Grants

NSF

Eleven percent of the world's recorded earthquakes occur in Alaska, with many notable historical events including the 1964 M9.2 Alaska earthquake, the second largest earthquake ever recorded, as well as the 2018 M7.1 Anchorage earthquake. Earthquake hazards in south-central Alaska are a serious concern because the area includes the city of Anchorage where more than a third (~280,000 people) of the state’s population live. To facilitate estimating seismic hazard for the region from future large earthquakes, this project will assemble the first version of a multi-scale three-dimensional Community Velocity Model (CVM) of the subsurface of south-central Alaska. The CVM will be built with existing model components, calibrating its parameters by comparison of simulated and recorded waveforms for small local earthquakes. The CVM will be freely available to local agencies, scientists, and communities, bridging advanced modeling with practical applications such as assessing the seismic hazard to critical infrastructure in this region. The project will train a graduate student in seismic wave propagation simulation, fostering the next generation of geoscientists. The researchers plan to assemble and distribute the first version of a multi-scale Community Velocity Model (CVM) for the south-central Alaska Region, SCAR-CVM V1.0, from existing model features. The accuracy of such a CVM is fundamental to estimates of ground motions for seismic hazard analysis using physics-based wave propagation. Features in the proposed CVM will include 3-D tomographic velocity variation, high-resolution surface topography, the depth to basement in the Cook Inlet basin, generic basin velocities combined with near-surface constraints in the sediments, and a low-velocity weathering layer constrained by Vs30 values. Modeling of 0-1 Hz ground motions and comparison to seismic observations for six local M4.6-5.9 earthquakes will allow calibration of the velocity and attenuation structure in the model, as well as help assess the efficacy of the model for waveform prediction. This project will demonstrate to what extent the model can forecast geographically specific ground motion patterns such as extended durations and amplitudes, or amplification above the sedimentary basins of south-central Alaska. These are all capabilities needed for physics-based seismic hazard analysis. The work will also incorporate into the CVM the best available geometry of the subducting slab south-southeast of Anchorage, allowing future simulations of megathrust simulations such as the 1964 M9.2 earthquake, as well as intra-slab events such as the 2018 M7.1 Anchorage earthquake. The planned CVM will be the first iteration of any future improvements when new parameter constraints become available for studies such as nonlinear analysis of the soils and critical lifelines, as well as help enhance seismic risk preparedness, bridging advanced modeling with practical applications. 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

Proteins known as “receptor tyrosine kinases” (RTKs) mediate the transmission of information across the cellular membrane, and thus allow the cell to respond to extracellular signals. Intercellular communication is a fundamental process in multicellular organisms and its precision is crucial for the control of growth and development. Multiple extracellular ligands can interact with an RTK to promote different intracellular events. The research project seeks to obtain quantitative information about the signaling properties of a member of the RTK family in response to its different ligands. Highly quantitative biophysical methods will be used in an effort to understand how diverse extracellular signals are processed by this receptor to promote distinct events. In this project, graduate students will be trained in state-of-the-art fluorescence microscopy techniques and the educational experience of undergraduate students will be enhanced. In addition, broad outreach activities will be conducted benefiting young scientists. The first objective is to acquire the first comprehensive data set of ligand-specific efficacies, potencies, and signaling preferences for multiple responses of the epidermal growth factor receptor (EGFR) to its ligands. This will entail acquisition of dose response curves for a variety of biological responses, yielding information about the potencies, efficacies and preferences of the ligands when inducing these responses. The second objective is to perform the first comprehensive physical-chemical characterization of the self-association of EGFR in the plasma membrane in response to its ligands. EGFR ligand-specific oligomer sizes (orders) and stabilities, and ligand binding coefficients, will be measured. The third objective is to uncover currently unknown correlations between measurable physical parameters and measurable signaling outcomes. 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

Polymers are encountered in everyday life in products ranging from earbuds to clothing. Their ability to have specific properties (e.g. soft like the silicone in earbuds) arises from the chemical makeup of the molecules (how many carbons, hydrogens, oxygens etc.), their shape (e.g. polymers can have simple linear forms like spaghetti or be circular like a bracelet) and how mixtures of polymers fit together when mixed. There has been a growing trend to synthesize polymers with shapes beyond a simple linear form. Two-dimensional sheet-like polymers are an emerging new class of polymers. Research to date has focused on understanding synthesis of these novel polymers. A better understanding is needed of how to assemble them into complex structures. This project will study how 2-dimensional polymers can be made to assemble into various structures based upon the addition of a second molecular component. A range of added components (both linear polymers and small droplets) will be explored to develop rules for their assembly and to introduce new functionality. A key part of the research entails using specialized cameras and microscopes to take movies of single polymer molecules within these complicated mixtures. The project will train students to enter the workforce for advanced engineering topics combining single molecule manipulations and microfabrication. The project will provide research opportunities for high school teachers and undergraduates. Demonstration kits will be developed which can be used by school teachers to introduce concepts in molecular connectivity in materials. Discoveries from the project will impact the design of future high-performance polymer systems. Single molecule studies of DNA have provided new insights in the fields of soft matter and rheology. There is an emerging interest in polymers with more complex topologies and mixtures thereof which can translate to new material properties. The research team will study clusters formed from 2-dimensional catenated DNAs (called kinetoplasts or kDNA) when mixed with linear DNA or nanoemulsions. The team has recently established kinetoplasts from the Crithidia parasite as a model 2-dimensional polymer system. kDNA are soft, cup-shaped, cell-sized colloidal entities composed of thousands of circular DNA that are topologically interconnected like chainmail. The research program entails: 1) understanding kDNA clustering when mixed with linear DNA, 2) modulating kDNA clusters by using depletants with various properties and 3) studying the nonequilibrium dynamics of kDNA clusters in microfluidic devices. Single molecule fluorescence microscopy combined with bespoke microfluidic devices will be used to study these systems. This award will result in work at the front edge of fundamental studies of soft colloidal assembly/dynamics and rheology of 2D polymer assemblies. New insights will be gained into how 2D polymers can be assembled into superstructures through mixing with linear polymers or smaller colloidal nanoemulsions. The use of DNA of a model polymer will be expanded to two-dimensional colloidal “sheets” called kinetoplasts to understand how catenated DNA demix from linear DNA to form superstructures. The fundamental discoveries from this project will result in contributions to polymer physics texts and journal articles. Results from this work can lead to improved polymer processing, new materials and deeper mechanistic insights into 2D DNA rheology. The research will inform the design of DNA-based superstructures for possible use in biomedicine or “organo-DNA” 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.

