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PubMed2005

Correlation of protein and gene expression profiles of inflammatory proteins after endotoxin challenge in human subjects.

Administration of endotoxin (LPS) in humans results in profound physiological responses, including activation of peripheral blood mononuclear cells and the release of inflammatory factors. The time course of the response of selected inflammatory proteins was examined in healthy subjects (n = 6) administered a single intravenous dose of the purified derivative of endotoxin (3.0 ng/kg). Microarray analysis demonstrated changes in the expression of a number of genes, which were confirmed in separate in vitro endotoxin stimulation experiments. Subsequent TaqMan analysis of genes of interest indicated time-dependent changes in the expression of many of these genes. This included pre-B cell enhancing factor, which was identified on microarray analysis as being markedly upregulated following endotoxin stimulation. Protein expression of the genes examined by TaqMan analysis was measured and demonstrated the appearance of tumor necrosis factor (TNF)-alpha and sTNF-R proteins in the plasma beginning within 1 h after dosing, followed by other cytokines/ inflammatory markers (e.g., IL-1ra, G-CSF, IL-6, IL-8, and IL-10) and suppressors of cytokine signaling (SOCS-1 and SOCS-3). In general, cytokine protein expression correlated well with gene expression; however, the temporal profile of expression of some genes did not correlate well with the protein data. For many of these proteins, the lack of correlation was attributable to alternate tissue sources, which were demonstrated on TaqMan analysis. Principal component analysis indicated that cytokines could be grouped according to their temporal pattern of response, with most transcript levels returning to baseline 24 h following endotoxin administration. The combination of cDNA microarray and TaqMan analysis to identify and quantify changes in gene expression, along with the analysis of protein expression, can be useful in investigating inflammatory and other diseases.

Adolescent↗

PubMed1999

Cultural diversity, stress, and depression: working women in the Americas.

Social support lengthens life, and stressors induce morbidity early in life and death later. Social supports and stressors, however, particularly those embedded in daily social interactions, exhibit important forms of cultural variation not yet incorporated into stress measurements. This article reports a clinically useful measure of stress applicable to culturally diverse populations. Ninety working women with a wide range of ages, educational attainments, class backgrounds, and historical origins (Africa, northwest Europe, Hispanic, and Native Americans) provided cultural data on the meaning of stress. Consensus analysis, principal components analysis and Cronbach's alpha, and logistic regression document content validity of the stress scale items and the reliability and construct validity of the stress scale. The meaning of social supports (words or acts that imply respect, equality, or help or otherwise lead one to feel special and important) and stressors (words or acts that demean, imply inferiority, impede achievement, or otherwise lead one to feel bad about oneself) experienced in the course of daily social interaction cuts across cultural differences in other realms of life. Informants with a recent history of stress experienced a risk of depressive symptoms 85 times higher than informants without such a history. Standardized cultural research methods yield an instrument based on potential cultural universals that can facilitate clinical assessment and management of stress and health outcomes, such as depression, in culturally diverse populations.

Achievement↗

PubMed1999

A kinetic study on benzoic acid pungency and sensory attributes of benzoic acid.

