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Transcriptome-Wide Association Study of the Plasma Proteme Reveals Cis and Trans Regulatory Mechanisms Underlying Complex Traits
Get PDFMost genetic variants associated with complex human traits exist in non-coding regions, and thus the mechanism by which they affect a trait can be unclear. Genetic regulation of transcription and translation are key mechanisms through which genetic variants impact traits. Quantitative trait locus (QTL) mapping studies leverage data produced by advanced sequencing and assay technology to identify variants associated with the abundance of a molecular trait like RNA expression (eQTL) or protein levels (pQTL). While proximal genetic variants (cis-acting), like those in promoter or enhancer regions of genes, tend to have the largest effect sizes on RNA transcript and protein levels, distal genetic variation (trans-acting) still contributes considerably to regulating transcription and translation. However, trans-QTL can be difficult to discover due to the high multiple testing burden, their comparatively low effect sizes, and their tendency to have tissue- or cell type-specific effects. Methods that prioritize testing cis-eQTL for trans-acting associations have proven effective because they reduce the multiple testing burden and many trans-eQTL colocalize with cis-eQTL. For example, a transcriptome-wide association study (TWAS) that used observed gene expression as trait found more trans-acting genes than a comparable eQTL study. We hypothesized that performing a TWAS using protein levels as trait would be effective at identifying trans-pQTL because it prioritized cis-eQTL for testing trans-acting genes. While gene expression and protein levels have previously been shown to have a low correlation, we hypothesized that GReX would have a higher correlation with observed protein levels because it excludes variation in expression due to environmental factors. We used genotype and plasma protein measurements from individuals participating in the INTERVAL study for our TWAS and replicated these results with genotype and plasma protein measurements from individuals in the TOPMed MESA cohort. We used transcriptome prediction models from 49 tissues trained with GTEx Project genotype and RNA-Seq data. Furthermore, we used RNA-Seq data from the TOPMed MESA cohort to compare the correlation of observed expression levels with protein levels to the correlation of predicted expression levels with protein levels. We discovered many replicable cis- and trans-acting gene-protein relationships and found that predicted expression had a higher correlation and true positive rate than observed expression for significant association with protein levels. These results indicate that predicted gene expression may better uncover the genetic mechanisms underlying complex traits than observed expression
Clinical Social Workers, Telemental Health and the COVID-19 Pandemic
Get PDFAs a result of the COVID-19 Pandemic, and due to the shelter in place order that most states required, licensed clinical social workers (CSW’s) were forced to switch from in person services to telemental health services almost overnight. Many did so without previous training, adequate technology, a confidential office, or professional support. While there is a growing body of research regarding the increased use of telemental health in the mental health field during COVID-19, there is minimal research which narrows in what it was like for the CSW’s who made this transition. The purpose of this study was to better understand the lived experience of CSW’s who transitioned to provide telemental health services during the national shelter in place order as a response to the global COVID-19 pandemic, and how this impacted them professionally and personally. A qualitative, phenomenological mode of inquiry was used, and data analysis was guided by an adaptation of Moustakas’ transcendental phenomenological method. Ten CSW’s were interviewed for this study between April 2023 and August of 2023 through Zoom. The interviews were transcribed verbatim, and the data were coded, analyzed, and organized into themes and subthemes. A textural and a structural description, and a composite textural-structural for each CSW interviewed were completed. Six themes emerged from the interviews with eleven subthemes. The themes are 1) the transition to telemental health, 2) professional insecurity, 3) working from home works, 4) the shared reality is harder, 5) self-care is a priority, 6) it is going to be ok. The subthemes are a) challenges, b) guidance on best practices for telemental health, c) insurance reimbursement, d) protection from COVID-19, e) more free time in the day, f) flexible work schedule, g) telemental health is preferred for some clients, h) fear of the unknown, i) amplified mental health problem, j) empathetic connections and disconnections, and k) connections. Finding suggest that CSW’s transitioned quickly to telemental health care and found they were able to provide effective therapy services for their clients, even though they initially struggled with feelings of professional insecurity due to lack of experience or training. The CSW\u27s interviewed for this study discovered that there were many benefits to working from home. Additionally, they experienced emotional and mental hardship due to the shared reality of living through the pandemic while simultaneously providing therapeutic care for their clients. Through the efforts of regular self-care, the CSW\u27s were able to mitigate the effects of compassion fatigue and burnout. Implications for future research in social work practice and education will be discussed, as well as suggestions for future research topics
