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[Possibilities for information processing and operations simplification in multidimensional tasks of morphokinetic synthesis].

The authors propose an iterative method for separating classes of objects by reduction of multidimentional space of sings, which describe objects by twodimentional space of two integral processings of the differences between sings. For this purpose the differences are evaluated by three steps rating: positive difference, negative difference and no difference. The proposed iterative algorhythm allows by finite and a small number of procedures to remove indeterminace which in the general case is contained in the so defined on the work integral processings. The application of the algorhythm does not require a special mathematical training. Represantation of the objects by integral characteristics is made in twodimentional space. In the paper the report the authors give a generalization for the case of M-steps rating for evaluation of the differences between the signs of the objects.

Information Theory↗

Analysis of options for mitigating hemodialysis access-related ischemic steal phenomena.

Steal phenomena associated with brachial bridge grafts for hemodialysis access may compromise blood flow to the forearm. This work is designed to investigate and compare, by means of a simple mathematical model, the potential of six surgical procedures to alleviate steal. A flow model based on an electrical analogue was developed. An untapered 6-mm prosthetic brachial-axillary access (PBAA) was selected as the prototype configuration, and the theoretical effect of six access modifications on forearm flow was analyzed. Major simplifications include the use of Poiseuille's law for estimating arterial resistance and ignoring the contribution of collateral circulation. Intra-operative flow measurements using a Transonic flowmeter were obtained in two individuals undergoing treatment for a steal syndrome. The flow model predicts that the greatest increase in distal flow is achieved by the distal revascularization-interval ligation (DRIL) procedure, followed by a 6-mm axillobrachial artery bypass graft without interval ligation, the conversion of the PBAA to an axillary-axillary loop access, and the conversion to an axillary-brachial access. Intra-operative measurements in two patients agreed closely with theoretical calculations. A simple flow model provides a tractable framework for comparing procedures designed to avoid or treat steal phenomena. Distal revascularization without interval ligation and the conversion of a PBAA to an axillary-axillary loop access or an axillary brachial access can be effective alternatives to the DRIL procedure in selected clinical settings.

Arm↗

Improving the industrial production of 6-APA: enzymatic hydrolysis of penicillin G in the presence of organic solvents.

The hydrolysis of penicillin G in the presence of an organic solvent, used with the purpose of extracting it from the culture medium, may greatly simplify the industrial preparation of 6-APA. However, under these conditions, PGA immobilized onto Eupergit displays very low stability (half-life of 5 h in butanone-saturated water) and a significant degree of inhibition by the organic solvent (30%). The negative effect of the organic solvent strongly depended on the type of solvent utilized: water saturated with butanone (around 28% v/v) had a much more pronounced negative effect than that of methylisobutyl ketone (MIBK) (solubility in water was only 2%). These problems were sorted out by using a new penicillin G acylase derivative designed to work in the presence of organic solvents (with each enzyme molecule surrounded by an hydrophilic artificial environment) and a suitable organic solvent (MIBK). Using such solvent, this derivative kept its activity unaltered for 1 week at 32 degrees C. Moreover, the enzyme activity was hardly inhibited by the presence of the organic solvent. In this way, the new enzyme derivative thus prepared enables simplification of the industrial hydrolysis of penicillin G.

Butanones↗

A general diagrammatic algorithm for contraction and subsequent simplification of second-quantized expressions.

We present a general computer algorithm to contract an arbitrary number of second-quantized expressions and simplify the obtained analytical result. The functions that perform these operations are a part of the program Nostromo which facilitates the handling and analysis of the complicated mathematical formulas which are often encountered in modern quantum-chemical models. In contrast to existing codes of this kind, Nostromo is based solely on the Goldstone-diagrammatic representation of algebraic expressions in Fock space and has capabilities to work with operators as well as scalars. Each Goldstone diagram is internally represented by a line of text which is easy to interpret and transform. The calculation of matrix elements does not exploit Wick's theorem in a direct way, but uses diagrammatic techniques to produce only nonzero terms. The identification of equivalent expressions and their subsequent factorization in the final result is performed easily by analyzing the topological structure of the diagrammatic expressions.

Algorithms↗

Cortical anatomy, size invariance, and spatial frequency analysis.

