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Counting the wins: extensions and applications of win statistics for time-to-event outcomes in randomized controlled trials
(2026) Pan, Stephanie; LaValley, Michael P.
This dissertation develops and evaluates extensions of win statistics for analyzing time-to-event outcomes in randomized controlled trials (RCTs). Win statistics, including the win ratio (WR), provide an alternative interpretation to the conventional hazard ratio (HR). Although win statistics, and particularly the WR, have been increasingly adopted in clinical trials, further methodological development and broader clinical applications are needed. Chapter 1 addresses settings of non-proportional hazards by introducing a novel nonparametric approach that partitions follow-up time into disjoint intervals to estimate the WR. This approach leverages a meta-analytic framework to detect and quantify treatment effect heterogeneity in contexts such as immuno-oncology and cardiology trials. Chapter 2 considers the challenge of censoring in generalized pairwise comparisons (GPC), where censored pairs often do not contribute information to the test statistic. We propose a method based on pseudo-observations to address this issue and compare its performance with existing GPC methods. Chapter 3 extends Kraemer’s composite-moderator framework to time-to-event outcomes using the expected win time against reference (EWTR). By combining multiple baseline moderators into a composite measure, we evaluate conditions under which personalized treatment recommendations (PTRs) outperform single moderators. Extensive simulation studies, along with illustrations using reconstructed and real clinical trial datasets, were conducted to assess these methods. Collectively, this work advances methodological tools for analyzing time-to-event data in RCTs by addressing three key challenges: non-proportional hazards, censoring, and treatment effect heterogeneity. These contributions aim to improve the detection of treatment effect heterogeneity and treatment effect estimation and support the development of personalized treatment strategies.
Dissecting disease pathways of NOS1AP variants that contribute to nephrotic syndrome
(2025) Ranga, Arathi; Kintsurashvili, Ekaterina
Glomerular diseases are a leading cause of end-stage kidney disease and characterized by dysfunction in the key kidney filtering cells, podocytes. Genetic podocytopathies (GP) are the most severe subset, in which patients frequently develop treatment-resistance and irreversible renal scarring (e.g. focal segmental glomerulosclerosis). Delineating the molecular pathways underlying these conditions can reveal therapeutic targets to reverse disease progression. We previously discovered that NOS1AP (nitric oxide synthase 1 adaptor protein) is a Mendelian glomerular disease gene that regulates the actin cytoskeleton, a major hub of disease proteins in GPs. Disease variants localize to its phosphor-tyrosine binding (PTB) domain and cause defective actin remodeling in immortalized podocytes. In this investigation, we strive to understand the key proteins and pathways through which NOS1AP regulates the podocyte actin cytoskeleton and that are impaired in disease. Quantitative proteomics was performed to determine the critical protein interactors of NOS1AP abrogated by disease and biological mutants. Wildtype and mutant tagged NOS1AP constructs were transiently transfected in immortalized human podocytes. Immunoprecipitation (IP) of NOS1AP proteins was performed followed by a non-denaturing elution, protein trypsinization and tandem mass tagging. Liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) was performed on biological triplicates. Peptide and protein calling was performed, and aggregate peptide signal was normalized per 100 peptides and to the signal of the bait. Co-expression of candidate interaction partners in podocytes with NOS1AP was assessed using kidney single cell mRNA sequencing datasets (z-score of % cell expression>1). Top candidates were confirmed by subsequent IP studies. Additionally, commercial PTPN14 antibodies were assessed through immunoblotting and immunofluorescence. PTPN14 antibody testing was also conducted with immortalized podocytes exhibiting PTPN14 overexpression or PTPN14 knockdown.
Quantitative-IP proteomics of wildtype NOS1AP, patient variant NOS1AP C143Y, and a biological mutant lacking the PTB domain (NOS1AP δPTB) resulted in the detection of 12761 peptides in 2351 proteins. Of these proteins, PTPN14 (protein tyrosine phosphatase non-receptor type 14) and KANK1 (KN motif and ankyrin repeat domains 1) were highly expressed (z-score>1) in the majority of datasets with NOS1AP in podocytes, suggesting these proteins may interact with NOS1AP in the disease-relevant cell type. Confirmatory co-IP studies showed that tagged PTPN14 as well as KANK1 co-precipitated with wildtype NOS1AP, and this co-precipitation was reduced with the disease mutant C143Y and biological mutant δPTB.
