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PubMed1997

Human biological decline and mortality rates.

Intercepts on the x (age)-axis of 107 normalized declining human biological functions were determined and assembled in 3 histograms, being placed in increasing order within each decade (10 year period). The histograms were classed accordingly as they contained properties associated with dividing cells, sensory properties and non-dividing cells respectively. Their cumulants were determined, multiple regressions calculated and compared with current death-rates for women and men respectively, for 10 amongst the longest living populations in the World. An alternative verification based on risk theory led to an estimate of an optimal life expectancy of 96 years. The survival curve turns out to be of the form (See text: Formula) where the inner integral represents the cumulant dimension (t') and the outer one age (t"). The premises underlying this study are compatible with the notion of a probable life-span, rather than a fixed one.

Adult↗
PubMed2000

Data mining in brain imaging.

Data mining in brain imaging is proving to be an effective methodology for disease prognosis and prevention. This, together with the rapid accumulation of massive heterogeneous data sets, motivates the need for efficient methods that filter, clarify, assess, correlate and cluster brain-related information. Here, we present data mining methods that have been or could be employed in the analysis of brain images. These methods address two types of brain imaging data: structural and functional. We introduce statistical methods that aid the discovery of interesting associations and patterns between brain images and other clinical data. We consider several applications of these methods, such as the analysis of task-activation, lesion-deficit, and structure morphological variability; the development of probabilistic atlases; and tumour analysis. We include examples of applications to real brain data. Several data mining issues, such as that of method validation or verification, are also discussed.

Algorithms↗
PubMedDate not supplied

An interventional strategy to strengthen integration of NLEP into primary health care.

The Government of Orissa implemented the Revised Operational Strategy in September 1999 to integrate the NLEP functions into primary health care activities. An interventional strategy, in the form of consensus on job responsibilities and capacity-building through training of PHC staff, was developed and adopted in a rural block under the Department of Community Medicine to strengthen the integration process. The impact was studied six months after the intervention by comparing it with the leprosy situation in the pre-intervention period. Data were collected by verification of registers at the block PHC and sub-centre levels. Analysis was done using different leprosy indices, such as new case-detection rate (NCDR), child rate, deformity rate, profile of leprosy cases and patient compliance, etc. This integrated approach was found to be more community-oriented and effective in early case-detection in children and women. It also helped in providing continuous MDT services because of the involvement of primary health care functionaries in the post-intervention period.

Adult↗
PubMed2001

Evaluation of frontal chromatograms.

Frontal chromatograms were investigated at low effluent concentrations, and deviations from the pertinent theory of chromatography were found in that region. These deviations are explained by a prerun in the column occurring between column wall and adjacent vertical particle layer. A model was devised for adapting these deviations to a mathematical function. According to that model, frontal chromatograms have an additional inflection point at low effluent concentrations with coordinates defined by the geometry of the column and the particles of the column bed. These coordinates are only altered by a packing density leading to particle distortion; on the premises of a reproducible column packing, these values are neither affected by kinetic parameters nor by a deterioration of the active particle surface. The experimental verification shows that the model can be employed to describe frontal chromatograms up to the second inflection point, when the effluent concentration reaches half of the feed concentration. A technical application is indicated in the paper.

Chromatography↗
PubMed2000

Current distribution in skeletal muscle activated by functional electrical stimulation: image-series formulation and isometric recruitment curve.

The present work develops an analytical model that allows one to estimate the current distribution within the whole muscle and the resulting isometric recruitment curve (IRC). The quasistatic current distribution, expressed as an image series, i.e., a collection of properly weighted and shifted point-source responses, outlines an extension for more than three layers of the classical image theory in conductive plane-stratified media. Evaluation of the current distribution via the image series expansions requires substantially less computational time than the standard integral representation. The expansions use a unique recursive representation for Green's function, that is a generic characteristic of the stratification. This approach permits one to verify which of the tissue electrical properties are responsible for the current density distribution within the muscle, and how significant their combinations are. In addition, the model permits one to study the effect of different electrode placement on the shape and the magnitude of the potential distribution. A simple IRC model was used for parameter estimation and model verification by comparison with experimentally obtained isometric recruitment curves. Sensitivity of the model to different parameters such as conductivity of the tissues and activation threshold was verified. The resulting model demonstrated characteristic features that were similar to those of experimentally obtained data. The model also quantitatively confirmed the differences existing between surface (transcutaneous) and implanted (percutaneous) electrode stimulation.