National Park Service

United States Department of the Interior, National Park Service (NPS) Notice of Intent to Award. This is not a request for applications. This posting is to provide public notice of NPS' intention to fund the following project activities without full and open competition: Task Agreement P15AC00756 under master Cooperative Agreement P13AC00848 with the Humboldt State University Sponsored Programs Foundation, for the project titled, "Assess Health and Function of Wetlands on the Lower Prairie Creek Floodplain".

Eastern Queens Alliance, Inc.

To collect air and noise pollution data to provide a better understanding of levels of pollution and health concerns of the community.

Eastern Queens Alliance, Inc.

To collect air and noise pollution data to provide a better understanding of levels of pollution and health concerns of the community.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY Sexual minority (SM) individuals (e.g., lesbian, gay, bisexual) are considered at higher cardiovascular disease risk due to the discrimination based on sexual orientation. Experiences of discrimination including internal and interpersonal discrimination have led to higher rates of risk factors like smoking, binge drinking, and substance use compared to straight adults. Additional studies have also suggested issues in health care access and quality of care and that minority stress may be adversely affecting physiologic processes. However, there is limited data on cardiovascular health conditions of SM adults and various demographic subgroups (e.g., sexual orientation x race). This makes it difficult to develop health programs to improve health and address disparities in this population. This project will examine disparities by sexual orientation in cardiovascular health conditions. Specifically, the team will: (1) assess disparities in prevalence and incidence according to sexual orientation of selected cardiovascular-related condition (cardiometabolic conditions, cardiovascular disease) and (2) examine and decompose the role of social determinants on cardiovascular health disparities. Further, in a sub-aim, the team will explore the mediating role of telomere length in explaining cardiometabolic health disease disparities by sexual orientation. These aims will be achieved by linkage of survey data from the Kaiser Permanente Research Bank (KPRB) datasets with the Kaiser Permanente electronic health records. The analysis will identify significant disparities and, through decomposition methods, quantify the role of selected social determinants (e.g., education, income, discrimination) in driving these disparities. Results of this work can be used to set health program targets while decomposition results can guide the selection of strategies to address disparities. It also serves as a foundational work for more in-depth epidemiologic, translational, and implementation research on SM disparities.

NSF

The goal of this research project is to gain insight into the growth and decline of cities through the examination of animal management and distribution within urban areas. There are a variety of definitions for urban centers and cities, and each emphasizes different factors such as geography, economics, demographics, and/or social aspects. However, these approaches do not consider that cycles of urbanism exist as cities grow or diminish in size and complexity and so change in form, function, or status over time. This research examines the changing nature of cities through archaeology, a discipline that is particularly well placed to provide relevant insight because it can trace changes over extended periods of time. The emergence of one set of Iron Age sites provides an excellent opportunity to study the fluidity of urbanism and the emergence of internal growth, shifting populations, and new political systems. All these factors impact the size and character of settlements. This study will extract and analyze stable isotope data. Stable isotope data is based on chemical variations in the chemical element (same number of protons but different number of neutrons). The stable isotope data is analyzed with mathematical models that rely on the use of artificial intelligence. Moreover, stable isotope data and methods relate to biotechnology as they assess data from non-radioactive element to examine and identify biological processes (e.g. food chains, migration, site of origin). This research builds a detailed picture of animal management systems during the phases of the Iron Age at four “urban” sites. These sites provide large, well-dated faunal assemblages from well-documented sites within a regional context. Researchers analyze archaeological domestic animal remains using both zooarchaeology and archaeological science. Zooarchaeology, the study of animal remains, determines species preferences, changes in the age and/or sex composition of herds and/or increased culling of select ages or species, as well as changes in butchery pattern and intensity and modifications. The differences in relative frequency of animal species demonstrate the differing preferences of animal husbandry and use practices at those sites, potentially related to different production strategies and levels of urbanization. Analyses (carbon, oxygen, and strontium) to characterize the diet of individual animals, management strategies (including birth and cull seasons, the contribution of grazing/browsing/foddering and water management) as well as animal mobility are also conducted. The research provides a robust understanding of human-animal interactions at this time as well as further information on the larger themes of foodways and trade which have not been fully explored for this period. 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.

