Pembrolizumab (brand name KEYTRUDA), is a monoclonal antibody therapy classified as an immune checkpoint inhibitor, a type of immunotherapy that works by facilitating the detection of cancer cells by T cells. Specifically, it blocks the PD-1 pathway that cancer cells use to suppress and evade the immune system. With neoadjuvant-adjuvant treatment, patients receive systemic therapy both before and after the surgical resection of their tumor(s). There is limited research evaluating the association between tumor responses (changes in tumor measurements) and survival time with neoadjuvant anti-PD-1 treatment. In this study, I analyzed the association between tumor measurements and event-free and overall survival in a clinical trial of patients receiving neoadjuvant-adjuvant anti-PD1-therapy. Event-free and overall survival were estimated using the Kaplan-Meier method, and associations with RECIST tumor size were evaluated using martingale residual plots and Cox proportional hazards regression models. In this study, I found significant associations between event-free survival and baseline tumor burden and changes (quantitative and categorized) in tumor size between baseline and the end of neoadjuvant therapy. Increases in tumor size were associated with a lower 2-year event-free survival. Larger values of baseline tumor burden were significantly associated with event-free survival but were not significantly associated with overall survival. The findings from this study may serve to better inform clinicians on making prognoses for patients on anti-PD-1 therapy and indicate a need for more research to be done on associations between tumor size and overall survival outcomes.

The Disability Inclusive Development Initiative (DIDI) is a project that brings together students and faculty from various fields to promote the human rights of persons with disabilities. Our current project builds upon the findings of a 2020 Memorandum of Understanding (MoU) between the International Disability Alliance (IDA) and the United Nations High Commissioner for Refugees (UNHCR). We are conducting a comparative analysis of asylum procedures in Uganda and Colombia, specifically examining how these procedures consider the rights of persons with disabilities. Our goal is to ensure that refugees and asylum-seekers with disabilities have access to fair and accommodating processes. We are also looking into the challenges faced by persons with disabilities during the asylum process and how governments are addressing these challenges. To achieve these aims, we are conducting a comprehensive literature review, including primary legal research, using resources from the University of Washington libraries. Additionally, we are consulting with experts working in this field. Our team is dedicated to producing a report for the United Nations High Commissioner for Refugees, which will outline our findings, highlight effective practices, and offer recommendations for future actions.

Coccidioidomycosis, also known as Valley Fever (VF) is caused by the fungus Coccidioides. Pigtail macaques (PTMs) bred at the Washington National Primate Research Center (WaNPRC) in Mesa, AZ are naturally infected with Coccidioides and are similar to humans in their physiology, symptoms, and immune responses. Populations with a weakened immune system, notably older individuals, are at risk for severe complications from infection. Additionally, there is evidence that males have a higher incidence of VF than females in endemic areas. I characterized the immune responses in a PTM model across age and sex to better understand how VF affects the immune response of these populations. Forty-two PTMs (2.25-19.24 years, 3.66-18.29 kg, 37 female, 5 male) at the WaNPRC were sampled for blood. The frequencies of immune cell subsets in whole blood were characterized by flow cytometry and compared for significant differences based on age and sex. I analyzed sex-based differences with Brown-Forsythe and Welch ANOVA t-tests and found no statistically significant differences. For age-based differences, we used a simple linear regression to analyze differences by age in immune cell subsets. We found that old PTMs (10.07-19.24 years) have higher activation of CD8+ T cells, myeloid dendritic cells, intermediate monocytes, and higher frequency of γΔ T cells and CD4+ γΔ T cells than young PTMs (2.25-9.69 years). Young PTMs have a higher frequency of CD45+ granulocytes, PD-1 High CD8+ T cells, plasmacytoid dendritic cells, and NK cells. By correlating older PTMs with higher immune cell activation, and younger PTMs with higher immune cell frequency, we have a better understanding of how a vaccine or treatment could be developed to support older individuals, who are at greater risk of severe infection.

