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StAR and progesterone producing enzymes (3beta-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage cytochromes P450) in human epithelial ovarian carcinoma: immunohistochemical and real-time PCR studies.

Steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage enzyme (P450scc) and 3 beta-hydroxysteroid dehydrogenase enzyme (3beta-HSD) are all involved in the transport of cholesterol and production of progesterone. In situ production of sex steroids including progesterone have been considered to play important roles in pathogenesis and/or development of common epithelial ovarian carcinomas. In this study, StAR, P450scc, and 3beta-HSD were immunolocalized in 100 cases of ovarian carcinoma and results were then correlated with clinicopathological and prognostic parameters of individual patients including status of progesterone receptor (PR) in tumor cells. Results of immunohistochemistry were further characterized by real-time PCR analysis in 20 cases of epithelial ovarian carcinomas in which frozen tissues were available for examination. StAR, P450scc, and 3beta-HSD immunoreactivity was detected predominately in the cytoplasm of carcinoma cells. Results of real-time PCR analysis were correlated with those of immunohistochemical studies. StAR, P450scc, and 3beta-HSD H scores demonstrated significant inversed statistical correlation with FIGO stage, residual size of the tumor, and Ki67 LI. A positive statistically significant correlation was detected between StAR H score and PR-B LI. Multivariate statistical analysis demonstrated that the status of intratumoral StAR, FIGO stage, and residual tumor size all turned out to be independent prognostic factors for the clinical outcome of the patient. The presence of StAR, a cholesterol transporter for steroidogenesis in human epithelial ovarian carcinoma, may reflect the ability of these tumors to produce progesterone in situ that could influence biological behavior of these tumors, especially through progesterone dependent inhibition of tumor cell proliferation.

17-Hydroxysteroid Dehydrogenases↗

[Geographical Information Systems and remote sensing technologies in parasitological epidemiology].

Parasites have natural habitats in the same way as a species: they are found in focal areas where the spatial distribution of the parasite, host, vector and required environmental conditions coincide. The spatial distribution of parasites is, therefore, a function of the interaction between abiotic and biotic environmental factors. The boundaries of distributions are not strictly fixed in space and time and may fluctuate with climate and other components of the environment or anthropical factors. Geographic Information Systems (GIS) and remote sensing (RS) technologies are being used increasingly to study the spatial and temporal patterns of disease. GIS can be used to complement conventional ecological monitoring and modelling techniques, and provide means to portray complex relationships in the ecology of disease. In addition, the use of GIS and RS to identify environmental features allows determination of risk factors and delimitation of areas at risk, permitting more rational allocation of resources for cost-effective control. Since 1996, GIS have been used in our territorial cross-sectional and longitudinal parasitological surveys in order to experiment new applications to plan sampling protocols and to display quickly, clearly, and analytically the spatial and/or temporal distribution of parasitological data. The use of GIS allowed us to draw the following types of descriptive parasitological maps: distribution maps, distribution maps with proportioned peaks, choroplethic maps with proportioned peaks, point distribution maps and point distribution maps with proportioned peaks. In a recent study, GIS and RS technologies have been used also to identify environmental features that influence the distribution of paramphistomosis in sheep from the southern Italian Apennines and to develop a preliminary risk assessment model. A GIS was constructed using RS and landscape feature data together with paramphistome positive survey records from 197 georeferenced ovine farms with animals pasturing in an area of the southern Italian Apennines. The GIS for the study area was constructed utilizing the following environmental variables: Normalized Difference Vegetation Index (NDVI), land cover, elevation, slope, aspect, and total length of rivers. In addition, data regarding the presence of watercourses smaller than rivers, namely, streams, springs and brooks were recorded in the field. All these variables were then calculated for "buffer zones" consisting of the areas included in a circle of 3 Km diameter centred on 197 farms. The environmental data obtained were analyzed by univariate and multivariate statistical analyses using the paramphistome farm coprological status (positive/negative) as the dependent variable. A multivariate stepwise discriminant analysis model was developed that included moors and heathland, sclerophyllus and coniferous forest vegetation, autumn-winter NDVI and presence of streams, springs and brooks on pasture. The variables entered in the model are consistent with the environmental requirements of paramphistomes and their snail intermediate host. In particular, the land cover types entered in the model in this area are indicators of marginal uncultivable and sloping zones where typically there is the presence of water (permanently or temporarily). In addition, since NDVI can be used as an indicator of regional thermal-moisture regime, the distribution of farms positive for paramphistomosis corresponding to relatively high values of winter NDVI indicated the presence of adequate moisture and temperatures favourable to the rumen fluke and the snails. In conclusion, GIS and RS are useful to define the habitats of parasites, especially for those with strong environmental determinants, and to produce forecasting maps requested for the planning and the monitoring of control strategies on small and large scale.

