Population pharmacokinetics of sevoflurane in conjunction with the AnaConDa: toward target-controlled infusion of volatiles into the breathing system

BACKGROUND: The Anesthetic Conserving Device (AnaConDa) uncouples delivery of a volatile anesthetic (VA) from fresh gas flow (FGF) using a continuous infusion of liquid volatile into a modified heat-moisture exchanger capable of adsorbing VA during expiration and releasing adsorbed VA during inspiration. It combines the simplicity and responsiveness of high FGF with low agent expenditures. We performed in vitro characterization of the device before developing a population pharmacokinetic model for sevoflurane administration with the AnaConDa, and retrospectively testing its performance (internal validation). MATERIALS AND METHODS: Eighteen females and 20 males, aged 31-87, BMI 20-38, were included. The end-tidal concentrations were varied and recorded together with the VA infusion rates into the device, ventilation and demographic data. The concentration-time course of sevoflurane was described using linear differential equations, and the most suitable structural model and typical parameter values were identified. The individual pharmacokinetic parameters were obtained and tested for covariate relationships. Prediction errors were calculated. RESULTS: In vitro studies assessed the contribution of the device to the pharmacokinetic model. In vivo, the sevoflurane concentration-time courses on the patient side of the AnaConDa were adequately described with a two-compartment model. The population median absolute prediction error was 27% (interquartile range 13-45%). CONCLUSION: The predictive performance of the two-compartment model was similar to that of models accepted for TCI administration of intravenous anesthetics, supporting open-loop administration of sevoflurane with the AnaConDa. Further studies will focus on prospective testing and external validation of the model implemented in a target-controlled infusion device.

Whole body postmortem angiography with a high viscosity contrast agent solution using poly ethylene glycol as contrast agent dissolver

Postmortem minimal invasive angiography has already been implemented to support virtual autopsy examinations. An experimental approach in a porcine model to overcome an initially described artificial tissue edema artifact by using a poly ethylene glycol (PEG) containing contrast agent solution showed promising results. The present publication describes the first application of PEG in a whole corpse angiographic CT examination. A minimal invasive postmortem CT angiography was performed in a human corpse utilizing the high viscosity contrast agent solution containing 65% of PEG. Injection was carried out via the femoral artery into the aortic root in simulated cardiac output conditions. Subsequent CT scanning delivered the 3D volume data of the whole corpse. Visualization of the human arterial anatomy was excellent and the contrast agent distribution was generally limited to the arterial system as intended. As exceptions an enhancement of the brain, the left ventricular myocardium and the renal cortex became obvious. This most likely represented the stage of centralization of the blood circulation at the time of death with dilatation of the precapillary arterioles within these tissues. Especially for the brain this resulted in a distinctively improved visualization of the intracerebral structures by CT. However, the general tissue edema artifact of postmortem minimal invasive angiography examinations could be distinctively reduced.

Angiofil-mediated visualization of the vascular system by microcomputed tomography: a feasibility study

Visualization of the vascular systems of organs or of small animals is important for an assessment of basic physiological conditions, especially in studies that involve genetically manipulated mice. For a detailed morphological analysis of the vascular tree, it is necessary to demonstrate the system in its entirety. In this study, we present a new lipophilic contrast agent, Angiofil, for performing postmortem microangiography by using microcomputed tomography. The new contrast agent was tested in 10 wild-type mice. Imaging of the vascular system revealed vessels down to the caliber of capillaries, and the digital three-dimensional data obtained from the scans allowed for virtual cutting, amplification, and scaling without destroying the sample. By use of computer software, parameters such as vessel length and caliber could be quantified and remapped by color coding onto the surface of the vascular system. The liquid Angiofil is easy to handle and highly radio-opaque. Because of its lipophilic abilities, it is retained intravascularly, hence it facilitates virtual vessel segmentation, and yields an enduring signal which is advantageous during repetitive investigations, or if samples need to be transported from the site of preparation to the place of actual analysis, respectively. These characteristics make Angiofil a promising novel contrast agent; when combined with microcomputed tomography, it has the potential to turn into a powerful method for rapid vascular phenotyping.

Optimal game theoretic distributed control methodologies in small scale power systems

This dissertation presents the competitive control methodologies for small-scale power system (SSPS). A SSPS is a collection of sources and loads that shares a common network which can be isolated during terrestrial disturbances. Micro-grids, naval ship electric power systems (NSEPS), aircraft power systems and telecommunication system power systems are typical examples of SSPS. The analysis and development of control systems for small-scale power systems (SSPS) lacks a defined slack bus. In addition, a change of a load or source will influence the real time system parameters of the system. Therefore, the control system should provide the required flexibility, to ensure operation as a single aggregated system. In most of the cases of a SSPS the sources and loads must be equipped with power electronic interfaces which can be modeled as a dynamic controllable quantity. The mathematical formulation of the micro-grid is carried out with the help of game theory, optimal control and fundamental theory of electrical power systems. Then the micro-grid can be viewed as a dynamical multi-objective optimization problem with nonlinear objectives and variables. Basically detailed analysis was done with optimal solutions with regards to start up transient modeling, bus selection modeling and level of communication within the micro-grids. In each approach a detail mathematical model is formed to observe the system response. The differential game theoretic approach was also used for modeling and optimization of startup transients. The startup transient controller was implemented with open loop, PI and feedback control methodologies. Then the hardware implementation was carried out to validate the theoretical results. The proposed game theoretic controller shows higher performances over traditional the PI controller during startup. In addition, the optimal transient surface is necessary while implementing the feedback controller for startup transient. Further, the experimental results are in agreement with the theoretical simulation. The bus selection and team communication was modeled with discrete and continuous game theory models. Although players have multiple choices, this controller is capable of choosing the optimum bus. Next the team communication structures are able to optimize the players’ Nash equilibrium point. All mathematical models are based on the local information of the load or source. As a result, these models are the keys to developing accurate distributed controllers.

DISTRIBUTED APPROACH FOR SOLVING OPTIMAL POWER FLOW PROBLEMS IN THREE-PHASE UNBALANCED DISTRIBUTION NETWORK

The objective of this report is to study distributed (decentralized) three phase optimal power flow (OPF) problem in unbalanced power distribution networks. A full three phase representation of the distribution networks is considered to account for the highly unbalance state of the distribution networks. All distribution network’s series/shunt components, and load types/combinations had been modeled on commercial version of General Algebraic Modeling System (GAMS), the high-level modeling system for mathematical programming and optimization. The OPF problem has been successfully implemented and solved in a centralized approach and distributed approach, where the objective is to minimize the active power losses in the entire system. The study was implemented on the IEEE-37 Node Test Feeder. A detailed discussion of all problem sides and aspects starting from the basics has been provided in this study. Full simulation results have been provided at the end of the report.

Method of Detecting System Function by Measuring Frequency Response

Methods of rapidly measuring an impedance spectrum of an energy storage device in-situ over a limited number of logarithmically distributed frequencies are described. An energy storage device is excited with a known input signal, and aresponse is measured to ascertain the impedance spectrum. An excitation signal is a limited time duration sum-of-sines consisting of a select number offrequencies. In one embodiment, magnitude and phase of each frequency ofinterest within the sum-of-sines is identified when the selected frequencies and sample rate are logarithmic integer steps greater than two. This technique requires a measurement with a duration of one period of the lowest frequency. In another embodiment, where selected frequencies are distributed in octave steps, the impedance spectrum can be determined using a captured time record that is reduced to a half-period of the lowest frequency.

A systematic review of the clinical performance of CAD/CAM single-tooth restorations

PURPOSE: This systematic review sought to determine the long-term clinical survival rates of single-tooth restorations fabricated with computer-aided design/computer-assisted manufacture (CAD/CAM) technology, as well as the frequency of failures depending on the CAD/CAM system, the type of restoration, the selected material, and the luting agent. MATERIALS AND METHODS: An electronic search from 1985 to 2007 was performed using two databases: Medline/PubMed and Embase. Selected keywords and well-defined inclusion and exclusion criteria guided the search. All articles were first reviewed by title, then by abstract, and subsequently by a full text reading. Data were assessed and extracted by two independent examiners. The pooled results were statistically analyzed and the overall failure rate was calculated by assuming a Poisson-distributed number of events. In addition, reported failures were analyzed by CAD/CAM system, type of restoration, restorative material, and luting agent. RESULTS: From a total of 1,957 single-tooth restorations with a mean exposure time of 7.9 years and 170 failures, the failure rate was 1.75% per year, estimated per 100 restoration years (95% CI: 1.22% to 2.52%). The estimated total survival rate after 5 years of 91.6% (95% CI: 88.2% to 94.1%) was based on random-effects Poisson regression analysis. CONCLUSIONS: Long-term survival rates for CAD/CAM single-tooth Cerec 1, Cerec 2, and Celay restorations appear to be similar to conventional ones. No clinical studies or randomized clinical trials reporting on other CAD/CAM systems currently used in clinical practice and with follow-up reports of 3 or more years were found at the time of the search.

System Architecture of a Mixed Reality Framework

In this paper the software architecture of a framework which simplifies the development of applications in the area of Virtual and Augmented Reality is presented. It is based on VRML/X3D to enable rendering of audio-visual information. We extended our VRML rendering system by a device management system that is based on the concept of a data-flow graph. The aim of the system is to create Mixed Reality (MR) applications simply by plugging together small prefabricated software components, instead of compiling monolithic C++ applications. The flexibility and the advantages of the presented framework are explained on the basis of an exemplary implementation of a classic Augmented Realityapplication and its extension to a collaborative remote expert scenario.

Distributed Repositories for Educational Content

In Part 1 of this article we discussed the need for information quality and the systematic management of learning materials and learning arrangements. Digital repositories, often called Learning Object Repositories (LOR), were introduced as a promising answer to this challenge. We also derived technological and pedagogical requirements for LORs from a concretization of information quality criteria for e-learning technology. This second part presents technical solutions that particularly address the demands of open education movements, which aspire to a global reuse and sharing culture. From this viewpoint, we develop core requirements for scalable network architectures for educational content management. We then present edu-sharing, an advanced example of a network of homogeneous repositories for learning resources, and discuss related technology. We conclude with an outlook in terms of emerging developments towards open and networked system architectures in e-learning.

Improving Management of Distributed Services Using Correlations and Predictions in SLA-Driven Cloud Computing Systems

Recent advancements in cloud computing have enabled the proliferation of distributed applications, which require management and control of multiple services. However, without an efficient mechanism for scaling services in response to changing environmental conditions and number of users, application performance might suffer, leading to Service Level Agreement (SLA) violations and inefficient use of hardware resources. We introduce a system for controlling the complexity of scaling applications composed of multiple services using mechanisms based on fulfillment of SLAs. We present how service monitoring information can be used in conjunction with service level objectives, predictions, and correlations between performance indicators for optimizing the allocation of services belonging to distributed applications. We validate our models using experiments and simulations involving a distributed enterprise information system. We show how discovering correlations between application performance indicators can be used as a basis for creating refined service level objectives, which can then be used for scaling the application and improving the overall application's performance under similar conditions.

New approach to direct stenting using a novel "all-in-one" coronary stent system via 5 French diagnostic catheters: a pilot study

OBJECTIVES We sought to evaluate the strategy success and short term clinical outcomes of direct stenting via 5 French (F) diagnostic catheters using a novel bare metal stent with integrated delivery system (IDS) (Svelte Medical Systems, New Providence, NJ) and compare the results to a conventionally treated matched group. METHODS Fifteen consecutive patients with lesions deemed suitable for direct stenting using a bare metal stent were included. The primary endpoint was the strategy success defined as the ability to successfully treat a target lesion via a 5 F diagnostic catheter with a good angiographic result (TIMI III flow, residual stenosis ≤20%). Procedure and fluoroscopy times, contrast agent use, cost, and short-term clinical outcomes were compared to a matched group treated via conventional stenting. RESULTS The primary endpoint was reached in 14/15 patients (93%). There were no significant differences in procedural (58.6 min ± 12.7 vs. 57.4 min ± 14.2) or fluoroscopy times (10.0 min ± 4.3 vs.10.1 min ± 3.9) or contrast agent use (193.7 ml ± 54.8 vs. 181.4 ml ± 35.6). However, there were significant reductions in materials used in the study group compared to the control group equating to cost savings of almost US $600 per case (US $212.44 ± 258.09 vs. US $804.69 ± 468.11; P = 0.001). CONCLUSIONS Direct stenting using a novel bare metal stent with an IDS via 5 F diagnostic catheters is a viable alternative to conventional stenting in selected patients and is associated with significant cost savings.

Antigens of the type-three secretion system of Aeromonas salmonicida subsp. salmonicida prevent protective immunity in rainbow trout

Aeromonas salmonicida subsp. salmonicida is the etiologic agent of furunculosis, a frequent and significant disease of fisheries worldwide. The disease is largely controlled by commercial oil adjuvanted vaccines containing bacterins. However, the mechanisms leading to a protective immune response remain poorly understood. The type-three secretion system (T3SS) plays a central role in virulence of A. salmonicida subsp. salmonicida and thus may have an influence on the immune response of the host. The aim of this study was to evaluate the role of the T3SS antigens in mounting a protective immune response against furunculosis. Rainbow trout were intraperitoneally vaccinated in two independent experiments with bacterins prepared from a wild-type A. salmonicida strain and an isogenic strain carrying a deletion in the T3SS (ΔascV). Fish were challenged with the wt strain eight weeks after vaccination. In both trials, the survival rate of trout vaccinated with the ΔascV strain was significantly higher (23-28%) in comparison to the group vaccinated with the wt strain. High-throughput proteomics analysis of whole bacteria showed the ascV deletion in the mutant strain resulted in lower expression of all the components of the T3SS, several of which have a potential immunosuppressive activity. In a third experiment, fish were vaccinated with recombinant AcrV (homologous to the protective antigen LcrV of Yersinia) or S-layer protein VapA (control). AcrV vaccinated fish were not protected against a challenge while fish vaccinated with VapA were partially protected. The presence of T3SS proteins in the vaccine preparations decreased the level of protection against A. salmonicida infection and that AcrV was not a protective antigen. These results challenge the hypothesis that mounting specific antibodies against T3SS proteins should bring better protection to fish and demonstrate that further investigations are needed to better understand the mechanisms underlying effective immune responses against A. salmonicida infection.

SLA-driven predictive orchestration for distributed cloud-based mobile services

We describe a system for performing SLA-driven management and orchestration of distributed infrastructures composed of services supporting mobile computing use cases. In particular, we focus on a Follow-Me Cloud scenario in which we consider mobile users accessing cloud-enable services. We combine a SLA-driven approach to infrastructure optimization, with forecast-based performance degradation preventive actions and pattern detection for supporting mobile cloud infrastructure management. We present our system's information model and architecture including the algorithmic support and the proposed scenarios for system evaluation.

User and Machine Authentication and Authorization Infrastructure for Distributed Wireless Sensor Network Testbeds

The intention of an authentication and authorization infrastructure (AAI) is to simplify and unify access to different web resources. With a single login, a user can access web applications at multiple organizations. The Shibboleth authentication and authorization infrastructure is a standards-based, open source software package for web single sign-on (SSO) across or within organizational boundaries. It allows service providers to make fine-grained authorization decisions for individual access of protected online resources. The Shibboleth system is a widely used AAI, but only supports protection of browser-based web resources. We have implemented a Shibboleth AAI extension to protect web services using Simple Object Access Protocol (SOAP). Besides user authentication for browser-based web resources, this extension also provides user and machine authentication for web service-based resources. Although implemented for a Shibboleth AAI, the architecture can be easily adapted to other AAIs.

The Aeromonas salmonicida subsp. salmonicida exoproteome: determination of the complete repertoire of Type-Three Secretion System effectors and identification of other virulence factors

BACKGROUND Aeromonas salmonicida subsp. salmonicida, the etiologic agent of furunculosis, is a major pathogen of fisheries worldwide. Several virulence factors have been described, but the type-three secretion system (T3SS) is recognized as having a major effect on virulence by injecting effectors directly into fish cells. In this study we used high-throughput proteomics to display the differences between in vitro secretome of A. salmonicida wild-type (wt, hypervirulent, JF2267) and T3SS-deficient (isogenic ΔascV, extremely low-virulent, JF2747) strains in exponential and stationary phases of growth. RESULTS Results confirmed the secretion of effectors AopH, AexT, AopP and AopO via T3SS, and for the first time demonstrated the impact of T3SS in secretion of Ati2, AopN and ExsE that are known as effectors in other pathogens. Translocators, needle subunits, Ati1, and AscX were also secreted in supernatants (SNs) dependent on T3SS. AopH, Ati2, AexT, AopB and AopD were in the top seven most abundant excreted proteins. EF-G, EF-Tu, DnaK, HtpG, PNPase, PepN and MdeA were moderately secreted in wt SNs and predicted to be putative T3 effectors by bioinformatics. Pta and ASA_P5G088 were increased in wt SNs and T3-associated in other bacteria. Ten conserved cytoplasmic proteins were more abundant in wt SNs than in the ΔascV mutant, but without any clear association to a secretion system. T1-secreted proteins were predominantly found in wt SNs: OmpAI, OmpK40, DegQ, insulinase ASA_0716, hypothetical ASA_0852 and ASA_3619. Presence of T3SS components in pellets was clearly decreased by ascV deletion, while no impact was observed on T1- and T2SS. Our results demonstrated that the ΔascV mutant strain excreted well-described (VapA, AerA, AerB, GCAT, Pla1, PlaC, TagA, Ahe2, GbpA and enolase) and yet uncharacterized potential toxins, adhesins and enzymes as much as or even more than the wt strain. Other putative important virulence factors were not detected. CONCLUSIONS We demonstrated the whole in vitro secretome and T3SS repertoire of hypervirulent A. salmonicida. Several toxins, adhesins and enzymes that are not part of the T3SS secretome were secreted to a higher extent in the extremely low-virulent ΔascV mutant. All together, our results show the high importance of an intact T3SS to initiate the furunculosis and offer new information about the pathogenesis.