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Pedigree discriminant analysis: a method to identify monogenic segregation.

We describe a method for obtaining a linear discriminant function to identify monogenic segregation in multivariate pedigree data. It differs from Fisher's linear discriminant function in that it does not assume that the genotype of each individual in the pedigree already known. The method consists of finding that linear function of the variables that maximizes the likelihood of a set of pedigree data, under the hypothesis of single gene segregation, subject to the constraint that the total sample variance of the function remains constant. To simplify the computation the variables are first transformed to their standardized principal components. Reanalysis of a set of pedigree data suggests that age and powers of age should be considered as extra variables from which the principal components are obtained, and virtually all of the variance should be accounted for by the principal components used to obtain the discriminant function.

Age Factors↗

Differences in in vitro pollen germination and pollen tube growth of cotton cultivars in response to high temperature.

UNLABELLED BACKGROUND AND AIMS: High-temperature environments with >30 degrees C during flowering reduce boll retention and yield in cotton. Therefore, identification of cotton cultivars with high-temperature tolerance would be beneficial in both current and future climates. * METHODS: Response to temperature (10-45 degrees C at 5 degrees C intervals) of pollen germination and pollen tube growth was quantified, and their relationship to cell membrane thermostability was studied in 12 cultivars. A principal component analysis was carried out to classify the genotypes for temperature tolerance. * KEY RESULTS: Pollen germination and pollen tube length of the cultivars ranged from 20 to 60 % and 411 to 903 microm, respectively. A modified bilinear model best described the response to temperature of pollen germination and pollen tube length. Cultivar variation existed for cardinal temperatures (T(min), T(opt) and T(max)) of pollen germination percentage and pollen tube growth. Mean cardinal temperatures calculated from the bilinear model for the 12 cultivars were 15.0, 31.8 and 43.3 degrees C for pollen germination and 11.9, 28.6 and 42.9 degrees C for pollen tube length. No significant correlations were found between pollen parameters and leaf membrane thermostability. Cultivars were classified into four groups based on principal component analysis. * CONCLUSIONS: Based on principal component analysis, it is concluded that higher pollen germination percentages and longer pollen tubes under optimum conditions and with optimum temperatures above 32 degrees C for pollen germination would indicate tolerance to high temperature.

Cell Membrane↗

Tuning of a basic coordination pattern constructs straight-ahead and curved walking in humans.

We tested the hypothesis that common principles govern the production of the locomotor patterns for both straight-ahead and curved walking. Whole body movement recordings showed that continuous curved walking implies substantial, limb-specific changes in numerous gait descriptors. Principal component analysis (PCA) was used to uncover the spatiotemporal structure of coordination among lower limb segments. PCA revealed that the same kinematic law accounted for the coordination among lower limb segments during both straight-ahead and curved walking, in both the frontal and sagittal planes: turn-related changes in the complex behavior of the inner and outer limbs were captured in limb-specific adaptive tuning of coordination patterns. PCA was also performed on a data set including all elevation angles of limb segments and trunk, thus encompassing 13 degrees of freedom. The results showed that both straight-ahead and curved walking were low dimensional, given that 3 principal components accounted for more than 90% of data variance. Furthermore, the time course of the principal components was unchanged by curved walking, thereby indicating invariant coordination patterns among all body segments during straight-ahead and curved walking. Nevertheless, limb- and turn-dependent tuning of the coordination patterns encoded the adaptations of the limb kinematics to the actual direction of the walking body. Absence of vision had no significant effect on the intersegmental coordination during either straight-ahead or curved walking. Our findings indicate that kinematic laws, probably emerging from the interaction of spinal neural networks and mechanical oscillators, subserve the production of both straight-ahead and curved walking. During locomotion, the descending command tunes basic spinal networks so as to produce the changes in amplitude and phase relationships of the spinal output, sufficient to achieve the body turn.

Adaptation, Physiological↗

Complexity analysis of the magnetoencephalogram background activity in Alzheimer's disease patients.

