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Beyond Level-1: Identifiability of a Class of Galled Tree-Child Networks.

Inference of phylogenetic networks is of increasing interest in the genomic era. However, the extent to which phylogenetic networks are identifiable from various types of data remains poorly understood, despite its crucial role in justifying methods. This work obtains strong identifiability results for large sub-classes of galled tree-child semidirected networks. Some of the conditions our proofs require, such as the identifiability of a network's tree of blobs or the circular order of 4 taxa around a cycle in a level-1 network, are already known to hold for many data types. We show that all these conditions hold for quartet concordance factor data under various gene tree models, yielding the strongest results from 2 or more samples per taxon. Although the network classes we consider have topological restrictions, they include non-planar networks of any level and are substantially more general than level-1 networks - the only class previously known to enjoy identifiability from many data types. Our work establishes a route for proving future identifiability results for tree-child galled networks from data types other than quartet concordance factors, by checking that explicit conditions are met.

Mathematical Concepts

[Concordance of risk factors for cerebro-cardiovascular diseases among spouses].

The present study was carried out to clarify the concordance or similarity of risk factors among 298 spouse pairs in a random sample who lived in Mizobe town of Kagoshima Prefecture. A sample of 298 spouse pairs was surveyed by using the house-to-house interviewing method and was classified into three groups by the marriage duration. The following results were obtained. 1) Statistically significant partial correlation coefficients were demonstrated among the spouses for blood pressure in the present study. However, they were smaller than among spouses in remote islands, this fact suggested that there was no higher spouse concordance in this surveyed area than in remote island areas, and also that there might be a difference in the shared environment of spouse pairs and the genetic effect on blood pressure between the former area and the latter. 2) In regard to the intake of salt in miso soup and the ratio of sodium to potassium (Na/K), an increasing gradient of partial correlation coefficients for the risk factors among the spouses was observed with increasing marriage duration, suggesting that the intake might be caused by the shared environment on the basis of a similar dietary pattern for the spouse pairs.

Adult

Spatial concordance metrics and related risk factors of brain-peripheral barrier axes: unveiling distinct concordance patterns for mental and neurological axes.

Numerous studies have documented bidirectional interactions between the central nervous system and barrier organs (skin, gut, and lung). While genome-wide association studies have revealed shared genetic factors across brain-peripheral barrier axes, investigating these connections from an environmental perspective in large populations remains difficult. Using data from the Global Burden of Disease (GBD) 2023, I extracted annual incidence rates for 56 diseases related to brain-peripheral barrier axes and exposure rates for the 70 most detailed risk factors across 204 countries and territories. By categorizing regional incidence rates into four quartiles for each disease, I pinpointed regions with concordance of these axes and constructed a spatial atlas of disease concordance within the brain-peripheral barrier axis from a macro-epidemiologic view. Subsequently, I calculated global spatial concordance percentages for each axis, which allowed the comparatively assessment of concordance patterns across different axes, specific diseases, and their variations over time, across the lifespan, and by gender. Finally, I applied machine learning models and Shapley additive explanations to identify risk factors related to the spatial concordance of each axis. From 1990 to 2023, the overall trend for most brain-peripheral barrier axis pairs remained stable. Spatial concordance patterns showed dynamic fluctuations across the lifespan, followed by a convergence toward stability in older age. Several risk factors are related to most brain-peripheral barrier axes. Notably, the mental and neurological axes exhibited distinct concordance patterns. Compared with neurological axes, concordance within mental axes showed a broader and more dispersed geographic distribution, with greater variation across sexes and over time. Furthermore, concordance percentages of mental and neurological axes exhibited opposing age-related trends, contrasting disease spectra for peripheral conditions, and inverse relationships with alcohol and sodium consumption. Those divergences suggest distinct mechanisms underlying the brain-peripheral barrier axes in mental and neurological diseases. Related risk factors offer population-based hypotheses for further investigation in individual-level studies.

Humans

Enzyme-linked immunosorbent assay of human factor VII based upon a monoclonal antibody that recognizes the native conformation of the protein.

