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ADAMTS13 in Human Health and Disease

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NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY This application proposes to study thrombotic disorders linked by the common thread of ADAMTS13 deficiency. The metalloprotease ADAMTS13 is responsible for cleaving ultra-large von Willebrand factor (VWF) multimers into smaller units, thereby regulating the thrombogenicity of this important circulating coagulation factor. Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening autoimmune hematologic disorder characterized by severe acquired ADAMTS13 deficiency (<10% activity, normal range: 50-150%) and diffuse microvascular thrombosis, end-organ damage, and death if left untreated. Beyond iTTP, moderately low ADAMTS13 (10-70% activity) has been hypothesized to contribute to common forms of macrovascular thrombosis, including stroke and myocardial infarction. We plan to study both iTTP and less severe ADAMTS13 deficiency. We organized the Harvard TMA Research Collaborative (HTRC), one of the world’s largest single- center registries for iTTP, to fuel innovative clinical and translational research of this understudied disease. Our group has pioneered the application of robust statistical modeling approaches to key questions in iTTP as well as the use of population-scale multidimensional datasets in hemostasis and thrombosis research. In Aim 1, we will leverage the HTRC registry to identify upfront predictors of negative outcomes in ITTP, including relapse and the composite of mortality, refractoriness, and need for critical care. Models developed in this Aim will facilitate risk stratification of iTTP patients and help guide therapeutic decision-making. In Aim 2, common germline genetic variants will be evaluated via the first genome-wide association and admixture mapping studies in iTTP with a view to understanding the disproportionate disease risk borne by some populations. Project results will provide avenues to develop novel screening, prevention, and intervention strategies for iTTP and serve as a model for the study of other classical hematologic disorders. In Aim 3, we will analyze genomic and proteomic data from nearly 800,000 individuals in the UK Biobank and NIH All of Us datasets to define the contribution of moderate ADAMTS13 deficiency to widespread thrombotic conditions, including stroke, myocardial infarction, peripheral artery disease, and venous thromboembolism. Our findings will have direct implications for clinical practice due to the recent FDA approval of recombinant ADAMTS13 and the hypothesis that ADAMTS13 supplementation could potentially aid the many patients suffering from these forms of thrombosis.

Up to $1.6M

2028-05-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adaptable and hemodynamic Gut-On-VascularNet models to mitigate radiation injury

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OD - NIH Office of the Director

Acute radiation syndrome (ARS) is a multi-organ failure (MOF) syndrome, resulting from accidental exposure to irradiation and/or nuclear terrorism. Acute and delayed effects of acute radiation exposure (DEARE) can also be seen in the clinic after radiotherapy. While there are FDA-approved drugs for mitigating hematopoietic ARS (H-ARS), there are no treatment for repairing irradiated intestines, primary cause of death and a critical component of gastrointestinal ARS (GI-ARS). A common feature of radiation injury is damage to the microvascular capillary endothelial cells (ECs) that are not only organotypically programmed to modulate metabolism but also provide tissue-specific angiocrine growth factors that orchestrate intestinal repair and regeneration post-radiation. Indeed, intestinal-specific microvascular ECs (InSECs), defined by the expression of transcription factor NKX2-3, establish instructive vascular niches that are essential for maintenance, repair and regeneration of intestinal stem cells (ISC) of irradiated intestines. We show that InSECs choreograph the polarization of the monocytes into reparative IL1beta macrophages that could play a key role in resolving radiation injury. The objective of this proposal is to leverage reproducible in vitro extra-corporeal perfusable vascularized intestinal organoids models to test approaches to restore normal homeostatic functions of InSEC. Thus, we hypothesize that radiation impairs NKX2-3+ InSEC-derived instructive signals and retards recruitment and programming of intestinotropic macrophages that convey reparative signals for intestinal repair. Restoration of NKX2-3 transcriptional signatures in InSECs would reconstitute angiocrine and intestinotropic macrophage functions, essential for resolution and recovery after radiation injury. Delivery of pro-reparative factors such as amphiregulins and epiregulins supplied by macrophages and InSECs could mitigate radiation-inflicted intestinal injury. These hypotheses will be tested through executing the following specific aims: Aim 1: Develop and characterize GI-ARS injury models in human Gut-On-VascularNet organoid extracorporeal platform. Aim 2: To characterize the “instructive” angiocrine signaling pathways of InSEC on pro-regenerative monocytic polarization that mitigate radiation injury to HIOs. Aim 3: To screen for intestinotrophic radiation MCMs to mitigate GI-ARS by using the Gut-On-VascularNet platform. To this end, Rafii and Guha groups plan to capitalize on an engineered scalable near-physiological and reproducible extra- corporeal human Gut-on-VascularNet platform to study radiation injury in GI-ARS. Leveraging this platform, also allows for examining the role of radiation in perfusable microfluidic devices harboring NKX2-3+ InSECs vascularized intestinal organoids to screen for angiocrine factors and reparative macrophages to mitigate GI- ARS. The human Gut-On-VascularNet platform would bridge the gap between animal models and humans for the approval of radiation countermeasures for mitigation of GI-ARS under the FDA “animal rule” guidance.

