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An electronic microemulsion phase emerging from a quantum crystal-to-liquid transition
No full textStrongly interacting electronic systems often exhibit a complicated phase diagram that results from the competition between different quantum ground states. One feature of these phase diagrams is the emergence of microemulsion phases, where regions of different phases self-organize across multiple length scales. The experimental characterization of these microemulsions can pose significant challenges, as the long-range Coulomb interaction microscopically mingles the competing states. Here, we observe the signatures of the microemulsion between an electronic Wigner crystal and an electron liquid in a MoSe2 monolayer using cryogenic reflectance and magneto-optical spectroscopy. We find that the transition into this microemulsion state is marked by anomalies in exciton reflectance, spin susceptibility, and umklapp scattering, establishing it as a distinct phase of electronic matter.Chemistry and Chemical BiologyPhysicsAccepted Manuscrip
Disease-Modifying Antirheumatic Drugs, Rheumatoid Arthritis-Associated Lung Disease, and Serious Infection: Risks and Associations
No full textAbstract for paper 1:
Objective: To investigate the association of disease-modifying antirheumatic drugs (DMARDs) and risk of incident interstitial lung disease (ILD) among patients with rheumatoid arthritis (RA) using a systematic literature review and meta-analysis.
Methods: We performed a systematic literature review and meta-analysis of studies examining the association of DMARDs with incident RA-ILD. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to November 2023 for randomized controlled trials (RCTs), observational studies, and post-marketing surveillance studies that investigated adults with RA and compared DMARDs of interest with placebo, no DMARDs, or other DMARDs. The outcome was incident ILD. We summarized the literature on DMARDs and incident RA-ILD risk. Among studies with sufficient quality, we performed meta-analyses to obtain odds ratios (OR) and 95% confidence intervals (95%CI) using the Mantel-Haenszel method.
Results: Among 3,612 studies, we identified a total of 40 papers that encompassed 486,465 patients with RA and 3,928 incident ILD outcomes that were included in the final systematic review and meta-analysis. Among the studies, 24 were RCTs, 4 were prospective cohort studies, 9 were retrospective cohort studies, 2 were case-control studies, and 1 was a post-marketing surveillance study. The pooled analysis from RCTs revealed no statistically significant difference in the odds of ILD development for any specific DMARD across all comparisons examined. The largest identified RCT (Oral Surveillance trial) of tofacitinib (n=2,911) vs. tumor necrosis factor inhibitor (TNFi, n=1,451) found no relationship with incident ILD (OR 0.94, 95%CI 0.52 to 1.69, p=0.828). In 7 observational studies, the use of methotrexate (MTX) yielded a pooled OR for ILD of 0.49 (95%CI 0.32 to 0.76, p.001) compared to those not using MTX. In a single observational study, tofacitinib users had an OR for ILD of 0.36 (95%CI 0.15 to 0.87, p=0.024) compared to TNFi users.
Conclusion: Observational data suggest no increased risk of MTX and tofacitinib for incident RA-ILD. However, these studies may be susceptible to bias, and no specific DMARD showed associations with incident RA-ILD in RCTs. Further well-designed prospective studies are warranted for definitive conclusions on the potential relationship between DMARDs and RA-ILD risk.
Abstract for paper 2:
Objective: To investigate the association between rheumatoid arthritis-associated lung disease (RA-LD) and serious infection risk.
Methods: We conducted a retrospective cohort study using the MGB Biobank (Boston, Massachusetts), comparing RA-LD to RA patients without lung disease (RA-no LD), matched by age, sex, and RA duration. RA-LD cases were verified by medical record review and chest imaging for clinically apparent RA-associated interstitial lung disease (RA-ILD) and/or RA-associated bronchiectasis (RA-BR). The primary outcome was serious infection. Incidence rates and propensity score-adjusted subdistribution hazard ratios (sdHR) were calculated using Fine and Gray models to account for competing risk of death.
Results: Among 221 RA-LD cases (151 RA-ILD and 70 RA-BR) and 980 RA-no LD comparators, RA-LD had a significantly higher serious infection risk compared to RA-no LD comparators (55.8 vs. 25.8 per 1,000 person-years, sdHR 1.60, 95%CI 1.20-2.12). The increased risk remained significant for RA-ILD cases (sdHR 1.79, 95%CI 1.33-2.41), but not for RA-BR (sdHR 1.19, 95%CI 0.72-1.97). Anatomic sites of infection that were more common in RA-LD included pulmonary, skin and soft tissue, and ear, nose and throat; RA-LD was associated with various pathogen types: virus, bacteria, fungus, and mycobacteria. Specific pathogens with higher frequency in RA-LD cases, particularly among RA-BR, included influenza virus, respiratory syncytial virus, Staphylococcus, Pseudomonas, and nontuberculous mycobacteria.
