy in a High-Density Novel Centrifugal Bioreactor System

Modeling Growth Kinetics of Cytotoxic T Lymphocytes for Cancer Immunotherapy in a High-Density Novel Centrifugal Bioreactor System

Primary author: Brenden Fraser-Hevlin
Co-author(s): Kitana Kaiphanliam; Bernard Van Wie
Faculty sponsor: Dr. Bernard Van Wie

Primary college/unit: Voiland College of Engineering and Architecture
Campus: Pullman

Abstract:

Cancer is the second leading cause of death in the United States and worldwide. Traditional cancer treatments such as chemotherapy, radiation, and surgery are designed to destroy cancer cells but often attack healthy tissue in the process. In immunotherapy, immune cells such as cytotoxic T lymphocytes (CTLs) are extracted, modified, expanded in a bioreactor, and transferred into a patient—this is known as adoptive cell therapy (ACT). There is a need for ACT-based treatments that are widely accessible, scalable, and relatively inexpensive. To address this need, our lab recently developed a high-density, lab-scale centrifugal bioreactor (CBR) which can rapidly expand infected CD8+ T cells from a bovine model. In this study, we aimed to optimize CTL growth by determining kinetic growth parameters based on the levels of glucose and inhibitory metabolites in the culture. It is hypothesized that if we can develop a reliable kinetic growth model, then it will be possible to predict optimal CTL expansion parameters for the bioreactor. Early kinetic studies were performed last fall in which six different glucose concentrations were tested, giving a maximum specific growth rate of 0.0112 1/h and a Monod constant of 2.12 mg glucose/dL. The experiments were repeated recently with different glucose concentrations and the results from those studies will be presented. The optimization of this bioreactor will have a major impact on the availability and efficiency of patient-specific immunotherapy.

Type IV Secretion System Effectors of Anaplasma phagocytophilum

Type IV Secretion System Effectors of Anaplasma phagocytophilum

Primary author: Deirdre Fahy
Co-author(s): Jason Park; Michael Dodd; Kelly Brayton

Primary college/unit: College of Veterinary Medicine
Campus: Pullman

Abstract:

Anaplasma phagocytophilum (Ap) is a tick-transmitted obligate intracellular zoonotic pathogen. Ap achieves intracellular infection by delivering effector proteins into the host cytosol utilizing a Type IV secretion system (T4SS). In contrast to other intracellular pathogens e.g. Legionella pneumophilia and Coxiella burnetii, where 100s of T4SS effectors have been found, only 4 have been identified in Ap. Our goal was to extend the repertoire of known Ap effectors. To predict effectors, we used the recently published T4SS effector prediction software OPT4e to identify Ap proteins containing features characteristic of T4SS substrates. To screen for T4SS translocation, effector candidates were fused to a reporter enzyme, which if translocated to the host cell cytoplasm generates a product detectable by ELISA. To overcome the genetic intractability of Ap, fusion constructs were assayed for translocation by the heterologous T4SS of Legionella pneumophila. Although only 7 of 70 screened proteins were translocated in a T4SS dependent manner, there are likely more effectors since a negative result may be due to the heterologous nature of the reporter system. Three of the translocated substrates localize to the host cell nucleus when ectopically expressed. Bioinformatic analysis identified putative C-terminal nuclear localization signals (NLS) in all three of these T4SS substrates. Deletion of these NLS sequences abrogated both nuclear-specific localization and also T4SS translocation, which is consistent with the requirement for specific C-terminal features in translocation of known effectors. Functional characterization of these and other effectors will inform their role in Ap replication, pathogenesis, and transmission.