In a recent application of an algorithm developed in computer and optical pattern recognition, Cavanagh has suggested that a composite of spatial frequency mapping and complex logarithmic mapping would provide translationally, rotationally, and size-invariant mechanism for human vision. In this work, Cavanagh has not made explicit the fact that this transformation is composite, that is, that the first step (global Fourier analysis) perceptually, anatomically, and physiologically inconsistent with primate vision, but that the second step (complex logarithmic mapping) is actually embodied in the anatomy of the primate retinostriate projection. Moreover, it is the complex logarithmic remapping step which is entirely responsible for the computational simplification of the symmetries of size and rotation invariance. These facts, which have been extensively discussed in a recent series of papers, are briefly reviewed and illustrated. Furthermore, it is shown that the architecture of the retinostriate map may provide an example of computational anatomy in vision, such that the spatial representation of a stimulus in the brain may be of direct functional significance to perception, and to the nature of certain visual illusions.

Afterimage↗

Computer-aided investigations of respiratory data.

In the first part of this paper a computerised evaluation of plethysmographic signals is presented. The off-line processing described eliminates some erroneous simplifications that routine plethysmography is bound to involve. (1) A subtraction of the box pressure baseline permits measurements with perfectly sealed constant volume plethysmographs even in the case of thermal disequilibrium. (2) Alveolar pressure is computed from the box pressure signal, using instantaneous values of the intrathoracic gas volume. (3) This technique enables one to utilise all the measured data for determinations of airway resistance and viscous work, thus yielding more exact values as compared to the graphic evaluations. In Part 2 a three-parameter model of transpulmonary mechanics, applied to fit data of cat experiments, is described. The aim of this study is to demonstrate how transpulmonary parameters (static pleural pressure, compliance and resistance) are modified by the actual state of the pulmonary vascular bed.

Airway Resistance↗

A mathematical investigation of a Clock and Wavefront model for somitogenesis.

Somites are transient blocks of cells that form sequentially along the antero-posterior axis of vertebrate embryos. They give rise to the vertebrae, ribs and other associated features of the trunk. In this work we develop and analyse a mathematical formulation of a version of the Clock and Wavefront model for somite formation, where the clock controls when the boundaries of the somites form and the wavefront determines where they form. Our analysis indicates that this interaction between a segmentation clock and a wavefront can explain the periodic pattern of somites observed in normal embryos. We can also show that a simplification of the model provides a mechanism for predicting the anomalies resulting from perturbation of the wavefront.

Algorithms↗

Determination of the attenuation map in emission tomography.

Reliable attenuation correction methods for quantitative emission CT (ECT) require accurate delineation of the body contour and often necessitate knowledge of internal anatomic structure. Two broad classes of methods have been used to calculate the attenuation map: transmission-less and transmission-based attenuation correction techniques. Whereas calculated attenuation correction belonging to the first class of methods is appropriate for brain studies, more adequate methods must be performed in clinical applications, where the attenuation coefficient distribution is not known a priori, and for areas of inhomogeneous attenuation such as the chest. Measured attenuation correction overcomes this problem and uses different approaches to determine this map, including transmission scanning, segmented magnetic resonance images, or appropriately scaled CT scans acquired either independently on separate or simultaneously on multimodality imaging systems. Combination of data acquired from different imagers suffers from the usual problems of working with multimodality images--namely, accurate co-registration from the different modalities and assignment of attenuation coefficients. A current trend in ECT is to use transmission scanning to reconstruct the attenuation map. Combined ECT/CT imaging is an interesting approach; however, it considerably complicates both the scanner design and the data acquisition and processing protocols. Moreover, the cost of such systems may be prohibitive for small nuclear medicine departments. A dramatic simplification could be made if the attenuation map could be obtained directly from the emission projections, without the use of a transmission scan. This is being investigated either using a statistical model of emission data or applying the consistency conditions that allow one to identify the operator of the problem and, thus, to reconstruct the attenuation map. This article presents the physical and methodologic basis of attenuation correction and summarizes recent developments in algorithms used to compute the attenuation map in ECT. Other potential applications are also discussed.

Algorithms↗

Ergonomic aspects of cold stress and cold adaptation.

