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At least 127 records · Page 7Linked to original sources

Three-dimensional reconstruction of temporal bone from computed tomographic scans on a personal computer.

The advantages of computer reconstruction of anatomical structures from computed tomographic scans are common knowledge by now. Unfortunately, to date most reconstructions have required the use of large computers and/or have entailed tedious manual contour tracing. The system described here allows largely automatic detection of surfaces in computed tomographic scans plus the usual display capabilities including feature selection, magnification, rotation, shading, and slicing as well as measurement of lengths and angles. It runs on a normal International Business Machines AT-compatible computer with a medium-resolution video card.

Child

Discontinuing therapy in childhood acute lymphocytic leukemia. A multicentric survey in Italy.

The results of discontinuing therapy in children with acute lymphocytic leukemia observed at four associated institutions are presented. Of the 247 patients who achieved complete remission, 122 (49.3%) reached the point of discontinuing therapy after 2-4 years of continuous remission. The median period off therapy was 13 months with a range of 1-69 months. Of the 122 children removed from therapy, 27 (22.1%) relapsed, mainly in the bone marrow; relapses occurred 1-32 months after cessation of therapy (median ten months) with only two relapses occurring later than two years. By actuarial analysis, 57% of the patients are projected in continuous remission after five years from cessation of therapy. Neither selected features at diagnosis nor single modalities of treatment were found to predict whether relapse would occur after discontinuing therapy. Long-term remission and possibly cure can be expected in over one-third of newly diagnosed children with ALL after 2-4 years of antileukemic treatment.

Adolescent

The functional significance of tumour-associated cell surface alterations of embryonic and unknown origin.

The study of the phenotype of tumours aims to elucidate cell surface alterations that could be used for diagnostic, prognostic or therapeutic purposes. As tumours tend to escape the homeostatic growth control mechanisms of the host, it can be assumed that plasma membrane alterations are also responsible for the antisocial behaviour of tumour cells. Selected features of the transformed phenotype, of fetal or unknown origin, namely tumour-associated antigens, isozymes and growth factors, are discussed in relation to the altered growth pattern of the tumour cell. It is concluded that definitive structure-function relationships have not yet been established, but areas for future investigation are suggested.

Animals

On fully automatic feature measurement for banded chromosome classification.

Procedures for fully automatic location of chromosome axis and centromere in metaphase chromosomes are described for a practical interactive chromosome analysis system that omits the usual stages of interactive axis and centromere correction. Accuracy of centromere finding and consequential determination of a chromosome's polarity, i.e., which end is which, is measured experimentally. The saving in interaction by not correcting centromeres is compared to the increase in errors at the classification stage and the consequent increase in interaction needed to correct these errors. Some previously unreported features for banded chromosome classification are described, and in particular a set of global shape features is introduced. The discrimination capability of the feature measurements is evaluated by use of simple statistics and by reference to the performance of classifiers trained with various feature subsets. Class discrimination capability of the global shape feature set is shown to be comparable to that of centromere position, a widely used local shape feature. The variability of feature measurements that might occur in data from different laboratories on account of differing tissue, preparation methods, and digitiser hardware is assessed using three data bases of G-banded human metaphase cells. It is shown that the differences can be considerable and that appropriate feature selection and classifier training substantially improve classification performance.

Chromosomes

Structure-activity studies of barbiturates using pattern recognition techniques.

The relationship between molecular structure and duration of depressant effect for barbiturates was investigated. A data set of 160 5,5'-disubstituted barbiturates with various acyclic substituents was coded using 47 numerical descriptors including fragments, substructures, environmental descriptors, and molecular connectivity indexes. All descriptors were derived directly from the connection tables of the barbiturates. Using an interactive error-correction feedback algorithm, linear discriminant functions were developed that could dichotomize the data set with respect to several thresholds separating longer from shorter acting compounds. Feature selection was used to focus on the relatively few structural descriptors sufficient to support linear separability. For three specific thresholds, nine, 11, and nine descriptors were sufficient. The importance of these descriptors and the utility of the technique are discussed. Predictive abilities of approximately 94% were obtained for known barbiturates of the same general molecular types.

Animals

A comparison of the chemical analyses of cell lipids with their complete proton NMR spectrum.

