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IMPLICIT BIAS IN VIDEO-BASED INTRA-OPERATIVE SURGICAL SKILL ASSESSMENT
No full textImplicit bias in surgery has the potential to significantly influence the assessment of residents and the selection of surgical trainees. In this thesis, we present a framework for evaluating implicit biases in algorithms used for video-based assessment of surgical skill. The framework involves rating pairs of videos and assigning a preference to each video in the pair based on the raters' assessment of surgical skill.
These preferences are used to compute percentile scores, which are then ranked. Implicit biases may affect the preferences assigned to videos when raters are provided with information about the attributes of surgeons in the videos.
The framework allows the intensity of implicit bias to be manually set to assess its impact on video ratings and the downstream effect on algorithms that predict the biased ground-truth ratings. The framework also allows for the analysis of implicit bias in manual ratings and the development and evaluation of networks to predict unbiased ratings
Enantioselectivity of Cu(II)-ATP Catalyzed Reactions
No full textArtificial enzymes have been widely applied in industrial settings such as pharmaceutical therapy, biosensing, and bioimaging. Artificial enzymes resolve the limitations of natural enzymes under certain conditions while reserving high catalytic efficiencies and high kinetic reaction rates. Artificial metalloenzymes (ArMs) were developed on the foundation of artificial enzymes. In ArMs, a large biomolecule acts as a chiral scaffold to bind the metal cation to achieve enantioselectivities in reactions. This report studied the enantioselectivity of Cu(II)-ATP catalyzed reactions using computational simulations such as Density Functional Theory (DFT), xTB Molecular Dynamics, and Nudged Elastic Band (NEB) theory. For the most energetically favored Cu(II)-ATP structure, it was found that the copper (II) ion binds to the (N7) nitrogen, one oxygen each on the β and γ-phosphate groups in the ATP molecule. Different catalyzed systems were studied, and while further simulations will be required, possible structures of each reaction system were obtained through converged calculations
Transcription Controlled Shape Change of PEGDA-co-DNA Hydrogels
No full textGenetic regulatory networks (GRNs) are used by living cells to regulate and direct complex behaviors. Synthetic regulatory networks aim to mimic this behavior to better understand how living cells control complex organizational behaviors through layers of biochemical networks. Transcriptional regulatory networks (TRNs) are a type of synthetic regulatory network that uses transcription process to control physiological processes and responses. Genelets are short transcriptional templates that are the basic units of synthetic TRNs and can be used to control and automate many different processes, such as hydrogel size change. Autonomous genelet controlled hydrogel actuation is key in achieving dynamic soft robot systems. Developing processes that can direct the behavior of synthetic materials also enable further advancements in areas such as smart medicine and programmable matter. The model system used in this was PEGDA-co-DNA hydrogels with biocompatible copolymer backbones and single-stranded DNA toeholds which initiate the hybridization chain reactions that lead to hydrogel shape change. To show that genelet controlled hydrogel shape change can be achieved, we aimed to show that shape change can be controlled with RNA signals. Shape change was defined as the sequential transition across three phases: swelling, shrinking, and reswelling. In this study, we investigated two different designs for achieving transcription-controlled shape change. In the first design, we aimed to control shape change by controlling the transcription and degradation of transcription products – RNA reversal strands. In the second design, we aimed to control shape change through the transcription of different products – RNA reversal strands and RNA anti-reversal strands. Both methods resulted in approximately 10% increase in size during the reswelling phase. These results suggest that the limits of reswelling may be because of the byproducts throughout the size change process. Overall, we found that shape change can be successfully controlled using transcription products and that reswelling can be controlled by both RNase degradation and transcription products
ELUCIDATING THE BIOLOGICAL ROLES OF ADP-RIBOSYLATION WITH CHEMICAL TOOLS
