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Ordinal regression model and the linear regression model were superior to the logistic regression models.

OBJECTIVE: Ordinal scales often generate scores with skewed data distributions. The optimal method of analyzing such data is not entirely clear. The objective was to compare four statistical multivariable strategies for analyzing skewed health-related quality of life (HRQOL) outcome data. HRQOL data were collected at 1 year following catheterization using the Seattle Angina Questionnaire (SAQ), a disease-specific quality of life and symptom rating scale. STUDY DESIGN AND SETTING: In this methodological study, four regression models were constructed. The first model used linear regression. The second and third models used logistic regression with two different cutpoints and the fourth model used ordinal regression. To compare the results of these four models, odds ratios, 95% confidence intervals, and 95% confidence interval widths (i.e., ratios of upper to lower confidence interval endpoints) were assessed. RESULTS: Relative to the two logistic regression analysis, the linear regression model and the ordinal regression model produced more stable parameter estimates with smaller confidence interval widths. CONCLUSION: A combination of analysis results from both of these models (adjusted SAQ scores and odds ratios) provides the most comprehensive interpretation of the data.

Adolescent↗

Evaluation of Rhubarb using antioxidative activity as an index of pharmacological usefulness.

We attempted to estimate the pharmacological activity by measuring the concentrations of a composition ingredient using a multivariate statistical analysis method. Medicinal herb of Rhubarb has been many largely unrecognized biochemical and pharmacological effect components. Therefore, we attempted to estimate the antioxidative activity of Rhubarb on low-density lipoprotein (LDL) of its components. Thirty specimens of Rhubarb from various origins were used, chose nine components of anthraquinones, two components of anthrones, two components of flavan-3-ols, one component of procyanidin, one component of naphthalene, two components of phenylbutanones and one component of stilbene. Quantitative analysis of 18 components was performed with high-performance liquid chromatography (HPLC) and antioxidative activities were measured with plasma taken from spontaneous familial hypercholesterolemia model rabbits. There was considerable variation among the specimens in the concentration of components and antioxidative activities on LDL. As a result of multiple regression analysis, significant multiple correlation coefficient for antioxidative activities on LDL (R=0.914, P<0.01) was found in relation to the concentrations of five components: aloe-emodin, chrysophanol, emodin 1-O-beta-D-glucoside, lindleyin and 6-hydroxymusizin 8-O-beta-D-glucoside. Three of the five components were not active in promoting antioxidative activity and there was no significant correlation between the concentrations of the most active component and the activity. We consider this a useful method for selecting of Rhubarb and propose a new scientific approach for the selection of natural medicines.

Animals↗

Antimalarial remedies in French Guiana: a knowledge attitudes and practices study.

A "knowledge attitudes and practices" study about malaria treatments was undertaken in French Guiana, along with an ethnopharmacological study. One hundred and seventeen people from five different groups and nationalities (Creole, Palikur, Galibi, Brazilian, and European) answered the questionnaire. The results were analysed using univariate and multivariate statistical analysis. First, we evaluated the overall knowledge about malaria from the interviewed people. According to bio-medical concepts, we noticed that they have a good knowledge of this illness. Secondly, we studied the treatment used by sick people during their last malaria attack. We demonstrated that, although bio-medical treatment is available in this area, people use both modern drugs and traditional remedies. Finally, preventive attitudes have been examined. One-third of the interviewed people drink regularly some herbal remedy to prevent febrile illnesses and malaria, thus displaying a strong concern about this disease. The ethnopharmacological study highlighted the frequent use of traditional remedies, along with their mode of preparation and administration. A total of 34 different species (both from flora and fauna) have been registered as antimalarial. Twenty-seven are used for curative purposes, 20 as preventive and 13 of them are used for both purposes. Quassia amara (Simaroubaceae) whose antimalarial activity has already been demonstrated was the species most frequently used as antimalarial for curative and preventive purposes.

Adult↗

Does space in the jaw influence the timing of molar crown initiation? A model using baboons (Papio anubis) and great apes (Pan troglodytes, Pan paniscus).