Whole cells are made up of molecules in different environments to which NMR spectroscopy is sensitive. In particular, malignant and transformed cells contain lipids not only in bilayers but in isotropically tumbling domains which give rise to high-resolution spectra. We have recently developed a technique for simultaneously analyzing broadline and high-resolution signals (M. Bloom, K. T. Holmes, C. E. Mountford, and P. G. Williams, J. Magn. Reson., in press) and we report here its application to a range of rat, mouse, and human cell lines. Some selected features of the NMR spectra were compared with the chemical analysis of the whole-cell lipid. We found that in general the proportion of protons in the narrow methylene resonance at 1.3 ppm increased with the neutral lipid content of the cells. This peak was chosen because its T2 relaxation behavior correlates with metastatic potential in a rat model system. This new technique could be applied to other high-resolution components both in healthy and in diseased states.

Animals

Eigenimage filtering in MR imaging: an application in the abnormal chest wall.

A postprocessing linear filter was applied to spin-echo images on 10 patients with known or suspected chest wall invasion due to bronchogenic carcinoma. This technique known as eigenimage filtering allows selective feature extraction of suspected abnormalities from conventional MR images. The final result is an image with marked increased contrast range through enhancement of a desired process (tumor) with suppression of an interfering process (e.g., normal surrounding tissue). This preliminary work demonstrates the ease with which the technique may be implemented, the contrast enhancement obtained between the desired and the interfering feature in the final eigenimage, and its ability to correct for partial volume averaging effects. Also demonstrated are artifacts that can interfere with the interpretation of the eigenimage and a method for minimizing these artifacts in the final eigenimage.

Carcinoma, Bronchogenic

Hierarchical Multi-Label Classification With Gene-Environment Interactions in Disease Modeling.

In biomedical studies, gene-environment (G-E) interactions have been demonstrated to have important implications for analyzing disease outcomes beyond the main G and main E effects. Many approaches have been developed for G-E interaction analysis, yielding important findings. However, hierarchical multi-label classification, which provides insightful information on disease outcomes, remains unexplored in G-E analysis literature. Moreover, unlabeled data are commonly observed in practical settings but omitted by many existing methods of hierarchical multi-label classification. In this study, we consider a semi-supervised scenario and develop a novel approach for the two-layer hierarchical response with G-E interactions. A two-step penalized estimation is then proposed using an efficient expectation-maximization (EM) algorithm. Simulation shows that it has superior performance in classification and feature selection. The analysis of The Cancer Genome Atlas (TCGA) data on lung cancer demonstrates the practical utility of the proposed method. Overall, this study can fill the important knowledge gap in G-E interaction analysis by providing a widely applicable framework for hierarchical multi-label classification of complex disease outcomes.

Humans

Vasopressin gene related products are markers of human breast cancer.

Immunohistochemical analysis for products of vasopressin and oxytocin gene expression was performed on acetone-fixed tissues from 19 breast cancers representing a variety of tumor sub-types. Studies employed the avidin-biotin complex (ABC) immunohistochemical procedure and utilized rabbit polyclonal antibodies to arginine vasopressin (VP), provasopressin (ProVP), vasopressin-associated human glycopeptide (VAG), oxytocin (OT), oxytocin-associated human neurophysin (OT-HNP), and a mouse monoclonal antibody to vasopressin-associated human neurophysin (VP-HNP). Western Blot analysis was performed on protein extracts of fresh-frozen tissues from 12 additional breast tumors. While VP gene related proteins were not detected in normal breast tissue, immunohistochemistry revealed the presence of VP, ProVP, and VAG in all neoplastic cells for all of the tumor tissues examined. Vasopressin-associated human neurophysin was evident in only one of 19 acetone-fixed tumor preparations. However, Western blot analysis for all 12 fresh-frozen tumor samples showed the presence of two proteins, 42,000 and 20,000 daltons, that were immunoreactive with antibodies to VP, VP-HNP, and VAG. Oxytocin and OT-HNP, by immunohistochemistry, were found to be common to cells of normal breast tissues. For tumors, positive staining for OT was observed in 8 of 18 tumors, while OT-HNP was not detected in any of the tumors examined. These findings indicate that VP gene expression is a selective feature of all breast cancers, and that products of this expression might therefore be useful as markers for early detection of this disease and as possible targets for immunotherapy.

