Brown University

NSF Awards · FY 2024 · 2024-09

Soft materials underpin important technologies such as adhesives, coatings, drug delivery, and energy storage. One key challenge with such materials is how they change when exposed to fluids, especially if these fluids contain dissolved salts (e.g., seawater, bodily fluids, or battery electrolytes). Soft materials will often dissolve, detach, or excessively swell in salty fluids, leading to their failure. This award supports research into a new class of soft materials designed for salty fluid environments. The influence of molecular scale design on the mechanical properties of these materials will be investigated. The resulting fundamental knowledge will provide a foundation for adhesives or structures that strengthen in environments such as seawater; components that aggregate in response to specific salt species, enhancing desalination plants; and as salt driven muscle-like components for soft robotics. This award will also result in the interdisciplinary education of students in New York and Rhode Island in mechanical engineering and chemical sciences. A novel zipper-like molecular topology of soft polymeric materials decorated with tethered cationic and aromatic groups, termed ZIPers, will be investigated. These materials are simple to prepare on large scale and preliminary data shows that these ZIPers have a complex dependence of equilibrium structure and mechanical properties on the concentration and type of anion present in solution, features that can be dynamically adjusted by changes in ionic content. This work will utilize a combination of synthetic, experimental, and modeling approaches to provide insight into three aspects of their mechanical behavior: (1) the equilibrium structures and corresponding small strain oscillatory response of the ZIPer system as a function of monomer ratio, salt type, and salt concentration; (2) how the structure and crosslink dynamics determine the time dependent large deformation mechanical response of the ZIPer system; (3) potential of the ZIPer system to exhibit salt-driven shape-morphing. New mesoscale and continuum polymer modeling techniques will enable this work and also be standalone contributions to the mechanics of polymers field. This project will advance knowledge of the mechanics of dynamically bonded polymers and provide key insights into the properties of dynamic and responsive soft materials. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Interpreting many of the results from astronomical observatories requires numerical simulations, often run on supercomputers. These include dynamical radiative magnetohydrodynamic (MHD) simulations with algorithmic innovations, many of which are not currently in hand. Many of these innovations can be described as structure-preserving; in other words. there is physics in the numerical partial differential equations (PDEs) that has to be mimicked at a discrete level in codes that are optimized for spherical geometry. Our current capabilities for computational astrophysics are deficient because the relevant applied mathematics has not been developed for solving these problems. A research collaboration between the University of Notre Dame, Brown University and ETH Zürich in Switzerland will work together to overcome some of these deficiencies by making targeted advances in applied mathematics, which would be transformative in how they enable unprecedentedly novel astrophysical simulations that help in the interpretation of valuable observational data. The students and postdocs trained in this project will find many fertile career trajectories in astrophysics, applied math, and other fields such as plasma physics. The PI also runs an after-school remedial math program for students in the Gary, Indiana area who have fallen far behind in their math education. The applied mathematics challenges come in three parts: 1) We need high order divergence-preserving methods for capturing MHD turbulence that occurs in the vicinity of massive stellar winds. 2) We need multigroup radiation hydrodynamics 3) For long-term, high-fidelity, simulation of planetary atmospheres, we need well-balanced methods that are implicit in the radial direction and can preserve angular momentum. To overcome deficiencies in current astrophysical codes, the team will develop: 1) Discontinuous Galerkin (DG) methods with non-oscillatory design and a capability for preserving geometrical conservation laws (GCL) 2) Divergence-free DG methods that can operate on geometrically complex cube sphere meshes. 3) An efficient multi-group method for radiation hydrodynamics based on DG schemes. 4) Well-balanced DG schemes that are implicit in the radial direction so that very thin zones in the radial direction can be handled. 5) DG schemes that are angular momentum preserving. The MHD and radiation hydrodynamics innovations will also find engineering applications in fields as plasma-based space propulsion and in simulating the physics of tokamaks. This collaborative U.S.-Swiss project is supported by the U.S. National Science Foundation (NSF) and the Swiss National Science Foundation (SNSF), where NSF funds the U.S. investigator and SNSF funds the partners in Switzerland. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2024 · 2024-09

PROJECT SUMMARY Polypharmacy, usually defined as the concurrent use of five or more medications, occurs in over 90% of nursing home (NH) residents with Alzheimer’s Disease and Related Dementias (ADRD). Prescribing cascades are a key driver of inappropriate polypharmacy. A prescribing cascade occurs when adverse events from one medication (the “precipitant medication”) are misinterpreted as manifestations of a new medical condition, resulting in the addition of another unnecessary medication to manage symptoms (the “resultant medication”). Because the underlying cause of the adverse event is never resolved and a new medication with additional risks is started, prescribing cascades may result in adverse outcomes such as hospitalizations, injurious falls, decreased physical and cognitive function, and death. Our research team’s preliminary data suggest over 50% of NH residents may experience prescribing cascades. There is a severe lack of evidence on the causal effects of prescribing cascades on health outcomes in NH residents, especially those with ADRD, who are at high risk of polypharmacy and its adverse effects. To optimize prescribing and deprescribing, it is essential to generate evidence on prescribing cascades and their effects among NH residents with and without ADRD. Without additional evidence, providers will be unable to identify clinically significant prescribing cascades that could be intervened on to improve NH resident health outcomes. Thus, the overall objective of this proposal is to understand how prescribing cascades arise in NH residents and to quantify their effects on outcomes. Our central hypothesis is that prescribing cascades increase the risks of adverse health outcomes (e.g., hospitalizations, decreased physical function, fall-related injuries, mortality) and the risks will be greatest among residents with severe cognitive impairment. This hypothesis will be tested through three specific aims: Aim 1, Identify risk factors for clinically relevant prescribing cascades among NH residents with and without ADRD; Aim 2, Estimate the effect of precipitant medication use on subsequent resultant medication use among NH residents with and without ADRD; and Aim 3, Quantify the effects of the prescribing cascades on adverse outcomes among all older adults in NHs and those in high-risk subgroups. To accomplish the proposed aims, we will leverage a large innovative database of NH electronic health record information linked to national Minimum Data Set clinical assessment records, Medicare health insurance claims, and other relevant datasets. We will also innovate by developing the use of novel causal inference approaches, including sequential target trial emulation and doubly robust estimation methods, for studying prescribing cascades and other related exposures. The proposed research is highly significant because it will provide clinically actionable empirical evidence to help guide the prescribing, deprescribing, and management of medications to minimize the risk of important prescribing cascades and adverse outcomes among NH residents with ADRD. This proposal is directly responsive to PAR- 22-093 and advances the National Institute on Aging’s Strategic Goal C to improve the safe use of medications.

