Goal 3: Advance Translational Research

Translational Bioinformatics Spanning Multiple Scales of Biologic Complexity to Implement Precision Pulmonary Medicine at the Po

What translational bioinformatics tools could be used in pulmonary medicine to allow multidimensional, multi-scale modeling of clinical and biomolecular data to assist clinical decision-making?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Deployment of bioinformatics tools to construct multi-dimensional, multi-scale models of pulmonary (mal)functioning from large heterogeneous data sets spanning biological molecules, subcellular compartments, signaling pathways, cells, tissues, organs, organ systems and clinical therapeutics trials to predict actionable precision medicine for clinicians at the point of pulmonary care.

Feasibility and challenges of addressing this CQ or CC :

A variety of existing powerful informatics methods for integrating a vast wealth of clinical and high-dimensional data across DNA to organism compartments to develop multi-scale modeling approaches to improve point-of-care precision medicine. Consistent with a continuous learning healthcare system, precision medicine modeling is recursive, tentative pending better understanding and therefore continuously learning.

Fundamental to implementation of precision medicine is the ability to extract heterogeneous data from basic and clinical research to be integrated systematically into clinical practice in a cohesive and large-scale manner. Deployment of precision medicine models to predict (mal)functioning progression and response the treatment in daily practice relies strongly on the availability of an efficient bioinformatics platform that assists in the translation of basic and clinical science knowledge.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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-2 net votes
10 up votes
12 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 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

Voting

31 net votes
38 up votes
7 down votes
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Goal 2: Reduce Human Disease

Additional research needed to identify various contributors of obesity

What are the specific contributors of obesity that lead to chronic positive energy balance and surplus energy storage?

Submitted by (@mturner)

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

Details on the impact of addressing this CQ or CC :

Obesity is a health crisis of epic proportions. About 34% of adults in the US have obesity, up from 31 % in 1999 and about 15% in the years 1960 to 1980. The chronic diseases that result from obesity annually cost over $150 billion in weight-related medical bills. Reduction of obesity improves cardiovascular and other health outcomes, yet what is currently known about obesity is inadequate to combat the global obesity epidemic. A comprehensive understanding about the mechanics of obesity may help in developing more effective preventive and treatment strategies, which in turn will substantially improve cardiovascular and other health measures.

Feasibility and challenges of addressing this CQ or CC :

Years of obesity research have revealed the complex nature of this disease and its multi-factorial etiology. While research has firmly established the role of energy balance in weight gain and weight loss, it is important to discover upstream factors that predispose only certain individuals to energy imbalance. This may be addressed by further focusing on newly identified putative contributors of obesity, including but not limited to the impact of sleep deprivation, ambient temperature, age at first pregnancy, intrauterine and intergenerational factors, neuro-endocrine factors, epigenetics, environmental chemicals and endocrine disruptors, gut microbes, infections and the immune system, and social and behavioral factors associated with obesogenic behaviors. These studies may provide mechanistic insight that may also lead to the development of new pharmacological approaches. It is possible that cause-specific prevention or treatment approaches may yield more effective results than generic approaches that do not necessarily consider upstream modulators of energy imbalance, or inter-individual differences.

Name of idea submitter and other team members who worked on this idea : The Obesity Society

Voting

8 net votes
18 up votes
10 down votes
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Goal 4: Develop Workforce and Resources

Shall we increase the transparency of the grant review process to prevent potential biases?

Financial and intellectual conflict(s) of interest are common in academic medical sciences. Those conflicts could potentially bias decisions of study section members and change grant application outcomes. During the grant review process, financial and/or intellectual conflict(s) of interest disclosures of the study section members are not readily available to the grant applicants or the public. Should the NHBI increase ...more »

Submitted by (@escalante.patricio)

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

Details on the impact of addressing this CQ or CC :

Increased transparency in the grant review process will provide a more plain level field for all applications, including new investigators with novel ideas.

Feasibility and challenges of addressing this CQ or CC :

Public disclosure of financial (more than intellectual) conflict(s) of interest are becoming the standard in medical societies and scientific publications.

Voting

18 net votes
24 up votes
6 down votes
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Goal 2: Reduce Human Disease

What is the effect of variant genes on AVM development in HHT

Natural genetic variation between individuals can influence the outcome of carrying an HHT mutation. Some gene variants may be protective while others may increase the risk of AVM or telangiectasis. By identifying the variant genes that alter risk of AVM may give clues to the molecular mechanisms of AVM formation and provide new drug targets

Submitted by (@mariannes.clancy)

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 : Marianne Clancy MPA

Voting

1 net vote
1 up votes
0 down votes
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Goal 3: Advance Translational Research

Direct thrombin inhibitors and anti-Xa (Ten A) inhibitors in trauma patients - physiologic effects and impact on outcomes

Direct thrombin inhibitors and anti-Xa (Ten A) inhibitors are new, undetectable and irreversible. We have no data on how well these drugs correlate with current measures of coagulopathy such as thromboelastography, or whether antifibrinolytics should be used in patients who are on these drugs. These drugs may increase incidence of traumatic brain injury after minor injury. They are also going to be used increasingly in ...more »

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Understanding pathophysiology of coagulopathy in trauma patients due to these drugs may lead to innovations in management of coagulopathy and help increase our ability to predict/prognostic poor clinical outcomes in patients on these new anticoagulants, detect these drugs in a timely manner and develop antidotes/reversal agents. 

