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PubMed1990

Variation and classification of human age patterns of mortality: analysis using competing hazards models.

The structure of variation in human mortality patterns is explored using a five-parameter competing hazards model and standard multivariate taxonomic procedures. The data consist of 281 national life tables representing a wide range of environmental and cultural regions of the world. A general or average age pattern of mortality was generated for the entire sample using multiple regression procedures. A K mean cluster analysis conducted on the residuals of the regression analysis identified seven distinct models of mortality that differ in characteristic ways from the general pattern. Four of the seven clusters have age patterns of mortality similar to the north, east, south, and west regions of the Coale and Demeny model life tables. The remaining three clusters represent regions of the world and age patterns of mortality that are not represented in the Coale and Demeny model life tables.

Age Factors↗

PubMed1989

[The genetic architecture of emotionality in rats using Mendelian cross analysis].

Two inbred strains of Tsukuba Emotionality Rat (THE and TLE) and four hybrids derived from them were observed for ambulatory response in a novel environment as a measure of emotionality. The Runway Test (modified "timidity test") was run for successive three days. Mean transformed (square root) scores of ambulation for generation were subjected to Mendelian cross analysis. Total ambulation scores showed significant additive genetic effect, maternal effect and environmental effect. Directional dominance toward low level of response was present only for males. Daily ambulation scores showed changes in the genetic architecture over three days and the difference between males and females. For females, directional dominance occurred toward low level on Day 1, toward high level on Day 3, but no directional dominance was observed on Day 2. Males' directional dominance toward low level, on the other hand, declined with days. These findings on the genetic architecture of emotionality were discussed with reference to evolutionary adaptation.

Affective Symptoms↗

PubMed2006

Survivorship and retrieval analysis of Sikomet metal-on-metal total hip replacements at a mean of seven years.

BACKGROUND: Second-generation metal-on-metal total hip replacements were introduced in the early 1990s with the aim of eliminating polyethylene wear and the resulting complications of osteolysis and aseptic loosening. The goal of the present study was to evaluate the intermediate-term results in a series of patients who were managed with one of these implants. METHODS: Between 1994 and 2002, we performed 640 total hip replacements in 591 patients with use of a Bicon-Plus cementless threaded cup with a polyethylene liner housing a metal inlay made of Sikomet low-carbon cobalt-chromium-molybdenum alloy that articulates with a Sikomet metal femoral head. Clinical and radiographic evaluation was performed retrospectively at a mean of 7.1 years postoperatively. Histologic analysis was performed on specimens retrieved from seventeen hips that were revised, and wear measurements were made for six hips that were revised. RESULTS: Thirty-four hips (thirty-four patients) were revised because of infection (six hips), aseptic loosening (twenty-three hips), pain without loosening (two hips), or other reasons (three hips). The survival rate of the prosthesis as a whole at ten years, with revision for any reason as the end point, was 0.91 (95% confidence interval, 0.88 to 0.95). The survival rate of the cup was 0.94 (95% confidence interval, 0.90 to 0.97), and that of the stem was 0.96 (95% confidence interval, 0.94 to 0.98). Linear or expansile osteolysis, or both, was observed on the radiographs of sixteen (64%) of the twenty-five hips that were revised because of aseptic loosening and/or pain. Histological analysis of pericapsular tissue was performed for seventeen of the twenty-five hips that were revised because of aseptic loosening and/or pain. Thirteen of these seventeen hips demonstrated a hypersensitivity-like reaction with aseptic inflammatory changes accompanied by moderate to extensive diffuse and perivascular infiltration of lymphocytes. In the six retrieved specimens that were subjected to wear analysis, the main wear mode was abrasive wear. The mean cumulative linear wear for the bearing was 31.3 microm, and the mean annual wear rate was 6.3 microm/yr. The mean clearance was 87.6 microm. CONCLUSIONS: After a mean duration of follow-up of seven years, aseptic loosening was the major reason for failure of Sikomet metal-on-metal prostheses. The histological findings and the prevalence of osteolysis suggest the possibility of a hypersensitivity-like immunological response to wear particles.

Adolescent↗

PubMed1984

Mechanisms of mediator release from neutrophils.