Biomedical Engineering↗
PubMed2006

An effective method to verify line and point spread functions measured in computed tomography.

This study describes an effective method for verifying line spread function (LSF) and point spread function (PSF) measured in computed tomography (CT). The CT image of an assumed object function is known to be calculable using LSF or PSF based on a model for the spatial resolution in a linear imaging system. Therefore, the validities of LSF and PSF would be confirmed by comparing the computed images with the images obtained by scanning phantoms corresponding to the object function. Differences between computed and measured images will depend on the accuracy of the LSF and PSF used in the calculations. First, we measured LSF in our scanner, and derived the two-dimensional PSF in the scan plane from the LSE Second, we scanned the phantom including uniform cylindrical objects parallel to the long axis of a patient's body (z direction). Measured images of such a phantom were characterized according to the spatial resolution in the scan plane, and did not depend on the spatial resolution in the z direction. Third, images were calculated by two-dimensionally convolving the true object as a function of space with the PSF. As a result of comparing computed images with measured ones, good agreement was found and was demonstrated by image subtraction. As a criterion for evaluating quantitatively the overall differences of images, we defined the normalized standard deviation (SD) in the differences between computed and measured images. These normalized SDs were less than 5.0% (ranging from 1.3% to 4.8%) for three types of image reconstruction kernels and for various diameters of cylindrical objects, indicating the high accuracy of PSF and LSF that resulted in successful measurements. Further, we also obtained another LSF utilizing an inappropriate manner, and calculated the images as above. This time, the computed images did not agree with the measured ones. The normalized SDs were 6.0% or more (ranging from 6.0% to 13.8%), indicating the inaccuracy of the PSF and LSE We could verify LSFs and PSFs for three types of reconstruction kernels, and demonstrated differences between modulation transfer functions (MTFs) derived from validated LSFs and inaccurate LSFs. Our technique requires a simple phantom that is suitable for clinical scanning, and does not require a particular phantom containing some metals or specific fine structures, as required in methods previously used for measurements of spatial resolution. Therefore, the scanned image of the phantom will be reliable and of good quality, and this is used directly as a confident reference image for the verification. When one obtains LSF, PSF or MTF values, verification using our method is recommended. Further, when another method for the measurement of LSF and PSF is developed, it could be validated using our technique, as illustrated in the method proposed by Boone [Med. Phys. 28, 356-360 (2001)] and used in this paper.

Algorithms↗
PubMed2001

The Zeiss-MKM system for frameless image-guided approach in epidural motor cortex stimulation for central neuropathic pain.

OBJECT: Twelve patients (seven female, and five male, mean age 55.6 years) suffering from refractory central (ischemic/traumatic [eight cases]) and neuropathic pain (trigeminal neuropathy [four cases]) underwent surgery for the implantation of an epidural motor cortex stimulation (MCS) device in which the authors used a frameless neuronavigation system, the Zeiss-MKM microscope. METHODS: The authors assessed the spatial accuracy of the neuronavigation system and its potential contribution to improve the quality of targeting pain. In these patients, the positions of the central sulcus, defined by stereotactic magnetic resonance MR imaging, intraoperative somatosensory evoked potentials (SSEPs) and subdural visual verification, were correlated into the stereotactic neuronavigation planning procedure. The mean spatial accuracy of distance between (MR) imaging-defined and actual central sulcus was 2.4 mm (range 5-10 mm). The intraoperative SSEPdefined central sulcus was close to that defined by MR imaging (mean distance 6.4 mm). Although very precise, intraoperative SSEP recordings were impaired by artifacts and wave attenuation in six of the 12 patients. Stereotactic correlations between anatomical and functional data in the navigation system corrected final targeting in 10 of 12 cases. Pain relief was obtained in eight patients. Indeed, inappropriate targeting probably explains the reported variable success rate of MCS and certainly underestimates the actual efficacy. CONCLUSIONS: Since intraoperative SSEP monitoring has, for many years, been considered the standard procedure to approach motor target, the development of an accurate stereotactic image guidance system could help to increase the efficacy of MCS on the alleviation of pain. The excellent spatial accuracy provided by the Zeiss-MKM navigation system allows precise data correlations that represent a remarkable means to validate functional MR imaging as an alternative to SSEP. The authors believe that developing stereotactic image guidance with such a navigation system could improve the success rate of MCS.