NIH Research Projects · FY 2024 · 2024-09

PROJECT ABSTRACT This application proposes to examine where and for whom rural residence is associated with Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) in the United States. Analyses will 1) produce novel and robust estimates of dementia prevalence in rural and urban America; and 2) characterize the types of rural places and people most affected by dementia. This research is motivated by growing concerns for the health of rural Americans, roughly 46 million people and 14% of the U.S population. Rural Americans have had poorer health profiles than their urban peers since at least the 1980s, and the gap has widened over time. Yet surprisingly little is known about rural-urban disparities in dementia, which is poised to become one of the most significant population health challenges of the century. Dementia currently affects approximately 6.1 million or 11% of Americans ages 65 and older, and numbers are expected to rise dramatically in the coming decades due to population aging. The challenges associated with dementia may be especially severe in rural communities, where access to quality healthcare and other services for people with dementia and their caregivers is often severely limited. To anticipate and plan for the challenges associated with dementia, its patterning across places and people must be understood. However, demographic estimates of dementia prevalence in rural and urban America are lacking, even at the national level. Moreover, it remains unknown how the prevalence of dementia varies among rural places and people, despite the fact that rural America is not monolithic. The proposed project will therefore develop a demographic overview of rural-urban dementia disparities, including novel analyses of heterogeneity across places (Aim 1) and people (Aim 2). In particular, Aims will explore variation in dementia prevalence at the intersections of rural residence and regional setting (Aim 1a), county context and composition (Aim 1b), and individual-level sociodemographic characteristics (Aim 2). Analyses will be conducted with data from the Health and Retirement Study, a nationally representative survey of older U.S. adults. This application, led by an early-stage investigator, responds to PAR-23-179, which encourages applications generating scientific insights about AD/ADRD, including estimates of disparities, from early-stage investigators and established researchers new to the study of AD/ADRD.

NIH Research Projects · FY 2025 · 2024-09

PROJECT SUMMARY Many older adults who are hospitalized for heart failure (HF) lose their ability to independently perform activities of daily living and then require long-term custodial care in a nursing home—an outcome that many seniors fear more than death. Yet, research to date on post-hospitalization outcomes has focused on readmission and mortality, and has overlooked important patient-centered outcomes like functional recovery and return to one’s own home. Understanding which factors promote functional recovery is critically necessary. Medications are one of the most easily modifiable potential factors, yet their effects on functional recovery are not well-understood. Thus, the overarching objective of this proposal is to examine the impact of medications on functional recovery and successful transition back to home following a HF hospitalization. The proposed research will focus on older adults discharged to a skilled nursing facility (SNF) after HF hospitalization because: 1) nearly one in five patients require SNF care following HF hospitalization; and 2) patients requiring SNF care are most vulnerable to prolonged functional impairment, loss of independence, and the need for long-term custodial care. The central hypothesis is that many commonly prescribed medications may impair participation in rehabilitation, interfere with functional recovery, and/or decrease the likelihood of successful discharge to home from SNFs. This hypothesis will be tested through three specific aims employing a series of rigorous observational studies: Aim 1, Estimate the effects of HF-specific and other medications administered in SNFs, including dose and duration, on function and successful discharge to home after HF hospitalization (outcomes), and examine potential mediators like rehabilitation minutes and cognition; Aim 2, Develop a novel risk score for the cumulative effects of harmful medications that interfere with function and successful discharge to home after HF hospitalization, and validate its predictive performance for key outcomes and mediators; Aim 3, Quantify individual medication and cumulative medication burden effects on function and successful discharge to home across important pre- defined subgroups of older adults with HF, including by dementia status and varying degrees of frailty, multimorbidity, and polypharmacy. To accomplish the three proposed aims, a large innovative database of SNF electronic health record information will be leveraged along with national Minimum Data Set 3.0 clinical assessment records, Medicare claims, Veterans Health Administration data, and other unique datasets. The proposed research is highly significant because it will provide foundational evidence for developing interventions to optimize medication use patterns (via prescribing and deprescribing) and subsequently facilitate functional recovery after HF hospitalization. This research directly addresses the National Institute on Aging's Strategic Goal C to improve the safe use of medications.

NSF Awards · FY 2024 · 2024-09

The signals that animals use to communicate with each other are critical to life, mediating a wide range of social interactions that determine whether individuals live or die, find mates, and compete for opportunities to breed. One of the most spectacular features of animal signals is that they are remarkably diverse, with each species appearing to evolve its own unique set of ornaments and displays. Understanding how these different signals evolve and diversify is a longstanding goal of organismal biology, yet this topic remains mysterious in several ways. We know, for example, very little about how the brain influences the process of social signal evolution. In this IRES project, undergraduate students from around the U.S. will be trained to conduct research that addresses this major knowledge gap. Student participants work with a group of international PIs, who together use integrative approaches to study the evolution and control of animal communication behavior. Study locations include Austria and India, where participants work for a 10-week period during the summer. Research activities center around both laboratory and field experiments that are performed in groups and through independent research projects. Their experience abroad is bookended by pre- and post-travel training to help prepare the participants with appropriate technical and cultural acumen to successfully complete their projects. Students also receive professional development throughout the entire experience, and they will work throughout the summer to help construct conservation exhibits for the local zoo in Vienna, Austria. In this way, the program focuses not only on building research and outreach skills, but also cultivating international proficiency and awareness. Our program fulfills the goals of the IRES program by producing college graduates who are ready to join the global STEM workforce in the 21st century. International collaboration is a critical part of ecology and evolutionary biology, driving major discoveries about the principles of life on Earth. Yet, undergraduate students from the U.S. often encounter hurdles that prevent them from engaging in such collaborative research. This is a problem because it means that our undergraduate population may be underprepared to join the modern STEM workforce, particularly in areas of ecology and evolution. The current research project aims to develop a program that addresses this problem by annually involving 6 undergraduate students from around the US and 1 graduate student in mentored research projects in both Austria and India. The program will last 10 weeks in the summer, and student participants will conduct work that explores how neural systems influence the evolution of elaborate visual displays in frogs. Students will work independently, as well as in large teams, to investigate: 1) how adaptive cognitive traits drive display evolution, and 2) how motor circuits in the spinal cord co-evolve with display diversification. All work will be done in the laboratory and field alongside mentors from the host countries. Thus, student participants are given the chance to not only address fundamental questions in animal communication, but to do so in an international context that helps prepare them for STEM careers in a global landscape. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2024 · 2024-09