Radiographic and histological studies of baboon (Papio hamadryas, P. anubis) and chimpanzee (Pan troglodytes) permanent tooth development have found that periods of molar crown mineralization overlap markedly in chimpanzees but are staggered in baboons. Here we test the hypothesis that these intertaxon differences in molar initiation are primarily due to the space available in the mandibles of each species for these teeth. This study includes radiographic, linear measurement, and three-dimensional (3D) coordinate landmark data taken from baboon (Papio anubis n=51) and great ape (Pan paniscus n=43, P. troglodytes n=60) mandibles and permanent molars across a broad developmental range for each taxon. Unexpectedly, 3D multivariate statistical shape analysis of the molar crypt, crown, and root data shows that all three species trajectories of molar row shape change are indistinguishable from each other. Qualitative analysis of these 3D data reveals subtle and inconclusive intergeneric differences in the space maintained between adjacent molars during growth. The space distal to each newly initiated molar is slightly greater in the baboon. Bivariate analyses comparing molar row and mandibular corpus proportions in Papio and Pan fail to show clear or consistent taxonomic differences in the ratio of space afforded developing molars in the alveolar bone. Thus, there is a poor correlation between mandibular proportion and both intermolar spacing and 3D molar development pattern. Contrary to earlier studies, these results suggest that pattern of molar crown initiation and temporal overlap of adjacent mineralizing crowns is not significantly different between Papio and Pan. This may be due in part to the inclusion here of not only 3D molar crown data but also 3D molar crypt data. This study strongly refutes the hypothesis that space available in the mandible directly underlies different times of permanent molar crown initiation between Papio and Pan.

Animals↗

Early Holocene human skeletal remains from Sumidouro Cave, Lagoa Santa, Brazil: history of discoveries, geological and chronological context, and comparative cranial morphology.

In this work, we present new evidence supporting the idea that the first Americans were very distinct from late and recent Native Americans and Asians in terms of cranial morphology. The study is based on 30 early Holocene specimens recovered from Sumidouro Cave (Lagoa Santa region, central Brazil) by Peter Lund in 1843. Sumidouro is the largest known collection of Paleoindian skulls deriving from a single site. Six different multivariate statistical methods were applied to assess the morphological affinities of the Sumidouro skulls in comparison to Howells' worldwide extant series and late archaic Brazilian series (Base Aérea and Tapera). The results show a clear association between Sumidouro and Australo-Melanesians and none with late Asian and Amerindian series. These results are in accordance with those of previous studies of final Pleistocene/early Holocene human skulls from South, Central, and North America, attesting to a colonization of the New World by at least two different, succeeding biological populations: an early one with a cranial morphology similar to that found today in the African and Australian continents, and a later one with a morphology similar to that found today among northeastern Asians.

Anthropology, Physical↗

Improved survival for sarcomas of the wrist and hand.

PURPOSE: To evaluate survival characteristics of malignant hand tumors compared with those occurring in other musculoskeletal locations over a 30-year period. METHODS: Patients were identified through a computerized database maintained at the authors' institution over the past 30 years. Each patient's records were reviewed retrospectively. Diagnoses were categorized and survival data for patients with hand malignancies were compared with those of patients having similar tumors in other musculoskeletal sites by using multivariate statistical analysis. RESULTS: The most common malignancies were epitheloid sarcoma, synovial sarcoma, and malignant fibrous histiocytoma. Improved survival during the follow-up period was found for hand malignancies versus those occurring in other musculoskeletal sites as a whole, and this difference was statistically significant. No significant survival benefit was identified for individual tumors. CONCLUSIONS: Patients presenting with primary malignancies of the hand may survive longer than those with similar tumors in other musculoskeletal locations TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic, Level II.

Adolescent↗

Combining principal component and spectral analyses with the method of moments in studies of quantal transmission.