Animals↗

Multivariate data analysis for outcome studies.

The use of multivariate statistical techniques for analyzing the complex data often gathered in outcome studies is discussed. The multivariate analysis of variance (MANOVA) is suggested for multiple group studies common to outcome studies. This technique can be utilized for a large number of specific research designs whenever multiple outcome measures are collected. MANOVA offers two specific advantages over more familiar univariate approaches: it presents better control over Type 1 error rates while preserving statistical power, and it allows more thorough analysis of complex data.

Humans↗

[Falsely positive values in multi-channel analysis: an estimation of their frequency with Sylvester's formula and their reduction by a multivariate test quantity (author's transl)].

The application of the binomial distribution for determining the number of "falsely positive values" is not suitable because of the partly strong correlations between the clinical chemical parameters. We have therefore tried to obtain more precise estimations for the number of falsely positive values by using a generalisation from Sylvester's formula and taking into account the correlations. We use multivariate statistics for testing a patient's value" when several laboratory parameters are simultaneously considered. The multivariate technique leads firstly to a significant reduction of the erroneously interpreted "falsely positive values" and secondly allows the detection of hidden implausible constellations of values.

Autoanalysis↗

Multidimensional statistical analysis applied to electron ionization mass spectra to determine steroid stereochemistry.

The differentiation of stereoisomers on the basis of their mass spectra only is usually a difficult challenge even when an informative ionization technique such as electron ionization is used; this is particularly the case for steroids. In this study, multivariate statistical techniques have been applied to the mass spectra of derivatized 5xi-androstane-3xi,17xi-diols (xi = alpha,beta) in order to investigate the possibility of discrimination among the different isomers. After collection of the data from the mass spectra (20 replicates for each of the 8 isomers), each ion was considered as a statistical variable and each mass spectrum as an observation. The more discriminative variables (42 out of the 160 initial ones) were selected using the analysis of variance technique (ANOVA). Thereafter, a linear discriminant analysis (LDA) allowed us to set up a predictive model for stereochemistry determination. The two-dimensional graphical display of the 160 observations on the basis of the canonical variables derived from LDA made it possible to separate the eight isomers. The discrimination of 5alpha and 5beta isomers as well as 3alpha and 3beta was unambiguous, whereas, the discrimination of 17alpha and 17beta epimers was less obvious. The robustness of the model was checked with 40 mass spectra recorded over a 6-month period on different quadrupole mass spectrometers and under different signal acquisition conditions. The percentage of correct assignment of these 'unknown' stereoisomers was 92%; only three 17alpha and 17beta epimers were not correctly plotted in the expected zone. Nevertheless, the performance score was better than those observed with traditional mass spectral libraries. Furthermore, this statistical approach allowed us to identify the main fragment ions involved in the discrimination between isomers: m/z 256 and 421 for isomers 5a-5b; m/z 241 and 331 for isomers 5alpha3alpha-5alpha3beta; m/z 143 and 162 for isomers 5beta3alpha-5beta3beta; and m/z 255 for epimers 17alpha-17beta.

Androstenediols↗

Determinants of satisfaction with prescription drug plans.

