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Familial resemblance for physique: heritabilities for somatotype components.

PRIMARY OBJECTIVE: To examine familial resemblance in the Heath-Carter anthropometric somatotype in a sample of 328 participants from 103 nuclear families in Northern Ontario (Canada). METHODS AND PROCEDURES: The three somatotype components (endomorphy, mesomorphy, ectomorphy) were subjected to principal components analysis and the resulting first principal component (PCI) was used as an additional index of physique. The four phenotypes were adjusted for age, sex and generation effects, while each of the three somatotype components was further adjusted for the effects of the other two components using regression procedures. A familial correlation model was fit to the data and used to estimate the degree of familial resemblance in somatotype. MAIN OUTCOME AND RESULTS: For all somatotype variables, the most parsimonious model was one in which there was no spouse resemblance and no sex or generation effects in the familial correlations. Maximal heritabilities were 56%, 68%, 56% and 64% for endomorphy, mesomorphy, ectomorphy and PCI, respectively, indicating significant familial resemblance for the Heath-Carter anthropometric somatotype. Further, the pattern of familial correlations suggests the role of genetic factors in explaining variation in human physique. CONCLUSIONS: In general, a pattern of no spouse but significant parent-child correlations implicates the role of genes on human physique, provided that mating is random with regard to these traits.

Adolescent↗

Relationship of remote sensing normalized differential vegetation index to Anopheles density and malaria incidence rate.

OBJECTIVE: To study the relationship of remote sensing normalized differential vegetation index (NDVI) to Anopheles density and malaria incidence rate. METHODS: Data of monthly average climate, environment, Anopheles density and malaria incidence rate, and remote sensing NDVI were collected from 27 townships of 10 counties in southeastern Yunnan Province from 1984 to 1993. The relationship of remote sensing ecological proxy index, NDVI, to Anopheles density and malaria incidence rate was studied by principal component analysis, factor analysis and grey correlation analysis. RESULTS: The correlation matrix showed that NDVI highly correlated with Anopheles density in 4 townships of Mengla, Jinghong, and Yuanjiang counties, but in other 23 townships the relationship was not clear. Principal component and factor analyses showed that remote sensing NDVI was the representative index of the first principal component and the first common factor of Anopheles density evaluation. Grey correlation analysis showed that in rainy season NDVI had a high grey correlation with Anopheles density and malaria incidence rate. The grey correlation analysis showed that in rainy season the grey degree of NDVI correlated with Anopheles. Minimus density was 0.730, and 0.713 with Anopheles sinensis density, and 0.800 with malarial incidence rate. CONCLUSION: Remote sensing NDVI can serve as a sensitive evaluation index of Anopheles density and malaria incidence rate.

Animals↗

High compression of nuclear medicine dynamic studies.

As data compression plays now an important role in the development of medical PACS, a technique has been developed for medical image sequences storage and transmission in order to obtain very high compression ratio: in dynamic nuclear medicine studies it can achieve a compression ratio as high as 100:1 without significant degradation. The implemented technique combines two methods which multiply their effects. In a first step, a principal component analysis (PCA) of the image series is performed. It extracts a limited number of principal components and their associated images. For data compression it is not necessary to perform an oblique factor analysis to estimate the so-called 'physiological functions' and their spatial distributions as in factor analysis of dynamic structures (FADS). In a second step, the principal images are compressed by means of a transform coding procedure: an adaptive block-quantization technique using the 2D discrete cosine transform (DCT) is implemented, followed by a statistical quantization method to encode the DCT coefficients. To reconstruct the principal images, an inverse DCT is applied. Then the original series is computed from the reconstructed images combined with the principal components which have been stored without any modification. The reconstructed series is compared to the original series, as well as the time activity curves generated on different regions of interest (ROI) and the factor estimates obtained using FADS performed on the two series. Method and evaluation are illustrated on an example of first pass radionuclide angiocardiography.

Humans↗

Profiling of gene expression in rat liver and rat primary cultured hepatocytes treated with peroxisome proliferators.

