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The arboricity of a graph is the minimum number of forests required to cover all its edges. In this paper, we examine arboricity from a game-theoretic perspective and investigate cost-sharing in the minimum forest cover problem. We introduce the arboricity game as a cooperative cost game defined on a graph. The players are edges, and the cost of each coalition is the arboricity of the subgraph induced by the coalition. We study properties of the core and propose an efficient algorithm for computing the nucleolus when the core is not empty. In order to compute the nucleolus in the core, we introduce the prime partition which is built on the densest subgraph lattice. The prime partition decomposes the edge set of a graph into a partially ordered set defined from minimal densest minors and their invariant precedence relation. Moreover, edges from the same partition always have the same value in a core allocation. Consequently, when the core is not empty, the prime partition significantly reduces the number of variables and constraints required in the linear programs of Maschler's scheme and allows us to compute the nucleolus in polynomial time. Besides, the prime partition provides a graph decomposition analogous to the celebrated core decomposition and the density-friendly decomposition, which may be of independent interest. [ABSTRACT FROM AUTHOR]

For vertex cover games (introduced by Deng et al. (1999) [2]), we investigate population monotonic allocation schemes (introduced by Sprumont (1990) [11]). We show that the existence of a population monotonic allocation scheme (PMAS for short) for vertex cover games can be determined efficiently and that a PMAS, if exists, can be constructed accordingly. We also show that integral PMAS-es for vertex cover games can be characterized with stable matchings and be enumerated by employing Gale-Shapley algorithm (introduced by Gale and Shapley (1962) [4]). [ABSTRACT FROM AUTHOR]

Rumor Blocking, an important optimization problem in social network, has been extensively studied in the literature. Given social network G = (V , E) and rumor seed set A , the goal is asking for k protector seeds that protect the largest expected number of social individuals by truth. However, the source of rumor is always uncertain, rather than being predicted or being known in advance in the real situations, while rumor spreads like wildfire on the Internet. This paper presents General Rumor Blocking with unpredicted rumor seed set (randomized A) and various personal profits while being protected (weights of nodes in V). We first show that the objective function of this problem is non-decreasing and submodular, and thus a (1 − 1 / e) approximate solution can be returned by greedy approach. We then propose an efficient random algorithm R-GRB which returns a (1 − 1 / e − ε) approximate solution with at least 1 − n − ℓ probability. We show that it runs in O (m (n − r) (k log ⁡ (n − r) + ℓ log ⁡ n) / ε 2) expected time, where m = | E | , n = | V | , r = | A | and k is the number of protector seeds. Finally, we conduct extensive experiments to evaluate the R-GRB and show that it is superior in both theory and experiment. [ABSTRACT FROM AUTHOR]

Cooperative games provide a framework for fair and stable profit allocation in multi-agent systems. Core , least-core and nucleolus are such solution concepts that characterize stability of cooperation. In this paper, we study the algorithmic issues of the least-core and nucleolus of threshold cardinality matching games (TCMG). A TCMG is defined on a graph G = ( V , E ) and a threshold T , in which the player set is V and the profit of a coalition S ⊆ V is 1 if the size of a maximum matching in G [ S ] meets or exceeds T , and 0 otherwise. We first show that for a TCMG, the problems of computing least-core value, finding and verifying least-core payoff are all polynomial-time solvable. We also provide a general characterization of the least-core for a large class of TCMG (cf. Theorem 2 ). Next, based on Gallai–Edmonds Decomposition in matching theory, we establish a concise formulation of the nucleolus for a special case of TCMG (when the threshold T equals 1). For arbitrary T , we prove that the nucleolus of TCMG can be obtained in polynomial time for bipartite graphs and graphs with a perfect matching. [ABSTRACT FROM AUTHOR]

Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model. [ABSTRACT FROM AUTHOR]

We study core stability and some related properties of flow games defined on simple networks (all edge capacities are equal) from an algorithmic point of view. We first present a sufficient and necessary condition that can be tested efficiently for a simple flow game to have a stable core. We also prove the equivalence of the properties of core largeness, extendability, and exactness of simple flow games and provide an equivalent graph theoretic characterization which allows us to decide these properties in polynomial time. [ABSTRACT FROM AUTHOR]

Abstract: In this work we discuss two related cooperative games, relaxed and rigid edge covering games, which arise from edge covering problems on graphs. On the basis of a new 0–1 program formulation for edge covering problems and LP duality theory, we obtain a common necessary and sufficient condition on the balancedness of both edge covering games. [Copyright &y& Elsevier]

Abstract: Pleiotrophin (PTN) is a heparin-binding growth/differentiation inducing cytokine that shares 50% amino acid sequence identity and striking domain homology with Midkine (MK), the only other member of the Ptn/Mk developmental gene family. The Ptn gene is expressed in sites of early vascular development in embryos and in healing wounds and its constitutive expression in many human tumors is associated with an angiogenic phenotype, suggesting that PTN has an important role in angiogenesis during development and in wound repair and advanced malignancies. To directly test whether PTN is angiogenic in vivo, we injected a plasmid to express PTN into ischemic myocardium in rats. Pleiotrophin stimulated statistically significant increases in both normal appearing new capillaries and arterioles each of which had readily detectable levels of the arteriole marker, smooth muscle cell α-actin. Furthermore, the newly formed blood vessels were shown to interconnect with the existent coronary vascular system. The results of these studies demonstrate directly that PTN is an effective angiogenic agent in vivo able to initiate new vessel formation that is both normal in appearance and function. The data suggest that PTN signals the more “complete” new blood vessel formation through its ability to stimulate different functions in different cell types not limited to the endothelial cell. [Copyright &y& Elsevier]