Overall, this data highlights new potential signaling pathways in genetic podocyte disorders (e.g. protein tyrosine phosphorylation) and suggests therapeutic targets for future investigation.
Preaching for progress: how the Social Gospel elevated the Canadian left beyond its U.S. counterpart
(2025) Paxton, Gabriel Noah; Seligman, Adam B.; Evans, Christopher H.
The following dissertation explores Werner Sombart’s century old question, “why is there no socialism in America?” from a comparative study of the Canadian Left and Social Christianity. I make the argument that the relative success of Left-liberal or ‘democratic-socialist’ politics in Canada is in no small part a product of social gospel efforts in the Canadian prairies. This importantly challenges the assumption by American historians that the “frontier” or agrarian nature of early 20th century North American life was a reason for socialism’s failure in the new world. Instead, through a comparison with Canadian prairie politics, historians can see that social gospelers in Canada viewed leftist politics as a natural extension of the nation-building process. Equipped with this view, radical Protestant ministers settled the Canadian prairies and turned rural-populist dissent into support for a strong welfare state. In the United States, the populist leanings of rural workers were either miscalculated, or worse ignored, by a middle-class social gospel ministry and an urban socialist movement. In the absence of a workable “spiritual” socialist movement in the American Heartland, populist politics were easily co-opted by ethno-nationalist, racialized, and fundamentalist reinterpretations of populism.
Community residential facilities for emotionally disturbed adolescents
(Boston University, 1982) Gurry, Susan Elizabeth
The purpose of this research was to study several concepts related to deinstitutionalization and community facilities for emotionally disturbed adolescents. This study proceeded in two phases.
In Phase I, a mail survey of licensed group care agencies in Massachusetts provided background data on residential facilities.
In Phase II, field research methods were used to collect data on five facilities, each serving between four and sixteen residents. An average of 35 hours was spent observing in each facility and a total
of 53 interviews were conducted with staff, administrators and residents.
Survey findings indicated that a total of 125 agencies in Massachusetts served 4081 residents of all ages and disabilities. Sixty of these group care agencies accepted adolescents. Seventy four
of them were also residential schools for youngsters with special needs.
One finding from the field research was that small group care facilities placed emphasis on therapeutic interventions and treatment.
The therapeutic activities of the five group care facilities shared many similar features. A classification system based upon their
formal and informal features was developed.
Two forms of community were noted: internal and external.
Facilities with a high degree of internal structure had fewer community-oriented activities. Living in small group care facilities did not insure integration into the external community. A four-point
scale was developed to measure the range of possible community oriented activities. Four origins of decision-making about community oriented
activities were noted.
Other findings indicated that group care facilities possessed some characteristics of total institutions, mediatory institutions, and families, but not all. The facilities were characterized by a high degree of staff/resident interaction, intensive therapeutic
effort, and varying levels of community orientation. Results indicated that group care facilities are a new type of social setting that have no direct correlation to known institutions in contemporary society.
Recent Print and Digital Resources Related to Christianity in Africa
(Dictionary of African Christian Biography, 2026-02) Restrick, Beth
Book excerpt: the story of the Copts: the true story of christianity in Egypt
(Dictionary of African Christian Biography, 2026-02) el Masri, Iris Habib
[61. While Abba Dionysius was so engaged in encouraging the people to face the fierce tempest of persecution raging about them, a solitary figure detached himself and turned
his face toward the desert, trudging on and on toward the fastnesses of its inner depth in search of peace through payer and fasting in its vast solitude. It was St. Paul [230-341 CE], who became the first Egyptian hermit. When he first set out into the desert, no one knew about his intentions, not even the man who sat on the Chair of St. Mark. At the outset of the persecutions of the Emperor Decius, he was a young man of twenty, very wealthy and well-educated in both the Coptic and the Greek literatures. He was of a gentle spirit and a strong lover of God. He had an only sister who was married. Her husband, coveting his wealth, went to the authorities and denounced his wife's beloved brother as a Christian. Hearing of it, Paul's sister went weeping to him, and entreated him to go into hiding. Thereupon, he fled into the desert. His idea at first was to hide temporarily, but the life of solitude both attracted him and appealed to him, and what had been his necessity became his free choice. He journeyed on, further and further, into that vast ocean of desert solitude, until he came to a cave beyond which were a fount of clear water and some palm trees. There he made his abode, from the time of his arrival, at the age of twenty, and there did he abide till he died, ninety years later, at the age of a hundred and ten. All these long years he spent in utter solitariness, unknown and unheard of by man, but in complete communion with God.]
