Lipoxin agonists: turn right! to path of resolving neutrophil

An impressive array of cellular and molecular adaptive responses achieves homeostasis. The inflammatory reaction is an adaptive response triggered by an insult to culminate into the overt cardinal signs of inflammation, eventually leading to resolution and returning the organism back to its original centered state. This article focuses on some aspects of the lipoxin A4 signaling pathway during the resolution phase, to better understand molecular mechanisms by which a neutrophil directs an inflammatory reaction to switch off and resume homeostasis. Defining the resolution state of a neutrophil at the molecular level will aid in treatments of diseases that are associated with an exaggerated and uncontrolled inflammation.

Assessment of left coronary artery beat-to-beat repositioning in order to propose an optimal acquisition window for coronary MRA

Introduction: Coronary magnetic resonance angiography (MRA) is a medical imaging technique that involves collecting data from consecutive heartbeats, always at the same time in the cardiac cycle, in order to minimize heart motion artifacts. This technique relies on the assumption that coronary arteries always follow the same trajectory from heartbeat to heartbeat. Until now, choosing the acquisition window in the cardiac cycle was based exclusively on the position of minimal coronary motion. The goal of this study was to test the hypothesis that there are time intervals during the cardiac cycle when coronary beat-to-beat repositioning is optimal. The repositioning uncertainty values in these time intervals were then compared with the intervals of low coronary motion in order to propose an optimal acquisition window for coronary MRA. Methods: Cine breath-hold x-ray angiograms with synchronous ECG were collected from 11 patients who underwent elective routine diagnostic coronarography. Twenty-three bifurcations of the left coronary artery were selected as markers to evaluate repositioning uncertainty and velocity during cardiac cycle. Each bifurcation was tracked by two observers, with the help of a user-assisted algorithm implemented in Matlab (The Mathworks, Natick, MA, USA) that compared the trajectories of the markers coming from consecutive heartbeats and computed the coronary repositioning uncertainty with steps of 50ms until 650ms after the R-wave. Repositioning uncertainty was defined as the diameter of the smallest circle encompassing the points to be compared at the same time after the R-wave. Student's t-tests with a false discovery rate (FDR, q=0.1) correction for multiple comparison were applied to see whether coronary repositioning and velocity vary statistically during cardiac cycle. Bland-Altman plots and linear regression were used to assess intra- and inter-observer agreement. Results: The analysis of left coronary artery beat-to-beat repositioning uncertainty shows a tendency to have better repositioning in mid systole (less than 0.84±0.58mm) and mid diastole (less than 0.89±0.6mm) than in the rest of the cardiac cycle (highest value at 50ms=1.35±0.64mm). According to Student's t-tests with FDR correction for multiple comparison (q=0.1), two intervals, in mid systole (150-200ms) and mid diastole (550-600ms), provide statistically better repositioning in comparison with the early systole and the early diastole. Coronary velocity analysis reveals that left coronary artery moves more slowly in end systole (14.35±11.35mm/s at 225ms) and mid diastole (11.78±11.62mm/s at 625ms) than in the rest of the cardiac cycle (highest value at 25ms: 55.96±22.34mm/s). This was confirmed by Student's t-tests with FDR correction for multiple comparison (q=0.1, FDR-corrected p-value=0.054): coronary velocity values at 225, 575 and 625ms are not much different between them but they are statistically inferior to all others. Bland-Altman plots and linear regression show that intra-observer agreement (y=0.97x+0.02 with R²=0.93 at 150ms) is better than inter-observer (y=0.8x+0.11 with R²=0.67 at 150ms). Discussion: The present study has demonstrated that there are two time intervals in the cardiac cycle, one in mid systole and one in mid diastole, where left coronary artery repositioning uncertainty reaches points of local minima. It has also been calculated that the velocity is the lowest in end systole and mid diastole. Since systole is less influenced by heart rate variability than diastole, it was finally proposed to test an acquisition window between 150 and 200ms after the R-wave.