Comparing Caregiver-Teacher-Adolescent Mental Health Reporting: Examining Changes Over Time and Related Outcomes Among Youth Involved in the Child Welfare System
Get PDFThe benefits of psychological assessment are particularly salient for children and youth in the child welfare system, as youth in contact with the system are more likely to experience mental health symptoms, disorders, and comorbidities as compared to youth in the general population. These assessments often utilize multiple reporters, as emerging evidence indicates that utilizing multiple more effectively captures the mental health experiences of children and youth. However, the extant literature has consistently observed only low-to-moderate (i.e., .2-to-.3) agreement across informants, including among dyads in contact with the child welfare system. Several factors are associated with level of agreement across reporters, including race, gender, age, behaviors and symptoms of interest, and relationship of the respondent to the child. Specific factors associated with child welfare involvement also contribute to discrepancies across reports, including maltreatment history and foster caregiver/biological parent status. The current study seeks to expand on this research about multi-informant reporter discrepancies by examining reporting discrepancies among caregivers, teachers, and 12-year-old adolescent dyads with prior and/or ongoing child welfare involvement, as well as capturing how teacher-caregiver discrepancies change over time via growth mixture modeling and how trajectory predicts child-rated mental health at age 18. In keeping with the extant literature, low-to-moderate discrepancies were observed across caregiver-child, child-teacher, and teacher-caregiver dyads regardless of symptom clusters. Discrepancies did not differ according to race or gender. Next, growth mixture modeling indicated that the best fit for internalizing symptoms was a three-class solution; trajectories included caregiver-teacher dyads with 1) consistently low levels of disagreement, 2) consistently high levels of disagreement, and 3) dyads with high to moderate decreasing disagreement. Regarding externalizing behaviors, the three-class solution was also most appropriate and included caregiver-teacher dyads with 1) consistently low levels of disagreement, 2) low to moderate increasing disagreement, and 3) moderate to low decreasing disagreement. Finally, in terms of total symptoms, the four-class solution was most appropriate and included caregiver-teacher dyads with 1) moderate to high increasing disagreement, 2) low to moderate increasing disagreement, 3) consistently low disagreement, and 3) high to moderate decreasing disagreement, though these trajectories differed depending on whether caregiver or teacher reported higher symptoms. Notably, only trajectories with increasing levels of disagreement predicted child-rated mental health outcomes at 18 when controlling for baseline mental health symptoms. Specifically, when trajectories including increasing discrepancies ending in the moderate range, children reported higher mental health symptomology at age 18; when trajectories including increasing disagreement ending in the high range, children reported significantly lower mental health symptoms at 18. The implications of these findings for research and clinical use are discussed
Understanding Stress, Strengths, and Strategies to Support Immigrant Youth: A Bundled Dissertation
Get PDFIn the study of child development and mental health of Latine and immigrant and refugee youth, it is necessary to understand their cultural experiences and stress experiences in the U.S. The present project aims to address culture, stress, and the development of internalizing outcomes among Latine, immigrant, and refugee youth across two important stages of development: middle childhood and adolescence. The first study provides a comprehensive review of Latine children’s immigration experiences, the effects of exposure to multiple stressors, cultural factors, and intervention implications. The second study provides a focused examination of the impact of two culturally relevant stressors among Mexican-origin families, which provides more tailored implications. Results highlighted the effects of economic strain and family cultural conflict on children’s internalizing outcomes, as well as considerations for the measurement of cultural factors and stressors. Finally, the third study evaluated a trauma-informed school-based intervention for immigrant and refugee youth, which highlighted important considerations for accessible, sustainable, group-based treatment. Results revealed the relevance and mental health benefits of delivering mental health interventions in a school setting for youth. Parent and student feedback also provided important considerations in improving the intervention to better suit newcomer family needs
