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Exploring the role of neuronal pentraxin 2 in neuropsychiatric diseases
No full textNeuropsychiatric diseases are a group of disorders that affect the brain and its functions, leading to disturbances in behavior, mood, and cognition. These diseases can range from relatively mild anxiety or depression to severe debilitating conditions including schizophrenia and Alzheimer’s disease. These disorders are understood to involve changes in synaptic connectivity between neurons and current models suggest an important role for inhibitory circuits. Inhibitory circuits function by balancing the activity of excitatory neurons and impose conditions necessary for network synchronicity that underlies attention and memory. Understanding the role of inhibitory circuits in neuropsychiatric diseases is critical for the development of effective treatments and therapies.
NPTX2 is an immediate early gene that functions at excitatory synapses and plays a unique role in regulating the strength of excitatory drive of parvalbumin interneurons (PV-INs). This action mediates excitatory homeostasis since increases of activity increase NPTX2 expression which has the effect to enhance inhibition and supports the creation of ensembles of neurons that encode information. According to recent evidence, there is a downregulation of NPTX2 in cerebrospinal fluid (CSF) in patients with Alzheimer’s disease and schizophrenia, suggesting that NPTX2 loss of function could contribute to cognitive deficits associated with neuropsychiatric diseases.
In the current study, I investigated NPTX2 protein expression and functional complex formation with other related proteins examining frozen human postmortem brain specimens of Alzheimer’s disease (AD) and frontotemporal dementia (FTD), as well as a cognitive-impaired rat model. I observed significant reduction of NPTX2 protein expression in the brain and corresponding decreased functional complex formation with GluA4, implicating altered regulation of PV-INs. I also investigated the role of NPTX2 in stress responses and observed a decrement of NPTX2 expression after chronic stress and elevated NPTX2 functional complex with GluA4 induced by ketamine after acute stress
Asymptotics and Statistical Inference in High-Dimensional Low-Rank Matrix Models
No full textHigh-dimensional matrix and tensor data is ubiquitous in machine learning and statistics
and often exhibits low-dimensional structure. With the rise of these types of data is the need to develop statistical inference procedures that adequately address the low-dimensional structure in a principled manner. In this dissertation we study asymptotic theory and statistical inference in structured low-rank matrix models in high-dimensional regimes where the column and row dimensions of the matrix are allowed to grow, and we consider a variety of settings for which structured low-rank matrix models manifest.
Chapter 1 establishes the general framework for statistical analysis in high-dimensional low-rank matrix models, including introducing entrywise perturbation bounds, asymptotic theory, distributional theory, and statistical inference, illustrated throughout via the matrix denoising model. In Chapter 2, Chapter 3, and Chapter 4 we study the entrywise estimation of singular vectors and eigenvectors in different structured settings, with Chapter 2 considering heteroskedastic and dependent noise, Chapter 3 sparsity, and Chapter 4 additional tensor structure. In Chapter 5 we apply previous asymptotic theory to study a two-sample
test for equality of distribution in network analysis, and in Chapter 6 we study a model for shared community memberships across multiple networks, and we propose and analyze a joint spectral clustering algorithm that leverages newly developed asymptotic theory for this setting.