No full textAdenosine diphosphate ribosylation (ADPr) refers to the transfer of ADP-ribose from oxidized nicotinamide adenine dinucleotide (NAD+) to a variety of biomolecules (metabolites, DNA, RNA, proteins). ADPr research has primarily focused on protein ADPr in human cells, which is enzymatically performed by poly(ADP-ribose) polymerases (PARPs). PARPs are best understood as proteins that initiate the repair of DNA strand breaks, but have recently been implicated in several other biological pathways. This thesis focuses on the development of chemical tools for ADPr research, with an emphasis on obtaining molecular, mechanistic information that complements correlative genetic studies. The first chapter describes human protein ADPr in detail, and overviews state-of-the-art methods for ADPr research. The second chapter details syntheses of photoaffinity-labeled poly(ADP-ribose) probes and their applications in proteomics. The third chapter describes how poly(ADP-ribose) controls the localization and biophysical properties of the FUS protein. The penultimate chapter presents a high-throughput assay for discovering inhibitors of enzymes that remove ADPr. The thesis concludes with a discussion of future ADPr research, and how the interface of chemistry and biology can accelerate discoveries in the field
EXPLORING THE ROLE OF PERCEPTUAL REASONING IN THE ORGANIZATION OF WRITTEN TEXT
No full textWritten expression has long been viewed as a verbal task. Although there is evidence that written expression requires a fluid interaction of multiple cognitive skills, including verbal comprehension, long-term memory, and working memory, there has been little or no attention paid to the role of perceptual reasoning skills. This study aimed to fill that gap by examining the hypothesis that writing is a problem-solving task that requires perceptual thinking in actively synthesizing or transforming knowledge into written text. When students translate their ideas into written language, they construct sentences out of words, paragraphs out of sentences, and essays out of paragraphs, a multi-level constructive process that is hypothesized to require perceptual reasoning. A correlational study was conducted on retrospective data from seventh grade students on verbal comprehension, perceptual reasoning, and written expression. The results suggest that for some aspects of written expression, perceptual reasoning has a significant contribution even after controlling for verbal comprehension skills. The results are discussed with respect to the inclusion of perceptual reasoning skills in interventions aimed at improving students’ written expression
APPLICATION OF A NOVEL WHOLE-GENOME HPV SEQUENCING APPROACH TO CLARIFY THE EPIDEMIOLOGY AND MOLECULAR PATHOGENESIS OF CERVICAL ADENOCARCINOMA
No full textCervical screening has not effectively controlled cervical adenocarcinoma (ADC), which now accounts for one-third of cervical cancer cases in the US. ADC has poorly-defined precursors, and its rarity compared to the precursors of the most common subtype of cervical cancer, squamous cell carcinoma (SCC), has made it challenging to study. The overarching research goal of this dissertation is to clarify the pathogenesis of ADC and possibly improve cervical cancer screening effectiveness as a result. By combining large-scale epidemiology cohort study with next-generation whole-genome sequence HPV data, this dissertation will explore the pathogenesis of ADC from three different level: 1) HPV type level, 2) HPV lineage/sublineage level, and 3) HPV variant level
TRANSCRIPTIONAL AND THREE-DIMENSIONAL PHENOTYPING OF MYOCARDIAL GRANULOMAS AT THE SINGLE-CELL LEVEL IN CARDIAC SARCOIDOSIS PATIENTS
No full textCardiac presentation of autoimmune sarcoidosis, known as cardiac sarcoidosis (CS), is a poorly understood disease with high mortality and low diagnosis rate. While CS is an immunological syndrome, little is known about how cardiac parenchymal and stromal cells mediate its pathogenesis. Moreover, while most current sarcoidosis research is based on research in pulmonary sarcoidosis (PS), it remains unclear how much both presentations of sarcoidosis overlap. To tackle these concerns, I leveraged publicly available sarcoidosis transcriptomic datasets. Two publicly available bronchoalveolar lavage single-cell RNA Sequencing datasets were integrated to analyze PS relative to control. Additionally, two publicly available cardiac single-nucleus RNA Sequencing datasets were integrated to analyze CS relative to control. Following integration, I ran cell-cell communication, transcription factor, and differential expression analyses on parenchymal, stromal, and immune subsets identified in our analysis. Our analysis revealed that there was an expansion of stromal