Brain network analysis of patients with Temporal Lobe Epilepsy

Patients with Temporal Lobe Epilepsy (TLE) suffer from widespread subtle white matter abnormalities and abnormal functional connectivity extending beyond the affected lobe, as revealed by Diffusion Tensor MR Imaging, volumetric and functional MRI studies. Diffusion Spectrum Imaging (DSI) is a diffusion imaging technique with high angular resolution for improving the mapping of white matter pathways. In this study, we used DSI, connectivity matrices and topological measures to investigate how the alteration in structural connectivity influences whole brain structural networks. Eleven patients with right-sided TLE and hippocampal sclerosis and 18 controls underwent our DSI protocol at 3T. The cortical and subcortical grey matters were parcellated into 86 regions of interest and the connectivity between every region pair was estimated using global tractography and a connectivity matrix (the adjacency matrix of the structural network). We then compared the networks of patients and controls using topological measures. In patients, we found a higher characteristic path length and a lower clustering coefficient compared to controls. Local measures at node level of the clustering and efficiency showed a significant difference after a multiple comparison correction (Bonferroni). These significant nodes were located within as well outside the temporal lobe, and the localisation of most of them was consistent with regions known to be part of epileptic networks in TLE. Our results show altered connectivity patterns that are concordant with the mapping of functional epileptic networks in patients with TLE. Further studies are needed to establish the relevance of these findings for the propagation of epileptic activity, cognitive deficits in medial TLE and outcome of epilepsy surgery in individual patients.

Effects of brood manipulation costs on optimal sex allocation in social hymenoptera.

In eusocial Hymenoptera, queens and workers are in conflict over optimal sex allocation. Sex ratio theory, while generating predictions on the extent of this conflict under a wide range of conditions, has largely neglected the fact that worker control of investment almost certainly requires the manipulation of brood sex ratio. This manipulation is likely to incur costs, for example, if workers eliminate male larvae or rear more females as sexuals rather than workers. In this article, we present a model of sex ratio evolution under worker control that incorporates costs of brood manipulation. We assume cost to be a continuous, increasing function of the magnitude of sex ratio manipulation. We demonstrate that costs counterselect sex ratio biasing, which leads to less female-biased population sex ratios than expected on the basis of relatedness asymmetry. Furthermore, differently shaped cost functions lead to different equilibria of manipulation at the colony level. While linear and accelerating cost functions generate monomorphic equilibria, decelerating costs lead to a process of evolutionary branching and hence split sex ratios.

Automatic self-configuration of the logical network using distributed software agents

We present a system for dynamic network resource configuration in environments with bandwidth reservation. The proposed system is completely distributed and automates the mechanisms for adapting the logical network to the offered load. The system is able to manage dynamically a logical network such as a virtual path network in ATM or a label switched path network in MPLS or GMPLS. The system design and implementation is based on a multi-agent system (MAS) which make the decisions of when and how to change a logical path. Despite the lack of a centralised global network view, results show that MAS manages the network resources effectively, reducing the connection blocking probability and, therefore, achieving better utilisation of network resources. We also include details of its architecture and implementation

An ATM distributed simulator for network management research

Due to the high cost of a large ATM network working up to full strength to apply our ideas about network management, i.e., dynamic virtual path (VP) management and fault restoration, we developed a distributed simulation platform for performing our experiments. This platform also had to be capable of other sorts of tests, such as connection admission control (CAC) algorithms, routing algorithms, and accounting and charging methods. The platform was posed as a very simple, event-oriented and scalable simulation. The main goal was the simulation of a working ATM backbone network with a potentially large number of nodes (hundreds). As research into control algorithms and low-level, or rather cell-level methods, was beyond the scope of this study, the simulation took place at a connection level, i.e., there was no real traffic of cells. The simulated network behaved like a real network accepting and rejecting SNMP ones, or experimental tools using the API node

Availability analysis of GMPLS connections based on physical network topology

This paper presents a study of connection availability in GMPLS over optical transport networks (OTN) taking into account different network topologies. Two basic path protection schemes are considered and compared with the no protection case. The selected topologies are heterogeneous in geographic coverage, network diameter, link lengths, and average node degree. Connection availability is also computed considering the reliability data of physical components and a well-known network availability model. Results show several correspondences between suitable path protection algorithms and several network topology characteristics

Dynamic bandwidth management as part of an integrated network management system based on distributed agents

We present a system for dynamic network resource configuration in environments with bandwidth reservation and path restoration mechanisms. Our focus is on the dynamic bandwidth management results, although the main goal of the system is the integration of the different mechanisms that manage the reserved paths (bandwidth, restoration, and spare capacity planning). The objective is to avoid conflicts between these mechanisms. The system is able to dynamically manage a logical network such as a virtual path network in ATM or a label switch path network in MPLS. This system has been designed to be modular in the sense that in can be activated or deactivated, and it can be applied only in a sub-network. The system design and implementation is based on a multi-agent system (MAS). We also included details of its architecture and implementation

The long and painful path towards arthroplasty: A qualitative study

Hip or knee arthroplasty is proposed after osteoarthritis or an accident. It is decided after a long path of pain and decrease in the quality of life. This research explores the period of illness until surgery. Twenty-four semi-structured interviews were conducted one month before surgery and a thematic discourse analysis performed. The diversity and complexity of the patient experience, in a commonly performed surgical intervention underlines important topics, requiring attention in order to improve patient preparations and information prior to arthroplasty: information adapted to individual concerns, needs and representations. Psychological and physical acceptance is necessary for integration of the prosthesis.