Throughout this dissertation we emphasize tools and techniques that are data-driven, nonparametric, and adaptive to signal strength, and, where applicable, noise distribution. The contents of Chapters 2-6 are based on the papers Agterberg et al. (2022b); Agterberg and Sulam (2022); Agterberg and Zhang (2022); Agterberg et al. (2020a) and Agterberg et al. (2022a) respectively, and Chapter 1 contains several novel results
ELECTROCHEMICALLY TUNABLE TWO-DIMENSIONAL MEMBRANES FOR IONIC AND MOLECULAR SIEVING
No full textPurifying mixtures is still a tough objection currently. Conventional separation processes based on thermal or chemical methods would higher global energy consumption and pollution emission. Hence, alternative routes need to be explored to separate chemicals more efficiently and eco-friendly. Membranes with preeminent perm-selectivity are essential for processes such as water purification and desalination, pharmaceutical manufacturing, resource mining, etc. Although traditional polymer membranes already showed substitutability in these fields, most of them were restricted by materials’ trade-off effect, that is, high permeability and selectivity couldn’t be achieved at the same time. In the past decade, nanolaminate membranes made of restacked two-dimensional (2D) materials such as reduced graphene oxide (rGO) are demonstrated to be promising candidates for ionic and molecular sieving via size-limited diffusion through the interlayer gaps. However, the biggest challenge is that the interlayer spacing is hard to control and manipulate continuously and reversibly, leading to limited and poor performance in separating ions or molecules of similar sizes. This project proposes a new concept of electrochemically tunable membranes by introducing redox-active molecular spacers between rGO nanolaminates via π-π interaction. Redox agents such as ferrocene and its derivatives are sensitive to electrochemical potential stimuli, which can lead to changes in charge density and hydration level of the interlayer environment to achieve precise tuning in interlayer spacing. This tunable membrane is a promising candidate for next-generation separations that can not only adapt to the demands of various scenarios in the chemical and pharmaceutical industries but also play a pivotal role in energy generation like reverse electrodialysis
Examining Family and Household Factors Related to HIV Self-Management Among Adolescents and Young Adults Living with HIV in Ndola, Zambia
No full textBackground: To end the AIDS epidemic by 2030, the health needs of adolescents and young people (AYA) aged 15 to 24 years living with HIV must be met. AYA often struggle to successfully manage their HIV and achieve viral load suppression (VLS) compared to their adult counterparts. Family and household members of AYA living with HIV are in a unique position to support their youth’s health and HIV self-management. The goal of this dissertation is to better understand how family level factors relate to and influence HIV self-management of among AYA in Zambia.
Methods: This iterative, mixed-methods study leveraged the data and infrastructure of the completed Project YES! study (NCT04115813). Project YES! that sought to improve VLS among AYA living with HIV in Ndola, Zambia. We conducted an inductive and deductive thematic analysis of in-depth interviews (IDIs) from 21 caregivers of AYA Project YES! participants. We developed a structural equation model using baseline data from 254 AYA Project YES! participants to quantify and explain associations between family connection and VLS. We conducted and thematically analyzed IDIs with 17 former AYA Project YES! participants and 13 of their caregivers. Finally, we integrated the qualitative and quantitative findings to enhance understanding of the results of this dissertation.
Results: Quantitatively, we found no associations between family connection and VLS and a positive association between perception of family recognition and treatment adherence self-efficacy. Qualitatively, AYA and caregivers described family influences on AYA’s HIV self-management; these included HIV beliefs and perceptions, family involvement, caregiver monitoring and supervision, family relationship quality, and family functioning. These influences collectively shaped: (1) opportunities for self-management support from family, (2) the youth’s self- perceptions, feelings about living with HIV, and self-management behaviors, and (3) the family environment in which the AYA practiced their HIV self-management.
Conclusion: This dissertation discerns how different dimensions of family and household relationships and support shape the self-management of AYA living with HIV in Ndola, Zambia. These results underscore the importance of intervention and research that address family and household influences and offer important insights to guide future efforts to this end
Essays on the Macroeconomic Fallout From Financial Crises
No full textThe first chapter studies the adverse long-term impact of a decline in lender health on aggregate productivity. I develop a simple model of productivity-enhancing investment where firm exposure to fragile banks leads to losses on both the intensive and the extensive margin. Using data on Spanish firm-bank relationships and bank bailouts, I implement an exit-adjusted measure of productivity growth and use it to quantify the output loss attributable to the financial friction. A decade after the crisis, output growth from the extensive margin recovers but the output shortfall from the intensive margin proves much more persistent. Together, these dynamics amount to a cumulative loss of 3 percent of pre-crisis GDP over ten years.
The second chapter is joint work with Clemens Possnig and Kyungchul Song and develops an empirical methodology for measuring the direction of spillover of economic outcomes between two groups linked through multiple networks. We develop a dynamic linear panel model and asymptotic inference with large n and small T. We employ the model in an empirical study of spillovers between bank weakness and zombie-firm congestion in industrial sectors, using firm-bank matched data from Spain between 2005 and 2012. Overall, we find that there is positive spillover in both directions between banks and sectors.