Coronary heart disease is currently the leading killer in the western world. Therapeutic angiogenic agents are currently being examined for treatment of this disease. We have recently demonstrated the effective use of Pleiotrophin (PTN) as a therapeutic agent for treatment of ischemic myocardium. We have also shown that injection of the biopolymer fibrin glue preserves left ventricular geometry and prevents a deterioration of cardiac function following myocardial infarction. Due to the low transfection efficiency of naked plasmid injections, we examined the use of PTN plasmid and the biopolymer as a gene-activated matrix in the myocardium. In this study, we demonstrate that delivery of PTN plasmid in fibrin glue increases neovasculature formation compared to injection of the naked plasmid in saline. [Copyright &y& Elsevier]

Let G=(V,E) be an undirected graph. Upper total domination number Γt(G) is the maximum cardinality over all minimal total dominating sets of G, and upper fractional total domination number Γt(G) is the maximum weight over all minimal total dominating functions of G. In this paper we show that: (1) Γt(G) is an optimal value of some linear programming and is always a rational number; (2) when G is a tree, Γt(G)=Γt(G); (3) the recognition problems corresponding to the problems of computing Γt(G) and Γt(G) are both NP-complete. [Copyright &y& Elsevier]

In Steiner tree game associated with a graph G=(V,E), players consist of a subset N⊆V of nodes. The characteristic function value of a subset S⊆N of the players is the minimum weight of a Steiner tree that spans S. We show that it is NP-hard to determine whether a Steiner tree game is totally balanced, i.e., cores for all its subgames are non-empty. In addition, the NP-hardness result is also proven for deciding whether the core is non-empty, or whether an imputation is a member of the core. [Copyright &y& Elsevier]

Let Γ = (N, v) be a cooperative game with the player set N and value function v : 2[supN] → R. A solution of the game is in the core if no subset of players could gain advantage by breaking away from the grand coalition of all players. This paper surveys theoretical results on the cores for some cooperative game models. These results proved that the linear program duality characterization of the core is a very powerful tool. We will focus on linear and integer programming techniques applied in this area. [ABSTRACT FROM AUTHOR]

Let г ≡ (N, ν) be a cooperative game with the player set N and characteristic function ν: 2[SUPN] → R. An imputation of the game is in the core if no subset of players could gain advantage by splitting from the grand coalition of all players. It is well known that, for the flow game (and equivalently, for the linear production game), the core is always non-empty and a solution in the core can be found in polynomial time. In this paper, we show that, given an imputation x, it is NP-complete to decide x is nota member of the core, for the flow game. And because of the specific reduction we constructed, the result also holds for the linear production game. [ABSTRACT FROM AUTHOR]

Purpose: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI.To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis.The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates.Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.Procedure: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI.To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis.The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates.Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.Results: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI.To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis.The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates.Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.Conclusions: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI.To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis.The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates.Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI. [ABSTRACT FROM AUTHOR]

Submodular optimization not only covers some classical combinatorial optimization problems, but also has a wide range of applications in fields such as machine learning and artificial intelligence. For submodular maximization problems with constraints, some work has been done including the design of approximation algorithms, the measurement of approximation algorithms in terms of quality and efficiency, etc. In this paper, we consider the problem of maximizing a non-negative monotone submodular function minus a non-negative modular function with the cardinality constraint. This model has been applied to many scenarios, such as team formation problem, influence maximization problem, recommender systems problem, etc. We propose a threshold algorithm that achieve a (1 / 2 − O (ε) , 2) -bicriteria approximation ratio and query complexity O (n log ⁡ n). Our algorithm makes a small sacrifice in the approximation ratio but improves the best query complexity result of existing deterministic algorithms from O (n 2) to O (n log ⁡ n) in the worst case. [ABSTRACT FROM AUTHOR]

Edge cover games are cooperative cost games arising from edge cover problems. In an edge cover game, each player controls a vertex and the cost of a coalition is the minimum weight of edge covers in the subgraph induced by the coalition. The approximate core is a relaxation of the core which is one of the most important concepts in cooperative game theory. A vector belongs to the α -core (0 ≤ α ≤ 1) if it recovers at least α -fraction of the total cost of the game when no deviating coalition is better off. In this paper, we show that the 3 4 -core of edge cover games is always non-empty and a vector in the 3 4 -core can be computed efficiently. We also show that 3 4 is the best constant ratio for the approximate core of edge cover games, as it is the reciprocal of the integrality gap for edge cover problems. [ABSTRACT FROM AUTHOR]