This chapter considers methods for measurements of postsynaptic responses and simple approaches to the estimation of parameters of quantal release in synapses of the central nervous system of vertebrates. The use of these methods is illustrated by the analysis of single-fibre and "minimal" monosynaptic postsynaptic potentials (PSPs) or currents (PSCs) recorded from neurons of the frog spinal cord and rat hippocampus. First, we briefly discuss traditional methods of the response measurements using peak amplitudes or areas, further focusing on a novel method based on multivariate statistical techniques of the principal component analysis (PCA). This approach provides typically better signal-to-noise ratios and is able to separate two or more response components, which can arise due to activation of more than one presynaptic fibre, axon collaterals, receptor subtypes or spatially separated transmission sites. Second, spectral analysis is introduced as the method of choice to verify whether the amplitude fluctuations of the postsynaptic responses have a quantal nature and to obtain estimations of the "basic" quantal parameters, i.e. the quantal size (Q) and mean quantal content (m), without introducing assumptions on release statistics. Third, we show how the method of moments could be applied in the framework of the Poisson and binomial models to estimate the basic quantal parameters and parameters p and n, which reflect the release probability and maximum number of quanta released (or the number of effective release sites), respectively. Fourth, we show that the analysis of the moments can also be instrumental to reveal non-uniformity of release probabilities and compare how several competing models of neurotransmitter release fit to multiple experimental data sets.

Animals↗

Conditioned spikes: a simple and fast method to represent rates and temporal patterns in multielectrode recordings.

Increasing evidence suggests that the brain utilizes distributed codes that can only be analyzed by simultaneously recording the activity of multiple neurons. This paper introduces a new methodology for studying neural ensemble recordings. The method uses a novel representation to provide complementary information about the stimuli which are contained in the temporal pattern of the spike sequence. By using this procedure, a high correlation of synchronized events with stimuli times is apparent. To quantify the results and to compare the performance of this method against the most traditional raster plot, we have used Fano factor and cross-correlation analysis. Our results suggest that several consecutive spikes from different neurons within an extended time window may encode behaviorally relevant information. We propose that this new representation, in addition to the other approaches currently used (standard raster plots, multivariate statistical methods, neuronal networks, information theory, etc.), can be a useful procedure to describe population spike dynamics.

Action Potentials↗

PSTH-based classification of sensory stimuli using ensembles of single neurons.

The problem of understanding how ensembles of neurons code for somatosensory information has been defined as a classification problem: given the response of a population of neurons to a set of stimuli, which stimulus generated the response on a single-trial basis? Multivariate statistical techniques such as linear discriminant analysis (LDA) and artificial neural networks (ANNs), and different types of preprocessing stages, such as principal and independent component analysis, have been used to solve this classification problem, with surprisingly small performance differences. Therefore, the goal of this project was to design a new method to maximize computational efficiency rather than classification performance. We developed a peri-stimulus time histogram (PSTH)-based method, which consists of creating a set of templates based on the average neural responses to stimuli and classifying each single trial by assigning it to the stimulus with the 'closest' template in the Euclidean distance sense. The PSTH-based method is computationally more efficient than methods as simple as linear discriminant analysis, performs significantly better than discriminant analyses (linear, quadratic or Mahalanobis) when small binsizes are used (1 ms) and as well as LDA with any other binsize, is optimal among other minimum-distance classifiers and can be optimally applied on raw neural data without a previous stage of dimension reduction. We conclude that the PSTH-based method is an efficient alternative to more sophisticated methods such as LDA and ANNs to study how ensemble of neurons code for discrete sensory stimuli, especially when datasets with many variables are used and when the time resolution of the neural code is one of the factors of interest.

Action Potentials↗

The effect of admission physiological variables on 30 day outcome after stroke.

INTRODUCTION: Potentially modifiable physiological variables may influence stroke prognosis but their independence from modifiable factors remains unclear. METHODS: Admission physiological measures (blood pressure, heart rate, temperature and blood glucose) and other unmodifiable factors were recorded from patients presenting within 48 hours of stroke. These variables were compared with the outcomes of death and death or dependency at 30 days in multivariate statistical models. RESULTS: In the 186 patients included in the study, age, atrial fibrillation and the National Institutes of Health Stroke Score were identified as unmodifiable factors independently associated with death and death or dependency. After adjusting for these factors, none of the physiological variables were independently associated with death, while only diastolic blood pressure (DBP) > or = 90 mmHg was associated with death or dependency at 30 days (p = 0.02). CONCLUSIONS: Except for elevated DBP, we found no independent associations between admission physiology and outcome at 30 days in an unselected stroke cohort. Future studies should look for associations in subgroups, or by analysing serial changes in physiology during the early post-stroke period.

