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“Bloody Brilliant”: A mixed methods approach to studying menstruation on Television and in Movies from 1970 to 2024
No full textAs reproductive and sexual health education declines in the United States, adolescents may turn to television shows and movies for this education. There is an opportunity to create informed edutainment with this in mind. However, there is no content analysis for the content already in the world. This paper serves as a preliminary content analysis for content containing menstrual themes from 1970 to 2024. Researchers examined the context in which menstruation is shown or discussed and collected data to analyze gender concordance between the character menstruating or mentioning menstruation, the director, and the topline writer of the media. There was not enough evidence to show that menstruation content is less distressing or is shown in a more nuanced way, but there is evidence that gender concordance has increased over time, particularly into the 2020s
Evaluating ferrets as a novel small animal model of aerosol exposure to encephalitic alphaviruses
No full textVenezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV) are positive-stranded RNA viruses belonging to the genus of Alphaviruses in the family of Togoviridae. These are arthropod-borne viruses, and natural disease outbreaks are typically associated with amplification in equine species. In humans, they cause severe viral encephalitis; while VEEV is rarely fatal, EEEV has a high mortality rate of >30%, and survivors have long-term neurological sequelae. There remains a considerable concern that these viruses could be used as biological weapons; hence, they are classified as Select Agents. Currently, no licensed medical countermeasures are available, and our knowledge of the disease caused by inhalation of these viruses is limited as aerosols are not the natural route of transmission. Therefore, for the licensure of vaccines and therapeutics, pivotal efficacy studies are required to be done in animals according to the FDA’s Animal Rule. We are investigating whether ferrets might serve as an alternative to the current mouse and non-human primate model for VEEV and EEEV, as their respiratory tract anatomy is similar to humans, and they are susceptible to other human viruses such as influenza, filoviruses etc. Moreover, the differences in human and rodent pharmacology underscores the need for an alternative small animal model
The Political Dimension of Restricting Gender-Affirming Care for Transgender and Gender Non-Conforming Adolescents in the United States
No full textBeginning in 2021, there has been a concerning surge in legislative measures aimed at restricting access to gender-affirming care for transgender and gender non-conforming (TGNC) adolescents despite its crucial role in their healthcare. These measures, often driven by political ideologies rather than evidence-based considerations, pose significant threats to the well-being and rights of TGNC individuals.
Gender-affirming care, encompassing medical interventions such as hormone therapy and surgeries, along with psychological support, has shown compelling evidence of improving mental health outcomes and overall well-being for TGNC individuals. However, the implementation of such care is hindered by political agendas and misconceptions, highlighting the need for evidence-based policies.
This paper conducts a comprehensive literature review to examine the evidence supporting the effectiveness of gender-affirming care in improving mental health, quality of life, and social functioning for TGNC individuals. By synthesizing existing research, this paper aims to provide insights into the importance of gender-affirming care and the need for policies prioritizing inclusive and evidence-based healthcare for TGNC individuals.
Restricting gender-affirming care for adolescents has severe implications from a public health perspective. The denial of affirming care contributes to adverse mental health outcomes, compromised physical well-being, and hinders social integration for TGNC adolescents. Public health policies should prioritize the removal of barriers to gender-affirming care, ensuring that these adolescents receive comprehensive healthcare to support their overall well-being and reduce disparities. Further research and advocacy are necessary to promote evidence-based policies prioritizing the rights and health of TGNC adolescents
Insurance Coverage for Genetic Testing in Puerto Rico: A Comparative Analysis
No full textGenetic testing is pivotal in modern healthcare, enabling personalized treatment strategies and early disease detection. However, disparities in insurance coverage for genetic testing can impede access to these crucial services. The New York Mid-Atlantic Caribbean (NYMAC) Regional Genetics Network collaborates with stakeholders in Puerto Rico to improve access to genetic services. This study examines coverage for genetic testing in Puerto Rico by analyzing health insurance benefits from major Puerto Rican commercial insurers. Data were sourced from insurance summary of benefits documents and clinical molecular testing criteria. Coverage areas included general genetic services, common testing indications (e.g., autism, hereditary cancers), reproductive genetic concerns, and rare diseases specific to Puerto Rico. Comparison with mainland U.S. commercial insurers revealed gaps between mainland U.S. and Puerto Rican insurance policies. While mainland U.S. insurers provided detailed criteria for genetic testing, Puerto Rican policies contained limited information, or the medical policies were so convoluted that it was difficult to ascertain whether specific tests would be covered. There is also a significant gap in coverage for carrier screening, which is particularly relevant given the region’s unique genetic profile. NYMAC and other public health genetics-focused organizations can use the information gained from this analysis as a starting point to conduct further assessments to highlight health equity gaps and policy needs. This work is of great public health importance as it underscores a health equity issue that requires policy change around genetic testing coverage in Puerto Rico and describes potential solutions
Mutations in the Inner Pore of a CaV2.1 Voltage-Gated Calcium Channel Differentially Affect the Efficacy, Potency, and Binding Kinetics of an (R)-Roscovitine-Derived Positive Allosteric Gating Modifier
No full textInsufficient release of neurotransmitter from motor neurons is a cause of debilitating muscle weakness in multiple types of neuromuscular disease, including Lambert-Eaton Myasthenic Syndrome and Spinal Muscular Atrophy. Neurotransmitter release from motor neurons is controlled by the CaV2 family of voltage-gated Ca2+ channels (VGCCs), which open in response to an action potential, causing an influx of Ca2+ that triggers vesicle fusion. The drug GV-58, an analog of the CDK inhibitor (R)-roscovitine, has been found to rescue neuromuscular transmission in animal disease models by selectively prolonging the opening of CaV2 VGCCs, thereby enhancing Ca2+ influx during action potentials and increasing the probability of vesicle fusion. Other analogs of (R)-roscovitine have been shown to have similar effects on VGCCs, with varying degrees of selectivity, potency, efficacy, and speed of action.