People living with untreated HIV have a compromised immune system, which increases the risk for enhanced inflammation and disease severity in those co-infected with SARS-CoV-2. This emphasizes the importance of understanding the underlying mechanisms during immunosuppression that impact SARS-CoV-2 pathogenesis and disease outcomes. Since the microbiome plays an important role in immunity, microbial dysbiosis during HIV infection could contribute to prolonged SARS-CoV-2 pathogenesis. Microbial dysbiosis can be determined through the loss of diversity and changes to the composition of the microbiome. There is an established link between the increase in HIV disease progression and gastrointestinal microbial dysbiosis, however, the understanding of HIV-induced microbial dysbiosis during COVID-19 progression is unknown. In this project, we will investigate the gastrointestinal microbiome diversity and composition during SIV infection, to serve as a basis for understanding this undefined association. Utilizing the SIV macaque model for AIDS, we will test the hypothesis that the microbiome diversity and composition during SIV infection will be dissimilar between different gastrointestinal areas (stool, rectal swabs). Seven female rhesus macaques were intravaginally infected with SIVmac251. Rectal swabs and stool samples from the macaques were collected at baseline: 17~34 weeks post-SIV infection, and 7 days pre-SARS-CoV-2 infection. We extracted genomic DNA using a QIAgen PowerFecal Pro DNA kit and sequenced the ribosomal RNA after 16s amplification. We use the bioinformatics platform, QIIME2, to analyze the sequencing data. I am probing the data for relative microbial abundance, and diversity of microbial communities through metrics of richness, evenness, and specific indexes. Preliminary findings report that during SIV infection, the overall diversity of the gut microbiome is similar in stool and rectal swabs, and the microbiota composition is different between them. The results from these studies will then be used to understand the role of SIV-induced microbial dysbiosis on SARS-CoV-2 virological and disease outcomes.
 

Matrescence, the transformative journey into motherhood, encompasses profound physical, emotional, and psychological changes with lifelong implications. Postpartum mothers face various challenges including recovery from childbirth, sleep deprivation, hormonal and cognitive changes, insufficient support, and social isolation, often leading to depression and anxiety. While traditional medical interventions address some issues, alternative modalities of care such as horticultural therapy (HT) are gaining traction in postpartum care due to their holistic approach. This paper investigates the potential benefits of incorporating HT into postpartum care, aiming to explore its effectiveness in treating stress and related conditions, addressing psycho-social challenges, and integrating insights from other alternative therapies like occupational therapy (OT) to enhance postpartum wellness. Through an exploration of existing literature and a proposed pilot study, this research aims to fill the gap in understanding HT's efficacy specifically for postpartum mothers. The study proposes a comprehensive approach targeting physical and psycho-social aspects of maternal well-being through 12-week HT sessions with 24 postpartum mothers aged 18-35, incorporating health screenings, socialization, and horticultural activities. The study anticipates improvements in mental health, reduced postpartum depression symptoms, enhanced social support, and positive mother-infant interactions. Statistical analysis and qualitative assessments will evaluate intervention effectiveness, engagement, and feasibility. Understanding the transformative potential of HT for postpartum mothers advocates for a paradigm shift in maternal healthcare towards holistic and patient-centered approaches. Integration of HT into postpartum care models aligns with the evolving healthcare landscape and addresses the multifaceted challenges of matrescence, particularly in marginalized populations, emphasizing early intervention and culturally sensitive practices. This research underscores the importance of innovative interventions like HT in addressing the complex needs of postpartum mothers and calls for further exploration and integration into healthcare practices.

Translation seeks to convey meaning between one form of communication and another. The ways in which translation is completed can concentrate power and influence in ways that favor those whose languages and communication methods are dominant. This distribution of power and influence has important historical and modern consequences. This social science research project explores how translation has impacted nation to nation relationships between Indigenous people and colonial governments in North America. The treaty making history of the Blackfoot Confederacy will be considered as a case study, with a focus on the making of Treaty 7 between the British Crown in Canada and the Blackfoot Nations of Siksika, Kainai, and Piikani as well as other First Nations. Treaty 7 was signed in 1877 in a geographical, social, ecological, and cultural context that was heavily influenced by treaties, colonial westward expansion, and diminished bison populations. This case study on translation is being conducted through a review of firsthand accounts of the making and signing of Treaty 7 and a literature review of documented Indigenous oral histories of the event. These reviews will be conducted with consideration for the shifting power dynamics at play during that time. Finally, current academic work on language reclamation will be considered for its potential to support Truth and Reconciliation efforts, and a greater respect for Indigenous sovereignty. Language is a tool for carrying out translation, and carries significant elements of culture. Indigenous languages have a connection to the lands where they come from that are important for understanding current social and ecological challenges. Modern language reclamation efforts may have potential for restoring a more balanced distribution of power and offering solutions to these challenges.

