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Quantum Simulation of Dipolar Itinerant Lattice Models with Magnetic Erbium Atoms
No full textLong-range interactions are important to complex physical systems. Specifically in quantum mechanical many-body systems, long-range interactions promote spatial structures, give rise to quantum frustration, and generate quantum entanglement. Nevertheless, quantum simulations of lattice systems have largely not been able to realize long-range interactions. Many efforts are underway to explore long-range interacting lattice systems using polar molecules, Rydberg atoms, and magnetic atoms. In this thesis, I present the realization of long-range interacting itinerant systems using magnetic erbium atoms. I start by discussing the construction of the Erbium quantum gas microscope, including the installation of an in-vacuum high-numerical-aperture objective, various optical lattices, and potential projection through the objective. Then, I present emerging quantum phases with half-filling and directly probe the spatial structures of dipolar quantum solids using site-resolved imaging. A kaleidoscope of phases emerges as we tune the dipolar interaction, demonstrating the great tunability of this experimental platform. The dipolar interactions can be tuned slowly to study first-order quantum phase transitions between different solids. Next, I discuss topological phases that emerge with unity filling. With a zoo of Fano-Feshbach resonances, erbium atoms are gifted with the flexibility of widely tunable on-site interaction, allowing continuous probing of the quantum phase transitions between topologically trivial and non-trivial phases. We explore average symmetry protected topological phases as an instance of the mixed state quantum order. Finally, I briefly discuss the observation of spin squeezing with itinerant systems and super- and sub-radiance in a sub-wavelength optical lattice.Physic
The Soul's Companion Altered Consciousness, Embodied Practices, and the Power of Rhythm
No full textVersion of Recor
Impact of Post Operative Recovery Pathways on Peri-Operative And Oncologic Outcomes in Head and Neck Squamous Cell Carcinoma Patients
No full textImpact of Enhanced Recovery After Surgery protocols on short term outcomes following Laryngectomy with or without pharyngectomy
An IPTW Analysis
Importance
Enhanced Recovery After Surgery (ERAS) protocols have demonstrated improvements in postoperative outcomes following major head and neck surgical procedures. However, their impact on patients undergoing Total Laryngectomy with or without pharyngectomy, with or without neck dissection and reconstruction procedures (TL ± P) remains unclear.
Objective
To assess the association of ERAS protocol implementation in patients undergoing TL ± P procedures with short-term postoperative outcomes, including length of stay (LoS), incidence of unplanned return to the operating room (RTOR) and readmission in the 30-days following TL ± P, surgical and donor site infections (SSI; DSI), and pharyngocutaneous fistula (PCF) formation, and time to initiation of enteral and oral feeds.
Study Design, Participants and Setting
This was a retrospective cohort study of 240 adult patients who underwent the TL ± P procedures for any indication between January 2016 and June 2023 at a single academic subspecialty hospital in the United States. Inverse probability weighted regression models were used in the analysis.
Exposure
This study compared a cohort of patients who underwent surgery under a site-specific Enhanced Recovery After Surgery (ERAS) protocol, implemented in June 2019, with a historical cohort of patients who received the standard Traditional Recovery After Surgery (TRAS) care.
Main Outcomes and Measures
The primary outcome measures were the postoperative LoS, incidence of readmission and RTOR in the first 30-days following TL ±P. The secondary outcomes were the incidence of SSI, DSI, PCF, and the time to enteral and oral feed initiation.
Results
Among the 240 patients who underwent TL ± P procedures (83 TRAS,157 ERAS) (Mean age 67 years, 82 % Male). The ERAS cohort did not demonstrate significant differences in LoS (ERAS Median 10 days [IQR 8 – 13] vs TRAS Median 9 days [IQR 8 – 15] ; p = 0.53), and 30-day RTOR incidence(21 % vs. 10 %; p = 0.23). ERAS was associated lower incidence of readmission within the first 30-days of TL ± P (TRAS 35 % vs ERAS 26 %; p = 0.05), fewer incidences of surgical site infections (TRAS 48 % vs ERAS 37 %; p = 0.03), with earlier enteral (TRAS : Mean 1.5 days vs ERAS : Mean 1.25 days; p = 0.002) and oral feed initiation (TRAS : Mean 17 days vs ERAS : Mean 12 days; p = 0.005), with no significant differences in the incidence of donor site infections (TRAS 7 % vs. ERAS 10 %; p = 0.17), or pharyngocutaneous fistula formation (TRAS 21 % vs ERAS 16%; p = 0.12).