Background: C-reactive protein (CRP) is an inflammatory marker that is associated with an increased risk of major adverse cardiovascular events (MACE) in ambulatory coronary artery disease (CAD). However, the association of longitudinal trends of CRP with subsequent MACE in ambulatory CAD is unknown. Hypothesis: We tested the hypothesis that an increase in CRP level over time is associated with an increased risk of subsequent MACE among patients with ambulatory CAD. Methods: We measured CRP levels at baseline and at 5-year follow-up in 629 participants enrolled in the Heart and Soul Study, a prospective cohort study of patients with ambulatory CAD. The outcomes evaluated were heart failure (HF) hospitalization, non-fatal myocardial infarction (MI), cardiovascular (CV) death and the combined outcome (MACE) occurring after the 5-year visit. We evaluated the association between change in CRP and outcomes using unadjusted and multivariable-adjusted Cox proportional hazards models. Results: The mean age of the participants was 71±10 years and 18% were female. Most of the participants (77%) had a fall in CRP over 5 years (median change -2.2 pg/ml, interquartile range (IQR) -6.4, -0.9), while 23% had a rise in CRP (median change +1.6 pg/ml, IQR +0.4, +5.4). During a mean follow-up of 4.2±1.4 years, 134 participants (21%) developed MACE. After full adjustment for demographic, clinical and laboratory variables, including year-1 CRP and year-5 N-terminal pro-brain natriuretic peptide (NT-proBNP) and high sensitivity troponin T levels, a rise in CRP was associated with an increased risk of developing HF (HR 3.3 [95% CI 1.3-8.0], p=0.01) and MI (HR 3.8 [95% CI 1.2-12.8], p=0.03). It was also associated with a two-fold risk of CV death (HR 2.2 [95% CI 1.0-4.7], p=0.05), and combined MACE (HR 2.0 [95% CI 1.2-3.5], p=0.01), although the risks of CV death and combined MACE were not significant after adjusting for year-5 NT-proBNP and troponin T levels. Conclusion: In patients with ambulatory CAD, a 5-year increase in CRP levels is independently associated with an elevated risk of non-fatal MI and HF hospitalization. An increase in CRP in this population identifies those who are at an increased risk of MACE and may therefore benefit most from aggressive preventive interventions. [ABSTRACT FROM AUTHOR]

Independent set games are cooperative games defined on graphs, where players are edges and the value of a coalition is the maximum cardinality of independent sets in the subgraph defined by the coalition. In this paper, we investigate the convexity of independent set games, as convex games possess many nice properties both economically and computationally. For independent set games introduced by Deng et al. [5] , we provide a necessary and sufficient characterization for the convexity, i.e., every non-pendant edge is incident to a pendant edge in the underlying graph. Our characterization implies that convex instances of independent set games can be recognized efficiently. Besides, we introduce a new class of independent set games and provide a necessary and sufficient characterization for the convexity. [ABSTRACT FROM AUTHOR]

Intramyocardial injection of hydrogels offers great potential for treating myocardial infarction (MI) in a minimally invasive manner. However, traditional bulk hydrogels generally lack microporous structures to support rapid tissue ingrowth and biochemical signals to prevent fibrotic remodeling toward heart failure. To address such challenges, a novel drug‐releasing microporous annealed particle (drugMAP) system is developed by encapsulating hydrophobic drug‐loaded nanoparticles into microgel building blocks via microfluidic manufacturing. By modulating nanoparticle hydrophilicity and pregel solution viscosity, drugMAP building blocks are generated with consistent and homogeneous encapsulation of nanoparticles. In addition, the complementary effects of forskolin (F) and Repsox (R) on the functional modulations of cardiomyocytes, fibroblasts, and endothelial cells in vitro are demonstrated. After that, both hydrophobic drugs (F and R) are loaded into drugMAP to generate FR/drugMAP for MI therapy in a rat model. The intramyocardial injection of MAP gel improves left ventricular functions, which are further enhanced by FR/drugMAP treatment with increased angiogenesis and reduced fibrosis and inflammatory response. This drugMAP platform represents a new generation of microgel particles for MI therapy and will have broad applications in regenerative medicine and disease therapy. [ABSTRACT FROM AUTHOR]

Background: Serial increases in high-sensitivity cardiac troponin (hs-cTnT) have been associated with death in community-dwelling adults, but the association remains uninvestigated in those with coronary artery disease (CAD). Methods: We measured hs-cTnT at baseline and after 5 years in 635 ambulatory Heart and Soul Study patients with CAD. We also performed echocardiography at rest and after treadmill exercise at baseline and after 5 years. Participants were subsequently followed for the outcome of death. We used a multivariable-adjusted Cox proportional hazards model to evaluate the association between 5-year change in hs-cTnT and subsequent all-cause mortality. Results: Of the 635 subjects, there were 386 participants (61%) who had an increase in hs-cTnT levels between baseline and year 5 measurements (median increase 5.6 pg/mL, IQR 3.2–9.9 pg/mL). There were 182 deaths after a mean 4.2-year follow-up after the year 5 visit. After adjusting for clinical variables, a >50% increase in hs-cTnT between baseline and year 5 was associated with a nearly 2-fold increased risk of death from any cause (hazard ratio 1.7, 95% confidence interval 1.1–2.7). When addition of year 5 hs-cTnT was compared to a model including clinical variables and baseline hs-cTnT, there was a modest but statistically significant increase in C-statistic from 0.82 to 0.83 (p = 0.04). Conclusion: In ambulatory patients with CAD, serial increases in hs-cTnT over time are associated with an increased risk of death. [ABSTRACT FROM AUTHOR]

Repairing cardiac tissue after myocardial infarction (MI) is one of the most challenging goals in tissue engineering. Following ischemic injury, significant matrix remodeling and the formation of avascular scar tissue significantly impairs cell engraftment and survival in the damaged myocardium. This limits the efficacy of cell replacement therapies, demanding strategies that reduce pathological scarring to create a suitable microenvironment for healthy tissue regeneration. Here, we demonstrate the successful fabrication of discrete hyaluronic acid (HA)-based microrods to provide local biochemical and biomechanical signals to reprogram cells and attenuate cardiac fibrosis. HA microrods were produced in a range of physiological stiffness and shown to degrade in the presence of hyaluronidase. Additionally, we show that fibroblasts interact with these microrods in vitro , leading to significant changes in proliferation, collagen expression and other markers of a myofibroblast phenotype. When injected into the myocardium of an adult rat MI model, HA microrods prevented left ventricular wall thinning and improved cardiac function at 6 weeks post infarct. [ABSTRACT FROM AUTHOR]