The Toxicogenomics project has been constructing a large-scale database of about 150 compounds exposed to rat (single dose, 3, 6, 9, 24 hrs and repeated dose for 3, 7, 14 28 days with 3 dose levels) and rat hepatocytes (2, 8, 24 hr with 3 concentrations) and data of transcriptome in liver using GeneChip, and the related toxicological measures are being accumulated. In the present study, the data of three ligands of peroxisome proliferator activated receptor alpha (PPARalpha), i.e., clofibrate, WY-14643 and gemfibrozil in our database were analyzed. Many of the beta-oxidation-related genes were commonly induced in vivo and in vitro, whereas expression changes in genes related to cell proliferation, apoptosis, were detected in vivo (single and repeated dose) but not in vitro. Changes in those related to the immune response, coagulation and the stress response were also detectable exclusively in vivo. Using the genes mobilized in two or three PPARalpha agonists, hierarchical clustering was performed on 32 compounds stored in our database. In the profiling of an in vivo single dose, benzbromarone and aspirin were located in the same cluster of the three PPARalpha agonists. The clustering of in vitro data revealed that benzbromarone, three NSAIDs (aspirin, indomethacin and diclofenac sodium) and valproic acid belonged to the same cluster of PPARalpha agonists, supporting the reports that benzbromarone,valproic acid and some NSAIDs were reported to be PPARalpha agonists. Using the genes commonly up-regulated both in vivo and in vitro, principal component analysis was performed in 32 compounds, and principal component 1 was found to be the convenient parameter to extract PPARalpha agonist-like compounds from the database.

Alanine Transaminase↗

Proteomic analysis of agar gel-entrapped Pseudomonas aeruginosa.

We have compared the protein maps of agar-entrapped Pseudomonas aeruginosa cells to those of free counterparts grown in the presence or absence of the immobilized-cell gel support. Principal component analyses (PCAs) were used to interpret spot quantity variations observed on electropherograms obtained by two-dimensional gel electrophoresis. PCA of the data matrix (923 rows x 6 columns) in which spot density values were standardized horizontally extracted three principal components (PCs) with eigenvalues higher than 1, accounting together for 71.6% of the variability in the data. Principal component 1 (PC1) opposed free (F) and agar-entrapped (AE) cultures, with a low contribution of agar-released, free (ARF) cultures to PC1. Inversely, the contribution of ARF cultures to PC2 was high, opposing those of AE and F cultures. Component 3 was related to the duration of incubation. Only 10% of total proteins were upregulated in AE cells during the first 18 h of incubation, the number of underexpressed peptides balancing that of overexpressed ones. Downregulation clearly became the dominant tendency when the incubation time was extended to 48 h. These results demonstrate that AE and ARF bacteria are physiologically different from F organisms.

Agar↗

Assessment of near-infrared spectral information for rapid monitoring of bioprocess quality.

Access to real-time process information is desirable for consistent and efficient operation of bioprocesses. Near-infrared spectroscopy (NIRS) is known to have potential for providing real-time information on the quantitative levels of important bioprocess variables. However, given the fact that a typical NIR spectrum encompasses information regarding almost all the constituents of the sample matrix, there are few case studies that have investigated the spectral details for applications in bioprocess quality assessment or qualitative bioprocess monitoring. Such information would be invaluable in providing operator-level assistance on the progress of a bioprocess in industrial-scale productions. We investigated this aspect and report the results of our investigation. Near-infrared spectral information derived from scanning unprocessed culture fluid (broth) samples from a complex antibiotic production process was assessed for a data set that incorporated bioprocess variations. Principal component analysis was applied to the spectral data and the loadings and scores of the principal components studied. Changes in the spectral information that corresponded to variations in the bioprocess could be deciphered. Despite the complexity of the matrix, near-infrared spectra of the culture broth are shown to have valuable information that can be deconvoluted with the help of factor analysis techniques such as principal component analysis (PCA). Although complex to interpret, the loadings and score plots are shown to offer potential in process diagnosis that could be of value in the rapid assessment of process quality, and in data assessment prior to quantitative model development.

Anti-Bacterial Agents↗

Grouping of amino acid types and extraction of amino acid properties from multiple sequence alignments using variance maximization.

