Goal 1: Promote Human Health

Theoretical division of NHLBI

Many functional physiology, cellular physiology , electrophysiology, and other aspects are amenable to rigorous mathematical methods.NHLBI lacks a theoretical division where IDEAS expressed mathematically make testable predictions at multi scale levels. NHLBI LACKS A THEORETICAL DIVISION- although history has shown that virtually all original ideas have a mathematically expressible foundation, particularly when dynamic, ...more »

Submitted by (@sjk000)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

the impact is obvious in the sense that predicton based on theory can lead to new discovery

Name of idea submitter and other team members who worked on this idea : Sandor j Kovacs

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-13 net votes
12 up votes
25 down votes
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Goal 4: Develop Workforce and Resources

Which factors are associated with systems performance?

What are the institutional factors, including structure and culture of care, that characterize systems performance? Which of these factors are potentially modifiable and/or scalable?

Submitted by (@rebecca.lehotzky)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea : AHA Staff & Volunteers

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-3 net votes
2 up votes
5 down votes
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Goal 2: Reduce Human Disease

Enhanced Pain Research in Sickle Cell Disease

There is a need for more enhanced pain research in order to help improve sickle cell disease patient outcomes and quality of life.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Pain is the most common clinical manifestation of sickle cell disease (SCD) and accounts for a large proportion of emergency department visits and hospitalizations. Due to its impact on the patients’ quality of life, there is a need for more basic and clinical research studies focused on understanding the mechanisms of different pain syndromes as well as the role of neurotransmitters and inflammation in acute and chronic SCD pain. Also, comparative effectiveness studies in the management of chronic pain will be crucial in helping to improve the patients’ overall quality of life.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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39 net votes
58 up votes
19 down votes
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Goal 2: Reduce Human Disease

How to organize artificial pulsatile propelling of blood maintaining the balanced circulation?

Venous pressure, being very low, distends (deforms) the ventricle - but due to elastic or viscous law of deformation? Elastic deformation depends on stress (pressure) only and the viscous one - on stress and time. When pressures are low you can't get large distention due to stress only (time-independent) unlike the case when you apply low stress and long time interval. If we want to use venous pressure as one of regulators ...more »

Submitted by (@yuri.astrakhan)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

The impact (in case of constructive solution of the problem) can be expected as a breakthrough in the field of engineering of extracorporal circulatory devices and artificial heart. More exactly: the impact will concern the dosage of blood while filling of the ventricle - without intrusion into the essential levels of venous pressure (the levels play the role of regulators together with levels of diastolic arterial pressure).

Feasibility and challenges of addressing this CQ or CC :

The feasibility of implementation (engineering of a device) of the above idea depends on preliminary supercomputer modeling of blood circulation based on simulation of viscous relaxation of ventricle combined with the controlling of circulation according to the deduced equation (see the reference).

Name of idea submitter and other team members who worked on this idea : Kamnev Yuri

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-9 net votes
2 up votes
11 down votes
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Goal 3: Advance Translational Research

Palliative and hospice care for COPD patients

Does palliative care and/or hospice care as practiced across communities improve end-of-life care for COPD – specifically, does it reduce the burden of symptoms, improve HRQoL and satisfaction, reduce utilization in last 6 months of life (i.e. hospital visits, cost, invasive ventilation use, etc), improve the end-of-life experience, and increase the concordance of place of death to expressed patient preferences?

Submitted by (@k.willard)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Voting

12 net votes
16 up votes
4 down votes
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Goal 2: Reduce Human Disease

RFA on EC-cardiomyocyte interactions in the mechanisms and treatments of cardiovascular diseases

Often under recognized, the cardiac endothelial cells are highly abundant in the heart, and may have important roles in modulating cardiac function, besides simply serving as structural component of blood vessels. Evidences of ours and others have indicated an emerging role of cardiac endothelial cells signaling to cardiomyocytes to mediate important pathophysiological responses. Nonetheless, detailed mechanisms of ...more »

Submitted by (@hcai00)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Successfully addressing this question would no double reveal novel mechanisms and ways of monitoring treatment responses of cardiovascular disease, ultimately leading to novel drug targets, valuable biomarkers and extended new directions of basic research as well.

Feasibility and challenges of addressing this CQ or CC :

Tools of studying these cells are mostly available. Both adult cardiomyocytes and endothelial cells from the heart can be isolated and cultured, although cardiomyotyes need to used within 24 hrs and cannot be passaged. However successful preparation of these cells from WT and transgenic animals would permit co-culture experiments and mechanistic studies. These cells can also be studied using in-situ techniques either detecting molecular changes/events or dynamic interactions. Potential challenges would side in selective targeting of these cells, for example, either ECs or cardiomyocytes, once a potential therapeutic is in the testing. Nonetheless, PECAM-ab conjugated techniques have been employed to specifically deliver proteins to endothelial cells, so I am confident most of the challenges can be worked out, particularly within a RFA awardees group with frequent exchanges of ideas.

Name of idea submitter and other team members who worked on this idea : Hua Linda Cai, University of California Los Angeles

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27 net votes
30 up votes
3 down votes
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Goal 2: Reduce Human Disease

Interactions between anticoagulant therapy and antiretroviral drugs

Cardiovascular pathology has become a major problem in the management of the HIV-infected patient during the ART era. A large number of HIV patients will receive anticoagulants drugs for secondary prevention of cardiovascular disease. It is therefore critical to understand the interactions between antiretroviral therapy and anticoagulant therapy to safely treat HIV patients.