Conclusion: RA-LD, particularly RA-ILD, is associated with a significant increased risk of serious infection across anatomic sites and diverse pathogen types. RA-BR is associated with increased pulmonary infections. Tailored infection prevention strategies, including vaccination, are essential for this vulnerable population.Graduate Educatio
From Crowded Classrooms to Empty Halls: How Enrollment Fluctuations Shape Students’ Academic Success
No full textThis thesis examines how enrollment fluctuations influence student academic performance through changes in school funding. Using data from Massachusetts and North Carolina, I leverage quasi-random variation in per-pupil funding generated by enrollment changes — a key determinant of district budgets under state funding formulas. Employing both Ordinary Least Squares (OLS) and instrumental variable (IV) approaches, with distance to Boston and local population growth as instruments, I estimate the causal effect of enrollment shifts on student outcomes in Math and English Language Arts (ELA). While OLS results suggest a positive relationship between enrollment growth and test scores, IV estimates reveal smaller and often insignificant effects, indicating that simple correlations may be biased by unobserved factors. Panel regressions show that in Massachusetts, higher enrollment levels are associated with declines in test performance, likely due to overcrowding and resource strain. In contrast, North Carolina schools with more stable or growing enrollment see modest improvements in ELA scores, highlighting different policy challenges in shrinking versus growing districts. These findings underscore the need for tailored policy interventions to manage the consequences of enrollment volatility and ensure sustained educational quality.Applied Mathematic
Ride Dedications: Caring for Memories and Ritual Transformation on the World's Longest Charity Bike Ride
No full textAuthor's Origina
Toward high-cooperativity spin-magnetomechanics with levitated micromagnets
No full textCoupling high-quality mechanical resonators to strong quantum nonlinearities has become an exciting field of research in recent years. These systems offer prospects for long-range entanglement between spins, cooling a mechanical resonator to its ground state, and even production of non-Gaussian states of motion. In this thesis, I will present our progress toward the high-cooperativity regime in a spin-mechanics system. For our mechanical resonator, we levitate micromagnets over a planar type-II superconductor (YBCO). The mechanical modes offer excellent environmental isolation and a high magnetic field gradient-to-mass ratio. We choose to work with nitrogen-vacancy (NV) centers in diamond as our spin due to their long coherence times, large magnetic coupling, and optical initialization and readout. I will present three approaches. First, a characterization of our levitated system and measurement of the coupling to a translational degree of freedom in devices of magnets isolated in silicon pockets. Then, I will describe an approach to shrinking the length scales of the system with patterned NbTiN films on a diamond substrate. Finally, I will discuss coupling to a rotational degree of freedom with an improved platform of NV centers implanted in a diamond membrane (∼ μm thick) placed on a YBCO sample. In addition to these three iterations, I will discuss our investigation into the quality factor limitations of the mechanical resonator. Such improvements pave a clear path to the high-cooperativity regime and will enable near-term milestones such as the detection of a single spin by the levitated system, a gateway for future quantum applications.Physic
Convergent and Sex-Differential Genetic Underpinnings of Autism
No full textAutism is a highly heritable neurodevelopmental disorder characterized by restricted or repetitive behaviors and interests as well as challenges with social communication. Epidemiologically, autism is both common – one out of every thirty children in the United States is diagnosed with autism – and strikingly male biased, with three to four males diagnosed with autism for every one female. Twenty years of large-scale sequencing studies of autistic individuals have implicated many genetic variants across many different genetic variant classes in autism, demonstrating its substantial locus heterogeneity and complex genetic architecture. These sequencing studies have also consistently found that autistic females tend to carry a higher genetic load of autosomal autism-associated variation compared to autistic males. That females require more autosomal genetic risk to manifest autism than males suggests that females are somehow intrinsically genetically “protected” from autism, and this phenomenon has thus come to be known as the “female protective effect” (FPE). However, the genetic basis for the FPE remains unknown.