Deep Brain Stimulation↗
PubMed2000

Transcriptional repressor CopR: structure model-based localization of the deoxyribonucleic acid binding motif.

The plasmid pIP501 encoded transcriptional repressor CopR is one of the two regulators of plasmid copy number. CopR binds as a dimer to a nearly palindromic operator with the consensus sequence 5'-CGTG. Intermediate sequence searches revealed a significant structural relationship between CopR and the bacteriophage P22 c2 and the 434 c1 repressors. In this report we describe the experimental verification of a CopR homology model, which is based on a fairly low-sequence identity of 13.8% to P22 c2 repressor. A model for the complex of CopR with the deoxyribonucleic acid (DNA) target was built on the basis of experimental footprinting data, the above-mentioned CopR homology model, and the crystal structure of the 434 c1 repressor-DNA complex. Site-directed mutagenesis was used to test the function of amino acids involved in sequence and nonsequence-specific DNA recognition and amino acids important for correct protein folding. CD measurements were performed to detect structural changes caused by the mutations. Exchanges of residues responsible for sequence-specific DNA recognition reduced binding to a nonspecific level. Mutations of amino acids involved in nonspecific DNA binding lead to decreased binding affinity while maintaining selectivity. Substitution of amino acids necessary for proper folding caused dramatic structural changes. The experimental data support the model of CopR as a helix-turn-helix protein belonging to the lambda repressor superfamily.

Amino Acid Motifs↗
PubMed1984

Fibrocapnography in the control of the respiratory airways passage.

With the authors' method of a fibrobronchoscopic investigation using a translucent catheter in the fibrinoscope Olympus with an operational channel of 1.9 mm there were determined in 8 patients in the sitting position possibilities of estimating the degree of free passage in the respiratory tract. Patients with relapsing bronchial inflammations were examined before and after the aspiration of bronchial secretions that was restricting the passage in the respiratory tract prior to the investigation. The measurement was done with apparatus URAS of the firm Jäger using recorder Hellige . Investigation after the aspiration of the bronchial secretions was supplemented by the inhalation of a highly concentrated O2 in two inspirations. In a well ventilated region there took place even regionally changes in the amplitude of the shape and slope of the end of the expiration curve of the capnographic record. The investigation is non-invasive and technically not very demanding. According to the results obtained in our conditions of investigation a further verification of the validity of the results attained can be recommended; also a modification of the capnographic devices in anaesthesiological apparatus is recommended for possible measurements to be done regionally at the level of the primary bronchi.

Bronchoscopy↗
PubMed1999

Multiplex relative RT-PCR method for verification of differential gene expression.

Differential display, suppression subtractive hybridization and other techniques for identification of differentially expressed genes produce fragments of cDNA from mRNAs whose differences in abundance must be verified. This report describes a relative multiplex RT-PCR assay that facilitates the analysis of large numbers of samples for differences in mRNA abundance without the use of radioactivity or blotting. The species of interest is co-amplified with 18S rRNA over a range of cycles followed by electrophoresis through ethidium bromide-agarose gels. Intensities of the bands of interest, normalized for 18S band intensities, are plotted as a function of cycle number. Regression equations fitted to the curves are used to calculate the number of cycles necessary for each sample's normalized signal to reach a threshold intensity. Differences between samples in the number of cycles required to reach that threshold reflect differences in the original abundances of those species. A comparison with results previously obtained using northern blots showed that relative differences as small as 20% and as large as an order of magnitude are accurately detected. The simplicity of the assay allows its routine application in both research and teaching laboratories.