Adolescent↗

Management of mandibular third molar extraction sites to prevent periodontal defects.

PURPOSE: Persistent periodontal defects on the distal aspect of the mandibular second molar (M2) is a reported complication of mandibular third molar (M3) extraction. The purpose of this study was to measure the efficacy of demineralized bone powder (DBP) or guided-tissue regeneration therapy (GTR therapy) in preventing periodontal defects on the distal aspect of the M2 following M3 extraction. MATERIALS AND METHODS: We implemented a single-blind, randomized, controlled clinical trial composed of a sample of subjects > or = 26 years of age who required extraction of bilateral M3s. The primary predictor variable was treatment group. Each subject was randomly assigned to receive either DBP or GTR therapy. Within subjects, 1 M3 site was randomly selected to be the experimental site and the opposite M3 served as a control and was permitted to heal without intervention. The primary outcome variable was the change in attachment levels (AL) and probing depths (PD) on the disto-buccal aspect of M2 between T 0 (immediate preoperatively) and T 4 (26 weeks postoperatively). Appropriate sample size estimates, descriptive, bivariate, and multivariate statistics were computed. RESULTS: Twelve subjects in the DBP group and 12 subjects in the GTR-therapy group completed the study. For both treatment and control sites, between T 0 and T 4, there were statistically significant improvements in AL (> or = 2.2 mm; P <.001) and PD (> or = 2.6 mm; P <.001). Within-subjects comparisons showed no significant differences in AL or PD between treatment and control M3 sites ( P > or =.3) at T 0 or T 4. CONCLUSION: The results of this study suggest that attachment levels and probing depths improve after M3 removal. In this sample, DBP or GTR therapy did not offer predictable benefit over no treatment.

Absorbable Implants↗

Structural studies of the archaeal MCM complex in different functional states.

The primary candidate for the eukaryotic replicative helicase is the MCM2-7 complex, a hetero-oligomer formed by six AAA+ paralogous polypeptides. A simplified model for structure-function studies is the homo-oligomeric orthologue from the archaeon Methanothermobacter thermoautotrophicus. The crystal structure of the DNA-interacting N-terminal domain of this homo-oligomer revealed a double hexamer in a head-to-head configuration; single-particle electron microscopy studies have shown that the full-length protein complex can form both single and double rings, in which each ring can consist of a cyclical arrangement of six or seven subunits. Using single-particle techniques and especially multivariate statistical symmetry analysis, we have assessed the changes in stoichiometry that the complex undergoes when treated with various nucleotide analogues or when binding a double-stranded DNA fragment. We found that the binding of nucleotides or of double-stranded DNA leads to the preferred formation of double-ring structures. Specifically, the protein complex is present as a double heptamer when treated with a nucleotide analogue, but it is rather found as a double hexamer when complexed with double-stranded DNA. The possible physiological role of the various stoichiometries of the complex is discussed in the light of the proposed mechanisms of helicase activity.

Adenosine Diphosphate↗

Integrating contaminant responses in indicator saltmarsh species.

A challenge in environmental management is to provide both methodology and a framework for assessing effects of pollutants in resident species and then applying the findings to management. The Pacific Estuarine Ecosystem Indicator Research (PEEIR) consortium advocates the development of an integrated portfolio of techniques using indicator species selected for various habitat types. We developed such a portfolio for California salt marsh ecosystems and evaluated the feasibility of our approach in management applications. PEEIR is employing a suite of biomarker responses in two indigenous species, the lined shore crab (Pachygrapsus crassipes) and the longjaw mudsucker (Gillichthys mirabilis). Detrimental effects such as apoptosis, endocrine disruption, and ovarian tumors have been observed in G. mirabilis at a site where toxicity test responses were relatively low. With P. crassipes, developmental abnormalities and several markers of decreased reproductive performance were quantified at the same site. Multivariate statistical techniques are used to examine the relationships between the responses and multiple contaminant and natural stressors. For the fish, findings are related to population-level parameters using dynamic energy budget (DEB) models.