PROJECT SUMMARY This collaborative project between Beijing Normal University, Brown University, and Emory University responds to PAR-23-190 by developing and testing a stigma reduction focused, gender affirmative mobile health (mHealth) program to engage Chinese transgender women (TW) in HIV prevention via promoting their mental and sexual health, HIV self-testing and use of HIV and gender-related community and medical resources. Chinese TW are at threefold higher odds of HIV infection compared to their cisgender men who have sex with men peers yet no intervention or public health initiative exists to address their HIV prevention needs. Chinese TW also face multi- levels gender minority stress in a high stigma societal context, which in turn adversely affects their behavioral health, awareness of services, and HIV service-seeking behaviors (e.g., testing), which ultimately contribute to heightened HIV risk. There is an urgent need for evidence-based gender affirmative program as a potential way to engage TW in HIV prevention services and enhance their psychological and sexual health in high-stigma, LMIC contexts such as China. Building on the Gender Minority Stress framework and Transgender Resilience Intervention Model, and informed by our team’s prior work mHealth for HIV-related mental and behavioral health, we propose to develop a mobile app-based intervention (entitled “Zhen Wo”/”True Self”) delivered by TW peer counselors, who will provide gender-affirmative counseling and skills training that aim to reduce internalized transphobia and sexual risk behaviors, enhance coping and mental health, self-advocacy skills and resource utilization to combat multi-levels gender stigma and structural barriers, and promote engagement in HIV prevention services. By developing a low-cost, mHealth program delivered by TW peers and establishing a protocol that engages with existing community resources, the True Self program has the potential to achieve scalability and sustainability, if proven to be efficacious. The aims of this early phase, clinical project include: (1) conduct formative interviews with Chinese TW (n = 25) and stakeholders (n = 10) to identify stigma-related factors at various levels that contribute to poor mental health, sexual risk, and HIV testing, coping strategies, resources, and preferences for intervention content and delivery procedures; (2) develop the True Self program for Chinese TW at risk for HIV, followed by a small open pilot (n = 10) to finalize intervention protocol; (3) evaluate the feasibility, acceptability, safety, and preliminary effects of the True Self program via a randomized controlled trial (RCT) with TW with recent condomless/PrEP-less sex (n = 60). We will conduct quantitative assessments at baseline, 3-month, and 6-months follow-ups. We will conduct exit-interviews with TW assigned to the True Self condition (n = 30) to identify areas for further improvement and understand barriers and facilitators of engagement, along with interviews with stakeholders (n = 18) to inform future efficacy and implementation study designs. This developmental grant will provide essential data to guide subsequent R-series application for a fully- powered RCT and invest in capacity development for researchers and transgender health professionals in China.

NSF Awards · FY 2024 · 2024-09

Algebraic geometry is the study of spaces that can be described as solution sets of systems of polynomial equations. Circles, parabolae, and hyperbolae are all examples, from classical plane geometry, of shapes which are governed by defining polynomials, in these cases polynomials in two variables. In algebraic geometry, the deep connection between algebra (the defining polynomials) and geometry (the resulting shape) is key. Both recently and over the past century, a large effort has been focused on the study of some very particular spaces of long-standing interest, called moduli spaces, of curves and abelian varieties. These are parameter spaces for certain kinds of geometric objects, and they have deep connections throughout geometry, as well as to mathematical physics and combinatorics. This project will develop and employ modern techniques to make new progress on the study of such spaces. The project will also provide research training opportunities for students. This research program is centered on compactifications of moduli spaces and their tropicalizations, i.e., the instantiations of these moduli spaces in the field of tropical geometry. The project uses tropical moduli spaces, which are certain polyhedral complexes, as a geometric instantiation of the boundary combinatorics of an appropriately compactified moduli space. The existence of the tropical space allows the application of combinatorial-geometric techniques, as well as connections to the study of the cohomology of arithmetic groups. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-09

Project Summary: The current proposal, developed in response to RFA-AG-24-031 (Consortium for Economic Research on AD/ADRD Prevention, Treatment, and Care) will leverage the last 15 years of Medicare claims and clinical assessment data and econometric methods to advance our understanding of how post-acute and long-term care use and health outcomes for persons living with ADRD are impacted by the changing landscape of health care financing. The 6.7 million Americans living with ADRD are the most frequent users of long-term care services. Unfortunately, the current long-term care system is characterized by substantial barriers to access, variation in service quality, and potentially inefficient resource allocation across community-based and institutional care settings. In nursing homes, the predominant institutional long-term care setting, persons with ADRD often experience adverse care outcomes such as falls, avoidable hospitalization, and excessive psychotropic medication use. Although home- and community-based care services (HCBS) are an increasingly used alternative to institutional long-term care, the efficacy of HCBS for individuals with ADRD is unclear and many barriers to accessing HCBS remain poorly understood. A signature feature of the long-term care system is its reliance on post-acute care and more broadly, the involvement of multiple payers. However, our understanding of recent significant changes to the Medicare and Medicaid financing landscape on post-acute and long-term care utilization and outcomes is limited. Aim 1 of this proposal focuses on the changing use of nursing home and home health services among persons with ADRD in the context of states’ expansion of HCBS funding and constraints on provider supply from certificate of need laws. Aim 2 focuses on the evolution of MA in long-term nursing home care, a largely ignored area despite the explosive growth of the MA program. This Aim also includes an evaluation of a potential promise of MA in long-term care: the institutional special needs plans model. Aim 3 focuses on changes to a post-acute care revenue stream on the quality of post-acute and long-term nursing home care. Post-acute care spending has been a consistent target for saving Medicare dollars despite the importance of these funds for nursing home quality. Our study takes advantage of federal policy that reduced cost-sharing revenues for nursing homes, but in application affected nursing homes differently based on whether their state Medicaid programs had ‘lesser-of’ payment rules. Completion of this entire project will be a significant contribution given the projected increase in the number of people living with ADRD whose health outcomes may be sensitive to these financing and supply-side policies. Each Aim also includes analyses that explore patterns of utilization and outcomes across different population subgroups, including those with varied socioeconomic characteristics or Medicaid eligibility. The findings may inform future policy efforts to improve the alignment of funding and service delivery in post-acute and long-term care, ultimately promoting appropriate care access and outcomes for the ADRD population.

