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PubMed1988

Substrate effects on the dynamics of neurite growth in vitro: a quantitative multi-parametric analysis.

Embryonic chick dorsal root ganglia were cultured in serum-free medium on natural (collagen, fibronectin and hyaluronic acid) and artificial (polylysine and polyornithine) substrata. The movement of individual growth cones was quantified by measuring five parameters using time-lapse cinematography combined with a digitizing-computer system, and the neurite behaviour was compared between the different substrata with multivariate statistical methods. For each substratum, the morphometry of the growth cone was quantified by measuring six morphological parameters. The most discriminative parameters proved to be mean velocity and straightness index for neurite extension, and projected area and cumulated length of filopodia for growth cone morphometry. A good correlation was obtained between behavioural and morphological parameters and the larger the cone area and the filopodia length, the faster and the straighter the neuritic growth. Both quantitative analyses showed highest values for polyornithine and the lowest for hyaluronic acid, and divided the substrata into two opposite groups, artificial and natural. It is concluded that growth cone behaviour and conformation is modulated by substratum properties.

Animals↗
PubMed1986

Facial morphology and obstructive sleep apnea.

In a sample of 25 adult male subjects with moderate to severe obstructive sleep apnea, the interaction among craniofacial, airway, tongue, and hyoid variables was quantified by means of a canonical correlation analysis. One lateral cephalometric radiograph with the teeth in occlusion was obtained for each subject together with overnight polysomnographic measurements before the initiation of therapy. A principal component analysis reduced the data base and one significant canonical correlation (r1 = 0.994) was identified for the 22 variables. Sleep apnea subjects showed a posteriorly positioned maxilla and mandible, a steep occlusal plane, overerupted maxillary and mandibular teeth, proclined incisors, a steep mandibular plane, a large gonial angle, high upper and lower facial heights, and an anterior open bite in association with a long tongue and a posteriorly placed pharyngeal wall. A multivariate statistical analysis extracted clinically significant associations among craniofacial, tongue, and airway variables. Subjects with sleep apnea demonstrated several alterations in craniofacial form that may reduce the upper airway dimensions and subsequently impair upper airway stability.

Adult↗
PubMed1989

A multivariate approach to analyzing the relation between occlusion and craniofacial morphology.

This study examined the association between occlusion and craniofacial morphology using univariate and multivariate statistical methods. Data were obtained from study casts and lateral cephalometric radiographs of 164 children in the early permanent dentition. The following multiple features of occlusion were assessed: molar relation, overjet, overbite, and anterior crowding. Angular skeletal measures assessed cranial base flexure, maxillary horizontal and vertical positions, mandibular horizontal and vertical positions, horizontal and vertical maxillary-mandibular relations, and positions of the incisors. The relation between the Occlusal Index, which is a malocclusion severity index, and skeletal morphology was also investigated. Associations were examined by use of linear correlation, stepwise multiple regression, and canonical correlation analyses. Individually and in combination, occlusal features were poorly associated with individual skeletal measures (r2 less than or equal to 0.35). The strongest association occurred between a linear combination of occlusal features and a linear combination of skeletal measures (R2 = 0.66, p = 0.0001). A malocclusion severity index did not aid in the identification of craniofacial morphology. The results suggested that combinations of certain occlusal characteristics may be associated with specific skeletal types; however, a generalized statement of this concept could not be supported.

Adolescent↗
PubMed1990

Cluster analysis of an insulin-dependent diabetic cohort towards the definition of clinical subtypes.

Clinical and biochemical data on 111 consecutive insulin-dependent diabetic children enrolled in a longitudinal prospective study were analyzed to determine if more than one clinical expression of Type I diabetes exists. Use of multivariate statistical methods, including Correspondence Analysis, kappa-means clustering and RECPAM (RECursive Partition and AMalgamation), show that there are two well differentiated clinical expressions of IDDM each characterized by a cluster. One is characterized by later age, less severe onset, longer symptom duration, less beta-cell disappearance after 12 months, more females; the other by earlier age, more sudden and severe onset, DR 3/4, earlier disappearance of beta-cell function and more males. RECPAM analysis provides further insight into the structure of the two clusters. An other RECPAM tree identifies low, medium and high risk groups of disappearance of beta-cell function at 12 months after diagnosis.