The third chapter is joint work with Olivier Jeanne and studies the macroeconomic adjustment mechanism inside a currency union. According to the textbook model, a country in a currency union can become more competitive through internal devaluation which requires a certain level of unemployment. This paper assesses the relevance of this mechanism in explaining trade rebalancing in the euro area during 2007-2019. On one hand, the model implies that the average euro area country must bear a cumulative unemployment rate of 3.3 percent in order to increase its export-to-GDP ratio by 1 percent. On the other hand, internal devaluation does not seem to be the main mechanism behind the largest increases in the trade balance of euro area countries between 2007 and 2019
A Hard Pill to Swallow: Using Shared Decision Making to Combat Online Misinformation About Hormonal Contraception
No full textHormonal contraception remains a monumental discovery in reproductive healthcare. Over the last decade the internet has become a hub of information about hormonal contraception.
While some information is helpful for women to access and better understand their health, the internet environment is vulnerable to misinformation. This misinformation coupled with a lack
of effective contraception counselling leaves women without the information and resources they want to make decisions about contraception that is right for them. In this paper I propose a
timeline demonstrating how ineffective contraceptive counselling leads to an increase in misinformation online about hormonal contraception. I then propose shared decision making as a
tool for providers to use to improve contraception counselling which will result in better contraception adherence, increased patient satisfaction and enhanced patient autonomy
ONE NATION, DIVIDED: THE COMPLICATED UNDERPINNINGS AND EXPRESSIONS OF PARTISANSHIP WITHIN THE INCREASINGLY HOSTILE AMERICAN ELECTORATE
No full textThere is broad consensus that the policy gap is widening between the Republican Party and Democratic Party platforms, between politicians in institutions at all levels of government, and between party activists and political elites. However, academic debate continues as to whether—and to what degree—this divide exists among average American voters. Evidence has been mixed, inconsistent, and subject to a number of interpretations and caveats. Persistent, though, is data that show opposing partisan voters are growing more hostile towards each other than differences in their policy differences, alone, can explain.
This thesis demonstrates that partisanship and inter-voter affect go far beyond the left-right divide; that the political and social are enmeshed in a complex, nuanced, and bidirectional web of interrelated identities; but also, and is importantly, that under the right conditions these attachments can be augmented, divisions—perceived and actual—softened, and hostility ameliorated.
Through exploration of the political, social, psychological, and even moral underpinnings of partisanship, this work underscores the criticality of continued investigation; the necessity in understanding and acknowledging partisans as individuals—not just voters; and that the disunion of the electorate need not be entirely erased to promote a more productive American polity
UNDERSTANDING AND IMPROVING DIVERSITY IN CLINICAL RESEARCH FOR BLACK PATIENTS: A QUALITATIVE META-ANALYSIS STUDY
Get PDFBlack patients remain underrepresented in clinical research, representing 5% of patients enrolled United States clinical trials (Alegria et al., 2021). Lack of diversity in clinical research creates blind spots about the effectiveness of treatments in underrepresented populations, resulting in substandard downstream care. Through analysis of available literature on Black patient engagement in clinical trials, proposals can be made to increase trial enrollment and equity.
A qualitative meta-analysis was conducted to interpret research completed to date on increasing clinical research diversity for Black patients. A PubMed literature search yielded 720 possible articles, 35 were used for meta-analysis. Each article underwent multiphasic review to identify research characteristics; generate enrollment promotors and barriers, identify themes; identify significant findings across multiple articles; identify under-investigation and contradictory findings; and review solutions applicable for future research.
Enrollment promotors included thorough explanation and information provision on study design, possible downstream beneficiaries; strong/longitudinal researcher-participant relationships and researcher-participant racial concordance; higher income and socioeconomic status of participants; research institution accessibility; compensation and increased study funding; community outreach and personal contact; and personal connections to research for both participants and researchers. Enrollment barriers included low income/socioeconomic status, low education, unfeasible time commitments, lack of transportation; lack of trust in medicine and clinical research teams; inadequate information on clinical research; studies requiring medical record review, blood samples, novel pharmaceutical interventions, and invasive procedures; and studies with comorbidities as exclusion criteria.