NSF Awards · FY 2024 · 2024-09

Many physical phenomena can be described by the principle of least action. This involves studying minima of certain functionals, called Lagrangians, named after the French mathematician and astronomer J-L Lagrange (1736-1813), that describe the energy of the system under consideration. For example, it is possible to derive Newton's laws of classical mechanics from the principle of least action. The principle can be applied also to more complicated systems, even infinite dimensional configuration spaces. One famous such example is the case of geodesics, paths minimizing the distance between two points in a smooth space. Another, more involved example is the case of harmonic maps. Here the Lagrangian energy is the total stretch of a map between two smooth spaces. In this project the PI proposes to study analogous situations for more complicated Lagrangians that have important applications. The project has also an educational component where the PI is planning to supervise graduate students towards their Ph.D. theses, undergraduates through seminar courses, and write expository notes for a wider audience. In slightly more technical terms, harmonic maps are critical points of the L-2 norm of the gradient (Dirichlet integral) of a map between two Riemannian manifolds. The PI proposes to study the calculus of variations of functionals associated with other function space norms like the L-infinity and L-1 norms. Minimizing functionals associated to the L-infinity norm yield solutions of fully non-linear degenerate elliptic PDE’s with very challenging regularity properties. Similarly, solutions of the dual non-linear problem for functionals involving the L-1 norm are equally challenging. The singular sets of these solutions provide geometric realizations of topological objects, like geodesic foliations and laminations, studied in topology. The PI proposes to develop the analytic methods to study these topological objects as well as others studied in Thurston theory. Examples are earthquakes and cataclysms. There is very little known in the literature about the analytic underpinnings of the theory so the PI has to develop most of the techniques from scratch. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Economic decision makers face an important constraint: while they need to know consumer preferences to identify welfare improvements, they can only observe choices made. Hence, welfare economics and its resulting implications rest heavily on the idea that choices are driven by one’s preferences. Under the classic model of rationality, a consumer has a stable preference over alternatives and systematically uses it to choose the best affordable option. Because neither decision process nor preference are observable, economists have had to content themselves with choices that, to the naked eye, are consistent with rational behavior under some preference. Choices look “as if they are rational” when, taken altogether, they do not lead to contradictory inferences about preferences (for an example of such a contradiction, imagine selecting option A when option B is affordable under some prices, but switching to option B when A remains affordable under some other prices). Comfortingly, a rich experimental literature establishes the prevalence of as-if rationality in a variety of economic contexts. It may seem natural to presume that as-if rationality is tightly coupled with the use of a rational decision process. The current research challenges this presumption. The researchers use a novel experimental design to show that even when experimental participants fail to maximize their welfare, they tend to use coherent decision rules, or choice procedures, that mimic properties of rational behavior. The ability to disentangle as-if rationality (which may be driven by rules of thumb or heuristics) from truly (i.e., substantively) rational behavior rationality has many important implications that this research investigates. For instance, given prior work establishing that as-if rationality correlates with wealth, is it substantive rationality or heuristic behavior that drives the correlation? Does heuristic behavior disappear given feedback and time to learn? Is the prevalence of substantive rationality responsive to the complexity of a decision problem? This research will also investigate multiple important questions arising in a society with some seemingly-rational consumers. These include how to aggregate choices, elect leaders, and minimize price distortions in markets. The experimental literature has documented, using various metrics of compliance with the General Axiom of Revealed Preference (GARP), that subjects tend to be highly as-if rational. Yet what drives this GARP compliance is unknown: there is an indeterminate relationship between the subject's welfare and the utility function(s) which seem to capture choices in these experiments. The researchers introduce a novel experimental design that pairs traditional experiments measuring subjects' natural preferences (i.e., their true preferences for risk, time, etc.) with isomorphic experiments that instead induce canonical preferences. Presuming only that money is desirable, this approach removes scope for subjects to rationally express unobserved ``home grown'' preferences: the utility-maximizing choice is the optimal demand under the induced preference. The initial finding, which is robust to multiple metrics of assessing substantive rationality, is that the majority of as-if rational subjects use suboptimal simplifying heuristics which only mimic rational demands. The researchers will extend and deploy this new experimental approach to address multiple questions on the nature and extent of this distinction. Do people become more procedurally rational in complex problems? Does procedural rationality correlate with classic behavioral biases? Which forms of rationality vary with experience? How do different forms of rationality correlate with socio-economic variables? The researchers will also experimentally investigate key questions relating to group rationality and the aggregation of choices. Is the pivotal agent in group decisions substantively rational? Are prices distorted in the presence of procedurally-rational agents, thereby impacting everyone’s welfare (including those who are substantively rational)? Does the fraction of substantively-rational choices decrease in strategic voting if being pivotal is unlikely? Do voters recognize and value candidates’ degrees of rationality? What becomes of the Coase theorem when bargainers fail to be substantively rational? The results have the potential to profoundly change how economists envision welfare economics, and to make significant contributions in applications to general equilibrium, strategic voting, and bargaining. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-09

PROJECT SUMMARY In the United States, women with disabilities are 32% less likely to use any contraceptive method compared to women without disabilities and have higher rates of unintended pregnancy and adverse pregnancy outcomes. In qualitative interviews, women with disabilities have stated that insufficient Medicare coverage of desired contraceptive methods is a barrier to contraceptive use. Medicare is a federal health insurance program that provides coverage to nearly 1.5 million women aged 20 to 49 years who receive Social Security Disability Insurance due to a chronic disability. Unlike private insurance plans and Medicaid, Medicare does not cover most contraceptive methods for pregnancy prevention. Individuals who are dual enrolled in Medicaid and Medicare due to a combination of low-income and disability receive contraceptive coverage through Medicaid. The goal of this proposed research is to evaluate the impact of Medicare’s contraceptive coverage policies on contraceptive use among women with disabilities. Using 2016-2021 inpatient, outpatient, carrier, and pharmaceutical Medicare and Medicaid claims data from all 50 states and D.C., I will examine differences in contraceptive use between women with disabilities enrolled in traditional Medicare, Medicare Advantage, Medicaid, and dual enrolled (Aim 1). I will then evaluate the impact of gaining contraceptive coverage through dual enrollment on contraceptive method use among Medicare enrollees with disabilities (Aim 2). This research will provide some of the first empirical evidence for policymakers on reproductive healthcare access and use among Medicare enrollees with disabilities. I will complete the analyses with support from collaborators with expertise in disability and reproductive health policy and claims data analysis, as well routine input from a community advisory board of women with disabilities. I am supported by an interdisciplinary research environment that includes the Center for Gerontology and Health Care Research and Center for Advancing Health Policy through Research at the Brown University School of Public Health. The training activities detailed in this application are focused on developing advanced methods in causal inference, best practices in conducting person-centered research, experience communicating research for policy impact, and teaching. These activities will prepare me for a career as an independent researcher and professor focused on improving reproductive healthcare access and outcomes among people with disabilities.