An enzyme-linked immunoassay (ELISA) was developed for measuring human factor VII antigen using two monoclonal antibodies, one of them reacting only with fully carboxylated factor VII. This assay permits to measure factor VII antigen in concentrations ranging from 0.78 to 100 ng/ml, with within- and between-assay coefficients of variation of less than 7%. In 53 normal subjects, 32 patients with liver cirrhosis, 21 pregnant women and 53 patients on oral anticoagulant therapy the plasma levels of FVII antigen were very similar to those of factor VII coagulant activity measured with a bioassay. The ELISA also gave very similar values of factor VII antigen in plasma and in serum, and in plasma before and after exposure to cold, indicating that the assay is not affected by factor VII activation. In five of 8 patients with severe congenital deficiency of factor VII values of factor VII antigen were higher than those of factor VII activity. The close concordance of factor VII values obtained by ELISA and bioassay in the majority of plasmas, including those from patients on oral anticoagulant therapy, indicates that the assay measures native factor VII and can perhaps replace the bioassay systems in clinical conditions associated with normal or high levels of factor VII.

Adult

Concordance for coronary risk factors among spouses.

Values for several coronary risk factors, including systolic and diastolic blood pressure, serum cholesterol, triglycerides, blood glucose, uric acid, hemoglobin, weight, vitral capacity and cigarette smoking have been found to be similar among spouses in the Framingham Study. However, longitudinal analyses show that this spouse concordance does not increase over a twelve-year observation period, suggesting that it has arisen through the marriage of similar people rather than through the sharing of a common marital environment. Apparent conflicts between cross-sectional and longitudinal findings have been resolved by showing that spouses who were concordant at the begining of the study are more likely to survive to later exams, while discordant spouse pairs tend to be dissolved through the death of one of their members.

Adult

Concordant expression of tissue factor and class II MHC antigens in human placental endothelium.

Villitis of unestablished etiology is a placental lesion frequently associated with high risk pregnancies: it is also found in placentae from normal term pregnancies. The etiology of the lesion is unknown. Vasculitis and thrombosis have been described in villitis areas of placentae from normal and high risk pregnancies. We asked if fetal stem vessel endothelium in villitis lesions expresses MHC class II antigens, and if this is associated with a thrombogenic activity of these vessels. We found that endothelium of fetal stem vessels in villitis areas was usually MHC class II (HLA-DR, DP and DQ) reactive. Reactivity of fetal stem vessel endothelium for MHC class II antigens was associated with the presence of tissue factor reactivity and the absence of thrombomodulin reactivity. These changes on endothelial plasma membranes can promote intravascular coagulation, ischemic necrosis, vasculitis and other histological changes characteristic of villitis.

Chorionic Villi

Insulin-like growth factor I receptor gene is concordant with c-Fes protooncogene and mouse chromosome 7 in somatic cell hybrids.

The insulin-like growth factor I (IGF-1) mediates the actions of pituitary growth hormone in a variety of tissues. Its receptor (IGF1R) displays considerable structural similarity to the insulin receptor. In humans, the IGF1R gene has been mapped near FES, the cellular counterpart of the feline sarcoma virus transforming gene v-fes, at the q25-q26 region of human chromosome 15 (HSA15). Here, we report the mapping of mouse Igf1r to mouse chromosome 7 (MMU7) by somatic cell hybrid analysis. This result, along with the prior assignment of the loci for mitochondrial isocitrate dehydrogenase and FES to human chromosome 15 and mouse chromosome 7, suggest a conserved autosomal synteny group on the distal long arm of HSA15 and in the center of MMU7.

Animals

[Control of oral anticoagulation: comparison between Quick and colorimetric factor X determination in 107 patients].

Since monitoring of oral anticoagulation (OA) by prothrombin time (PT) is a source of standardization difficulties, the authors have tested another approach. 107 patients under long term OA were monitored by both PT and a colorimetric factor X assay (in vitro activation of factor X with RVV and assessment of amidolytic activity towards S-2222). The PT values were between 10 and 34% (therapeutic range 15--25%), and factor X levels were between 10 and 44% (therapeutic range 16--24%). The correlation between the two methods was highly significant (r = 0.65, p less than 0.001). In 68% of the patients the two tests gave the same information (55 subjects were adequately, 16 insufficiently and 2 over-anticoagulated). For a slightly broader therapeutic range (PT 15--30%, corresponding to 16--28% factor X) concordant information was obtained in 82% of the patients. During stable OA, PT and factor X assay gave very similar information. An advantage of the latter method is the possibility of automation, while a disadvantage is its insensitivity to factor VII.