Satisfaction among health plan members with their prescription drug coverage was studied. Interviews of patrons of 10 randomly selected community pharmacies in the Pittsburgh area were conducted by entry-level Pharm.D. students during spring 1999. Survey participants were asked to indicate their level of satisfaction with each of nine items dealing with various components of pharmacy benefit plans and to provide health-related and sociodemographic information. Differences in responses were assessed with univariate and multivariate statistics. A total of 504 people were interviewed. The results of general linear model and multivariate procedures indicated that the sociodemographic characteristics of respondents did little to explain variations in satisfaction. Differences were governed primarily by having a choice of plans in which to enroll and of perceptions of plan limitations. Most respondents were overwhelmingly satisfied with the quality of their prescription drug plans. Government-sponsored plans were rated at least as well as private plans. Members of health care plans in a metropolitan region were satisfied with their prescription drug coverage. Satisfaction was primarily determined by perceptions about coverage limitations and having a choice of plans.

Analysis of Variance↗

Gender differences in perinatal HIV acquisition among African infants.

OBJECTIVE: We investigated gender-specific risks of mother-to-child transmission (MTCT) at birth and at 6 to 8 weeks among infants born to HIV-infected African women. DESIGN: Follow-up study of infants enrolled in 2 randomized, phase III, clinical trials to prevent MTCT, conducted in Blantyre, Malawi, in southeast Africa. METHODS: Infants were enrolled at birth and monitored postnatally, and their HIV status was assessed at birth and at 6 to 8 weeks (assessment beyond 6-8 weeks is ongoing). Statistical analyses were stratified according to gender, and comparisons were made with descriptive, univariate, and multivariate statistical tests. MTCT was estimated at birth and at 6 to 8 weeks among infants who were not infected at birth. RESULTS: Overall, 966 boys and 998 girls were enrolled. The rate of HIV transmission at birth was 9.5% (187 of 1964 infants). However, at birth significantly more girls (12.6%) than boys (6.3%) were infected with HIV. This association remained significant after controlling for maternal viral load and other factors. Among infants who were uninfected at birth, 8.7% (135 of 1554 infants) acquired HIV by 6 to 8 weeks; of these infants, more girls acquired HIV (10.0%), compared with boys (7.4%). CONCLUSIONS: Female infants may be more susceptible to HIV infection before birth and continuing after birth. Alternatively, in utero mortality rates of HIV-infected male infants may be disproportionately higher and thus more HIV-infected female infants are born. In areas of sub-Saharan Africa, where HIV infection rates are high among women of reproductive age, the magnitude of the gender transmission differences observed in this study could have clinical, preventive, and demographic implications.

Birth Weight↗

The problem of multiple inference in psychiatric research.

This paper deals with the problem of multiple inference in psychiatric research, an issue which arises whenever a researcher has to make more than one statistical inference in a single research study. It frequently arises in psychiatric research because of multivariate study designs, with subjects being measured on more than one dependent variable with the intention of studying differences between groups in mean scores. The disadvantages of the commonly adopted strategy of using multiple univariate tests (e.g. multiple t-tests) are outlined. Two broad strategies--Bonferroni-adjusted univariate tests and multivariate statistical analysis--are introduced. Their advantages and disadvantages are discussed in terms of their usefulness in confirmatory and exploratory research in psychiatry.

Analysis of Variance↗

Participation in a women's breast cancer risk counseling trial. Who participates? Who declines? High Risk Breast Cancer Consortium.

