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Groundless Belief in Conspiracies
No full textThe central question of my dissertation is: What, if anything, justifies laypeople in rejecting conspiracy theories? Nevertheless, before discussing the relevant epistemological considerations, I begin by clarifying what “conspiracy theory” means in Chapter 1. It has been suggested that conspiracy theories must always posit preternaturally effective conspirators, be irrational to believe, and conflict with some official explanation. I evaluate which of these entailments hold and which do not. After clarifying the subject matter, I consider a popular objection to conspiracy theories: namely, conspiracy theories must be false because, if they were true, someone would have leaked them to the public. In chapter 2, I note several limitations of this argument: It does not apply to small conspiracies or new conspiracies, and it begs the question by ignoring conspiracy theorists’ arguments. In chapter 3, I consider a different rationale for rejecting conspiracy theories. I argue that, based on evidence from credentials and expert consensus, laypeople are justified in trusting mainstream sources of information that reject conspiracy theories. Conspiracy theorists often allege that trusting mainstream sources is naïve, so it is important to show that it is rational. Nevertheless, testimonial justification is defeasible. So, it might be objected that our justification for rejecting conspiracy theories is often defeated by arguments cited by conspiracy theorists. In chapter 4, I argue that this objection is mistaken because, as laypeople, it should be unsurprising that someone can cite arguments for a conspiracy theory that seem tempting at first glance
From Design to Delivery: The Development of Regenerative Therapies From Immune-compatible, Non-human Donors
Get PDFRegenerative medicine is an interdisciplinary field that aims to achieve restoration of lost function via stimulation of the body’s natural healing mechanisms. Allotransplantation has been the predominant modality, but remains fraught with unresolved challenges and ethical concerns, especially regarding the use of materials obtained from the deceased. Adverse immunological responses against non-self-antigens, especially those of the major histocompatibility complex (MHC), result in few compatible donor-recipient pairs, requiring toxic, immunosuppressive drugs to prevent transplant rejection. Consistently achieving FDA manufacturing standards such as sterility, purity, and potency with human tissues remains cumbersome. Consequently, safety issues persist, and an adequate, equitable supply remains elusive. We hypothesized that immune-compatible, non-human transplant donors may offer a practical alternative. Given their highly conserved homologous genome and well-documented phenotypic similarities with Homo sapiens, we reasoned Sus scrofa to be the ideal basis for a xenogeneic, therapeutic platform. To evaluate this empirically, we developed manufacturing and regulatory protocols to procure skin xenotransplants for use in the first, US-FDA clinical trial of a live, xenotransplant, wherein we replaced the eviscerated skin of severely burned patients with whole, intact skin from a porcine donor with a single genomic alteration leading to complete wound closure. The success of this major in vivo proof-of-concept led to investigations into the feasibility of other acute xeno-solutions, such as peripheral nerve reconstruction. Beyond elimination of the alpha-Gal carbohydrate, utilizing CRISPR-Cas-9, we reprogrammed sections of Class I, II, and Beta-2-microglobulin exonal regions of the Sus scrofa MHC to improve immune-compatibility without impairment to biological function. Our overall engineering strategy was to mimic the MHC configuration of the syncytiotrophoblast, the cell lineage covering the placental villi that establishes circulation between embryo and mother, in utero. By transferring the nucleus of these immune-corrected cells into an enucleated oocyte, followed by their implantation into the oviducts of hormonally synchronized surrogates, optimized, “prefabricated” animal-transplant donors can be created under cGMP conditions. This dissertation discusses this longitudinal process and the therapeutic implications of the use of functionally equivalent cells, tissues, and organs from immune-compatible non-human donors toward unlocking the full potential of regenerative medicine
THE MENTAL HEALTH IMPACT OF ENGAGING MEN IN WOMEN’S HEALTH INTERVENTIONS
Get PDFBackground
There has been a global push in the field of public health to increase men’s involvement in women’s health. In the last decade, maternal and child health and women’s reproductive health programs have lead the way in engaging men in the intervention. There is ample evidence showing that engaging men in women’s health interventions improves women’s physical health outcomes. Yet there is a need to further explore the impact of male engagement on women’s mental health.