NIAID - National Institute of Allergy and Infectious Diseases

Understanding how adaptation of mosquitoes to persist at low humidity affects their potential to be successful vectors of human pathogens can lead to novel ways to help prevent or slow the spread of vector-borne diseases. Environmental variation can create novel habitats, such as those with low humidity, for mosquitoes to thrive in. The ability to persist in habitats with low humidity results in mosquitoes with increased desiccation tolerance and can result in new molecular pathways governing interactions with human pathogens. Our understanding of the environmental and genetic factors that contribute to virus emergence and transmission is limited. In populations outside the U.S., success of Aedes aegypti in areas of reduced rainfall have been accompanied by an increased susceptibility for Zika virus. However, the genetic mechanisms driving these traits and their relationship to relative humidity remain poorly understood. We have identified two genes with dual roles in regulating midgut infection and in desiccation tolerance, suggesting that genes regulating midgut infection have a pleiotropic effect on desiccation tolerance or vice versa. We identified a peritrophic matrix (PM: a sac that envelops the bloodmeal in the midgut and can block arbovirus infection) gene that is upregulated in response to desiccation stress, and whose expression controls midgut susceptibility to Zika and chikungunya viruses. Additionally, we have identified a detoxification gene that is upregulated in midgut cells in response to dengue virus infection, and is also highly expressed in oenocytes, the site of cuticular hydrocarbons (CHC) biosynthesis in the fat body (main metabolic organ). This proposal will address the central hypothesis that desiccation tolerance is accompanied by pleiotropic effects on vector competence through changes in midgut physiology and metabolism. In Aim 1 we will identify desiccation tolerance-induced changes in midgut physiology and structure that facilitate arbovirus infection by 1) demonstrating that PM formation alters midgut susceptibility by changing viral access to the midgut epithelium, 2) measuring PM-associated phenotypes and midgut cellular and molecular responses in lines maintained under low humidity, and 3) measuring PM-associated phenotypes and midgut cellular and molecular responses in mosquito Iines from the U.S naturally adapted to low humidity to validate our findings in natural populations. In Aim 2 we will investigate shared metabolic processes underlying desiccation tolerance and midgut infection by 1) identifying metabolites and metabolic processes underlying midgut infection and validate metabolites’ roles in midgut infection, 2) comparing metabolic profiles between mosquito lines maintained at low humidity, and 3) comparing metabolic profiles between U.S. field-collected lines naturally adapted to low humidity to determine if desiccation tolerance is correlated with metabolic profiles underlying dengue virus susceptibility. Our findings will crucially inform new genetically based control approaches such as gene drive technology.

NCI - National Cancer Institute

Project Summary/Abstract One in five patients are readmitted following major cancer surgery in the United States. These readmissions are associated with increased morbidity and mortality, lead to care fragmentation, delay adjuvant treatments, and result in substantial costs to the healthcare system. A wide spectrum of interventions have attempted to minimize this burden, yet readmissions following these procedures have remained stagnant. In large part, this can be attributed to the fact that the drivers of these readmisisons are multifactorial, arising from the interplay between a complex surgery and an older patient population with multiple medical problems. This concept is clearly evident among bladder cancer patients undergoing cystectomy where readmissions have plateaued at 25% for decades, making this the ideal population to study potential interventions aimed at decreasing readmission burden. Prior interventions have failed to reduce readmissions because they were broad and non-specific for the cystectomy population and limited by low intensity, sub-optimal timing or duration, were resource intensive, and failed to engage the spectrum of stakeholders. Our group has created a novel, multifaceted intervention that can potentially reduce the burden of readmissions on patients and the healthcare system. This intervention consists of an electronic health record (EHR)-integrated application designed to monitor cystectomy-specific convalescence and engage patients postoperatively through daily symptom monitoring, streamlined communication (bi-directional with both patient- and provider-facing components) when concerning symptoms arise, and targeted patient education. This approach allows for high-intensity monitoring throughout the post- operative period, facilitates early identification of complications by both patients and providers, removes barriers to timely communication allowing for more effective management, and does so with relatively low resource utilization by leveraging existing EHR and clinical infrastructure. The project proposes the following aims: 1) Determine the feasibility of using an EHR-integrated multifaceted intervention to monitor convalescence and trigger timely medical intervention in bladder cancer patients undergoing cystectomy; 2) Evaluate intervention acceptability; and 3) Identify facilitators and barriers to implementation across intended multi-institutional randomized trial sites. The preparatory work in this proposed R34 will result in creation of both the necessary infrastructure and stakeholder engagement to facilitate optimal implementation of our proposed future, multi-site randomized controlled trial intended to measure the efficacy of our intervention in reducing the burden of readmissions following cystectomy. If proven efficacious, our intervention is purposely designed to be easily scalable to other major cancer surgery and beyond.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT Emerging and re-emerging viruses represent a serious and ongoing threat to human health, and both the frequency and impact of emerging viruses are expected to increase due to factors such as modernization, environmental degradation, and changes in human population density. Many high consequence viruses for humans have recently emerged from stable relationships with bats, but we know very little about these viruses in their natural reservoirs, including their host range, prevalence and various factors that influence virus shedding and spillover risk. A better understanding of these viruses is needed to enable a more predictive and proactive approach for preventing emergence. This proposal seeks to address some of these knowledge gaps through an innovative combination of longitudinal molecular surveillance, highly-multiplexed serology, and whole genome virus sequencing in two nearby colonies (one captive and one wild) of straw-colored fruit bats (Eidolon helvum) in Ghana. E. helvum is a member of the Pteropodidae family, which includes natural hosts for several highly-pathogenic zoonotic viruses, and there are multiple documented interfaces for the transmission of viruses from E. helvum to humans, livestock, and other wild animals throughout its range in sub-Saharan Africa. Studies of viral epidemiology in this species of bat have been enabled by a unique long-term, captive breeding colony at the University of Ghana. Here, we propose to utilize this captive colony of E. helvum to study mechanisms of virus persistence and transmission, which relate directly to the prevalence and magnitude of virus shedding and therefore also to spillover risk. There is mounting evidence that many viruses are capable of establishing persistent infections in bats, characterized by recurrent episodes of virus shedding, which may be triggered by environmental factors. However, existing data lack the resolution needed to directly test this hypothesis, and it is unknown how common such infections are across different virus groups. We will investigate this hypothesis through individual-level longitudinal surveillance of viruses within our unique captive colony of E. helvum, in combination with a multi-pronged analysis comparing the variety and prevalence of viruses between captive and wild populations. First, we will use longitudinal sample collection and broad-range PCR to monitor virus shedding over time (Aim 1). Second, we will use highly-multiplexed serology to obtain an unprecedented view of the viruses infecting E. helvum bats and to identify differences in infection histories between captive and wild animals (Aim 2). Third, we will use whole genome sequencing to examine the evolutionary relationships among viruses shed in the captive colony (with individual-level resolution) and those circulating in wild bats (Aim 3). If chronic infections play an important role in virus persistence in these bats, we expect to see similar types of viruses in both colonies, recurrent shedding of the same viruses, and individual level phylogenetic clustering of viral genomes.