Conclusion/Relevance
Implementation of site-specific ERAS protocols was associated with earlier enteral and oral feed initiation, fewer incidences of 30-day readmissions and SSI, but was not associated with shorter LoS, RTOR incidence, or short-term complications (DSI, and PCF).
IMPACT OF ENHANCED RECOVERY AFTER SURGERY PROTOCOLS ON SURVIVAL AND PERI-OPERATIVE OUTCOMES IN HEAD AND NECK CANCER SURGERY
AN IPTW WEIGHTED RETROSPECTIVE COHORT STUDY
Importance
Enhanced Recovery After Surgery (ERAS) protocols are widely adopted for their peri-operative benefits across multiple surgical disciplines. However, their association with long-term oncologic outcomes in head and neck squamous cell carcinoma (HNSCC), remains unexplored, especially considering the heterogeneity of tumor subsites.
Objective
To evaluate the association between ERAS protocols and long-term oncological outcomes, and peri-operative metrics, in patients undergoing curative-intent surgery for mucosal HNSCC.
Study Design, Setting, and Participants
This retrospective, single-center cohort study included 389 adult patients with histologically confirmed mucosal HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx who underwent ablative and reconstructive surgery between January 2016 and August 2024 at a tertiary academic medical center. Inverse Probability of Treatment Weighting (IPTW) was use to balance the baseline characteristics between the ERAS and Traditional Recovery After Surgery (TRAS) cohorts.
Intervention/Exposure
Patients were assigned to either an ERAS-based postoperative care pathway (implemented institutionally in June 2019) or a TRAS pathway, determined by the date of surgery.
Outcomes
The main outcomes were 60-month overall survival (OS), loco-regional recurrence-free survival (LRFS), metastasis-free survival (MFS), and disease-free survival (DFS). Secondary outcomes included the rate of starting adjuvant therapy within 8 weeks, time to adjuvant treatment, length of hospital stay (LoS), and 30-day rates of readmission and return to the operating room (RTOR), incidence of surgical and donor site infections (SSI, DSI) and time to initiation of per-oral feeds.
Results
Of 389 patients, 294 received ERAS-based care and 95 received TRAS based care. After IPTW adjustment, baseline characteristics were well-balanced. In the analysis of the entire cohort, no significant association was observed between the ERAS pathway and evaluated survival endpoints (OS : HR 1.09; 95% CI, 0.75,1.56; p = 0.64; LRFS : HR 1.13, 95% CI: 0.76,1.68; p = 0.53; MFS: HR 1.40, 95% CI: 0.83,2.36; p = 0.19 and DFS: HR 1.05, 95% CI: 0.76,1.46; p = 0.75). However, a statistically significant interaction was identified between the recovery pathway and primary tumor site for all survival outcomes (all p 0.001). In site-specific analyses, ERAS was associated with worse survival outcomes for oral cavity cancers (OS HR 1.67; LRFS HR 1.98; MFS HR 2.64 and DFS HR 1.65; all p 0.05). In contrast, an association with improved survival was observed for patients with oropharyngeal and hypopharyngeal cancers (OS HR 0.40; LRFS HR 0.26 and MFS HR 0.30; all p 0.05, and laryngeal cancers(OS HR 0.50; LRFS HR 0.44; MFS HR 0.48 and DFS HR 0.45; all p 0.05. Perioperatively, ERAS implementation was associated with a shorter LoS (median ERAS: 10 vs. TRAS: 12 days; p = 0.05) and lower incidences of RTOR (ERAS: 15 % vs TRAS: 29%; p = 0.003). No statistically significant association was observed between the ERAS and RIOT rate (TRAS: 42% VS ERAS: 45%; p = 0.67), time to initiation of adjuvant treatment (Median - TRAS: 56 days vs ERAS 55 days; p = 0.58), 30- day readmission (TRAS: 29 % vs ERAS: 29%; p = 0.46), post-operative infections [(SSI – TRAS: 58% vs ERAS: 48%; p = 0.37); (DSI - TRAS: 20% vs ERAS: 16%; p = 0.60)] and per-oral feed initiation (Median TRAS: 15 days vs ERAS: 10 days; p = 0.83).