Methods
In Chapter 4 we provide a systematic review of women’s health interventions that have engaged male partners and reported women’s mental health outcomes. In Chapter 5 we quantitatively characterized subgroups of couples who differ in their attitudes towards gender norms and power sharing practices and examine how women in these heterogenous couples may vary in their mental health after participating in an intervention that engaged their male partners using a latent profile analysis. In Chapter 6 we explored male partner’s perspectives on being engaged in an intervention specifically aiming to address postpartum depression.
Results
In Chapter 4, our review revealed that most studies that engage men in a women’s health intervention found positive impacts on women’s mental health. We also found that there is a gap in the research on the best practices for measuring male engagement beyond taking attendance. In Chapter 5 we identified three different patterns of gender attitudes and power sharing in couples: 1) men held inequitable gender attitudes and unequal power sharing views and women held neutral gender attitudes and power sharing views; 2) both men and women held equitable gender attitudes; and, 3) both men and women held similar average viewpoints about gender norms and power sharing, meaning they held less equitable viewpoints. Class membership did not predict women’s depressive symptoms. In Chapter 6 we found that husbands of women who experienced a reduction in their postpartum depression described holding more equitable gender norms and attitudes in their household and provided emotional support on top of instrumental support.
Conclusions
The findings from this dissertation highlight the need to measure male engagement in a more robust standardized manner, the need to address gender norms and power imbalances if men are engaged in an intervention, and the importance of emotional support from male partners
MODELING POLLINATOR BEHAVIOR THROUGH SURVIVAL ANALYSIS
Get PDFThis study applies survival analysis to pollinator-plant relationships, modeling floral-resource utilization by pollinators. Three types of survival analysis models are compared, including the Cox proportional hazards model, a binary classification model using stacking, and a Logistic Hazards neural network model. These models are trained on a dataset of pollinator arrival times. Weather data covariates are included with the pollinator arrivals. The models demonstrate the effectiveness of survival analysis in understanding and predicting pollinator behavior. The factors influencing the resource utilization of different pollen-producing plants is better understood. The findings have significant implications for pollinator conservation, habitat restoration and the sustainability of our agricultural systems. Additionally, the research advances the field of survival analysis by its comparison of different survival analysis models, its inclusion of time-dependent covariates and its application to novel ecological data
Development of the Novel Sutureless Anastomosis Device, VasoLock
Get PDFVascular anastomosis is a surgical procedure that connects vessels to each other. [1] The current gold standard for vascular anastomosis procedures is via suturing. However, this procedure requires very skilled vascular surgeons who undergo long training, is costly, not free of complications, and has inconsistent results. Additionally, suturing vessels causes vascular wall damage. [2] A novel sutureless anastomosis stent device, VasoLock, provides a less invasive anastomosis alternative. [3] The VasoLock stent device is comprised of a hollow cylindrical stent with anchors on its outer ends, inspired by the Rosa Arvensis Splendens rose, whose prickles allow it to adhere to and grow along wall surfaces. When inserted inside of vessels, it allows for rapid directional interlocking with tissue. The VasoLock has been further developed in this study. The VasoLock device and its anchors can be varied in their geometry, density, and arrangement to be optimized for adhesion to a given surface/tissue. In this essay, the density and device outer diameter were optimized for a porcine carotid artery tissue model using artificial intelligence models with iterative testing. Additionally, the VasoLock device was further developed for shunt applications. The VasoLock shunt system is composed of a set of newly designed VasoCuff devices joined by flexible PTFE graft secured with Surgical Adhesive BioGlue. Additionally, the VasoLock device deployment was further studied for easier deployment of the original device for users
Factors Impacting Injection Forces of High Concentration Monoclonal Antibody Formulations: The Significance of Needle Dimensions and Fluid Viscosity