Up to $608K

2031-03-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adaptation and Evolution of Resistance to Pan-RAS inhibition in PDAC

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NCI - National Cancer Institute

“The Adaptation and Evolution of Resistance to Pan-RAS Inhibition in Pancreatic Ductal Adenocarcinoma” Abstract: Pancreatic ductal adenocarcinoma (PDAC) kills over 52,000 people annually in the United States. The current standard therapies are chemotherapy cocktails that provide modest survival benefits along with significant side effects. For 30 years, we have known that the vast majority of PDAC cases (~94%) are driven by activating mutations in the KRAS protooncogene, but until recently, this knowledge could not be leveraged for therapeutic benefit. The recent development of drugs that selectively inhibit specific mutant variants of KRAS (including KRASG12C and KRASG12D) have demonstrated the benefit of targeting KRAS. However, these agents only work in a subset of patients whose tumors harbor these specific alleles. Furthermore, recurrence can happen rapidly as tumors can develop alternative RAS mutations that circumvent these drugs’ function. Recently, we led a large consortium in describing the preclinical performance of RMC-7977, a novel pan- RAS inhibitor that effectively inhibits the active (GTP-bound) forms of mutant and wild type KRAS, NRAS, and HRAS. Remarkably, we found that this agent was well tolerated in mice. Across multiple classes of preclinical models, RMC-7977 exhibited strong anticancer activity, and yielded the longest extension of overall survival in the (highly chemo-refractory) KPC mouse model that has been reported to date. When tumors eventually did recur, they frequently exhibited focal Myc copy number gains, providing a means to activate the downstream mitogenic programs of RAS. The investigational analog of this agent, RMC-6236, is now in Phase 3 trials after demonstrating tolerability and showing remarkable responses in the Phase 1 setting. Here, we propose to study the development of resistance to pan-RAS inhibition in PDAC. Building from our previous work, we will utilize samples from mouse- and human derived model systems as well as human clinical trial samples to understand the evolution of genetic resistance mechanisms in response to RAS inhibition. Studies will focus on how these alterations impact tumor biology and what new therapeutic vulnerabilities they may confer. In addition, we will study how short-term adaptation allows tumors to survive pan-RAS inhibition long enough to evolve genetic resistance. We found that within days of treatment, the heterogeneity of KPC mouse pancreatic tumors collapses, with selective depletion of the most aggressive, poorly differentiated malignant cells. Strikingly, we also show that RAS inhibition induces the formation of primary cilia in the malignant cells of PDAC, enabling activation of pro-survival pathways including autocrine Hedgehog signaling. We will test how targeting ciliogenesis and cilia signaling pathways may potentiate RAS inhibition by overcoming early adaptive responses to treatment. The proposed experiments will combine innovative experimental techniques, advanced computational approaches, high quality model systems, human tissues, and clinical trial samples to comprehensively study the development of resistance to pan-RAS inhibitors in PDAC.

Up to $683K

2031-04-30

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adaptation and Validation of Tablet-based Cognitive Assessments for Diverse Populations in Cameroon

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NIA - National Institute on Aging

Project Abstract Dementia prevalence in Sub-Saharan Africa is projected to increase by over 300% within the next 25 years as the population aged 60 years and older triples to more than 235 million. Beyond the demographic transition and population growth, a major driver of these increases is the growing burden of communicable and non- communicable diseases, which contributes to disability and adverse brain health outcomes. Currently, there are limited data on Alzheimer's Disease and related dementias to inform healthcare and research policies within resource-strained health systems in SSA. This gap is especially evident in French-speaking African countries (30-40% of SSA), which are critically underrepresented in ADRD research. Indeed, our recent review highlights the cultural, ethnic, linguistic, and socioeconomical challenges to dementia research in this setting. In Cameroon, ADRD mortality has increased by over 130% in 20 years and ADRD represents 12.4% of outpatient neurology consultations. Our prior work highlights the urgent need to develop and validate scalable and accessible assessment tools for ADRD to establish a robust infrastructure to support dementia diagnosis, care, and research nationwide. The growing field of digital cognitive tools offers an innovative opportunity for developing easily accessible and highly accurate neuropsychological tools for cost- and time-efficient case identification. Standardized administration, automated scoring/interpretation, and cross platform integration features can address several challenges and support the development of dementia registries – a valuable resource for dementia research and care. The main objectives of this proposal are to culturally adapt and validate a brief multi-domain digital cognitive assessment tool in Cameroon and to develop and pilot the infrastructure needed for improved dementia care and research. Specifically, we plan to culturally adapt TabCAT-BHA digital cognitive assessment in Cameroon, evaluate demographic effects on performance and generate regression-based norms in a community representative sample of healthy adults in rural and urban areas (Aim 1). Concurrently, we will examine TabCAT-BHA’s diagnostic accuracy to detect mild cognitive impairment (MCI) and dementia in the existing BRAIN Cohort and examine its neuroanatomical validity to domain specific regional patterns of brain atrophy on MRI (Aim 2). Finally, as an exploratory aim, we will determine implementation barriers to cognitive testing and dementia diagnosis in a clinical setting in Cameroon to develop the infrastructure needed for improved dementia care and research (Aim 3). These proposed studies will begin to fill the data gap on dementia research in French-Speaking Sub-Saharan Africa (FS-SSA) and provide the first ever neuroimaging data in people living with dementia in Cameroon and set the stage for more comprehensive dementia studies in FS-SSA. For future research following this proposal, we anticipate that valid digital neuropsychological tools coupled with blood biomarkers that still need validation in this setting, could be a scalable and sustainable path for ADRD research, diagnosis and care (R01 proposal)