Animals↗

Albuminuria and hypertension are independently associated with circulating antipericyte autoantibodies in type 2 diabetic patients.

AIMS: To determine whether albuminuria, hypertension, or HbA 1c are independently associated with antipericyte autoantibodies (APAAs) in type 2 diabetes mellitus. METHODS: Two hundred ninety-nine subjects with different degrees of retinopathy according to the Early Treatment Diabetic Retinopathy Study Scale participated in this study. Albuminuria was defined as an albumin/creatinine ratio above the normal cutoff limit, that is, 2.0 g/mol for men and 2.8 g/mol for women. Hypertension was defined as a diastolic blood pressure more than 90 mm Hg, a systolic blood pressure more than 140 mm Hg, or pharmacological antihypertensive treatment. Serum APAAs were detected by immunofluorescence on tissue-cultured bovine retinal pericytes. Association analysis was performed using univariate and multivariate statistical tools. RESULTS: In type 2 diabetes, APAAs were independently associated with albuminuria (OR = 0.56; P < .04), hypertension (OR = 2.21; P < .01), as well as with proliferative retinopathy (OR = 0.39; P < .01). CONCLUSIONS: The increased prevalence of APAA in patients with hypertension may suggest that these antibodies are related to tissue damage and repair and that the decline in frequency with albuminuria may serve as a marker for more advanced angiopathy. Future longitudinal studies are needed to determine whether the frequency of APAA is associated with the progression of angiopathy, and to determine the biological activity and antigens recognized by the antibody.

Aged↗

Analysis of factors shaping codon usage in the mitochondrion genome of Oryza sativa.

In this paper, the main factors shaping codon usage in the mitochondrion genome of rice were reported. Correspondence analysis, a commonly used multivariate statistical approach, was carried out to analyze synonymous codon usage bias. The results showed that the main trend was strongly correlated with the gene expression level assessed by the 'Codon Adaptation Index' value, a result that was confirmed by the distribution of genes along the first axis. From the results that there were two significant correlations between axis 1 coordinates and the GC, GC3s content at silent sites of each sequence, and clearly significant correlations between the 'Effective Number of Codons' values and GC, GC3s content, we inferred that codon usage bias was affected by gene nucleotide composition also. In addition, the hydrophobicity of each protein also played some roles in shaping codon usage in this organelle, which could be confirmed by the significant correlation between the positions of genes placed on the first axis and the hydrophobicity value of each protein. In summary, natural selection played a crucial role, nucleotide mutational bias and amino acid composition only in a minor way, in shaping codon usage in the mitochondrion genome of rice. Notably, 21 codons defined firstly as 'optimal codons' might provide some more useful information for gene engineering and/or evolution studying.

Journal Article↗

Subdivisions of human parietal area 5 revealed by quantitative receptor autoradiography: a parietal region between motor, somatosensory, and cingulate cortical areas.

Brodmann's area (BA) 5 of the human superior parietal cortex occupies a central anatomical position between the primary motor (BA 4), somatosensory (area 3b and BA 2), cingulate (area 23c), and superior parietal association cortex (BA 7). We studied the regional and laminar distributions of the binding sites of 12 different neurotransmitter receptors (glutamatergic: AMPA, kainate, NMDA; GABAergic: GABAA, GABAB; cholinergic: muscarinic M2, nicotinic; adrenergic: alpha1, alpha2; serotoninergic: 5-HT1A, 5-HT2; dopaminergic: D1) in human postmortem brains by means of quantitative receptor autoradiography, since the structural and functional aspects of human BA 5 are widely unknown, and previous observations have demonstrated characteristic differences in receptor distribution between motor and somatosensory areas. Binding site densities were measured in the cytoarchitectonically defined BA 5 and surrounding regions. Similarities and differences of receptor distribution between cortical areas were studied by cluster analysis of mean binding site densities averaged over all cortical layers, univariate and multivariate statistics, and by density profiles representing laminar receptor distribution patterns. Based on regional heterogeneities of binding site densities and of the cytoarchitecture within BA 5, we suggest a subdivision into three subareas: medial area 5M, lateral area 5L, and area 5Ci in the region around the cingulate sulcus. BA 5 is therefore a heterogeneous cortical region, comprising three subareas showing receptor expression patterns similar to the adjoining higher order somatosensory, multimodal parietal, or cingulate regions. These findings suggest that human BA 5 constitutes a higher order cortical area, clearly distinct from the primary somatosensory and motor cortex.