The COVID-19 pandemic has created an overwhelming shift to using technology to connect with others. Coinciding with a growing mental health crisis among youth, mental health therapy has been largely moved to digital spaces. Three years later, providers are having to choose if they will provide their services through in person, remote, or hybrid interventions. My initial hypothesis is that there will be access barriers for youth of certain demographics when utilizing digital interventions. I conducted a systematic literature review to look at the effectiveness of the use of digital mental health therapy services among adolescents using PubMed, PsychInfo, and UW Libraries databases. The journals assess barriers and facilitators of digital mental health services for youth. Articles are found through systematic searches using combinations of the MeSH terms ‘digital mental health’, ‘adolescents’, ‘accessibility’ and ‘depression’. The demographics of the adolescents are compared with their preferences for digital therapy. Preliminary results indicate that youth who identify as lower income, rural residents, or BIPOC will face greater barriers to accessing mental healthcare and may benefit from continuing digital therapy. This synthesis of peer reviewed journals will prove to be useful in helping providers move forward with their practice in a way that aligns with their client’s needs.

Human Immunodeficiency Virus (HIV) is a rapidly evolving pathogen with no effective vaccine for eliciting broad protection against HIV infection. The HIV Envelope protein (Env) is a trimeric glycoprotein that is responsible for host-cell membrane fusion and infection initiation. As the only protein on the HIV virion surface, Env is the sole target for neutralizing antibodies. Characterizing the local structural dynamics of Env provides valuable insight into HIV host-virus interaction mechanisms. HDX-MS is an excellent tool for determining structural dynamics by measuring local backbone amide solvent accessibility. Generally, less structured protein regions uptake deuterium more rapidly compared to buried regions or those that are stabilized by secondary structure. We can use mass spectrometry to measure the kinetics of deuterium uptake for peptides throughout the Env protein. HDX-MS provides a detailed portrait of local structural dynamics and order, effectively identifying switching between completely closed prefusion and more open conformational states. A particular HIV Env isolate, A4, is of interest due to its unusually dynamic nature compared to other well-studied Env isolates, such as BG505. Dynamic Env exhibit more conformational flexibility, allowing them to sample various intermediary conformations between open and closed. We hypothesize that this attribute could increase HIV resistance to broadly neutralizing antibodies (bnAbs) that selectively target the closed Env conformation to prevent virus entry in immune cells. We may be able to correlate antibody binding to local dynamics measured in A4 versus BG505 Env trimers to verify this hypothesis. Biolayer interferometry will be applied to quantify antibody association and dissociation rates, as well as binding affinities. These studies will advance existing knowledge in Env-based vaccine therapeutics to improve immune responses to HIV.

Children diagnosed with Autism Spectrum Disorder (ASD), often experience co-occurring language impairments, including grammatical and lexical difficulties. Word segmentation, or the ability to identify word boundaries in continuous speech, is done through statistical learning and identification of speech cues. Recent studies in typically developing infants have shown a linear relationship between the ability to recognize words from continuous speech and the size of an individual's lexicon. The neural activity of the cerebral cortex, specifically the delta frequency band (1-4 Hz), contains the time scale of words and phrases. The delta band was found to track speech rhythm, along with semantic dissimilarity between successive words. Extracting acoustic features from sound signals and their linguistic representations (syllables, words, and phrases) is essential for speech comprehension. This study aims to look at the relationship between delta power recorded via scalp electroencephalogram (EEG) and communication skills in children with and without ASD. 193 participants (ASD = 96) from the NIH study on sex differences in autism were included in the sample. EEG recordings were collected while participants listened to phonemes that were statistically presented to result in 4 learned nonsense words. Parents completed a semi-structured interview on their child’s communication skills. EEG delta power was calculated over frontal, central and posterior regions of interest (ROIs). We expect children with ASD (compared to typically developing children) to have decreased delta power during nonsense word perception and lower delta power will be related to lower communication ability. This study will provide insight into the relation between neural perception of language and verbal communication in children with ASD.