The encounter of neutrophils with immune complexes and complement components - in the bulk phase or on a surface - leads to their secretion of lysosomal hydrolases, especially neutral proteases, which provoke tissue injury. Secretion of lysosomal enzymes and generation of reactive oxygen species (e.g., O2-. generation are stimulus-specific and can be dissected to establish cause and effect relationships by means of: a) kinetic analysis, b) variations in the stimulus, and c) use of impermeant reagents to block discrete responses. Neutrophils also generate products of 11-cyclooxygenase (e.g., PGE2, TxA2) and of the 5- and 15-lipoxygenases (mono-, di-, and tri-HETEs, LTB4, and their isomers). But the cyclooxygenase products (save TxA2) are not phlogistic by themselves: they inhibit the functions of neutrophils, platelets, macrophages, and mast cells. The most potent pro-inflammatory agent yet identified as a product of arachidonate is LTB4. LTB4 is a potent Ca ionophore, constricts airways, is a potent chemoattractant, and induces local inflammation.

Alprostadil↗

PubMed1982

Neutrophils: release of mediators of inflammation with special reference to rheumatoid arthritis.

The encounter of neutrophils with immune complexes and complement components, in the bulk phase or on a surface, leads to their secretion of lysosomal hydrolases, especially neutral proteases, which provoke tissue injury. Secretion of lysosomal enzymes and generation of reactive oxygen species (e.g., O(2)) is part of a stimulus-secretion response to a variety of secretagogues, including immune complexes and complement components. However, the pathways of secretion and O(2) generation are stimulus-specific and can be dissected to establish cause and effect relationships by means of: a) kinetic analysis, b) variations in the stimulus, and c) use of impermeant reagents to block discrete responses. Neutrophils also generate products of 11-cyclooxygenase (e.g., PGE2, TxA2) and of the 5-and 15-lipoxygenases (mono-, di-, and tri-HETEs, LTB4, and their isomers). But the cyclooxygenase products (save TxA2) are not phlogistic by themselves: they inhibit the functions of neutrophils, platelets, macrophages, and mast cells. The most potent pro-inflammatory agent yet identified as a product of arachidonate is LTB4. LTB4 is a potent Ca ionophore, constricts airways, is a potent chemoattractant, and induces local inflammation.

Animals↗

PubMed2003

eXPatGen: generating dynamic expression patterns for the systematic evaluation of analytical methods.

MOTIVATION: Experimental gene expression data sets, such as those generated by microarray or gene chip experiments, typically have significant noise and complicated interconnectivities that make understanding even simple regulatory patterns difficult. Given these complications, characterizing the effectiveness of different analysis techniques to uncover network groups and structures remains a challenge. Generating simulated expression patterns with known biological features of expression complexity, diversity and interconnectivities provides a more controlled means of investigating the appropriateness of different analysis methods. A simulation-based approach can systematically evaluate different gene expression analysis techniques and provide a basis for improved methods in dynamic metabolic network reconstruction. RESULTS: We have developed an on-line simulator, called eXPatGen, to generate dynamic gene expression patterns typical of microarray experiments. eXPatGen provides a quantitative network structure to represent key biological features, including the induction, repression, and cascade regulation of messenger RNA (mRNA). The simulation is modular such that the expression model can be replaced with other representations, depending on the level of biological detail required by the user. Two example gene networks, of 25 and 100 genes respectively, were simulated. Two standard analysis techniques, clustering and PCA analysis, were performed on the resulting expression patterns in order to demonstrate how the simulator might be used to evaluate different analysis methods and provide experimental guidance for biological studies of gene expression. AVAILABILITY: http://www.che.udel.edu/eXPatGen/

Algorithms↗

PubMed2004

Analysis of QTLs for yield, yield components, and malting quality in a BC3-DH population of spring barley.