and immune cells in PS and CS. I also observed upregulation of Th17.1 and attenuated activation transcriptional profiles in the immune cells of CS and PS relative to control. Additionally, I found upregulation of pro-inflammatory and pro-fibrotic transcriptional profiles in the cardiac stromal cells of CS relative to control. I also found that cardiomyocytes exhibited upregulated cardiac stress and proliferation transcriptional profiles in CS relative to control. Our integrative transcriptomic analysis shows that despite tissue-specific differences, there are shared transcriptional trends between CS and PS. It also showed that stromal and parenchymal populations exhibit transcriptional trends that could explain their pathogenic role in CS. To gain better insights about the structure of CS granulomas, I utilized a novel 3D reconstruction methodology, called CODA, to reconstruct CS granulomas at the micrometer resolution. This analysis showed that there is great heterogeneity in the size of CS granulomas and their proximity to blood vessels, yet such granulomas do not display any correlation between their size and their giant cell foci content. I further supplemented my analysis by integrating my model with CD3 and CD68 IHC. This integration revealed that while all granulomas had a high content of macrophages, high T cell content was not a critical defining feature of CS granulomas
FINGERPRINTING OF WALKING USING DATA FROM WRIST AND ANKLE-WORN ACCELEROMETERS
No full textIdentifying an individual from accelerometry data collected during walking without reliance on step-cycle detection has not been achieved with high accuracy. Therefore, we propose an open-source reproducible method to: (1) create a unique, person-specific
“walking fingerprint” from a sample of un-landmarked high-resolution data collected by wrist and ankle-worn accelerometers; and (2) predict who an individual is from their walking fingerprint.
Accelerometry data were collected during walking from 32 individuals (19 females) aged from 23 to 52 years old for at least 380 s each. For this study’s purpose, data are not landmarked, nor synchronized. Individual walking fingerprints were created by:
(1) partitioning the accelerometer time series in adjacent, non-overlapping one-second intervals; (2) transforming all one-second interval data for a given individual into a three-dimensional (3D) image obtained by plotting each one-second interval time series by the lagged time series for a series of lags; (3) partitioning these resulting participant-specific 3D images into a grid of cells; and (4) identifying the combinations of grid cells (areas in the 3D image) that best predict the individual. For every participant, the first 200 s of data were used as training and the last 180 s as testing. This approach does not segment individual strides but instead walking, resulting in reduced dependence on complementary algorithms and increasing its generalizability.
This method correctly identified 100% of the participants in testing data for left-wrist worn accelerometry [1] and highlighted unique features of walking that characterize the individuals. This is significant as predicting the identity of an individual from their walking patterns has immediate implications that can complement or replace those of actual fingerprinting, voice, and image recognition. Furthermore, as walking may change with age or disease burden, individual walking fingerprints may be used as biomarkers of change in health status with potential clinical and epidemiologic implications
After Realism: Leftist Art in Italy 1958 - 1978
No full textStudies of politically engaged art in postwar Italy remain circumscribed to two distinct historical episodes: the so-called realist debates provoked by the divisive, Cold War era cultural policy of the Italian Communist Party (PCI), and the militant affinities of the following generation’s most paradigmatic grouping, Arte Povera. In contrast to these isolated approaches, this dissertation looks comprehensively at the aftermath of the realist controversies and the rise of the New Left spurred by the seismic effects of the Marshall Plan. Tracing key ideological debates through the work of four artists variously involved in Marxist politics—Renato Guttuso, Carla Accardi, Nanni Balestrini, and Mauro Staccioli—this study reframes and expands our understanding of the nexus between political commitment and artistic creation in Italy. The picture that emerges is of a multigenerational, internally fractured field in which the PCI and its most emblematic artist, Guttuso, remained powerful, yet polarizing forces notwithstanding the rise of more militant positions.
