Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

Goal 2: Reduce Human Disease

Improve ineffective treatments for circadian rhythm disorders

I have extreme delayed sleep phase disorder (DSPD), a circadian rhythm disorder (CRD). I fall asleep at dawn and wake up early afternoon. My dim light melatonin onset (DLMO) is at 5:30 am. A normal person’s DLMO may be at 9 pm, for example. CRD treatment—prolonged bright light after temperature nadir, dark restriction/melatonin starting several hours before natural bedtime, darkness till temperature nadir—does not work ...more »

Submitted by (@susanpl)

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

Details on the impact of addressing this CQ or CC :

Circadian rhythm disorders (delayed sleep phase disorder, non-24-hour sleep-wake disorder, irregular sleep-wake disorder) have been ignored by many sleep researchers. They should not be. First, they reduce lives to rubble: education, employment, partnering, and parenting suffer or are not possible. Second, nocturnals who force themselves to live a diurnal life are at higher risk of disease (as are diurnals who work 3rd shift) and accidents. Third, evidence is mounting that circadian rhythms play a significant role in immunity, cancer, heart disease, diabetes, obesity, metabolic (dys)regulation, mental health, medication administration, and public health (think of the spike in accidents after spring and fall time changes).

Feasibility and challenges of addressing this CQ or CC :

To date, most circadian research has been conducted on "normals" who don't have CRDs. But their responses to light and dark cues differ from those of CRD patients. Please conduct circadian research on CRD patients--just as you would conduct diabetes research on diabetics.

 

Also needed: convenient ways to test for dim light melatonin onset, temperature nadir, and other circadian biomarkers. Right now, such tests are limited to study settings.

Name of idea submitter and other team members who worked on this idea : Maya Kochav

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Goal 2: Reduce Human Disease

CVD as a comorbidity of HIV-1 Infection

Even in cART treated HIV-1 infected subjects, development of CVD is a major co-morbidity. Research is needed to evaluate the role of various biomarkers as well as anti-retrovirals .Role of ethnicity and gender also seems to be important. Since these persons are rather younger, Framingham concept may not applicable.

Submitted by (@mkumar)

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 about one million HIV-1 infected individuals in the U.S. more than 50% of them are at a risk to develop CVD despite their infection under control. If the risk factors are known, intervention can be introduced.

Feasibility and challenges of addressing this CQ or CC :

Very much doable. It may be carried across the United States so that role of environments, ethnicity and dietary practices may also be taken into consideration.

Name of idea submitter and other team members who worked on this idea : Mahendra Kumar, Debrah Jones Weiss

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11 up votes
14 down votes
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Goal 2: Reduce Human Disease

Making It Real: Affordable Physiologically Relevant In Vitro Environments

We have done the best we can to mimic the human internal environment in vitro for the discovery, testing, and validation of therapeutics, but there is a critical need to do better. The use of more complex cell-based in vitro models is the result of the recognition of how little predictive power there is in current experimental conditions, even with animal models. With an in vitro environment that goes beyond temperature ...more »

Submitted by (@ahenn0)

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

Details on the impact of addressing this CQ or CC :

Physiologically relevant in vitro environments could potentially impact research on every tissue type, disease, and intervention, including transfusion-based treatments. Basic research, drug-testing, and translational medicine would all be fundamentally altered. Individualized medicine, cellular therapies, and regenerative medicine could all benefit from in vitro conditions that best support the care of the patient's cells and guide those cells in the direction needed for effective treatment.

Feasibility and challenges of addressing this CQ or CC :

Research and Industry are in the early stages of developing the techniques and know-how needed to address the technical challenges in establishing human-relevant in vitro environments. We already have the technology to control in vitro oxygen and other critical gas components. Mimicking cell-cell interactions and variable cell states such as states of differentiation or stress are areas under active research. Computational and analytical techniques are being developed that can gain insight from large data sets. More of a challenge may be assessing distant effects like metabolism of drugs by the liver or potential drug and cellular interactions with the external environment. However, making a human-predictive in vitro environment affordable is the challenge that could define success or failure of any particular approach. It is feasible within the next ten years to have truly predictive in vitro environments for drug cellular therapy development.

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Goal 2: Reduce Human Disease

New models for clinical trials

There is a need to educate the scientific community and program staff about the use of metrics, results-based accountability, and other business models to improve the science, productivity, and efficiency of clinical trials and clinical trial networks.

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 :

Improve the efficiency of clinical trials and a return on research investments

Feasibility and challenges of addressing this CQ or CC :

Yes, this is feasible.

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

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4 net votes
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6 down votes
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Goal 2: Reduce Human Disease

Harnessing the Tsunami of Patient-Generated Health Data

How can the NHLBI foster the development of effective tools and methodologies to harness the tsunami of patient-generated health data into a valuable resource for conducting patient-centered research? Some challenges to overcome might include a) how to enable the collaboration of the more traditional clinical scientists with scientists from other disciplines such as informatics or computational and data-enabled science ...more »

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 :

Methodological research results in this area could be translated into clinical settings – specifically, they could help physicians interpret such data without being overwhelmed by their sheer volume, and even further use them as helpful adjunct tools to more traditional ways of diagnosing and/or treating diseases.

Feasibility and challenges of addressing this CQ or CC :

The increasing number of smartphones, mobile apps, and remote monitoring devices are producing a vast amount of patient-generated health-related data. However, there are no widely established tools, methodologies, or strategies to ensure optimal use and management of these data. The time is right to move forward quickly in furthering research in this field over the next 5 to 10 years.

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

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Goal 2: Reduce Human Disease

What causes the structural abnormalities that cause sleep apnea, and how can they be prevented?