Themes in research conducted to date include cancer research, investigations into Black women, and historical, structural, and personal factors. Historical factors that affect enrollment for Black patients include mistrust of the medical establishment, research institutions, and researchers. Structural barriers include income, socioeconomic status, time commitment and lack of transportation as well as exclusionary study designs and lack of resources for better clinical research engagement. Personal factors showcase the need for nuanced engagement around personal connections to research subjects, and benefits and pitfalls of utilizing religious institutions as partners depending on the research study subject. Solutions from current literature included better research explanation, improving diversity of clinical research teams, increasing interactive instruction, and using unique methods of increasing community around clinical research
STUDYING H3N2 EVOLUTION THROUGH THE 2021-2022 AND THE 2022-2023 INFLUENZA SEASON
No full textThe H3N2 viruses circulating during the 2021-2022 influenza season predominantly belonged to the clade 3C.2a1b.2a.2. Sequence analysis of circulating viruses in North America, that have evolved from viruses from the clade 3C.2a1b.2a.2, such as 3C.2a1b.2a.2a, 3C.2a1b.2a.2a.1, 3C.2a1b.2a.2a.1a. 3C.2a1b.2a.2a.1a and 3C.2a1b.2a.2a.3 showed that the viruses contained a truncation of 11 amino acids was present in the small, 90 amino acid immunomodulatory protein PB1-F2. Viruses from the clade 3C.2a1b.2b that were in circulating during the 2018-2019 flu season expressed a full-length PB1-F2. Translated from the +1 ORF of the PB1 segment of some Influenza viruses, this protein serves to promote apoptosis and antagonizes interferon responses in infected cells. To assess if this truncation had any effect on viral fitness, plaque assays were performed with viruses from both the 2018-19 and 2021-22 influenza seasons. Viruses from 3C.2a1b.2b had smaller plaques compared to the viruses circulating during the 2021-2022 season. Viral replication was also quantified with low MOI growth curves on primary, differentiated human nasal epithelial cells cultures. Viruses from both seasons replicated to similar peak titers indicating no distinct replication advantage change across seasons. When production of IFN- λ was measured, viruses from 2018-2019 produced less IFN- λ than viruses from 2021-2022, suggesting an altered induction of antiviral responses.
The 2022-2023 Influenza season came much earlier than expected and had very high levels of virus circulation in the United States. The clade 3C.2a1b.2a.2 evolved into several smaller clades including 3C.2a1b.2a.2a.1, with additional E50K, D53G, K276R H156S and I192V HA mutations, 3C.2a1b.2a.2a.3 with D53N, H156S and I192F HA mutations, 3C.2a1b.2a.2a.3a.1 containing E50K, D53N, H156S, I192F and I140K mutations on HA, and 3C.2a1b.2a.2b with E50K and I140K mutations. Subsequent analysis of the other genome segments revealed complex reassortments with viruses from the clade 3C.2a1b.1a. Plaque assays and hNEC growth curves were used to determine whether there were fitness changes associated with the 2022-23 H3 clades
Strengthening the North American Nuclear Supply Chain: A Framework for Canada - U.S. Collaboration in the Deployment of New Nuclear
No full textIn the nuclear arena, Small Modular Reactors have transitioned from development projects to commercialization with the first consortium formed and contract signed at the end of 2022. As the industry tries to transition from its legacy large infrastructure-type developments to these sleek “New Nuclear” designs, there will be many challenges, not the least of all to grow a supply chain to support this industrialization. As deglobalization, a global pandemic and a war in the Ukraine disrupt supply chains and threaten national security, the challenge is intensified. Strengthening partnerships with existing allies, like the relationship between Canada and the United States, may lead to some obvious solutions. By performing a bottom-up comparative analysis of the nuclear supply chain in Canada and the United States, a framework can be created to identify strengths and weaknesses, as well as opportunities on both sides of the border. An integrated collaborative development plan will maximize efforts going forward to create an effective supply chain for New Nuclear. Some policy suggestions are offered, and evaluation of real opportunities considered in this dynamic development process