Aqueous solutions of benzoic acid (BA) were evaluated by two methods: (i) sensory profile: a descriptive test of sensory attributes combined with semiquantitative analysis; and (ii) pungency intensity measures as a function of time: a computerized recording using specific software. Kinetic parameters evaluated were maximal intensity (I(MAX)), total time of pungency (Ttot), rates of increase (V1) and decrease (V2), half-life (T1/2), area under curve (AUC) and time to maximal intensity (T(IMAX)). Results were analyzed by ANOVA, LSD test, iterative calculations and adjustment to equations according to mathematical models, regression analysis, principal component analysis (PCA) and clusters analysis. Pungency was the main sensory attribute of BA (3-36 mM) in the tongue and epiglottis. The seven kinetic parameters showed concentration-dependency (P < 0.001) and were described by different functions: (i) lineal: I(MAX) = 2.24 +/- 0.14C - 3.06 +/- 2.58, R2 = 0.98; T(IMAX) = 0.19 +/- 0.02C + 6.87 +/- 0.47, R2 = 0.92; V1 = 0.68 +/- 0.03C + 0.10 +/- 0.69, R2 = 0.99; AUC = 49.10 +/- 3.17C - 230.78 +/- 59.66, R2 = 0.98; (ii) potency: T1/2 = 6.62 +/- 0.61C(0.39+/-0.03), R2 = 0.97; V2 = 1.07 +/- 0.11C(0.53+/-0.04), R2 = 0.98; Ttot = 8.08 +/- 1.01C(0.43+/-0.04), R2 = 0.96. PCA revealed high correlation between (i) T(IMAX) and Ttot; (ii) T1/2 and V2; and (iii) I(MAX) and V1. Stimuli grouped across three main clusters: (i) 3 and 6 mM; (ii) 9, 12 and 18 mM; and (iii) 24 and 36 mM. Maximal pungency intensity best correlated with both concentration and persistence among kinetic parameters. Prototypical prickling of BA was observed at 12 and 18 mM.

Adult↗

PubMed2003

Quality of psychiatric care: validation of an instrument for measuring inpatient opinion.

OBJECTIVES: To validate a brief self-completed questionnaire for routinely assessing patients' opinions on the quality of care in inpatient psychiatric wards (Rome Opinion Questionnaire for Psychiatric Wards). DESIGN: A preliminary version was assessed for face and content validity by eight psychiatrists and two patient focus groups. The final version was evaluated for acceptability, factor structure, internal consistency, and test-retest reliability. SETTING: An inpatient psychiatric ward in a general hospital in Rome. STUDY PARTICIPANTS: The questionnaire was administered to all consecutive inpatients admitted over a 6-month period (n = 169). Test-retest reliability was evaluated by administering the questionnaire for a second time to 27 inpatients. MAIN OUTCOME MEASURES: Face and content validity: psychiatrists and focus groups' opinions on relevance, importance, and clarity, acceptability: inpatients' opinions on user-friendliness; factor analysis: principal component analysis; internal consistency: Cronbach's alpha; test-retest reliability: Cohen's weighted kappa coefficient, intraclass correlation coefficient RESULTS: After evaluating face and content validity, the questionnaire was reduced to 10 items. Inpatients found the questionnaire to be acceptable. Factor analysis revealed that three factors-professional qualities of staff, information received, and physical environment-explained 67.2% of total variance. Cronbach's alpha was 0.82 for the questionnaire and 0.61, 0.71, and 0.35 for the three factors, respectively. Test-retest reliability was good; weighted kappa higher than 0.9 for three items and 0.6-0.9 for seven items. The intraclass correlation coefficient was 0.80. CONCLUSIONS: The questionnaire seems to be adequate for evaluating patients' opinions on care in inpatient psychiatric wards. Because of its user-friendliness, it may be particularly suitable for routine use.

Adult↗

PubMed2004

Refinement and validation of a French in-patient experience questionnaire.

The objective of this study was to check psychometric properties of a French-language in-patient experience questionnaire in a test sample different from the development sample. The questionnaire was sent out to 5,736 in-patients, within two to four weeks of discharge from a teaching hospital of 2,200 beds. Overall 4,095 questionnaires (71.4 per cent) were returned. Of these, 3,879 questionnaires were analyzed. In principal component analysis, seven principal components accounted for 62.4 per cent of the total variance. Cronbach's alpha coefficient ranged from 0.62 to 0.90, with the exception of the seventh scale (convenience scale, two items, Cronbach = 0.39). The overall patient experience score increased with increasing patient age (except for patients older than 65), male sex, low education level, use of a single room, and prior stay in the department. It also differed with respect to patients' behavioral intentions, answers to an overall satisfaction item, and open-ended comments.