Autism Spectrum Disorder (ASD) is a neurological and developmental disorder that affects around 1 in 6 children and 1 in 65 adults in the United States. Autistic individuals experience difficulties in social communication, interaction amongst peers, and language skills; any of the symptoms of ASD cause an influx of other problems that continue into adulthood; these differences may impact self-esteem and feelings of acceptance. Previous research has shown that a history of mental health concerns is related to worse Quality of Life (QoL) in individuals with autism as they transition into adulthood. This project aims to examine mental health comorbidities and self-reported QoL in adults with autism. 44 autistic adults from the NIH funded study on sex differences in autism were included. Participants completed a self history of current mental health diagnosis (anxiety, depression, OCD, ADHD etc.) and self reported QoL. Participants were grouped into 3 groups based on diagnosis: 1 (no diagnosis), 2 (1 diagnosis), and 3 (2+ diagnosis). QoL scores for each group will be calculated from the World Health Organization Quality-of-Life Scale (WHOQOL-BREF). I predict that individuals with more comorbid mental health diagnoses will have lower QoL scores. These data will inform us of how additional mental health struggles may impact quality of life in individuals with autism.

Autism Spectrum Disorder (ASD) is a developmental disorder that is characterized by difficulty in social cognition, communication, and behavior. Social cognition refers to mental processes related to how individuals perceive, process, and respond to social information. Elpers and Coyle (2021) found that there is a correlation between social cognition and general intelligence for adults with ASD. However, there is limited research on this relationship in younger age groups and for individuals without ASD. The goal of this study is to replicate the findings from Elpers and Coyle (2021) examining the relationship between social cognition and the intelligence quotient (IQ) in adolescents and young adults with and without autism. 193 participants (ASD = 96) from the NIH funded study on sex differences in autism were included in the sample. To measure social cognition, participants completed the Reading the Mind in the Eyes Test (RMET), a 36-item assessment measuring Theory of Mind or the individual's ability to recognize that others may have different mental states. Participants also completed the differential ability scale (DAS-2) as a measure of verbal IQ. We expect positive correlations for RMET scores and verbal score, in that as RMET scores increase, verbal IQ scores will also increase for adolescents and young adults with and without ASD. We will also explore how age impacts the scores, as we expect older children and young adults to have more verbal skills, hence performing better on the RMET measure. The results of this study will contribute to our understanding of the relationship between social cognition and intelligence from adolescents and young adults to the existing data that has been previously gathered. 