Effect of race and ethnicity on pediatric pain management and perceptions of care in the emergency department as a result of long bone fractures
(2025) Nott, Elijah; Gerstenfeld, Louis; Rufo, Paul
Pediatric pain management represents an area in which studies into the impact of race and ethnicity on equitable care have yet to be fully elucidated. In this study, we assessed the effects of real or perceived differences in pain management Studying the effects of race and ethnicity on long bone fractures allows data to be collected on the and perceptions of care. Parents of eligible patients completed a survey regarding their experience in the emergency room during their follow-up visit to the orthopedic clinic. Patients were also asked if they would be interested in participating in a semi-structured interview, which would provide them with an opportunity to provide more details about their interactions in the Emergency Department. Initial data collection has recently begun. We anticipate that the data collected in this project will contribute to the development of policies and recommendations ensuring equitable pain management in the Boston Children’s Hospital Emergency Department. Research studies of this type, which assess the impact of demographic factors on equitable pain management, are crucial for identifying and addressing systemic and historical biases that exist in current clinical practice. These inequities can contribute to a culture of misunderstanding and generational mistrust in healthcare if not recognized and properly addressed.
Overview and comparative analysis of the efficacy and safety of current and emerging treatment regimens for diffuse large B-cell lymphoma: implications for future patient outcomes
(2025) Reid, Zuri N.; Walsh, Carol T.; Sloan, Mark
Diffuse large B-cell lymphoma (DLBCL) makes up 30% of non-Hodgkin’s lymphoma (NHL) cases and is widely considered the most common of the NHL subtypes. Most patients are responsive to the 1st-line therapy, R-CHOP; however, 40-50% of cases relapse, are refractory, or completely unresponsive. The available 2nd and 3rd-line therapies include CAR T-cell therapy, salvage ASCT + HDT, immunotherapies, and bispecific monoclonal antibodies, although some 2nd and 3rd-line therapies have modest efficacies, ORR, and CR rates. Moreover, therapies such as CAR T-cell and salvage ASCT + HDT are associated with high-grade AEs and CRS symptoms. In the battle to cure DLBCL, it is imperative to develop treatment options that provide durability while not affecting quality of life. Thus, more targeted therapies such as ADCs, immune checkpoint inhibitors, and novel therapeutic combinations may be key for the future of DLBCL. This thesis provides an overview of the etiology and pathogenesis of DLBCL and comments on the current treatments, their limitations, and the emerging therapies that are promising for the future of DLBCL treatment and outcomes.
The optimization of extracting foreign DNA from fingernails
(2025) Reverendo, Caroline; Cotton, Robin W.
Fingernail samples are submitted to a forensic laboratory for the analysis of endogenous deoxyribonucleic acid (DNA) for purposes of human identification or for the analysis of exogenous, or foreign, DNA on the nail surface. The presence of foreign DNA on nail samples may be a result of physical contact between two individuals, for example a victim and their attacker. The purpose of this study was to optimize the recovery of foreign DNA from fingernails. Phase 1 focused on length of incubation for fingernail samples to evaluate recovery of endogenous DNA; this informed Phase 2, which aimed at comparing the recovery of foreign DNA from fingernail samples when using a soaking or swabbing collection method.In Phase 1, fingernails of three donors were used to assess the average recovery of DNA in nanograms per milligram of nail (ng DNA/mg nail) after extraction incubation times of 15, 30, 45, and 60 minutes (min). The recovery of DNA in nanograms per microliter of whole blood (ng DNA/μl whole blood) after extraction was also evaluated using neat blood controls. The objective was to select an incubation time for nail samples that would effectively extract foreign DNA with minimal release of endogenous DNA from the sample. An incubation time of 15 minutes was chosen for Phase 2 to minimize the potential of endogenous DNA recovery from the nail samples.
In Phase 2, the comparison of DNA recovery was assessed between the soaking and swabbing collection methods using nails spiked with various volumes and dilutions of blood. Results indicate that the soaking method recovers more total DNA (both nail DNA and blood DNA) present in the sample compared to the swabbing method; however, the difference in DNA recovery between the collection methods was not statistically significant.
