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THE RIGHT OF EQUAL ACCESS: HOW PUBLIC ACTION DOCTRINE CONSTITUTIONALIZES THE U.S. CIVIL RIGHTS FRAMEWORK
Get PDFThe way we draw the line between public and private action is vital to the advancement of our collective equality and the survival of the American experiment with democracy, contract and property rights. However, the Court’s nineteenth century “state action” interpretation of the Fourteenth Amendment, which says discrimination is constitutional, has dominated how we draw this line for the past century and a half. This thesis analyzes the history of state action doctrine in U.S. constitutional law and demonstrates that the injustice and instability resulting from its flawed premise and inconsistent application in cases concerning equality precipitates the need for a new approach. To address this problem, this thesis introduces public action theory revealing a path to consistent legislative and judicial interpretation of Equal Protection under the law with a new framework defining what is public and private in our society.
Public action theory is a constitutionally sound reading of the Fourteenth Amendment that combines five legal and legislative precedents into a cohesive, operational whole. The strategy to implement public action doctrine in U.S. congressional and judicial policy includes (1) statutory codification of the English common law right of equal access to public accommodations, (2) grounding of this congressional legislation in the Fourteenth Amendment, (3) coordination of this new legislation with the landmark Americans Disabilities Act, (4) statutory codification of the Supreme Court super precedent set in Shelley v. Kraemer that revised state action doctrine and, (5) a definition of the “state” as a political community of citizens and their government within a geographic boundary.
The public action theory also responds to the Supreme Court’s history of degrading congressional Commerce Clause power in Equal Protection cases and its current aggressive pattern of renovating the architecture of twentieth century U.S. judicial policy by upending precedent on central issues, putting critical civil rights precedents at risk for reversal. This paper demonstrates how public action secures the individual right to access public accommodations and other parts of political, social and economic life free from arbitrary discrimination, holding the potential to stabilize the U.S. civil rights framework
International Human Rights Law Clinic Report
Get PDFThis year, the Johns Hopkins University School of Advanced International Studies Human Rights Law Clinic has investigated what international human rights law has to say about the right to safe, adequate, and accessible water. We have studied the situation in the Hashemite Kingdom of Jordan, because it is among the most water-deprived nations on Earth. During our visit to Amman in January, we were able to meet with key stakeholders inside and outside of government in Jordan, and we are immensely grateful for the cooperation we were offered by every single person we met. This Report, prepared by our students, following a brief explanation of our study goals, methodology, and limitations, is presented in five parts. We begin with a brief introduction to Jordan’s history, demographics, economy, and foreign relations, and a survey of relevant international legal instruments and institutions. We then present our research and observations with respect to four major questions: How serious is the problem of water scarcity in Jordan? How does water allocation affect disadvantaged groups? What internal barriers have impeded Jordan’s ability to address the problem, and what steps has it taken overcome them? And finally, how do applicable treaties and customary international law bear on the right to water, and how has Jordan worked with its neighbors to mitigate its water shortage?Johns Hopkins University, School of Advanced International Studies (SAIS
Evaluating the effect of osteoarthritis on the distant tumor microenvironment and response to immunotherapy
No full textDespite unprecedented outcomes associated with immune checkpoint blockade (ICB), most cancer patients either do not respond or relapse after a partial response. The mechanisms responsible for heterogeneous ICB responses are poorly understood. Acute and chronic stressors are known to influence cancer development. The induction of senescent tumor cells and their senescence-associated secretory phenotype (SASP) has been shown to remodel tumor vasculature, increasing ICB responsiveness. Further, clinical studies have reported patients with osteoarthritis (OA), a disease associated with senescent cell (SnC) accumulation, have slower solid tumor progression and a lower risk of cancer-related mortality. Thus, by understanding the impact of cellular senescence and other systemic responses induced by OA on tumor growth, we sought to elucidate the characteristics of therapy resistance.