Understanding of amino acid type co-occurrence in trusted multiple sequence alignments is a prerequisite for improved sequence alignment and remote homology detection algorithms. Two objective approaches were used to investigate co-occurrence, both based on variance maximization of the weighted residue frequencies in columns taken from a large alignment database. The first approach discretely grouped amino acid types, and the second approach extracted orthogonal properties of amino acids using principal components analysis. The grouping results corresponded to amino acid physical properties such as side chain hydrophobicity, size, or backbone flexibility, and an optimal arrangement of approximately eight groups was observed. However, interpretation of the orthogonal properties was more complex. Although the principal components accounting for the largest variances exhibited modest correlations with hydrophobicity and conservation of glycine, in general principal components did not correspond to physical properties of amino acids. Although not intuitive, these amino acid mathematical properties were demonstrated to be robust and to improve local pairwise alignment accuracy, relative to 20 amino acid frequencies alone, for a simple test case.

Amino Acids↗

Non-rigid image registration using a statistical spline deformation model.

We propose a statistical spline deformation model (SSDM) as a method to solve non-rigid image registration. Within this model, the deformation is expressed using a statistically trained B-spline deformation mesh. The model is trained by principal component analysis of a training set. This approach allows to reduce the number of degrees of freedom needed for non-rigid registration by only retaining the most significant modes of variation observed in the training set. User-defined transformation components, like affine modes, are merged with the principal components into a unified framework. Optimization proceeds along the transformation components rather then along the individual spline coefficients. The concept of SSDM's is applied to the temporal registration of thorax CR-images using pattern intensity as the registration measure. Our results show that, using 30 training pairs, a reduction of 33% is possible in the number of degrees of freedom without deterioration of the result. The same accuracy as without SSDM's is still achieved after a reduction up to 66% of the degrees of freedom.

Algorithms↗

Composite method to quantify powder flow as a screening method in early tablet or capsule formulation development.

The flow properties of typical tablet and capsule formulation excipients, active compounds, and representative formulation blends were tested with current and novel flow measurement techniques to identify a reliable bench test to quantify powder flow as a screening method in early tablet and capsule formulation development. Test methods employed were vibrating spatula, critical orifice, angle of repose, compressibility index, and avalanching analysis. Powder flow results from each method were compiled in a database, sorted, and compared. An empirical composite index was established and powder flow was ranked in accordance with formulator experience. Principal components analyses of the angle of repose, percent compressibility, and critical orifice of the powder materials were also performed. The first principal component accounted for 72.8% of data variability; scores associated with this principal component score can serve as an index of flowability. Data generated from vibrating spatula and avalanching methods were not reproducible and were inconsistent with formulator experience and cited vendor references for flow. Improvements of test instruments and further studies are necessary for better assessment of these approaches.

Capsules↗

Relationship of total body fatness and five anthropometric indices in Chinese aged 20-40 years: different effects of age and gender.

OBJECTIVES: We aim to evaluate the ethnic-specific relationship of total fat mass and anthropometric indices in Chinese. DESIGN: Cross-section study. SETTING: This study was performed at the College of Life Sciences, Hunan Normal University, P.R. China. SUBJECTS AND METHOD: To increase our understanding of the relationship of total fat mass and anthropometric indices in Chinese, 793 females and 1091 males aged 20-40 years were randomly recruited from Changsha city of P. R. China. Hip circumference (HC) and waist circumference (WC) were measured using standardized equipments, and other three anthropometric indices of body mass index (BMI), waist-to-hip ratio (WHR), and conicity index (CI) were calculated using weight, height, HC and WC. Total body fatness (TBF) in kg was measured using a Hologic QDR 4500 W dual-energy X-ray absorptiometry (DEXA) scanner. RESULTS: There was an increasing trend of TBF, %TBF (percent total body fatness) and the five anthropometric indices in successively older age groups. Compared with females, males generally had high average BMI, WC, HC, WHR and CI, but had low average TBF and %TBF. Except for some correlations in 25-29 years age groups, TBF and %TBF were significantly correlated with five anthropometric indices with the Pearson's correlation coefficients ranging from 0.07 to 0.87. Principal component analysis (PCA) was performed to form four principal components (PCs) that interpreted over 99% of the total variation of the five related anthropometric indices in all age groups, with over 53% of the total variation accounted for by the PC1. Multiple regression analyses showed that four PCs combined explained a greater variance (R (2)=55.2-80.8%) in TBF than did BMI alone (R (2)=40-74.9%). CONCLUSION: Our results suggest that there is an increasing trend of total fat mass and five anthropometric indices with aging; that age and sex have the important effects on influencing the correlations of TBF and the studied anthropometric indices; and that the accuracy of predicting the TBF using five anthropometric indices is higher than using BMI alone.