In contrast to the simplified, unvarying, and rigidly controlled conditions that characterize laboratory studies of human responses to cold, normal work in cold regions is characterized by a complex and unstable thermal environment, intermittent cold exposure and exercise, and the freedom to adjust clothing and activity for comfort. These "ergonomic" aspects profoundly modify the impact of a cold environment on people's health, comfort, and performance. A review of recent field studies in the Antarctic shows that the supposed "tropical microclimate" of clothed people in the cold is an over-simplification. People tend to be alternately chilled and overheated, and the accompanying exercise of the vascular responses provides a potential stimulus for vasomotor adaptation. Significant and substantial changes in men's responses to standardized whole-body cold exposures, observed on eight Antarctic expeditions, show that general acclimatization to cold develops as an increase in tissue insulation, which is mediated by an enhanced vascular response to cold.

Acclimatization↗

Integration of field measurements and reactive transport modelling to evaluate contaminant transport at a sulfide mine tailings impoundment.

Over a decade of field observations including geochemical, mineralogical and hydrological information are available on the generation of acid mine drainage from the Pistol Dam region of the P-area of Inco's tailings impoundment in Copper Cliff, Ontario. This work focuses on the integration and quantitative assessment of this data set using reactive transport modeling. The results of the reactive transport simulations are in general agreement with the field observations; however, exact agreement between the field and simulated results was not the objective of this study, and was not attained. Many factors contribute to the discrepancies between the field observations and simulation results including geochemical and hydrogeological complexities and necessary model simplifications. For example, fluctuating water levels observed at the site were averaged and described using a steady state flow system. In addition, the lack of representative thermodynamic and rate expression data contributed to the discrepancies between observations and simulation results, thus further research into the applicability of laboratory-derived thermodynamic and rate expression data to field conditions could minimize these discrepancies. Despite the discrepancies between the field observations and simulated results, integrating field observations with numerical modelling of the P-area tailings impoundment allowed for a more complete understanding of what affects the complex geochemical reactions.

Geological Phenomena↗

Quantitative affinity chromatography: increased versatility of the technique for studies of ligand binding.

The potential of affinity chromatography for the characterization of strong solute-ligand interactions is explored by studying the NADH-dependent elution of rabbit muscle lactate dehydrogenase from a column of trinitrophenyl-Sepharose in 0.067 M phosphate, pH 7.2. An interesting development is the simplification of the general affinity chromatography theory that emanates from the use of affinity matrices with a high concentration of immobilized reactant groups. The resultant expression allows evaluation of the intrinsic association constant for solute-ligand interactions from a single series of either zonal or frontal affinity chromatographic experiments conducted in the presence of a range of free ligand concentrations. Thus, contrary to previous belief, an affinity matrix designed for solute purification work should prove to be an asset for, rather than an impediment to, the study of solute-ligand interactions by quantitative affinity chromatography.

Adsorption↗

Modelling cell signalling and differentiation in the urothelium.

Urothelial cells line the bladder. If the urothelium is damaged, it is vital that it repairs itself quickly. Experimental results shedding light on how this repair process works are presented, revealing in particular the dependence of the response on the length of time for which the drug Troglitazone (TZ) is applied. A simple mathematical model for the basic mechanism (comprising ordinary differential equations) is then developed and analysed, seeking specifically to clarify and quantify the mechanisms governing the dependence of the cell differentiation response on the TZ administration time, rather than providing a comprehensive model of differentiation. Through biologically justified simplifications, analysis reveals that the model gives results in accord with the experimental observations, and suggests new experiments that may aid further understanding. Directions in which this preliminary modelling of the PPAR gamma (peroxisome proliferator activated receptor gamma) pathway could be usefully extended are also indicated.

Cell Differentiation↗

Automated method for characterization of diastolic transmitral Doppler velocity contours: late atrial filling.