Stochastic optimal bid to electricity markets with environmental risk constraints

There are many factors that influence the day-ahead market bidding strategies of a generation company (GenCo) in the current energy market framework. Environmental policy issues have become more and more important for fossil-fuelled power plants and they have to be considered in their management, giving rise to emission limitations. This work allows to investigate the influence of both the allowances and emission reduction plan, and the incorporation of the derivatives medium-term commitments in the optimal generation bidding strategy to the day-ahead electricity market. Two different technologies have been considered: the coal thermal units, high-emission technology, and the combined cycle gas turbine units, low-emission technology. The Iberian Electricity Market and the Spanish National Emissions and Allocation Plans are the framework to deal with the environmental issues in the day-ahead market bidding strategies. To address emission limitations, some of the standard risk management methodologies developed for financial markets, such as Value-at-Risk (VaR) and Conditional Value-at-Risk (CVaR), have been extended. This study offers to electricity generation utilities a mathematical model to determinate the individual optimal generation bid to the wholesale electricity market, for each one of their generation units that maximizes the long-run profits of the utility abiding by the Iberian Electricity Market rules, the environmental restrictions set by the EU Emission Trading Scheme, as well as the restrictions set by the Spanish National Emissions Reduction Plan. The economic implications for a GenCo of including the environmental restrictions of these National Plans are analyzed and the most remarkable results will be presented.

Lack of correlation between the optimal glycaemic control and coronary micro vascular dysfunction in patients with diabetes mellitus: a cross sectional study.

Background Coronary microvascular dysfunction (CMD) is associated with cardiovascular events in type 2 diabetes mellitus (T2DM). Optimal glycaemic control does not always preclude future events. We sought to assess the effect of the current target of HBA1c level on the coronary microcirculatory function and identify predictive factors for CMD in T2DM patients. Methods We studied 100 patients with T2DM and 214 patients without T2DM. All of them with a history of chest pain, non-obstructive angiograms and a direct assessment of coronary blood flow increase in response to adenosine and acetylcholine coronary infusion, for evaluation of endothelial independent and dependent CMD. Patients with T2DM were categorized as having optimal (HbA1c < 7 %) vs. suboptimal (HbA1c ≥ 7 %) glycaemic control at the time of catheterization. Results Baseline characteristics and coronary endothelial function parameters differed significantly between T2DM patients and control group. The prevalence of endothelial independent CMD (29.8 vs. 39.6 %, p = 0.40) and dependent CMD (61.7 vs. 62.2 %, p = 1.00) were similar in patients with optimal vs. suboptimal glycaemic control. Age (OR 1.10; CI 95 % 1.04–1.18; p < 0.001) and female gender (OR 3.87; CI 95 % 1.45–11.4; p < 0.01) were significantly associated with endothelial independent CMD whereas glomerular filtrate (OR 0.97; CI 95 % 0.95–0.99; p < 0.05) was significantly associated with endothelial dependent CMD. The optimal glycaemic control was not associated with endothelial independent (OR 0.60, CI 95 % 0.23–1.46; p 0.26) or dependent CMD (OR 0.99, CI 95 % 0.43–2.24; p = 0.98). Conclusions The current target of HBA1c level does not predict a better coronary microcirculatory function in T2DM patients. The appropriate strategy for prevention of CMD in T2DM patients remains to be addressed. Keywords: Endothelial dysfunction; Diabetes mellitus; Coronary microcirculation

On optimal learning schedules and the marginal value of cumulative cultural evolution.

The age-dependent choice between expressing individual learning (IL) or social learning (SL) affects cumulative cultural evolution. A learning schedule in which SL precedes IL is supportive of cumulative culture because the amount of nongenetically encoded adaptive information acquired by previous generations can be absorbed by an individual and augmented. Devoting time and energy to learning, however, reduces the resources available for other life-history components. Learning schedules and life history thus coevolve. Here, we analyze a model where individuals may have up to three distinct life stages: "infants" using IL or oblique SL, "juveniles" implementing IL or horizontal SL, and adults obtaining material resources with learned information. We study the dynamic allocation of IL and SL within life stages and how this coevolves with the length of the learning stages. Although no learning may be evolutionary stable, we find conditions where cumulative cultural evolution can be selected for. In that case, the evolutionary stable learning schedule causes individuals to use oblique SL during infancy and a mixture between IL and horizontal SL when juvenile. We also find that the selected pattern of oblique SL increases the amount of information in the population, but horizontal SL does not do so.