Advanced backcross (AB)-quantitative trait locus (QTL) analysis has been successfully applied for detecting and transferring QTLs from unadapted germplasm into elite breeding lines in various plant species. Here, we describe the application of a modified AB breeding scheme to spring barley. A BC3-doubled haploid (DH) population consisting of 181 lines derived from the German spring barley cultivar 'Brenda' (Hordeum vulgare subsp. vulgare) as the recurrent parent and the wild species line 'HS213' (H. vulgare subsp. spontaneum) as the donor line was evaluated for yield and its components as well as malting quality traits. A set of 60 microsatellite markers was used to genotype the population, and phenotypic data were collected at two locations in Germany in continuous years. Altogether, 25 significant QTLs were detected by single-marker regression analysis and interval mapping. Most positive QTLs originated from the recurrent parent 'Brenda'. A QTL, Qhd2.1, on chromosome 2HS from 'Brenda' explained 18.3% and 20.7% of the phenotypic variation for yield and heading date, respectively. Due to the small percentage of donor-parent genome of 6.25%, the BC3-DH lines could be directly used for the extraction of near-isogenic lines (NILs) for Qhd2.1. Consequently, it was possible to determine the precise location of the locus hd2.1 within a region of 6.5 cM, using an F2 population consisting of 234 individuals developed from a cross between an NIL containing a defined donor segment at this locus and 'Brenda'. The location of this QTL was consistent with the presence of a major photoperiod response gene, Ppd-H1, previously reported in this region, which is associated with pleiotropic effects on yield components. In summary, the analysis of a BC3-DH population in barley provides a compromise between the analysis of QTLs by means of an AB scheme and the generation of defined substitution lines. Several lines carrying defined different donor segments for only one single chromosome or trait in the genetic background of 'Brenda' could be selected for further genetic studies.

Breeding↗

PubMed1987

The impact of acidification on macroinvertebrate assemblages in welsh streams: towards an empirical model.

The acidification of surface waters has profound ecological consequences. There is a need to predict the effects of possible future patterns of acid deposition on the biological components of fresh waters. This paper describes a model of the relationships between water chemistry and macroinvertebrate assemblages in eighteen streams in the upper Tywi whose catchments are subject to different land uses. Using established statistical techniques on data sets derived from riffle and margin samples taken in spring and summer, the macroinvertebrate assemblages were classified into three groups, which corresponded with streams draining conifer afforested catchments, acidic moorland streams and circumneutral moorland streams. Following principal components analysis to select key environmental variables, the application of multiple discriminant analysis generated two discriminant functions which were related most strongly to mean filterable aluminium concentration and mean total hardness, respectively. The discriminant functions were used to assign site-group membership with 100% success in the case of the spring data set with combined habitats. In addition, multiple regression of the primary ordination axis of each data set on mean aluminium concentration and mean hardness or pH, produced equations which explained 62.0%-87.2% of the variance. We conclude that the methods used here provide an effective analytical and potentially predictive tool for use in the understanding and management of the impact of acidification on freshwater ecosystems.

Journal Article↗

PubMed2004

The self-administration of WIN 35,428 and cocaine: comparisons of satiety threshold and elimination half-life in rats.

Rats that self-administered cocaine at unit doses between 0.75 and 12 micromol/kg with mean inter-injection intervals between approximately 2 and 18 min also reliably self-administered the cocaine analogue WIN 35,428 (beta-CFT; (-)-3 beta-(4-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester) at unit doses between 0.1 and 1.6 micromol/kg with mean intervals between 10 and 116 min. The long inter-injection intervals of WIN 35,428 necessitated sessions of more than 12 h. The inter-injection intervals were regular and proportional to the unit dose, consistent with the satiety threshold model. Analysis of the mean intervals as a function of unit doses generated values for the mean satiety threshold of cocaine and WIN 35,428 of 6.10 and 0.87 micromol/kg, respectively. The mean t(1/2) for cocaine and WIN 35,428 were 11.1 and 69.4 min, respectively. The approximately 43-fold lower rate of consumption of WIN 35,428 relative to cocaine was a product of the seven-fold greater pharmacodynamic potency and the six-fold greater pharmacokinetic potency.

Animals↗

PubMed1997

A regulatory perspective on the potential uses of microbial risk assessment in international trade.

