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PubMed2001

Towards more optimal medical diagnosing with evolutionary algorithms.

Efficiency in hospital performance is becoming more and more important. Studies showed that diagnosis can considerably reduce the inefficiency, so one of the most important tasks in achieving greater hospital efficiency is to optimize the diagnostic process. For the best of the patient the diagnostic process has to be optimized regarding the number of the examinations and individualized in order to maximize accuracy, sensitivity and specificity. In addition the duration of the diagnostic process has to be minimized and the process has to be performed on the most reliable equipment. The main contribution of our paper is the introduction of the integrated computerized environment DIAPRO enabling the diagnostic process optimization. The DIAPRO is based on a single approach--evolutionary algorithms.

Algorithms↗
PubMed2006

The product and process of referral: optimizing general practitioner-medical specialist interaction through information technology.

With the growing complexities of health care delivery in western industrialized countries, the need for inter-organizational communication is increasingly emphasized. In this paper, we focus on a system - ZorgDomein - that was developed to optimize GP-medical specialist communication. Contrary to the notion of 'shared' or 'integrated care' that often assumes a 'seamless' health care, we will focus on the negotiated order of GP-specialist cooperation, showing the precarious localized arrangements that allow both a bridging and a separation of professional activities concerning patient care. Furthermore, we analyze how ZorgDomein changes the arrangements to maintain a working order. The main focus of the article is on the way GP-specialist referrals are on the one hand conceptualized as discrete events of information sharing, while on the other hand are part of a process of care. We will argue that in standardization attempts by national and local actors, embodied within the technology, information exchange between first and secondary care is made into a product. This conceptualization and materialization neglects the process in which this information comes about or is being created. We discuss the consequences of this for the design and use of the technology.

Hospital Information Systems↗
PubMed1993

Cytologic evaluation of serous effusions. Processing techniques and optimal number of smears for routine preparation.

A double-blind retrospective review of 90 pleural and ascitic fluids was performed to determine the optimal number of smears necessary to produce an accurate evaluation, and to analyze the utility of different preparation techniques. Each case had four Papanicolaou-stained smears (two alcohol fixed and two Saccomanno fixed) and one Diff-Quik-stained, air-dried smear. Forty cases originally were reported as positive (37 adenocarcinoma, 1 lymphoma, and 2 Pneumocystis carinii) and 50 were reported as negative. The results showed that the diagnostic yield of evaluating five smears compared with three (one of each preparation) is identical. Air-dried smears were the most sensitive in identifying malignant cells and infectious organisms. It is concluded that (1) the diagnostic accuracy is enhanced by the use of several preparation techniques to include air-dried smears and (2) when variable processing methods are used, the evaluation of more than three smears does not increase the diagnostic yield.

Adenocarcinoma↗
PubMed2004

Production of Carbopol 974P and Carbopol 971P pellets by extrusion-spheronization: optimization of the processing parameters and water content.

Pellets obtained by extrusion-spheronization represent multiparticulate dosage forms whose interest in intestinal drug delivery can be potentiated and targeted through bioadhesive properties. However, adhesion itself makes the process difficult or even impossible. The problem of tackiness encountered with bioadhesive wet masses was previously eliminated by the use of electrolytes such as CaCl2. This approach is known to reduce the viscosity of polyacrylic acids by disturbing the interactions between carboxylate groups on adjacent polymer molecules, thereby decreasing their bioadhesive properties. The present study aimed at producing pellets containing carbomers without addition of electrolytes in order to maintain their bioadhesive potentiality at its maximum. Carbopol 974P (10%, 15% and 20%) and Carbopol 971P (10%) were used in combination with Avicel PH101. The extrusion speed (30, 45, 60, 90, and 150 rpm), spheronizer speed (350, 700, 960, 1000, and 1300 rpm), spheronization time (5, 10, 15, and 20 minutes) and amount of water (45%, 50%, 54%, and 58%) were optimized in order to obtain the highest yield of spherical pellets ranging 710-1000 microm in diameter. For pellets containing 10%, 15% Carbopol 974P or 10% Carbopol 971P and 45% water content, 30 rpm extrusion speed, 960 rpm, and 10 minutes spheronization speed and time led to the highest yields and sphericities, respectively, 72% and 0.91, 67% and 0.78, and 76% and 0.80. Production of pellets with 20% Carbopol 974P could be achieved through the increase of the water content up to 58% and implementation of 30 rpm extrusion speed, 1300 rpm, and 10 minutes spheronization speed and time. The yield and sphericity were 42% and 0.78 respectively.

