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Bioethics Crafted by Artificial Intelligence: Review of Organ Transplantation Decision-Making Using AI
No full textArtificial intelligence is increasingly used in healthcare to improve efficiency, consistency, and predictive accuracy. This paper critically examines the ethical and social implications of bias in artificial intelligence systems, particularly in the context of liver transplantation and medical imaging. While artificial intelligence is often promoted as a neutral and objective tool, its outputs are shaped by the data and design choices that inform its development. The paper analyzes how algorithmic bias can emerge from nonrepresentative datasets and design decisions, leading to unequal outcomes for marginalized populations. In liver allocation, artificial intelligence models may reinforce existing disparities by deprioritizing patients based on behavioral or cultural factors. In medical imaging, underdiagnosis and false positives disproportionately affect underserved communities due to limited representation in training data. These findings highlight the need for ethical oversight, inclusive data practices, and interdisciplinary collaboration to ensure that artificial intelligence supports equitable healthcare outcomes. The paper argues that artificial intelligence must be developed and deployed with a solid foundation in bioethical principles such as autonomy, beneficence, nonmaleficence, and justice.Extension Studie
Exploiting Apoptotic Vulnerabilities in AL Amyloidosis
No full textAL Amyloidosis (AL) is a rare disorder characterized by the excessive production and secretion of misfolding light chains by a clonal population of abnormal plasma cells. This results in the formation of amyloid fibrils in extracellular spaces within healthy tissues, which compromises organ function and is eventually fatal. Despite its low incidence, AL significantly impairs patients' quality of life and carries a poor prognosis; for individuals diagnosed at stage IV, the median survival is approximately five months. Currently, no standard-of-care therapies have been developed specifically for AL. Instead, treatments are adapted from those for multiple myeloma (MM), a more prevalent plasma cell malignancy that shares many similarities in pathophysiology with AL. Standard AL treatments typically include chemotherapeutic agents that modulate the activity of BCL-2 family proteins to induce apoptosis in the abnormal clonal plasma cells, followed by autologous stem cell transplantation. However, after successful initial responses, many patients experience relapses, and late-stage patients with multi-systemic organ failure exhibit poor tolerance to these regimens and are unable to receive transplantation. This highlights the critical need for more effective and tolerable therapeutic strategies for AL, especially those that can potentially leverage the unique biology and vulnerabilities of AL clonal plasma cells.
This dissertation investigates novel vulnerabilities in AL as potential apoptosis-promoting therapeutic targets. Initially, we explored the use of BH3 mimetics—synthetic small molecules designed to mimic the pro-apoptotic activity of BH3-only proteins in the BCL2 family—in combination with selective standard-of-care agents. Our findings demonstrated that the BCL-XL inhibitor A1331852 and the BCL-XL degrader DT2216 sensitize the AL cell line to dexamethasone-induced apoptosis, highlighting BCL-XL as a viable therapeutic target in AL. Subsequently, we examined the potential of targeting light chain secretion as a novel therapeutic approach. We observed that brefeldin A, a commercially available general secretion inhibitor, along with GB-001 and GB-002, two novel Sec61 translocon inhibitors, effectively induce apoptosis in AL cells while sparing healthy peripheral blood mononuclear cells (PBMCs). Mechanistic studies revealed that brefeldin A induces apoptosis through light chain-mediated endoplasmic reticulum (ER) stress and MCL-1 depletion, whereas GB-001 and GB-002 trigger apoptosis by inducing proteasomal stress and upregulation of Noxa. These agents produce apoptotic signaling and increase apoptotic priming, sensitizing AL cells to other standard-of-care therapies. Finally, we evaluated the in vivo efficacy of brefeldin A in AL xenograft mouse models. Low-dose brefeldin A treatment significantly inhibited xenograft growth, while a higher dose treatment resulted in xenograft remission comparable to the standard therapy dexamethasone and was well tolerated. Together, our results uncover previously unexplored apoptotic vulnerabilities, including BCL-XL dependency and light chain secretion, in AL and provide a framework for developing targeted therapies with the potential for clinical application.Population Health Science
Implementation and Evaluation of an mOral Health Training Program for Community Health Workers in Kenya
No full textGiven the acute shortage of oral health professionals, the WHO Global Strategy for Oral Health adopted at the 75th World Health Assembly recommended the development and implementation of workforce models that enable sufficient numbers of adequately trained, motivated, and well-distributed health workers to provide oral health services through a collaborative and interprofessional network. The Consortium of Universities for Global Health (CUGH) provided guidance on competency-based oral health education and in 2023, the Harvard School of Dental Medicine in partnership with the WHO-AFRO developed the first competency-based m-oral health curriculum designed specifically for CHWs in Africa. This study evaluates the effectiveness of the pilot implementation of the mOral health curriculum in preparing CHWs to deliver oral health care to underserved communities and identifies barriers and facilitators to implementing the training program to inform future scalability.
