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The Methodology of Curation for Scientific Research Findings

OPINION LEADERSHIP on Cardiovascular Diseases

 Volume Two

Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation

Epilogue to Volume Two

Aviva Lev-Ari, PhD, RN, Editor-in-Chief, BioMed e-Series of e-Books

Part 1: Curation is another Methodology for Creation of Scientific Knowledge.

OPINION LEADERSHIP: We are developers of new methodologies for Research Finding exposition and dissemination

The Curation process involves development of numerous avenues for exposition of the scientific product and its dissemination, among them:

• scientific articles on Scientific Journals,
• Books, e-Books
• Addresses by Leader Scientists,
• multimedia presentations (Audio and Video),
• Expert Panel Discussions,
• Correspondence among Scientists,
• archive of experiment results, thematic Literature surveys,
• Libraries of Open Source Code,
• Comprehensive Thematic Bibliographies,
• Shareable Libraries of Annotated Genomics Research

In our curations we have used several from the above list. We take great pride in our presentations of critiques and synthesis of research results. We represent one alternative to Academic Publishing. Instead of divergence into millions of publications per year, we focus on the Frontier, we select several seminal articles and aggregate the outcomes, their significance in context and creatively we identify interrelationsnot included in each of the components of the assembly.

Part 2: Cardiovascular Diseases – Predicted Cost of Care and the Affordable Care Act

• Cost of Care for Cardiovascular Medical Diagnoses
• Impact of 2013 HealthCare Reform in the US
• Patient Protection and Affordable Care Act Featured at RAND

OPINION LEADERSHIP: We identify the potential of Cardiac Regeneration to be the frontier for Cardiovascular Disease near-cure

In the United States, heart failure afflicts about 6 million people (1), costs $34.4 billion each year (2), and is now the single most common discharge diagnosis in those over 65 (3). Although enormous progress has been made in managing acute cardiovascular illnesses such as heart attacks, many patients go on to develop late sequelae of their disease, including heart failure and arrhythmia. Thus, the growing number of these patients in some ways represents a burden of our success. It also reflects the incomplete success of most current therapies, which mitigate and manage but do not cure the disease.

https://www.sciencemag.org/content/338/6114/1549.summary

OPINION LEADERSHIP: We identify ACCESS to HealthCare Services to be the cardinal factor of success for the Affordable Care Act (ACA).

On  January 10, 2014 Jonathan Cohn wrote in the New Republic: The Kids Are Alright: Another Obamacare Lesson from Massachusetts 

Youth is not be the same thing as health. A 33-year-old with diabetes will run up bigger physician and drug bills than a 61-year-old with no serious medical problems. But, as a general rule, younger means healthier. And the early numbers haven’t seemed that encouraging.

Overall, according to a study by the Kaiser Family Foundation, about 40 percent of the people who could eventually buy coverage through Obamacare marketplaces are between the ages of 18 and 34. But, as of December, just 22 percent of the people signing up for coverage in California were in that demographic. Other states reported similar data. The federal government hasn’t yet provided an age breakdown for people getting insurance through healthcare.gov, the website it operates on behalf of 36 other states. But it will probably provide that information soon. When it does, the numbers may not look any better.

Is this a big deal? One way to answer that question is by looking at the best test case available: Massachusetts, which introduced a similar reform scheme in 2007. Thanks to analysis from Jonathan Gruber, the MIT economist who was an architect of both the Massachusetts and federal reforms, we know that enrollment was slow to get rolling in Massachusetts—and that, relatively speaking, healthy people came into the system late. Now Gruber has done a new analysis, breaking down enrollment specifically by age, and provided it to the New Republic.

The graph above tells the story. Over the course of the first year, the proportion of young people (in this case, ages 19 to 34) who had obtained health coverage through the Massachusetts insurance exchange grew. In other words, they were more likely to sign up late.

The precise figures don’t mean a lot, in part because the Massachusetts analogy is hardly perfect. John Sexton of Breitbart (yes, that Breitbart) has written about some of the key distinctions. But the trend is pretty clear—and, according to Gruber, it provides some important lessons. “These data aren’t 100 percent predictive for every state, most importantly because of differences across states in the share of the potential market that is young,” Gruber says. “But these facts highlight two things. First, you don’t need a huge/majority share of enrollees to be young for markets to function well. Second, the young tend to wait to sign up until closer to the deadline.

Obamacare could obviously unfold differently, with plenty of variation from state to state. In some places, participation among the young might not rise the way it did in Massachusetts—or, at least, it might not reach the same levels. But that doesn’t mean those states are destined for an insurance “death spiral,” in which carriers jack up rates so high that only the very sick stay in the system.