We develop an automated method of characterizing the late atrial filling phase of diastole by fitting a kinematic model for diastolic filling to the clinical Doppler A-wave contour. The result is a set of model parameters which completely characterizes the contour. We have previously derived a parameterized diastolic filling (PDF) model, which predicts the time-dependent transmitral blood flow velocity obtained by Doppler echocardiography. An automated method to determine the PDF model parameters for early rapid filling from the clinical Doppler E-wave has also been developed and validated. The method consists of digitizing the acoustic Doppler waveform, recreating the Doppler velocity profile, extracting the maximum velocity envelope, and fitting the PDF model for early filling to the envelope. In the current work, we apply the same general approach for PDF parameter determination for the late atrial filling phase of diastole. To assess the presence and significance of near-degeneracies in the model parameter set, numerical experiments (consisting of fitting the model to a model-generated contour to which Gaussian noise was added) were performed. These revealed a two-dimensional degeneracy in four-dimensional parameter space which could be removed by using two kinematic simplifications: critical damping and resonant forcing. We show that these degeneracy-eliminating approximations do not limit the ability of the model to predict clinical A-wave contours.

Atrial Function↗

Molecular dynamics in the endgame of protein structure prediction.

In order adequately to sample conformational space, methods for protein structure prediction make necessary simplifications that also prevent them from being as accurate as desired. Thus, the idea of feeding them, hierarchically, into a more accurate method that samples less effectively was introduced a decade ago but has not met with more than limited success in a few isolated instances. Ideally, the final stages should be able to identify the native state, show a good correlation with native similarity in order to add value to the selection process, and refine the structures even further. In this work, we explore the possibility of using state-of-the-art explicit solvent molecular dynamics and implicit solvent free energy calculations to accomplish all three of those objectives on 12 small, single-domain proteins, four each of alpha, beta and mixed topologies. We find that this approach is very successful in ranking the native and also enhances the structure selection of predictions generated from the Rosetta method.

Automation↗

Identification of determinants of the between-operator variation of the total protein S antigen assay: a collaborative study of the Dutch Working Group on Haemostasis Laboratory Diagnosis.

In a previous study, a between-operator variability (CVOBETWEEN) of 9.6% and 15.0%) was observed for total protein S antigen assays in 11 laboratories using a frozen or lyophilized reference plasma, respectively, and the need to standardize the use of lyophilized reference plasma was identified. The aim of the present study was to identify further determinants of this CVOBETWEEN in order to improve between-laboratory comparisons of test results for one method for protein S antigen assay. Two protocols were carried out: the first again involving local execution but using a joint standardized and detailed prescription of the technical performance in each laboratory; the second using a central session for all operators with the same prescription but with joint reagent and equipment. In the present study, improved handling of lyophilized reference plasma was included and resulted in comparable CVOBETWEEN of 10.9% and 9.6% for the use of frozen and lyophilized reference plasma for the local test performance. An improvement was found in the CVOBETWEEN in the central session compared with the standardized local performance, showing lower values for the central performance of 8.5 and 6.6% for frozen and lyophilized reference plasma, respectively. Further analysis of the difference between the local and central test performance identified the use of different curve fit options of data evaluation software as a significant source of this difference. Interestingly, the within-operator variability in the central performance was around 2% lower (5.9 and 6.0% for frozen and lyophilized plasma, respectively) than that in the local performance (8.1 and 8.0% for frozen and lyophilized plasma, respectively). Although the reduction is not statistically significant, it suggests an effect of reduction of the workload and simplification of procedures for individual operators on the within-operator variability. In this study, in which 11 operators/laboratories participated, the lowest variability between operators andwithin laboratories was obtained in the central test performance, which is suggested to be the lowest attainable variability for the measurement of total protein S antigen. The practical factors involved in local performance that require attention to reach similar levels of variability are mainly liquid handling, curve-fit procedures and simplicity of practical procedures.

Adult↗

The new GMS contract: impact and implications for managing the changes.