In this dissertation, I address two major questions in autism genetics. First, how do the many diverse genes and genomic loci implicated in autism molecularly converge on this shared phenotype? Second, what mechanisms underlie the reduced genetic susceptibility of females to autism, as evidenced by the FPE? In Chapter 1, I discuss the genetic architecture of autism across three major axes (scale of variation, mode of inheritance, and allele frequency). I then
summarize the evidence supporting the “convergence in autism” hypothesis, which proposes that the significant locus heterogeneity observed in autism can be explained by the convergent disruption of a core set of autism-associated genes and pathways by a wide array of distinct risk loci. Next, I discuss our current understanding of the origins of the male bias and FPE in autism. I emphasize that the male bias in autism cannot be fully explained by underdiagnosis of autistic females or X-linked causes of autism. Rather, the FPE suggests a generally decreased susceptibility of females to autosomal genetic risk for autism—a pattern I show extends to at least sixteen other male-biased congenital, developmental, or pediatric disorders. This suggests a more generalized FPE beyond autism. Finally, motivated by recent insights regarding the “inactive” X (Xi) and Y chromosomes – and particularly the recent realization that Xi and Y act in trans to modulate thousands of autosomal genes across the genome – I propose that a generalized FPE arises from genetic divergence between Xi and Y: the largest, oldest, and most common variation in the human genome.
In Chapter 2, I demonstrate that genetic knockdown of autism risk genes in human neural progenitor cells and cortical organoids leads to convergent transcriptional changes due to shared disruption of a small set of key upstream regulators that coordinate tightly connected gene regulatory networks of autism genes. I further investigate convergence in autism through the creation and analysis of Consensus-ASD, a comprehensive and public-facing database integrating autism-associated variants across seven different genetic variant classes. Finally, I examine the role of X-linked genes, particularly those that are expressed from Xi, in driving both the male bias and FPE within autism.
In Chapter 3, I analyze sequencing data from >400,000 healthy adults in two independent population cohorts to demonstrate that females in the general population harbor a significantly higher burden of deleterious autosomal variation, including both deleterious autosomal deletions and single-nucleotide variants, compared to males. Moreover, I demonstrate that this deleterious autosomal variation is concentrated in highly constrained and dosage- sensitive genes, suggesting that females may be more resilient to disruptions in autosomal gene dosage compared to males. This observation provides important context to the FPE in autism and further suggests a generalized FPE beyond autism, as hypothesized in Chapter 1.
Finally, in the Appendix, I include three additional first-author works from my dissertation research that highlight the role of genetic variation in shaping phenotypes beyond autism, including Alzheimer’s disease, focal cortical dysplasia, and cardiac metabolism. Thus, while the main body of my thesis focuses on the genetics of autism, these additional works from my dissertation illustrate the broader application of genetic and genomic approaches to understanding complex human traits.
In summary, my dissertation provides novel insights into how genetic variation contributes to both shared molecular features of autism and sex-specific patterns of genetic vulnerability.Biomedical Informatic
The Marianas Adrift: Indexing Modernity in The Archipelago Beyond Tourism
No full text“The Marianas Adrift” examines the cultural power of sight in the Pacific, questioning the authority of “complete vision” and its colonial origins. Engaging the oscillation between the illegible and the hyper-legible, the project interrogates how landscape is visualized, archived, and designed through the epistemic frameworks of islands and archipelagos.
Set across the island of Pagan, the project embraces an archipelagic approach to interconnection, intervening in episodes of manifestation and dissolution—where lava flows repopulate islands and bomb craters become foundations for cultural resurgence. Here, design operates as an index, simultaneously revealing the accumulated histories of landscape and reorienting its spectacle.Department of Landscape Architectur
Remarcation: Redefining, Remaking, and Reclaiming Disability in Public Space
No full textDespite legislation to ensure that disabled people have access to public space, like the Americans with Disabilities Act (ADA), many disabled people are still unable to access public spaces and services. Though this is in part due to a culture of minimum compliance in architecture, it also stems from the false belief that when a building is labeled as “accessible,” it is accessible to everyone. However, because many accommodations that help some disabled people harm others, there is no such thing as universal access as people would like to believe. By examining the intersection of the objective, static nature of physical architecture with the personal, ephemeral experience of the user, this thesis attempts to create a more realistic understanding of what accessibility can and should look like in public space. Through the exploration of common spaces at Harvard University with individuals of diverse physical, mental, and sensorial disabilities, this thesis has produced a set of guidelines and assessment tools to map the plethora of factors that influence the accessibility of a space. This framework aims to help end modern segregation of the disabled community from the broader public by giving educators, designers, developers, lawmakers, and others who have jurisdiction over shared spaces the tools they need to prioritize accessibility and ensure that everyone has access to a beautiful world.Department of Architectur
More Than the Sum of Our Parts: Identity, Bioethics, and Plastination in China
No full textPlastination, a unique tissue preservation method, has been the subject of misunderstandings and controversies related to claims of negligent sourcing of human bodies and body parts in the People's Republic of China (PRC), an authoritarian state. The International Society for Plastination (ISP) has maintained an informal consensus on rigorous ethical standards, yet they do not have an established ethical framework for their globally dispersed members. This thesis asserts the ISP must create a codified ethical framework that aligns with internationally agreed upon standards while also ensuring culturally sensitive protocols inclusive of identity acknowledgement and continuity. Policy implications for the ISP were determined through examination of the complex history and current state of plastination in the PRC, the function of identity and how it translates to plastinated bodies and body parts, the use of anonymity, authoritarianism's role in shaping historical and current methods of body procurement in the PRC, and how medical practitioners in the PRC are working within their communities to rebuild trust in body and organ donation processes. Qualitative research involved ethnographic methods, including unstructured interviews with six individuals in the plastination community; the ethnographic interviews were complemented by analysis of secondary source materials. Formulation of a codified ethical framework for the ISP is essential to both solidify and strengthen the current standards plastinators adhere to. Further, clarification of history, current practices, and pathways forward dispels the misconceptions about plastination so that fictional claims do not prevail or further impede progress
Statistical Advances Under Dependence: Multiple Studies, Stein Variational Methods, and Limit Theorems
No full textThis dissertation presents contributions to statistical inference and probabilistic modeling, with a focus on uncertainty quantification, variational inference, and dependence structures in limit theorems.