Antibodies, Monoclonal

Digital Immunophenotyping of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Subtypes With Specific Tumor-Immune Microenvironment Features.

Atypical carcinoids (ACs) and large cell neuroendocrine carcinomas (LCNECs) are defined by the WHO as intermediate- and high-grade lung neuroendocrine neoplasms, respectively, based on morphological criteria; however, treatment strategies remain debated. Given the emerging role of the tumor microenvironment (TME) and tumor-infiltrating lymphocytes (TILs) in cancer prognosis and therapy response, this study aimed to characterize the immune landscape of ACs and LCNECs comprehensively. Immunohistochemistry for T-cell markers (CD3, CD8), immune checkpoints (PD-1, PD-L1), HLA molecules (HLA-DR, HLA-I), and fibroblasts (&#x3b1;-SMA) was performed on a re-evaluated cohort of 56 ACs and 104 LCNECs. Digital image analysis quantified intra-tumor (iTILs) and stromal (sTILs) CD3 and CD8 TILs in the whole slide and in specific tumor regions (invasive margin [IM] and central tumor [CT]). LCNECs exhibited significantly higher stromal T-cell infiltration, immune checkpoint expression, and HLA compared to ACs (p&#x2009;<&#x2009;0.001), while &#x3b1;-SMA was more prominent in ACs. No ACs showed PD-L1 tumor expression. Digital quantification confirmed greater iTILs and sTILs in LCNECs across all regions, with moderate concordance to manual counts. Interestingly, TIL parameters were higher at the IM than in the CT (p&#x2009;<&#x2009;0.001). Using Boruta feature selection algorithm, Principal Component Analysis and Hierarchical Clustering, three patient clusters were identified: Cluster 1 (mainly ACs, low TILs, favorable prognosis), Cluster 2 (mixed histology, intermediate TILs, moderate prognosis), and Cluster 3 (mostly LCNECs, high TILs, poor prognosis), with distinct TME marker profiles. PD-L1 tumor expression was strongly linked to Cluster 3. These findings suggest that ACs and LCNECs may be stratified into three distinct immune clusters, highlighting the heterogeneity of their tumor microenvironment and providing a rationale for further translational studies.

Humans

On AR modelling for MEG spectral estimation, data compression and classification.

The use of the autoregressive (AR) model for magnetoencephalogram (MEG) processing is examined and compared to other methods. Spectral estimation, classification and data compression of MEG signals are studied. In application to spectral estimation the AR model is compared to the classical modified periodogram method. Also, AR modelling appears to perform very successfully when used for the classification of normal and epileptic MEG signals. Finally, the 17:1 to 23:1 data compression achieved by AR modelling, along with the above-mentioned advantages, render it suitable for storage applications. For comparison, the method of feature selection via orthogonal expansion is used as a tool to achieve data reduction. It is seen that while effective, this is less drastic than the compression of data volume achieved by AR modelling.

Brain Mapping

Dynamic decision models for clinical diagnosis.

A unified approach to clinical decision-making is presented. This combines partially observable Markovian decision processes (Markov or semi-Markov) with cause-effect models as a probabilistic representation of the diagnostic process. Pattern recognition techniques are used in a first stage of system state identification. This new class of dynamic models has a direct application to medical diagnosis and treatment and specific physiological examples are emphasised. The methodology is given for combining the patient state of health, the clinician's state of knowledge of the cause-effect representation from the observation space (measurements), feature selection using pattern recognition techniques and, finally, the treatment decisions with which to restore the patient to a more desirable state of health. A cost functional for the decision process has then to be optimised according to some pre-assigned objective function (social return from the patient state of health or treatment cost for the patient), when the process has an infinite time horizon.

Computers

Becoming a nurse: the ethical perspective.

This paper examines selected features of neophyte nursing students' approach to the moral dimension of their future practice. It argues that rapid changes in medical technology and in social perceptions of morality necessitate a critical examination of the content, sequence and methods of introductory ethics education in nursing. It suggests that greater emphasis should be placed upon individual moral development; and that Codes of Ethics and Bills of Rights should be presented as ideal statements, to serve as guides in assessing the ethical situation of the client. Some reactions of students are reported.

Curriculum

Evoked potential estimates of the time course of adaptation and recovery to counterphase gratings.

