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Carbon in the Coastal Foredune: Implications for the Barrier Island Carbon Budget
Get PDFCoastal dunes are widespread, occurring globally on sandy shorelines, however, they remain underrepresented in blue carbon research. We quantified carbon stocks and vegetation–carbon relationships across foredunes of different types and ages on a barrier island located on the east coast of the U.S. Sediment cores, vegetation surveys, and topographic profiles across three dune types (primary, secondary and tertiary) and three age classes (~7, ~11, and >20 years) reveal mean total carbon to 0.5 m depth is 1.07 kg C m⁻², divided between belowground biomass carbon (65%), sand carbon (34%), and aboveground biomass carbon (1%), with no significant differences by dune position, age, or type. Vegetation communities differed significantly with dune type and age, suggesting that ecological succession in dune systems may precede measurable differences in carbon. Our results caution against extrapolating from vegetation patterns to carbon stocks.Master of Scienc
Coronals of San Juan Quiahije Chatino
Get PDFThis study documents the phonetics of the coronal consonants of the Otomanguean language San Juan Quiahije Chatino, which is an underdocumented language. Like other Chatino languages, San Juan Quiahije Chatino has two series of coronal consonants, which contrast across multiple manners of articulation. This study proposes that the two series are best described as alveolar and postalveolar, in contrast to earlier work defining them as apical-dental and laminal-alveolar. However, the exact place of articulation is affected by manner of articulation. The acoustics of each series are more unified: the second formant transition coming out of a postalveolar is consistently higher than coming out of an alveolar. These results add to our knowledge of coronal contrasts across languages and the acoustic differences between coronal places of articulation.Master of Art
DEVELOPING COMPUTATIONAL TOOLS TO EXPLORE CHROMATIN DYNAMICS
Get PDFThe three-dimensional organization of the genome shapes gene regulation, ultimately affecting development and disease. Chromosome conformation capture technologies like Hi-C have transformed our ability to map this at a genome-wide scale. These approaches have revealed that chromatin loops play central roles in connecting enhancers with promoters, insulating genes from improper activation, and enabling cell-type-specific transcription. With wider adoption of these methods, we are discovering how structural variation, environmental cues, and disease states reshape the 3D genome in ways that alter cellular identity and function.Despite this progress, major barriers remain. Hi-C experiments are costly and sequencing-intensive, restricting their scalability. The data produced is noisy and sparse, making it difficult to distinguish true loops from background signal. Although powerful statistical frameworks exist for gene expression and differential loop detection, their accuracy hinges on the quality of the underlying data, and very little guidance exists on how to design experiments that will provide datasets with the necessary statistical rigor. These problems limit how effectively researchers can plan, analyze, and interpret 3D genomics experiments.I have developed computational tools that strengthen both the experimental and analytical sides of exploring the dynamics of 3D chromatin structure. Hi-C Poweraid is a web application that provides quantitative guidance for experiment design by estimating sequencing depth and replicate requirements needed for well-powered differential loop detection. Loopcity is an R/Bioconductor package for identifying interactions of groups of loops, enabling investigation of higher-order chromatin communities and their dynamics across conditions. These tools reveal that deeper sequencing than is typically performed is often required to detect condition-specific loop changes, particularly for subtle differences or long-range interactions, and they provide recommendations for planning future experiments accordingly. They also show that chromatin communities act cooperatively to influence regulation, underscoring their importance as a distinct and relatively underexplored layer of genome organization. Overall, this work advances both experimental design and biological insight, enabling new explorations of 3D genome dynamics across conditions and its impact on gene regulation, disease, and human health.Doctor of Philosoph
Applying a systems approach to identify strengths and opportunities to support Black breastfeeding families in Southeastern North Carolina
Get PDFBackground: Breastfeeding rates continue to rise in the United States, yet, inequities persists among racial groups. Multi-level factors spanning clinical and community settings influence breastfeeding outcomes, especially for Black families that have some of the lowest rates of breastfeeding continuation. To understand how the confluence of structural, societal, and interpersonal forces produce the inequities in breastfeeding seen in North Carolina and to identify opportunities for improved support, I will apply a systems thinking approach to critically assess breastfeeding services and map the experiences of Black families living in coastal, southeastern North Carolina.Methods: Circle of care modeling, causal loop diagraming, and group model building were used understand and map strengths and opportunities for improving breastfeeding support for Black families in Southeastern North Carolina. Analyses were conducted using thirty-three key informant interviews were conducted along with shadowing sessions in the inpatient settings. Discussion: There are significant strengths in the system that support Black families including familial support and the lactation workforce. Some opportunities for improvement include expanding, supporting, and diversifying the workforce and improving delivery of care for breastfeeding support during the inpatient setting. Additionally, group model building participants identified and prioritized actions for change. Conclusion: The findings of this dissertation can be used by health system leaders, community-based organizations, and WIC staff that are interested in supporting breastfeeding within their settings. Next steps for this research include disseminating findings by contributing to the literature and engaging with individuals and organizations who are interested in supporting breastfeeding. The actions for change identified can be further developed into feasible solutions and adapted for the local context in southeastern North Carolina. Future research should investigate how to meaningfully support, expand, and diversify the lactation workforce particularly in healthcare systems serving patients across counties such as in this project.Doctor of Philosoph
DNA mismatch repair mediated by Mlh1-Pms1 endonuclease-catalyzed mispair excision.