The cohesive subgraph k-core is a maximal connected subgraph with the minimum degree δ ≥ k of a simple graph, where integer k ≥ 0. Define the core number of a vertex w as the maximum k such that w is contained in a k -core. The core decomposition problem which is calculating the core numbers of all vertices in static graphs, and the core maintenance problem which is updating the core numbers in dynamic graphs are our main concern. Although, core numbers can be updated by the core decomposition algorithms, only a small part of vertices' core numbers have changed after the change of a graph. Thus, it is necessary to update core numbers locally to reduce the cost. In this paper, we study the core maintenance problem on edge-weighted graphs by using the vertex sequence k-order which is ordered by the order that the core decomposition algorithm removes vertices. We design the core maintenance algorithms for inserting one edge at a time and the method of updating the k -order, which reduce the searching range and the time cost evidently. For the removing case, we use the existing subcore algorithm to do the core maintenance and modify it with the method of updating k -order we design. Finally, we do extensive experiments to evaluate the effectiveness and the efficiency of our algorithms, which shows that the order based algorithm has a better performance than the existing for the core maintenance on edge-weighted graphs. • We solve the core maintenance problem on edge-weighted graphs with a tool named weighted k -order. • The weighted k -order, a vertex sequence, is defined on edge-weighted graphs for the first time. • We give the properties of vertices whose core numbers increase on the k-order for inserting case on edge-weighted graphs. • The order based core maintenance algorithm for inserting case on edge-weighted graphs is given, which is the best. • We give the methods to update the k-order after inserting or removing one edge for the next core maintenance. [ABSTRACT FROM AUTHOR]

Background: Little data exist regarding interreader variability of diastolic measurements and their application by the 2016 American Society of Echocardiography left ventricular (LV) diastolic function guidelines. Methods: Volunteers (n = 49) were recruited from an outpatient cardiology practice. The presence and grade of diastology dysfunction (DD) was determined by the 2016 LV diastology guideline algorithm. We determined the mean, standard deviation, coefficient of variation, and intraclass correlation coefficient (ICC) for each measurement and Fleiss K‐statistic to define differences in grading DD. We determined predictors associated with disagreement of DD grade using odds ratios. Results: The mean LVEF was 56%, LAVI 32 ml/m2, and peak TR velocity was 2.3 m/s. The ICC for mitral inflow and tissue Doppler velocities were >.90, for LV volumes were.80–.86, and for LA volume was.56. The Fleiss K‐value for the agreement of the presence of DD was.68 and for DD grade was.59. Variables with increased odds of disagreement were (1) at least one reader considering a TR signal uninterpretable (OR 12.0; 95% CI 1.3–109.6), (2) at least one reader assessing both LVEF 50%–55% and LAVI 29–39 ml/m2 (OR 9.3; 95% CI 1.0–87), and (3) at least one reader assessing LVEF 50–55% (OR 3.8; 95% CI 1.1–13.4). Conclusions: Using the 2016 ASE/EACVI diastology guidelines, we found excellent interrater reliability of Doppler measurements, moderate‐good interrater reliability of volumetric measurements, and moderate‐good but not excellent agreement for diastology grade. [ABSTRACT FROM AUTHOR]

Background: Transient ischemic dilation of the left ventricle (LV) during stress echocardiography indicates extensive myocardial ischemia. It remains unclear whether the change of LV end‐systolic volume (ESV) or end‐diastolic volume (EDV) better correlated with significant coronary artery disease (CAD). Meanwhile, the clinical significance of the extent of the volumetric change post‐stress has not been investigated. Methods: One hundred and five individuals (62 ± 12 years and 75% men) who underwent coronary angiography following exercise treadmill echocardiography were enrolled retrospectively. An additional 30 age‐ and sex‐matched healthy subjects were included for comparison. LV dilation was defined as any increase in LV volume from rest to peak exercise. Patients who had at least two coronary arteries with significant stenosis were considered as having multi‐vessel CAD. Results: Thirty‐four patients had ESV dilation during exercise echocardiography. On the contrary, ESV decreased at peak exercise in all healthy subjects. Forty‐one patients had multi‐vessel CAD, and its prevalence was higher in patients with ESV dilation (65% vs 27%, p = 0.001). The extent of ESV increase correlated with CAD severity. ESV dilation is associated with multi‐vessel CAD (Odds ratio [OR] 5.02, 95% confidence interval [CI] 2.09 – 12.07, p < 0.001). After adjustment for EDV increase, clinical, electrocardiographic, and echocardiographic variables, the association remained significant (adjusted OR 5.57, 95% CI 1.37‐22.64; p = 0.02). Conclusions: ESV dilation independently correlated with multi‐vessel CAD, whereas EDV dilation did not. The amount of ESV increase correlated with the severity of CAD. Our findings provide a rationale for incorporating volume measurements into stress echocardiography practice. [ABSTRACT FROM AUTHOR]