Absorptiometry, Photon↗

Modified neonatal growth assessment score: a multivariate approach to the detection of intrauterine growth retardation in the neonate.

The objective of this investigation was the development of a modified Neonatal Growth Assessment Score (mNGAS) for use in the evaluation of neonatal growth status. The growth of 74 fetuses at risk for intrauterine growth retardation (IUGR) was followed longitudinally, beginning in the first or early second trimester. Rossavik growth models derived from data obtained in the second trimester were used to predict the weight (WT), crown-heel length (CHL) and head (HC), abdominal (AC) and thigh circumferences (ThC) at birth, which were then actually measured within 24 h after delivery. These measurements were compared to age-specific size curves and used to calculate sets of five growth potential index (GPRIi) values, which in turn were used to calculate five-variable Neonatal Growth Assessment Scores (NGAS5). Neonates were initially classified as normal or IUGR on the basis of NGAS5, GPRIi, and anatomic measurements. A final classification based on principal component analysis and linear discriminant analysis was carried out. The score obtained using the first principal component function was defined to be mNGAS51. The effectiveness of mNGASij values, determined from 1-4 GPRIi values, in separating normal and IUGR neonates was also evaluated. Neonates initially considered to be normal had very few abnormal GPRI values or anatomic measurements, whereas the frequency of these abnormalities in IUGR neonates was significantly increased. However, no single anatomic variable was 100% normal in the normal neonates and 100% abnormal in IUGR neonates. Only 40% of IUGR neonates were small for gestational age. Classification of these neonates using principal component analysis and linear discriminant analysis was essentially the same (98.6%) as that made initially after reclassification of two IUGR neonates as normal. The characteristics of the initial and final normal and IUGR groups were very similar and the mNGAS51 was strongly correlated with the NGAS5 in the IUGR group. The effectiveness of mNGASij in separating normal and IUGR neonates increased with the number of GPRIi values included and the types used. GPRIThC and GPRIWT were the most important, followed by GPRIAC. GPRICHL and GPRIHC were much less important and in some cases detrimental. These findings support the concepts of a decrease in soft tissue mass as the initial step in the development of IUGR and the protection of head growth (brain-sparing). The characteristics of mNGAS51, particularly its comprehensiveness, its independence of differences in growth potential, its weighting of GPRIi values according to their importance in the detection of IUGR and its ability to detect different manifestations of IUGR in different individuals, indicate that this should be a most effective parameter for separating normal and IUGR neonates.

Embryonic and Fetal Development↗

A vision specific functional index for use in patients with age related macular degeneration.

AIM: To develop and evaluate a new vision specific functional index for use in individuals with age related macular degeneration (AMD). METHODS: Following consultation with patients with AMD and healthcare professionals, a questionnaire entitled the Daily Living Tasks Dependent on Vision (DLTV) was constructed. It was administered by interview to three separate groups of individuals aged 50 years or older: people with AMD, people with cataract, and people with no visual disability. The relations between DLTV, distance visual acuity, and disorder were examined using Pearson's product moment correlation coefficients, stepwise regression, and principal component analysis. RESULTS: There was a positive correlation between DLTV items and distance visual acuity in the better eye. Principal component analysis showed that the DLTV has a major single dimension within it. This first principal component accounted for 59% of the variation and correlated well with distance visual acuity in the better eye. Other components were found, one of which correlated with the difference in vision in the two eyes and one which featured in the differentiation of AMD subjects from individuals with cataracts. CONCLUSIONS: The DLTV provided information on visual impairment in patients over and above that obtained from a measure of visual acuity. It also showed that patients with AMD experience greater difficulty with daily living tasks for any given level of acuity than do patients with cataract.