NCCIH - National Center for Complementary and Integrative Health

PROJECT SUMMARY/ABSTRACT Major Depressive Disorder (MDD) afflicts more than 280 million people worldwide and is the leading cause of life years lost to disability. Current treatments have important limitations in efficacy and, in the case of medication, substantial side effects. There is thus a compelling need for additional effective, well-tolerated treatments. Body heating practices, such as saunas, sweat lodges, and hot yoga, have rich traditions across cultures as healing practices. Additionally, recent basic and clinical research, as well as the investigative team’s pilot data, suggest that whole-body hyperthermia (WBH) holds promise for depression treatment. The investigative team therefore hypothesizes that WBH, a body-based heat treatment, may decrease depression symptoms. Additionally, pilot data suggest benefit from combining WBH and cognitive behavioral therapy (CBT), an established mind-based treatment for depression. The UCSF investigative team led an NCCIH- funded project testing WBH and CBT in adults with major depressive disorder and have found the combined treatment to be feasible and acceptable. Additionally, preliminary data from this project suggest a clinically meaningful and statistically significant reduction in depression symptoms. Despite promising initial data from such pilot studies, rigorous and well-designed clinical trials are required to evaluate the efficacy of depression treatments that include WBH. Before the investigative team can conduct a definitive efficacy trial, they must assess the feasibility of key study design components. This proposal will test the feasibility of a multi-site 2 x 2 factorial trial design that randomizes adults (N=60) with MDD to two treatment factors: WBH (yes/no) and CBT (yes/no). The three-site investigative team (University of California San Francisco, Cleveland Clinic Foundation, Massachusetts General Hospital) will capitalize on their established collaborative relationships to assess the feasibility of recruitment, enrollment, randomization, and retention (Aim 1), intervention fidelity and acceptability (Aim 2), and consistency of data collection (Aim 3). The study will include a 2-week screening period, a 10-week intervention period, and a 12-week follow-up period. During the intervention period, participants randomized to WBH will receive four biweekly sessions, and participants randomized to CBT will receive eight weekly sessions. If successful, the proposed multi-site feasibility R01 trial will lay key groundwork for a future multi-site 2 x 2 factorial efficacy trial that will test the effects of WBH, CBT, and their combination on depression symptoms. If successful, this program of research may yield novel non-drug treatment options for millions of individuals struggling with depression.

Bureau of International Labor Affairs

This Notice of Intent (NOI) is not a request for funding applications. Subject to the availability of funds, USDOL s Bureau of International Labor Affairs (ILAB) intends to award, through a competitive and merit-based process, one or more cooperative agreements to organizations to conduct research on child labor in the cocoa sectors of Ghana and C te d Ivoire. The proposed objective of the research is to assess progress in reducing the worst forms of child labor (WFCL) in cocoa-producing areas of the two countries. The project will include the following three components: (1) a mapping of stakeholder interventions to reduce WFCL in the cocoa sector; (2) an assessment of the effectiveness of funded efforts in reducing WFCL; and (3) a survey of incidence of child labor in cocoa production in C te d Ivoire and Ghana in the 2018/19 growing season. The Employment and Training Administration (ETA) s Office of Grants Management anticipates publishing the Funding Opportunity Announcement (FOA) before the end of September 2015 (this date is subject to change). Please refer to: http://www.dol.gov/ilab/grants/ and http://www.dol.gov/ilab/grants/SGAguidelines.htm for general guidelines and examples of previous cooperative agreement applications. This NOI does not include an FOA or any attachments. It only constitutes a notice of USDOL s intent to publish an FOA at a later date. Interested applicants are encouraged to monitor www.grants.gov for the FOA because this is the method by which it will be made available to the public. No email or paper copies will be provided.