The aim of the present study was to analyse the magnetoencephalogram (MEG) background activity in patients with Alzheimer's disease (AD) using the Lempel-Ziv (LZ) complexity. This non-linear method measures the complexity of finite sequences and is related to the number of distinct substrings and the rate of their occurrence along the sequence. The MEGs were recorded with a 148-channel whole-head magnetometer (MAGNES 2500 WH, 4D Neuroimaging) in 21 patients with AD and in 21 age-matched control subjects. Artefact-free epochs were selected for complexity analysis. Results showed that MEG signals from AD patients had lower complexity than control subjects' MEGs and the differences were statistically significant (p<0.01). In order to reduce the dimension of the LZ complexity results, a principal components analysis (PCA) was applied, and only the first principal component was retained. The first component score from PCA was graphically analysed using a box plot and a receiver-operating characteristic (ROC) curve. A specificity of 85.71%, a sensitivity of 80.95% and an area under the ROC curve of 0.9002 were obtained. These preliminary results suggest that cognitive dysfunction in AD is associated with a decreased LZ complexity in the MEG signals.

Aged↗

Subjective experiences and the psychopathological dimensions in schizophrenia.

The aim of this article was to explore the relationships between subjective experience (SE) and objective symptoms in schizophrenia. Exploratory principal component analysis was used to determine the latent organization of the variables. A group of 310 chronic patients with schizophrenia who met ICD-10 criteria for F20 schizophrenic disorder were included in the study. SE and objective symptoms were rated using, respectively, the 24-item version of the Frankfurt Complaint Questionnaire (FCQ-24) and the Positive and Negative Syndrome Scale (PANSS). An exploratory principal component analysis was performed on the correlation matrix comprising items from both the FCQ-24 and the PANSS. Using several guidelines to select the number of factors, the exploratory principal component analysis yielded a six-factor solution with no overlap of the significant factor loadings for the items from each scale. These six factors represent, respectively, the subjective, negative, positive, disorganization, hostility and anxious-depressive dimensions of the schizophrenic phenomenology. The findings support the view that SE is a construct that is separate and distinct from the objective symptomatology in schizophrenia.

Adult↗

Development of a COPD severity score.

OBJECTIVE: Treatment of chronic obstructive pulmonary disease (COPD) is based on symptom control. This suggests that COPD severity can be determined by analyzing treatment intensity. The objective of this analysis was to develop and validate a severity score for adult COPD based on treatments. RESEARCH DESIGN: Using principal components analysis, a COPD severity score was developed using data based on treatments extracted from an employer claims database (development group). Variables included were identified from literature review and clinical expert opinion. External validity was tested in a separate group of adult chronic bronchitis patients in whom principal components analysis was re-conducted and factor loadings were compared to the development group. Construct validity was tested by comparing the incidence of acute exacerbations of chronic bronchitis (AECB) in patients with high and lower severity scores. To illustrate the use of the COPD severity score, effectiveness of alternative AECB antibiotic treatments was compared in a separate patient sample categorized by severe versus mild/moderate COPD. RESULTS: In the development group (n = 2068), principal components analysis produced a single main factor for severity scoring. Of the 12 variables contributing to this factor, the 6 with the highest factor loadings were treatment related. The factor performed similarly in the external validity group (n = 9127) as it did in the development group. In construct validity testing, severe COPD patients were 4 times more likely to have AECB episodes than mild/moderate patients. Patients with severe COPD and an AECB were more likely to fail treatment with antibiotics than those with mild/moderate COPD. Based on the COPD severity score developed, we found that treatment of patients with severe COPD and an AECB with fluoroquinolones was more likely to result in treatment failure than treatment with macrolides (OR = 2.01; p = 0.03). CONCLUSIONS: The analysis was successful in developing and validating a method to score COPD severity based on treatments. This method may prove useful in providing insights about the benefits of COPD treatments.

Anti-Bacterial Agents↗

Dietary patterns and lifestyle factors in the Norwegian EPIC cohort: the Norwegian Women and Cancer (NOWAC) study.