Adult↗

PubMed1996

The factor structure of the Maslach Burnout Inventory in two Swedish human service organizations.

The Maslach Burnout Inventory, MBI, is a well established measure of burnout. Its validity outside the USA is, however, uncertain. The aim of the present study was therefore to apply the MBI on personnel in two Swedish human service organizations, comparing factor solutions and scoring norms to the original results. The population consisted of 5730 employees in the Social Insurance Organization (SIO) and the Individual and Family Care section (IFC) of the social welfare agencies. Principal components analysis, principal axes and alpha factor analyses were performed, all with varimax rotation. The suggested three factor solution showed to be remarkably stable irrespective of type of analysis. Score levels were somewhat lower on two subscales in the Swedish population. The conclusion is that the psychometric properties of the MBI seem to be very satisfactory and stable, at least in comparison between Sweden and USA. It is suggested that the dimensionality of MBI is rather invariant, but that the score levels covary with national, cultural, or professional contexts within the human services.

Adult↗

PubMed1984

Biochemical heterozygosity as a predictor of developmental homeostasis in man.

The relationships between the variability of 48 morphological traits and the heterozygosity of four blood group loci were studied in 200 Israeli Jewish males of Eastern European origin aged 18-22 years. A definite correlation was observed between the level of heterozygosity and the variability of 17 traits and two indices. Of the latter traits only 10 were chosen for further analysis. Principal component analysis showed that seven of these traits were independent. For six of them, the frequency of modal individuals (average +/- 0.67 S.D.) in the tetraheterozygous group was the highest, diminishing proportionally with decreasing heterozygosity levels. The degree of heterozygosity also had a significant negative correlation with the coefficient of variation of the morphological characters and was positively associated with the kurtosis values. Only the variability of one of 10 traits showed an opposite trend and a correlation with biochemical homozygosity. The results are discussed in terms of developmental homeostasis.

Adolescent↗

PubMed2004

Development and psychometric evaluation of the Professional Practice Environment (PPE) scale.

PURPOSE: To describe the Professional Practice Environment (PPE) scale, its conceptual development and psychometric evaluation, and its uses in measuring eight characteristics of the professional practice environment in an acute care setting. DESIGN AND METHODS: The 38-item PPE Scale was validated on a sample of 849 professional practice staff at the Massachusetts General Hospital in Boston. Psychometric analysis included: item analysis, principal components analysis (PCA) with varimax rotation and Kaiser normalization, and internal consistency reliability using Cronbach's alpha coefficient. FINDINGS: Eight components were shown, confirming the original conceptually derived model's structure and accounting for 61% of explained variance. Cronbach's alpha coefficients for the eight PPE subscales ranged from .78 to .88. CONCLUSIONS: Findings showed the 38-item PPE Scale was reliable and valid for use in health outcomes research to examine the professional practice environment of staff working in acute care settings.

Acute Disease↗

PubMed1986

Development of a measure of job satisfaction for dentists and dental auxiliaries.

This paper describes the development of a multidimensional, 38-item measure of job satisfaction appropriate for dentists, dental hygienists, and dental assistants. Items were grouped into the following 12 subscales: income, recognition, opportunity to develop professionally, time to develop professionally, responsibility, non-patient tasks, staff relations, quality of care, leisure time, fatigue, time pressure and general satisfaction. The measure was developed from a set of 45 items included in questionnaires administered to dentists and staff of 126 dental practices in Washington State, USA. Questionnaires were returned by 117, 121 and 106 dentists; 69, 80, and 82 hygienists; and 322, 329, and 320 assistants, respectively, in each of the 3 yr (1979, 1980, 1981). Factor analysis (principal components analysis with varimax rotation) plus categorization of items by a panel of professionals were used to initially group items into subscales. Contribution to internal consistency was the final criterion for an item's inclusion in a subscale. Internal consistency reliability of subscales ranged from 0.68 to 0.95. Statistically significant relationships were found between individual job satisfaction subscales and intent to change job for hygienists and assistants.

