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PubMed1978

The measurement of change in endogenous affective disorders.

Psychopathological syndromes, as originally revealed by clinical observation, can also be detected by multivariate statistical analyses of symptom ratings. Changes in the course of psychiatric syndromes may be rated simply by improvement scales or by consecutive quantifications of symptoms and their comparison in chronological order. For the latter approach, which is less liable to bias, clinical ratings of psychopathology by staff members, self-ratings by the patients, analyses of patients' overt behavior (including video and speech records), or objective measurements of psychological and/or physiological variables can be used. Advantages and limitations of these different methods are discussed and illustrated by examples from ongoing clinical research in affective disorders. Generally, the combined use of different rating procedures is recommended. Self-ratings are economical, but they may represent aspects of psychopathology other than clinical ratings. In endogenous depression, mood scales are valid (supplementary) tools for the quantification of long-term as well as short-term changes, including diurnal variations. In severe conditions of mania, however, clinical rating has been--until now--the only valid basis for quantifying the degree of psychopathology and its changes with time. Precise evaluation of changes in psychopathology is essential in longitudinal investigations of endogenous affective disorders, since psychopathology up to now seems to have been the most sensitive and the most specific indicator of the hypothetical underlying abnormalities of cerebral functioning.

Affect↗

PubMed1979

[Original method of multivariate analysis, adapted for comparison of mean evoked potentials: E2 test].

This paper describes a multivariate statistical method of analysis for the comparison of 2 paired series. For such paired series, this test, called E2, is analogous to the generalized Hotteling T2 test, as epsilon test (pairing method) is analogous to Student's t test. Here we give an example of its application to a comparison of curves, in this particular case average auditory evoked potentials, picked up at symmetrical points on the scalp.

Acoustic Stimulation↗

PubMed2026

Flavoromics-based profiling reveals taste and aroma differences between infant formula and breast milk.

Flavor differences between infant formula (IF) and breast milk (BM) are considered a potential factor affecting infants' acceptance of IF. This experiment employs flavoromics combined with multivariate statistical analysis to systematically compare the flavor profiles of IF and BM. Electronic tongue analysis and amino acid correlation revealed that IF was characterised by pronounced saltiness and umami richness, whereas BM exhibited greater bitterness and astringency. Volatile compound profiling identified five key flavor constituents in IF, predominantly aldehydes such as hexanal and pentanal. In contrast, BM contained a broader array of compounds-including acids, aldehydes, and esters-resulting in a more complex flavor profile. Kyoto Encyclopedia of Genes and Genomes (KEGG)-based metabolic pathway annotation, together with fatty acid profiling, suggested that some volatiles may be associated with lipid oxidation, Maillard reaction and sulfur-containing amino acid degradation pathways, offering a theoretical basis for the targeted optimisation of IF flavor.

Humans↗

PubMed1979

Multivariate analysis and quantitative structure-activity relationships. Inhibition of dihydrofolate reductase and thymidylate synthetase by quinazolines.

Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained with 50 quinazolines were similar. On the other hand, for the inhibition of thymidylate synthetase from murine L1210S cells and from Lactobacillus casei, QSAR's formulated on the basis of data measured with 33 compounds were different, indicating that the two enzymes are dissimilar. The use of multivariate statistics including cluster analysis, factor analysis, and discriminant analysis is shown to facilitate the formulation of a satisfactory correlation equation. The procedure is demonstrated by the development of QSAR for the inhibition of thymidylate synthetase.

Analysis of Variance↗

PubMed1979

Research in endorphins and schizophrenia.

It has been suggested that the newly discovered endogenous opiate peptides (called endorphins) might play a role in the symptoms of schizophrenia. The administration of narcotic antagonists provides both a test of the hypothesis and a potential treatment. In this article, we review the methods by which data have been gathered to test endorphin involvement in schizophrenia. Alternative strategies, which hold greater promise of producing conclusive positive or negative evidence, include exploitation of individual differences, use of psychophysiological measures, genetic strategies, and multivariate statistical techniques with larger sample sizes.

Antipsychotic Agents↗

PubMed1977

An analysis of the determinants of nephron filtration rate.