OBJECTIVE: To identify different dietary patterns in Norway using a combination of cluster and factor analysis. DESIGN: Cross-sectional study. SETTING: Nation-wide, population-based study. SUBJECTS: The Norwegian EPIC cohort is a subcohort of the Norwegian Women and Cancer study (NOWAC), and consist 37.226 women aged 41-56 y who answered a food frequency questionnaire (FFQ) in 1998. INTERVENTIONS: The associations among 50 food variables were first investigated by using principal component analysis. Five important factors were found. The five principal components were then used as input in the cluster analysis. Different socioeconomic and lifestyle variables were examined. RESULTS: Six clusters of dietary patterns were found, and were labelled accordingly: 'traditional fish eaters', 'healthy eaters', 'average, less fish, less healthy', 'Western', 'traditional bread eaters', and 'alcohol users'. The traditional fish eaters and the traditional bread eaters were both highly represented in the north and west of Norway and were more likely to be present among persons with lower income and lower education. The healthy and the alcohol drinkers were found mostly in the south and east and were more likely to have higher income. Persons in the alcohol group were more likely to be current smokers. The western group had the highest percentage of three or more persons in the household and the shortest time since last birth, indicating that families with children dominate this group. CONCLUSION: Our data indicate six different dietary patterns in Norway, each with different socio-demographic and lifestyle characteristics. SPONSORSHIP: The Norwegian Cancer Society (E 04038/006).

Adult↗

Investigation of trace element content of cheese.

Nine trace elements (Al, Cr, Mn, Fe, Ni, Cu, Zn, Cd, Pb) were determined in cheese by atomic absorption spectrophotometry with electrothermal atomization in a graphite tube, using the ashing procedure. Associations among mineral constituents were studied by means of principal component analysis, which allows determination of interdependences among trace elements in foods. A test for normality was used to investigate monovariate distributions, in order to estimate the symmetry of data vector. The correlation matrix was used as a starting matrix for principal component analysis; nine variables were reduced to four principal components. The clusters of elements appear to be determined by their origin.

Cheese↗

Odor-structure relationships in n-hexenols and n-hexenals.

The relationships between the chemical structures and the odor characteristics were examined on a series of highly purified n-hexenols and n-hexenals-(14 isomers). The C6-enals and the corresponding alcohols resembled in odor characteristics each other. However, the odor strength of the aldehydes was 100-1000 times higher than those of the alcohols. In the principal components analysis, the position of carbon-carbon double-bond in the C6-compounds was closely related to the scores of the first principal component, whereas the functional groups, hydroxy and formyl groups, were related to those of the second principal component except for (Z)-3-hexenol.

Alcohols↗

Metabolomic fingerprinting of plant extracts.

The standardization and quality control of plant extracts is an important topic, in particular, when such extracts are used for medicinal purposes. Consequently, the development of fast and effective analytical methods for metabolomic fingerprinting of plant extracts is of high interest. In this investigation, electrospray mass spectrometry (ESI-MS) and (1)H NMR techniques were employed with further statistical analyses of the acquired data. The results showed that negative ion mode ESI-MS is particularly effective for characterization of plant extracts. Different samples of the same species appear well-clustered and separated from the other species. To verify the effectiveness of the method, two other batches of extracts from a species, in which the principal components were already identified (Cynara scolymus), were analyzed, and the components that were verified by the principal component analysis (PCA) were found to be within the region identified as characteristic of Cynara Scolymus extracts. The data from extracts of the other species were well separated from those pertaining to the species previously characterized. Only the case of a species that was strictly correlated from a botanical point of view, with extracts that were previously analyzed, showed overlapping.

Achillea↗

Analysis of heavy metal distribution in superficial estuarine sediments (estuary of Bilbao, Basque Country) by open-focused microwave-assisted extraction and ICP-OES.