Adolescent↗
PubMed1990

The epidemiological relationship of hypercholesterolemia, hypertension, diabetes mellitus and obesity to coronary heart disease and atherogenesis.

Coronary heart disease (CHD) is an imprecise, inappropriate monitor of atherosclerosis severity and by inapplicable extrapolation CHD risk factors are incorrectly assumed to be causes of atherosclerosis. Taking into account (1) the misuse and substantial diagnostic error of CHD, (2) errors in determining the prevalence of risk factors, (3) the use of a young non-representative minority of sufferers of CHD, (4) bias posed by inclusion of familial hypercholesterolemia (FH) in clinical studies and (5) mutual inter-relationships, genetic influence and age dependence of hypercholesterolemia, hypertension, diabetes mellitus and body mass or obesity, it is unlikely that multivariate statistical analyses can adequately differentiate between their effects. These factors are age dependent and so are CHD and atherosclerosis. The importance of hypercholesterolemia in atherogenesis is suspect particularly since the vascular pathology of familial hypercholesterolemia and of cholesterol-fed animals has been misrepresented and does not provide support for the role of hypercholesterolemia in atherogenesis.

Age Factors↗
PubMed1989

Special aspects of timing of liver transplantation in patients with liver cirrhosis.

The introduction of liver transplantation as a therapeutic procedure in the treatment of chronic liver disease has accelerated efforts to establish objective criteria in the evaluation of the prognosis of chronic liver disease. Evaluation of the optimum time for liver replacement involves the estimation of the spontaneous prognosis and the possible prognosis after transplantation. Because both items develop dynamically in different directions, criteria for the best time for the indication of liver transplantation are controversial; clinical deterioration of the patient seems to mark the beginning of this time even if the dynamic process of the evolution of clinical complications are taken into account. The change in biochemical parameters is more likely to define the end-point of this period when transplantation could be performed with reasonable success. The development of scores from multivariate statistical analyses has to include the aetiology of the underlying liver disease, but also the specific dynamics of the course of the disease. If these presumptions are fulfilled, the use of such scores seems to be a great step forward to the goal of objective criteria to define the optimum time for liver transplantation.

Hepatitis B↗
PubMed1994

Cryofixation, cryosubstitution, cryoembedding for ultrastructural, immunocytochemical and microanalytical studies.

Cryofixation, cryosubstitution and cryoembedding are a set of low-temperature methods for immunocytochemical and microanalytical ultrastructural studies. This review covers the theoretical and practical aspects of these cryomethods, simple, low-cost, safe devices that provide reproducible results and a summary of recent results. Sections prepared by these three cryomethods can be used to determine elemental composition, molecular composition, functions and 3-D ultrastructure. The information obtained can be treated by multivariate statistical methods. Thus, each cellular compartment can be identified by its morphology, molecular and elemental composition and function and changes in these data during physiological and pathological processes can be monitored.

Acrylic Resins↗
PubMed1991

Electron microscopy study of GroEL chaperonin: different views of the aggregate appear as a function of cell growth temperature.

We have studied two members of the family of morphogenetic factors or chaperonins, the GroEL-like factors from Escherichia coli and Bacillus subtilis, in order to determine the possible structural basis of their related function in promoting the correct and efficient assembly of biological oligomers. The main objective of this work has been to study by transmission electron microscopy the possible changes that these factors may undergo when subjected to a number of different conditions such as changes in temperature in vivo and in pH in vitro. We applied both rotational and multivariate statistical analyses of single particles to images of GroEl-like aggregates from the two bacteria. The most striking result is the finding of two distinct "front views" of these aggregates, from both E. coli and B. subtilis. One view, which has not been described earlier, shows a sixfold symmetry and is most abundant at growing temperatures below 37 degrees C. After heat shock, a view showing seven morphological units becomes dominant. On the basis of our analysis it is clear that GroEL-like morphogenetic factors from two unrelated bacteria such as E. coli and B. subtilis present two distinct views: one sixfold and the other sevenfold. Their relative percentage of appearance is related to the temperature at which the cells were grown and also to the storage conditions (pH).