Studies on glomerular filtration in the Munich-Wistar rat, a strain with surface glomeruli, have permitted for the first time the evaluation of the four factors that determine filtration rate: 1) the rate of nephron plasma flow (RPF), 2) the glomerular hydrostatic pressure gradient (deltaP) from capillary to Bowman's space, 3) systemic oncotic pressure (piA), and 4) the glomerular permeability coefficient (LpA), and their respective roles in producing change in filtration rate. The process of filtration in the Munich-Wistar rat is characterized by filtration pressure equilibrium and, therefore, filtration should be highly plasma flow-dependent. Analysis of data from this strain suggests that multiple factors can change LpA, and, at least in animals which do not achieve filtration pressure equilibrium, these alterations in LpA can influence the final filtration rate. Multivariate statistical analysis in a variety of experimental conditions in the Munich-Wistar rat suggest that changes in RPF remain the major mediator of change in nephron filtration rate, both in rats at filtration pressure equilibrium and in disequilibrated animals. Although the glomerulus is an ultrafilter driven by hydrostatic forces, changes in deltaP assume a lesser role in producing alterations in filtration rate.

Angiotensin II↗

PubMed2026

Metabolomics Reveals Metabolic Characteristics of Functional Cure in Chronic Hepatitis B Treated With Entecavir Combined With Pegylated Interferon Alpha.

BACKGROUND: Entecavir (ETV) combined with pegylated interferon alpha (PEG-IFNα) improves chronic hepatitis B (CHB) functional cure rates, but therapeutic heterogeneity and underlying metabolic mechanisms remain unclear. This study used untargeted metabolomics to identify metabolic signatures, mechanisms, and predictive biomarkers of functional cure with ETV-PEG-IFNα. METHODS: Thirty-eight CHB patients were grouped into ETV monotherapy (Group E, n = 12) and ETV-PEG-IFNα combination therapy (Group Z, n = 26); Group Z was subdivided into cured (Group A, n = 13) and noncured (Group B, n = 13). Serum metabolomic profiling, multivariate statistics, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified differential metabolites. A random forest model was built using key metabolites. RESULTS: Three hundred eighty-eight metabolites were identified. Four differential metabolites distinguished Group A and B (upregulated guanidinoacetic acid, uracil 5-carboxylate; downregulated L-methionine S-oxide, oleamide), enriching amino acid metabolism pathways. Nine differential metabolites between Group E and Z implicated amino acid, immune, and fatty acid pathways. The random forest model based on the four Group A/B metabolites showed 88.5% cross-validation accuracy (AUC = 0.920), with L-methionine S-oxide and oleamide as key predictors. CONCLUSIONS: This study reveals metabolic rewiring in CHB functional cure via ETV-PEG-IFNα therapy, involving energy metabolism, oxidative stress, and immunomodulation, based on which we propose a tentative metabolism-immunity synergy model to guide future research. Key metabolites, especially L-methionine S-oxide and oleamide, show exploratory predictive potential for functional cure that warrants further validation in independent cohorts.

Humans↗

PubMed1977

Non-human primate dental arch form.

Multivariate statistical analysis, based upon a number of dimensions, showed significant contrasts in dental arch form between four primate groups, which was difficult to identify from subjective visual inspection. Furthermore, analysis of dental arch size was shown to differ from dental arch shape, although whether this reflected predominantly genetic or environmental factors, requires further research.

Anatomy, Comparative↗

PubMed1979

Morphometric studies in the taxonomy of the orang-utan (Pongo pygmaeus. L. 1760.

The purpose of this study is to verify the subspecific level of the two recent refugial groups of Orang-utan on Borneo and Sumatra. A total of 47 skulls from both regions were studied by means of 32 craniometric characters. Univariate analysis showed highly significant differences only in males, whereas multivariate statistical analysis led to complete discrimination in both sexes. These results support the assumption that the geographically isolated Orang groups are subspecies.

Animals↗

PubMed1979

Absence of synergism between exposure to asbestos and cigarette smoking in asbestosis.

To assess both independent and synergistic effects of exposure to asbestos and cigarette smoking on the development of asbestosis, survey data from 4 groups of workers exposed to asbestos were analyzed with multivariate statistical models. Survey methods were standardized and included for the 383 subjects a respiratory symptoms questionnaire, occupational history, physical examination, pulmonary function testing, and a chest radiograph. Exposure to asbestos and cigarette smoking were assessed by questionnaire. Synergism between the 2 exposures was not present for previously identified manifestations of asbestosis including bilateral fine crackles, clubbing, dyspnea, radiographic abnormality, decreased forced vital capacity, and decreased single-breath diffusing capacity of the lung for CO. However, additive, independent effects of these 2 exposures were present for each of these parameters.