Open-focused microwave-assisted extraction and ICP-OES determination of As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn from surface sediments of the estuary of Bilbao (Basque Country, North of Spain) was carried out. All the samples were collected at three different tributaries of the estuary (Asua, Galindo and Nerbioi-Ibaizabal) every two months during 1999. The digestion procedure was proposed from the conclusions of a fractionated factorial design, and the precision and accuracy of the method was verified using a certified reference sediment (RTC008-050). The results of the analysis were statistically treated by means of principal component analysis and correlation analysis. The principal component analysis of sediment data (32 samples x 9 metals) indicated different patterns of contamination regarding the tributary and sampling station. The two main patterns observed were a steady increment of the metal concentration along all the campaigns in the samples collected in the Galindo River and a seasonal variation in the Nerbioi-Ibaizabal River, with higher metallic content during summertime and lower content during wintertime.

Ecosystem↗

Mobility and profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans in sediment of Ya-Er Lake, China.

The sediment of Ya-Er Lake had been heavily polluted by polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from the former chloralkali industry. The total amounts of PCDD/Fs and I-TEQ decreased along the water flow direction and also decreased from top to bottom layers of sediment cores. Sediment of Pond 1 was dominated by PCDF. especially TCDF. In contrast, in the other four ponds, PCDD dominated in all layers and octachlorinated dibenzo-p-dioxin (OCDD) predominated in all of the homologues. When homologue profiles from sediments and water samples were compared using principal component analysis (PCA), the first two principal components represented 95.2% of the variance in the data. The first component explained 75.9% of the variance and the second one 19.3%. Two clusters were most distinct, presenting a shift in PCDD/Fs composition from PCDF to heptachlorinated dibenzo-p-dioxin (HpCDD) and OCDD in sediments and water from Pond I to Ponds 2-5. The pattern variation between Pond I and Ponds 2-5 in Ya-Er Lake was most likely due to the change of process in the chemical plant after the dams between the ponds were built. The results of the present study also showed that log Koc of PCDD/Fs calculated from data of sediment and water in the field were comparable with theoretical log Koc. The results also implied that the concentrations of PCDD/Fs in water and sediments could be predicted from each other by log Koc.

Benzofurans↗

CoMFA-based prediction of agonist affinities at recombinant D1 vs D2 dopamine receptors.

We have previously shown that using agonist affinity at recombinant receptors selectively expressed in clonal cells as the dependent variable in three-dimensional quantitative structure-activity relationship studies (3D-QSAR) presents a unique opportunity for accuracy and precision in measurement. Thus, a comparison of affinity's structural determinants for a set of compounds at two different recombinant dopamine receptors represents an attainable goal for 3D-QSAR. A molecular database of bound conformations of 16 structurally diverse agonists was established by alignment with a high-affinity template compound for the D1 receptor, 3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4, 5-tetrahydro-1H-benzazepin. A second molecular database of the bound conformations of the same compounds was established against a second template for the D2 receptor, bromocriptine. These aligned structures suggested three-point pharmacophore maps (one cationic nitrogen and two electronegative centers) for the two dopamine receptors, which differed primarily in the height of the nitrogen above the plane of the catechol ring and in the nature of the hydrogen-bonding region. The ln(1/KL) values for the low-affinity agonist binding conformation at recombinant D1 and D2 dopamine receptors stably expressed in C6 glioma cells were used as the target property for the CoMFA (comparative molecular field analysis) of the 16 aligned structures. The resulting CoMFA models yielded cross-validated R2 (q2) values (standard error of prediction) of 0. 879 (1.471, with five principal components) and 0.834 (1.652, with five principal components) for D1 and D2 affinity, respectively. The simple R2 values (standard error of the estimate) were 0.994 (0.323) and 0.999 (0.116), respectively, for D1 and D2 receptor. F values were 341 and 2465 for D1 and D2 models, respectively, with 5 and 10 df. The predictive utility of the CoMFA model was evaluated at both receptors using the dopamine agonists, apomorphine and 7-OH-DPAT. Predictions of KL were accurate at both receptors. Flexible 3D searches of several chemical databases (NCI, MDDR, CMC, ACD, and Maybridge) were done using basic pharmacophore models at each receptor to determine the similarity of hit lists between the two models. The D1 and D2 models yielded different lists of lead compounds. Several of the lead compounds closely resembled high-affinity training set compounds. Finally, homology modeling of agonist binding to the D2 receptor revealed some consistencies and inconsistencies with the CoMFA-derived D2 model and provided a possible rationale for features of the D2 CoMFA contour map. Together these results suggest that CoMFA-homology based models may provide useful insights concerning differential agonist-receptor interactions at related receptors. The results also suggest that comparisons of CoMFA models for two structurally related receptors may be a fruitful approach for differential QSAR.