NSF

The impact of spatial ability on STEM achievement has gained significant attention from researchers, yet progress remains limited by inadequacies in available spatial assessment tools. Current spatial tests present numerous challenges: limited accessibility, questionable psychometric properties, theoretical inconsistencies, and gaps in STEM-relevant skill measurement. In fact, there is a lack of consensus about what a taxonomy of spatial skills would look like and how those skills should be assessed. This project will advance the field by addressing these critical limitations through a transformative methodological approach. Researchers will conduct comprehensive scoping reviews to examine current test usage and develop recommendations for improvement. They will then develop and make publicly available a series of open-source spatial tests, featuring refined existing assessments and new tools developed through collaboration with cognitive science and education research communities. The research team will determine the underlying psychometric structure of spatial abilities and their relationship to STEM learning by implementing rigorous evaluations of multiple spatial tests and using such approaches as Rasch modeling and exploratory factor analysis. They will develop new assessments, building upon scoping review findings, ensuring high visual quality and open-source compatibility. The project will implement Open Science Standards for data sharing, enabling researchers to access and contribute to publicly available test development and analyses. Through these methods, the team will answer fundamental questions about the impact of spatial skills on STEM achievement while establishing a framework for future investigations. This work will ultimately enhance understanding of spatial abilities' nature and determinants, leading to more precisely targeted interventions that facilitate STEM learning and address potential obstacles to success. This project is funded by the EDU Core Research (ECR) program. ECR supports fundamental research that generates foundational knowledge to advance the research literatures in STEM learning and learning environments. 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

Hazards such as hurricanes or wildfires are notorious for their severity in frontline and coastal communities and their difficulty to predict and mitigate. Scientists have increasingly investigated why systemically designed models often fail to meet their objectives and reduce vulnerability. This project tests the adaptability of resilience models across multiple scales. Lessons learned from this research will be ever more important for communities facing disasters of increased intensity. Findings will be widely shared and made available open access, to improve the public’s understanding of science and the scientific method. In addition, the research offers a range of broader impacts such as integrating research and teaching and building research infrastructure. This research asks how adaptation of models from one context to another is possible, and how communities can craft resilience plans addressing local realities. This research also identifies factors that facilitate or hinder implementation. Answering these questions, this research employs a mixed-method, multi-sited approach including public conferences, hazard mapping, and risk perception surveys. Resilience plans are crafted at workshops bringing together scholars/students, organizations, elected officials and community leaders learning about other successful disaster risk reduction models. Finally, the research facilitates the development of a workable process to reduce vulnerability and adapt to environmental variability. 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.

NCIPC - National Center for Injury Prevention and Control

PROJECT SUMMARY Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based comprehensive approach that can 1) quickly screen individuals for at-risk alcohol and other substance use and mental health issues, 2) utilize in-the-moment delivery of brief (i.e., 5-10 minute) intervention with motivational interviewing techniques and 3) when needed, provide referral to treatment. Regarding alcohol-impaired driving, SBIRT has been shown to be efficacious in reducing self-reports of drinking and alcohol-impaired driving, reports of alcohol-related vehicle crashes, and increasing referrals to treatment. Given the success of SBIRT for alcohol- impaired driving it may also be impactful for polysubstance-impaired driving. However, to date there has been limited evaluations of SBIRT regarding its effects for polysubstance-impaired driving. Despite the potential of SBIRT to reduce polysubstance-impaired driving, reported barriers include competing priorities for staff to provide SBIRT, staff turnover, and availability of treatment options. Brief motivational interventions (BMI) have evidence for reducing alcohol and cannabis use and consequences among young adults with additional previous support for reducing impaired driving. Web-based personalized feedback intervention (PFI) adapted from these in-person BMI may also be effective in reducing impaired driving and would address limitations within the SBIRT framework. Our team is contracted to roll out SBIRT training with 200 facilitators between Jan 2025-Sept 2025, which will include updated material specific to alcohol- and polysubstance-impaired driving. The proposed project would leverage this newly trained network and provide a web-PFI (SBIRT+PFI) to their young adult clients who screen at moderate or moderate to high risk or have any reports of impaired driving. Consented young adults would be randomized to receive the PFI or waitlist control and be assessed at enrollment and 3 months later. We also will collect data from the SBIRT facilitators to garner information on sustainability and barriers of implementing SBIRT. Thus, the objectives of this project will be to 1) examine the changes in polysubstance-impaired driving among young adults among those who receive the expanded SBIRT+PFI, and 2) using both qualitative and quantitative approaches, document real-word successes and difficulties in sustaining SBIRT models including: a) barriers to implementing with fidelity and b) percentage of staff turnover. Findings of the project can help inform decisionmakers and policymakers on the value of SBIRT and SBIRT+PFI for polysubstance-impaired driving as well as considerations for continued sustainability.