Get PDFEukaryotic DNA mismatch repair (MMR) involves several excision pathways, including those mediated by exonuclease 1 (Exo1) and by the flap endonuclease Rad27 (human FEN1) coupled with DNA polymerase δ. Simultaneous inactivation of both excision mechanisms causes an MMR defect that is at most 5 to 13% of that caused by complete inactivation of MMR. Here, we reconstituted nicked-strand-specific MMR with the Saccharomyces cerevisiae proteins Msh2-Msh6 or Msh2-Msh3, DNA polymerase ε, RFC, PCNA, RPA, and Mlh1-Pms1 (human Mlh1-Pms2) under conditions lacking Exo1, Rad27, or strand-displacement synthesis by DNA polymerase δ. These reactions required the Mlh1-Pms1 endonuclease activity, its activation by RFC and PCNA, and its recruitment by Msh2-Msh6 or Msh2-Msh3. MMR was mediated by nicked-strand-specific excision by Mlh1-Pms1 through formation of single-strand DNA gaps having a broad range of sizes. This reaction is consistent with genetic data demonstrating redundancy between the Exo1, Rad27, and Mlh1-Pms1 excision pathways in MMR
Unequal Effects of the Lockdown on Mental Health in Shanghai: The Moderating and Mediating Role of Neighborhood Environment and Online Social Connections
Get PDFThe COVID‐19 pandemic profoundly impacted population mental health worldwide. Few studies examined how the neighborhood environment and online social connections might influence the social gradient in mental health during the pandemic lockdown. We aim to examine the moderating and mediating role of neighborhood environment and online social connections in the association between socioeconomic status (SES) and mental health outcomes. We conducted a cross‐sectional online survey of 3763 Shanghai residents during the COVID‐19 lockdown between April 29 and June 1, 2022. Employing OLS linear regression analyses, our findings reveal that SES was negatively associated with depressive symptoms ( B = 0.173, p < 0.001) and anxiety ( B = 0.147, p < 0.001). The findings supported our hypotheses that this disparity in mental health was partially mediated by neighborhood social capital, community management, and the extent of online social connections measured by the frequency of social connection through the social media WeChat (all p < 0.05). Additionally, neighborhood social capital, community management, and online social connections also mitigated SES‐driven mental health inequalities (all p < 0.05). The study underscores the significance of the neighborhood environment and online social interactions in amplifying SES‐related mental health effects, offering valuable insights for urban planning and health equity strategies
Electrocardiogram-based machine learning for risk stratification of patients with suspected acute coronary syndrome
Get PDFBACKGROUND AND AIMS: The importance of risk stratification in patients with chest pain extends beyond diagnosis and immediate treatment. This study sought to evaluate the prognostic value of electrocardiogram feature-based machine learning models to risk-stratify all-cause mortality in those with chest pain. METHODS: This was a prospective observational cohort study of consecutive, non-traumatic patients with chest pain. All-cause death was ascertained from multiple sources, including the CDC National Death Index registry. Six machine learning models were trained for survival analysis using 73 morphological electrocardiogram features (80% training with 10-fold cross-validation and 20% testing), followed by a variational Bayesian Gaussian mixture model to define distinct risk groups. The resulting classification performance was compared against the HEART score. RESULTS: The derivation cohort included 4015 patients (age 59 ± 16 years, 47% women). The mortality rate was 20.3% after a median follow-up period of 3.05 years (interquartile range 1.75-5.32). Extra Survival Trees outperformed other forecasting models, and the derived risk groups successfully classified patients into low-, moderate-, and high-risk groups (log-rank test statistic = 121.14, P < .001). This model outperformed the HEART score, reducing the rate of missed events by >90% with a negative predictive value and sensitivity of 93.4% and 85.9%, compared to 89.0% and 75.0%, respectively. In an independent external testing cohort (N = 3095, age 59 ± 15 years, 44% women, 30-day mortality 3.5%), patients in the moderate [odds ratio 3.62 (1.35-9.74)] and high [odds ratio 6.12 (2.38-15.75)] risk groups had significantly higher odds of mortality compared to those in the low-risk group. CONCLUSIONS: The externally validated machine learning-based model, exclusively utilizing features from the 12-lead electrocardiogram, outperformed the HEART score in stratifying the mortality risk of patients with acute chest pain. This may have the potential to impact the precision of care delivery and the allocation of resources to those at highest risk of adverse events
