Developing a synthetic control group using electronic health records: Application to a single-arm lifestyle intervention study.

The electronic health records (EHR) infrastructure offers a tremendous resource for identifying controls who match the characteristics of study participants in a single-arm trial. The objectives are to (1) demonstrate the feasibility of curating a synthetic control group for an existing study cohort through EHR data extraction and (2) evaluate the effect of a lifestyle intervention on selected cardiovascular health metrics. A total of 711 university employees were recruited between 2008 and 2012 to participate in a health partner intervention to improve cardiovascular health and were followed for five years.

Comprehensive Multiple eQTL Detection and Its Application to GWAS Interpretation.

Expression QTL (eQTL) detection has emerged as an important tool for unraveling the relationship between genetic risk factors and disease or clinical phenotypes. Most studies are predicated on the assumption that only a single causal variant explains the association signal in each interval. This greatly simplifies the statistical modeling, but is liable to biases in scenarios where multiple local causal-variants are responsible.

Relation of Changes in Body Fat Distribution to Oxidative Stress.

Android fat is a surrogate measure of visceral obesity in the truncal region. Both visceral adiposity and oxidative stress (OS) are linked to cardiometabolic risk factors and clinical cardiovascular disease. However, whether body fat distribution (android vs gynoid) is associated with OS remains unknown.

Constraints on eQTL Fine Mapping in the Presence of Multisite Local Regulation of Gene Expression.

Expression quantitative trait locus (eQTL) detection has emerged as an important tool for unraveling of the relationship between genetic risk factors and disease or clinical phenotypes. Most studies use single marker linear regression to discover primary signals, followed by sequential conditional modeling to detect secondary genetic variants affecting gene expression. However, this approach assumes that functional variants are sparsely distributed and that close linkage between them has little impact on estimation of their precise location and the magnitude of effects.

Health Care Expenditures for University and Academic Medical Center Employees Enrolled in a Pilot Workplace Health Partner Intervention.

Objective: To evaluate the impact of a pilot workplace health partner intervention delivered by a predictive health institute to university and academic medical center employees on per-member, per-month health care expenditures.

Methods: We analyzed the health care claims of participants versus nonparticipants, with a 12-month baseline and 24-month intervention period. Total per-member, per-month expenditures were analyzed using two-part regression models that controlled for sex, age, health benefit plan type, medical member months, and active employment months.

A Longitudinal Study of Health Improvement in the Atlanta CHDWB Wellness Cohort.

The Center for Health Discovery and Wellbeing (CHDWB) is an academic program designed to evaluate the efficacy of clinical self-knowledge and health partner counseling for development and maintenance of healthy behaviors. This paper reports on the change in health profiles for over 90 traits, measured in 382 participants over three visits in the 12 months following enrolment. Significant changes in the desired direction of improved health are observed for many traits related to cardiovascular health, including BMI, blood pressure, cholesterol, and arterial stiffness, as well as for summary measures of physical and mental health.

Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults.

Objective: Redox status and inflammation are important in the pathophysiology of numerous chronic diseases. Epidemiological studies have linked vitamin D status to a number of chronic diseases. We aimed to examine the relationships between serum 25-hydroxyvitamin D [25(OH)D] and circulating thiol/disulphide redox status and biomarkers of inflammation.

Vascular endothelial function and self-reported sleep.

Background: The authors investigated the relationship between self-reported sleep characteristics and brachial artery flow-mediated dilation (FMD) in a community-based population. Previous studies document that sleep apnea may be related to endothelial dysfunction but disagree whether subjective reports of sleep may also reflect such associations.

Methods: In 684 subjects (32% male) aged between 37 and 60 years enrolled in the Emory-Georgia Tech Predictive Health Institute study, the authors measured reported sleep characteristics using the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index (PSQI) along with cardiovascular risk factors.

Whole genome sequencing in support of wellness and health maintenance.

Background: Whole genome sequencing is poised to revolutionize personalized medicine, providing the capacity to classify individuals into risk categories for a wide range of diseases. Here we begin to explore how whole genome sequencing (WGS) might be incorporated alongside traditional clinical evaluation as a part of preventive medicine. The present study illustrates novel approaches for integrating genotypic and clinical information for assessment of generalized health risks and to assist individuals in the promotion of wellness and maintenance of good health.

Fluid flux and clearance in acute lung injury.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), were presciently described nearly two centuries ago by René Laennec, later to be described clinically in the 1950s and 1960s. Substantial advances have been made in understanding the pathogenesis of these forms of permeability pulmonary edema, including Starling forces and cellular transport mechanisms involved in the generation and resolution of this form of lung injury. Functional animal models and clinically applicable case definitions for ALI and ARDS were instrumental in gaining these new insights.

Blood-informative transcripts define nine common axes of peripheral blood gene expression.

We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB) cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses.

Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model.

Introduction: The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice.

Methods: A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood.

Genetic risk prediction in a small cohort of healthy adults in Atlanta.

Compared with single markers, polygenic scores that evaluate the joint effects of multiple trait-associated variants are more effective in explaining the variance of traits and risk of diseases. In total, 182 CHDWB (Emory-Georgia Tech Center for Health Discovery and Well Being study) adults were genotyped to investigate the common variant contributions to three traits (height, BMI, serum triglycerides) and three diseases (coronary artery disease (CAD), type 2 diabetes (T2D) and asthma). Association was contrasted between weighted and simple allelic sum polygenic scores with quantitative traits, and with the Framingham risk scores for CAD and T2D.