Understanding where (R)-roscovitine analogs bind to VGCCs and the mechanism by which they prolong channel opening would aid in the design of new analogs with improved therapeutically-relevant characteristics, as well as providing new insight into the structural basis of VGCC gating. To investigate these questions, my colleagues and I used homology models of the structure of the VGCC subtype CaV2.1 to guide mutagenesis experiments aimed at identifying specific amino acid residues that may interact with (R)-roscovitine analogs.
In Chapter 3, we describe our in silico predictions of GV-58 binding, which support the interpretation that the (R)-roscovitine analog binding site is accessible from the plasma membrane through a fenestration in the channel protein. In Chapter 4, we present whole-cell patch clamp electrophysiology data from channels in which we had individually mutated amino acid residues that are unique to CaV2 channels and were predicted in silico to bind (R)-roscovitine analogs. We found multiple mutations that affect the drug’s ability to bind the channel and/or the extent to which drug binding prolongs channel opening. In chapter 5, we show how mutating key residues implicated in VGCC gating affects (R)-roscovitine analog action. Finally, in Chapter 6, we propose a mechanistic hypothesis of (R)-roscovitine analog action in VGCCs
Between a Rock and Hard Place: Three Essays on The Role of Domestic Politics during Economic Sanctions
No full textHow do economic sanctions affect the behavior of the sanctioned states? How does domestic politics moderate this relationship? Over the last few decades, a large body of literature has emerged that examines the effectiveness of sanctions. However, significant gaps in knowledge exist regarding the role of domestic public and politics in the target state. Particularly, I argue that we need to better incorporate the counter-veiling incentives the sanctioned states face. On the one hand, they have incentives to give in to avoid economic costs. But they also have incentives to stand firm to avoid the audience cost. Two factors likely play an important role in either aggravating or alleviating this dilemma the targets
face. In three essays, I examine the effect of target regime type and sender behavior. The first essay examines the role of regime type in whether targets meet the sender demands using a longitudinal analysis. I build a counter-intuitive theory regarding the non-linear effect of democracy challenging some of the existing approaches and find robust empirical support. The second essay explores the effect of sanctions on targets’ foreign policy behavior. Specifically, whether and how they affect the likelihood of a target’s taking militarized action. I find that sanctions increase the risk of a militarized inter-state dispute, even though
this risk is lower for some regimes than others. The third essay examines the effect of sanctions on public opinion in the target state through an original survey experiment fielded in Turkey. The effect on public opinion is a question which has long been seen as critical to understanding sanction effectiveness but one which has attracted scant empirical investigation. Taken together, this dissertation seeks to advance our understanding of the effect of economic sanctions on the target by employing a mixed-method approach and building on insights from multiple disciplines. The findings from this study also have broader implications
for the studies that focus on the role of domestic politics in coercive diplomacy and inter- and intra-state conflict
Diversity in spatial activities and parent spatial talk utterance length predict growth in preschoolers’ spatial skills
No full textSpatial cognition refers to a range of abilities related to visualizing, manipulating, and transforming objects and spaces. Previous research has shown that greater spatial cognition in childhood uniquely predicts later math skills and is linked to greater educational and occupational outcomes, especially in STEM fields. Additional research has shown that engaging in spatially related activities and play (e.g., puzzles, block building) positively influences spatial thinking and reasoning in children and adults, and increased exposure to spatial language is positively correlated with children’s spatial word comprehension and performance on mental rotation and mapping tasks. In this study, we investigated potential origins of variability in preschool-aged children’s spatial cognition (N=113, mean age=4 years 4 months) by examining how various measures of children’s daily spatial activities as well as parental spatial language input during different activities with their child predicted growth in children’s spatial skills from 4 to 5 years of age. More diversity in daily spatial activities was associated with greater growth in children’s spatial skills. Moreover, parents who used longer spatial talk utterances during a spatial activity with their child had children with more growth in spatial skills, even when controlling for overall utterance length and verbosity. Finally, the diversity of spatial activities and parents’ spatial utterance lengths were both unique predictors of growth in children’s spatial skills suggesting that parental reports of spatial activities and direct observations of parents’ spatial language input capture different and meaningful aspects of the home learning environment that supports children’s spatial skill development
Applications of ML/DL overcoming current challenges in structure-based drug design
No full textIn the rapidly evolving landscape of drug discovery and development, the application of structure-based drug design (SBDD) methods has become increasingly crucial. Despite the advancements in this field, several challenges continue to impede progress, particularly in the areas of binding heterogeneity, targeted ligand development, and the exploration of the vast chemical space for drug-like molecules. This dissertation addresses these challenges by integrating traditional SBDD techniques with advanced machine learning (ML) or deep learning (DL) methodologies, paving the way for more efficient and targeted drug discovery processes.