Bacillus subtilis↗
PubMedDate not supplied

Patch averaging of electron images of GP3*I crystals with variable thickness.

The combination of Fourier and correlation averaging techniques with multivariate statistical analysis and classification, a method known as patch averaging, is used to analyze untilted and tilted images of negatively stained GP32*I crystals, which exhibit variable thicknesses in a single crystal. Within a single image, coherent areas of the same apparent thickness can be distinguished from areas of differing thicknesses. Analysis using the phase relationships among symmetry-related reflections from reconstituted images obtained from untilted micrographs confirms the ability of the method to classify these variable thicknesses properly. Furthermore, the phases from some of the reconstituted images obtained from both untilted and tilted micrographs were found to match well with the phases in a previously determined three-dimensional data set of this crystal with pg symmetry along the crystallographic b axis. These results indicate the utility of the patch averaging procedures in the structural determination of protein crystals with different thicknesses.

Crystallization↗
PubMed2004

Cephalometric variables predicting the long-term success or failure of combined rapid maxillary expansion and facial mask therapy.

The aim of this study was to select a model of cephalometric variables to predict the results of early treatment of Class III malocclusion with rapid maxillary expansion and facemask therapy followed by comprehensive treatment with fixed appliances. Lateral cephalograms of 42 patients (20 boys, 22 girls) with Class III malocclusion were analyzed at the start of treatment (mean age 8 years 6 months +/- 2 years, at stage I in cervical vertebral maturation). All patients were reevaluated after a mean period of 6 years 6 months (at stage IV or V in cervical vertebral maturation) that included active treatment plus retention. At this time, the sample was divided into 2 groups according to occlusal criteria: a successful group (30 patients) and an unsuccessful group (12 patients). Discriminant analysis was applied to select pretreatment predictive variables of long-term treatment outcome. Stepwise variable selection of the cephalometric measurements at the first observation identified 3 predictive variables. Orthopedic treatment of Class III malocclusion might be unfavorable over the long term when a patient's pretreatment cephalometric records exhibit a long mandibular ramus (ie, increased posterior facial height), an acute cranial base angle, and a steep mandibular plane angle. On the basis of the equation generated by the multivariate statistical method, the outcome of interceptive orthopedic treatment for each new patient with Class III malocclusion can be predicted with a probability error of 16.7%.

Adolescent↗
PubMed2005

Facial attractiveness: a longitudinal study.

BACKGROUND: The aim of the study was to investigate various factors that might affect facial attractiveness from ages 11 to 31 years. METHODS: Sixty subjects were selected from a sample participating in the longitudinal Cardiff Survey. Three-quarter-view facial photographs were taken of the subjects smiling and not smiling. Photos were taken in 1981, when the subjects were aged 11 years, and in 2001, when they were aged 31. Twelve judges used a 9-point Likert scale to evaluate overall facial attractiveness and the attractiveness of various facial features. The judges were also asked to estimate the adults' ages. Univariate and multivariate statistical tests and the generalizability theory were used. RESULTS AND CONCLUSIONS: Overall facial attractiveness does not depend on any single feature; smiling and youthful facial appearance make women look more attractive; facial attractiveness tends to decrease over time from ages 11 to 31; people tend to retain their relative levels of attractiveness throughout their life spans; orthodontic treatment improves dental appearance, but it does not necessarily make a person more attractive in the long term. Nevertheless, the positive effect of orthodontic treatment could still be observed, especially in men with lower levels of facial attractiveness in childhood.

Adult↗
PubMed2005

Development of public health priorities for end-of-life initiatives.