Up to $216K

2028-01-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adaptation Fund — Climate Adaptation Projects

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Adaptation Fund

Funds concrete climate adaptation projects in developing countries vulnerable to climate change, with $1B deployed.

$250K – $10M

Rolling

climate adaptationresiliencedeveloping countries

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adaptation of Project Yes+ to improve mental health and reduce HIV-related stigma among adolescent and young men who have sex with men living with HIV in Vietnam

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FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

In Vietnam, adolescent and young men vulnerable to HIV through sexual behaviors are among those most affected by the infection, with an HIV prevalence that quadrupled from 3% in 2011 to 13% in 2020. More than 20% of Vietnamese young men living with HIV had moderate-to-severe depression and anxiety symptoms. These youths experienced extensive stigma related to their HIV status and sexual behaviors. There is a dearth of youth-friendly mental health services in Vietnam where there is less than one psychiatrist per 100,000 people. Project YES+ is an intervention integrating two evidence-based interventions, Project YES! and Self-Help+ to improve mental health, stigma, and HIV outcomes among youth living with HIV in Zambia (5R01TW012411). Youth Engaging for Success (Project YES!) is an HIV clinic-based peer mentoring CDC-designated intervention that successfully decreased HIV self-stigma and increased viral suppression. Self-Help+ is a group-based lay-delivered program endorsed by WHO that effectively prevents the onset of mental disorders and reduces mental health symptoms in different cultures. We propose to adapt Project YES+ for adolescent and young men living with HIV in Vietnam to create To Hieu (I Understand) and to pilot test the adapted intervention. The specific aims are to (1) Adapt Project YES+ to create To Hieu to improve mental health and reduce internalized HIV stigma for adolescent and young men living with HIV in Vietnam and (2) Examine acceptability and feasibility of To Hieu among adolescent and young men living with HIV through a pilot randomized controlled trial. In Aim 1, the adaption will follow the 8-step ADAPT-ITT framework.38 We will conduct in-depth interviews with adolescent and young men living with HIV (N=20) to explore preferences for the core components and formats of To Hieu. We will hold a human-centered design workshop to engage adolescent and young men living with HIV in co-design activities to refine To Hieu. In Aim 2, we will recruit 80 adolescent and young men living with HIV with depression or anxiety symptoms at two HIV clinics in Hanoi, Vietnam and randomize them 1:1 into two arms. The intervention arm will receive To Hieu in 4 months, while the control arm will receive standard of care at the clinics. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework will guide the measurement of the outcomes. We will calculate participation rates of participants (Reach) at baseline. We will assess acceptability through the Client Satisfaction Questionnaire and feasibility through intervention attendance (Adoption) at 4 months. Depression, anxiety symptoms, internalized HIV and sexual stigma, ART adherence and viral suppression of participants will be evaluated at baseline, 4 months and compared between groups (preliminary Effectiveness). We will conduct exit interviews with participants, youth peer mentors and HIV providers (N=30) to explore acceptability, feasibility (Implementation) and sustainability (Maintenance) of To Hieu. This research will build local capacity and develop networks for collaborative research on mental health and stigma among adolescent and young men living with HIV between Vietnam and the US.

Up to $167K

2028-02-29

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adaptation of the TEN-T to civilian-defence dual use - studies, works or mixed

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European Commission - CEF2027

Adaptation of the TEN-T to civilian-defence dual use - studies, works or mixed. Call: CEF 2 Transport - Adaptation of the TEN-T to civilian-defence dual use - Military mobility envelope. Programme: CEF2027. Open call from the EU Funding & Tenders Portal.