NIAID - National Institute of Allergy and Infectious Diseases

Abstract In this proposal, we will determine the influence of oral pre-exposure prophylaxis (PrEP) on the pharmacokinetics (PK) of passively administered monoclonal antibodies (mAbs) and vaccine-induced polyclonal antibodies (Abs) in females vulnerable to HIV-1, using data and specimens from past HIV-1 prevention trials. This research will have a significant impact on global health because oral PrEP is currently the most accessible pharmaceutical HIV-1 prevention option, and Abs are critical for immune protection and therapeutic efficacy. Aim 1 focuses on determining whether oral PrEP affects the PK of VRC01, a broadly neutralizing HIV-1 mAb, in female participants from the recently completed Antibody Mediated Prevention (AMP) study. We will identify biomarkers of PrEP use that correlate with increased mAb clearance, with a specific emphasis on assessing PrEP’s effects on two intestinal Ab clearance mechanisms: disruption of the epithelial barrier and increased Fc receptor (FcR) mediated Ab degradation. Aim 2 extends this investigation by examining the impact of oral PrEP on the magnitude and durability of HIV-1 vaccine-induced antibodies (Abs) in female participants from two completed HIV-1 vaccine efficacy trials. To extend beyond HIV-1, we will also assess durability of Hepatitis B (HB) vaccine-induced Abs in female and male participants from AMP and the vaccine trials. Consistent with what was observed for VRC01 PK in males from the AMP trial, our preliminary data in two pre-efficacy vaccine trials suggest an association between PrEP use and faster decay of HIV-1 vaccine-induced Abs. We plan to identify PrEP biomarkers associated with vaccine Ab kinetics. In biopsy donors, we will also determine the association between HB vaccine Ab kinetics and identified biomarkers with the two potential intestinal mechanisms of Ab clearance. Characterizing any PrEP effects on Abs is crucial for people who take oral PrEP and rely on mAb immunotherapies and/or Ab-inducing vaccines for protection against pathogens. Aim 3 focuses on developing a pharmacokinetic and statistical modeling framework to rank and select mAb regimens for efficacy testing. This framework will account for PrEP use and mAb PK biomarkers identified in Aim 1. It will also incorporate mAb levels in serum and rectal tissue from both males and females, recognizing the importance of tissue levels in predicting protection against HIV-1 and intestinal PrEP effects on mAb PK. By building and validating advanced PK models and statistical methods for bridging differences in study populations, we seek to enhance the accuracy of selecting the most promising mAb regimens for future clinical trials, ultimately contributing to more effective HIV-1 prevention strategies.

NSF

In recent years there have been increasing calls from fields such as medicine to expand the use of digital technologies in providing healthcare in low-resource settings. Particularly in rural areas, people may not be able to easily visit a healthcare provider in person, but they often have access to devices such as mobile phones. This project examines efforts to develop digital health services in a low-resourced and predominantly rural setting. The research contributes to the improvement of digital health services, offers training for graduate students, postdoctoral scholars and undergraduate students, and enhances the infrastructure for research and education. This study addresses the following interrelated questions: (1) How do digital health technologies create new treatment experiences? (2) How do they affect communication strategies and relationships between patients and providers and (3) Are they considered an effective means of delivering treatment by providers and patients? Methods include the use of in-depth interviews and behavioral observations across a stratified sample of healthcare providers in three organizations, with patients and their family members. This project allows a rare opportunity to explore experiential dimensions of communication and human-technology interfaces. The long-term contribution to the science of medicine is an understanding of how new health technologies remake treatment strategies and patient-provider relationships, and how these processes affect whether therapies are considered effective. An emphasis on provider and patient interactions also moves forward investigation of robustness as a theoretical concern in the health sciences. 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.

NIAAA - National Institute on Alcohol Abuse and Alcoholism

ABSTRACT Background: Converging lines of evidence suggest that neuromodulation of the neural mechanisms underlying alcohol use disorder (AUD) are an innovative next step in improving treatment outcomes and reducing risk of relapse. Emerging research supports the salience network (SN) as a promising target to accomplish these goals. Deep transcranial magnetic stimulation (dTMS) is one type of neuromodulation technique that allows for deeper stimulation of cortical neurons, thus reaching core nodes of the SN, such as the dorsal anterior cingulate cortex (dACC). Objective: The aim of this proposal is to 1) evaluate the efficacy of active dTMS in increasing dACC activation and reducing drinking relative to a sham (placebo) condition, 2) to assess the trajectory of target engagement changes (i.e., increased dACC activation) that are evident after 15 sessions versus 30 sessions, and 3) evaluate the durability of the neural changes and how this might impact treatment outcomes (i.e., % days abstinent and % heavy drinking days). Methods/Design: We will enroll 100 adults with AUD into a 2-arm randomized, double-blind, sham-controlled mechanistic trial to confirm target engagement relative to sham, assess the impact of the protocol on drinking behaviors, and determine moderators of treatment response. Participants will be randomized in a 1:1 ratio to receive either 30 sessions of active 20Hz dTMS to the mPFC and dACC using the H7 coil, or an equivalent sham condition. Participants will receive 3 dTMS treatments per day for 10 consecutive business days (30 total treatment sessions) and will complete neuroimaging assessments at baseline, after one-half of treatment sessions, post-treatment and 1 month after treatment. Specific Aims: We aim 1) to evaluate the efficacy of active dTMS relative to sham dTMS in reducing 3-month post-treatment drinking rates and target engagement, 2) evaluate the relationship between degree of target engagement to drinking rates and identify individual variability in target engagement trajectory, and 3) to evaluate the association of target engagement durability of dTMS for relapse prevention. Impact: The proposed research will elucidate mechanisms of brain and behavior change, accelerate the development of new, device-based, treatment options and will be the basis for developing a large-scale, dose- varying, clinical trial to test new treatment strategies for AUD.