Acrylates↗
PubMed2005

Demand-driven evolution of IT systems in healthcare--a case study for improving interdisciplinary processes.

OBJECTIVES: To analyze and to optimize interdisciplinary clinical processes, to introduce an IT-supported model for demand-driven system evolution in healthcare, and to demonstrate the feasibility of the approach for a clinical example and to present an evaluation. METHODS: System evolution and change management are viewed as two sides of the same coin, thus formal methods for process analysis and IT system evolution were embedded into a goal-oriented change management model. Based on a process model, a Failure Mode and Effects Analysis (FMEA) and a computer simulation were performed. A tool for rapid application development (RAD) was used to incrementally improve the healthcare information system according to newly arising needs. RESULTS: Each of the formal methods used contributed to the successful reorganization of the interdisciplinary clinical process. An evaluation demonstrated significant improvements. An integrated IT application was implemented to support the optimized process. CONCLUSIONS: Process improvement is feasible and effective when formal methods for process analysis and requirements specification are used in a reasonable and goal-oriented way. It might be necessary to trade off costs and benefits or simplify a given method in the context of a particular project. As the same information is utilized in different tools, it is supposed that the efforts for process analysis, documentation and implementation of adapted applications could be reduced if different tools were integrated and based on a single coherent reference model for description of clinical processes.

Computer Simulation↗
PubMed1984

Model aided dynamic process analysis and optimization for the nourseothricin fermentation.

The relation between product formation and growth kinetics could be characterized by two facts: the specific product formation rate depends on the ageing of the population and on the specific growth rate. These relation was formulated and quantified by a mathematical model, which was fitted to experimental data of a representative fermentation run und used to predict an optimal fermentation mode. In the result of this discussion cyclic fed batch fermentation was found to be optimal.

Anti-Bacterial Agents↗
PubMed1979

The role of glucocorticoid hormones as biological amplifiers.

Recent research in hormone action has been aimed at studying single effects in well-defined systems. As exemplified in several chapters of this book, it has been possible to deduce a general mechanism of action of the glucocorticoids using this approach. Most hormones, and the glucocorticoids in particular, do not act as independent agents in the intact animal. Although the best known example of how glucocorticoids interact with other hormones is the amplification of the effect of those whose action is mediated by cAMP, these steroids also augment the effects of a variety of other hormones and effectors. Such interactions are of interest in clinical medicine as well, since glucocorticoid hormones are used in combination with other drugs in a number of conditions, including the treatment of asthma, allergies, and certain kinds of shock and cancer. Neither the biochemical nor the pharmacologic basis for the effects of the glucocorticoids is known. In some cases the actions of other hormones are not observed unless the tissue has first been exposed to glucocorticoids. In these instances the glucocorticoids are said to exert a "permissive effect," since they allow a process to proceed at a maximal rate even though the steroid itself has no effect on this process. There is no doubt that such examples exist, as documented above: thus the concept of a "permissive effect" does have utility. The term fails to describe the more general role the glucocorticoids play, since in many instances the steroid also has a direct effect on the process itself, or optimizes a process in which the primary effector is not as yet known. Because of these cases, and because the historically more general usage first proposed by INGLE [1] seems to have been forgotten, use of the term "permissive effect" has been avoided in this chapter. An ultimate goal in glucocorticoid hormone research is to identify the mechanisms involved in the amplification effect these hormones exert. Now that the actions of these hormones and of the hormones they interact with are being defined, such work is within the realm of feasibility.

Animals↗
PubMed2003

[Accessible price lists at the anaesthesiologist's workplace enhance cost consciousness as a part of process and cost optimization].