Chapter 1 addresses Guttuso’s efforts to update the realist paradigm in light of changed historical and cultural circumstances while remaining loyal to party ideology. Chapter 2 turns to Carla Accardi, a founding member of the avant-garde Marxist collective FORMA 1, and contextualizes her abstract canvases with respect to her interest in structuralist and feminist thought to reveal the progressive thrust of her practice. Chapter 3 concentrates on the collages of Nanni Balestrini, reading them through the lens of the dissident Marxist philosophical current of operaismo. Chapter 4 addresses the site-specific sculptures of Mauro Staccioli, which, despite their abstract lexicon, nonetheless reveal strong commonalities with PCI attitudes. As a whole, the dissertation reveals that the question of a progressive art in Italy during the 1960s and 1970s remained radically unsettled and deeply marked by both the previously contested actions of the PCI and the newly emergent ideas of the New Left
Oral History of Susan Sherwin
No full textThis interview with Susan Sherwin, PhD, was conducted by Suzanne Snider on February 17 and February 18, 2023 in Halifax, Nova Scotia, Canada as part of Moral Histories: Voices and Stories from the Founding Figures of Bioethics, an oral history project of the Johns Hopkins Berman Institute of Bioethics. Prof. Sherwin is a Professor Emerita of Philosophy and Gender and Women's Studies at Dalhousie University. She was awarded the Killam Prize in the Humanities in 2006 by Canada Council for the Arts. Prof. Sherwin’s areas of expertise include feminist health ethics and philosophy, women in health research, abortion, and reproductive technologies.On Day 1 of the interview, Prof. Sherwin discusses growing up in a small, Jewish neighborhood in Toronto, Canada, and the Jewish values instilled in her. Prof. Sherwin describes her education: completing her undergraduate education at York University in both philosophy and math, earning a PhD in philosophy at Stanford University, and completing a postdoctoral fellowship at Case Western Reserve University. She reflects on the sexism she experienced in high school and other academic environments. While at Stanford, Prof. Sherwin was part of the 1970s feminist consciousness-raising movement. She describes her pivot at Stanford from philosophy of math to feminist philosophy. She explains that her dissertation, Moral Foundations of Feminism, is believed to be the first dissertation in the United States on feminist ethics. Prof. Sherwin describes her participation in the Moral Problems in Medicine Project as a postdoctoral fellow at Case Western in the early 1970s, emphasizing the collaborative and interdisciplinary nature of bioethics compared to philosophy. Prof. Sherwin describes Ruth Macklin as a mentor, friend, and collaborator. She discusses the terms “bioethics” and “medical ethics,” and her preference for “health ethics.”Prof. Sherwin describes working in a neonatal intensive care unit (NICU) as a postdoc, initially feeling unprepared and like an intruder but learning how to offer a theoretical or philosophical frame for patients navigating difficult medical decisions. She narrates her realization that feminist philosophy and medical ethics were more related than she initially thought. Prof. Sherwin describes her career at Dalhousie University, beginning as a professor of philosophy in 1974 and concluding with her recent retirement, including a description of her longtime collaboration with other women faculty at Dalhousie. She discusses the problems with underrepresentation of women in health research, especially pregnant people.On Day 2, Prof. Sherwin discusses abortion historically and in light of the recent US Supreme Court decision Dobbs v. Jackson Women’s Health Organization, offering comparative abortion history in the United States and Canada. She explores relational theory, using philosopher Annette Baier’s coined phrase “second persons” to consider the role of social construction in personal development. She offers an overview of her first book, No Longer Patient: Feminist Ethics and Health Care. Prof. Sherwin maintains that the feminist lens expands the scope of inquiry. She distinguishes between agency (the ability to make a choice) and autonomy (having choices available that actually serve your needs and well-being). Prof. Sherwin describes serving on the Royal Commission on New Reproductive Technologies which advised on reproductive technology legislation in Canada. She reflects on how bioethics has mostly explored rights instead of responsibility, describing her advocacy for a public health ethics that encourages relational solidarity, especially during a pandemic. Prof. Sherwin discusses the role of metaphor in a health context, especially militaristic metaphors such as “battling” a disease. She shares her advocacy for the prohibition of performance-enhancing drugs. Prof. Sherwin reflects on her retirement and self-care. Toward the end of the interview, she emphasizes the importance of environmental ethics, stating that global climate change should be a major focus for bioethicists.This interview may be of interest to those seeking to learn more about: bioethics and the history of the field; philosophy and early feminist philosophy; feminist health ethics; abortion and comparative abortion history in the US and Canada; relational theory and bioethics; agency and autonomy; Jewish upbringing; Case Western Reserve University and bioethics; and bioethics in Canada