Abstract: The combination of scaffold material and cell transplantation therapy has been extensively investigated in cardiac tissue engineering. However, many polymers are difficult to administer or lack the structural integrity to restore LV function. Additionally, polymers need to be biological friendly, favorably influence the microenvironment and increase stem cell retention and survival. This study determined whether human mesenchymal stem cells (hMSCs) encapsulated in RGD modified alginate microspheres are capable of facilitating myocardial repair. The in vitro study of hMSCs demonstrated that the RGD modified alginate can improve cell attachment, growth and increase angiogenic growth factor expression. Alginate microbeads and hMSCs encapsulated in microbeads successfully maintained LV shape and prevented negative LV remodeling after an MI. Cell survival was significantly increased in the encapsulated hMSC group compared with PBS control or cells alone. Microspheres, hMSCs, and hMSCs in microspheres groups reduced infarct area and enhanced arteriole formation. In summary, surface modification and microencapsulation techniques can be combined with cell transplantation leading to the maintenance of LV geometry, preservation of LV function, increase of angiogenesis and improvement of cell survival. [Copyright &y& Elsevier]

In this work, we consider a public facility allocation problem decided through a voting process under the majority rule. A location of the public facility is a majority rule winner if there is no other location in the network where more than half of the voters would have been closer to than the majority rule winner. We develop fast algorithms for interesting cases with nice combinatorial structures. We show that the computing problem and the decision problem in the general case, where the number of public facilities is more than one and is considered part of the input size, are all NP-hard. Finally, we discuss majority rule decision making for related models. [ABSTRACT FROM AUTHOR]

Abstract: Rank aggregation, originally an important issue in social choice theory, has become more and more important in information retrieval applications over the Internet, such as meta-search, recommendation system, etc. In this work, we consider an aggregation function using a weighted version of the normalized Kendall- distance. We propose a polynomial time approximation scheme, as well as a practical heuristic algorithm with the approximation ratio two for the NP-hard problem. In addition, we discuss issues and models for the dynamic rank aggregation problem. [Copyright &y& Elsevier]

Objectives: In this study, we determined whether fibrin glue improves cell transplant retention and survival, reduces infarct expansion, and induces neovasculature formation.Background: Current efforts in restoring the myocardium after myocardial infarction (MI) include the delivery of viable cells to replace necrotic cardiomyocytes. Cellular transplantation techniques are, however, limited by transplanted cell retention and survival within the ischemic tissue.Methods: The left coronary artery of rats was occluded for 17 min followed by reperfusion. One week later, bovine serum albumin (BSA), fibrin glue, skeletal myoblasts in BSA, or skeletal myoblasts in fibrin glue were injected into the infarcted area of the left ventricle. The animals were euthanized five weeks after injection, and their hearts were excised, fresh frozen, and sectioned for histology and immunohistochemistry.Results: After five weeks, the mean area covered by skeletal myoblasts in fibrin glue was significantly greater than the area covered by myoblasts injected in BSA. Myoblasts within the infarct were often concentrated around arterioles. The infarct scar size and myoblasts in the fibrin group were significantly smaller than those in the control and BSA groups. Fibrin glue also significantly increased the arteriole density in the infarct scar as compared with the control group.Conclusions: This study indicates that fibrin glue increases cell transplant survival, decreases infarct size, and increases blood flow to ischemic myocardium. Therefore, fibrin glue may have potential as a biomaterial scaffold to improve cellular cardiomyoplasty treat and MIs. [Copyright &y& Elsevier]

• We study deterministic mechanism design for k -facility location games with envy ratio. • For the homogeneous setting, the best deterministic strategyproof mechanism is obtained. • For the heterogeneous setting, an optimal and group strategyproof mechanism is devised when k is even. We study deterministic mechanism design without money for k -facility location games with envy ratio on a real line segment, where a set of strategic agents report their locations and a social planner locates k facilities for minimizing the envy ratio. The objective of envy ratio, which is defined as the maximum over the ratios between any two agents' utilities, is derived from fair division to measure the fairness with respect to a certain facility location profile. The problem is studied in two settings. In the homogeneous k -facility location game where k facilities serve the same purpose, we propose a 2 k 2 k − 1 -approximate deterministic group strategyproof mechanism which is also the best deterministic strategyproof mechanism. In the heterogeneous k -facility location game where each facility serves a different purpose, when k is even, we devise an optimal and group strategyproof mechanism; when k is odd, we provide a k + 1 k − 1 -approximate deterministic group strategyproof mechanism. [ABSTRACT FROM AUTHOR]

Generic submodularity ratio γ is a general measurement to characterize how close a nonnegative monotone set function is to be submodular. In this paper, we make a systematic analysis of greedy algorithms for maximizing a monotone and normalized set function with a generic submodularity ratio γ under Cardinality constraints, Knapsack constraints, Matroid constraints and K -intersection constraints. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac adaptation to sustained exercise in the athletes is established. However, exercise‐associated effect on the cardiac function of the elderly has to be elucidated. The aim of this study was to analyse left (LV) and right ventricular (RV) characteristics at different levels of chronic exercise in the senior heart. Materials and methods: We studied 178 participants in the World Senior Games (mean age 68 ± 8 years, 86 were men; 48%). Three groups were defined based on the type and intensity of sports: low‐, moderate‐ and high‐intensity level. Exclusion criteria were coronary artery disease, atrial fibrillation, valvular heart disease or uncontrolled hypertension. LV and RV size and function were evaluated with an echocardiogram. Results: LV trans‐mitral inflow deceleration time decreased in parallel to the intensity of chronic exercise: 242 ± 54 ms in low‐, 221 ± 52 ms in moderate‐ and 215 ± 58 ms in high‐intensity level, p =.03. Left atrial volume index (LAVI) was larger in high‐intensity group, p =.001. The LAVI remained significantly larger when adjusting for age, gender, heart rate, hypertension and diabetes (p =.002). LV and RV sizes were larger in the high‐intensity group. LV ejection fraction and RV systolic function evaluated by tissue Doppler velocity, atrioventricular plane displacement and strain did not differ between groups. Conclusion: Left ventricular diastolic filling is not only preserved, but may also be enhanced in long‐term, top‐level senior athletes. Moreover, LV and RV systolic function remain unchanged at different levels of exercise. This supports the beneficial effects of endurance exercise participation in senior hearts. [ABSTRACT FROM AUTHOR]