$50K

2026-10-06

infrastructurepublic_safety

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adapting a Brief Dyadic Intervention for Co-occurring Post-Traumatic Stress Disorder and Alcohol Use Disorder

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NIH

The proposed CDA-2 will support Dr. Giff’s pursuit of a VA research career focused on improving the psychosocial functioning of Veterans with co-occurring post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD). Significance to VA: PTSD and AUD are highly comorbid, which presents a unique set of challenges for Veterans and their loved ones. Experiencing PTSD-AUD exponentially increases Veterans’ risk for debilitating mental health sequelae, poor physical health, and deleterious social and occupational outcomes. COPE is a robustly evidence-based treatment for PTSD-AUD that is widely used in VA clinics. While COPE outcomes related to PTSD symptom reduction are consistently outstanding, there is room to improve both AUD outcomes and rates of retention. COPE shows moderate effects on Veterans’ drinking reductions, indicating a critical need for research examining novel ways to bolster drinking outcomes. Innovation and Impact: Results from separate literatures indicate that integrating a family member or significant other (SO) is a promising method to improve AUD recovery and AUD and PTSD treatment retention. Veterans with AUD and PTSD often report conflictual relationships, which can interfere with AUD recovery, and including SOs is likely to foster more effective dyadic support and communication. The brief inclusion of SOs in Veterans’ treatment of PTSD-AUD is yet to be studied, despite strong potential for this model to improve treatment effectiveness, retention, and dyadic functioning. Pairing COPE with Brief Family-Involved Treatment for Alcohol Use Disorder (B-FIT) is one promising method to bridge this persistent gap in treatment programming for Veterans. B-FIT is a 3-session dyadic intervention designed to be delivered alongside evidence-based individual AUD treatments. Distilled from the original 12-session Alcohol Behavioral Couple Therapy, B-FIT focuses on enhancing family support for alcohol behavior change efforts and improving communication skills. A recent pilot of B-FIT demonstrated large effects for reductions in risky drinking. The objective of the proposed study is to examine the preliminary feasibility and acceptability of combining B-FIT with COPE among Veterans with co-occurring PTSD and AUD. Specific Aims: 1. Adapt the B-FIT manual to be delivered as an adjunct intervention to COPE; 2. Examine the feasibility and acceptability of BFIT + COPE through a one-armed open-label pilot trial as assessed by (a) rates of enrollment and treatment completion; and (b) participants’ quantitative ratings and qualitative perceptions of the intervention; and 3) Explore the effects of BFIT + COPE from pre- to posttreatment and at 3-month follow-up on (a) AUD outcomes, (b) psychosocial and relationship functioning, and (c) PTSD outcomes. Methodology: Aim 1 will include qualitative interviews with 10 Veteran-SO dyads and 10 VHA mental health clinicians to inform an adaptation of the B-FIT manual to be relevant for Veterans with PTSD-AUD. Once completed, the adapted manual will be piloted through a single-arm, open feasibility trial of 40 Veteran-SO dyads with primary outcomes of feasibility and acceptability. Secondary outcomes of AUD (AUDIT & TLFB); psychosocial functioning (B-IPF, Q-LES-Q-SF, DAS-7); and PTSD (PCL-5 & CAPS) will be explored. Path to Translation/Implementation: This project will provide critical pilot data on feasibility and implementation to support a subsequent Merit award testing the effectiveness and implementation of this intervention in VA clinics. The following training aims will ensure that the candidate is poised to continue this work: (1) Veteran-centered intervention development/adaptation and clinical trials management; (2) Knowledge of AUD; (3) Advanced statistical analysis; (4) Preliminary education in dissemination and implementation; and (5) Scholarly productivity and professional development. The candidate will accomplish these aims through devoted mentorship, didactic opportunities, and by leading the proposed project. She will conduct this work with support from the scientific community at the Ralph H. Johnson VAHCS and MUSC. The research and training proposed can address urgent needs within VHA and will prepare the candidate to be an expert in family-supported interventions to improve the lives of Veterans.

2031-03-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adapting a Diabetes Self-Management Support Intervention for Adults with Cognitive Dysfunction