A multi-kinase inhibitor screen identifies inhibitors preserving stem-cell-like chimeric antigen receptor T cells
Get PDFChimeric antigen receptor T cells (CAR T cells) with T stem (TSCM) cell-like phenotypic characteristics promote sustained antitumor effects. We performed an unbiased and automated high-throughput screen of a kinase-focused compound set to identify kinase inhibitors (KIs) that preserve human TSCM cell-like CAR T cells. We identified three KIs, UNC10225387B, UNC10225263A and UNC10112761A, that combined in vitro increased the frequency of CD45RA+CCR7+TCF1hi TSCM cell-like CAR T cells from both healthy donors and patients with cancer. KI-treated CAR T cells showed enhanced antitumor effects both in vitro and in vivo in mouse tumor models. The KI cocktail maintains TSCM cell-like phenotype preferentially in CAR T cells originating from naive T cells and causes transcriptomic changes without arresting T cell activation or modulating the chromatin organization. Specific kinases, ITK, ADCK3, MAP3K4 and CDK13, targeted by the KI cocktail in a dose-dependent manner are directly associated with the preservation of TSCM cell-like CAR T cells. Knockdown of these kinases individually or in combination enriches for TSCM cell-like CAR T cells, but only CAR T cells generated in the presence of the KI cocktail show robust expansion and differentiation on stimulation with tumor cells. Overall, transient pharmacological inhibition of strategically targeted kinases maintains stem-like features in CAR T cells and improves their antitumor activity
Assessing patient-reported outcomes in primary sclerosing cholangitis: an update.
Get PDFPURPOSE OF REVIEW: Patient-reported outcome (PRO) measures validated in primary sclerosing cholangitis (PSC) are needed for clinical trials. This review describes the recent US Food & Drug Administration (FDA) Patient-Focused Drug Development (PFDD) guidelines, existing PRO measures used in PSC studies, and the design of PSC-specific symptom measures adherent with the guidelines. RECENT FINDINGS: FDA released updated guidance reflecting best practices for the design and evaluation of clinical outcome assessments (including PROs) and the design of trial endpoints. Two recent systematic reviews (2018, 2020) identified multiple PRO measures used in PSC studies, with two additional measures published since. Of these, four were developed in samples inclusive of PSC patients and six have been psychometrically evaluated in PSC. Published evidence to sufficiently support alignment with the recent guidance is sparse. We review the design of three symptom measures for PSC to illustrate alignment with FDA guidance, including qualitative and quantitative studies to provide evidence for their validity for use in adult PSC trials. SUMMARY: Investigators planning to use PRO measures as study endpoints for PSC need to be adherent with the recent FDA guidelines and build the evidence base to support the measure as fit-for-purpose as an endpoint for clinical trials
CONSORT 2025 explanation and elaboration: updated guideline for reporting randomised trials
Get PDFCritical appraisal of the quality of randomised trials is possible only if their design, conduct, analysis, and results are completely and accurately reported. Without transparent reporting of the methods and results, readers will not be able to fully evaluate the reliability and validity of trial findings. The CONSORT (Consolidated Standards of Reporting Trials) statement aims to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996 and was updated in 2001 and 2010. CONSORT comprises a checklist of essential items that should be included in reports of randomised trials and a diagram for documenting the flow of participants through a trial. The CONSORT statement has been updated (CONSORT 2025) to reflect recent methodological advancements and feedback from end users, ensuring that it remains fit for purpose. Here, we present the updated CONSORT explanation and elaboration document, which has been extensively revised and describes the rationale and scientific background for each CONSORT 2025 checklist item and provides published examples of good reporting. The objective is to enhance the use, understanding, and dissemination of CONSORT 2025 and provide guidance to authors about how to improve the reporting of their trials and ensure trial reports are complete, and transparent