BACKGROUND: Little is known about what factors influence women to participate its trials designed for women at high risk for breast cancer. Yet the recruitment phase is of utmost importance in determining whether the trial can achieve its goals. The purpose of this study was to examine predictors of participation in a risk counseling trial for first-degree relatives of breast cancer patients. METHODS: Subjects were identified by their relatives who had received a diagnosis of breast cancer at one of six institutions. Letters of introduction were sent to potentially eligible, unaffected relatives. They were informed about the risk counseling study and given the opportunity to decline. Letters were sent to 1392 first-degree relatives; of these, 1149 women were contacted for an interview and 14% refused. Of the 987 respondents, 47% accepted and 53% declined to participate. Bivariate and multivariate statistics were used to examine predictors of participation. RESULTS: In the total sample, there were five significant multivariable predictors of participation: level of education, recent clinical breast examination (CBE), objective and perceived breast cancer risk, and any current use of alcohol. Participation was moderated by time since the relative's diagnosis. There was a statistically significant relationship to education such that women with a higher level of education were significantly more likely to participate if they were approached within 2 months of their relative's diagnosis of breast cancer. CONCLUSIONS: Like many other kinds of trials, participants in this risk counseling trial were significantly more likely to have more than a high school education and more likely to be nonsmokers than the nonparticipants. They also were significantly more likely to drink alcohol (dichotomous measure), have had a recent CBE, and have higher subjective and objective breast cancer risks. Different types of recruitment strategies may be needed depending on the characteristics of the people being recruited and the timing of the invitation.

Adult↗

Deer herd health and production profiling in New Zealand. 2. Preliminary results.

A 2 yr observational study of 15 commercial red deer farms is being conducted in New Zealand and statistical analysis initiated. Preliminary results for weaner deer growth, reproduction and deer mortality data are presented. Multivariable statistical analyses are used to identify risk factors for these various outcomes. Factors associated with yearling hind conception status were included in a putative path diagram and logistic regression was used to identify important factors.

Animals↗

Evaluation of clinical parameters and estrogen receptor alpha gene polymorphisms for patients with endometriosis.

Endometriosis is a chronic inflammatory disease, which is especially found in women with subfertility problems with an incidence of up to 30%. The disease is considered an estrogen-dependent disorder, where DNA polymorphisms of the estrogen receptor alpha (ERalpha) in connection with endometriosis are controversially discussed. From a German population of women, clinical data associated with the disease, including the American Fertility Society (AFS) I-IV classification, and non-clinical parameters were evaluated statistically in endometriosis patients (n = 98) and in control women (n = 98) without endometriosis. Using a multivariate statistical analysis, significant associations of endometriosis with dysmenorrhea (P < 0.001) and allergies against medicaments (P = 0.042) were found. A positive trend between first grade family history of endometriosis and allergies against medicaments was also observed, suggesting a genetic relationship. From both collectives, DNA from peripheral blood was analyzed for the frequency of the ERalpha DNA polymorphisms Xba1 (A/G) and PvuII (T/C) in intron 1 and the ERalpha exonic DNA polymorphism (G229A) with an amino acid exchange (Gly77Ser) in the transactivation domain. DNA samples from endometriosis lesions and control tissues from the same collectives were also analyzed for the exonic G229A polymorphism. Only homozygote wild-type alleles for the polymorphism G229A were found, making it a rare polymorphism in mid-European individuals. Allele types for the PvuII and Xba1 polymorphisms were analyzed with the observed statistically significant clinical parameters and showed no significant association with endometriosis; however a trend with AFS IV was noted, which could contribute to lesion severity. In conclusion, the analyzed polymorphisms in the ERalpha do not have a functional role concerning specific clinical parameters associated with endometriosis.

Adolescent↗

Sixteen-slice spiral CT versus MR imaging for the assessment of left ventricular function in acute myocardial infarction.