Anterior cruciate ligament transection (ACLT), a model of post-traumatic OA, leads to SnC accumulation in the joint and systemic SASP-mediated effects. Here, we investigated the immunological and stromal changes arising with distant ACLT-induced OA (ACLT-OA) and ICB within various murine syngeneic tumor models. ACLT, performed prior to tumor injection, significantly delayed tumor growth and increased ICB responsiveness. Additionally, distant ACLT-OA induced an increase in T cell, especially CD8+ tumor-specific, infiltration into the tumor. Proteomic profiling revealed elevated serum-levels of pro-inflammatory cytokines and factors associated with vessel maturation in ACLT-OA mice. scRNAseq identified transcriptional changes in endothelial cells associated with vascular remodeling. Immunostaining validated the predicted tumor vascular maturation effects; ACLT-OA increased tumor vascular integrity to support anti-tumor immune infiltration and induced the accumulation of vascular-associated SnCs. SnC deletion, using the transgenic INK-ATTAC model, abrogated all of the ACLT-OA-induced effects on the tumor microenvironment, highlighting the critical role of senescence in this interaction. Our findings suggest that the response to OA induces SnC accumulation within the tumor, remodeling the tumor vasculature to promote immune cell infiltration and overcome ICB resistance.
In summary, this work explores the senescent-vascular-immune axis to reveal factors that influence favorable responses to ICB to help predict non-responders and develop sensitizing therapies. Future work seeks to identify the systemic factors of OA that promote ICB sensitivity and design combination therapies to overcome ICB resistance
Advances in Medical Image Guided Autonomous Robotic Tumor Resection
No full textTumor resection surgery, pivotal in cancer treatment, requires the complete and precise removal of tumors and adjacent healthy tissues for optimal oncologic outcomes. Robot-assisted surgery (RAS) is increasingly utilized in various resection surgeries, and has enhanced surgeon’s visualization, dexterity, precision, and ergonomics mainly through teleoperation systems. However, two major limitations persist. First, surgeons may lose track of tumor edges due to intraoperative challenges like lack of direct visual access to the tumor, bleeding, and tissue charring under electrosurgical settings. Second, surgical outcomes vary significantly with individual surgeon experience and performance, and current teleoperated systems help ease but not eliminate surgeon fatigue and burnout, which might lead to major medical errors. This thesis aims to develop a novel robotic solution, focusing on autonomous tracking, planning, and manipulation, to perform accurate tumor resections on animal tissues, ultimately enhancing surgical precision, consistency, and outcome.
This dissertation reports the step-by-step development of the Autonomous System for Tumor Resection (ASTR), and its deployment in various medical image-guided autonomous soft tissue cutting scenarios: (i) A near-infrared fluorescent (NIRF) marking strategy for surgical guidance is introduced, outperforming traditional ink marking in visibility, durability, and biocompatibility as validated through animal studies. (ii) A landmark-guided deformable image registration method using NIRF markers is developed for precise tumor margin tracking, enabling accurate autonomous incisions in animal tissues. (iii) A vacuum grasping robot is developed and integrated with an electrosurgical robot, demonstrating the feasibility of autonomous tissue resection. (iv) The ASTR is developed and applied in a clinically simulated environment to autonomously resect porcine tongues, achieving precision comparable to manual resections by an experienced otolaryngologist. (v) A physics-based tissue cutting simulation, predicting and compensating for tissue deformation during incisions, is developed and integrated into the ASTR, improving surgical accuracy. (vi) The ASTR2 is developed by integrating optical tracking and ultrasonography, with a major software architecture upgrade. Additionally, a novel 3D tumor mimic is developed using animal tissues. Together, these enhancements pave the way towards autonomous 3D tumor resection.