Administration, Oral

A Danish twin study of manic-depressive disorders.

The existence of a nation-wide twin register and central psychiatric register has made possible a catamnestic investigation of an unselected and representative sample of twins with manic-depressive disorders. From a total population of 11,288 same-sexed twin pairs born 1870-1920 in Denmark 126 probands from 110 pairs were ascertained. Among the co-twins of 69 monozygotic probands there were found 46 with manic-depressive disorders, and a further 14 had presented other psychoses or marked affective personality disorders or had committed suicide, yielding a proband rate of strict concordance, C1 = 0-67 and of broad, partial concordance, C2 = 0-87. The corresponding direct pairwise concordance rates were 32/55 = 0-58 and 46/55 = 0-84 respectively. For the dizygotic twins the proband concordance rate of C1 was 11/54 = 0-20 and of C2 20/54 = 0-37, and the direct pairwise rates were 9/52 = 0-17 and 18/52 = 0-35 respectively. The differences between the pairwise rates for the monozygotic and dizgotic twins are significant (P less than 0-001 at X2 analysis). This finding is in accordance with previous twin studies of manic-depressive disorders and confirms the evidence of a strong genetic factor. The concordance with respect to unipolar and bipolar forms was not in contradiction to recent evidence of a genetic difference between the bipolar and unipolar form, the latter probably related to the female sex.

Aged

The family profile: a new self-report instrument for family assessment.

The Family Profile is a new self-report family assessment instrument that is grounded in family theory and designed following a construct validation approach to instrument design that integrated theoretical concepts with test construction and empirical analysis. Development consisted of three component phases: rational theoretical design, empirical structural analysis, and psychometric validation. The first theoretical design phase resulted in a 231-item instrument with 13 construct scales. Structural analysis data were collected from a pilot sample of 160 patients selected from 6 family practice clinics in urban, suburban, and rural locations. After revision based on item and scale analysis, a 129-item instrument was administered to a random sample of 876 patients from family practices throughout Minnesota. Responses were analyzed for item- and scale-distribution characteristics, item-scale and scale-scale correlations, correlation with social desirability, factor analysis to confirm or disconfirm the existence of the theoretical dimensions, internal consistency reliability, and test-retest reliability. This analysis reduced the instrument to 90 items from all 13 postulated constructs that cluster into 6 main factors--Family Concordance, Family Discordance, Marital Strength, Active Involvement, Religiosity, and Parental Leadership. The Family Profile is also temporally stable and free from social desirability bias. Validation (construct and criterion) and normative data studies of various populations are in progress.

Family

Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region.

Based on the map location of the aniridia (AN) locus in human chromosomal band 11p13, we have cloned a candidate AN cDNA (D11S812E) that is completely or partially deleted in two patients with AN. The less than 70 kb smallest region of overlap between the two deletions encompasses the 3' coding region of the cDNA. This cDNA, which spans over 50 kb of genomic DNA, detects a 2.7 kb message specifically within all tissues affected in AN. The predicted polypeptide product possesses a paired domain, a homeodomain, and a serine/threonine-rich carboxy-terminal domain, structural motifs characteristic of certain transcription factors. The concordance between expression and pathology, map location, structure, and predicted function argues that the cDNA corresponds to the AN gene.

Amino Acid Sequence

Severe hyponatremia in spinal cord injury.

A male quadriplegic (C6--complete) with persistent chronic hyponatremia (serum sodium values ranging consistently from 117-132 mmol/L) developed acute hyponatremia with a serum sodium concentration of 98 mmol/L. This extreme hyponatremia related, in part, to a reversible defect in the excretion of a water load, while on a low (46 mmol/day) sodium diet. Subsequent ingestion of a normal sodium diet (150 mmol/day), with or without 0.1 mg of fludrocortisone (Florinef), reestablished his ability to excrete a water load normally. The etiology of this patient's hyponatremia is discussed as well as the unique concordance of factors which make hyponatremia a common occurrence among spinal-cord injured patients.

Acute Disease

Acquired factor VII deficiency associated with aplastic anaemia: correction with bone marrow transplantation.