BACKGROUND: In February 2003, a new General Practitioner (GP) contract was agreed between the profession's leaders and the government, which was later accepted following a national ballot of GPs. However, the ballot simply required respondents to vote for or against the proposal; it did not provide any opportunity to identify which aspects of the new contract were more or less acceptable. Since the proposed changes were far reaching, the implications of implementing and managing these were considerable. Consequently, some information about how GPs viewed various components of the new contract would enable a more targeted and effective management strategy to be developed that would facilitate the introduction of all aspects of the contract. OBJECTIVES: To survey GPs working within the West Midlands region regarding their opinions on each of the key features of the new contract. METHOD: A postal survey of 360 GPs was undertaken, using a specially devised questionnaire. RESULTS: Four factors emerged as the most acceptable aspects of the contract: option to opt out of out-of-hours work, flexibility in the services provided, prediction of future income levels and linking practice to performance targets. Least acceptable were: performance monitoring systems, the new financial formula for calculating income, greater patient involvement in service development and 24/48 hour access. With regard to potential outcomes of the contract, the most positive were considered to be increased proportion of salaried GPs, increased salaries, appropriate quality standards for care, earlier retirement; the factors least likely to be of potential benefit were: reduction in occupational stress, simplification of the regulatory framework, improved equity of workload and improved staff retention. Further analysis of the results using inferential statistics revealed a range of subgroup differences in reaction to the contract. CONCLUSION: Overall, those aspects of the new contract that are perceived to reduce workload and enhance salary were supported, while those that increase targets and bureaucracy were not. Generally, there was only moderate support for the changes, which could be explained by a general scepticism about any top-down modifications, the practicality and power of the changes to impact upon practice and/or a genuine belief that the modifications are unacceptable. Taken together, these results provide an indicative focus for managing the implementation of the new contract, especially with regard to its least acceptable components and the emerging differences between subgroups of GPs.

Attitude of Health Personnel↗

Radionuclide ventriculography (equilibrium gated blood pool scanning)--its present clinical position and recent developments.

Myocardial scanning (MS) and radionuclide ventriculography (RNV) are the foundation of nuclear cardiology. These procedures aim in two completely different directions: RNV tries to image heart motion, that is, mechanical (pump) function, and therefore belongs to the group of first-order functional imaging (FI, imaging mechanical function), whereas MS is based on myocardial metabolism, and therefore can be attributed to third-order functional imaging (metabolism). This statement is relevant for the assessment of the clinical position of RNV: Third-order (metabolism) functional imaging is the domain of nuclear medicine (NM), whereas first-order FI has to face the competition of alternative noninvasive procedures such as ultrasound (US), digital subtraction angiography (DSA), computer tomography (CT), and nuclear magnetic resonance (NMR). The domain of RNV includes stages two (acute infarction) and three (postinfarction period) of coronary arterial disease (CAD). The advantageous combination of quantitative data on global, left ventricular (LV) function and imaging of regional motion ensures the superiority of RNV over US. However, RNV is inferior to MS in physical examinations in the preinfarction stage of CAD, whereas US is clearly inferior to both NM procedures. Recent progress could be attained by gated SPECT (GASPECT). A proposal is presented for simplification of this time-consuming procedure. Technetium-labeled isonitriles offer the chance for the combination of "perfusion-motion" imaging of the myocardium. However, even standard RNV offers new possibilities. The multitude of parameters produced by quantitation has not yet been exploited completely. This can be done by discriminant analysis. The computer finds out an optimal subset from the whole set of parameters for the solution of a significant clinical problem. The software "learns" to find the "label" of a special pathognomonic entity. This computer work is supported by a relational data bank (Oracle) and an optical disk. Two examples for the effectiveness of the computer in problem solving are presented. It is concluded that RNV, even in the very competitive class of first-order functional imaging, enjoys a preferred position. The future indeed seems brighter because labeled isonitriles offer the chance for the combination of perfusion-motion imaging of the myocardium.

Coronary Disease↗

Alternatives for coupling sequential injection systems to commercial capillary electrophoresis-mass spectrometry equipment.

On-line coupling of an automated flow system with a commercially available capillary electrophoresis (CE) system with an electrospray interface (ESI) for mass spectroscopic (MS) detection is described. The peculiarities of CE-ESI-MS interfaces, in which a high electrical field must be applied to the capillary end where the sample is provided by the flow system, introduce significant difficulties for the appropriate work of the entire arrangement. Experimental strategies are proposed for achieving stable conditions for on-line sample pre-treatment, conditioning of the separation capillary, sample injection, as the proper separation. The versatility and robustness of the proposed arrangement is discussed, taken as example the separation of a variety of amines. Connection of the CE system's pressure to the automated flow system enables hydrodynamic introduction of sample with high precision. The developed hyphenated system is of practical relevance as it opens an avenue for the simplification and automation of the whole analytical process required when using powerful CE-ESI-MS equipments.

Butylamines↗