The first part introduces a robust method for integrating evidence across multiple dependent studies. Recently, there has been a surge of interest in hypothesis testing methods for combining dependent studies without explicitly assessing their dependence. Among these, the Cauchy combination test (CCT) stands out for its approximate validity and power, leveraging a heavy-tail approximation insensitive to dependence. However, CCT is highly sensitive to large p-values and inverting it to construct confidence regions can result in regions lacking compactness, convexity, or connectivity. This article proposes a “heavily right” strategy by excluding the left half of the Cauchy distribution in the combination rule, retaining CCT's resilience to dependence while resolving its sensitivity to large p-values. Moreover, the Half-Cauchy combination as well as the harmonic mean approach guarantees bounded and convex confidence regions, distinguishing them as the only known combination tests with all such desirable properties. Efficient and accurate algorithms are introduced for implementing both methods. Additionally, we develop a divide-and-combine strategy for constructing confidence regions for high-dimensional mean estimation using the Half-Cauchy method, and empirically illustrate its advantages over the Hotelling T^2 approach. To demonstrate the practical utility of our Half-Cauchy approach, we apply it to network meta-analysis, constructing simultaneous confidence intervals for treatment effect comparisons across multiple clinical trials.
The second part examines Stein Variational Gradient Descent (SVGD) for Gaussian variational inference. Stein Variational Gradient Descent (SVGD) is a nonparametric particle-based deterministic sampling algorithm. Despite its wide usage, understanding the theoretical properties of SVGD has remained a challenging problem due to the complicated dependency structures between particles in their updates. Notably, for sampling from a Gaussian target, the SVGD dynamics with a bilinear kernel will remain Gaussian when the initializer is Gaussian. Inspired by this fact, we undertake a detailed theoretical study of the Gaussian--SVGD, i.e., SVGD projected to the family of Gaussian distributions via the bilinear kernel, or equivalently Gaussian variational inference (GVI) with SVGD. We present a complete picture by considering both the mean-field PDE and discrete particle systems. When the target is strongly log-concave, the mean-field Gaussian--SVGD dynamics is proven to converge linearly to the Gaussian distribution closest to the target in KL divergence. In the finite-particle setting, there is both uniform in time convergence to the mean-field limit and linear convergence in time to the equilibrium if the target is Gaussian. In the general case, we propose a density-based and a particle-based implementation of the Gaussian--SVGD, and show that several recent algorithms for GVI, proposed from different perspectives, emerge as special cases of our unifying framework. Interestingly, one of the new particle-based instance from this framework empirically outperforms existing approaches. Our results make concrete contributions towards obtaining a deeper understanding of both SVGD and GVI.
The third and fourth parts of the dissertation investigate classical probability problems concerning Wasserstein-p bounds in central limit theorems under dependence. The central limit theorem is one of the most fundamental results in probability and has been successfully extended to locally dependent data and strongly mixing random fields. In this work, we establish the rate of convergence in the central limit theorem in terms of transport distances. In specific, for arbitrary p>=1 we obtain an upper bound on the Wasserstein-p distance between the law of the scaled sum and the limiting normal distribution for (i) locally dependent random variables and (ii) strongly mixing stationary random fields. Our proofs extend the Stein's dependency neighborhood method for the Wasserstein distance of a general order p>=1 and provide new tools to study the deviation behaviors for dependent random variables. Moreover, as an application we demonstrate how our results can be used to obtain tail bounds that are asymptotically tight and decrease polynomially fast for the empirical average under weak dependence.
Collectively, these works provide new insights into statistical inference under dependence, advancing both methodological and theoretical understanding.Statistic