Conclusion/Relevance
In this cohort, the association between ERAS protocols and long-term oncologic outcomes in HNSCC surgery appears to be dependent on the primary tumor site. The implementation of this protocol was associated with survival benefits for patients with oropharyngeal, hypopharyngeal, and laryngeal tumors but with worse survival outcomes among patients with oral cavity cancers. These findings highlight the potential limitations of a "one-size-fits-all" ERAS approach and suggest that the relationship between recovery pathways and oncologic outcomes in HNSCC is complex and may require the development of site-specific protocols.MMSC
Immune Landscape and Differential Gene Expression in Hepatocellular Carcinoma: A Comparative Transcriptomic Analysis of Murine Models and Human TCGA Data
No full textHepatocellular carcinoma (HCC) remains a major global health challenge, exhibiting poor prognosis and limited therapeutic options. Although programmed death receptor 1 (PD-1)-based immunotherapy can extend survival in some patients, its overall response rates in HCC are modest. To elucidate mechanisms underlying immunotherapy resistance, we studied transcriptomic data from RNA-seq analyses of two orthotopic murine HCC models—RIL-175 (responsive, “immunologically hot” tumor) and HCA-1 (resistant, “immunologically cold” tumor)—and 369 human HCC samples from The Cancer Genome Atlas (TCGA-LIHC). We used bulk RNA-seq deconvolution and differential gene expression analysis (DGEA) to examine how TP53 mutation influences immune infiltration and the potential effect of immune checkpoint blockade on the TME. Our findings reveal that only high-impact TP53 mutations aligned with reduced immune effector cell infiltration, implicating dysfunctional p53 in fostering an immunosuppressive microenvironment. Furthermore, our evaluation of differentially expressed genes highlighted E2F1 as a key factor enriched in the resistant HCA-1 model. Elevated E2F1 expression correlated negatively with cytotoxic T-cell presence in murine tumors and was associated with significantly poorer survival in TCGA-LIHC patients. These data suggest that reactivating p53 (e.g., via mRNA nanoparticle delivery) could synergize with PD-1 blockade, whereas E2F1’s central role in immunoevasion makes it a compelling therapeutic target. Collectively, this study underscores how careful mutation stratification and targeted immunomodulatory strategies hold promise for improving clinical outcomes in advanced HCC.Graduate Educatio
Concurrent Composition of Interactive Mechanisms with Adaptive Privacy-loss Parameters
No full textOver recent decades, the predominance of data analysis algorithms has made privacy an increasingly greater concern. Differential privacy is one framework for providing privacy guarantees for analysis of sensitive data. A persistent research direction in differential privacy is providing theoretical support for all the variety of ways a data analyst can interact with a dataset, so that practical implementations can have provable privacy guarantees.
This thesis is concerned with the setting in which an analyst interacting with a set of differentially-private mechanisms is interested in both adaptively interleaving queries between mechanisms and also creating new ones. Previous work has provided provable guarantees for the sequential composition of non-interactive mechanisms with adaptive privacy-loss parameters, and the concurrent composition of interactive mechanisms with pre-fixed privacy-loss parameters, but no work has addressed the setting in which both the interaction and the privacy-loss parameters can both be chosen adaptively. Hence, we study the concurrent composition of interactive differentially-private mechanisms with adaptively chosen privacy-loss parameters. We provide formulations of privacy filters and odometers, specialized interactive mechanisms that allow for concurrent composition and adaptive composition, and also provide support for privacy-loss tracking. We prove that every valid privacy filter and odometer for non-interactive mechanisms extends to the concurrent composition of interactive mechanisms if privacy loss is measured using -DP, -DP, or R\'enyi DP of fixed order.