No full textSubcutaneous injection of concentrated biologics is hindered by the need to apply large forces to deliver a full drug dose. End-users are limited by their strength and may not be able to manually administer high concentration formulations due to their high viscosity. Several factors impact injection forces, including drug product formulation, syringe design, lubrication, and storage conditions. The present thesis provides a comprehensive review of these factors, among which needle dimensions, drug product viscosity, and barrel lubrication have the most significant impact on forces required for safe and comfortable administration. The effects of needle length, needle inner diameter, and drug product viscosity are further explored by measuring the forces required to inject monoclonal antibody (mAb) solutions of increasing protein concentrations through various needle types. The glide force increased exponentially with drug product concentration and decreased by a power-law relationship with widening needle inner diameters. A rheological evaluation of the drug product was also conducted to measure viscosity at different concentrations and various shear rates to characterize the Newtonian or non-Newtonian behavior of the products. All force measurements were compared to calculations from a modified Hagen-Poiseuille equation and two non-Newtonian models, all of which predicted the injection forces with less than 25% error. However, deviations from all three models were identified in drug product concentrations above 230 mg/mL and in thin needles (27G, 30G) potentially due to complex interactions in the bulk flow and insufficient characterization of high shear viscosity behavior and needle dimensions. Additional product- and patient population-specific development studies characterizing barrel lubricant layer quality, long-term syringe storage, and human factors can reveal potential worst-cases to enhance the injection of high concentration drug products to be of utmost comfort for the patient
Canine Behavior in Egyptian Art: A Behavioral Analysis of the Domestic Dog Icon in 18th Dynasty Theban Tombs
No full textThe wall scenes of the rock-cut Theban tombs of the New Kingdom are filled with richly painted imagery that captures the lives and beliefs of the people who built them, offering modern viewers a window through which to recognize and relate to a distant past. Scholars have long been drawn to canine imagery in Egyptian tombs, but past approaches to dogs in Egyptian art have largely taken an anthropocentric view, focusing on what the dog tells us about the lives of people while ignoring the dog’s unique ethology and role in art.
Eighty-nine domestic dog icons appearing across 28 Theban tombs dated to the 18th Dynasty serve as the primary focus of this study. Contemporary and non-contemporary representations of the domestic dog within and outside of Thebes and across a variety of media are considered secondarily as points of comparison of the icon’s changing role in Egyptian funerary art through time.
Through applying modern ethological studies and the author’s observations of modern village dogs in Luxor to representations of the domestic dog icon in Egyptian tomb scenes, this dissertation investigates the relationship between canine ethology and funerary art. The ethological method allows for a neutral approach to the domestic dog in Egyptian art without ascribing their presence in tomb scenes wholly or foremost to their status as pets.
The dog icons studied in this dissertation were grouped and analyzed within the contexts of the scenes in which they appear, namely hunting, natural resource, offering and banqueting, nursing, and tribute scenes, in order to establish canine behavioral trends and suggest their significance in the tomb context.
The behaviors depicted by artists were those deemed most essential to the scene in which they appear, thus alluding to the role that the dog icon played within the scene. Behaviors that deviate from these trends, or from established forms and sequences of behavior in living canines, offer unique insights into how ancient artists manipulated established behavioral forms to reinforce the meaning of the scene itself and fulfill the needs of the tomb owner
Essays on Saving and Portfolio Choices
No full textThis dissertation comprises three independent chapters. The chapters combine individual level data with models of life-cycle saving to study various sources of heterogeneity in wealth and portfolios, and the welfare effects of policy changes.
The first chapter studies survey measurements of households' expectations about U.S. equity returns, which show substantial heterogeneity and large departures from the historical distribution of actual returns. I build a life-cycle model of saving and portfolio choices that incorporates beliefs which match these survey measurements. Historically, models explaining risky portfolio choices have required much higher estimates of the coefficient of relative risk aversion than models which match wealth age-profiles; the introduction of beliefs that match survey measurements relaxes this tension and allows the model to better explain both phenomena. The change in estimated preferences has significant implications for the welfare effects of various social programs.