Scalp-recorded evoked potentials (VEP) were sequentially sampled in humans during adaptation to and recovery from prolonged viewing of counterphase sinusoidal grating targets. The sum of the power at the first and second harmonics of the Fourier-transformed VEP components was found to decrease during adaptation and increase during recovery. Time constants (T) for the adaptation and recovery processes as estimated from exponential functions ranged from 2.9 to 19 sec, varying non-monotonically with the spatial frequency and contrast of the stimulus. The observed T values are shorter than those reported in psychophysical studies of adaptation but overlap estimates derived from single cell studies. An unexpected finding was the occurrence of a 3-6 sec delay in the appearance of the maximum VEP response after the onset of the adaptation stimulus. The delay occurred in all subjects and at all spatial frequencies when moderate to high adapting contrasts (e.g. greater than 0.2) were used. The data support a feature-selective, multi-channel lateral inhibitory model of spatial vision and suggest the presence of tonic inhibition between the channels.

Adaptation, Ocular

BMDP program for piecewise linear regression.

Piecewise linear regression has potentially broad applications in medical data analysis as well as other types of regression. Various kinds of algorithms have been proposed for finding optimum piecewise linear regressions. This paper presents a BMDP program for obtaining near optimum piecewise linear regression equations. An idea intrinsic to the method is that restricting parameter space to a discrete set makes the difficult problems become standard problems. Any software having the variable selection feature in the multiple linear regression can be used to apply the method.

Computers

Beneficial effects of nicotine administered prior to a delayed matching-to-sample task in young and aged monkeys.

Our earlier studies have demonstrated that administration of low micrograms/kg doses of nicotine to young adult monkeys prior to a delayed matching-to-sample (DMTS) task resulted in a centrally mediated improvement in performance of the task, particularly when delay intervals which most greatly challenged the animal's capabilities were involved. The present study confirmed these findings using a completely computer driven and automated procedure. In addition, performance on the DMTS was observed to be enhanced when animals were again tested 24 h after the dose of nicotine. Further analysis of the data indicated that the majority of enhancement to nicotine could be accounted for by a greatly increased performance at the least preferred stimulus color. Position preference (left vs. right stimulus) was not a factor in nicotine-induced enhancement. Two aged monkeys (34 years old Macaca mulatta) were significantly more difficult to train in the DMTS task and their longest delay capabilities were significantly shorter than the young animals (Macaca fascicularis). Nevertheless, the aged animals were essentially similar in most respects in their responses to nicotine administration. These data are consistent with a role for central nicotinic systems in memory performance and with the ability of nicotine to produce enhancement of selective features of mnemonic strategy in young and old monkeys. Furthermore, it is possible that either model, the aged animal, or the young animal stressed to his mnemonic capability may provide a good model for learning and memory disorders in humans.

Aging

Lung collagen and elastin after ozone exposure in vitamin B-6-deficient rats.

The effects of vitamin B-6 deficiency and ozone exposure on selected features of connective tissue metabolism in lung were investigated in groups of weanling male rats fed one of three diets: B-6-supplemented, fed ad lib; B-6-deficient, fed ad lib; or B-6-supplemented, restricted to the food intake of deficient rats for 5 weeks. Also, perinatal rat pups were studied that were nursed from dams fed one of the 3 diets from parturition to day 15 of lactation. During the final week of each experiment, half of the rats in each of the groups were exposed to 0.64 ppm of ozone (23.5 h per day). The collagen and elastin content, collagen synthesis rate, total protein synthesis rate, and lysyloxidase activity of lungs were measured. Perinatal pups rendered vitamin B-6-deficient were particularly sensitive to ozone exposure (65% died as compared to fewer than 5% of the ad lib or food-restricted controls). When L-proline incorporation into collagen and total protein was investigated using lung minces, food restriction and B-6-deficiency resulted in about one-half the incorporation normally observed. Total lung lysyl oxidase activity was also decreased in B-6-deficient and food-restricted rats compared to B-6-supplemented rats fed ad lib. Exposure to ozone resulted in increased lysyl oxidase activity and collagen synthesis in lungs from B-6-supplemented rats, but such responses were not observed in B-6-deficient or food-restricted (FR) rats exposed to ozone.

Aging