Given a social network G and a positive integer k , the influence maximization problem seeks for k nodes in G that can influence the largest number of nodes. This problem has found important applications, and a large amount of works have been devoted to identifying the few most influential users. But most of existing works only focus on the diffusion of a single idea or product in social networks. However, in reality, one company may produce multiple kinds of products and one user may also have multiple adoptions. For multiple kinds of different products with different activation costs and profits, it is crucial for the company to distribute the limited budget among multiple products in order to achieve profit maximization. The Profit Maximization with Multiple Adoptions (PM2A) problem aims to seek for a seed set within the budget to maximize the overall profit. In this paper, a Randomized Modified Greedy (RMG) algorithm based on the Reverse Influence Sampling (RIS) technique is presented for the PM2A problem, which could achieve a (1 − 1 / e − ε) -approximate solution with high probability and is also the best performance ratio of the PM2A problem. Comprehensive experiments on three real-world social networks are conducted, and the results demonstrate that our RMG algorithm outperforms the algorithm proposed in [16] and other heuristics in terms of profit maximization, and could better allocate the budget. [ABSTRACT FROM AUTHOR]

Viral marketing has become one of the most effective marketing strategies. In the process of real commercialization, in order to let some seed individuals know the products, companies can provide free samples to them. However, for some companies, especially famous ones, they are more willing to offer coupons than give samples. In this paper, we consider the Profit Maximization problem with Coupons (PM-C) in our new diffusion model named the Independent Cascade Model with Coupons and Valuations (IC-CV). To solve this problem, we propose the PMCA algorithm which can return a (1 3 − ε) -approximate solution with at least 1 − 2 n − l probability, and runs in O (log ⁡ (n p) ⋅ m n 3 log ⁡ n (l log ⁡ n + n log ⁡ 2) / ε 3) expected time. Furthermore, during the analysis we provide a method to estimate the non-monotone submodular function. [ABSTRACT FROM AUTHOR]

Introduction: Although systolic and diastolic dysfunction must coexist, they are most often considered in isolation. Therefore, a simple and reproducible quantitative measurement that integrates systolic and diastolic function is desirable. We hypothesize that the absolute sum of lateral mitral annular systolic and early diastolic peak velocities is predictive of overall cardiac function. Methods: In this study, lateral mitral annular systolic (S′) and early diastolic (E′) peak velocities were measured in healthy subjects and compared against subjects with progressive degrees of systolic and diastolic dysfunction. Results: A total of 149 subjects (56% male, mean age 48 years) were enrolled and stratified according to global left ventricular function: 76 normal, 40 mild‐moderate dysfunction, and 33 moderate‐severe dysfunction. Adjusting for baseline differences including age, univariate analysis showed mean S′ + E′ values were significantly different between subjects with normal, mild‐moderate, and moderate‐severe global left ventricular function (27, 17, 13 cm/s; P < 0.001 for all comparisons). The absolute sum of S′ + E′ ≥ 20 cm/s identified normal global left ventricular function with a sensitivity of 95%, specificity of 85%, and ROC area under the curve of 0.924. Conclusions: In a cohort of subjects with varying levels of combined systolic and diastolic function, the easily obtainable composite score of S′ + E′ ≥ 20 cm/s is strongly predictive of normal global left ventricular function with a high degree of sensitivity and specificity. Additional studies should be considered to expand this concept to additional populations. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of cardiomyopathy associated with premature ventricular contractions (PVCs) remains unclear.Objectives: This study prospectively explored cardiomyopathy development in a swine model of paced ectopic beats.Methods: A total of 35 swine underwent pacemaker implantation. A group exposed to paced bigeminy from the right ventricular apex (RVA) for 14 weeks (RVA PVC) (n = 10) were compared with a group exposed to regular pacing from the RVA at 140 beats/min (RV-140) (n = 5) and a control group (n = 5). To test the role of ectopic beat dyssynchrony, further groups were exposed for 12 weeks to bigeminy from the right ventricular free wall (RVFW PVC) (n = 5), the left ventricular epicardium (LV Epi PVC) (n = 5) or the right atrium (premature atrial complex) (n = 5).Results: After 14 weeks, the mean left ventricular ejection fraction (LVEF) was significantly lower in the RVA PVC group than in the RV-140 or control groups (p < 0.05). LVEF declined significantly in the LV Epi PVC (65.2 ± 2.4% to 39.7 ± 3.0%; p < 0.01) and RVFW PVC (66.1 ± 2.6% to 48.6 ± 2.7%; p < 0.01) groups, with final LVEF significantly lower and ventricular fibrosis significantly higher in the LV Epi PVC group compared with all others (p < 0.05). Protein levels of pRyR2, NCX-1, CaMKII-α, and PLN were up-regulated and levels of SERCA2a were down-regulated in the LV Epi PVC group compared with the control group (p < 0.05). Longer ectopic beat QRS duration and greater LV dyssynchrony were significantly associated with larger declines in LV systolic function.Conclusions: In a swine model of paced ectopic beats, PVC-induced cardiomyopathy is phenotypically distinct from a tachycardia-induced cardiomyopathy. Cardiomyopathy severity is strongly associated with severity of the hemodynamic derangement associated with the paced ectopic beats, particularly the extent of LV dyssynchrony. [ABSTRACT FROM AUTHOR]

