Static platelet adhesion, flow cytometry and serum TXB2 levels for monitoring platelet inhibiting treatment with ASA and clopidogrel in coronary artery disease: a randomised cross-over study

<p>Abstract</p> <p>Background</p> <p>Despite the use of anti-platelet agents such as acetylsalicylic acid (ASA) and clopidogrel in coronary heart disease, some patients continue to suffer from atherothrombosis. This has stimulated development of platelet function assays to monitor treatment effects. However, it is still not recommended to change treatment based on results from platelet function assays. This study aimed to evaluate the capacity of a static platelet adhesion assay to detect platelet inhibiting effects of ASA and clopidogrel. The adhesion assay measures several aspects of platelet adhesion simultaneously, which increases the probability of finding conditions sensitive for anti-platelet treatment.</p> <p>Methods</p> <p>With a randomised cross-over design we evaluated the anti-platelet effects of ASA combined with clopidogrel as well as monotherapy with either drug alone in 29 patients with a recent acute coronary syndrome. Also, 29 matched healthy controls were included to evaluate intra-individual variability over time. Platelet function was measured by flow cytometry, serum thromboxane B₂(TXB₂)-levels and by static platelet adhesion to different protein surfaces. The results were subjected to Principal Component Analysis followed by ANOVA, t-tests and linear regression analysis.</p> <p>Results</p> <p>The majority of platelet adhesion measures were reproducible in controls over time denoting that the assay can monitor platelet activity. Adenosine 5'-diphosphate (ADP)-induced platelet adhesion decreased significantly upon treatment with clopidogrel compared to ASA. Flow cytometric measurements showed the same pattern (r²= 0.49). In opposite, TXB₂-levels decreased with ASA compared to clopidogrel. Serum TXB₂and ADP-induced platelet activation could both be regarded as direct measures of the pharmacodynamic effects of ASA and clopidogrel respectively. Indirect pharmacodynamic measures such as adhesion to albumin induced by various soluble activators as well as SFLLRN-induced activation measured by flow cytometry were lower for clopidogrel compared to ASA. Furthermore, adhesion to collagen was lower for ASA and clopidogrel combined compared with either drug alone.</p> <p>Conclusion</p> <p>The indirect pharmacodynamic measures of the effects of ASA and clopidogrel might be used together with ADP-induced activation and serum TXB₂for evaluation of anti-platelet treatment. This should be further evaluated in future clinical studies where screening opportunities with the adhesion assay will be optimised towards increased sensitivity to anti-platelet treatment.</p

Aerodynamic Loss and Mixing Over a Cavity Flame Holder Located Downstream of Pylon-Aided Fuel Injection

Cavity-based fuel injection and flame holding found in hydrocarbon-fueled scramjet applications are of interest. The Air Force Research Lab (AFRL) and the Air Force Institute of Technology (AFIT) at Wright-Patterson Air Force Base in Ohio are investigating the enhancement of fuel-air mixing with small pylons that project into the supersonic flow upstream of a flame holder cavity. This follows previous qualitative (Mie scattering and NO-PLIF visualizations) results which suggested that injection behind pylons, may improve fuel-air mixing. Three pylons geometries (medium, tall, and wide) shaped as thin triangular wedges with a 30o inclination angle were tested and compared to baseline transverse injection without pylons at two injection pressures. The AFRL provided facility, was a supersonic (Mach 2) continuous flow wind tunnel with existing cavity and pylon setup. The goal was to measure mixing efficiency and shock loss of each pylon setup for comparison to the baseline condition of transverse injection without pylons. Non-reacting flow was measured using conventional probing and spontaneous Raman spectroscopy to obtain pitot pressure, total temperature, cone-static pressure and species concentration over the cavity downstream of the injection. Results demonstrated that pylons increase fuel penetration, while not adding significantly to shock losses or overall mixing compared to baseline

Towards a unified execution model for transactions in TLM

Even though Transaction Level Modeling(TLM) with SystemC is widely being used and despite the existence of several formal models for TLM, there is no generally accepted definition of what a transaction is and how exactly to define Transaction Level Modeling. The key contribution of this paper is the analysis of TLM characteristics and a definition of transactions resulting in better analyzability of TLMs. For this purpose, transactions are restricted to the ACID properties (atomicity, consistency, isolation, and durability) known from database systems. Based on these results, a finite state machine model well suited for formal analysis will be proposed along with an implementation of the basic concepts in SystemC

Actor-oriented modeling and simulation of sliding window image processing algorithms

Embedded real-time image processing systems have to process huge amounts of data with limited resources and energy. Hence high efficiency is not only required for manual, but also for automatic system generation. Therefore, in order to allow for different optimizations, a system specification must be such that important algorithm properties are accessible to the system design software. In this paper, we present a new method how multidimensional image processing algorithms can be modeled by actor-oriented dataflow semantics. Using the example of a binary morphological reconstruction, we investigate the modeling requirements posed by point, local and global image processing algorithms. We show how they can be taken into account in our approach, so that efficient implementation and analysis in terms of buffer size and throughput is possible. In particular, by the explicit specification of the communication behavior, both static and data dependent algorithms are supported allowing for a complete system specification