NSF Awards · FY 2024 · 2024-09

Large earthquakes have the potential to have catastrophic impacts on humans and infrastructure when risks are not mitigated. Earthquakes nucleate at depth, but it is the upper ~1 km of a fault zone where seismic waves, rocks and sediments, fluids, humans, and their built environment intersect to drive earthquake hazard. This is the critical zone for earthquakes. This Frontier Research in Earth Sciences (FRES) project investigates how material properties that vary in space and time in the earthquake critical zone impact earthquake rupture propagation, radiation of seismic waves, ground shaking intensity, and surface deformation in between earthquakes. This research targets two similar faults, each with significant human impact, that are at different points in their earthquake cycle: the southern San Andreas fault, CA, in a quiet period between earthquakes, and the Çardak-Çığlık fault, Turkey, in the immediate aftermath of the 6 February 2023 Mw 7.6 Elbistan earthquake, part of the devastating Kahramanmaraş earthquake sequence. The research team will bridge geoscience and engineering concepts, approaches, data, and models, as well as leverage shared-use equipment and cyber-infrastructure, to deliver publicly available products on the NSF-funded Natural Hazards Engineering Research Infrastructure DesignSafe Data Depot that can improve earthquake hazard models and seismic site response analyses near seismogenic faults, which are needed for increased resilience of communities to earthquakes. Research and broader impacts are anchored in intellectual, educational, and cultural reciprocity to broaden STEM knowledge, perspectives, and participation. Research pathways will meaningfully intersect by training the next generation of Earth scientists at the nexus of geosciences and engineering, strengthening international partnerships with Turkish colleagues, and expanding a Utah State University (USU) mentoring program through geoscience-engineering research experiences to increase the transition rate of students from a 2-year campus at USU Blanding, UT, to the 4-year campus in Logan, UT. This FRES project investigates how the earthquake critical zone accumulates, redistributes, and releases earthquake energy on major strike-slip faults. Models of earthquake rupture, seismic wave propagation, and local surface ground shaking are commonly decoupled and limited because the detailed properties of the earthquake critical zone are generalized. This FRES research will overcome these limitations by characterizing the earthquake critical zone of two major continental strike-slip faults with five intersecting research pathways that will yield geologic, geophysical, geochemical, mechanical, and engineering data. The pathways are: (1) a field-based geologic framework, (2) time-series CO2 flux data, a proxy for fault permeability and healing, (3) in-situ earthquake engineering geophysics to characterize material moduli, attenuation, and fault architecture, (4) deformation experiments to quantify fault healing, permeability, and attenuation at conditions designed to inform different stages of a seismic cycle, and (5) geochemical, microstructural, and fault rock chronology analyses to bridge natural and experimental earthquake cycle processes. These datasets will be integrated in a sixth pathway to produce stacked quasi-static, dynamic, and seismic site response numerical models. Research and broader impact activities bring together six PIs with diverse but overlapping geoscience and engineering expertise to train the next generation of Earth scientists at the intersection of these fields (three postdoctoral fellows, four PhD students, one MSc student, and undergraduate researchers). Undergraduate researchers will be recruited through the USU Honors Program, a Brown REU, and California State University Fullerton (CSUF) Project RAISE. International partnerships will be strengthened by having two Turkish colleagues participate in field work along the SSAF and lead Turkey-based research and by having US-based researchers connect with Turkish counterparts at public seminars at Istanbul Technical University. PIs and mentees will create and offer a new multi-year program to expand a USU-based student mentoring program with a goal to improve recruitment and retention of students. These students will be hosted at PI labs at USU Logan, with help from Brown and CSUF researchers, where they will be taught earthquake and engineering concepts, and subsequently be taken to the south San Andreas fault for field work. Their progress will be tracked and assessed by evaluating learning outcomes and STEM engagement through these experiences. This project is funded by the Frontier Research in Earth Science (FRES) program as well as Education and Human Resources (EHR) in support of Research Experiences for Undergraduates and Postdoctoral Scholars. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Volcanic eruptions connect the Earth’s deep interior with its surface and atmosphere, and they have wide-ranging effects. As natural hazards, eruptions pose risks to human lives, infrastructure, and economies. Magma in the crust provides a favorable environment for development of geothermal energy systems. Gases, like carbon dioxide, and tiny particles released into the atmosphere by volcanoes can affect weather and climate. Therefore, there is a need to understand how magma forms, ascends to the surface, and erupts. This project is studying how and where magma is currently being stored in the deep crust under three recently active volcanoes: Yellowstone and the Cascades Arc in North America, and the Altiplano-Puna Volcanic Complex in South America. The project is measuring the speed of seismic waves, which were generated by distant earthquakes, as they travel beneath the volcanoes. The speed of seismic waves is sensitive to the abundance of magma and whether it is stored in flat horizontal layers or tall vertical columns. A key outcome of the project will be to advance knowledge of how the storage and migration of magma affect the eruptibility of volcanoes. A second important outcome is the research training of one graduate student and two undergraduate students. Mapping the distribution of melt in the crust and upper mantle is a long-standing goal in the Earth sciences that bears on a wide range of scientific and societal issues. One such issue is how the storage and migration of magma affect the eruptibility of volcanoes. There is emerging consensus that the magmatic system beneath active volcanoes spans the entire crust. However, in volcanic settings, there are large error bars on crustal melt-fraction estimates, and the depth distribution of melt is challenging to resolve, especially in the lower crust. This project is studying the crustal architecture beneath active volcanoes with two types of seismic analyses that have thus far been rarely used in these settings. One is radial anisotropy as estimated from intermediate-period (25-75 s) surface waves from teleseismic earthquakes, which provides constraints on the lower crust and uppermost mantle that complement the more commonly used ambient-noise studies. The other is Rayleigh wave amplification, which is sensitive to P-wave and S-wave speed in the lower crust and uppermost mantle. The VP/VS ratio depends only weakly on temperature but is strongly sensitive to melt. These new data sets will be jointly inverted together with Rayleigh wave phase velocities from ambient noise and teleseismic earthquakes and Love wave phase velocities from ambient noise to produce depth-dependent models for VS, VP/VS, and radial anisotropy for three volcanic regions: Yellowstone and the Cascades Arc in North America, and the Altiplano-Puna Volcanic Complex in South America. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2024-08