Activities of Daily Living↗

Application of a new statistical method to derive dietary patterns in nutritional epidemiology.

Because foods are consumed in combination, it is difficult in observational studies to separate the effects of single foods on the development of diseases. A possible way to examine the combined effect of food intakes is to derive dietary patterns by using appropriate statistical methods. The objective of this study was to apply a new statistical method, reduced rank regression (RRR), that is more flexible and powerful than the classic principal component analysis. RRR can be used efficiently in nutritional epidemiology by choosing disease-specific response variables and determining combinations of food intake that explain as much response variation as possible. The authors applied RRR to extract dietary patterns from 49 food groups, specifying four diabetes-related nutrients and nutrient ratios as responses. Data were derived from a nested German case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam study consisting of 193 cases with incident type 2 diabetes identified until 2001 and 385 controls. The four factors extracted by RRR explained 93.1% of response variation, whereas the first four factors obtained by principal component analysis accounted for only 41.9%. In contrast to principal component analysis and other methods, the new RRR method extracted a significant risk factor for diabetes.

Alcohol Drinking↗

Quantitative validation of a general competency composite assessment evaluation.

OBJECTIVES: The authors sought to modify and validate a composite assessment evaluation process that assesses resident acquisition of the Accreditation Council for Graduate Medical Education (ACGME) general competencies (GCs). METHODS: This study critically analyzed the evaluation process used in a multicenter study (150 emergency medicine resident evaluations) to determine whether the procedure was psychometrically valid. For each GC, principal component analysis (PCA) was used to determine whether certain evaluation items could be eliminated, as well as to determine the magnitude of variability explained by up to three linear combinations or "principal components." The factor proportions (factor loadings) of various eigenvectors were measured to determine the degree of variability (determined by the square of the factor proportion) within a data or item set. The factor proportions essentially measure the length of the eigenvector as determined from a correlation matrix. RESULTS: The first three principal components are reported as factor proportion sum (% of total variability) as follows: patient care 0.91 (83%), medical knowledge 0.87 (76%), practice-based learning and improvement 0.90 (81%), interpersonal and communication skills 0.84 (71%), professionalism 0.74 (55%), and systems-based practice 0.80 (64%). PCA showed that evaluating certain traditional categories such as medical knowledge seemed to capture a single element, whereas professionalism appeared to measure a more complex, multidimensional phenomenon. CONCLUSIONS: By using a structured development process, the authors were able to create valid evaluation items for determining resident acquisition of the ACGME GCs.

Clinical Competence↗

Validation of a pediatric voice quality-of-life instrument: the pediatric voice outcome survey.

OBJECTIVE: To validate a parent proxy instrument to study the voice-related quality of life (VR-QOL) for the pediatric population. METHODS: The voice outcome survey (VOS) was administered to 108 caregivers of children aged 2 to 18 years, who either had a tracheotomy or had achieved surgical decannulation. The VOS was altered so that each item was addressed to the parent proxy as opposed to the child. A scoring paradigm was developed to report the scores on a range of 0 to 100. Structural properties of the instrument examined include validity, reliability, and principal component analysis. The VOS was then revised to suit the results of this analysis. RESULTS: The mean +/- SD (range) score for the pediatric VOS was 49.8 +/- 27.1 (0-100). Reliability analysis and principal component analysis supported the reduction of 1 item from the final pediatric VOS. The revised instrument demonstrated an overall Cronbach alpha value of.86. Substratification by age revealed robust Cronbach alpha values from ages 2 to 18 years. Construct validity analysis also supported statistical significance (P =.004). Principal component analysis of the revised instrument supports its internal structure and design. CONCLUSIONS: The pediatric VOS is a simple, short, health status instrument designed to measure the VR-QOL in the pediatric population. Cross-sectional analysis suggests that children and adolescents with tracheotomies have a poorer VR-QOL than do those who have achieved decannulation.

Adolescent↗

Bombesin decreases yawning in a high-yawning subline of Sprague-Dawley rats.