We study the competitive profit maximization problem in a social network, which can be viewed as the profit maximization problem in a game-theoretic setting. We formulate two models called the profit maximization-agent (PM-A) game and the profit maximization-society (PM-S) game. By reducing them to be valid utility systems, we show that any Nash equilibrium provides an excepted social utility within a factor 1/2 (subject to a function-dependent additive term) of the optimum in the PM-A game and a factor of 1/2 of the optimum in the PM-S game. Furthermore, for the PM-S game, a polynomial-time algorithm is given for each player that can approximate the best response within a factor ( 1 − 1 / e ) . [ABSTRACT FROM AUTHOR]

To further define the age‐related distribution of diastolic function as defined by E/A ratio, in healthy male adults. The age‐sensitive ratio of mitral inflow E‐wave to A‐wave (E/A) velocity is often considered in the evaluation of diastolic function. To appropriately direct a comprehensive evaluation of diastolic function, we sought to improve the characterization of the influence of age on E/A ratio. We analyzed echocardiographic data from the Mind Your heart Study, a cohort of outpatients recruited from two San Francisco Veterans centers to examine the effect of mental health on cardiovascular outcomes. Individuals with a history of heart disease or hypertension were excluded, leaving 313 veterans for analysis. We examined E/A by 5‐year increments and performed linear and logistic regression analysis to predict trends in E/A and E dominance. Within the age ranges of population (54.9 ± 11.5), there is a steady gradual decline in absolute E/A ratio (beta coefficient/year‐ 0.018, P < .001) and the odds of E dominance similarly declines with age (odds ratio/year = 0.89, P < .001). Despite this decline, 90% of individuals below the age of 50 years maintain E dominance. Beyond age 50, 55% maintain E dominance, and beyond age 70, only 28% have E dominance. In this adequately healthy population, age‐related progression of delayed relaxation appears to be a state of normality rather than diastolic dysfunction. Careful attention to specific cutoff points in age and E/A ratio could avoid misinterpretation or inappropriate management. [ABSTRACT FROM AUTHOR]

Background Aging is associated with higher incidence of heart failure and death following myocardial infarction ( MI). The molecular and cellular changes that lead to these worse outcomes are not known. Methods and Results Young and aging mice underwent induction of MI by LAD ligation. There was a significant increase in mortality in the aging mice. Neither the young nor aging hearts after MI had inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after MI in young and aging mice, but to a much greater degree in the aging mice. Caspase inhibition with Ac- DEVD- CHO resulted in a 61% reduction in activated caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice ( P < 0.05), but not in aging mice. Gene pathway profiling demonstrated activation of both the caspase and Map3k1/ Mapk10 pathways in aging mice following MI, which may contribute to their resistance to caspase inhibition. Conclusions Aging hearts activate distinct apoptotic pathways have more cardiomyocyte apoptosis and are resistant to antiapoptotic therapies following MI. Novel or combination approaches may be required to improve outcomes in aging patients following MI. [ABSTRACT FROM AUTHOR]

Abstract: Myocardial infarction is the main contributor to heart failure. In this study we examined whether modification of a thermo-reversible cellulose-based polymer with extracellular-matrix derived functional groups could promote wound healing and improve cardiac function in a chronic rodent model of ischemic cardiomyopathy. To beneficially influence the microenvironment of the injured myocardium, we conjugated either the RGD peptide or the HepIII peptide to the polymer. In vitro cell adhesion studies showed that the peptide-modified polymer promoted cell attachment to the polymer surface. Injection of the thermo-reversible polymer into the aneurismal infarct region of the left ventricle showed that the peptide-modified polymer exhibited significantly improved left ventricular function, increased angiogenesis, decreased infarct size, and an increase in cardiomyocytes within the infarct region at 5 weeks post-treatment (P < 0.05). The results of this study demonstrate that a peptide-modified thermo-reversible polymer has the capability to alter left ventricular (LV) geometry, increase LV function, and promote myocardial regeneration in a chronic model of ischemic cardiomyopathy. [Copyright &y& Elsevier]

Purpose: Semi-quantitative, static positron emission tomography (PET) has been used to perform an initial approach to the assessment of [13N]-ammonia perfusion studies aimed to elucidating the effect of injecting human embryonic stem cell-derived (hES) hemangioblasts on infarcted rat hearts. Procedures: Female NIH nude rats underwent occlusion of the left anterior descending coronary artery for 30 min before reperfusion. Either one million hES-derived hemangioblasts ( n = 5) or control media ( n = 4) were injected into the site of the infarct 1 day post-myocardial infarction (MI) under high-resolution echocardiography guidance. PET imaging was performed 6 weeks after MI induction, and uptake polar maps were created by sampling the left ventricle at equidistant slices from the base to the apex and measuring the average myocardium value at three contiguous voxels to minimize partial volume effects. Statistical comparison between treatment and control groups was done with a Mann-Whitney U test. Results: Myocardium uptake ratios for treated and untreated subjects show statistically significant difference (98% certainty). Conclusions: The straightforward procedure described here (similar to those commonly used in clinical routine) was sufficient to yield statistically significant perfusion differences between the treated and untreated animals despite the small sample size. [ABSTRACT FROM AUTHOR]