Exploring the Relationship between Teachers\u27 Religious Identity and Culturally Responsive Pedagogy
Get PDFThe Separation of Church and State Clause prohibits religious practices in public schools; however, this does not inherently allow for the exploration of how religion/faith influences K-12 education and school dynamics. Administrators’ and teachers’ religious affiliation contributes to their positionality and shapes their moral ethics. To assume that K-12 teachers are not engaging with their faith and allowing it to influence how they view their students, and their teaching practice is naïve and negligent. Additionally, explicitly discussing faith is prohibited and to this end, this restriction can breed ‘unchecked’ unconscious bias. This leads to a lack of training and reflexivity for religious identity in teacher education programs. This establishes a need for teacher candidates and existing teachers to consider how their faith influences their pedagogy in school systems where faith is both engaged and restricted. Culturally responsive pedagogy is a valuable and beneficial approach to addressing the diversity reflected in schools across the United States. It is an approach widely respected among practitioners, has been widely researched, and is the focus of countless amounts of scholarship. There is a gap in the literature addressing culturally responsive pedagogy and religious identity, and teacher training programs are not engaging their faith identity and how it may shape or contribute to their teaching practices. Employing FaithCrit as a lens and framework, this qualitative study aims to examine the religious identity of urban K-12 schoolteachers and how their religious identity is related to and influences their culturally responsive pedagogy
Hardening Interpretable Deep Learning Systems: Investigating Adversarial Threats and Defenses
Get PDFDeep learning methods have gained increasing attention in various applications due to their outstanding performance. For exploring how this high performance relates to the proper use of data artifacts and the accurate problem formulation of a given task, interpretation models have become a crucial component in developing deep learning-based systems. Interpretation models enable the understanding of the inner workings of deep learning models and offer a sense of security in detecting the misuse of artifacts in the input data. Similar to prediction models, interpretation models are also susceptible to adversarial inputs. This work introduces two attacks, AdvEdge and AdvEdge + , which deceive both the target deep learning model and the coupled interpretation model. We assess the effectiveness of proposed attacks against four deep learning model architectures coupled with four interpretation models that represent different categories of interpretation models. Our experiments include the implementation of attacks using various attack frameworks. We also explore the attack resilience against three general defense mechanisms and potential countermeasures. Our analysis shows the effectiveness of our attacks in terms of deceiving the deep learning models and their interpreters, and highlights insights to improve and circumvent the attacks
Revisiting Marcuse on Repressive Tolerance: A Twenty-First Century Retrospective
No full textHerbert Marcuse’s essay Repressive Tolerance (RP) has been praised by the Left and vilified by the Right for its alleged promotion of censorship targeting reactionary opinions and actions. I argue that this interpretation of the text is mistaken. According to my alternative reading of the text, RP should be understood as an exercise in provocation and irony aimed at defending civil disobedience and dissent. Marcuse’s defense of dissent, however, appeals to a critique of pure tolerance that exposes the unavoidably partisan practice of tolerance, which invariably favors the reigning undemocratic status quo. The choice whether to tolerate in a manner that discriminates in favor of opinions and actions that are likely to advance the democratic conditions essential to a more just and epistemically sound exercise of toleration or to discriminate in favor of those that hinder them ---a distinction, as Marcuse sees it, that corresponds to the distinction between the Left and the Right---is dictated by reason itself, whose exercise depends on toleration. Because toleration must discriminate in the absence of full reason, its fallible exercise in favor of reason and democracy must proceed cautiously, not by suppressing voices on the Right so much as selectively encouraging those on the Left. I conclude that because this equation of impartial reason with a partisan view of society is unavoidable regardless of one’s political sympathies accusing Marcuse of being elitist and hypocritical is itself hypocritical