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NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Project Summary/Abstract The population of American adults is aging, leading to a growing number of adults experiencing both diabetes and cognitive dysfunction. Diabetes is a recognized risk factor for cognitive dysfunction and for progressing from mild cognitive dysfunction to dementia. Managing diabetes is a cognitively complex endeavor that requires understanding one’s condition, glycemic monitoring, adhering to medication regimens, and maintaining diet and exercise routines. Adults with cognitive dysfunction may struggle to meet these demands. This relationship may be reciprocal, with increased disease severity worsening cognitive dysfunction, which in turn impairs disease management and worsens severity over time. There is an urgent need to develop interventions that (1) integrate evidence-based rehabilitation methods to support diabetes management and (2) are scalable to reach the growing population of adults with diabetes and cognitive dysfunction. This proposal represents the first effort, to our knowledge, to leverage rehabilitation techniques to provide a technology- delivered self-management support intervention for adults with type 2 diabetes and cognitive dysfunction and their support persons. During this K01, the principal investigator (PI) will address these gaps in the extant literature while participating in a mentored training experience that will prepare her as an independent investigator who adapts interventions to the unique needs of people with cognitive dysfunction to support them in managing diabetes. Specific training goals include: (1) deepen content knowledge and experience in clinical diabetes management, (2) develop skills in mixed methods for intervention adaptation, (3) hone expertise in cognitive screening in primary care and community settings, and (4) lead a clinical trial and strengthen responsible conduct of research skills. The proposed research includes two specific aims. Aim 1: The PI will follow the ADAPT-ITT framework to iteratively adapt an existing technology-delivered intervention for adults with cognitive dysfunction based on end user feedback. Aim 2: The PI will conduct a pilot trial to determine feasibility and acceptability of the intervention and study design. Improvements, if needed, will be made prior to proposing a fully-powered clinical trial for a future R01. At the conclusion of this work, the PI will have robust preliminary data on an adapted self-management support intervention for adults with type 2 diabetes and cognitive dysfunction to inform an R01-funded clinical trial. This work is consistent with NIDDK’s strategic goals to (1) leverage technology to make healthcare more feasible and (2) take a precision medicine approach to support health across the lifespan. This K01 will accelerate the PI’s independent research career adapting interventions that incorporate evidence-based rehabilitation techniques with diabetes management and are scalable to support the growing group of adults with type 2 diabetes and cognitive dysfunction.

Up to $146K

2030-02-28

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adapting a telehealth intervention for suicide prevention among patients with Alcohol Use Disorder in Tanzania

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NIMH - National Institute of Mental Health

Globally, alcohol use disorders (AUD) cause 3.3 million deaths each year and account for nearly 100 million disability-adjusted life years (DALYs). Alcohol use is also one of the most prominent risk factors for death by suicide, as people with AUD have a lifetime risk of suicide more than 7 times higher than the general population. Efforts to prevent suicide can reduce disruptions and fragility of the U.S. health system and serve as a public health good to benefit Americans. We are developing innovative approaches to bridge mental health and substance use treatment gaps, including telehealth and nurse-led counseling interventions with clear potential to reduce suicide in the United States and other settings. In our preliminary study, 7% of patients with AUD were experiencing suicidal thoughts or behavior. Despite this high comorbidity, routine screening and treatment for both suicide risk and alcohol use disorder are extremely rare in emergency care settings. Thus, there is a critical need for innovative, resource-efficient treatments for suicide prevention among people with AUD. In an earlier NIMH-funded study, our team adapted an evidence-based Motivational Interviewing intervention, MI-SafeCope, to develop IDEAS for Hope, a telehealth intervention for suicide prevention in HIV care. In the current grant, we will revisit this process by adapting MI-SafeCope to reduce suicide risk among people with AUD who are presenting for care in a Tanzanian Emergency Department. The resulting intervention, IDEAS-AUD, will address suicide risk with a four-pillared approach: reducing alcohol-related harm, building social support, enhancing emotional health, and meeting basic needs. The pillars are integrated with Motivational Interviewing-enhanced safety planning and referral for psychiatric care as appropriate. Intervention refinement in a low-cost, high-burden global setting has great potential for adaptation and implementation in the rural U.S., where mental health needs are high. The aims of this grant are to: 1) adapt IDEAS-AUD for the AUD population; 2) rigorously evaluate the acceptability and feasibility of IDEAS-AUD; and 3) develop our intervention package for a future implementation evaluation and a clinical trial in the rural U.S. In Aim 1 of the current study, we will identify drivers of suicide risk and desired intervention characteristics to prevent suicide in the AUD population. In Aim 2, we will adapt an evidence-based suicide prevention intervention to existing AUD care, guided by a community coalition. In Aim 3, we will pilot test the telehealth intervention to assess its feasibility and acceptability for reducing suicide risk in the AUD population. By the end of this proposed project, we will have a framework-guided, resource-adapted, piloted protocol for IDEAS-AUD, including screening tools, programmatic, and implementation components. The research is innovative, yet fundamentally essential, and supports NIH Strategic Objectives to prevent suicide across the lifespan, address mental health comorbidities such as AUD, and develop interventions that can be rapidly implemented to strengthen mental health outcomes in the U.S. and improve the health of Americans.

Up to $62K

2029-06-30

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adapting an evidence-based physical activity program to reduce pain and enhance quality of life for older women living with HIV

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NIMHD - National Institute on Minority Health and Health Disparities