This thesis represents the first study introducing an autonomous robotic system for precise tumor resection in animal tissues, underscoring the potential of robotic technology to elevate the level of autonomy in interventional oncology and a wider range of resection surgeries
SYNERGISTIC EFFECTS OF IVOSPEMIN AND DFMO ON POLYAMINE METABOLISM IN AN OVARIAN CANCER MODEL
No full textPolyamines such as putrescine, spermidine, and spermine are critical regulators of DNA stabilization, gene transcription, and cell proliferation. In ovarian cancer, dysregulated polyamine metabolism supports tumor progression and contributes to chemoresistance, distinguishing this pathway as a compelling therapeutic target. Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, blocks polyamine biosynthesis. While ivospemin, a synthetic spermine analogue, disrupts polyamine homeostasis by inducing catabolic enzymes and competing for polyamine transport. This study evaluates the combinatorial effects of DFMO and ivospemin in OV90 high-grade serous ovarian cancer cells, demonstrating that combination treatment results in profound depletion of intracellular polyamines alongside a marked increase in intracellular ivospemin accumulation. Synergistic antiproliferative effects were confirmed through Chou-Talalay analysis, with combination index values less than 1. Mechanistic studies revealed elevated reactive oxygen species (ROS) levels and disruption of cytoskeletal dynamics, leading to significantly reduced migration in Boyden chamber assays and impaired spheroid growth in three-dimensional culture models. Importantly, DFMO-induced polyamine depletion enhanced cellular uptake of ivospemin, accelerating the disruption of polyamine pools and contributing to the observed synergy. These findings establish dual targeting of polyamine metabolism as a promising strategy to induce metabolic stress, inhibit tumor progression, and suppress invasive behaviors in ovarian cancer. Further studies are required to validate these findings in vivo, identify predictive biomarkers, and explore the integration of polyamine-targeted therapies with existing treatment regimens
Advances in Autonomous Vision-Guided Robotic Soft Tissue Surgery
No full textSoft tissue surgery involves treatments of non-bony structures such as muscles, blood vessels, and internal organs within the human body to address health issues and restore normal physiological function. Surgeons undergo extensive training to master the technical expertise required for these procedures, ensuring patient safety and minimizing complications. Robot-assisted surgery (RAS) has improved surgical outcomes through teleoperated systems in general surgery, urology, and gynecology, yet patient outcomes remain largely dependent on surgeon proficiency and complications persist.
Autonomous robotic surgery has the potential to reduce human errors by using superior precision and consistency of robots to achieve better surgical outcomes. However, approaches to achieve a fully automated procedure in soft tissue surgery remain a complex challenge. Unlike rigid anatomical structures such as bones, highly deformable soft tissues with constant changes in position and shape during surgery pose significant challenges in surgical planning and execution. To ensure safe and successful surgical tasks, a robot requires accurate and reliable methods to identify and track target tissue, robust motion planning that accounts for tissue deformation, and precise and fail-safe execution of plans with control algorithms that are adaptable to dynamic surgical environments.
This thesis aims to advance autonomous robots in soft tissue surgery to achieve high-quality surgical results in unpredictable and deformable environments with minimal human dependence. The thesis focuses on designing tracking, planning, and control algorithms that account for tissue deformation during operations, improving robot precision and consistency in vision-guided soft tissue surgery. The proposed integrated system solutions automate suturing and electrocautery in soft tissue surgeries, achieving surgical outcomes comparable to those of skilled surgeons. The developed robotic systems were evaluated through tissue phantom experiments, ex vivo cadaver studies, and preclinical in vivo animal trials to validate the feasibility of the proposed solutions. By achieving consistent expert-level results, autonomous robotic systems show the potential to improve patient outcomes in current surgical procedures and expand access to high-quality healthcare
The Central Nucleus of The Amygdala Mediates Opioid Reinforcement
Get PDFDespite decreases in opioid prescriptions, the number of opioid-overdose deaths has continued to rise, driven primarily by overdoses including synthetic opioids such as fentanyl. Studies in both humans and animal models have implicated the amygdala in opioid use disorders. Within the amygdala, the central nucleus (CeA) is a key motivator of motivation and emotion, integrating information from relevant aversive and appetitive stimuli to direct behavior. The CeA appears to play a key role in many aspects of substance use disorders, in particular biasing behaviors toward one drug or natural reward over another, yet the role of the CeA in continued opioid use after opioid use has been well-established remains unclear. In this dissertation we sought to assess how the central amygdala mediates opioid reinforcement in male and female rats trained to self-administer fentanyl.