Adult↗

PubMed2025

Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis.

BACKGROUND: In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case-control study utilized plasma proteomics to explore protein alterations associated with severe DKA and to identify signaling pathways that associate with clinical variables. METHODS: We conducted a proteome analysis of plasma samples from 17 matched pairs of pediatric patients with T1D; one cohort with severe DKA and another with insulin-controlled diabetes. Proximity extension assays were used to quantify 3072 plasma proteins. Data analysis was performed using multivariate statistics, machine learning, and bioinformatics. RESULTS: This study identified 214 differentially expressed proteins (162 upregulated, 52 downregulated; adj P < 0.05 and a fold change > 2), reflecting cellular dysfunction and metabolic stress in severe DKA. We characterized protein expression across various organ systems and cell types, with notable alterations observed in white blood cells. Elevated inflammatory pathways suggest an enhanced inflammatory response, which may contribute to the complications of severe DKA. Additionally, upregulated pathways related to hormone signaling and nitrogen metabolism were identified, consistent with increased hormone release and associated metabolic processes, such as glycogenolysis and lipolysis. Changes in lipid and fatty acid metabolism were also observed, aligning with the lipolysis and ketosis characteristic of severe DKA. Finally, several signaling pathways were associated with clinical biochemical variables. CONCLUSIONS: Our findings highlight differentially expressed plasma proteins and enriched signaling pathways that were associated with clinical features, offering insights into the pathophysiology of severe DKA.

Humans↗

PubMed1979

Canonical correlation analysis: potential for environmental health planning.

There is a challenging need to identify the relationships between environmental quality and health status. It may be especially important to be able to isolate key variables which can be consolidated into a few indices of environmental conditions as they are related to health. Such indices might be used to identifying associations among groups of variables, such as specific geographic area. The indices may also provide insights into environmental health relationships which are worthy of further epidemiological investigation. Canonical correlation analysis is a multivariate statistical technique which provides a means of identifying associations among groups of variables, such as health and environmental measures. The technique can produce weighted indices of environmental conditions as they are related to health within a city or region. This paper describes what canonical correlation is, and outlines how it might be used for these purposes. An illustrative application based on data collected for Philadelphia, Pennsylvania is also presented.

Aged↗

PubMed1978

Discriminant analysis.

Discriminant analysis (DA) is a pattern recognition technique that has been widely applied in medical studies. It allows multivariate observations ("patterns" or points in multidimensional space) to be allocated to previously defined groups (diagnostic categories). The relationships between DA and other multivariate statistical techniques of interest in medical studies will be briefly discussed. The main emphasis is on linear discriminant functions (LDF). The theoretic assumptions underlying DA using LDFs will be presented, and the effect of violations to these assumptions will be reviewed in detail. Alternative methods will be presented when violations cause serious problems. It has been shown that the familiar LDF is fairly robust to departures from the assumptions. The application of the LDF in less than ideal situations therefore often does not cause much harm (if the violations are not too grotesque). Another set of problems reviewed is how to estimate the misallocation probabilities when using discriminant functions. The selection of the "best" subset of variables out of the complete set will be discussed. Practical guide lines are given based on the theoretic studies reviewed. When possible, available computer programs for various problems of DA will be indicated. The review does not aim at covering all medical studies where DA has been applied, since emphasis is on the practical conclusions of the theory of DA.

Discriminant Analysis↗

PubMed1975

The program of the cooperative study of the Veterans Administration.

A computer program for the automatic analysis of the electrocardiogram is described with details about wave recognition, measurements, and the calculation of the posterior probabilities of each diagnosis. The advantages and disadvantages of this multivariate statistical procedure are discussed. Classification statements result from separate analysis of the QRS-T complex, P wave, and ST segment. Criteria for inclusion of the patients forming the data base are given, with tables of measurements, means and standard deviation, as well as investigation of agreement between calculated and observed probabilities. Estimated error rates are given in the form of misclassification matrices, computed from large numbers of tracings collected by a Veteran Administration Cooperative Study, where the correct diagnoses are taken from clinical, laboratory, and autopsy information.