Modified Project Summary/Abstract Section Arthritis is one of the most common debilitating chronic conditions experienced by older adults, leading to chronic pain, reduced mobility, and loss of independence. Older women living with HIV (OWWH) are disproportionately affected by arthritis, experiencing nearly twice the prevalence compared to the general population. OWWH also face unique barriers to managing arthritis, including socioeconomic challenges, HIV-related social and interpersonal challenges, and limited access to evidence-based interventions. Addressing these challenges is critical to reducing comorbidities, alleviating pain, and improving quality of life. Physical activity programs that include aerobic and strengthening exercises effectively manage arthritis by maintaining muscle strength, reducing bone loss, and controlling joint pain and stiffness. However, fewer than 16% of older adults report participating in arthritis management programs, with participation rates significantly lower among racial, ethnic, and persons with low socioeconomic status, including persons living with HIV. Guided by the NIMHD research framework, this study prioritizes individual, interpersonal, and community factors that contribute to differences in health outcomes. By applying this comprehensive approach, we aim to address multi-level challenges to physical activity participation and foster access to arthritis management for OWWH. The goal of this study is to adapt and test the Fit & Strong! (F&S) evidence-based physical activity and education intervention to address the specific physical and psychosocial needs of women, aged 50 years and older, living with HIV. The tailored intervention will integrate group-based physical activity and behavior change strategies, fostering social support and self-efficacy while addressing modifiable influences identified by OWWH. Our study aims are: 1) Collaborate with a Community Advisory Board of OWWH to tailor the F&S program using the ADAPT-ITT model and pilot test the new intervention; 2) Conduct a fully powered randomized waitlist-controlled trial with 300 participants to evaluate the intervention’s impact on participant health outcomes; and 3) Evaluate the acceptability, feasibility, and sustainability of the program at the individual, instructor, and organization levels. This project addresses a critical public health gap in an understudied population disproportionately affected by arthritis and co-morbid health challenges. By leveraging community-driven input and emphasizing an in-person, group-based approach, this study aims to increase physical activity, reduce pain, improve physical function, and enhance quality of life for OWWH.

Up to $907K

2030-12-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adapting an Intervention to Reduce Stigma among MSM and Healthcare Providers in Vietnam

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FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Abstract Despite advancements in HIV prevention and treatment and the expansion of services, HIV prevalence among men who have sex with men (MSM) in Vietnam has risen dramatically, from 6.6% in 2015 to 12.5% in 2023. Persistent stigmatization of MSM as "social evils," exacerbated by government campaigns associating MSM with the spread of HIV during the early period of HIV epidemic in Vietnam and reinforced by collectivist cultural norms against homosexuality, has exacerbated intersectional stigmas among MSM in Vietnam. This has led to discrimination, fear of disclosure, and avoidance of healthcare services, severely limiting MSM's access to HIV prevention and care services. To address these challenges, this study will culturally adapt a patient-provider stigma-reduction intervention-Finding Respect and Ending Stigma around HIV (FRESH) intervention- into DONGHANH ( meaning “companionship, understanding, and mutual support" in Vietnamese), for implementation among Vietnamese MSM (the patients) and healthcare providers (HCP- the providers). FRESH is a workshop-based intervention that has been successfully used to reduce stigma among healthcare workers and marginalized populations, including MSM, globally. Toward the end of the DONGHANH intervention, participants are expected to work together to develop stigma reduction strategies that they can take back to their respective communities, thus increasing the impact of the intervention. The intervention will also involve the creation of an e-module (a website), allowing participants to determine its delivery and engage in ongoing learning at their convenience. The study will be conducted in three phases: Phase I: using the ADAPT-ITT framework, we will adapt FRESH intervention based on findings from in-depth interviews and focus group discussions to create the culturally tailored DONGHANH intervention. Phase II: We will use a randomized wait-list control trial design to pilot test DONGHANH intervention among 180 participants (MSM=120; HCP=60). Ninety participants (MSM=60, HCPs=30) will participate in the intervention, while the remaining 90 participants (MSM=60, HCPs=30) will be assigned to the 3-month wait-list control. We will assess the intervention’s feasibility, acceptability, and fidelity as well as assess the preliminary efficacy of the intervention on reducing experiences of intersectional stigma and discrimination, increasing HIV testing, PrEP uptake and PrEP/ART adherence. Phase III: We will evaluate assess facilitators and barriers to implementation through interviews with MSM, HCP and project intervention staff, using the Consolidated Framework for Implementation Research to identify contextual factors of the intervention for future scale-up. If the DONGHANH intervention is successful, it can provide a scalable model for reducing intersectional stigmas and improve HIV prevention and care among MSM in Vietnam and other low-and middle- income countries.

Up to $46K

2029-03-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adapting and Pilot Testing Mindfulness-Based Relapse Prevention for Substance Use Peer Workers

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NIDA - National Institute on Drug Abuse