OBJECTIVE: Recently, end-of-life (EOL) issues have captured the attention of the public health community. This study reports a project to help state health departments better understand their potential role in addressing EOL issues and develop initial priorities for EOL activities. METHODS: The project involved two studies. Study 1 (October 2002 to September 2003) involved a concept mapping process to solicit and organize recommendations from key stakeholders. Concept mapping integrates qualitative group processes with multivariate statistical analysis to represent the ideas of stakeholders visually through maps. A key-informant approach was used to identify stakeholder participants with expertise in aging, cancer, public health, and EOL. In two meetings, stakeholders used the maps to develop short-, intermediate-, and long-term recommendations for EOL initiatives. Study 2 (October 2003 to September 2004) involved a modified Delphi process with three iterations to prioritize recommendations for initial action from among a group of short-term recommendations. RESULTS: Study 1 resulted in 103 recommendations for EOL initiatives across nine domains. Study 2 resulted in consensus on five initial recommendations from three domains: identifying an EOL point of contact in state health departments, collecting and analyzing data about EOL, incorporating EOL principles into state comprehensive cancer control plans, educating the public about hospice and palliative care, and educating the public about the importance of advance directives. CONCLUSIONS: Diverse perspectives of key public health stakeholders resulted in a series of short- and longer-term recommendations for EOL action. These recommendations can guide future efforts by state health departments and other public health agencies to address EOL issues.

Humans↗
PubMed2004

Impact of fluoride and other aquatic parameters on radon concentration in natural waters.

Radon (222Rn) accumulation in water in relation to stable elements was studied for the purpose of determining factors influencing the transfer of 222Rn to and from water. In 72 groundwater samples, 222Rn and about 70 analytical parameters were analysed using radiometric and ICP-MS techniques. Using multivariate statistics (partial least squares), it was observed that 222Rn has a positive correlation with fluoride and uranium. The correlation with fluoride was further investigated by a laboratory time-scale experiment to measure the emanation of 222Rn from water as a function of fluoride, pH and carbonate. The transfer of 222Rn from water was measured by continuous monitoring in air in a closed loop set-up. It was observed that fluoride in water adhere or trap 222Rn preferably in acidic water (pH 3). It is suspected that natural physical processes (such as diffusion and microbubble phenomenon) are less effective to transport 222Rn in the presence of fluoride.

Air↗
PubMed2006

An overview of the BEEP Stavanger workshop.

Within the three-year European Research Project BEEP (Biological Effects of Environmental Pollution in marine ecosystems), a workshop was carried out at the facility of Akvamiljø a.s. with the scientific support of IRIS (International Research Institute of Stavanger) researchers. Validation of newly developed biomarkers, especially at the molecular level, was the core part of the activity. Two large scale mesocosm exposures were done and samples shared between the participants (about 30 Institute), allowing an integrated approach for studying the effects of several pollutants selected as environmentally important issues (i.e. PAHs, alkyl phenols, bisphenol A, diallyl phthalate and polybrominated diphenyl ether). In addition, a field study (Visne, Norway) has been performed for the validations of biomarkers under environmental conditions. The Stavanger workshop demonstrates the importance of collaboration between researchers to establish common ways to proceed in biomarker analysis. The common exposures encourage a joint strategy for planning biomonitoring activity. A clarification in this direction is needed to coordinate results from numerous studies about the environmental impact of pollutants which are currently carried out all over Europe and around the world. Expertise in various disciplines is required to plan and perform a successful monitoring activity and to study/predict the effect of environmental pollutants. Biologists, chemists, statisticians and environmental researchers should always be included. The Stavanger workshop also indicated the importance of developing multivariate statistical methods to enable interpretation of complex data sets. It is of interest to develop statistical tools which can integrate the results from a battery of biomarkers in order to obtain a more complete picture of environmental impact.

Animals↗
PubMed2005

Seropositivity for anti-Borrelia IgG antibody is independently associated with carotid atherosclerosis.