We report a patient with severe aplastic anaemia found to have a prolonged prothrombin time due to acquired factor VII deficiency. No evidence for a factor VII inhibitor or inactivator was demonstrable. Laboratory studies identified deficiency both of factor VII activity and factor VII antigen. The factor VII deficiency persisted from clinical presentation until approximately 50 d after allogeneic marrow transplantation when restoration of factor VII activity and antigen was noted. The patient's serum could be depleted of factor VII activity by in vitro incubation with Protein A bound to Sepharose, suggesting the presence of an IgG or IgG containing complex able to bind factor VII, but not neutralize its procoagulant activity. A dual specificity solid phase immunoassay identified a factor VII binding immunoglobulin which was detectable throughout the course of factor VII deficiency. The concordant appearance of this factor VII reactive immunoglobulin and the factor VII deficiency suggested the pathologic role of this immunoglobulin in the aetiology of the factor VII deficiency. This factor VII binding immunoglobulin may have induced rapid plasma clearance of the factor VII molecule or, alternatively, may have modified factor VII synthesis. The immunosuppressive therapy and subsequent lymphohaematopoietic engraftment following allogeneic marrow transplant was accompanied by complete resolution of the factor VII deficiency.

Adolescent

Concordance of familial characteristics in Crohn's disease and ulcerative colitis.

The diagnosis of inflammatory bowel disease (IBD) in a proband increases the probability of a parallel IBD diagnosis in a family member. In this study, we were able to confirm the IBD diagnosis in 35 (9.9 percent) of the relatives of 352 registry probands. To confirm a proband's report of a positive family history of IBD, efforts were made to directly contact all first-degree relatives regardless of their IBD status (parents, siblings, and children). Consent to contact family members was obtained from the proband, who furnished the registry personnel with names, addresses, and phone numbers. We then attempted to contact each identified relative by phone. After verbal consent was obtained, family members were asked if they had been diagnosed with IBD. This diagnosis was confirmed by contacting the relative's physician. A McNemar (chi 2 Mc) matched-pair analysis was used to analyze concordance between the proband and the affected family member. Within the CD/CD (Crohn's disease) concordant pairs, sex was a significant risk factor. Sex was not a significant risk factor within the UC/UC (ulcerative colitis) concordant pairs. In the concordant surgery pairs, no surgical procedure was a significant risk factor for the prediction of a similar surgical procedure for the affected relative. In concordant extraintestinal complications, only the appearance of a skin rash was significantly related to the appearance of a skin rash in the affected relative.

Colitis, Ulcerative

Twin studies of psychopathology: why do the concordance rates vary?

Many current discussions of hereditary factors in psychopathology focus on twin studies as the primary source of evidence supporting the importance of genetic determinants. In summarizing the results of these studies, authors often derive estimates of concordance rates by collapsing across studies and presenting mean or median rates. This practice implicitly assumes that the concordance rates yielded by different studies represent equally reliable estimates of the population mean. The present study evaluates the validity of this assumption. Reports of twin studies of schizophrenia and affective disorder were reviewed. A meta-analysis was conducted to examine the influence of methodological factors on concordance rates. Analyses indicated that both sample-selection and zygosity-determination procedure are systematically associated with concordance rates. For schizophrenia, MZ concordance rates are significantly lower when samples are selected from a twin register as opposed to a psychiatric facility. Lower MZ concordance rates are also yielded by studies that employ laboratory procedures to determine zygosity. Implications of the findings for future research are discussed.

Affective Disorders, Psychotic

Recurrence after coronary angioplasty.