Our results offer strong theoretical foundations for enabling full adaptivity in composing differentially private interactive mechanisms, showing that concurrency does not affect the privacy guarantees. This thesis allows simplifications for existing code repositories, and also widens the range of scenarios in which differentially-private mechanisms can be applied with robust privacy guarantees.Computer Scienc
Transferrin Receptor Targeting Chimeras (TransTACs) for Membrane Protein Degradation
No full textAbstractCancer cells require high levels of iron for rapid proliferation, leading to a significant upregulation of the iron carrier protein Transferrin Receptor (TfR) on their cell surface. Leveraging this phenomenon and the exceptionally fast endocytosis rate of TfR, we introduce Transferrin Receptor TArgeting Chimeras (TransTAC), a novel molecular archetype for membrane protein degradation in cancers and other cell types. TransTACs repurpose the naturally recycling receptor TfR1 for protein degradation. To accomplish this, we utilized a combination of protein engineering strategies to redirect the target protein from recycling-endosome trafficking to lysosomal degradation. We show that TransTACs can highly efficiently degrade a diverse range of single-pass, multi-pass, native, or synthetic membrane proteins, establishing new possibilities for targeted cancer therapy.Accepted Manuscrip
Technology and Transition
No full textWhat role should emerging technologies such as carbon removal and solar geoengineering play in our response to the climate crisis? To critics, these technologies fail to address the root cause of climate change and allow wealthy nations to evade their climate responsibilities. To supporters, these technologies could make it easier to meet climate targets and even contribute to making the energy transition fairer. Indeed, carbon removal is widely considered to be a necessary component of the energy transition. This dissertation aims to advance this debate by unearthing and critiquing a web of normative and conceptual errors that confuse and constrain it. In doing so, this work contributes to broader questions concerning the relationship between technology, fairness, efficiency, and growth.Philosoph
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No full textNIH Public Access Policy Key Requirements
The Policy applies to any Author Accepted Manuscript resulting from NIH funding that has been accepted for publication on or after July 1, 2025. This replaces the 2008 Policy.
FREE COMPLIANCE
Authors do not have to pay a fee to comply with the Policy. See the NIH’s Supplemental Guidance on Publication Costs. https://grants.nih.gov/grants/guide/notice-files/NOT-OD-25-048.html
AUTHOR ACCEPTED MANUSCRIPT
The Policy applies to the Author Accepted Manuscript, or author’s final version that has been accepted for publication in a journal that meets NIH’s criteria.
PUBMED CENTRAL
Authors must submit the Author Accepted Manuscript to PubMedCentral
NO EMBARGO
Author Accepted Manuscripts deposited in PubMed Central must be made publicly available no later than the article’s official date of publication, eliminating the previous 12-month embargo.Version of Recor
Beyond Better Babies: Religion and Eugenic Maternalism in Progressive Era Child Welfare Reform
No full textThis dissertation explores the role of eugenic environmental reform in urban child and maternal welfare from 1900-1935. It centers on the New York City Babies Welfare Association (BWA), a federation of over one hundred private philanthropic and religious organizations, including settlement houses, education extension societies, clinical dispensaries, and educational clubs for children. Though its members reported to the hub, they remained relatively autonomous, and, as a result, much of the day-to-day work of public health programming was done not by public health officials alone but also by Protestant, Catholic, and Jewish women with religious missions.
I identify a vast network of reformers across these movements who collectively promoted and perpetuated the integration of public health and child welfare practices. I refer to these reformers as eugenic maternalists to demonstrate how eugenic ideas about heredity and the environment permeated discourses about religion, immigration, maternity, and child welfare in the first half of the twentieth century. This sprawling network of philanthropic, religious, and municipal organizations comprised a wide range of scientific, theological, and political views, offering a way of visualizing how eugenic maternalists created a unifying conception of American citizenship built around health and hygiene behavior and defined by perceived moral, mental, and physical fitness.History of Scienc