The second chapter studies the relationship between wealth and genetic endowments previously linked with education. We use a life-cycle model of consumption, savings, and portfolio decisions, to quantify the various channels through which these genetic endowments contribute to wealth differences. Even accounting for completed education, childhood socioeconomic status, and inheritances, we estimate that these genetic factors increase wealth both through life-cycle income profiles and through rates of return on invested wealth. Counterfactual exercises predict how social security reforms would modify these relationships. We find that some policies may simultaneously flatten gene-wealth gradients but increase gene-welfare inequality.
The third chapter studies the aggregate and distributional effects of monetary policy in a Heterogeneous Agent New Keynesian model that explicitly represents the life-cycle of households. The model matches the age-patterns in the level and dispersion of labor income and financial wealth in the U.S. Monetary policy affects the consumption of young households mainly through labor income, and the consumption of old households mainly through asset returns. More than half of the aggregate consumption response to an expansionary monetary policy shock comes from those below the age of 40. The shock redistributes welfare from the wealthiest old to the poorest young and increases average welfare of most cohorts
THE IMPACTS OF DYSREGULATED CLAUDIN7 EXPRESSION ON BREAST CANCER CELL INVASION
No full textMetastasis is the primary cause of deaths in breast cancer. Invasion is the first step of this multi-step metastatic cascade and requires alterations in cell-cell adhesion. Claudin proteins are part of the tight junctions that help maintain epithelial intercellular adhesion and barrier function. Claudin 3, 4, and 7 are downregulated in the aggressive breast cancer subtype, claudin-low, which is associated with poor prognosis. The correlation between the low expression of claudins and breast cancer cell invasion is not fully understood. Here, we were specifically interested in claudin 7 (Cldn7) and whether this protein has a causal effect on cell aggressiveness. Therefore, we used two human breast cancer cell lines and a non-tumorigenic human mammary epithelial cell line to knockout, knockdown, and overexpress claudin 7 (Cldn7) to assess its effects on cancer cell behavior. We employed both conventional 2D cell culture and 3D spheroid culture assays to examine roles of Cldn7 in invasion. We found that either Cldn7 knockout or knockdown is sufficient to promote invasion. We also demonstrated that Cldn7 loss increased spheroid growth and decreased cell-cell adhesion. In addition, overexpression of Cldn7 is also adequate to inhibit invasion. Taken together, our data reveal that Cldn7 suppresses breast cancer cell invasion, cell growth, and cell-cell adhesion
UNDERSTANDING THE VIROLOGICAL FEATURES OF SARS-CoV-2 XBB VARIANT SPIKE PROTEIN
Get PDFFollowing the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.5, the Omicron XBB variant and its sublineages, XBB.1.5 and XBB.1.16, outcompeted BA.5 in
2022. Combining the genomes of two Omicron BA.2 lineages, Omicron XBB poses significant concerns due to its heightened transmission and ability to evade the immune system. Numerous mutations are present in the XBB spike protein, which is an important factor in the process of SARS-CoV-2 infection. This study explores the impact of four spike mutations (E180V, G252V,
T478R, and F486P) present in the Omicron XBB variant and its two sublineages, XBB.1.5 and XBB.1.16, using non-codon optimized spike sequences. The syncytia assay was utilized to assess syncytia formation, a process often considered a means by which viruses infect neighboring cells without eliciting an immune response, of the spike protein of the XBB variant and its four single mutant counterparts. Results from syncytia assays indicate that, compared to the Delta variant's spike, the XBB variant spike and its three single mutant spikes (excluding G252V) exhibited reduced fusogenicity. However, the fusogenicity of the four single mutant spikes did not differ
from that of the parental XBB spike. Additionally, flow cytometry data revealed no disparity in spike expression on the cell surface among the Delta spike and the four single mutant spikes, except the XBB spike showed a slightly lowered expression level, indicating differences in XBB
spike fusogenicity were likely not due to spike surface expression differences. Overall, the findings of this study align with those of previous studies employing codon-optimized spike sequences. Further research is needed to elucidate the impact of these four mutations on virus replication kinetics