Feasibility and challenges of addressing this CQ or CC :

These are eminently feasible with adequate support from the NHLBI. Challenges will be finding collaborations or institutions that have enough clinical volume and adequate basic science/translational research infrastructure to look at these questions seriously.

Name of idea submitter and other team members who worked on this idea : Sudha Jayaraman

Voting

-7 net votes
6 up votes
13 down votes
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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 1: Promote Human Health

Enhancing Understanding of Determinants of Health in Rural Areas & Developing Solutions

What are the biological, environmental, social and economic determinants of health in rural areas related to COPD and other lung disease.

Submitted by (@gacdk0)

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

Details on the impact of addressing this CQ or CC :

There are extreme disparities in the impact of COPD in rural areas, especially in rural Appalachia. These areas experience much larger prevalence rates and higher rates of hospitalization, readmissions and other health indicators that contribute to increased cost and decreased quality of life. These are also areas with the least ability to make improvements. Research that can inform both the causes of these disparities and identify proven methods for systematically confronting these issues has the potential to dramatically improve overall health status in rural America

Name of idea submitter and other team members who worked on this idea : Grace Anne Dorney Koppel

Voting

7 net votes
8 up votes
1 down votes
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Goal 2: Reduce Human Disease

Prodromal symptoms and signs of a heart attack/acute coronary syndrome

Can early warning symptoms and signs of a heart attack (acute coronary syndrome) be quantified through standardized symptom surveys, biochemical measures, electrocardiographic, or other diagnostic means to enable earlier evaluation and treatment?

Submitted by (@mmhand)

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

Details on the impact of addressing this CQ or CC :

If patients could detect symptoms that have been demonstrated prospectively to herald an impending heart attack and/or if there were sensitive biochemical, electrocardiographic, or other tests that could be performed by patients/bystanders (e.g., in the home setting), by emergency medical services personnel, primary care providers or others in community settings to assist with decision support about seeking intervention for early symptoms/signs of an acute coronary syndrome, this would potentially save thousands of lives from heart attacks and sudden cardiac death.

Feasibility and challenges of addressing this CQ or CC :

Prodromal heart attack symptoms (waxing and waning of symptoms in advance of complete vessel occlusion) have not been prospectively described or quantified. The standard symptom constellations from epidemiologic surveys have been described for heart attack symptoms (ACS) though there is variability in symptom data collection among heart attack surveys as well. Also while there are biochemical tests for muscle damage (troponin), there is not a biochemical test for ischemia such as could be applied in the home or work setting. Similarly it would be helpful if a self-applied electrocardiogram by patients/bystanders could give a diagnosis of early ischemia (prior to occlusion) so patients could seek observational care.

Name of idea submitter and other team members who worked on this idea : Mary Hand

Voting

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

Detection of inflammatory monocytes as a biomarker of CVD

Coronary artery disease (CAD), of which atherosclerosis is a major contributor, costs the United States $108.9 billion each year. While a number of conventional risk factors such as smoking, diabetes and hypertension have been associated with CAD, their predictive performance is poor in the prevention of acute coronary syndrome (ACS). Despite the prevalence of ACS in our society, there are currently no molecular biomarkers ...more »

Submitted by (@scottsimon)

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

Details on the impact of addressing this CQ or CC :

Need more opportunities to put forth innovative diagnostic and therapeutic solutions than currently vetted through the CTSC process.

We have developed the Artery-on-a-chip (A-chip), currently in a research tool format, which accurately measures the extent of inflammatory monocyte activation in a whole blood sample by shearing it along a molecular sensor and enumerating monocyte capture.

Name of idea submitter and other team members who worked on this idea : Scott I Simon, Greg Foster, Ehrin Armstrong

Voting

-6 net votes
8 up votes
14 down votes
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Goal 3: Advance Translational Research

Vascular disease awareness

Increase awareness of vascular disease in the population. Public recognition and understanding is poor, despite high prevalence. ­ Improve public education about vascular diseases, the risk factors, early signs, and treatment.

Submitted by (@societyforvascularsurgery)

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

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

Voting

1 net vote
2 up votes
1 down votes
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