Sensory processing is a process in which the nervous system receives, processes, and integrates incoming sensory input from the environment to allow individuals to perceive and respond to their surroundings. Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social and behavioral skills. Many individuals with ASD experience hypersensitivity to sensory stimuli, thus individuals with ASD may experience more difficulty when navigating the world around us. These sensory challenges may result in increased anxiety symptoms. The purpose of this study was to explore the relationship between sensory processing and anxiety in autistic and typically developing (TD) adults. 256 participants (ASD = 149) ages 18-35 from a NIH funded study on sex differences in autism were included. Participants completed two self-report questionnaires: “Sensory Processing 3-Dimensions Scale” (SP3D) measuring sensory processing difficulties in auditory, visual, and tactile domains, and the “Screen for Adult Anxiety Related Disorders'' (SCAARED), measuring the intensity or frequency of anxiety symptoms and assessing four factors of anxiety (panic disorder, generalized anxiety disorder, separation anxiety disorder, and social phobis disorder). Correlations will be used to compare SP3D scores and SCAARED scores. Given the hypersensitivity to sensory stimuli in ASD, we hypothesize the effects of anxiety symptoms will be increased in the ASD group who experience more domains of hypersensitivity. The results of this study will contribute to a greater understanding of the effect sensory sensitivity has on anxiety in adults with ASD.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, and restricted or repetitive patterns of behavior or interests. ASD is associated with features beyond its core characteristics, including alexithymia and anxiety. Alexithymia is characterized by difficulty recognizing and describing one’s own emotions, it influences physical and mental health, and it is associated with symptoms of anxiety. Despite current research demonstrating the correlation between alexithymia and anxiety in both ASD and the general population, there remains a significant research gap in how alexithymia and autism traits individually and collectively influence anxiety levels among the participants. This study has two aims: 1) To explore the relationship between alexithymia and anxiety in participants with ASD and TD. 2) To analyze the role of alexithymia as a mediator of the relationship between autism traits and anxiety in adolescents and young adults. This sample includes 149 participants (93 ASD) ages 15-34, from the NIH funded study on sex differences in autism. Measures included alexithymia via the 20-Item Toronto Alexithymia Scale (TAS-20), anxiety via the Screen for Adult Anxiety Related Disorders (SCAARED), and autism traits via the Social Responsiveness Scale (SRS-2). We will first conduct regression analyses to examine the relationships between alexithymia, anxiety, and autism traits. Then, we will employ Preacher and Hayes’ INDIRECT Method to investigate the mediating role of alexithymia in the relationship between autism traits and anxiety. We expect to see a significant relationship between alexithymia and anxiety in both groups and the relationship between alexithymia and anxiety in the ASD group to be significantly different than TD group. Understanding the relationship between anxiety and alexithymia could aid in the development or improvement of interventions for anxiety in people with ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects social and behavioral development. Although autism is most associated with social difficulties, it is also correlated with issues such as sleep disturbances. Previous literature suggests that 50-80% of autistic individuals experience sleep difficulties. One common feature of autism is differences in sensory processing compared to typically developing (TD) individuals. These differences may result in behaviors that are detrimental to sleep habits. This project aims to identify the relationship between sensory processing and sleep quality in autistic and TD adults and to identify a type of sensory concern that correlates to increased sleep disturbance. 150 participants (ASD = 94) ages 18-25 from the (National Institutes of Health) NIH funded multisite study on sex differences in autism were used in the analysis. Participants completed self-reports on sensory systems using the Sensory Profile, and on sleep quality using the Pittsburg Sleep Quality Index (PSQI). The Sensory Profile scores participants among 4 quadrants: low registration, sensation seeking, sensory sensitivity, and sensation avoiding. The scores reflect the participants sensory systems compared to their age range separated into five groups. The PSQI takes participant responses and assigns a score with “0” being no difficulty and “3” being severe difficulty across 7 components of sleep. Component scores are then summed for a global score. A t-test will be performed to compare the mean global PSQI score for the five groups across each quadrant on the Sensory Profile and for autistic and non-autistic populations. We expect to see higher mean global PSQI scores for those with autism and for those with higher Sensory profile scores within the ASD population. Increased differences in sensory processing in autistic individuals is important to investigate because studies have shown that filtering out sensory input is key to falling and remaining asleep which leads to improved quality of life.

In this study, I investigated distinctive electroencephalogram (EEG) patterns associated with processing social and nonsocial information in both typically developing individuals and those with Autism Spectrum Disorder (ASD). A total of 139 youth and young adults aged 10-24 years participated, including 63 individuals with ASD (23 females, 40 males, mean age = 17.57) and 76 typically developing youth (35 females, 41 males, mean age = 17.47). Data collection occurred across four sites as part of the multisite ACE Network GENDAAR Wave 2 study (R01 MH10028, Pelphrey). EEG data were collected using a 128-channel Geodesic sensor net, concurrently capturing live social and nonsocial attention responses. During the social condition, participants viewed videos featuring social stimuli (vignettes of women telling or singing nursery rhymes), while during the nonsocial condition, they viewed videos of objects (dynamic toys). Additionally, all participants underwent assessment using the Vineland Adaptive Behavior Scales-2 (VABS-2). I calculated power spectral density (PSD) values for 8 channels based on the 10-20 system across various frequency bands, and performed analysis using this data. The results indicated a main effect of condition (social vs. nonsocial) at several frequency bands and electrodes. Furthermore, a main effect of the group revealed higher alpha power in typically developing individuals compared to those with ASD. Notably, no significant relationships were observed between Vineland Adaptive Behavior Scales-2 (VABS-2) subscores and neural responses. This study highlights a difference in neural activity during attention to social vs. nonsocial information in both groups of participants and underscores the importance of understanding these neural correlates in individuals with ASD.