The DNA profiles of the blood-spiked nail samples were interpreted to compare each collection method’s efficiency at extracting foreign DNA while also minimizing the recovery of endogenous DNA. The difference in average peak height from unique nail alleles and unique foreign alleles, observed across loci where there were no shared alleles between nail and blood donors, were both not statistically significant between collection methods. However, the difference in the average percent recovery of unique nail alleles for nail samples spiked with 10, 5, and 2 microliters (μl) of whole blood was statistically significant between collection methods (p= 0.017), with 69.1% recovery using the soaking method and 32.7% recovery using the swabbing method. These results suggest that the potential for recovering endogenous DNA from samples is lower when using the swabbing method as compared to the soaking method.
However, there was no statistical significance in the difference of percent recovery of unique nail alleles for the samples spiked with the second set of blood volumes and concentrations (2 μl of whole blood, 2 of μl 1:2 blood dilution, and 2 μl of 1:5 blood dilution). Furthermore, similar to the first set of blood-spiked nails, both the soaking and swabbing collection methods recovered 100% of foreign DNA alleles from the fingernail samples. As a result, no conclusion was made on the efficiency of recovery foreign DNA between collection methods.
The percent recovery of unique foreign alleles was 100% across all samples of Phase 2, indicating that the amount of whole blood and blood dilution samples chosen to be aliquoted onto the nail samples may have been too large to effectively assess the recovery of foreign DNA from nail samples between collection methods. As a result, no conclusion was made on the effectiveness of the soaking and swabbing collection methods on the recovery of foreign DNA from fingernail samples.
Investigating the relationship between select dietary elements and cognitive functioning in Gulf War veterans
(2025) Reyna, Kathleen Bailey; Sullivan, Kimberly; Peters, Junenette
BACKGROUND: Gulf War Illness (GWI) is a chronic multisymptom condition that affects approximately one-third of all 1990-1991 Gulf War (GW) veterans and is characterized by debilitating fatigue, chronic pain and cognitive difficulties. Cognitive decrements are some of the most common and distressing symptoms of the disorder. Although multiple studies have investigated cognitive outcomes in GWI, little is known about the relationship between dietary elements and cognitive functioning in GW veterans.
AIMS: The study aims were to investigate the relationship between select dietary elements (zinc, magnesium, and manganese) and a cognitive test battery (including attention/executive functioning, learning & memory, and mood) in GW veterans.
METHODS: Urine samples and cognitive test battery data from 187 participants of the Boston Biorepository, Recruitment, and Integrated Network (BBRAIN) study for GWI were compared in this study. Urine samples were used to assess zinc, magnesium, and manganese levels. The Conners Continuous Performance Test Third Edition (CPT3) and the Delis–Kaplan Executive Function System Color-Word Interference Test (CWIT) were used to assess for attention and executive functioning, specifically sustained attention and interference inhibition. The California Verbal Learning Test – Second Edition (CVLT-II) and the Rey-Osterrieth Complex Figure Test (ROCFT) scores were used to assess verbal and visual memory. Lastly, the Profile of Mood States (POMS) and Center for Epidemiologic Studies Depression Scale (CESD) questionnaires were used to assess for both elevated mood complaints and depression. To assess the potential relationships between the selected dietary element levels and the cognitive outcomes of interest, the 187 GW veterans were stratified into quartiles based on their element concentrations. Histograms, box plots, generalized linear models, and the stargazer function in R Studio were used to visualize and analyze the data.
RESULTS: All analyses referenced the first (lowest) concentration quartile. In assessing executive attention and function, the CPT3 results most significantly indicate an association between higher levels of Mn and potential impulsivity. For the CWIT, Zn was associated with a marginal increase in trial times, Mg was associated with a marginal decrease in trial times but significant decrease in uncorrected errors, and the highest levels of Mn were associated with an increase in trial times. For learning and memory, the CVLT-II trials 1-5 showed marginal associations between the highest quartile of Zn and the second quartile for Mg and an increase in the number of words learned and recalled, while the highest quartile of Mn was associated with a decrease in the number of words learned and recalled. For mood, on the POMS questionnaire, the fourth quartile for Mg was associated with a marginal decreased Fatigue-Inertia scale scores and the second quartile for Mn was associated with a marginal decrease in Depression-Dejection scale scores. Associations were not found between the dietary elements and the ROCFT and CESD questionnaire.
CONCLUSION: The relationship between cognitive functioning and select dietary elements (zinc, magnesium, and manganese) indicate more positive cognitive outcomes with higher levels of Zn and Mg, and lower levels of Mn. The results suggest that dietary changes or supplementation could have some potential as therapeutic targets for GW veterans’ cognitive decrements upon further investigation and validation. Key words: Gulf War Illness, Veterans’ health, cognition, elements