Psychosocial factors associated with diet quality in a working adult population.

The associations between specific intra- and inter-personal psychosocial factors and dietary patterns were explored in a healthy, working adult sample of university and health center employees (N = 640) who were enrolled in a prospective predictive health study. Participants had a mean age of 48 (SD = 11) years and were 67% women and 30% minority. Baseline psychosocial measures of perceived stress, depressive symptoms, social support, and family functioning were examined for their relationships with three diet quality indices-AHEI, DASH, and the Mediterranean.

The role of mitochondrial oxidation in endotoxin-induced liver-dependent swine pulmonary edema.

Unlabelled: We reported previously studies in an in situ perfused swine preparation demonstrating that endotoxemia induced lung injury required the presence of the liver and that the response was accompanied by oxidative stress. To determine whether lung and liver mitochondrial oxidative stress was important to the response, we compared the effects of equimolar amounts of two antioxidants, n-acetylcysteine, which does not replenish mitochondrial glutathione, and procysteine which does, on endotoxemia induced lung injury in the swine preparation. In a swine perfused liver-lung preparation, we measured physiologic, biochemical and cellular responses of liver and lung to endotoxemia with and without the drugs.

High-performance metabolic profiling of plasma from seven mammalian species for simultaneous environmental chemical surveillance and bioeffect monitoring.

High-performance metabolic profiling (HPMP) by Fourier-transform mass spectrometry coupled to liquid chromatography gives relative quantification of thousands of chemicals in biologic samples but has had little development for use in toxicology research. In principle, the approach could be useful to detect complex metabolic response patterns to toxicologic exposures and to detect unusual abundances or patterns of potentially toxic chemicals. As an initial study to develop these possible uses, we applied HPMP and bioinformatics analysis to plasma of humans, rhesus macaques, marmosets, pigs, sheep, rats and mice to determine: (1) whether more chemicals are detected in humans living in a less controlled environment than captive species and (2) whether a subset of plasma chemicals with similar inter-species and intra-species variation could be identified for use in comparative toxicology.

Circulating endothelial progenitor cells inversely associate with organ dysfunction in sepsis.

Purpose: Endothelial dysfunction is a primary contributor to sepsis-related organ dysfunction and death. In sepsis animal models, endothelial progenitor cells (EPC) have contributed to vascular repair. The role of endothelial progenitor cells as a biomarker for organ dysfunction is still unknown.

Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans.

Objectives: The primary objective of this study was to elucidate mechanisms underlying the link between vitamin D status and cardiovascular disease by exploring the relationship between 25-hydroxyvitamin D (25-OH D), an established marker of vitamin D status, and vascular function in healthy adults.

Background: Mechanisms underlying vitamin D deficiency-mediated increased risk of cardiovascular disease remain unknown. Vitamin D influences endothelial and smooth muscle cell function, mediates inflammation, and modulates the renin-angiotensin-aldosterone axis.

Oxidative stress is associated with impaired arterial elasticity.

Aims: Arterial stiffening may lead to hypertension, greater left ventricular after-load and adverse clinical outcomes. The underlying mechanisms influencing arterial elasticity may involve oxidative injury to the vessel wall. We sought to examine the relationship between novel markers of oxidative stress and arterial elastic properties in healthy humans.

Integrating comparative effectiveness research programs into predictive health: a unique role for academic health centers.

The growing burden of chronic disease, an aging population, and rising health care costs threaten the sustainability of our current model for health care delivery. At the same time, innovations in predictive health offer a pathway to reduce disease burden by preventing and mitigating the development of disease. Academic health centers are uniquely positioned to evaluate the comparative effectiveness of predictive and personalized health interventions, given institutional core competencies in innovative knowledge development.

Effect of bone marrow-derived mesenchymal stem cells on endotoxin-induced oxidation of plasma cysteine and glutathione in mice.

Bone marrow-derived mesenchymal stem cells (BMDMSC) are emerging as a therapeutic modality in various inflammatory disease states, including acute lung injury (ALI). A hallmark of inflammation, and a consistent observation in patients with ALI, is a perturbation in the systemic redox environment. However, little is known about the effects of BMDMSC on the systemic redox status.

Predictive health: the imminent revolution in health care.

Increasing social, economic, and political pressures to reform the U.S. approach to medical care makes change likely.

A senescence accelerated mouse model to study aging in the larynx.

Objective: Age-related changes in the larynx lead to significant voice impairment and reduced quality of life. There is a need for aged animal models that have practical generation times to study the fundamental changes and new therapeutics for the aging voice. The senescence accelerated prone mouse strain (SAMP) animals experience rapid aging without any experimental manipulation.

Slow-release nanoparticle-encapsulated delivery system for laryngeal injection.

Objectives/hypothesis: There is a need for a slow-release system for local delivery of therapeutics to the larynx. Most therapeutic substances, such as steroids or chemotherapeutic agents that are injected into the larynx are cleared rapidly. Repeated laryngeal injection of these substances at short intervals is impractical.