Part 3: Causes of Cardiovascular Diseases

• Human Genome: Congenital Etiological Sources of Cardiovascular Disease
• The Role of Calcium in Health and Disease
• Vasculature and Myocardium: Diagnosing the Conditions of Disease

OPINION LEADERSHIP: We identify two pivotal research directions in the effort to understand the Etiology of Cardiovascular Diseases

1. The Research Frontier on Cardiac Regeneration by Anthony Rosenzweig, M.D. 

Professor of Medicine, Beth Israel Deaconess Medical Center on Cardiac Regeneration and How does Excercise help the Heart

• We are still relatively early in the development of new approaches to cardiovascular disease. It will be some time before we know the conclusion of what will likely be a long and challenging road ahead.
• Almost as challenging is conveying to patients and policymakers an appropriate perspective that balances unmitigated enthusiasm for the scientific discoveries, cautious optimism for the broader implications, and humble acknowledgment that though even the most appealing ideas may fail, there is only one way to find out.

Science 338, 1549 (2012)

We are interested in why the heart fails. Heart failure is an enormous and growing cause of death and disability throughout the world. In addition, the heart provides a model system for studying fundamental cellular processes from cell growth and programmed death, to cell-lineage determination and regeneration. Recently we’ve been interested in understanding how exercise protects the heart against heart failure. A variety of high throughput profiling techniques are being used to identify pathways differentially regulated in heart growth associated with exercise in comparison to the heart growth that precedes heart failure. A recently identified transcriptional pathway involved C/EBPβ and CITED4 not only reproduces many of the effects of exercise and protects the heart from heart failure, but appears to enhance the heart’s regenerative capacity(Bostrom et al Cell, 2010). In vivo gain- and loss-of-function models are being used to explore the functional effects and molecular mechanisms of this pathway in more detail. Other ongoing studies are investigating cardiac micro-RNAs regulated by exercise and their potential protective effects in the heart.

http://connects.catalyst.harvard.edu/Profiles/display/Person/10161

2. Biology of the Nucleus and Gene Expression @ Spiegelman Lab, Harvard Medical School

• Transcriptional Basis of Energy Metabolism
• Regulation of Fat Cell Differentiation
• Metabolic Control through the PGC-1 Coactivators
• Chemical Biology of the PGC-1 Coactivators

β-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic β-Oxidation and Is Inversely Correlated with Cardiometabolic Risk Factors. Cell Metab. 2014 Jan 7;19(1):96-108. doi: 10.1016/j.cmet.2013.12.003.

Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 2013 Nov 5;18(5):649-59. doi: 10.1016/j.cmet.2013.09.008. Epub 2013 Oct 10.

http://research4.dfci.harvard.edu/spiegelmanlab/research.htm

Part 4: Risks and Biomarkers for Cardiovascular Diseases

OPINION LEADERSHIP: We identify as fruitful area of further study –

1. Genetic Determinants of Potassium Sensitivity and Hypertension. Integrated Computational and Experimental Analysis of the Neuroendocrine Transcriptome in Genetic Hypertension Identifies Novel Control Points for the Cardiometabolic Syndrome

2. Essential hypertension, a common complex disease, displays substantial genetic influence. Contemporary methods to dissect the genetic basis of complex diseases such as the genomewide association study are powerful, yet a large gap exists betweens the fraction of population trait variance explained by such associations and total disease heritability.

3. There are many roles for biomarkers to be subject for further research:

• risk assessment
• disease status
• mechanism of injury
• severity of disease
• response to interventions

The following topics address a small set of examples from an exhausting list of biomarkers:

• The Role of Calcium in Health and Disease
• Vasculature and Myocardium: Diagnosing the Conditions of Disease
• Conduction Dysfunction and ElectroPhysiology of the Heart
• Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment

Part 5: Advances in Treatment of Cardiovascular Diseases

• Vasculature and Myocardium: Diagnosing the Conditions of Disease
• The Role of Calcium in Health and Disease
• Conduction Dysfunction and ElectroPhysiology of the Heart
• Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment

OPINION LEADERSHIP: We identify the frontier of Treatment for Cardiovascular diseases to embrace potentially the following trends:

Sources of Evidence in Identifying Risk Factors for Cardiovascular Disease will continue to be derived from a combination of research methodologies:

• Basic research
• Epidemiological research
• Descriptive
• Analytical
• Observational
• Case-control studies
• Cohort studies
• Randomized trials

Physical Activity:

• Cumulative long-term PA has a protective effect on incidence of all-cause and CVD-attributable mortality compared with long-term physical inactivity.
• In men, but not women, long-term PA also appears to have a protective effect on incidence of CVD.

Is it Hypertension or Physical Inactivity: Cardiovascular Risk and Mortality – New results in 3/2013

Heart doi:10.1136/heartjnl-2012-303461

Cardiovascular Imaging: