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- Weiss, Lars, et al.
(författare)
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BIOCOMPATIBILITY AND TOLERABILITY OF A PURELY BICARBONATE-BUFFERED PERITONEAL DIALYSIS SOLUTION
- 2009
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Ingår i: Peritoneal Dialysis International. - 1718-4304 .- 0896-8608. ; 29:6, s. 647-655
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Tidskriftsartikel (refereegranskat)abstract
- Background: Novel peritoneal dialysis solutions are characterized by a minimal content of glucose degradation products and a neutral pH. Many studies have shown the biocompatibility of neutral lactate-buffered solutions; however, until now, the effect of purely bicarbonate-buffered solutions has not been intensively studied in vivo. Methods: This study was an open label, prospective, crossover multicenter trial to investigate the biocompatibility of a purely bicarbonate-buffered solution (bicPDF) by measuring biocompatibility parameters such as cancer antigen 125 (CA125) in peritoneal effluent. 55 patients were enrolled in the study. After a 2-week run-in phase, 53 patients could be randomized into 2 groups, starting with either standard lactate-buffered peritoneal dialysis fluid (SPDF) for 12 weeks (phase 1) and then switching to bicPDF for 12 weeks (phase 2), or vice versa. Overnight peritoneal effluents were collected at baseline and at the end of phases 1 and 2 and were tested for CA125, hyaluronic acid, vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interferon gamma (IFN gamma), and transforming growth factor-beta 1 (TGF-beta 1). Total ultrafiltration and residual renal function were also assessed. At the end of the study, pain during fluid exchange and dwell was evaluated using special questionnaires. Results: 34 patients completed the study; 27 of them provided data for analysis of the biocompatibility parameters. CA125 levels in overnight effluent were significantly higher with bicPDF (61.9 +/- 33.2 U/L) than with SPDF (18.6 +/- 18.2 U/L, p < 0.001). Hyaluronic acid levels were significantly lower after the use of bicPDF (185.0 +/- 119.6 ng/mL) than after SPDF (257.4 +/- 174.0 ng/mL, p = 0.013). Both TNF-alpha and TGF-beta 1 showed higher levels with the use of bicPDF than with SPDF. No differences were observed for IL-6, VEGF, or IFN gamma levels. We observed an improvement in the glomerular filtration rate with the use of bicPDF but no differences were observed for total fluid loss. Pain scores could be analyzed in 23 patients: there was no difference between the solutions. Conclusions: The use of a purely bicarbonate-buffered low-glucose degradation product solution significantly changes most of the peritoneal effluent markers measured, suggesting an improvement in peritoneal membrane integrity. Additionally, it seems to have a positive effect on residual renal function.
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| 2. |
- Berntsson, Lars-Olof, et al.
(författare)
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EAST-ADL 2.0 Specification
- 2008
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Rapport (refereegranskat)abstract
- This specification of the EAST ADL 2.0 is based on the EAST-ADL developed in the EAST EEA projectand has been further refined and harmonized with on-going modelling appraches in the automotiveindustry. It presents the modeling infrastructure, i.e. how the modeling elements should be represented inthe language and the UML representation. For each package a usage example is provided.The EAST-ADL 2.0 is harmonized with AUTOSAR.The metamodel and UML profile of EAST ADL 2.0 is defined in two steps: A domain (automotive)metamodel is defined, capturing only the domain specific needs of the language, without adding the UML2details. The basic concepts of UML are used for this purpose, such as classes, compositions andassociations. Based on the domain metamodel, a UML2 profile for the domain metamodel is defined,specifying stereotypes with properties and constraints.Comments on the content of this document are welcomed, and should be directed to .Please download the latest available specification and the XMI file ready for use in UML2 tools from the website.
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| 3. |
- Cuenot, Philippe, et al.
(författare)
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Engineering support for automotive embedded systems : beyond Autosar
- 2008
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Ingår i: FISITA World Automotive Congress 2008, Congress Proceedings - Electronics. ; , s. 180-189
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Konferensbidrag (refereegranskat)abstract
- The future de-facto standard for automotive electric/electronic (E/E) architectures, AUTOSAR (1), is becoming more and more mature. In December 2007 there has been a release of the version 3.0, and automotive OEMs are already using AUTOSAR technology in their series production projects. Even though there has been an evolution of which engineering information and concepts are part of AUTOSAR and there are still things to be defined, there will always be a number of issues outside the scope of this standardization initiative. As AUTOSAR has become a de facto standard, there is an obvious possibility now to define general systems engineering concepts complementary to and thus going beyond the current AUTOSAR specifications. In this paper we describe the advantages of having an integrated architecture description language (ADL) specific for the development of E/E systems in the automotive domain. We present the core concepts for such an integrated ADL which targets an overall systems engineering approach: the EAST-ADL2. The original EAST-ADL was developed in the EAST-EEA project (7) and basic concepts were reused in the AUTOSAR standardization initiative. Lately, the original EAST-ADL has been refined and extended in the ATESST project (www.atesst.org) to EAST-ADL2. The EAST-ADL2 conceptually integrates and links engineering information related to multiple engineering disciplines such as product line engineering, requirements engineering, control engineering, software engineering, safety engineering and real-time systems engineering. The ADL docs not prescribe a specific development process and it lends itself to top-down, bottom-up and middle-out development approaches and methods. As a central part, the EAST-ADL2 defines a system model which is organized in parts representing different levels of abstraction, reflecting different views and levels of details of the vehicle E/E architecture. By identifying AUTOSAR as belonging to only one certain level of abstraction, namely the implementation level, we also show that there is a way to define complementary ADL concepts without interfering with AUTOSAR. These describe engineering information that is more abstract, with different engineering focus and thus - from the EAST-ADL2 perspective - on different levels of abstraction.
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| 7. |
- Sjöstedt, Carl-Johan, et al.
(författare)
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Developing Dependable Automotive Embedded Systemsusing the EAST-ADL; representing continuous timesystems in SysML
- 2007
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Ingår i: EOOLT 2007 - Proceedings of the 1st International Workshop on Equation-Based Object-Oriented Languages and Tools, In Conjunction with ECOOP 2007. ; , s. 25-36
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Konferensbidrag (refereegranskat)abstract
- The architectural description language for automotive embedded systems EAST-ADL is presented in this paper. The aim of the EAST-ADL language is to provide a comprehensive systems modeling approach as a means to keep the engineering information within one structure. This facilitatessystems integration and enables consistent systems analysis. The EAST-ADL encompasses structural information at different abstraction levels, requirements and variability modeling. The EAST-ADL is implemented as a UML2 profileand is harmonized with AUTOSAR and a subset of SysML. Currently, differentways to model behavior natively in the language are investigated. An approachfor using SysML parametric diagrams to describe equations in composed physical systems is proposed. An example system is modeled and discussed. Itis highlighted that parametric diagrams lacks support for separation between effort and flow variables, and why this separation would be desired in order tomodel composed physical systems. An alternative approach by use of SysML activity diagrams is also discussed.
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| 8. |
- Wibom, Carl, 1977-
(författare)
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Multivariate analyses of proteomic and metabolomic patterns in brain tumors
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glioblastoma multiforme (GBM) is the most common primary brain tumor. Given the current standard of care, the prognosis for patients diagnosed with this disease is still poor. There consequently exists a need to improve current treatments, as well as to develop new ones. Many obstacles however need to be overcome to facilitate this effort and one of these involves the development of improved methods to monitor treatment effects. At present, the effects of treatment are typically assessed by radiological means several months after its initiation, which is unsatisfactory for a fast growing tumor like GBM. It is however likely that treatment effects can be detected on a molecular level long before radiological response, especially considering many of the targeted therapies that are currently being developed. Biomarkers for treatment efficacy may be of great importance in the future individualization of brain tumor treatment. The work presented herein was primarily focused on detecting early effects of GBM treatment. To this end, we designed experiments in the BT4C rat glioma model in which we studied effects of both conventional radiotherapy and an experimental angiogenesis inhibitor, vandetanib. Brain tissue samples were analyzed using a high throughput mass spectrometry (MS) based screening, known as Surface Enhanced Laser Desorption/Ionization - Time of Flight - Mass Spectrometry (SELDI-TOF-MS). The vast amounts of data generated were subsequently analyzed by established multivariate statistical methods, such as Principal Component Analysis (PCA), Partial Least Squares (PLS), and Orthogonal Partial Least Squares (OPLS), developed for analysis of large and complex datasets. In the radiotherapy study we detected a protein spectrum pattern clearly related to tumor progression. We notably observed how this progression pattern was hampered by radiotherapy. The vandetanib study also revealed significant alterations of protein expression following treatment of different durations, both in tumor tissue and in normal brain contralateral to the tumor. In an effort to further elucidate the pathophysiology of GBM, particularly in relation to treatment, we collected extracellular fluid (ECF) samples from 11 patients diagnosed with inoperable GBM. The samples were collected by means of stereotactic microdialysis, both from within the contrast enhancing tumor and the brain adjacent to tumor (BAT). Samples were collected longitudinally from each patient in a time span of up to two weeks, during which the patient received the first five fractions of radiotherapy. The ECF samples were then analyzed by Gas Chromatography Mass Spectrometry (GC-MS) to screen them with respect to concentrations of low molecular weight compounds (metabolites). Suitable multivariate analysis strategies enabled us to extract patterns of varying metabolite concentrations distinguishing between samples collected at different locations in the brain as well as between samples collected at different time points in relation to treatment. In a separate study, we also applied SELDI-TOF-MS and multivariate statistical methods to unravel possible differences in protein spectra between invasive and non-invasive WHO grade I meningiomas. This type of tumor can usually be cured by surgical resection however sometimes it grows invasively into the bone, ultimately causing clinical problems. This study revealed the possibility to differentiate between invasive and non-invasive benign meningioma based on the expression pattern of a few proteins. Our approach, which includes sample analysis and data handling, is applicable to a wide range of screening studies. In this work we demonstrated that the combination of MS screening and multivariate analyses is a powerful tool in the search for patterns related to treatment effects and diagnostics in brain tumors.
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