Animals↗
PubMed1993

Verification of protein structures: patterns of nonbonded atomic interactions.

A novel method for differentiating between correctly and incorrectly determined regions of protein structures based on characteristic atomic interaction is described. Different types of atoms are distributed nonrandomly with respect to each other in proteins. Errors in model building lead to more randomized distributions of the different atom types, which can be distinguished from correct distributions by statistical methods. Atoms are classified in one of three categories: carbon (C), nitrogen (N), and oxygen (O). This leads to six different combinations of pairwise noncovalently bonded interactions (CC, CN, CO, NN, NO, and OO). A quadratic error function is used to characterize the set of pairwise interactions from nine-residue sliding windows in a database of 96 reliable protein structures. Regions of candidate protein structures that are mistraced or misregistered can then be identified by analysis of the pattern of nonbonded interactions from each window.

Carbon↗
PubMed2004

Dynamic light scattering microscopy. A novel optical technique to image submicroscopic motions. II: Experimental applications.

An experimental verification of an optical microscope technique to create spatial map images of dynamically scattered light fluctuation decay rates is presented. The dynamic light scattering microscopy technique is demonstrated on polystyrene beads and living macrophage cells. With a slow progressive scan charge-coupled device camera employed in a streak-like mode, rapid intensity fluctuations with timescales the order of milliseconds can be recorded from these samples. From such streak images, the autocorrelation function of these fluctuations can be computed at each location in the sample. The characteristic decay times of the autocorrelation functions report the rates of motion of scattering centers. These rates show reasonable agreement to theoretically expected values for known samples with good signal/noise ratio. The rates can be used to construct an image-like spatial map of the rapidity of submicroscopic motions of scattering centers.

Animals↗
PubMed2000

[Perinatal and newborn care in the Emilia-Romagna Region health planning].

The report summarizes the contents of a conclusion of a document of the workshop "Neonatal and Prenatal Intensive Care" activated by the Emilia-Romagna Region to set up the third Regional Health Planning 2000-2002. The proposals, wholly taken from the Regional Program, aim to improve the care improving the outcomes in terms of mortality and maternal-infant disability. The organizing model proposed is that of integrated networks of services distributed according to a hierarchy of functions (Hub & Spoke model): 1st, 2nd, and 3rd level of functions. The network services should function as an integrated system, governed by agreed clinical and organizational guidelines, in which requirements of equipment sets and professional abilities are identified, as well as, relationship criteria among the different levels that regulate the by-directional course of the patients and/or the operators: the continuous training activity, the monitoring of a set of process indicators and results and also the clinical-organizational audit activity, are the instruments identified for results verification and for continuous actions of improvements.

Female↗
PubMed1980

[Clinical and neurohistological aspects of constipation in newborn and early childhood].

This study is based on a collection of 385 cases of constipation in newborn infants and young children, investigated clinically and by means of histological and neurohistological examination of biopsies taken from the rectal mucosa. Neurohistological techniques proved superior for the differential diagnosis and, hence, of greater value for determining further therapeutic management, both medical and surcival. Four special problems are discussed: Hirschsprung's disease in different neurohistological and clinical findings in these cases, functional ileus of the large intestine in newborn infants, chronic constipation and, lastly, the problems of anal stenosis and anal atresia. The present series of cases serves to illustrate that colostomy, carried out at the right time, can be a life-saving procedure in coping with the grave problem of a potentially lethal enterocolithis in constipation of different aetiology of the newborn or somewhat older infant. Neurohistological investigation is, however, essential for verification of the diagnosis because in Hirschsprung's disease emergency colostomy prevents the development of megacolon.

Adolescent↗
PubMed1999

Comparing two prevalence rates in a two-phase design study.