Cardiomegaly↗

PubMed1979

Conceptual and methodological considerations towards the development of computer-controlled research on the electro-physiology of sleep.

A critical discussion of the visual scoring approach to the measurement of sleep electrophysiology details some theoretical shortcomings of that procedural model. An alternative approach employing high-speed, general purpose digital computers is then presented. It is argued that the measurement potential of computers is barely tapped by using computers to score sleep stages and the advantages of collecting data which are suitable for parametric and multivariate statistical analysis are described. Researchers are urged to include detailed reports on their procedural choices along with a discussion of the methodological implications of these procedures. Examples of computer collected data are presented along with a description of some simple data reduction strategies.

Computers↗

PubMed1979

The physiologic recovery trajectory as the organizing principle for the quantification of hormonometabolic adaptation to surgical stress and severe sepsis.

Preoperative and serial postoperative clinical, cardiovascular, physiologic, and metabolic studies were carried out on 86 patients undergoing coronary artery bypass surgery (CABG); and 48 patients undergoing abdominal general surgical procedures (GSEL). Multivariable statistical analysis of these data showed the patients to be in different physiologic states and to manifest several types of recovery trajectories that could not be discerned on clinical grounds alone. The CABG patients followed one of three types of cardiogenic recovery trajectories. In contrast, GSEL patients show a normal recovery trajectory different from all CABG types. When sepsis develops, and exaggerated stress response (A state) occurs, with increased oxygen consumption and a pattern of amino acids, fat, and glucose breakdown products, which is heightened but similar to the response of nonseptic GSEL patients. With progression of sepsis severity, an unbalanced hyperdynamic recovery trajectory (B state) develops in which a decrease in oxygen consumption is associated with increases in the aromatic amino acids tyrosine, tryptophane, and phenylalanine; and decreases in the branched-chain amino acids, leucine and isoleucine. Triglycerides rise as keto acids fall, but both lactate and pyruvate rise. Glucagon is persistently high, regardless of insulin levels. The quantifiably different physiologic recovery trajectories reflect altered hormone and metabolic states and imply different responses to therapy.

Abdomen↗

PubMed1979

[The postnatal growth of the skull in the house mouse Mus musculus Linné, 1758, and in 2 different large subspecies of the field mouse Microtus arvalis Pallas, 1779. I. Introduction, materials and methods].

In order to describe postnatal skull growth in Mus musculus, Microtus arvalis arvalis and M. a. asturianus, a total of 408 animals were raised and measured. The growth rate of single bones was followed by means of a maximum-likelihood estimator for the parameters A, B and C of the growth function Y(t) = A-B exp(-Ct). Supplementary techniques used to estimate the morphological divergence of the different taxa included methods of allometry research and multivariate statistical methods such as discriminate analysis and MANOVA. Drawings of selected stages of skull-bone ossification are provided to assist researchers in determining the age of undated specimens.

Animals↗

PubMed1979

Ventilation:perfusion maldistribution secondary to the hyperdynamic cardiovascular state as the major cause of increased pulmonary shunting in human sepsis.

Cardiovascular and respiratory parameters were obtained in 374 studies from 151 patients (64 septic or septic shock and 87 with nonseptic cardiogenic syndromes). Cardiac output and related measures, respiratory parameters, pulmonary blood volume (DV/m2), cardiac ejection fraction (EFx), left ventricular end-diastolic volume (LVEDV), peripheral resistance (TPR), pulmonary shunt (QS/QT), physiologic dead space (VD/VT) and mean ventilation perfusion ratios (VA/QT) were calculated. Both physiologic evaluation and multivariable statistical analyses of the data were performed. For a given level of (A-aO2 gradient/PaO2) septic patients have a higher QS/QT than cardiogenic patients. Hyperdynamic septic patients have a larger QS/QT, a greater VD/VT, and a lower VA/QT and TPR than cardiogenics. The decrease in VA/QT and the rise in VD/VT are strong functions of the increased EFx, which raises cardiac index (CI) and reduces LVEDV and the mean dispersion of pulmonary blood volume, thus causing hemodynamic redistribution of flow. QS/QT is mainly a direct function of the increase in CI which also tends to reverse the EFx-mediated rise in VD/VT. The role of the septic mediated decrease in TPR as a contributing pathologic feature and the use of volume infusion to raise LVEDV and VA/QT in high-CI septics with large QS/QT is discussed.

Blood Circulation↗