Project Summary Approximately 12% of couples are infertile and 1% of the female population worldwide experiences primary ovarian insufficiency (POI) which results from a reduction of the ovarian follicle reserve that often leads to premature menopause and infertility. Important pathological outcomes associated with early menopause include osteoporosis, cardiovascular and early cognitive decline. Although several genes have been linked to women with POI, about 90% of the cases are idiopathic. By uncovering the developmental and molecular mechanisms underlying the establishment of the initial pool of primordial follicles and the maintenance of the adult ovarian reserve in the mouse, we will be poised to better understand, diagnose and treat POI in the future. We have discovered and characterized the roles of a protein called TAF4b that is essential for establishing the healthy ovarian follicle reserve in the mouse ovary. TAF4b is a gonadal-enriched subunit of the general transcription factor TFIID, a large multiprotein complex composed of the TATA-box binding protein (TBP) and 14 TBP-associated factors (TAFs). Our approach to studying the regulation of ovarian follicle development by TAF4b has elucidated the ovarian functions of TAF4b in the context of a TAF4b-deficient mouse model. Collectively, these studies have revealed that TAF4b-deficient female mice suffer from hallmarks of POI including persistent estrous, elevated serum follicle stimulating hormone (FSH) and accelerated ovarian reserve depletion. In addition to our own work, a number of additional studies have linked the potential function of human TAF4b in the regulation of fertility in women. Strikingly, the genetic networks regulated by TAF4b in the mouse ovary appear to be conserved during human fetal oocyte development. Together, these data implicate the potential deregulation of TAF4b-regulated processes in the context of human POI and female infertility. Based upon our previous studies, we hypothesize that related TAF4b- regulated transcriptional events and chromatin modifications in the developing mammalian oocyte serve to properly establish the initial ovarian reserve and fertility in women. By uncovering the late embryonic oocyte- specific molecular and developmental functions of TAF4b in transcription, chromatin modification and fetal oocyte attrition, we aim to identify novel genes, pathways and expression mechanisms in place to ensure the successful production of high-quality oocytes in women and perhaps one day better diagnose and/or manage patients with POI and other related deficits of human ovarian health.

NSF Awards · FY 2024 · 2024-08

This award funds the research activities of Professor Savvas M. Koushiappas at Brown University. Despite exciting experimental progress over the last two decades, several problems remain and new ones have appeared with the increased precision of cosmological experiments. The nature of dark matter and dark energy remain elusive, the distribution of dark matter in halos may hint to physics beyond the Standard Model of particle physics, and the search for quantum gravity remains an open question. New physics is necessitated to address these questions. The award bridges the gap between cosmology, particle physics, and astrophysics, and is in line with the national interest by promoting the progress of science in one of its most fundamental directions: the discovery and understanding of new physical laws. The projects in this award have also significant broader impacts. Professor Koushiappas will involve graduate students in his research and provide critical training for junior scientists in a STEM field. In addition, he will present public lectures on contemporary topics in cosmology as well as develop new courses that stem from the results of this research. Under this award, Professor Koushiappas will explore the effects of ultra-light dark matter in the accumulation of angular momentum in galactic systems. Angular momentum in dark matter halos is built-up in the linear and quasi-linear regime from the coupling between the mass distribution of the dark matter halo and the mass distribution of the neighboring density fluctuation field. Ultra-light dark matter has a different mass distribution compared to cold dark matter. This award will explore the effects of ultra-light dark matter in the angular momentum content of dark matter halos, with the goal of using current and future observables as constraints on the nature of dark matter. In addition, this award will investigate new possible interactions between dark matter and collision-less particles (stars and black holes) in dark matter dominated systems. Furthermore, work under this award will search for imprints quantum and/or modified gravity on cosmological observations through the growth of structure. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2024 · 2024-08

PROJECT SUMMARY Hospice programs have been historically less experienced in caring for beneficiaries with Alzheimer’s and Related Dementia (ADRD), although ADRD represents one of the fastest growing primary diagnoses among hospice beneficiaries. A majority of hospice beneficiaries in long-term-care (LTC) settings have ADRD,and it is possible for certain hospice programs (i.e. those with higher volumes of beneficiaries with ADRDand/or in LTC settings) to be better at caring for the challenging end-of-life care needs of ADRD beneficiaries. Such specialization could be achieved through hospice programs’ greater clinical experience in dementia care and/or collaboration with LTC staff. However, it requires more research to understand the quality implications when a hospice program have a higher volume of LTC beneficiaries (i.e. an LTC hospice). This is because LTC hospices may target LTC beneficiaries with financial incentives, given that LTC beneficiaries have overall longer lengths of hospice stay, who are more profitable to the hospice program under the Medicare Hospice Benefit payment structure. A lack of knowledge on this issue prevents the identification of best hospice care practices for ADRD beneficiaries and an effective modification to the Medicare Hospice Benefit. Building on our ongoing research and in response to PAS-19-391, our proposed study has two aims: 1) Describe individual-, nursing home/assisted living-, hospice-, and neighborhood-level characteristics associated with receiving care from LTC hospices, overall trend and by care settings (i.e. nursing home, assisted living, community); 2) Compare the quality outcome between beneficiaries with ADRD who receive care from LTC hospices with a those receiving care from non-LTC hospices, using difference-in-difference cross-temporal matching. This study is innovative in that we include assisted living in defining LTC hospices, given that assisted living is an increasingly common site of hospice care for beneficiaries with ADRD. We will examine whether/how quality outcomes differ by hospice specialization and care settings, given that prior research shows care setting to be an important determinant for hospice quality outcome. The application of difference-in-difference cross- temporal matching addresses several important selection issues (i.e. personal preference for hospice by specialization type, selections between nursing home/assisted living and hospice) in examining the quality performance of LTC hospices. The use of national claims data will enhance our knowledge at the national level about the quality of LTC hospices, because prior research relies mostly on survey data. By the end of this project, we will determine whether beneficiaries with ADRD, who receive care from LTC hospices in different care settings, experience better outcomes. The expected outcome of this project is to provide empirical evidence on how hospice programs’ specialization impacts the quality of care among ADRD beneficiaries. These contributions represent the first step of a larger research project that further examines the impact of recent policy changes and market shifts on the quality of hospice care delivered to ADRD beneficiaries.

NIH Research Projects · FY 2025 · 2024-08

Project Summary/Abstract Alcohol use is the leading risk factor for premature death among young adults globally. Brief motivational interventions (BMIs) can help young adults reduce their drinking. However, recent research has suggested that these interventions often have modest overall effects. Research exploring novel ways of boosting the effects of BMIs could help expand their impact. Studies exploring why interventions based on motivational interviewing (MI) work suggest that a key mechanism may be that they help develop a sense of discrepancy in clients, or a sense of incongruence between their current drinking and important priorities or goals. MI counselors often expand that discrepancy by asking open-ended questions that encourage clients to consider the inconsistency between their current behavior and important values and life priorities. To be successful, however, these techniques depend on clients’ engagement and investment in the exercise. Virtual Reality (VR) could provide a method of encouraging more meaningful reflection on discrepancies between drinking and desired goals that reduces client resistance to change. VR has been used as an adjunct to counseling to help treat a variety of behavioral, cognitive, and mental health problems with considerable success, but very few such programs exist to address hazardous drinking, and those that do are only fitting for those who have already decided to change. Recently, interest has grown in using VR to create transformative experiences that inspire awe, increase empathy, and encourage positive change. Through collaborations with local VR experts, we designed an immersive VR experience to help develop discrepancy and elicit change talk in MI sessions that uses an approach similar to the “looking forward” technique. We then constructed a prototype and tested it with 15 hazardous drinking young adults. At 30-days post-intervention, participants reported 54% fewer heavy drinking days and 60% fewer alcohol-related problems. Qualitative data also suggested that the immersive nature of the experience may have accounted for much of its impact. The goal of the proposed research is to design, build, and pilot test a complete VR experience using user-centered design research methods and the input of subject matter experts. In Phase 1, we will build the VR experience through an iterative process of up to five build-test-refine cycles in which progressively more complete versions of the experience are evaluated through several rounds of testing with intended users (hazardous drinking adults, N=15 each). Findings from these cycles will be used to refine the experience. In Phase 2, we will test the efficacy of the completed experience in 96 young adult (age 18-34; target N=82 ) hazardous drinkers, who will be randomly assigned to receive either (1) BMI with VR, or (2) BMI only. We will assess feasibility, tolerability, and alcohol outcomes over 6-months post-intervention. Finally, we will conduct qualitative in-depth interviews with college and community addiction treatment center directors (N=30) to explore clinic-level barriers and facilitators to implementation of VR.

