Goal 2: Reduce Human Disease

Identification and validation of surrogate endpoints for long-term morbidity in Sickle Cell Disease

Research in sickle cell disease (SCD) has mostly focused on preventing or treating acute medical events, such as vaso-occlusive pain, acute chest syndrome, and, in pediatric patients, acute strokes. Chronic SCD complications such as chronic kidney disease or pulmonary hypertension, develop over decades, thus are poor choices for clinical trial endpoints. There is a great need to develop surrogate endpoints that predict ...more »

Submitted by (@hulbertm)

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

Details on the impact of addressing this CQ or CC :

Longitudinal cohorts of SCD patients, spanning childhood and adulthood, with biobanking DNA, plasma, and serum, and standardized clinical and imaging assessments will allow identification predictors of negative clinical outcomes. An NHLBI-funded national SCD clinical registry with biobanking will be necessary to validate any surrogate endpoints.

Name of idea submitter and other team members who worked on this idea : Monica Hulbert

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13 net votes
16 up votes
3 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.

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

Fundamental stress-response mechanisms in the heart.

What are the primary molecules and cellular signals associated with prolonged hypertensive stress that cause adverse myocardial tissue remodeling, and what strategies that prevent or reverse adverse remodeling can be developed and tested?

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 :

Could potentially contribute to the development of new therapies for heart disease and cardiomyopathies.

Feasibility and challenges of addressing this CQ or CC :

Yes, addressing this CQ may be feasible. Since it is likely that a multitude of signaling mechanisms are involved, an unbiased, global approach may be necessary to identify the key molecular pathways. However, experimental challenges remain and even developing appropriate animal models has been challenging.

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

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14 net votes
21 up votes
7 down votes
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Goal 3: Advance Translational Research

Move beyond the use of self-report for dietary intake quantification

There is a need to move beyond the use of self-report for dietary intake quantification towards funding the development of new technology and broader use of objective measures. There is no question that the effects of diet on health, quality of life, and longevity are of great interest to many and plausibly of great importance. Because of that, tremendous research resources have been provided to study this topic. Given ...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 :

Virtually all authors and investigators in this area recognize that such measurements are limited in their validity; the common mantra is that while limited, these methods nevertheless have sufficient validity to merit being used in scientific investigations. In contrast, a growing group of investigators, ourselves included, think that this common mantra is not reasonable. Virtually all authors and investigators in this area recognize that such measurements are limited in their validity; the common mantra is that while limited, these methods nevertheless have sufficient validity to merit being used in scientific investigations. In contrast, a growing group of investigators, ourselves included, think that this common mantra is not reasonable. Instead we believe that the evidence clearly shows that with at least respect to self-reported energy intake, the measurements are so inaccurate that they do not warrant being used as a basis for scientific investigations and conclusions, even when no better measurement is available. Therefore, at least in investigations involving energy intake, we believe that self-report methods should be abandoned for purposes of drawing scientific conclusions about energy intake, and that funds made available for human dietary investigations be directed toward development of new, objective methods and technologies that can replace self-report methods.

Feasibility and challenges of addressing this CQ or CC :

We believe that the scientific community would benefit from development of methods of measuring dietary intake that do not rely upon self-report. We are not recommending that more investment go into refining self-report methods but rather that replacement methods be sought. Some investigators are interested in devices such as smartphone photography as a way of enhancing self-report. It is our intuition that such methods will only be modest enhancements and will be subject to very substantial biases, since they rely on subject cooperation. Instead, we believe that that methods based on principles of physics, engineering, and chemistry (and generally less prone to human filtering/interference) are likely to be more useful in the long run. Investing in such methods could take at least two forms. First, funders could invest in the development of new technologies and techniques. Second, funders could invest in ways that alter the economic conditions for the use of existing techniques, notably doubly-labelled water (DLW). It is remarkable how much the cost of genotyping has decreased in the last several decades, driven by market incentives and a market initially catalyzed by NIH investment. This is not the case with DLW, which has stayed at a fairly constant price for 30 years. We suggest that it may be possible for the NIH to create a market incentive for reductions in price by initially catalyzing a large demand through an infusion of funding for research using DLW.

Name of idea submitter and other team members who worked on this idea : David B. Allison, Ph.D.; Kevin Fontaine, Ph.D.; Kathryn A. Kaiser, Ph.D.; Andrew W. Brown, Ph.D.; Edward C. Archer, Ph.D.

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1 net vote
2 up votes
1 down votes
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Goal 2: Reduce Human Disease

Sleep Apnea - Diagnostic Test

The notion that in order to be treated with CPAP for sleep apnea you first must have a diagnostic test, which involves either a sleep laboratory or a home study, needs to be examined.

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 :

This idea is far reaching and possibly ahead of the curve a bit but it represents a direction that the sleep apnea field eventually should explore. Consider developing a clinical diagnosis of sleep apnea based on clinical symptoms and exam findings and then randomized those patients meeting the definition to a trial of autocpap for 3 months or to a traditional evaluation (home diagnostic test then APAP) for 3 months. Close follow up is necessary but with wireless telephony now available for CPAP and estimates of AHI available through CPAP adherence downloads, this study is feasible. If such a case diagnosis of sleep apnea can be developed (and I believe it can), then many more patients may be able to be treated. This approach, if successful, would shake-up the field considerably and potentially opens up treatment to many more OSA sufferers.