Subtherapeutic drug levels can lead to the failure of antiretroviral therapy (ART) regimens used in Human Immunodeficiency Virus (HIV) treatment and prevention. However, gold-standard HIV drug level monitoring techniques—such as mass spectrometry—require bulky and expensive instruments that are not widely accessible at the point-of-need. Our group developed the REverSe TRanscrIptase Chain Termination (RESTRICT) enzymatic assay to rapidly (30 min) and inexpensively measure tenofovir diphosphate (TFV-DP), a nucleotide analog used in >90% of oral ART regimens and in all approved prevention regimens. However, RESTRICT currently requires trained operators to perform multiple time-sensitive liquid-handling steps. To reduce user intervention and minimize the need for laboratory equipment, we harnessed 3D-printed capillaric microfluidics to self-propel liquids using only surface tension effects encoded in microchannel geometry and surface chemistry. Specifically, we translated the manual tube-based RESTRICT to an automated microfluidic protocol by using autonomous trigger valves to pre-load multiple RESTRICT assay reagents and serpentine channels to control assay timing. Currently, RESTRICT reactions are incubated for 30 minutes at 37˚C, but we decreased the reaction time to 15 minutes and removed the need for an external heating source by incubating at room temperature (25˚C). There was only a 15% decrease in overall signal intensity in the faster, room temperature assays, and measured readout was distinguishable between clinically relevant concentrations of TFV-DP. Our results represent a first step towards integrating RESTRICT reactions and fluorescence readout onto a rapidly fabricated microfluidic chip. We hope to achieve a device that increases the accessibility of HIV drug level monitoring at the point of need without specialized equipment or highly trained operators.

There is a strong need for rapid and inexpensive tests for monitoring human immunodeficiency virus (HIV) drugs to prevent treatment failure. The REverse TranscrIptase Chain Termination (RESTRICT) Assay provides fast and inexpensive measurement of HIV reverse transcriptase (RT) inhibitors by measuring the extent of DNA synthesis with the HIV RT enzyme in the presence of a patient’s blood. RESTRICT uses an intercalating dye, PicoGreen, to provide fluorescence as a function of the amount of DNA synthesized. However, PicoGreen interrupts DNA synthesis and binds to any double-stranded DNA (dsDNA) present in the sample including background DNA in blood samples, precluding real-time measurements and potentially decreasing the accuracy of results. This project uses RESTRICT in conjunction with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) complexes and reporters to accurately measure RESTRICT results in real-time. Fluorescence is produced by reporters which are made up of a quencher and a fluorophore. When the CRISPR complex detects a specific complementary sequence formed from the single-stranded DNA (ssDNA) template, the Cas enzyme is activated and cleaves the fluorescent reporter. Once cleaved, the fluorophore is released from the quencher thus generating fluorescence. Because the CRISPR complex binds only to specific segments of DNA produced by RESTRICT, we can obtain more specific results without interference from background DNA. In addition, CRISPR complexes and reporters do not interfere with DNA synthesis and can be added at the same time as other RESTRICT reagents, enabling real-time monitoring of RESTRICT reactions. Using a portable fluorescence reader (T8-ISO, Axxin Pty Ltd.), positive control reactions containing RT enzyme provided at least 5X more fluorescence than negative controls without RT. Future work will focus on measuring clinically relevant levels of HIV drugs in aqueous buffers using RESTRICT with CRISPR readout.