Systems analysis approach to the evaluation of health hazards due to air contaminants in the development and deployment of the Fleet Ballistic Missile Weapon System.
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OBJECTIVES: To evaluate the validity of a leg-to-leg bioimpedance analysis (BIA) system in predicting body composition as measured by dual-energy X-ray absorptiometry (DXA) in postmenopausal women. SUBJECTS AND METHODS: Body fat mass (FM), %Fat and fat free mass (FFM) were measured in 124 postmenopausal women (age: 51-63 y, body mass index (BMI): 17-38 kg/m2) first by the leg-to-leg BIA system, and then by DXA as reference method. Bland-Altman analysis was used to determine the bias and 95% limits of agreement between the two methods for the assessment of the individual. Precision error (CV%) of the BIA system was obtained by repeated measurements with intermediate repositioning. RESULTS: The leg-to-leg BIA system had a high reproducibility with within-day CVs being 0.6% for FFM and 1.1% for FM, and between-day CVs about twice that. The impedance index (Ht2/Z) obtained by the leg-to-leg BIA was moderately correlated to FFM measured by DXA (r=0.66). A significant, systematic bias was observed between the two methods. The BIA system overestimated FM by a mean of 3.1 kg, and underestimated FFM by 2.7 kg. The analysis of 95% limits of agreement showed that for most individuals, %Fat estimated by the BIA might differ from that measured by DXA by 12% below to 45% above, indicating the lack of agreement between the two methods for the assessment of the individual. CONCLUSIONS: The leg-to-leg BIA system can provide simple, rapid and highly reproducible measurements of body composition for groups, but it has limited accuracy for the assessment of the individual. Population-specific equations will be needed to improve its accuracy in estimating body composition in postmenopausal women.
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The heterogeneity of regional pulmonary blood flow (RPBF) can be assessed by fractal analysis. The fractal dimension (FD) is a scale-independent measure of spatial heterogeneity of blood flow. The relative dispersion (RD) is often used to obtain the heterogeneity of RPBF but it is influenced by the resolution of measurement. The Blood Flow Analysis (BFA) System was developed in Delphi to represent the three-dimensional structure of lung blood flow and calculates statistics of FD, RD, spatial correlation of neighbored tissue samples and shows histograms of blood flows at diverse time points during different experiments. The BFA System reads a text file with flows, measured with fluorescent microsphere technique, and constructs the lung anatomy with volumetric pixels showing the flows with a color schema. It is possible to rotate the lungs into two axis (XY) and the statistics are shown with 3D graphics. The System maintains a database with data from various studies at same time. The BFA System was validated with four data sets from previous experiments. The BFA System has shown consistency and it is a new tool to help researchers during lung perfusion studies.
We demonstrate a general approach for metabolic engineering of biocatalytic systems comprising the uses of a chemostat for strain improvement and radioisotopic tracers for the quantification of pathway fluxes. Flux determination allows the identification of target pathways for modification as validated by subsequent overexpression of the corresponding gene. We demonstrate this method in the indene bioconversion network of Rhodococcus modified for the overproduction of 1,2-indandiol, a key precursor for the AIDS drug Crixivan.
The diagnosis and management of convergence insufficiency (CI) is discussed through a control systems model of the combined accommodation and disparity vergence mechanisms. The emphasis is put on drawing definite clinical implications such that CI can be understood as a logical continuum from its etiology, through symptoms, signs, and finally through its treatment.
BACKGROUND: Transmission electron micrographs are widely used to demonstrate tissue damage. However, the results are qualitative and dependent on the experience of the investigator. Recently, a new multiscale object-based quantitative image analyzing systems (Cellenger) has been introduced to study highly textured black-and-white images. It is unknown, whether this system permits the quantitative image analysis of electron micrographs of parenchymal tissue. Therefore, we analyzed whether the Cellenge system permits the quantitative evaluation of electron micrographs of murine liver under normal conditions and after ischemia-reperfusion injury. The results were compared with those obtained by conventional qualitative classification. - METHOD: Transmission electron micrographs from murine liver that had been exposed to isolated reversible ischemia at hypothermic conditions of 4 degrees C, 15 degrees C, 26 degrees C and 37 degrees C, and of sham-operated animals, which served as controls (2 images per animal, n = 3 in each group), were analyzed qualitatively by an investigator with experience in electron microscopy. For quantitative analysis, the Cellenger was used and the following damage parameters were studied: ratio of area of endothelial cell nucleus to area of endothelial cell (N/C ratio), ratio of area of hepatocellular vacuoles to area of total hepatocyte cytoplasm (V/C ratio) and ratio of area of microvilli in the space of Disse to area of the sinusoids (M/S ratio). All values were sampled within one group (n=6) and the data given in [%] (MW +/- SEM). P-values were accepted as significant below 0.05. RESULTS: After normothermic ischemia, all quantitative damage parameter were significantly altered as compared to sham-operated animals (N/C 15 +/- 9% vs. 37 +/- 7%, V/C 18 +/- 4% vs. 0, and M/S 0 vs. 10 +/- 1%) and all hypothermia groups. The qualitative electron micrograph section analysis corresponded very well with these results. CONCLUSION: We demonstrate that an multiscale object-based quantitative analysis of transmission electron micrographs from mouse liver under control conditions and after I/R provide accurate classification of relevant tissue damage parameter. The system is now ready to use for further applications within the field of highly textured electron micrographs.