NIA - National Institute on Aging

ABSTRACT Floods account for the majority of global climate change-attributable deaths in the 21st century and are predicted to increase substantially as the climate continues to rapidly change. As such, the health toll of floods stands to increase and will disproportionately affect the most vulnerable populations – particularly older adults. Older adults face heightened flood vulnerability due to disproportionate residence in floodplains, frailty, diminished hearing and vision, pre-existing chronic conditions, reliance on electricity-dependent medical equipment, and dependence on healthcare access. Thus, identifying policies to safeguard older adults' health during and following floods is paramount. In the US, the Federal Emergency Management Agency (FEMA) is tasked with prevention and mitigation of the effects of climate disasters. Two programs that are particularly important in the relief efforts from flood events are FEMA's National Flood Insurance Program (NFIP) and the Individuals and Households Program (IHP). These programs provide resources and services to individuals before, during, and after climate disasters – including major floods. As the rate of floods dramatically increases, understanding the ways in which floods affect mortality and these programs stand to buffer those effects is paramount. A critical research gap remains about (1) the effects of these FEMA programs on health, and (2) how long major floods may affect health beyond the initial days. This project will examine the effect of these programs on all-cause mortality among older adults, and will estimate both the short- and long-term effects of floods on all-cause, cardiorespiratory, and injury- related mortality at various time lags. Our overarching hypothesis is that floods affect health for up to a year following a major flood and that programs such as NFIP and IHP mitigate these effects. To test this hypothesis, we aim to (1) estimate the effect of NFIP availability on ZCTA-level mortality among Medicare enrollees after major floods and use an agent-based model to simulate NFIP mortality benefits, (2) estimate the effect of FEMA IHP application approval rate on mortality among Medicare enrollees after major flood exposure and use an agent-based model to simulate IHP mortality benefits, and (3) assess the relationship between exposure to major floods and all-cause, cardiorespiratory, and injury-related mortality at the county level in the short- and long-term. The proposed research includes a high-quality training plan that includes academic and scientific support for the success of the applicant in demographic methods, epidemiologic methods, causal inference and quasi-experimental design, climate epidemiology, Bayesian methods, agent-based modeling, and professional development. All of the proposed research will be supported by an interdisciplinary team and environment at the University of Washington. Collectively, the project will provide evidence that can inform future climate adaptation and FEMA policies to reduce preventable flood-attributable mortality.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Human subjects research with novel neural devices raises unique ethical issues, such as post-trial responsibilities, privacy of brain data, and atypical risks such as changes to personality. To manage the discrepancy between research practices and ethics oversight, in 2018 the NIH added a mandatory neuroethics section to a subset of neuroscience grants in addition to the standard protection of human subjects component. However, despite the unique nature of this requirement, to date there have been no systematic efforts to assess stakeholders’ experiences with and attitudes toward these mandates. This represents both a critical gap and opportunity. Without empirical research evaluating the impact of neuroethics mandates, we risk implementing ineffective requirements, lack the information needed to make useful modifications, and remain unaware of their strengths and weaknesses. Furthermore, given that there is no established pathway nor guidance for investigators to address neuroethics requirements, examining researchers’ experiences offers a valuable opportunity to understand how they devise neuroethics plans as well as barriers they might encounter when implementing them. The overall objective of this short-term R21 exploratory proposal is to assess the impact of mandatory NIH neuroethics guidelines on the ethical design and conduct of brain-related research and to identify effective strategies that investigators have utilized to address neuroethics in their research. This will be achieved through two complementary aims that involve interviewing researchers who have been funded through NIH grants requiring neuroethics sections (Aim 1) and surveying those who review neuroethics components of grant applications (Aim 2). This project directly addresses the broad area of RFA-MH-25-171 (“enhance integration of neuroethics and neuroscience”). The expected outcomes of this two-year exploratory R21 project are a set of multistakeholder perspectives on the impact of neuroethics mandates and recommendations for improving them, an identification of strategies that researchers have utilized to address neuroethics mandates, and a determination of areas of unmet needs regarding resources for addressing neuroethics requirements. Our findings will benefit funders, by providing insights into the impact of neuroethics requirements and recommendations for improving them; researchers, by providing a set of effective strategies that have been used to address neuroethics sections; neuroethicists, by determining areas of unmet need regarding neuroethics resources; and the public, by identifying pathways for enhancing the ethical conduct of neurotechnology research. This project is significant because it has the potential to impact the way that the ethics is integrated and assessed across BRAIN Initiative research and in other scientific endeavors.