The aim of this study was to assess global left ventricular (LV) function and regional wall motion using retrospectively ECG-gated 16-slice computed tomography (CT) in comparison with magnetic resonance imaging (MRI). Twenty-one patients (18 male, 65.5+/-8.6 years) with acute myocardial infarction underwent multislice spiral CT (MSCT) and MRI. From manually drawn endo- and epicardial contours, LV volumes including myocardial mass, peak filling rate (PFR), peak ejection rate (PER), time to PER (TPER) and time from end-systole to PFR (TPFR) were calculated. Regional wall motion was assessed from cine loops using a 16-segment model of the left ventricle. LV function was analyzed using the Bland-Altman method, Pearson's correlation coefficient, multivariate analysis and post hoc t tests. Regional wall motion was evaluated with weighted kappa-statistics. Multivariate analysis revealed significant differences for global LV function as determined by MSCT and MRI. Post hoc t-tests showed significant differences for end-diastolic volume (EDV), PFR and TPER (P<0.05), while there was a good agreement for the LV volumes with an ejection fraction of 46.9+/-8.4% for MSCT and 46.9+/-8.9% for MRI. PER, PFR, TPER and TPFR presented a poor correlation and a wide range of scattering between MSCT and MRI. Regional wall motion scores showed a good agreement with kappa=0.791. Sixteen-slice spiral CT allows for reliable assessment of LV volumes, but is not yet suited for the evaluation of all functional parameters. Assessment of regional wall motion at rest is feasible.

Female↗

Clinical and psychological diversity of non-specific low-back pain. A new approach towards the classification of clinical subgroups.

This study explored the clinical and psychological features of non-specific low-back pain (LBP) using multivariate statistical methods including correspondence analysis, cluster analysis and discriminant analysis. An unselected population of subjects (n = 330) complaining of localized LBP to hospital rheumatologists during 1988 was studied. 41% of the subjects (n = 136) were classified as having a psychiatric disorder according to the DSM-III criteria (Axis I). A number of different organic syndromes were identified and the importance of psychological influences on the clinical presentation of LBP was demonstrated. Cluster analyses provided further evidence for a four-group typology of LBP, which may be interpreted through the relationships or interactions between psychological disturbances and the clinical features of LBP. This study highlights the need, in etiological research, to take into account the clinical diversity of non-specific LBP and to investigate further the complex relationships between psychological disturbances and back pain.

Adult↗

Who worries that something might be wrong with the baby? A prospective study of 1072 pregnant women.

BACKGROUND: Little is known about the normal range and pattern of pregnant women's worry about something being wrong with the baby, or how this relates to other factors. The objective of this study was to examine the extent to which women are worried about the possibility of something being wrong with the baby relative to other worries they may have, and to determine whether demographic, experiential, attitudinal, and personality characteristics are associated with this worry. METHODS: Longitudinal data were collected from 1072 pregnant women who completed postal questionnaires at 16, 22, and 35 weeks of pregnancy. Multivariate statistical techniques were used to determine which variables were independently related to worry about the baby. RESULTS: Worry that something might be wrong with the baby was one of the most prevalent worries at 16 weeks, although not as widespread a source of extreme worry as miscarriage or giving birth. Worry dropped in midpregnancy but rose again at 35 weeks. The most important factors related to this worry were perceived likelihood that something might be wrong with the baby and trait anxiety, although negative mood, previous pregnancy outcomes, and initial reactions to the current pregnancy all demonstrated significant, independent effects. CONCLUSIONS: Women who answered "Don't know" to "Have you any reason to think that your baby might be more likely than any other to have some sort of a problem?" had consistently high anxiety throughout pregnancy. We suggest that this question be asked routinely in early pregnancy to identify these potential worries and, it is to be hoped, reassure them at an early stage.

Adolescent↗

[The factor structure of the adult psychiatry morbidity questionnaire in a community sample of Brazilian cities].