The imminent introduction of the DRG (diagnosis-related-group) system is putting hospitals in Germany under considerable pressure. This requires that personnel are efficiently allocated by optimizing organizational procedures and that the limited resources be distributed in a cost-effective manner. One prerequisite for this is a marked cost-consciousness on the part of those who "incur costs" in providing a service. To increase the awareness of costs in clinical physicians, the cost structures must be transparent. In order to achieve this goal, a project was initiated at the Department of Anaesthesiology at the University Hospital of Heidelberg, which aimed to enhance the cost-consciousness of the staff by making price lists available to anaesthesiologists at the workplace. In addition to the price lists, the 25 most expensive medications and medical products were added as an ABC analysis. The departmental staff was interviewed by questionnaire as to whether this project was reasonable. After 1 year the interview was repeated. The results of the questionnaire showed that in the opinion of the staff, price lists are an effective tool, as cost-consciousness on the part of clinical physicians can be enhanced by making price structures transparent. This is a major prerequisite for individual motivation in the cost-effective management. Although the ABC analyses demonstrate no long-term effect of the price-transparency on the cost structures, the staff showed increased cost-consciousness and individual motivation for economic tasks.

Anesthesia Department, Hospital↗
PubMed2000

A process for ensuring optimal cardiovascular intervention and identifying candidates for glycoprotein IIb/IIIa receptor inhibitor therapy.

Data from trials with glycoprotein (GP) IIb/IIIa receptor inhibitors have led to a new standard of care for patients with unstable angina or non-wave myocardial infarction (MI) who are undergoing percutaneous coronary intervention. Additional data are necessary to compare patient responses to various GP IIb/IIIa agents in a nontrial setting with results from clinical trials. Seton Medical Center has designed a database to accommodate this task. Data from >20,000 patients have been collected since 1979 and the interventional experience from the years 1997 through 1999 has been analyzed for patients who were candidates for receiving these agents. The data are being used to evaluate the outcomes of therapy and to devise models that can stratify patients according to risk, thereby ensuring optimal cardiovascular intervention and choice of the most cost-effective GP IIb/IIIa inhibitor agent.

Abciximab↗
PubMed1997

Purification of rubella virus E1-E2 protein complexes by immunoaffinity chromatography.

A murine monoclonal antibody directed against the E1 membrane glycoprotein of rubella virus was immobilized on an N-hydroxysuccinimide-activated chromatographic support. The antibody was used to purify rubella virus E1-E2 protein complexes from Tween-80/diethyl ether extracts of cell culture supernatants containing virus particles. The adsorption behaviour of immunosorbents with ligand densities of 2.9, 5.4 and 11.1 mg monoclonal antibody per millilitre of gel was investigated using batchwise conditions. Then the immunoaffinity purification process was optimized with regard to adsorption efficiency by adjusting the flow rate, the bed height and the amount of sample loaded onto the column. The optimized immunoaffinity purification process which is reproducible and relatively simple (one-step) had a yield of 73%, a concentration factor of 5-8 and a purification factor of about 2600. No mouse IgG due to ligand leakage could be detected in the immunopurified product using an enzyme immunoassay. High-performance size exclusion chromatography, sodium dodecyl sulphate polyacrylamide gel electrophoresis, immunoblotting and electron microscopy showed that the immunopurified product contained rosette-like structures formed by complexes of E1 and E2 proteins. The product retained its hemagglutinating activity and proved to be suitable for application in a fluorescent enzyme immunoassay for determination of anti-rubella IgG in human serum.

Animals↗
PubMed2001

Optimization of epitope processing enhances immunogenicity of multiepitope DNA vaccines.

Experimental DNA vaccines comprised of multiple minimal cytotoxic T lymphocytes (CTL) epitopes can effectively induce broad CTL responses; however, such constructs frequently exhibit significant variation in epitope immunogenicity. Antigenicity assays utilizing human cells transfected with one such multiepitope construct revealed that the epitopes with poor immunogenicity were inefficiently processed in transfected cells. Compilation of a database of 94 epitope/flanking region combinations, for which immunogenicity was measured experimentally, revealed that the type of residue immediately following the carboxyl-terminus of the epitope exerted a prominent effect on immunogenicity. Experiments utilizing a variety of HBV-specific vaccine constructs demonstrated epitope immunogenicity could be modulated by the insertion of a single amino acid and the effect on immunogenicity could be ascribed to modulation of processing efficiency. These findings demonstrate that multiepitope DNA vaccines can be engineered to enhance CTL immunogenicity by increasing processing efficiency.