A comprehensive system for the acquisition and analysis of neurophysiological data is described, with a focus on intracellular data. The software comprising the system will evaluate a number of neuronal signals, including intracellular as well as extracellular recordings from neurons, evoked potentials and computer simulation data. Significant enhancements enable sampling at high resolution (50 kHz throughput to disk; +/- 15 bit or 96 db), concurrent with extensive on-line analysis capabilities and display. Modifications of existing software and development of new types of input and output devices and analysis can be incorporated as needed, using a binary digital database as the primary storage for the experimental signals and device-independent graphics.
The white-noise method of system identification has been applied to the transient light-growth response of a set of seven mutants of Phycomyces with abnormal phototropism, affected in genes madA to madG. The Wiener kernels, which represent the input-output relation of the light-growth response, have been evaluated for each of these mutants and the wild-type strain at a log-mean blue-light intensity of 0.1 W m-2. Additional experiments were done at 3 X 10(-4) and 10 W m-2 on the madA strain C21 and wild-type. In the normal intensity range (0.1 W m-2) the madA mutant behaves similarly to wild-type, but, at high intensity, the madA response is about twice as strong as that of wild-type. Except for C21 (madA), the first-order kernels of all mutants were smaller than the wild-type kernel. The first-order kernels for C111 (madB) and L15 (madC) show a prolonged time course, and C111 has a longer latency. The kernels for C110 (madE), C316 (madF), and C307 (madG) have a shallow and extended negative phase. For C68 (madD), the latency and time course are shorter than in the wild-type. These features are also reflected in the parameters estimated from fits of the analytical model introduced in the previous paper to the experimental transfer functions (Fourier transforms of the kernels). The kernel for L15 (madC) is described better by a model that lacks one of the two second-order low-pass filters, because its response kinetics are dynamically of lower order.
Elements of a systems approach to analysing service delivery are outlined. A specific example--St George's Hospital Addiction Behaviour Department--is detailed. Dynamics of the system--from the client's perspective and the workers viewpoint--demonstrate some of the ways in which emotional conflict surrounding the task is handled. The conclusions focus on what might constitute adaptive resolution of systems dilemmas as well as highlighting the public-health concerns relating to AIDS which, we argue, compromise the primary task of an addiction service at the present time.
A total systems approach is necessary to draw in integral concept of the pathological process as exemplified by investigations of morphogenesis of the infectious process. For this purpose a concept of the Mm-system is introduced and analysed which helps to study the infectious process as a special object: a system of microbial population (m) and macroorganism cells (M). The ontogenesis of the Mm-system is suggested consisting of 3 stages: formation, existence, and death. Considering the infectious process from the systemic point of view the author found many microbe-host cell interactions observed in infections to be characteristic not for the infectious pathology but to the particular manifestations of well-known but frequently ignored general biological regularities. A number of models of infectious diseases demonstrate the earliest morphological changes of the disturbed homeostasis in tissues containing microbes and the associated features of the infectious process. Comparing the time evolution of the Mm-system with the course of real infectious processes, one may approach the solution of some disputable aspects of the pathogenesis of infections, in particular, to elucidate the importance of intracellular accumulation of microbes observed in enteric infections. The Mm-system concept may find practical application in explaining pathomorphosis of infectious lesions under conditions of current methods of intensive specific therapy as well as in evaluating the mechanism of action of drugs when tested on models.
In this paper we introduce a systematic approach for the modelling of complex biological systems which is especially useful for the analysis of signal transduction mechanisms in cell biology. It is shown that systems analysis in form of top-down levelled dataflow diagrams provides a powerful tool for the mathematical modelling of the system in terms of a stochastic formulation. Due to the exact formulation, the consistency of the model with the experimental results can be tested by means of a computer simulation. The method termed Structured Biological Modelling (SBM) is illustrated by modelling some aspects of the second messenger network which regulates cell proliferation. As an example for the straightforward development of a mathematical description a stochastic computer model for intracellular Ca2+ oscillations is presented.
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