It is estimated that up to 28% of the population suffer from sleep apnea, which impairs functioning and reduces quality of life, while increasing risk of accidents and a variety of cardiovascular, metabolic, and neuropsychiatric diseases. A large portion of sleep apnea cases are caused by abnormal oro-nasal-maxillo-mandibular features that result in crowding of the upper airway, making it vulnerable to collapsing or ...more »

Submitted by (@bmdixon)

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

Details on the impact of addressing this CQ or CC :

Obstructive sleep apnea (OSA) is a common condition, which causes chronic fatigue and daytime sleepiness, as well as cognitive impairments affecting learning, concentration, and memory. Over the long term, it increases many health risks, including accidents, cardiovascular disease, and depression. OSA is characterized by partial, or complete, blockage of the airway during sleep, so that breathing repeatedly pauses or airflow is limited, causing repeated arousals from sleep. It is usually secondary to a narrow, or collapsible, airway due to either 1) obesity or overweight, or 2) abnormal morphology of the mandible or maxilla bones, which crowds facial structures, such as the tongue and nose, narrowing the pharynx. The causes of obesity are already being well studied, but there is relatively little research on the etiology of the structural abnormalities involved in OSA. Abnormalities of facial structure are widespread in the population causing, not only OSA, but also orthodontic problems that require many to get braces or have wisdom teeth extracted, and widespread temporomandibular joint (TMJ) problems. However, multiple studies have documented that these abnormalities are almost completely absent from populations living a preindustrial, agrarian or forager, lifestyle, making them a “disease of civilization”. In particular, the abnormalities are associated with consumption of a modern diet of processed foods during prenatal, infant, and early childhood development.

Feasibility and challenges of addressing this CQ or CC :

Current evidence implicates three factors in the development of these structural abnormalities: prenatal maternal nutrition (especially vitamin K2 status), breastfeeding vs. bottle-feeding, and frequency of consumption of tough foods after weaning (which provides exercise to the jaw). We need to form a large cohort and study orthodontic development prospectively from fetal development through mid-childhood, with data on diet, feeding practices, and physiological measures of nutrient status. Measurement methods are available using existing technologies to collect the necessary data on each of these measures. Determining the causes responsible for these structural abnormalities will enable further research to demonstrate effective methods of preventing them. Given that many patients with OSA are rendered so miserable by it that they undergo maxillomandibular advancement surgery to correct it, an expensive procedure with a lengthy recovery period, prevention would be a far better solution. This research will move us a big step closer to a future without sleep apnea and its formidable collection of negative effects on health and functioning.

Name of idea submitter and other team members who worked on this idea : Bonnie Dixon

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Goal 2: Reduce Human Disease

Reducing Disparities

Given the dearth of information on cardiovascular, lung, and hematologic outcomes in minorities, NHLBI should develop strategic aims that promote evaluation of these outcomes and potential interactions with kidney disease that disproportionately affect minorities.

Submitted by (@golan0)

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

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Goal 2: Reduce Human Disease

Using "omics" for therapeutic targets

How do we identify potential targets for therapy in the age of systems biology/genomics?

Submitted by (@nhlbiforumadministrator)

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 : NHLBI Staff

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Goal 2: Reduce Human Disease

Risk factors for sleep-disordered breathing in patients with COPD

What are the risk factors for sleep-disordered breathing in patients with COPD (the “overlap syndrome")?

Submitted by (@nhlbiforumadministrator)

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 : American Thoracic Society member

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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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Goal 2: Reduce Human Disease

Detection of rupture prone small aortic aneurysms

Critical challenges in the assessment of aortic aneurysms are: (1) Availability of reliable animal models that simulate the human pathology, (2) Availability of molecular imaging resources – identification of biomarkers, development of targeted imaging probes and pre-clinical imaging methods, and plasma markers that predict whether an aneurysm is prone to rupture or dissection, (3) Bringing together a wide array of multi-disciplinary ...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 :

Developing clinically viable methods to detect rupture prone aneurysms can lead to better methods of diagnosis and intervention and avoid preventable fatalities

Feasibility and challenges of addressing this CQ or CC :

Several other disease areas including oncological that had similar gap was filled by NIH (NCI) and the challenges were overcome in less than 10 years. The scientific expertise to fill the gap exists, however they work in silos, which need to be brought together to fulfil this gap and is achievable in less than 10 years

Assessment of aortic aneurysms that are prone to rupture or dissection has been an elusive target. Current clinical practice measures the aortic diameter and fails to relate to the pathophysiology and biomechanical properties of the aneurysm in deciding preventive surgery. Critical gap exists in the diagnosis of aneurysm especially with small aneurysms (3 - 5 cm in diameter) that are rupture prone. Based on autopsy about 10 percent of individuals with small abdominal aneurysms had undergone fatal rupture, while 40 percent with diameters of 7-10 cm had intact aneurysm and died from other causes. International Registry of Aortic Dissection found that 40% of thoracic aneurysms dissected at diameters smaller than 5 cm.

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

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11 down votes
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Goal 2: Reduce Human Disease

Defining percision medicine based on biological signatures

What are the unique bio-informatics time-series signatures that identify health, disease, response to therappy and can predict impending deterioraiton and select correct therapes base don individual patient performance characteristics.

Submitted by (@pinskymr)

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

Details on the impact of addressing this CQ or CC :

Use machine learnign principles to data mine complex biological time series signals to define patterns uniquely characterizing health, disease, improvement in response to therapy and the lack thereof.

Feasibility and challenges of addressing this CQ or CC :

Need high quality time series data linked to low dimensional demographic data and treatment records to create a library of similar experiences defining cohorts.

Name of idea submitter and other team members who worked on this idea : HIPPA compliant data sharing across institutions

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