Principal Components Analysis is a multivariate statistical technique for the purpose of examining the interdependence among variables. The main characteristic of this technique is the ability to reduce data, and it is currently used as an adjunct for the development of psychiatric research tools and the classification of psychiatric disorders. It has been applied to the study of the Factorial Structure of a Brazilian screening questionnaire, the Adult Psychiatric Morbidity Questionnaire (QMPA). The questionnaire is made up of 45 yes/no items for the identification of psychiatric symptoms and the use of psychiatric services and psychotropic drugs. The questionnaire was applied to 6.470 subjects over 15 years old in representative samples from three urban areas: Brasília, Porto Alegre and S. Paulo. Seven factors were found to explain 42.7% of the total variance: Anxiety/Somatization (eigenvalue = 3.81, 10.9%); Irritability/Depression (eigenvalue = 2.41, 6.9%); Cognitive Impairment (eigenvalue = 2.01, 5.8%); Alcoholism (eigenvalue = 1.90, 5.4%); Mood Elation (eigenvalue = 1.62, 4.6%); Hallucinatory/Delusional Disorders (eigenvalue = 1.60, 4.6%); and Drug/Therapies (eigenvalue = 1.60, 4.5%). A similar pattern of results was found when the analysis was carried out in the three places. It is suggested, on the banis of these findings, that some questions should be modified and some excluded in any future version of the questionnaire.

Adolescent↗

[Risk factors for low birthweight in a Cuban hospital, 1997-2000].

OBJECTIVE: To determine what maternal risk factors that are present during pregnancy are associated with low birthweight (less than 2 500 g). METHODS: A case-control study was conducted with 764 products of single births weighing less than 2 500 g at birth, and 1 437 controls from Hospital Gineco-Obstétrico Provincial in Sancti Spiritus, Cuba, during the 1997-2000 quadrennium. The data were obtained from clinical records, reports of labor, and personal interviews with mothers. A bivariate analysis was performed, and possible confounders were controlled for through dichotomous logistic regression using SPSS. A final multivariate statistical model used was to identify maternal risk factors for low birthweight. RESULTS: The results of multivariate analysis showed a significant association between low birthweight, the presence of anemia when the pregnancy was detected, urinary tract infection during pregnancy, bronchial asthma, total maternal weight gain under 8 kg during pregnancy, smoking while pregnant, a history of previous children with low birthweight, arterial hypertension since before pregnancy, and inadequate timing of visit for follow-up of initial prenatal care. CONCLUSIONS: On the basis of these results it was concluded that, regardless of the impact measurement method used, it is important to try to reduce the risk factors identified in the study in order to lower the incidence of low birthweight in the province of Sancti Spiritus.

Adult↗

Theoretical calculation and prediction of drug transport processes using simple parameters and partial least squares projections to latent structures (PLS) statistics. The use of electrotopological state indices.

A method of modeling and predicting drug transport processes using simple, theoretically computed molecular descriptors and multivariate statistics has been investigated in four data sets related to Caco-2 cell permeability, human intestinal absorption, brain-blood partitioning, and immobilized artificial membrane (IAM) chromatography. The program Molconn-Z was used to compute theoretical molecular descriptors related to electrotopological state indices. Additional parameters related to size and lipophilicity [i.e., calculated molar refraction (CMR) and octanol-water partition coefficient (CLOGP)] were also used in the statistical modeling. Good statistical models were derived (r(2) and Q(2) values ranged from 0.75 to 0.93 and 0.70 to 0.89, respectively) that permit fast computational (electronic) screening and prioritization of virtual libraries.

Blood-Brain Barrier↗

Prediction of drug transport processes using simple parameters and PLS statistics. The use of ACD/logP and ACD/ChemSketch descriptors.

A method of modelling and predicting biopharmaceutical properties using simple theoretically computed molecular descriptors and multivariate statistics has been investigated for several data sets related to solubility, IAM chromatography, permeability across Caco-2 cell monolayers, human intestinal perfusion, brain-blood partitioning, and P-glycoprotein ATPase activity. The molecular descriptors (e.g. molar refractivity, molar volume, index of refraction, surface tension and density) and logP were computed with ACD/ChemSketch and ACD/logP, respectively. Good statistical models were derived that permit simple computational prediction of biopharmaceutical properties. All final models derived had R(2) values ranging from 0.73 to 0.95 and Q(2) values ranging from 0.69 to 0.86. The RMSEP values for the external test sets ranged from 0.24 to 0.85 (log scale).

ATP Binding Cassette Transporter, Subfamily B, Mem↗