Animals↗

Arthropod faunal composition on Kentucky equine premises.

Thirty-nine arthropod species representing the families Muscidae, Chloropidae, Tabanidae, Simuliidae, Culicidae, and Ixodidae were collected from Kentucky equine premises using dry ice-baited canopy traps, light traps, water samples, tick drags, and animal inspections during late April to mid-October 1987 and 1988. Thirty-three species were collected from canopy traps, consisting of 74.3% muscid, 16.7% chloropid, 5.0% simuliid, 3.8% tabanid, and 0.2% culicid species. Light traps attracted eight culicid and water samples yielded three culicid species. One ixodid species was collected with drags, and animal inspections yielded two muscid and two ixodid species. Comparison of species assemblages among farms and across years using multivariate principal component analysis (PCA) yielded three distinct principal components, and PCA scores for each farm per year were correlated with biotic and abiotic environmental factors and management practices. The proximity to cattle herds was the best predictor of similarity in species assemblages among farms, reflecting the high percentage of muscid species collected. Poor management practices were partially responsible for proportionally larger populations of culicids, ixodids, and muscids on some farms.

Animal Husbandry↗

Ablation spectra of the human cornea.

Ablation of human corneal tissue with 193 nm excimer laser energy generates fluorescence in the near ultraviolet and visible regions of the spectrum. The fluorescence spectra from five human corneas were collected during ablation in vitro. We find that the fluorescence spectrum changes continuously as the cornea is ablated from the epithelial surface towards the endothelium. We reduced the dimensionality of the large data set resulting from each cornea by a principal components analysis. The three most significant principal component eigenvectors suffice to describe the observed spectral evolution, and independent analysis of each tissue sample produces a similar set of eigenvectors. The evolution of the calculated eigenvector weighting factors during ablation then corresponds to the observed spectral evolution. In fact, this evolution is qualitatively consistent between corneas. We suggest that this spectral evolution offers promise as a real-time surgical feedback tool.

Algorithms↗

Serum Proteomic Profiling Implicates a Dysregulated Neurohormonal-Inflammatory Axis in Post-Fontan Sinus Tachycardia.

BACKGROUND: Postoperative sinus tachycardia is a poorly understood complication following the Fontan procedure. The molecular signaling cascades triggering acute tachycardia remain uncharacterized, limiting therapeutic innovation. Here, we present a retrospective study leveraging serum proteomics and machine learning to identify the molecular drivers of postoperative Fontan sinus tachycardia. METHODS: We integrated a clinically relevant ovine Fontan model with continuous telemetric heart rate monitoring and human patient data. Serum proteomics coupled with least absolute shrinkage and selection operator and Boruta machine learning algorithms were used to identify protein panels predictive of postoperative sinus tachycardia. Cross-species validation was performed by comparing proteomic signatures from sheep and pediatric patients undergoing Glenn or Fontan surgery. RESULTS: Ovine Fontan animals demonstrated significant heart rate elevation beginning on postoperative day 1, peaking at postoperative day 3 (159.4&#xb1;11.7&#x2009;bpm versus preoperative, 105.3&#xb1;10.5&#x2009;bpm; P=0.0002), before trending toward baseline by postoperative day 10. This pattern was mirrored in human patients with a more modest magnitude. Surgical controls did not exhibit tachycardia. The principal component most correlated with heart rate (principal component 1: r=0.78, P=2.2&#xd7;10-4) was enriched for inflammatory and neural pathways. The Boruta algorithm identified an 11-protein panel with strong predictive power (area under the receiver operating characteristic curve, 0.963). Cross-species comparison demonstrated that angiotensinogen, angiotensin-converting enzyme, and pentraxin 3 were similarly dysregulated in both species postoperatively. CONCLUSIONS: This study provides molecular evidence implicating a dysregulated neurohormonal-inflammatory axis in acute postoperative Fontan sinus tachycardia and establishes a foundation for developing targeted diagnostics and therapeutics for this complication.