The research began with a focus on cannabinoid receptors, employing a set of molecular modeling methods, to predict binding affinity and selectivity of compounds. This approach aids in identifying key interaction sites, facilitating the development of potent and selective ligands. The study also explored complexities of drug-drug interactions, providing insights into the dynamic interplay of pharmacodynamic and pharmacokinetic factors.
To combat the issue of binding heterogeneity, novel computational approaches were introduced. One involves the creation of an advanced computational algorithm that combines structure-based docking scores with ligand-based structural similarities. Another is the development of an ML-based scoring function using ligand-residue interaction profiles. These innovative methods have shown a marked improvement in the accuracy of binding affinity predictions compared to traditional techniques.
A function-based screening methodology was also presented to predict the functionality of CB2 ligands. The success of this approach in the development of CB2 agonists, with a significant success rate, demonstrates its potential in overcoming challenges in ligand design and fulfilling specific biological functions.
Additionally, the dissertation introduced DRUG-GAN, a deep learning model for the de novo generation of molecular structures. This model, when integrated with similarity search methods, significantly narrows the chemical search space and accelerates the process of lead compound identification in the drug discovery and development.
In conclusion, this research successfully demonstrates the effectiveness of combining computational modeling techniques with artificial intelligence in addressing key challenges in SBDD. The methodologies developed herein not only enhance the precision of drug design but also expand the horizons for discovering novel drug candidates, setting a new benchmark in the field of pharmaceutical research
Xilinx inputs for nanosecond anomaly detection with decision trees for two photons and two jets
No full textFiles include the Xilinx IP core for xvcu9p and a generic testbench with test vectors for the 8-variable autoencoder for the dataset with two photons and two jets. The design corresponds to the dataset on Mendeley at http://doi.org/10.17632/44t976dyrj.
Refining Research through Dialogue: Lessons from Older Adult Community Engagement Studio Feedback
No full textIntroduction: Medical and experimental research across various fields continues to underrepresent older adults (aged 60+), potentially limiting findings' generalizability and ethical implications. Recognizing this gap, this study introduces Older Adult Community Engagement Studios (OA-CES), a platform fostering culturally and linguistically competent research design by directly engaging key stakeholders – older adults. OA-CES empowers older adults to provide valuable feedback throughout research, ensuring their voices and perspectives shape studies impacting their communities.
Data and Methods: Following OA-CES events held between November 2022 and February 2024, all 13 participating researchers completed a 12-question digital survey via Qualtrics assessing their experiences and the impact of OA-CES. Quantitative analysis measured the extent of feedback received on research questions (n=13). The thematic analysis further identified recurring themes, notably if researchers' perceptions of their studies changed after engaging with older adult community experts.
Results: Quantitative analysis revealed significant feedback from older adults on research questions, confirming their active engagement. Qualitative analysis identified key themes, including enhanced understanding of target populations, refinement of research questions, and adjustments to recruitment strategies. Notably, four researchers reported a shift in their research perception, underscoring the value of older adult feedback and their intention to integrate it further throughout their projects. Overall, researchers acknowledged the role of input in enriching their studies and solidifying the importance of target population involvement in research design.
Conclusion: Despite the limitations of a small sample size, this study highlights the significant impact of direct older adult feedback on research validity and reliability. OA-CES emerges as a powerful tool with the potential to elevate the public health significance of research across diverse fields. This feedback technique promotes research inclusion, empowers communities to shape research processes actively, and aligns with core principles of ethical and responsible public health practice