An epidemiological study often uses a two-phase design to estimate the prevalence rate of a mental disease. In a two-phase design study, the first phase assesses a large sample with an inexpensive screening test, and then the second phase selects a subsample for a more expensive diagnostic evaluation. Furthermore, disease status may not be ascertained for all subjects who are selected for disease verification because some subjects are unable to be clinically assessed, while others may refuse. Since not all screened subjects are selected for diagnostic assessments, there is potential for verification bias. In this paper, we propose the maximum likelihood (ML) and bootstrap methods to correct for verification bias for estimating and comparing the prevalence rates under the missing-at-random (MAR) assumption for the verification mechanism. We also propose a method to test this MAR assumption. Finally, we apply our methods to a large-scale prevalence study of dementia disorders.

Aged↗
PubMed1993

Development of a second-generation fiber-optic on-line image verification system.

PURPOSE: We have previously reported the development of a fiber-optic fluoroscopic system for on-line imaging on radiation therapy machines with beam-stops because of space limitation. While the images were adequate for clinical purposes in most cases, an undesirable grid artifact existed and distracted visualization. The resolving power of the system, limited by the 1.6 mm x 1.6 mm dimension of the input fibers, appeared insufficient in some cases. This work identifies solutions to reduce grid artifact and to improve the resolution of the system. METHODS AND MATERIALS: In the clinical system, it was found that the scanning mechanism of the newvicon camera was deflected differently at various gantry positions because of the different orientation of the earth's magnetic field. The small image misregistration produced grid artifact during image normalization, particularly near boundaries of the fiber bundles. One approach taken to reduce magnetic field effects was to shield the camera with mu-metal. Alternatively, a charged-coupled-device camera was used instead of the newvicon camera. As for improving spatial resolution, fibers with smaller input dimension were used. A 20 cm x 20 cm high resolution fiber-optic prototype consisting of 250 x 250 fibers, each with an input dimension of 0.8 mm x 0.8 mm was constructed. Its performance was tested using several phantoms studies. RESULTS: Both shielding the newvicon camera with mu-metal or replacing it with a charge-coupled-device camera reduced grid artifact. However, optimal shielding could not be made for our clinical system because of the space limitation of its housing. High contrast resolution was improved, the 30% value of the modulation transfer function occurred at 0.3 linepairs per mm for the clinical system and at 0.7 linepairs per mm for the high-resolution prototype. However, because of the larger degree of transmission non-uniformity of the prototype, it was less effective using the current setup in detecting low contrast objects. CONCLUSIONS: The results are encouraging and demonstrate successful reduction of grid artifact and improvement of high contrast spatial resolution using the proposed methods. The less effective low contrast detection was related to reduced light collection efficiency due to use of prototype fibers whose productions were not closely monitored. The findings are being considered in our construction of a second generation clinical fiber-optic on-line image verification system.

Diagnostic Imaging↗
PubMed2005

Comparison of modified supports on the base of glycoprotein interaction studies and of adsorption investigations.

The features of matrices, suitable for affinity chromatography, have been extensively investigated and got subject for several reviews. But these investigations show, that there is still a lack in adsorbent characterization and a demand of comparative investigations of adsorbents, based on different materials with a range of different surface functionalities. In this work the performance of self-prepared silica and cellulose-based adsorbents were compared with commercially available polymeric supports. A model system was chosen comprising the lectins concanavalin A (ConA) and wheat germ agglutinin (WGA), which were covalently attached to the support matrices, combining the selectivity of the lectin-sugar interaction with the chemical and mechanical properties of the support that influence the efficacy of the prepared adsorbent. The verification of the different supports provides information about tayloring carbohydrate specific lectin adsorbents. The characterization outlines the main features of the different adsorbents and takes into account the properties of the pure supports. It encompasses immobilization kinetics and isotherms as well as the description of the binding capacity of the adsorbents by depicting adsorption isotherms. The separation performances were also investigated in terms of glycoprotein purification factors and recoveries. Further, detailed information about binding of GOD to immobilized ConA are obtained.

Adsorption↗
PubMed2000

Genetic network inference: from co-expression clustering to reverse engineering.

MOTIVATION: Advances in molecular biological, analytical and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-cluster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e. who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting and bioengineering.

Animals↗