Animals↗

Responses to the postural change and orthostatic dysregulation symptoms: a population study on Japanese junior and senior high school students.

Unselected 580 male and 779 female junior and senior high school students were subjected to the tilting test and informations on 11 autonomic dysregulation symptoms and complaints were taken by interviews. Results of the analyses of the data are summarized as follows: 1) Number of symptoms and complaints possessed by each individual distributes continuously but nonrandomly among testees; that is, individuals having no symptom and those having 5 or more symptoms are significantly more numerous than those expected from random distribution, indicating accumulation of the symptoms into some individuals. 2) Some specific symptoms tend to coincide with each other. 3) Principal component analyses disclosed that the first principal component can explain only 16-20% of the observed variation in the presence or absence of symptoms and complaints, suggesting that numerous factors are responsible for the occurrence of the symptoms. 4) Measurements of the blood pressures and the pulse rate, and their responses to the postural change show continuous, normal distributions, and significantly correlate to each other. 5) The responses to the tilting test are increased with the increase of number of symptoms and complaints possessed by the testees.

Adolescent↗

Genome-Wide SNP Characterisation of Three Kazakh Sheep Breeds: Kazakh Fat-Tailed Coarse-Wool, Degeres, and Etti Merino.

Kazakhstan's sheep portfolio underpins much of the country's mutton and wool production, yet several of its principal breeds remain genomically uncharacterised. The aim of this study was to characterise the genomic diversity, population structure, and global phylogenetic placement of three economically important Kazakh breeds and to determine whether they constitute separate gene pools requiring independent management. We present the first genome-wide SNP characterisation to include the Degeres (DE), the Etti Merino (EM), and the Kazakh fat-tailed coarse-wool (KKG) breeds simultaneously. A total of 1497 animals (DE = 354, EM = 642, KKG = 501) sampled across seven production households were genotyped and, after quality control, analysed at 42,279 SNPs, of which 22,766 LD-pruned markers were used for principal component analysis and AMOVA. We applied principal component analysis (PCA), pairwise FST, analysis of molecular variance (AMOVA), neighbour-joining phylogenetics, model-based ancestry estimation (ADMIXTURE), and Hill-number diversity profiling, and projected the breeds against the global Ovine SNP50 HapMap panel (74 reference breeds, 2819 animals; 37,685 shared SNPs). All three breeds retained uniformly high within-breed diversity (expected heterozygosity 0.413-0.417) with fixation indices at or near zero. AMOVA partitioned 94.03% of variance within breeds (&#x3a6;ST = 0.060, p < 0.001). PCA, phylogeny, and ADMIXTURE concordantly resolved three breed-specific clusters at K = 3, with a maximum interbreed FST of 0.038 within the study dataset. Against the global panel, EM was genetically closest to Merino and Merino-derived reference breeds (pooled FST = 0.017) and substantially more distant from Southwest Asian sheep (FST = 0.045), whereas DE and KKG showed the reciprocal pattern (FST = 0.027 and 0.020 to Southwest Asia, 0.052 to the Merino group). DE additionally displayed the heterozygote excess and partial admixture expected of an incompletely consolidated composite. These results delineate three distinct gene pools and carry direct implications for breed management and the conservation of genomic diversity in Kazakhstani sheep.

ADMIXTURE↗