Submitted by (@pandrea)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

With over 50% of HIV-infected patients in the US anticipated to be > 50 years of age by 2015, the overall risk of CVD will be significantly higher and could become the main challenge for the management of chronic HIV infection. A large number of HIV-infected patients with CVD will therefore need treatment for primary and secondary prevention of atherothrombotic events. The secondary prevention of CVD almost invariably includes prescription of one or multiple anticoagulants drugs. It is therefore conceivable that anticoagulant therapies will be frequently associated with ART for the management of HIV patients, which already developed CVD. The interactions between these therapies are not well studied and are critical for the management of the HIV-infected patients.

Feasibility and challenges of addressing this CQ or CC :

Feasibility: 1) retrospective studies on a large number of HIV patients that had cardiovascular events and were treated with antiretroviral drugs; 2) prospective studies comparing different antiretroviral regimens associated with the most current anticoagulant therapy recommended for secondary prevention of CV disease; 3) use of animal models of AIDS for testing new anticoagulants and the interaction with the antiretroviral drugs.

Name of idea submitter and other team members who worked on this idea : Ivona Pandrea

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2 net votes
5 up votes
3 down votes
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Goal 2: Reduce Human Disease

Improve vascular healing and extend long term benefit of interventions

How can we develop new approaches to improve vascular healing and extend the long term benefits of vascular interventions for more patients?

Submitted by (@societyforvascularsurgery)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

­The response to vascular injury, whether it be catheter interventions, bypass surgery, or chronic implants, is a reactive process characterized by inflammation, cell proliferation, and fibrosis leading to failure. Better understanding of the mechanisms of vessel remodeling, and restoring homeostasis, is needed to improve prediction, develop and translate new treatments. This remains the leading scientific problem in vascular medicine and surgery. New approaches such as proteomics, lipidomics, molecular imaging offer new opportunities in this realm.

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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0 net votes
1 up votes
1 down votes
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Goal 4: Develop Workforce and Resources

Training of Clinical & Translational Scientists

Although the NCRR and NIGMS used to have a mechanism to train new generation of clinical & translational scientists, this program was stopped. Why?

What is the possibility of other institutes to come up with the priority of funding resources in this regard?

Submitted by (@dkagr0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

In view of the health care models, strong control of insurance companies in determining the remuneration, lack of protective time for qualified clinicians to continue their research, no incentive to the institute for promoting such activities, lack of available tenure-track jobs, pool of effective and well-trained clinical & translational researchers is decreasing rapidly. Even though NIH invests resources to train MD-PhD students, a very minor pool of these graduates continue curiosity and passion in advancing new knowledge and discovering newer approaches.

Feasibility and challenges of addressing this CQ or CC :

1. Additional resources must be developed by NHLBI, NIAID, NIDDK and other major institutes to support this endeavor.

2. Institutes/medical schools who provide protective time to their faculty to continue their efforts in clinical & translational research, must be acknowledged and incentivized.

3. There has been no effective way of measuring outcomes from such investments. All of us must take ownership in utilizing the resources more effectively and more productively.

Name of idea submitter and other team members who worked on this idea : Devendra K. Agrawal, PhD

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31 net votes
38 up votes
7 down votes
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Goal 3: Advance Translational Research

Develop relevant large animal models for various disease conditions

What is the possibility of investing funds primarily in clinically-relevant models where the findings could be translated in to human diseases?

Submitted by (@dkagr0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Strong emphasis on the use of a clinically-relevant large animal model would hopefully be more productive in developing better therapeutic approaches and management of patients.

Feasibility and challenges of addressing this CQ or CC :

In view of the lack of facility at many institutions and the cost involved, and the rules and regulations by the USDA and other regularity bodies, special emphasis will be required to build the animal facility at an institution. Where will the funds come from? Similar to many other core facilities set up by the NIH at various institutions, what is the possibility of developing specialized centers for testing a new idea in a clinically-relevant large animal facility?

Name of idea submitter and other team members who worked on this idea : Devendra K. Agrawal, PhD

Voting

-5 net votes
11 up votes
16 down votes
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Goal 3: Advance Translational Research

Animal models of vascular diseases

How can we better model human vascular disease in all its complexity?

­This is key to more effective translation of both diagnostics and therapeutics. Develop improved animal models of vascular diseases including PAD, aneurysm, venous diseases, to facilitate fundamental research and preclinical development.

Submitted by (@societyforvascularsurgery)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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2 net votes
3 up votes
1 down votes
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Goal 3: Advance Translational Research

Improving patient-clinician communication and decision-making for patients wiith serious heart, lung or blood diseases

How can we ensure that patients with serious heart, lung, or blood diseases fully understand their prognosis, treatment options, and the risks and benefits of those options and help them make decisions that fully incorporate their own personal values, goals, and treatment preferneces?

Submitted by (@jrc000)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Patients with serious heart, lung and blood diseases are often faced with dificult treatment decisions that involve tradeoffs and long-term consequences without adequate understanding of their prognosis and the risks and benefits of treatment. There is emerging consensus that a shared decision-making approach provides the best support for patients and their families in this situcation, but there is evidence that this is not happening and there is inadequate data to guide the best approach to ensuring it does happen. Dramatic advances in treatment technologies make treatment choices ever more complex and often make the tradeoffs more difficult to fully understand. Advances in our ability to help patients and their families through this decision-making process have not kept up with these advances in treatment options.

Feasibility and challenges of addressing this CQ or CC :

Incorporation of palliative care approaches, decision aides, and improvements in clinician-patient communication provide the opportunity to make important advances in this area, but have not been fully developed or incorporated. There is an opportunity to advance the communication, decision-making, and implementation science to have a dramatic impact on enhancing healthcare and quality of life for patients and thier families.

Name of idea submitter and other team members who worked on this idea : J. Randall Curtis, MD, MPH

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27 net votes
33 up votes
6 down votes
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