NSF Awards · FY 2024 · 2024-08

This project develops a new framework for the Nash embedding theorems in order to align the foundations of mathematics with cutting edge scientific applications, especially in AI. In the 1950s, Nash amazed the mathematical world by unifying two distinct ways of thinking about space. In two papers, he established that an abstractly defined space with a notion of length (an intrinsic Riemannian manifold) can be realized as the solution of a system of nonlinear differential equations (an extrinsic embedded manifold). These theorems are strikingly original. For example, a counterintuitive conclusion is that it is possible to crumple the surface of the globe into an arbitrarily small region without any change in length. In a remarkable development in the past decade, these theorems are now known to lie at the foundation of outstanding scientific challenges, especially the description of turbulence in fluids and the description of big data with deep learning. This project tackles both theory and practice. On one hand, a rigorous mathematical framework is developed for the Nash embedding theorems using probability theory, shedding new light on the underlying concepts and techniques. On the other hand, algorithms and models are developed that align the theory with scientific applications. The project contributes to the training of personnel in STEM fields through the mentoring of Ph.D students. The technical core of this project is the rigorous analysis of Riemannian Langevin equations (RLE). The RLE provides a unified model in geometric deep learning, random matrix theory, and the isometric embedding problem (and related nonlinear PDE). In each setting, the goal of this project is to rigorously construct Gibbs measures in tandem with the development of fast optimization and sampling algorithms. Regarding mathematical foundations, the primary focus is on new intrinsic constructions of Brownian motion on Riemannian manifolds and the construction of stochastic flows with critical regularity. This framework is then extended to turbulence and other h-principles in PDE, replacing Nash's iterative scheme with RLE in each case. Matrix models, especially the deep linear network (DLN), provide the bridge between geometry and algorithms. On one hand, the Riemannian geometry of DLN is used to guide the analysis of (nonlinear) deep learning. On the other hand, the use of stochastic gradient descent is used to develop numerical schemes for sampling Gibbs measures for nonlinear PDE. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

The National Science Foundation (NSF) Graduate Research Fellowship Program (GRFP) is a highly competitive, federal fellowship program. GRFP helps ensure the vitality and diversity of the scientific and engineering workforce of the United States. The program recognizes and supports outstanding graduate students who are pursuing research-based master's and doctoral degrees in science, technology, engineering, and mathematics (STEM) and in STEM education. The GRFP provides three years of financial support for the graduate education of individuals who have demonstrated their potential for significant research achievements in STEM and STEM education. This award supports the NSF Graduate Fellows pursuing graduate education at this GRFP institution. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-08

Children living near industrial activities are at a heightened risk for poorer health, including stress, asthma, and other respiratory illnesses. As a result of prior studies linking adverse health effects to fossil fuel activities, there has been a shift towards alternative energy sources such as wood biomass. As a result, the market for wood pellets is booming, and plants are springing up across the US, especially in the deep south. Despite growing concerns about environmental health impacts on communities living near wood pellet plants, few studies have been conducted to gauge impacts. Previous epidemiologic research suggests that living near industrial manufacturing, generally, and wood-related manufacturing, specifically, is associated with negative respiratory health and psychological distress in children. However, these studies are limited due to their inability to holistically characterize the pollutants emitted from industrial production when assessing pediatric health impacts. We are proposing place-based research in Mississippi, a state ranked the least healthy for childhood respiratory diseases, as 1 in every 10 children under the age of 18 has asthma. Mississippi also has seven wood pellet plants, four of which are fully operational and three of which are either soon to be open or in early development. These upcoming plants are slated to be the largest wood pellet plants in the world. This unique situation of open and soon-to-be-open wood pellet plants presents an opportunity to conduct a natural experiment looking at both exposures and epidemiology. Preliminary exposure data that we have collected suggest that communities with active wood pellet plants have higher air and sound levels than communities without active plants. Our research goals are to build on this preliminary data and carry out an extensive air and noise pollution exposure assessment in three types of communities in Mississippi: those with an operational wood pellet plant, communities with a proposed plant, and background communities with no industrial manufacturing at all. We propose to conduct a combined ambient and indoor sound and air pollution assessment (Aim 1 and Exploratory Aim) and will use these measurements to assess their impact on children’s respiratory health and stress, also examining the extent to which neighborhood resources and community stressors may modify these associations (Aim 2). We will also invest in local human capital by providing research training to and partnering with faculty and students at community colleges, which are often overlooked in the research grant space. We will also engage communities through a host of environmental health literacy activities, including our smartphone app, NoiseScore, and our environmental science activity book series, which currently covers noise pollution, air quality, visual pollution, and water quality. We will, together, create a cohort of local researchers who will become first authors in their future stories. Together, we can develop strategies, policies, and interventions to improve community health and well-being.

NSF Awards · FY 2024 · 2024-08

Many biological and physical systems exhibit high degrees of internal complexity that resist direct mathematical description. Examples include ecological dynamics in a varied environment and fluctuating flame fronts in combustion. Nonetheless, such systems often exhibit tractable behavior when viewed at large or fine scales. This "asymptotic" behavior plays a major role in applications, and often has a universal character that unites the study of disparate systems. In this project, the principal investigator (PI) will combine several mathematical methods to identify and justify asymptotic phenomena in partial differential equations (PDEs) originating in the sciences. This work has the potential to shed light on a variety of systems including ecological invasion, atomic deposition, and fluid shock formation. The PI is committed to undergraduate and graduate mentorship, with the particular aim of supporting students from underrepresented backgrounds. This project will explore the asymptotic behavior of various deterministic and stochastic PDEs in significant limiting regimes. The project comprises three interconnected lines of work. (1) The PI will study the long-time propagation speed and front structure of solutions to reaction-diffusion equations in heterogeneous and random environments. This investigation encompasses a dual analysis of associated branching particle systems. (2) The PI will combine analytic and probabilistic methods to study long-time and white-noise limits of several physically motivated stochastic PDEs, including stochastic conservation laws and stochastic heat equations near criticality. (3) The PI will investigate the action of weak viscosity on internal shock formation in the compressible Navier--Stokes equations. This involves a delicate coupling between hyperbolic and parabolic approximations. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2024 · 2024-08