The recent ratification of the World Trade Organisation Agreement will arguably be the most important factor in developing new sanitary measures for the international trade in food over the next decade. There is a markedly increased desire for quantitative data on the microbial risks associated with different classes of foods, and traditional good manufacturing practice (GMP)-based food hygiene requirements are coming under increasing challenge. As the risk assessment paradigm is increasing applied and as decision-making criteria for risk management become established, more emphasis will be placed on predictive microbiology as a means of generating exposure data and establishing critical limits for Hazard Analysis Critical Control Point (HACCP) plans. In this respect, developing international guidelines for risk management arguably presents the greatest challenge in establishing and maintaining quantitative Sanitary and Phytosanitary (SP) measures for food in international trade, and for judging their equivalence. Where specific industry sectors and regulators do not have jurisdiction over the entire food chain, from production of raw materials through to consumption, it will be difficult to apply the risk assessment paradigm in the design of HACCP plans. Thus, it appears that default to food safety objectives for many segments of food production chains subject to application of HACCP plans is inevitable in the medium term.

Food Microbiology↗

PubMed2001

Functionalization of silicone rubber for the covalent immobilization of fibronectin.

Surface modification techniques were employed in order to provide functionalized silicone rubber with enhanced cytocompatibility. Acrylic acid (AAc), methacrylic acid (MAAc) and glycidylmethacrylate (GMA) were graft-co-polymerized onto the surface of silicone induced by an argon plasma and thermal initiation. The polymerizations were carried out in solution, in the case of acrylic acid a vapor phase graft-co-polymerization subsequent to argon plasma activation was carried out as well. Human fibronectin (hFn), which acts as a cell adhesion mediator for fibroblasts, was immobilized by making use of the generated carboxylic or epoxy groups, respectively. Surface analysis was accomplished by means of X-ray photoelectron spectroscopy (XPS), infrared spectroscopy in attenuated total reflection mode (IR-ATR), scanning electron microscopy (SEM), atomic force microscopy (AFM) and dynamic contact angle measurements using the Wilhelmy-plate method. The amount of immobilized active hFn was semiquantified by enzyme-linked immunosorbent assay (ELISA) using a structure-specific antibody against the cell-binding domain of hFn. In vitro testing showed a remarkable difference between surfaces exposing adsorbed-only and surfaces with covalently immobilized hFn.

Journal Article↗

PubMed2006

A new generation videokymography for routine clinical vocal fold examination.

OBJECTIVE: This study aims to introduce a new-generation videokymographic system, which provides simultaneous laryngoscopic and kymographic image, for routine clinical vocal fold examination. STUDY DESIGN: The authors explored a new imaging method for diagnosis and evaluation of voice disorders. METHODS: The new-generation videokymographic system includes two charge-coupled device image sensors, a color area image sensor, and a monochromic high-speed line-scan image sensor. The high-speed line-scan image sensor is used to capture the kymogram, and the color area image sensor is used to obtain the laryngoscopic image. The two images can be displayed simultaneously on a video monitor or stored in a standard video recorder. Three subjects with nonpathologic voice were investigated in detail with the new videokymographic system. RESULTS: The high-quality laryngoscopic image and kymogram can be used directly for clinical purposes with no further postprocessing. The scan position of the kymogram is always indicated in the laryngoscopic image, which provides feedback for the operator to easily locate the expected scanning position. All varieties of vocal fold vibration, including irregular vibrations, phonation onset and offset, can be observed with the presented method. The continuous kymogram of the vocal fold vibration can be retrieved from a kymographic image sequence for quantitative analysis. CONCLUSIONS: The new-generation videokymography provides a simple, quick means to investigate vocal fold vibration, especially for voice disorders. It can emerge as an important tool for routine clinical vocal fold examination.

Data Display↗

PubMed1987

Effect of monoclonal antibody to pertussis toxin on toxin activity.