Name of idea submitter and other team members who worked on this idea : ATS Member

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

Tissue engineered constructs for vascular disease

Can we develop improved, clinically effective tissue engineered constructs for vascular disease?

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 :

We need a better alternative to coronary and lower extremity bypass surgery for patients lacking adequate vein.

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

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1 net vote
2 up votes
1 down votes
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Goal 1: Promote Human Health

Combinatorial intervention of immune dynamics to combat cariovascular disease

Human health and disease are modulated by complex and inter-connected dynamic processes. With particular significance, a well-balanced immune environment may play a key role in maintaining health and preventing the pathogenesis of cardiovascular disease. Defining the dynamic programming and balance of immune environment will be the key for combinatorial therapies to reset homeostasis.

Submitted by (@lwli00)

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 : Liwu Li

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8 net votes
10 up votes
2 down votes
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Goal 3: Advance Translational Research

Nucleic Acid Delivery and Gene Editing

For lung diseases, how can new technologies for nucleic acid delivery and gene editing be promoted?

Submitted by (@skrenrich)

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 : Cystic Fibrosis Foundation

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

T4 Implementation Research Platform in Low Income Countries

What are the best strategies to stimulate development of a T4 Implementation Research network within low income countries (LICs)?

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

• Currently there are huge implementation challenges within LIC contexts and only limited progress is being made to address the gaps

• Conducting research in the context where its finding will be scaled up will vastly increase its appropriateness, adoption and uptake, fidelity, and sustainability

• Small improvements in the challenging context of LICs should provide opportunities to make a large burden reduction

Feasibility and challenges of addressing this CQ or CC :

• Currently there are formative efforts to engage biomedical research in LICs with H3Africa, Global Alliance for Chronic Diseases, and others

• NHLBI Think Tanks and Workshops have found much interest and demand to T4 Implementation research engagement

• Key non-traditional partners (World Bank, USAID) are working on implementation strategies in LICs currently and will be strong partners

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

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-22 net votes
7 up votes
29 down votes
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Goal 1: Promote Human Health

Critical Windows in Early Development to Maximize Lung Health

Is there a critical window of growth and development for maximizing lung function?

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 :

Low lung function during childhood tracks to early adulthood and contributes to early onset disease. Lung health promotion is needed, but we know little about what can enhance and protect human health during rapid phases of lung development in utero and growth postnatally to adulthood.

Feasibility and challenges of addressing this CQ or CC :

Researchers could turn their attention on healthy and “maximally” health populations (human and model organisms) to understand genetic and environmental exposures that influence lung function at upper ends of the spectrum (>2 SD from the mean).

Recent findings suggest that there is an urban-rural continuum of lung function in specific ethnic groups; and interventions with maternal dietary supplements can enhance lung function in offspring. These set the stage for further study on developing knowledge of early life events that can inform lung health promotion.

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5 net votes
17 up votes
12 down votes
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Goal 2: Reduce Human Disease

Redox regulation of cardiovascular and lung disease through thiols

Redox imbalance as represented by alterations in oxidative versus reductive stresses are well appreciated to occur during nearly all forms of cardiovascular and lung diseases. However, specific molecular mechanisms responsible for these changes remain largely unknown and poorly organized. Study of redox biology principals has revealed that protein cysteine thiols are a unique target for redox posttranslational modifications ...more »

Submitted by (@ckevil)

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

Details on the impact of addressing this CQ or CC :

Protein cysteine thiols are recognized to be important for multiple signaling and cell biology functions due to unique properties of oxidation/reduction resulting in a 'thiol switch'. However, oxidative modifications of thiols are highly complex involving nitrosation, sulfhydration, sulfenylation, and glutathiolyation among many others. It has become increasingly clear that these posttranslational modifications are associated with cardiovascular and pulmonary pathophysiology. Yet, many important questions remain such as: how these thiol modifications occur during disease and differ from health? How do these thiol switches impact protein function involved in cellular pathophysiology? And can thiol switch manipulation be exploited for therapeutic purposes to maintain cellular and organ health or treat disease? In order to begin to answer these questions, careful and comprehensive investigations are required to understand thiol-switching principals employing a host of molecular, biochemical and pathophysiological approaches.

Feasibility and challenges of addressing this CQ or CC :

Given the significant advances in quantitative analytical chemical and molecular techniques, molecular redox mediators and pathways, non-invasive imagine modalities and comprehensive translational study designs; multiple fields are uniquely poised that could provide significant insight into this critical challenge. Primary objectives would be to establish consensus analytical methodologies, chemical and molecular biology approaches, and cellular and animal models in conjunction with rigorous clinical investigations. Results from efforts at understanding the importance of ‘thiol switches’ will make significant clinical impact on cardiovascular and lung pathogenesis and would feasibly be accomplished in 5-10 years.

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-5 net votes
5 up votes
10 down votes
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