This study analysed the effect of the intracerebroventricular administration of bombesin (BN) at doses of 0.001, 0.005, 0.1 and 1.0 microg/2 microl on yawning, grooming and other behavioral correlates in two inbred strains of male rats. These were selected for high-yawning (HY) and low-yawning (LY) frequency, a difference that correlates with novelty-induced grooming. Grooming increased with BN in a strain-specific manner, and yawning decreased in HY rats. Principal component analysis (PCA) showed that rats' behaviors changed from yawning to grooming with BN. Such change differed between the strains. While the first principal component was dominated by grooming in both strains, the second principal component was dominated by stretching and penile erections in HY rats, and by scratching in LY rats. While LY rats spent more time in scratching both within and outside grooming bouts, HY rats tended to favour the latter category. An increment in mean duration of grooming bouts characterized the effect of the highest dose. These findings show that BN inhibits yawning and increases grooming, suggesting that this peptide enhances the initial response to novel environments. The study shows the importance of combining studies on inbred strains with appropriate multivariate methods to separate drug-induced behavioral patterns.

Animals↗

Nasal biomarker profiles in acute and chronic rhinosinusitis.

BACKGROUND: Clinical manifestations of rhinosinusitis include acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyps and CRS without polyps. OBJECTIVE: Possible mechanisms defining these three forms of rhinosinusitis should be investigated assessing biomarker profiles in nasal secretions. METHODS: Fifteen cytokines, three cellular activation markers and total IgE were determined in nasal secretions of seven patients with acute rhinosinusitis, 12 patients with CRS without polyps, 13 patients with CRS with polyps and six healthy controls. Principal component analysis was used to extract relevant factors. RESULTS: Irrespective of the clinical manifestation, all biomarkers assessed were increased in patients with rhinosinusitis when compared with controls (P<0.001). Principal component analysis allowed the extraction of three factors explaining 83% of data variance. The general inflammatory activation was mainly reflected by the first factor. The second factor differentiated acute from CRS. This factor correlated with IL-12, which is involved in pathogen-related immune activation by antigen-presenting cells. It was also positively correlated with IL-4, IL-10 and IL-13, which play an important role in the resolution of infections. The third factor differentiated CRS with polyps from CRS without polyps (P=0.001). It represented IL-5 and nasal IgE (nIgE), whereas eosinophil cationic protein and tryptase were not specific for CRS with polyps. CONCLUSION: In mucosal infection, numerous inflammatory mediators are activated. Simple correlations of few biomarkers with a specific disease process bear the risk of overestimating a possibly unspecific effect. To assess biomarker profiles, more complex analytic tools may be more appropriate to delineate mechanisms underlying mucosal disease. Using principal component analysis, it was found that high nIgE and IL-5 levels are specific for CRS with nasal polyps.

Acute Disease↗

Genetic covariance structure of growth in the salamander Ambystoma macrodactylum.

The size of an organism at any point during ontogeny often has fitness consequences through either direct selection on size or through selection on size-related morphological, performance, or life history traits. However, the evolutionary response to selection on size across ontogeny (a growth trajectory) may be limited by genetic correlations across ages. Here we characterize the phenotypic and genetic covariance structure of length and mass growth trajectories in a natural population of larval Ambystoma macrodactylum using function-valued quantitative genetic analyses and principal component decomposition. Most of the phenotypic and genetic variation in both growth trajectories appears to be confined to a single principal component describing a pattern of positive covariation among sizes across all ages. Higher order principal components with no significant associated genetic variation were identified for both trajectories, suggesting that evolution towards certain patterns of negative covariation between sizes across ages is constrained. The well-characterized positive relationship between size at metamorphosis and fitness in pond-breeding amphibians predicts that the across-age covariance structure will strongly limit evolution only if there is negative selection on size prior to metamorphosis. The pattern of genetic covariation observed in this study is similar to that observed in other vertebrate taxa, indicating that size may often be highly genetically and phenotypically integrated across ontogeny. Additionally, we find that phenotypic and genetic analyses of growth trajectories can yield qualitatively similar patterns of covariance structure.

Animals↗