Two distinct monoclonal antibodies, one to pertussis toxin subunit S2, called 9G8, and another to subunits S2 and S3, called 11E6, were generated from the hybridomas of myeloma SP2/0 and spleen cells of BALB/c mice immunized mainly with the subunit S234 complex. Binding ability of 9G8 and 11E6 to the subunits was confirmed by the enzyme-linked immunosorbent assay and immunoblotting analysis. Generation of 11E6 bound to both S2 and S3 might mean that there is common antigenicity between S2 and S3. Neutralizing activities of 9G8 and 11E6 on various biological activities of pertussis toxin, including ADP-ribosyltransferase and leukocytosis-promoting, islet-activating, permeability-increasing. Chinese hamster ovary (CHO) cell-clustering, and hemagglutinating activities, were compared with those of anti-S1 monoclonal antibodies 1B7 and 3F10, which were isolated and characterized in a previous study (H. Sato, A. Ito, J. Chiba, and Y. Sato, Infect. Immun. 46:422-428, 1984). 1B7 and 3F10 neutralized ADP-ribosyltransferase activity of pertussis toxin or S1, but 9G8 and 11E6 did not. 1B7 showed very potent neutralization against leukocytosis-promoting, islet-activating, permeability-increasing, and CHO cell-clustering activities of pertussis toxin, but 3F10 did not, although anti-ADP-ribosyltransferase activities of both antibodies were identical. 11E6 neutralized leukocytosis-promoting, islet-activating, CHO cell-clustering, and hemagglutinating activities but not permeability-increasing activity. 9G8 showed slight neutralization of leukocytosis-promoting and CHO cell-clustering activities. Specific activities of 1B7 and 11E6 in each neutralization test were higher than or almost comparable to those of polyclonal antibodies to pertussis toxin. The neutralizing mechanism of 1B7 and 11E6 in leukocytosis-promoting activity was compared. 11E6 seemed to interfere with the binding of pertussis toxin to receptors on mouse spleen cells.

Animals↗

PubMed1999

A cluster analysis of alcohol-related attitudes and behaviors in the general population.

OBJECTIVE: Alcohol use typologies have previously focused on chronic alcohol abusers and alcohol-dependent populations. This empirical typology was created to profile lifestyle patterns associated with nonclinical patterns of alcohol use. METHOD: This study used two surveys sent to a commercial mailback panel, sampled to construct a study population demographically representative of the general U.S. population (N = 2,910). A K-means cluster analysis of alcohol use predictor variables and alcohol use generated the typology. RESULTS: The results suggest five distinct psychobehavioral clusters, referred to by the modal patterns of alcohol use for each cluster: nondrinkers, light drinkers, moderate drinkers, episodic drinkers and regular heavy drinkers. These clusters were found to have predictive validity using related health behaviors, psychosocial variables, personality self-descriptors, and media use as criteria. In particular, moderate drinkers had double the income of any other cluster and showed consistently healthy exercise, cigarette use, and diet patterns as well as a relatively high ranking of health as a personal value. Episodic drinkers had the highest levels of sensation-seeking and drug use and were not health oriented in values and behaviors, although their total weekly consumption was only marginally greater than the moderate drinkers. CONCLUSIONS: The profile of the moderate drinker cluster is consistent with concerns about lifestyle confounds in the relationship between moderate alcohol consumption and cardiovascular health. The episodic drinker profile is consistent with relatively high risk behaviors; this cluster may be a good target for harm-reduction education and intervention efforts.

Adult↗

PubMed1989

[Validation of an instrument to measure Exercise of Self Care Agency and its predictors].

The aim of this investigation was to delineate concepts contributing to the Exercise of Self-Care Agency (E.S.C.A.) Scale developed by Kearney & Fleischer (1979) and to test its construct validity and its predictors. The results are summarized as follows: 1. By means of principal factor analysis and maximal likelihood factor analysis upon data generated from 280 undergraduate students, the factors of Concern about Health Knowledge, Self-Concept, Information-Seeking Behavior, Decision-making and Responsibility, Self-esteem, and Passivity emerged. The total percent of variance explained by the 6 factors was 75.1%. 2. To assess factor independence and instrument homogeneity, correlations among the 6 factors were computed. The correlations ranged from .24 to .46 indicating that the factors and the items were not too similar or redundant. 3. Test-retest reliability of the total scale is r = .70. Cronbach's alpha coefficient for internal consistency of the total scale is .86 and that of the factors ranged from .750 to .661 (only factor 6 .497). 4. In additional analysis of the Exercise of Self-Care Agency Scale in relationship to Multiple Health Locus of Control, Family Environmental Scale, and Cornell Medical Index using stepwise multiple regression, the Internal Health Locus of Control Score predicted 21.8%(F = 53.34, P = .0001), Family Environmental Score 8.3%(F = 22.59, P = .0001), Modified Cornell Medical Index Score 5.4%(F = 15.74, P = .0001) of the score of the E.S.C.A.

Family↗

PubMed2002

[Seroprevalence of hepatitis C virus in the general population].