• Left atrial mass has not been defined. • Normal left atrial mass using anatomic specimens was defined. • A simple echocardiographic measurement correlated well with anatomic measurement. Left atrial (LA) enlargement is associated with increased risk of adverse cardiovascular outcomes. Unlike the left ventricular mass, LA mass has not been described. We sought to define the anatomic mass of the LA using anatomic specimens from autopsy. We hypothesized that LA mass could be estimated by echocardiography. Using anatomic specimens of 22 subjects who died and underwent post mortem examination as well as echocardiogram, we defined normal LA mass by weighing anatomic specimens of those with normal LA volume on echocardiogram. Using 17 subjects with normal LA volume on echocardiogram, we found their LA mass on anatomic specimens to be 25.5 ± 6.3 grams (14.4 ± 3.2 g/m2). We developed an echocardiographic measure of LA mass and validated this measurement with paired LA anatomic specimens. We found the normal LA mass on echocardiogram to be 25.4 ± 6.3 g (14.4 ± 2.8 g/m2) which correlated well with anatomic specimens (β = 0.99; Confidence interval CI 0.6–1.4, P <.0001; Pearson correlation coefficient r = 0.83). Furthermore, we defined the normal LA volume to mass ratio as 1.38 ± 0.45. LA mass is an additional parameter with which may contribute to the study of LA morphology. [ABSTRACT FROM AUTHOR]

Introduction: Serial increases in high-sensitivity cardiac troponin (hs-cTnT) have been associated with death in community-dwelling adults, but the association remains uninvestigated in those with ambulatory coronary artery disease (CAD). Hypothesis: An increase in hs-cTnT over 5 years predicts subsequent all-cause mortality in ambulatory CAD. Methods: We measured hs-cTnT at baseline and after 5 years in 635 participants with ambulatory CAD. We defined "undetectable" levels of hs-cTnT as < 5 pg/mL, "detectable" as between 5 and 14 pg/mL, and "elevated" as >14 pg/mL. We used an unadjusted and a multivariable-adjusted Cox proportional hazards model to evaluate the association between 5-year change in hs-cTnT and subsequent all-cause mortality. Results: There were 386 participants (61%) who had an increase in hs-cTnT levels between baseline and year 5 measurements (median increase 5.6 pg/mL, IQR 3.2-9.9 pg/mL). There were 182 deaths after a mean 4.2 years of follow-up after year 5. After adjusting for clinical variables, a > 50% increase in hs-cTnT between baseline and year 5 was associated with a nearly 2-fold increased risk of death from any cause (HR 1.7, 95% CI 1.1-2.7). Additional hazard ratios for death from any cause, categorized by levels of baseline and year 5 hs-cTnT, are displayed in the figure. Conclusion: In ambulatory CAD, serial increases in hs-cTnT predict death, suggesting that preventive strategies may be warranted in this setting. Figure: Hazard ratios for death from any cause, categorized by levels of baseline and year 5 high-sensitivity cardiac troponin (hs-cTnT), adjusted for clinical variables. Error bars represent 95% confidence intervals. Data for patients who had detectable baseline but undetectable year 5 levels, as well as patients with elevated baseline but undetectable year 5 levels are not displayed due to small numbers of deaths in these categories. [ABSTRACT FROM AUTHOR]

Introduction: C-reactive protein (CRP) level stratifies risk for events in coronary heart disease (CHD) and is independently associated with increased risk of heart failure (HF). It is unknown how CHD-associated risk of stroke, HF, and all-cause mortality is affected by CRP and if it is modifiable. Hypothesis: The risk associated with elevated CRP in patients with CHD can be modified by beta blocker and statin use. Methods: A cohort of outpatients with CHD from the Heart and Soul Study (N = 985) had serum CRP measured. Outcomes after 7.1 years ± 3.2 years including non-fatal MI, HF, stroke, cardiovascular death, and all-cause mortality were analyzed and modifying factors were compared using Kaplan Meier estimates. Results: Elevated CRP level > 3mg/L (CRPH) was associated with an increased risk of stroke (hazard ratio (HR) 2.4, p = 0.01), HF (HR 1.9, p = 0.001), and all-cause mortality (HR 1.4, p = 0.005), compared to low CRP level < 3mg/L (CRPL). CRPH patients not taking a statin had more HF events (HR 2.9, p = 0.001) and increased risk of all-cause mortality (HR 1.5, p = 0.045) compared to CRPL patients not taking a statin. CRPH patients not taking a beta blocker had more HF events (HR 2.5, p = 0.001) and increased risk of all-cause mortality (HR 1.7, p = 0.003) compared to CRPL patients not taking a beta-blocker. CRPH patients on neither beta blocker nor statin had more HF events (HR 2.7, p = 0.002) and increased risk of all-cause mortality (HR 2.0, p = 0.004) compared to CRPH patients on both medications. CRPL patients on both beta blocker and statin had reduced risk of all-cause mortality (HR 0.6, p = 0.04) compared to CRPL patients on neither medication. Conclusions: Among outpatients with CHD, CRPH is associated with an increased risk of adverse CHD outcomes including stroke, HF, and all-cause mortality. The risk of HF and all-cause mortality is considerable but modified by beta blockers and statins. Among those with CRPL, the use of beta blockers and statin reduces risk of all-cause mortality. [ABSTRACT FROM AUTHOR]