ABSTRACT Peer workers (PWs) are essential frontline workers addressing the opioid epidemic, yet their effectiveness is impeded by high rates of occupational burnout and relapse. Approximately 70% of PWs report elevated levels of burnout, and up to 40% of addiction professionals in recovery have relapsed. Further, the United States is experiencing a substance use workforce crisis due to staff shortages and high turnover rates. Interventions tailored to the unique needs of PWs to support workforce retention and long-term recovery are urgently needed. To date, there are no interventions that prevent burnout and relapse due to occupational stress among PWs. This K01 research and training award addresses this gap by being the first to adapt and test the acceptability and effectiveness of Mindfulness-Based Relapse Prevention (MBRP) for substance use PWs. A three-phase approach to adapt, refine, and pilot test the intervention will be conducted across three study aims: Aim 1 will include in-depth qualitative interviews with PWs to understand their experiences related to occupationally triggered substance use relapse and perspectives on intervention characteristics to optimize the effectiveness of MBRP for PWs. Aim 2 will include manual development, interventionist training, field testing, and further manual refinement. Aim 3 will include a small, 2-armed (intervention vs. standard of care) pilot hybrid type 1 randomized controlled trial with 80 PWs to assess preliminary effectiveness and implementation outcomes of the adapted MBRP intervention. Feasibility, acceptability, and preliminary indication of improvement in relapse risk and burnout symptoms will be examined in 1-, 3-, and 6-month follow-ups. The long-term goal of this work is to improve the retention and effectiveness of the peer workforce by reducing occupational burnout and substance use relapse. To enable the PI to pursue this long-term research agenda, she will work with experienced mentors to build four areas of expertise: (1) skills in intervention development and testing via randomized controlled trial design and execution, (2) proficiency in workforce development for the substance use disorder peer workforce, (3) expertise in longitudinal and multi-level statistical analysis methods, and (4) proficiency in dissemination and implementation science frameworks and hybrid implementation-effectiveness designs. This K01 proposal addresses a key priority in strengthening the nation’s substance use peer recovery support workforce, and it will fully prepare the PI for an independent research career as an addiction recovery behavioral intervention scientist, leading innovative research that advances the field and ultimately improves the addiction recovery system of care. This proposal directly aligns with NIDA’s Strategic Plan of improving the implementation of evidence-based strategies in real-world settings and identifying approaches to develop personalized interventions informed by people with lived experience and workforce development.

Up to $195K

2031-04-30

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adapting and testing an evidence based digitally delivered healthy relationship and violence prevention intervention with Native American adolescents

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NINR - National Institute of Nursing Research

Dating violence (DV) is common among U.S. high school age adolescents and has significant and lifelong negative health consequences, including suicide behaviors. Native American (NA) adolescents are at increased risk for violence victimization and/or perpetration in their dating violence, given their high rates of violence exposure in their homes and communities. Key challenges for dating violence prevention are the lack of services, fear of stigma and discrimination, and limited trust in and access to skilled professionals. The Fort Peck Reservation is home to the Assiniboine and Sioux Tribes in rural Montana. The reservation community reports high rates of violence and suicide behavior with underfunded and limited health and social service, especially for adolescents. The wide range of negative health and social outcomes associated with violence experienced by reservation-based NA adolescents underscores the call for innovative and targeted behavioral health interventions using appropriate technology. myPlan Teen, is an evidence-based healthy relationship and dating violence prevention intervention for adolescents and is delivered through a secure and confidential web based and mobile app. myPlan Teen provides adolescents with immediate access to information about healthy and unhealthy behaviors, safety strategies tailored to their situation with links to youth friendly resources, to reduce confusion, feelings of isolation and stigma associated with unhealthy relationships. In our CDC funded randomized control trial (RCT) with a national sample of 609 adolescents aged 15-17, we found adolescents randomized to myPlan Teen had a significant increase in use and helpfulness of safety behaviors compared to control group (adolescent health website). Further adolescents who used myPlan Teen reported a significant reduction in physical/sexual violence perpetration and suicide behaviors compared to control group. To advance the relevance and use of myPlan Teen with NA adolescents, our interdisciplinary team in partnership with Tribal Health leaders and Youth Advisory Board (YAB) will adapt myPlan Teen by integrating culturally relevant content, including tribal identity and communal mastery for NA adolescents to build healthy relationships, develop safety skills and access culturally relevant resources. Following the adaptation process, the team will evaluate the effectiveness of the culturally adapted myPlan Teen app on health and safety outcomes with 550 NA adolescents. In addition, we will examine the mechanisms by which myPlan Teen improves health and safety outcomes. The study will advance violence prevention interventions with NA adolescents and inform future processes to adapt and disseminate a digital intervention with adolescents nationally.

Up to $2.0M

2029-02-28

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

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DEPT OF DEFENSE.DEPT OF THE AIR FORCE.AIR FORCE MATERIEL COMMAND.AIR FORCE RESEARCH LABORATORY.FA8750 AFRL RIK

ADAPTIVE FUSION, & REASONING OF MULTI-SOURCE DATA (AFAR)

Rolling

general

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Adaptive Immune Regulation of Enteric Neurogenesis Directs Intestinal Inflammation