Dental Assistants↗

PubMed2005

Factor analysis of clustered cardiovascular risks in adolescence: obesity is the predominant correlate of risk among youth.

BACKGROUND: Clustering of cardiovascular (CV) risks begins in childhood, yet studies of the factor structure underlying this clustering have focused on adults. The increasing rates of obesity and type 2 diabetes and the growing importance of metabolic syndrome among adolescents make assessment of CV risk clustering even more urgent in this age group. METHODS AND RESULTS: Exploratory factor analysis (principal components analysis) was performed with data from 1578 healthy seventh to 12th graders from the Princeton School District Study, a school-based study in Cincinnati, Ohio. Measured CV risks included cholesterol, triglycerides, fasting insulin and glucose, body mass index (BMI), waist circumference, fibrinogen, and blood pressure. Factor analysis yielded 4 uncorrelated factors (adiposity [BMI, waist, fibrinogen, insulin], cholesterol [LDL and total cholesterol], carbohydrate-metabolic [glucose, insulin, HDL cholesterol, triglycerides], and blood pressure [systolic and diastolic blood pressure]). These factors explained approximately 67% of the total variance. A summary cumulative risk scale was derived from factor scores, and high risk was defined as scoring in the top 5%. Although insulin loaded onto both the adiposity and carbohydrate-metabolic factors, obesity was a much stronger correlate of high cumulative risk (odds ratio=19.2; 95% CI, 7.6 to 48.5) than hyperinsulinemia (odds ratio=3.5; 95% CI, 1.8 to 6.8). A sizable proportion (18.5%; n=12) of those who were at high cumulative risk were not at high risk for any of the individual factors. CONCLUSIONS: The patterning of CV risk clustering seen among adults is present in healthy adolescents. Among youth, obesity is the predominant correlate of cumulative risk.

Adolescent↗

PubMed2005

Monocyte activation on polyelectrolyte multilayers.

The adherence and activation of primary human monocytes was investigated on a polyelectrolyte multilayer film containing hyaluronic acid (HA) and poly-L-lysine (PLL). The sequential layer-by-layer deposition of the multilayer film was characterized by surface plasmon resonance. Eight alternating bilayers displayed an effective thickness of 16.15 nm with a total polymer coverage of 2.10 microg/cm2. For cell studies, HA-PLL multilayers were constructed on tissue culture polystyrene (TCPS) substrates and characterized by time of flight second ion mass spectrometry (ToF-SIMS) analysis. Principal component analysis of the ToF-SIMS spectra resolved no significant difference in surface chemistry between PLL-terminated and HA-terminated multilayer surfaces. Monocyte adhesion on PLL- and HA-terminated surfaces was measured by the lactate dehydrogenase assay and showed a significant decrease in cell adhesion after 24 h incubation. Cell viability measured by Live/Dead fluorescent staining showed significant cell death in the adherent cell population over these 24 h. Tumor necrosis factor-alpha (TNF-alpha) production, a measure of monocyte activation, was quantified by ELISA and normalized to the number of adherent monocytes. The activation of monocytes on PLL-terminated and HA-terminated surfaces was nearly identical, and both surfaces had TNF-alpha levels that were 8-fold higher than TCPS. These results demonstrate that sufficient PLL had diffused into the surface layer to direct monocyte adherence and to induce cytokine activation and cell death on the HA-terminated multilayer films. The diffusion of the second multilayer component to the coating surface should, thus, be taken into account in the design of polyelectrolyte-based biomaterial coating strategies.

Cell Adhesion↗

PubMed2006

DNA molecule classification using feature primitives.