PROJECT SUMMARY The Brown University Proteomics Core Facility seeks to acquire cutting-edge instrumentation to advance research in cancer biology, aging, neurodegenerative diseases, immunology, and infectious diseases. Specifically, we propose to acquire an Eclipse Tribrid Mass Spectrometer, Vanquish Neo UHPLC, and FAIMS Pro Duo Interface through an S10 HEI Grant. This acquisition will benefit major and minor users at Brown University and the broader research community in Rhode Island in a state designated by the NIH as an IDeA state identified as needing increased research infrastructure support. The proposed instruments will significantly enhance the capabilities of our Proteomics Core Facility, enabling advanced, accurate, and precise analysis of proteins and peptides. The Orbitrap Eclipse Tribrid Mass Spectrometer combines high-resolution mass spectrometry with sensitivity, speed, and dynamic range. This instrument will enable the identification and quantification of proteins, post-translational modifications, and protein-protein interactions with unparalleled precision and accuracy. The Vanquish Neo UHPLC is a high-performance liquid chromatography system that delivers exceptional separation and resolution. It will allow for efficient sample preparation and increased throughput for large-scale proteomic experiments at nanoliter amounts. The FAIMS Pro Duo Interface provides additional selectivity and sensitivity in protein and peptide analysis. It enhances ion separation and increases the dynamic range of mass spectrometry, enabling the detection of low-abundance peptide species with greater accuracy. In support of the newly formed Legorreta Cancer Center at Brown, these instruments will benefit research in cancer biology, where the ability to detect and quantify specific proteins and their modifications is critical for understanding disease mechanisms and developing new therapies. The instruments will also facilitate research in the Center on the Biology of Aging, and the Carney Institute for Brain Science, where identifying disease-related biomarkers from precious samples is essential. In immunology and infectious diseases, the instruments will enable the identification and quantification of immune system proteins and parasite or pathogen- derived molecules, aiding in the development of vaccines and therapies. Overall, the acquisition of these instruments will enhance the Proteomics Core Facility's capabilities and enable cutting-edge research in major disease areas. The benefits will extend beyond Brown University to the broader research community in Rhode Island, including undergraduate institutions. This proposal aligns with the NIH's mission to support research that advances our understanding of disease mechanisms and improves human health.

NSF Awards · FY 2024 · 2024-08

The area of study of this project lies within algebraic geometry, the branch of mathematics devoted to geometric shapes called algebraic varieties, defined by polynomial equations. Algebraic geometry has significant applications in in coding, industrial control, computation, and in theoretical physics, where physicists consider algebraic varieties as a piece of the fine structure of our universe. One focus of this project is moduli theory, which studies a remarkable phenomenon in which the collection of all algebraic varieties of the same type is often manifested as an algebraic variety, called a moduli space, in its own right. Thus in algebraic geometry, the metaphor of thinking about a community of "organisms" as itself being an "organism" is not just a metaphor but a rigorous and quite useful fact. A second focus in this project is birational geometry, focusing here on resolution of singularities. Resolution of singularities is a fundamental procedure where "bad" points of an algebraic variety are removed and replaced by "good" points; it is the most powerful tool in the hands of a binational geometer. The project will provide research training opportunities for graduate students. In more detail, regarding moduli spaces the PI will study the enumerative geometry of certain moduli spaces of surfaces, a decades-old challenge. In an area where birational geometry and moduli spaces overlap, the PI will continue to study the birational geometry of stack theoretic weighted blowups, a transformation that occurs frequently on moduli spaces that has proven instrumental in describing their geometry. Regarding resolutions of singularities, new algorithms will be developed for logarithmic resolution that are remarkably simpler than earlier ones, an algorithm for resolution in the presence of a nested family of foliations will be developed, and singularity invariants in positive characteristic will be studied that will lead to new insights into the formidable challenges of resolution in positive characteristic. These efforts will serve as platforms to directly mentor PhD students and young researchers, and for lectures and training programs reaching broader audiences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2024 · 2024-08

PROJECT ABSTRACT Objective: The purpose of this application is to identify a rate of normative cognitive aging (i.e., cognitive aging in individuals without a neurocognitive disorder), and determine how much quicker cognitive aging is among individuals living with Alzheimer disease or related dementias (AD/ADRD). Using data from the Children of the Depression (CODA) cohort of the Health and Retirement Study (HRS), we will first identify a latent variable estimate of general cognitive performance (Aim 1). Afterwards, we will identify the pace of normative cognitive aging in standard deviations per year (SD/year), both unadjusted and adjusted for known covariables that influence cognition (e.g., age, sex, race and ethnicity, education; Aim 2). Finally, we will use Centers for Medicare & Medicaid Services (CMS) data linked to the HRS to identify participants who receive a dementia diagnosis during follow-up, and determine how much faster cognitive aging is among individuals living with AD/ADRD (Aim 3). In line with PAR-23-179, this proposal will also develop the career for early-stage investigator, Dr. Kunicki, and will serve as a basis for future NIH grant proposals. Significance: Cognitive ability declines with age, and tends to aging quicker later in life. Whereas neurocognitive disorders such AD/ADRD are known to increase the rate of cognitive aging, there is no well- established reference of normative cognitive aging. Lacking this reference pace makes it difficult for researchers to evaluate the results of their studies (i.e., determining if a cohort is declining at a normal or quicker than usual pace). Moreover, we will estimate how much quicker cognitive aging is among individuals living with AD/ADRD. Approach: We will use data from the CODA cohort of the HRS, which is comprised of over 2,000 participants aged 68-74 at baseline with 22 years of follow-up data available. Using the HRS cognitive measures, we will identify a latent variable of cognitive aging, and use the latent variable to identify the pace of normative cognitive aging in SD/year. Then, using CMS data, we will identify participants who received a dementia diagnosis during follow-up and determine how much faster cognitive aging is among individuals living with AD/ADRD. Sensitivity analyses will also examine the pace of normative cognitive aging by different cognitive domains. Innovation: This study is innovative because it addresses a major gap in the literature in cognitive aging by identifying a pace of normative cognitive aging and among individuals living with AD/DARD. These paces will be useful for researchers to use as reference points to interpret results of clinical trials to slow cognitive aging. Despite a lack of normative cognitive aging rates being a well-known issue in the field of aging, this study will be the first to identify a nationally representative rate of cognitive aging among older adults.