A mixed-methods evaluation was conducted using a convergent parallel design. Quantitative data were obtained from the OpenWHO platform, and a structured course feedback survey was distributed to all registered course participants in English, French and Portuguese through the platform. Qualitative data were collected through focus group discussions with CHWs and designated trainers (DTs) selected through purposeful sampling in four pilot counties in Kenya. Observational data collected through participation in planning meetings and digital ethnographic analysis of stakeholder discussions, were used to triangulate findings and assess implementation dynamics. Descriptive statistics were applied to quantitative survey data, while qualitative data were thematically analyzed to identify key facilitators and barriers to implementation.
The online course enrolled 5,957 learners globally, with 2,403 earning a record of achievement. The feedback survey in English received 371 responses, French had 123 responses and Portuguese had 46 giving us response rates of 6.2%, 10.9% and 8.9% respectively. Survey responses demonstrated high engagement, with 90% of participants affirming the course’s relevance to their work. A total of 1,265 CHWs and 39 DTs participated in the pilot implementation in Kenya. Focus group discussions were conducted with 40 CHWs (10 from each county) and 18 DTs. Qualitative findings highlighted the program’s success in addressing a critical knowledge gap, increasing CHW confidence in oral health promotion, and fostering interprofessional collaboration and quantitative findings confirmed their high satisfaction with the course curriculum and features. Implementation challenges included digital access barriers, insufficient logistical and financial support, and highlighted gaps in integration of CHWs into formal referral systems.
The study provides evidence supporting the feasibility of integrating CHWs into oral health service delivery through digital training. Key facilitators included the flexibility of the online format, the effectiveness of the mOral health curriculum, and the strong peer support networks among CHWs and DTs. Challenges such as technological barriers, and a lack of formalized referral pathways must be addressed for effective scale-up. While Kenya had a strong strategic plan that guided this work with highly engaged stakeholders, strengthening implementation through strategic policy support, provision of offline training resources, and sustainable funding mechanisms will be critical for expanding this model across other low and middle income settings. These study findings contribute to the broader discourse on workforce capacity-building and the role of digital learning in advancing universal health coverage.Dental Public Healt
Embracing the Enemy: How Henry Luce used his Time, Inc. Media Empire from 1944 to 1950 to Persuade Americans to Embrace Japan as a Key Cold War Ally
No full textThis thesis assesses the role of Henry Robinson Luce, founder and Editor-in-Chief of the Time, Inc. media empire, in convincing the American public to soften their perceptions towards Japan following the racial hatred propagated during World War Two. In doing so, it argues that Luce, in coordination with high level government officials and business leaders, made a concerted and successful effort through his most popular magazine, Life, to make Americans see Japan as an important ally in the fight against communist encroachment in the Far East during the Cold War, as well as a country opened to the spread of Christianity, and a viable and lucrative new market for American business interests.
The research is based on a close study of Luce’s calculated use of advocacy, changes in language, repetition, calculated symbolism, and terminology throughout Life magazine from 1944 to 1950, combined with public opinion polls and conversations between Luce and elite Washington policy makers. It imputes significant influence on Luce in persuading Americans to embrace the Japanese due to the massive circulation of Time, Inc. publications and the wide-ranging demographics of Life’s readers in particular. By 1945 Time Inc. publications had a combined readership of thirty million Americans and Life was the most popular magazine in America, read by 13.5 million people – ten percent of the population. Life was Luce’s main conduit to the general population of the U.S. and readers abroad. Due to this wide reach, this thesis deduces significant influence from Luce and Time Inc. but also acknowledges it was part of a larger media ecosystem reporting on similar topics and themes at the time.