Aged↗

Transmitter receptors reveal segregation of cortical areas in the human superior parietal cortex: relations to visual and somatosensory regions.

Regional distributions of ligand binding sites of 12 different neurotransmitter receptors (glutamatergic: AMPA, kainate, NMDA; GABAergic: GABA(A), GABA(B); cholinergic: muscarinic M2, nicotinic; adrenergic: alpha1, alpha2; serotonergic: 5-HT1A, 5-HT2; dopaminergic: D1) were studied in human postmortem brains by means of quantitative receptor autoradiography. Binding site densities were measured in the superior parietal lobule (SPL) (areas 5L, 5M, 5Ci, and different locations within Brodmann's area (BA) 7), somatosensory (BA 2), and visual cortical areas (BA 17, and different locations within BAs 18 and 19). Similarities of receptor distribution between cortical areas were analyzed by cluster analysis, uni- and multivariate statistics of mean receptor densities (averaged over all cortical layers), and profiles representing the laminar distribution patterns of receptors. A considerable heterogeneity of regional receptor densities and laminar patterns between the sites was found in the SPL and the visual cortex. The most prominent regional differences were found for M2 receptors. In the SPL, rostrocaudally oriented changes of receptor densities were more pronounced than those in mediolateral direction. The receptor distribution in the rostral SPL was more similar to that of the somatosensory cortex, whereas caudal SPL resembled the receptor patterns of the dorsolateral extrastriate visual areas. These results suggest a segregation of the different SPL areas based on receptor distribution features typical for somatosensory or visual areas, which fits to the dual functional role of this cortical region, i.e., the involvement of the human SPL in visuomotor and somatosensory motor transformations.

Aged↗

The human inferior parietal cortex: cytoarchitectonic parcellation and interindividual variability.

The inferior parietal cortex (IPC) integrates information from different sensory modalities and plays an important role in a variety of higher cognitive functions. Brodmann (Brodmann, K., 1909. Vergleichende Lokalisationslehre der Grosshirnrinde. Barth, Leipzig) proposed a cytoarchitectonic subdivision of the IPC into only two cortical areas, a rostral (BA 40) and a caudal (BA 39) area. Although his scheme was repeatedly challenged by other observers, it is still used for the anatomical localization of functional imaging data. The apparent differences between all these cyto- and myeloarchitectonic maps may be caused partly by the observer-dependent procedure of defining cytoarchitectonic borders by pure visual inspection of histological sections and partly by the interindividual variability of cytoarchitecture. The present observations and the resulting cortical map of the IPC are based on quantitative, observer-independent definitions of cytoarchitectonic borders and take into account each area's topographical variability across brains. Ten human postmortem brains were scanned using an MRI 3-D FLASH sequence prior to histological processing. After embedding in paraffin, serial sections through whole brains were prepared, and the sections were stained for cell bodies. Following high-resolution digitization of sections containing the IPC, we defined the cytoarchitecture and borders of each cortical area of this brain region using a multivariate statistical analysis of laminar cell density profiles. In contrast to previous observations, we found seven cytoarchitectonic areas in the IPC: five in the rostral (covering the region of BA 40) and two in the caudal part (covering the region of BA 39). We observed considerable interindividual variability in the topography of each area. A consistent correspondence between macroanatomical landmarks and cytoarchitectonic borders was not found. This new cytoarchitectonic map of the human IPC demonstrates regional differences in the cortical microstructure that is suggestive of functional differentiation. Furthermore, the map is registered in three dimensions and thereby provides a robust anatomical base for interpreting functional imaging studies.

Adult↗