AIDS Vaccines↗
PubMed2002

Process standardization for optimal virus recovery and removal of substrate DNA and bovine serum proteins in Vero cell-derived rabies vaccine.

Purification of a rabies vaccine by a single zonal centrifugation run was replaced by two runs with optimal standardization of the sucrose density gradient. As a result, significant reductions in the levels of substrate DNA and bovine serum protein in the Vero cell-derived human rabies vaccine were achieved. Following many trials, for the first run, loading of the 3.2-l capacity K-3 rotor with 1800 ml of 60% sucrose solution and 1400 ml of vaccine PBS buffer solution gave a satisfactory linear gradient. However, after the first run, the substrate DNA and bovine serum contents exceeded the required levels. After protamine sulphate and Tween-80 treatment of the concentrated inactivated material, a second run using the same procedure as in the first run was tried. However, these purification procedures resulted in low virus recovery. To achieve optimal virus recovery, and removal of substrate DNA and bovine serum protein, the peak fractions from the first run as indicated by the haemagglutination, sucrose concentration, and optical density values were pooled and the sucrose concentration of the pooled fractions was increased to 60%. A second (flotation) run was then carried out. Using this method, the virus recovery rate was more than 95% that of the first run, and the levels of cellular DNA and bovine serum protein were well within the acceptable limits of less than 100 pg/dose and one part per million, respectively. The substrate DNA was quantified by both radioactive labeling and non-radioactive biotin labeling methods. For the quantification of calf serum protein, a counter-immunoelectrophoresis method was developed and effectively applied. A potency assay was performed using the National Institutes of Health (NIH) and well-standardized in vitro single radial immuno diffusion (SRD) methods. Finally, an immunogenicity study was conducted with human volunteers and the results were confirmed by a rapid fluorescent focus inhibition test (RFFIT).

Journal Article↗
PubMed2004

Performance optimization of spectroscopic process analyzers.

To increase the power and the robustness of spectroscopic process analyzers, methods are needed that suppress the spectral variation that is not related to the property of interest in the process stream. An approach for the selection of a suitable method is presented. The approach uses the net analyte signal (NAS) to analyze the situation and to select methods to suppress the nonrelevant spectral variation. The empirically determined signal-to-noise of the NAS is used as a figure of merit. The advantages of the approach are (i). that the error of the reference method does not affect method selection and (ii). that only a few spectral measurements are needed. A diagnostic plot is proposed that guides the user in the evaluation of the particular suppression method. As an example, NIR spectroscopic monitoring of a mol-sieve separation process is used.

Journal Article↗
PubMedDate not supplied

Optimal synthesis of protein purification processes.

There has been an increasing interest in the development of systematic methods for the synthesis of purification steps for biotechnological products, which are often the most difficult and costly stages in a biochemical process. Chromatographic processes are extensively used in the purification of multicomponent biotechnological systems. One of the main challenges in the synthesis of purification processes is the appropriate selection and sequencing of chromatographic steps that are capable of producing the desired product at an acceptable cost and quality. This paper describes mathematical models and solution strategies based on mixed integer linear programming (MILP) for the synthesis of multistep purification processes. First, an optimization model is proposed that uses physicochemical data on a protein mixture, which contains the desired product, to select a sequence of operations with the minimum number of steps from a set of candidate chromatographic techniques that must achieve a specified purity level. Since several sequences that have the minimum number of steps may satisfy the purity level, it is possible to obtain the one that maximizes final purity. Then, a second model that may use the total number of steps obtained in the first model generates a solution with the maximum purity of the product. Whenever the sequence does not affect the final purity or more generally does not impact the objective function, alternative models that are of smaller size are developed for the optimal selection of steps. The models are tested in several examples, containing up to 13 contaminants and a set of 22 candidate high-resolution steps, generating sequences of six operations, and are compared to the current synthesis approaches.

Biotechnology↗