This thesis concludes Luce used Life to publish editorials, articles from outside contributors, photojournalism, and curated letters to the editor to successfully persuade Americans to embrace the Japanese in a remarkably short period of time. Through these various aspects of Life, Luce seized on feelings of guilt and sympathy felt by Americans due to the destruction wrought by the use of atomic bombs, appealed to Americans’ inherent Christian values, and rehabilitated the image of Hirohito so he could be used as an American-approved puppet in the postwar occupation of Japan. Public polling conducted between 1945 and 1950 highlighted the positive change in attitudes amongst Americans towards the Japanese within only five years of being bitter enemies and confirms the success of Luce’s coordinated campaign of persuasion.Extension Studie
Decoding Germline Genetic Influence on Cancer Somatic Mutation Acquisition
No full textIn this paper we investigate the impact of germline variants on the somatic mutation profiles of key cancer drivers, focusing on TP53 and KRAS, in a cohort of 35,914 patients (16,424 TP53-mutated and 6,297 KRAS-mutated). Candidate genes were selected based on protein–protein interaction data from STRING and BioGrid, yielding tailored panels for TP53 (including BRCA1, MDM2, ATM, among others) and KRAS (including RAF1, BRAF, EGFR, etc.). Using a multi-model machine learning framework—incorporating logistic regression, random forests, and feed-forward neural networks—we captured both linear and non-linear associations in high-dimensional SNP data. Our analysis revealed a significant association between BRCA1 variants and TP53 mutation status in breast carcinoma, supporting the role of inherited DNA repair deficiencies in promoting somatic TP53 alterations. In contrast, no single germline driver was identified for KRAS mutations, suggesting a more complex interplay of factors in KRAS-driven oncogenesis. These findings underscore the value of integrating biologically informed candidate gene selection with advanced computational models to enhance our understanding of cancer genomics and inform future risk assessment and therapeutic strategies.Applied Mathematic
Episodic warm climates on early Mars primed by crustal hydration
No full textGeological records indicate that the surface of ancient Mars harbored substantial volumes of liquid water, a resource gradually diminished by processes such as the chemical alteration of crustal materials by hydration and atmospheric escape. However, how a relatively warm climate existed on early Mars to support liquid water under a fainter young Sun is debated. Greenhouse gases like H2 in a CO2-rich atmosphere could have contributed to warming through collision-induced absorption, but whether sufficient H2 was available to sustain warming remains unclear. Here we use a combined climate and photochemical model to simulate how atmospheric chemistry on early Mars responded to water-rock reactions and climate variations, as constrained by existing observations. We find that H2 outgassing crustal hydration and oxidation, supplemented by transient volcanic activity, could have generated sufficient H2 fluxes to transiently foster warm, humid climates. We estimate that Mars experienced episodic warm periods of an integrated duration of ~40 million years, with each event lasting ≥105 years, consistent with the formation timescale of valley networks. Declining atmospheric CO2 via surface oxidant sinks or variations in the planet’s axial tilt could have led to abrupt shifts in the planet's redox state and transition to a CO-dominated atmosphere and cold climate.Author's Origina
How has the Depiction of the Folkloric Figure of the Fairy Evolved?
No full textThis thesis examines the evolution of the folkloric figure of the fairy, tracing how various societies imagined, depicted, and represented fairies across time and space. Unlike previous academic works, this thesis argues that five key “evolution causations” contributed to collective understandings of the fairy’s characteristics, attributes, and capabilities. Paying special attention to early fairy depictions in Ireland, Scotland, and England; Victorian era depictions in Britain and America; and contemporary Pop Culture depictions in America, I will analyze this evolution in connection with how the folkloric figure has been presented in various forms during its evolution in the locations of Ireland, Scotland, Britain, and America. Some of these cited evolution causations have been major factors in the evolution of the depiction of the fairy figure, while others have been minor but have still had some effects on the evolution of the depiction of the folkloric figure. By examining these causations, several paths of evolution are identified as well as several depictions of the folkloric figure of the fairy. This approach is important because by looking at the folkloric figure of the fairy in this new way, this approach allows us to understand how the figure has been used by several cultures for identity purposes, as a tool to record cultural history, and for its ability to create cultural cohesiveness. We also are able to see how the figure was used in cross-cultural exchanges and how the figure was used by different cultures for their own purposes.Extension Studie
Identifying Risk Factors for Vomiting during Diarrhea: A Secondary Analysis of a Randomized Trial of Zinc Supplementation
No full textObjectives
Supplemental zinc during acute diarrhea reduces illness duration but also increases vomiting. In a recent trial, we found that children receiving lower daily doses of zinc (5 mg or 10 mg vs. 20 mg) had lower rates of vomiting with comparable stool output and duration of diarrhea. We performed a secondary analysis to identify sociodemographic and clinical factors associated with vomiting in children with acute diarrhea.
Methods
We performed a secondary data analysis of 4500 children aged 6-59 months with an acute episode of diarrhea (< 72 hours before enrollment) in a randomized, double-blind controlled trial in India and Tanzania. To identify clinically important risk factors for overall, regimen-related and regimen-unrelated vomiting, we created log-binomials models with relative risks (RRs) and 95% confidence intervals (CIs).
Results
The trial enrolled 4500 children of whom 1203 (26.7%) had any vomiting. After adjusting for multiple demographic and clinical characteristics, presence of dehydration (RR 1.45, CI 1.10 – 1.92), being underweight (RR 1.22, CI 1.05 – 1.41), receipt of the rotavirus vaccine (RR 1.89, CI 1.69 – 2.12), and household wealth above the median (RR 1.17, CI 1.07 – 1.29) were factors associated with an increased risk of vomiting. Older age and lower zinc dosing were associated with a lower risk of vomiting.
Conclusions
Young, underweight or dehydrated children are more likely to have concurrent vomiting with zinc supplementation. Identification of these factors may allow providers to better monitor such children, thus reducing the chances of recurrent dehydration or inadequate dietary intake.Author's Origina