BACKGROUND: We present a novel strategy for classification of DNA molecules using measurements from an alpha-Hemolysin channel detector. The proposed approach provides excellent classification performance for five different DNA hairpins that differ in only one base-pair. For multi-class DNA classification problems, practitioners usually adopt approaches that use decision trees consisting of binary classifiers. Finding the best tree topology requires exploring all possible tree topologies and is computationally prohibitive. We propose a computational framework based on feature primitives that eliminates the need of a decision tree of binary classifiers. In the first phase, we generate a pool of weak features from nanopore blockade current measurements by using HMM analysis, principal component analysis and various wavelet filters. In the next phase, feature selection is performed using AdaBoost. AdaBoost provides an ensemble of weak learners of various types learned from feature primitives. RESULTS AND CONCLUSION: We show that our technique, despite its inherent simplicity, provides a performance comparable to recent multi-class DNA molecule classification results. Unlike the approach presented by Winters-Hilt et al., where weaker data is dropped to obtain better classification, the proposed approach provides comparable classification accuracy without any need for rejection of weak data. A weakness of this approach, on the other hand, is the very "hands-on" tuning and feature selection that is required to obtain good generalization. Simply put, this method obtains a more informed set of features and provides better results for that reason. The strength of this approach appears to be in its ability to identify strong features, an area where further results are actively being sought.

Computational Biology↗

PubMed2003

Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling.

PURPOSE: To develop a genome-based classification scheme for clear-cell sarcoma (CCS), also known as melanoma of soft parts (MSP), which would have implications for diagnosis and treatment. This tumor displays characteristic features of soft tissue sarcoma (STS), including deep soft tissue primary location and a characteristic translocation, t(12;22)(q13;q12), involving EWS and ATF1 genes. CCS/MSP also has typical melanoma features, including immunoreactivity for S100 and HMB45, pigmentation, MITF-M expression, and a propensity for regional lymph node metastases. MATERIALS AND METHODS: RNA samples from 21 cell lines and 60 pathologically confirmed cases of STS, melanoma, and CCS/MSP were examined using the U95A GeneChip (Affymetrix, Santa Clara, CA). Hierarchical cluster analysis, principal component analysis, and support vector machine (SVM) analysis exploited genomic correlations within the data to classify CCS/MSP. RESULTS: Unsupervised analyses demonstrated a clear distinction between STS and melanoma and, furthermore, showed that CCS/MSP cluster with the melanomas as a distinct group. A supervised SVM learning approach further validated this finding and provided a user-independent approach to diagnosis. Genes of interest that discriminate CCS/MSP included those encoding melanocyte differentiation antigens, MITF, SOX10, ERBB3, and FGFR1. CONCLUSION: Gene expression profiles support the classification of CCS/MSP as a distinct genomic subtype of melanoma. Analysis of these gene profiles using the SVM may be an important diagnostic tool. Genomic analysis identified potential targets for the development of therapeutic strategies in the treatment of this disease.

Algorithms↗

PubMed2002

Testing the metals hypothesis in Spokane, Washington.

A >7-year, time-series, epidemiologic study is ongoing in Spokane, Washington, to examine the associations between ambient particulate constituents or sources and health outcomes such as emergency department (ED) visits for asthma or respiratory problems. One of the hypotheses being tested is that particulate toxic metals are associated with these health outcomes. Spokane is a desirable city in which to conduct this study because of its relatively high concentrations of particulate matter, low concentrations of potentially confounding air pollutants, variability of particulate sources, and presence of several potential particulate metals sources. Daily fine- and coarse-fraction particulate samples are analyzed for metals via energy-dispersive X-ray fluorescence (EDXRF) and instrumental neutron activation analysis. Particulate sources are determined using receptor modeling, including chemical mass balancing and positive matrix factorization coupled with partial source contribution function analysis. Principal component analysis has also been used to examine the influence of sources on the daily variability of the chemical composition of particulate samples. Based upon initial analyses using the EDXRF elemental analyses, statistically significant associations were observed between ED visits for asthma and increased combustion products, air stagnation, and fine particulate Zn. Although there is a significant soil particulate component, increased crustal particulate levels were not found to be associated with ED visits for asthma. Further research will clarify whether there is an association between specific health outcomes and either coarse or fine particulate metal species.