OD - NIH Office of the Director

ABSTRACT Tobacco product brand/line extensions continue to proliferate as manufacturers seek to maintain or grow their market share. The Tobacco Control Act (TCA) introduced a number of potential pathways for marketing tobacco products, including a substantial equivalence (SE) process. Typically, SE determinations are made by comparing the “new” product to a pre-existing product in terms of design and emissions, with an eye toward whether the new product raises different questions of public health than what was previously on the market. The SE process raises important questions and concerns as to its impacts on the market and on public health. This understudied area of regulatory science could be leveraged by the tobacco industry to retain or attract consumers while avoiding the stricter regulatory standard applied to new products. Under the SE regulatory model in its present form, cigarettes and cigars can continue to evolve through accumulation of small changes and proliferation of line extensions that bear functional similarity to existing products. Notably, human studies are not explicitly required for SE determinations, which raises concerns as to whether a product that receives an SE Order on technical grounds is experienced in the same way as the predicate by consumers. Our Specific Aims are to evaluate the state of the market with respect to SE determinations and assess consumer product differentiation in two combustible tobacco product classes – cigarettes and cigars. These are the products of focus as they are clearly the most associated with health risks, and both of these markets were very well established prior to the TCA. In Aim 1 we will characterize the marketplace, leveraging Nielsen data and laboratory techniques to assess the design, contents, and emissions of 15 leading subbrands of cigarettes and cigars. In Aim 2 we will assess consumer behaviors with respect to substantial equivalence. In Study 2.1 we will leverage PATH data, which contains self-reported brands and sub-brands, to examine trends in the market share of brands. In Study 2.2, we will recruit a panel of adults (21+) who currently use one of the 15 leading subbrands of cigarettes and cigars as identified in Aim 1. The goal of this study is to examine whether consumers using these products can identify changes to their brand during the course of multiple year follow-up. In Aim 3, we assess industry behaviors with respect to substantial equivalence by compiling and integrating SE determinations and other orders posted on FDA’s website to examine trends in product characteristics and predicate product usage. A key goal is to determine if there are commonalities to what aspects of product design or emissions are changing, or if there are common predicate products employed. This proposal addresses the Product Composition and Design, Behavior, and Impact Analysis priority research domains.

NSF

With the support of the Macromolecular, Supramolecular and Nanochemistry Program of the Division of Chemistry, Prof. Milliron and Prof. Truskett at the University of Michigan seek to develop a fundamental understanding of the forces that keep nanoscale particles of metal oxides (nanocrystals) suspended as soluble inks or can lead to their precipitation. The results will be relevant for the understanding how nanocrystals can be effectively integrated in electronic or optical devices, and the concepts can be extended to help rationalize biomolecular interactions. Researchers participating in this project will receive training in computation and analytical techniques. A related symposium and webinar series will be organized, with a corresponding podcast to share knowledge across the scientific community and with a broader public audience. Since nanocrystal interactions are challenging to measure directly, the team will combine information from small angle X-ray scattering measurements, optical spectroscopy, and simulations to develop and validate models. The team will apply this strategy to analyze attractive and repulsive interactions between nanocrystals as they depend on experimentally accessible parameters like the concentration of added polymers and salts, pH, and solvent dielectric constant. Each of these parameters will be explicitly included in the models for interaction potentials, and the predicted trends in how they influence the nanocrystal dispersions will be quantitatively compared to the experiments. Further, the team will apply a recently developed simulation method to predict trends in the plasmonic optical spectra of the nanocrystal ensembles, providing additional validation of the interaction potentials inferred from small angle X-ray scattering. 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.

NIA - National Institute on Aging

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease is a progressive neurodegenerative disorder with a complex etiology affecting over six million individuals in the United States alone, with numbers projected to rise significantly as the population ages. Concomitant changes in gut microbiome and metabolome composition have been observed over the course of Alzheimer’s-related cognitive decline, suggesting host microbiota may mediate the pathophysiological processes of Alzheimer’s disease and related dementias. Gut microbes contribute to host metabolism through the production and modification of metabolites, such as bile acids, which collectively influence overall metabolic health. Lifestyle interventions, such as diet modification, are promising strategies for lowering dementia risk, and these modifications are also influential in regulating the gut microbiome. However, the long-term effects of specific dietary interventions on microbially-mediated bile acid profiles and their impact on cognitive decline remain poorly understood, motivating further investigation. This proposal seeks to apply advanced computational and algorithmic approaches to identify compositional and functional changes in the gut microbiome and metabolome over the course of longitudinal dietary interventions. Aim 1 of this proposal will unify three independent cohorts assessing the impact of adherence to the Mediterranean diet, a diet high in plants and healthy fats, on cognitive decline. By conducting phylogenetically-aware metagenomic analyses and network-based untargeted metabolomic analyses, this proposal aims to identify changes in microbial communities and bile acid profiles during Mediterranean dietary interventions, and correlate these changes with host phenotypes indicative of Alzheimer’s risk. Complementarily, Aim 2 of this proposal will assess the prognostic potential of gut microbiome and metabolome features by constructing and evaluating machine learning models to predict cognitive outcomes over the course of intervention. These efforts will deepen our understanding of the relationship between diet, the gut microbiome, bile acid proliferation, and cognitive health by employing standardized and reproducible methodological analyses across large cohorts. Ultimately, this research is poised to reveal mechanistic targets for future study, facilitating the development of novel diagnostic and therapeutic strategies for Alzheimer's disease in at-risk populations.