Swimming Performance of the Threatened Leopard Darter in Relation to Road Culverts

We investigated the relationship between swinming performance of the leopard darterPercinn pantherina evaluated in the laboratory and current velocities measured at the ends ofcorrugated-pipe and open-box culverts through road crossings. We tested leopard darters at eachof six current velocities ranging from 0 to 60 cmls and measured burst frequency and distance.We uscd analysis of variance (ANOVA) to analyze burst frequency and total distance coveredduring a 10-min period and found that at a current velocity of 25 cids, fish swam more frequentlyand for greater total distances than at higher or lower velocitics. When a nested ANOVA was usedto remove variation duc to individual fish, we found that distancesof individual bursts also differedsignificanlly and that fish in intermediate velocilies had longer bursts. Current velocitics in boxand pipe culverts tcnded to be higher than the velocitics measured in the lab, and sevcral crossingshad structural barriers, in addition to high current velocitics. Although there is no evidence thatculverts act as long-term barriers to n~igration or dispersal of leopard darters, they may preventmigratory activity during certain years, thereby negatively affecting localized populations

HIERARCHICAL SYNTHESIS OF EMBEDDED SYSTEMS USING EVOLUTIONARY ALGORITHMS -- A Multi-Objective Approach

In this chapter, we propose an approach for the synthesis of heterogenous embedded systems, including allocation and binding problems. For solving these in general NP-complete problems, Evolutionary Algorithms have been proven to provide good solutions for search spaces of moderate size. For realistic embedded system applications, however, two more challenges must be considered: a) the complexity of the search space, and b) the multi-objective nature of the optimization problem to solve. I.e., the desired result of system synthesis is a design space exploration that provides the set of so-called Pareto-optimal solutions or an approximation thereof instead of just a single solution. Here, we propose a solution based on a Multi-Objective Evolutionary Algorithm (MOEA) which denotes a class of Evolutionary Algorithms that have recently proposed for design space exploration problems. Secondly, in order to reduce the complexity of typical search spaces, we propose a hierarchical problem and solution structure

Performance analysis of weakly-consistent scenario-aware dataflow graphs

The timed dataflow model of computation is a useful performance analysis tool for electronic system level design automation and embedded software synthesis. Its determinism gives it strong analyzability properties. Its monotonic temporal behavior provides hard real-time guarantees on throughput and latency. It is expressive enough to cover a large class of applications and platforms. The trend however, in both embedded applications and their platforms is to become more dynamic, reaching the limits of what the model can express and analyze with tight performance guarantees. Scenario-aware dataflow (SADF) allows more dynamism to be expressed, introducing a controlled amount of non-determinism into the model to represent different scenarios of behavior. We investigate so-called weakly consistent graphs in which the scenario changes are not tightly coupled with periods of repetitive behavior of the static dataflow behavior in scenarios as in previous methods. We define the semantics of such graphs in terms of (max,+)-algebra and we introduce a method to analyze throughput using a generalization of (max,+)-automata. We show that weakly-consistent SADF generalizes many of the existing analyzable dynamic dataflow models, such as CSDF, PDF and CFDF and we present an algorithm to convert CSDF graphs to SADF

Performance analysis of weakly-consistent scenario-aware dataflow graphs

The timed dataflow model of computation is a useful performance analysis tool for Electronic System Level Design automation and embedded software synthesis. Its determinism gives it strong analysability properties. It is expressive enough to cover a large class of applications and platforms. The trend however, in both embedded applications and their platforms is to become more dynamic, reaching the limits of what the model can express and analyse with tight performance guarantees. Scenario-aware dataflow (SADF) allows more dynamism to be expressed, introducing a controlled amount of non-determinism into the model to represent different scenarios of behaviour. We investigate so-called weakly consistent graphs in which the scenario changes are not tightly coupled with periods of repetitive behaviour of the static dataflow behaviour in scenarios as in previous methods. We define the semantics of such graphs in terms of (max, +)-algebra and we introduce a method to analyse throughput using a generalisation of (max, +)-automata. An extended version of this paper can be found in [15]

Electronic system-level synthesis methodologies

With ever-increasing system complexities, all major semiconductor roadmaps have identified the need for moving to higher levels of abstraction in order to increase productivity in electronic system design. Most recently, many approaches and tools that claim to realize and support a design process at the so-called electronic system level (ESL) have emerged. However, faced with the vast complexity challenges, in most cases at best, only partial solutions are available. In this paper, we develop and propose a novel classification for ESL synthesis tools, and we will present six different academic approaches in this context. Based on these observations, we can identify such common principles and needs as they are leading toward and are ultimately required for a true ESL synthesis solution, covering the whole design process from specification to implementation for complete systems across hardware and software boundaries