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NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY Inflammatory bowel diseases (IBD), which include ulcerative colitis and Crohn’s disease, are estimated to affect 3 million individuals in the United States, and the number of people living with IBD continues to rise. Currently available treatment options are ineffective for some patients, costly and pose serious long-term complications, such as opportunistic infections, autoimmunity, and cancer. Thus, there is an urgent need to improve our understanding of the modulators of intestinal inflammation and repair in order to identify novel therapeutic targets to treat and prevent IBD. Emerging studies have demonstrated that the peripheral and enteric nervous systems regulate intestinal immunity to infection and inflammation via complex neuro-immune circuits, including the production of neuropeptides such as calcitonin gene-related peptide (CGRP) and adrenomedullin 2 (ADM2) that directly regulate inflammation and restore tissue homeostasis in the gastrointestinal mucosa. However, little is known about whether and how these tissue protective enteric neurons are generated and regulated during the pathogenesis of IBD. In new preliminary data I demonstrate a new neuro-immune interaction wherein the enteric nervous system undergoes neurogenesis which is immunologically regulated during recovery from intestinal damage and inflammation. Newly generated neurons were found to highly express CGRP and ADM2. During recovery from intestinal inflammation, IL-17RA expression was enriched in enteric neurons, coinciding with the recruitment of IL-17A–producing CD4⁺ T cells to the colonic enteric nervous system. Further, mice with neuron- intrinsic deficiency in IL-17RA expression exhibit impaired neurogenesis and exacerbated disease severity compared to control mice with intact neuronal IL-17A signaling. Based on our new preliminary data, we hypothesize that the IL-17RA-IL-17A pathway is a previously unrecognized neuronal circuit that induces colonic enteric neurogenesis to promote tissue protection in the context of intestinal inflammation. We propose to generate a detailed understanding of how the IL-17RA-IL-17A axis promotes enteric neurogenesis and mediates tissue protection in murine models of intestinal inflammation. In Aim 1, we will test the hypothesis that the generation of new CGRP and ADM2 expressing enteric neurons are modulated during homeostasis and intestinal inflammation. Further we will identify the contribution of the microbiota to the generation and maintenance of CGRP and ADM2 expressing neurons in the colon under normal and inflammatory conditions. In Aim 2, we will use viral and genetic mouse models to selectively delete IL-17RA in enteric neurons and IL- 17A in CD4+ T cells, respectively, to investigate how the immune system regulates enteric neurogenesis during development and in response to intestinal damage and inflammation. In addition to uncovering fundamental and novel neuro-immune circuits and its roles in the pathogenesis of IBD, these studies could provide further insights to support the development of novel therapeutics that target the enteric nervous system.

Up to $92K

2028-05-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Adaptive Neural control of Respiration in Drosophila

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NINDS - National Institute of Neurological Disorders and Stroke

Project Summary Energy-intensive behaviors demand high oxygen supply, presenting a fundamental physiological challenge across the animal kingdom. Respiratory organs have evolved diverse forms - from insect spiracles to fish gills to human lungs. Yet their neural control systems serve a conserved purpose. They need to actively monitor respiratory gases and regulate both gas exchange and energy consumption during behavior. The neural mechanisms coordinating respiration with behavior remain poorly understood. In particular, we know little about how respiratory circuits interact with motor control systems during varying metabolic demands. Here I propose to investigate the neural basis of respiratory control during behavior. I have made two important discoveries that uniquely position me to investigate the neural control of respiration. I have identified the complete set of motor neurons controlling respiration in flies, and I have discovered novel gas- sensing neurons in muscles and respiratory tracts that detect respiratory state and modulate behavior. I have made genetic drivers that label both populations of neurons. With these advantages, I will investigate three fundamental aspects of respiratory control by combining genetics, connectomics, behavioral tracking, and in vivo imaging. First, I will examine the neuromuscular basis of respiratory control during locomotion. Second, I will investigate interoceptive mechanisms of respiratory gas sensing. Third, I will study the neural integration of respiratory and metabolic signals. This work will reveal how animals optimize respiratory control while maintaining homeostasis during behavior. The principles uncovered in this tractable system will provide an experimental and conceptual framework for studying respiratory control across species. My long-term goal is to establish an independent research program on neural control of respiration and energy homeostasis. The research and career development in this proposal will provide essential experimental, theoretical, and mentorship training. To support my transition to independence, I will be co-mentored by two experts at the University of Washington: Dr. John Tuthill, an expert on sensorimotor control in flies, and Dr. Jan-Marino Ramirez, an expert on mammalian respiratory control.

Up to $123K

2028-02-29

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

ADAPTIVE TA PRETRIAL GOVERNANCE (SS)

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Maximized Good, LLC

Education and Training Services

2026-10-23

Education

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Adaptive Watersports Day in Magnuson Park

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Sail Sand Point

Sail Sand Point provides numerous services to people with disabilities each year in partnership with Outdoors for All, Children's Hospital and Wounded Warriors. This year we will host a large kickoff day in May to invite interested participants to our site to learn about our program options, explore our boats and gear, meet the volunteers and staff running programs, and understand how they might participate. This project will be completed by July 2025.

Up to $4K

Rolling

environmentHealth

Free to search & build · $99 one-time to unlock the application pack · No subscription