Air Pollutants↗

PubMed2004

Identification of putative gene based markers of renal toxicity.

This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants--cisplatin, gentamicin, and puromycin--to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity.

Animals↗

PubMed2006

Factorial coding of natural images: how effective are linear models in removing higher-order dependencies?

The performance of unsupervised learning models for natural images is evaluated quantitatively by means of information theory. We estimate the gain in statistical independence (the multi-information reduction) achieved with independent component analysis (ICA), principal component analysis (PCA), zero-phase whitening, and predictive coding. Predictive coding is translated into the transform coding framework, where it can be characterized by the constraint of a triangular filter matrix. A randomly sampled whitening basis and the Haar wavelet are included in the comparison as well. The comparison of all these methods is carried out for different patch sizes, ranging from 2x2 to 16x16 pixels. In spite of large differences in the shape of the basis functions, we find only small differences in the multi-information between all decorrelation transforms (5% or less) for all patch sizes. Among the second-order methods, PCA is optimal for small patch sizes and predictive coding performs best for large patch sizes. The extra gain achieved with ICA is always less than 2%. In conclusion, the edge filters found with ICA lead to only a surprisingly small improvement in terms of its actual objective.

Algorithms↗

PubMed1997

Stomach cancer incidence in Brazil: an ecologic study with selected risk factors.

Contrary to many industrialized countries in which a sharp decline in stomach cancer incidence has been observed, Brazil still shows intermediate to high incidence rates. An ecologic analysis was performed to explore variables possibly associated with the development of stomach cancer. Cluster analysis, principal component analysis, and factor analysis were carried out with population data, including the following: stomach cancer incidence rates in the early 1990s obtained from population-based cancer registries in Porto Alegre, Campinas, Fortaleza, Belém, and Goiânia; and data from a Brazilian national survey on family expenditures (several diet consumption items and availability of home refrigerators) carried out in 1974-75. The results suggested that past availability of a home refrigerator, i.e. food preservation, may have played an important role in currently observed differences in stomach cancer incidence among the various populations studied in Brazil. Differences in living standards among populations in these cities also appear to have played an important role in the observed incidence differences.

Journal Article↗

PubMed2006

Correlation between multielement stable isotope ratio and geographical origin in Peretta cows' milk cheese.

The aim of this study was to characterize the isotopic composition and protect "Peretta" cows' milk cheese, a typical product of Sardinia, against other cheeses of the same appearance sold under the same name, but made of raw materials from northern Europe. The study was concerned with 3 types of cheese: those produced in local dairies from milk from free-grazing or pasture-grazing cows in Sardinia (local dairy product), cheeses made on an industrial scale from milk produced by intensive farming in Sardinia (factory cheese), and cheeses made with raw materials imported from other countries (imported product). To distinguish the Sardinian cheeses from the imported product, the stable isotope ratios 13C/12C, 15N/14N, D/H, 34S/32S, and (18)O/(16)O were used. Determination of the isotopic data delta13C, delta15N, delta2H, and delta34S was performed in the casein fraction, whereas delta(18)O and delta13C were determined in the glycerol fraction. Measurements were performed by isotope ratio mass spectrometry. A comparison between mean values of the isotope ratios by statistical analysis (ANOVA and Tukey's test) showed that the greatest difference between the 3 types of cheese (local dairy, factory, and imported products) was in the 13C/12C, 34S/32S, and (18)O/(16)O isotope ratios. In the other parameters, either no differences (delta15N) or minimal differences (delta2H) were found. Evaluation of the data by multivariate statistical analysis (principal component analysis and hierarchical cluster analysis) revealed that the isotope characteristics of the factory products were similar to those of the cheeses produced from imported raw materials, whereas a difference was found between the local dairy-produced cheeses and the products in the other 2 categories.

Analysis of Variance↗