First, after extensive fentanyl self-administration training, rats received micro-infusions of GABA receptor agonists, Muscimol and Baclofen, to temporarily inactivate the CeA, or the opioid receptor antagonist, naltrexone, to assess the role of the CeA and CeA opioid receptors, respectively. We demonstrated that pharmacological inactivation of the CeA reduced fentanyl self-administration, while intra-CeA opioid receptor antagonism resulted in a dose dependent increase in fentanyl self-administration.
Next, we hypothesized that optogenetic stimulation of the CeA would increase motivation for fentanyl in rats with a long fentanyl self-administration history. While pairing fentanyl delivery with optogenetic CeA stimulation increased fentanyl self-administration, CeA stimulation was highly reinforcing and was pursued over fentanyl despite mounting effort requirements, delays, and sporadic reward availability. These results demonstrate that optogenetic stimulation of a population within the anterior CeA is highly reinforcing and drives robust, single-minded responding. These results suggest that recruitment and activation of these ensembles in opioid use disorder may potentiate drug reinforcement, allowing it to outcompete alternative reinforcers
BUBBLES IN THE BRAIN AND LICKING ROCKS A COLLECTION OF WRITINGS
No full textThis collection of personal essays handles two overarching themes: family medical history, with a focus on brain aneurysms and aphasia, and geology, with explorations into its quirky characters and interesting elements. Pieces range from emotional to humorous
Intelligent Assistance Systems for X-Ray Image-Guided Interventions via Surgical Simulation Environments
No full textArtificial Intelligence (AI) is currently enhancing healthcare systems with automated capabilities across the spectrum of care, from medical imaging to data science to surgery. However, the benefits of AI are generally limited to areas where data are available for training. This is not the case for image-guided surgeries, where image collection is hampered by ethical and logistical barriers and the annotations necessary for learning are not generated in the course of routine care. Nevertheless the potential benefits of intelligent systems in image-guided surgery are pronounced, from reducing radiation from excess acquisitions to mitigating the challenges of manipulating instruments through narrow incisions. In silico simulation offers a highly controllable environment for replicating surgical interventions. With a focus on minimally invasive pelvic fracture fixation as the motivating clinical application, this dissertation introduces methods in machine learning, computer vision, and human-computer interaction that realize the pipeline from simulation to real world embodiment for intelligent systems in X-ray image-guided surgery.
Compared to current practice, the use of intelligent surgical systems envisioned in this dissertation amounts to a decoupling of physicians from imaging devices, transforming them into information acquisition systems capable of determining what information is needed, efficiently acquiring the images necessary to derive it, and effectively conveying that information to physicians
EXPLORING ARTIFICIAL INTELLIGENCE-ENABLED DIGITAL LUNG AUSCULTATION FOR INFORMING BUBBLE CONTINUOUS POSITIVE AIRWAY PRESSURE TREATMENT FOR CHILDREN WITH SEVERE PNEUMONIA IN MALAWI
Get PDFPneumonia remains a leading cause of pediatric mortality in sub-Saharan Africa, with infants under two years old at greatest risk. The need for rapid diagnosis and timely treatment is not adequately addressed by traditional diagnostic methods, as WHO clinical guidelines often rely on subjective clinical signs, while gold standard imaging remains cost-prohibitive in low-resource settings. Digital lung auscultation tools powered by artificial intelligence (AI) offer promising alternatives to traditional auscultation and syndromic diagnosis, particularly in environments with limited healthcare infrastructure. This thesis builds upon a randomized controlled trial conducted at Salima District Hospital in Malawi, which compared bubble continuous positive airway pressure (bCPAP) and low-flow oxygen therapy among children under five years of age hospitalized with severe pneumonia and high-risk conditions. The parent trial found higher mortality among children receiving bCPAP compared to low-flow oxygen. Using AI-enabled digital lung sound classification, we further explored whether lung sound abnormality modified the association between treatment modality and mortality. In our analysis, we produce important evidence of the subpopulations of children in which bCPAP was consistently associated with a higher risk of death compared to low-flow oxygen, stratifying by age, sex, malnutrition status, oxygen saturation level and HIV status. These findings highlight the potential of AI-assisted digital auscultation to inform treatment decision-making in pediatric pneumonia and reduce child mortality and suggest that careful patient selection is critical when considering bCPAP therapy in low-resource settings