BACKGROUND: Various infectious agents are associated with atherosclerosis. This analysis was performed to investigate relation between seropositivity for anti-Borrelia IgG and carotid atherosclerosis. METHODS: The cross-sectional Study of Health in Pomerania was conducted in a general community living in a region with endemic Lyme disease. A random sample of 2483 individuals aged 45-79 years was available for the present analysis. Carotid atherosclerosis was sonographically assessed as intima-media thickness of the common carotid artery and as prevalent atherosclerotic plaques in the extracranial carotid arteries. IgG antibodies to Borrelia were determined by ELISA. RESULTS: IgG antibodies to Borrelia were found positive (> 10 IU/mL) in 108 subjects (4.3%). Persons with and without positive anti-Borrelia IgG antibodies differed with respect to carotid intima-media thickness values (0.863 +/- 0.017 mm versus 0.792 +/- 0.004 mm; p < 0.001) and prevalent carotid plaques (odds ratio 2.65, 95% confidence interval 1.53-4.61; p = 0.001), respectively. Seropositivity for anti-Borrelia IgG was also associated with both atherosclerotic endpoints when age, sex and further atherogenic risk factors and confounders were included in multivariable statistical models. CONCLUSIONS: In a region with endemic Lyme disease, seropositivity for anti-Borrelia IgG antibodies is independently associated with atherosclerosis. Our findings add support to the hypothesis that exposure to infectious pathogens increases the atherosclerosis risk.

Adult↗
PubMed2006

A combinatorial approach to substrate discrimination in the P450 CYP1A subfamily.

A comparison of all known mammalian CYP1A sequences identifies nineteen sequence regions that are conserved within all 1A1s or within all 1A2s but at the same time systematically differ between any 1A1 and any 1A2. The purpose of this study was to explore links between these specific CYP1A sequence signatures and substrate specificity shift through the kinetic analysis of combinatorial variants of increasing complexity. The less complex variants correspond to multiple mutations within a short segment of their sequence. The more complex variants correspond to mosaic P450s recombining 1A1 and 1A2 sequences (up to 5 crossovers per sequence). Fifty-eight such functional CYP1A variants and parental wild-type enzymes were expressed in yeast and assayed with 7-alkoxyresorufins and ethoxyflurorescein ethyl ester as substrates. Observed kinetic data were analyzed by multivariate statistical analyses and hierarchical clustering in order to highlight correlations and identify potential sequence-activity relationships within the three-dimensional function space investigated. Several variants are outliers in these representations and show a redistribution of their substrate specificity compared to wild-type CYP1As. Some combinations of sequence elements were identified that significantly discriminate between 1A1 and 1A2 for these three substrates. The comparison of this combinatorial approach with previous results of site-directed mutagenesis is discussed.

Amino Acid Sequence↗
PubMed2006

Cell-cycle-dependent variations in FTIR micro-spectra of single proliferating HeLa cells: principal component and artificial neural network analysis.

We have previously reported spectral differences for cells at different stages of the eukaryotic cell division cycle. These differences are due to the drastic biochemical and morphological changes that occur as a consequence of cell proliferation. We correlate these changes in FTIR absorption and Raman spectra of individual cells with their biochemical age (or phase in the cell cycle), determined by immunohistochemical staining to detect the appearance (and subsequent disappearance) of cell-cycle-specific cyclins, and/or the occurrence of DNA synthesis. Once spectra were correlated with their cells' staining patterns, we used methods of multivariate statistics to analyze the changes in cellular spectra as a function of cell cycle phase.

Cell Cycle↗
PubMed2006

Brain tissue characterisation by infrared imaging in a rat glioma model.

Pathological changes associated with the development of brain tumor were investigated by Fourier transform infrared microspectroscopy (FT-IRM) with high spatial resolution. Using multivariate statistical analysis and imaging, all normal brain structures were discriminated from tumor and surrounding tumor tissues. These structural changes were mainly related to qualitative and quantitative changes in lipids (tumors contain little fat) and were correlated to the degree of myelination, an important factor in several neurodegenerative disorders. Lipid concentration and composition may thus be used as spectroscopic markers to discriminate between healthy and tumor tissues. Additionally, we have identified one peculiar structure all around the tumor. This structure could be attributed to infiltrative events, such as peritumoral oedema observed during tumor development. Our results highlight the ability of FT-IRM to identify the molecular origin that gave rise to the specific changes between healthy and diseased states. Comparison between pseudo-FT-IRM maps and histological examinations (Luxol fast blue, Luxol fast blue-cresyl violet staining) showed the complementarities of both techniques for early detection of tissue abnormalities.

Animals↗