Recurrence (restenosis) after coronary angioplasty has undermined the initial success of the procedure and has compromised, to some extent, the attractiveness of the technique in the treatment of ischemic heart disease. Assessment of recurrence predictors has been problematic due to lack of coordination of angioplasty recurrence research and includes: incomplete angiographic documentation, variations in definitions of restenosis anatomically and the results of restenosis physiologically (ie, myocardial ischemia), the dirth of morphologic specifications of subsets under investigation and late outcome pathology, limitations in statistical analyses used, and minimal efforts to classify the available data on recurrence. A review of the literature suggests that all findings regarding recurrence after angioplasty can be organized in four categories: clinical, morphologic, technical (or procedural), and pharmacologic. The reported findings with high concordance as risk factors for recurrence after angioplasty include the clinical factors of diabetes mellitus, hyperlipidemia, and angina of short duration or unstable presentation. Morphologic factors which have been corroborated vis-à-vis recurrence include stenoses with diameter reduction of greater than 90% before and greater than 30% after angioplasty, residual trans-stenotic pressure gradients of greater than 20 mmHg after angioplasty, and lesions that are diffuse, long, eccentric, or calcified. Technical factors associated with recurrence include lower balloon/vessel (or graft) ratios and the absence of (uncomplicated) "intimal dissection." The category most deficient in research regarding recurrence after angioplasty is pharmacologic. Since there are statistically documented and reproducible factors predictive of restenosis, to ignore or minimize these findings or resist further evaluation (because of the ease and safety of performing repeat angioplasty) is to deny the opportunity to understand the mechanisms and favorably affect the incidence of recurrence. This review concludes with two major implications of the restenosis research: certain clinical, technical, and pharmacologic factors, if addressed, may predictably decrease the rate of restenosis and certain clinical and morphologic factors may increase the risk of restenosis; these factors may be less readily modified (eg, diabetes, lesion calcification) and thus must be considered in the decision for angioplasty.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged

Anaphylaxis to muscle-relaxant drugs: study of cross-reactivity by skin tests.

Intradermal skin tests (two dilutions) carried out systematically with 5 muscle-relaxant drugs were used to study the cross-reactivity between these drugs in 131 patients who had suffered from anaphylaxis. The skin tests were positive for at least 2 drugs in 65.6% of the cases. We observed a significant concordance (positive-positive or negative-negative skin tests) between pancuronium and vecuronium (p less than 0.01) and a significant correlation between the skin test diameters obtained with these 2 drugs (p less than 0.02 for wheals and p less than 0.01 for flares). Conversely, the lack of concordance between pancuronium and suxamethonium was significant (p less than 0.05). When comparing all the concordances obtained with each pair of drugs, it appeared that the concordance between pancuronium and vecuronium was significantly higher than all others. For other concordances, 2 main factors seemed to play a role: the N+ of the ammonium ions included in a ring as in pancuronium and the presence of a 'choline-like' side chain as in suxamethonium. But there was no significant correlation between skin test diameters. Altogether, these results suggest that in vivo there is no 'true' cross-reactivity between the drugs except frequently between pancuronium and vecuronium. In all other cases, the patients have probably specific IgE antibodies for each drug, all these antibodies being able to recognize the ammonium determinant; this common property may be insufficient to induce a clinical allergy.

Adolescent

Prediction of prognosis in primary breast cancer by detection of a high molecular weight mucin-like antigen using monoclonal antibodies DF3, F36/22, and CU18: a Cancer and Leukemia Group B study.

Three monoclonal antibodies (MAbs) (DF3, F36/22, CU18) were used to monitor expression of distinct epitopes present within a family of mucin-like, breast carcinoma-associated molecules. Primary tumor specimens from more than 190 stage II breast cancer patients were evaluated for expression of the high molecular weight antigens. With a median follow-up of 6 years, patients whose tumors exhibited high immunoperoxidase staining scores (greater than 50% positive cells) with MAb DF3 had a superior disease-free survival ([DFS] 56% +/- 6% v 37% +/- 5% at 6 years; P = .0088) and overall survival ([OS] 72% +/- 5% v 59% +/- 5% at 6 years; P = .025). Staining scores with the other two antibodies did not correlate with improved prognosis. For MAbs DF3 and CU18, patients whose tumors exhibited predominantly apical cellular reactivity patterns had improved DFS, although differences reached conventional levels of statistical significance only with MAb CU18. In multivariate analyses, the prognostic value of MAb DF3 staining was independent of other identified prognostic factors. Furthermore, the concordance between primary and axillary lymph node metastases staining with each MAb was 73%, 80%, and 85% for MAbs DF3, F36/22, and CU18, respectively. These results suggest that staining with MAb DF3 identifies a group of node-positive women with a relatively favorable prognosis. Expression of the DF3 mucin-like glycoprotein is related to better differentiation, and staining with MAb DF3 provides an accurate and objective estimate of clinical outcome independent of histopathologic evaluation.

Adult