AIM: To determine the prevalence of hepatitis C virus (HCV) infection and to study associated risk factors in the general population of the province of Zamora. PATIENTS AND METHODS: For this transversal, observational, descriptive, population study, we randomly selected 1973 individuals over 14 years old and grouped them according to age and sex. The study included completion of a questionnaire containing socio-demographic information and data on risk factors. Serum samples were collected for analysis of antibodies to HCV by means of a third-generation ELISA, and were confirmed by an immunoblot technique. Viral load and genotype analyses were carried out in positive cases by polymerase chain reaction technique. RESULTS: Among the total, 600 complete studies (questionnaires and serum samples) 657 questionnaires and 675 samples were obtained. Eleven serum samples tested positive for HCV and among these, 5 were confirmed by immunoblot. The positive samples corresponded to 3 men and 2 women; 4 lived in urban settings and all 5 had one or more known risk factors for acquiring the infection. CONCLUSIONS: The prevalence of HCV infection in our geographical area was 0.74% (95% CI, 0.27-1.82). The seropositive individuals detected in this population screening study had a history of parenteral risk activities and most lived in urban areas.

Adolescent↗

PubMed1997

Prognostic role of cyclin D1 in non small cell lung cancer: an immunohistochemical analysis.

Lung cancer is a worldwide problem and in many countires it is the most lethal malignancy. Because relapse is frequent after resection of non small cell lung cancer, an urgent need exists to define prognostic factors which could help in choosing the best therapeutic approach. We performed immunohistochemistry on 60 formalin-fixed paraffin-embedded non small cell lung cancer specimens in order to evaluate the frequency of cyclin D1 overexpression, and to relate it to the degree of malignancy of these tumors and to the overall survival time of the patients. All specimens were positive for cyclin D1 immunostaining. We found cyclin D1 overexpression in 30 (50%) of our specimens, with no significant difference among the different histological types. Cyclin D1 overexpression correlates in a statistical manner with short-term patient survival. Mantel-Cox analysis of these data generated a significant P value = 0.003. The mean survival time and the five-year survival rate also differed statistically. We did not find any statistically significant correlation between cyclin D1 overexpression and histological grading, tumor stage or TNM status. We concluded that cyclin D1 overexpression in 30 patients is a frequent event in non small cell lung cancer pathogenesis and may have prognostic relevance.

Biomarkers, Tumor↗

PubMed2006

Assessment of airways with three-dimensional quantitative thin-section CT: in vitro and in vivo validation.

PURPOSE: To prospectively validate the ability of customized three-dimensional (3D) software to enable bronchial tree skeletonization, orthogonal reconstruction of the main bronchial axis, and measurement of cross-sectional wall area (WA) and lumen area (LA) of any visible bronchus on thin-section computed tomographic (CT) images. MATERIALS AND METHODS: Institutional review board approval and patient agreement and informed consent were obtained. Software was validated in a phantom that consisted of seven tubes and an excised human lung obtained and used according to institutional guidelines. In vivo validation was performed with multi-detector row CT in six healthy subjects (mean age, 47 years; range, 20-55 years). Intra- and interobserver agreement and reproducibility over time for bronchial tree skeletonization were evaluated with Bland-Altman analysis. Concordance in identifying bronchial generation was assessed with the kappa statistic. WA and LA obtained with the manual method were compared with WA and LA obtained with validated software by means of the Wilcoxon test and Bland-Altman analysis. RESULTS: WA and LA measurements in the phantom were reproducible over multiple sessions (P > .90) and were not significantly different from WA and LA assessed with the manual method (P > .62). WA and LA measurements in the excised lung and the subjects were not different from measurements obtained with the manual method (intraclass correlation coefficient > 0.99). All lobar bronchi and 80.8% of third generation bronchi, 72.5% of fourth generation bronchi, and 37.7% of fifth generation bronchi were identified in vivo. Intra- and interobserver agreement and reproducibility over time for airway skeletonization and concordance in identifying bronchial generation were good to excellent (intraclass correlation coefficient > 0.98, kappa > 0.54, respectively). CONCLUSION: This method enables accurate and reproducible measurement of WA and LA on reformatted CT sections perpendicular to the main axis of bronchi visible on thin-section CT scans.

Adult↗