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PubMed1987

[A mathematical description of microecologic correlations].

Due to the diversity of microbiological interrelations results of animal experiments concerning the effect of nutrition factors on the microecological system in the intestinal tract are often difficulty to interpret. In order to reveal deeper correlations multivariate statistical methods particularly the non-linear multiple regression analysis are tried to use. First results show that correlations between nutrition factors and microecological signs of the colon content can be depict by quadratic polynoms, whereas for biochemical signs also a linear dependence appears possible.

Animals↗
PubMed2001

Recurrent falls are associated with increased length of stay in elderly psychiatric inpatients.

OBJECTIVES: To identify factors which may contribute to prolonged length of stay in an elderly psychiatric inpatient setting. DESIGN: Retrospective case note study. METHODS: A list of all patients over the age of 65 discharged from a private psychiatric hospital over a three-year period excluding those with a length of stay of over 365 days was obtained (n = 1147). A random sample of 150 patients was selected from the study population. A case note study was then performed looking at a number of variables which have been postulated to affect length of stay. The resulting data was analysed using multivariate statistics. RESULTS: There was no statistically significant association found between baseline factors (including age, gender, cognitive impairment, marital status, order of admission and preadmission living arrangement) and length of stay. Having recurrent falls whilst an inpatient was associated with prolonged hospital stay (p = 0.0006). CONCLUSION: Experiencing recurrent falls whilst an inpatient is associated with prolonged length of stay. Recurrent falls in the elderly may be associated with both physical illness and the use of psychotropic medications. A prospective study examining factors contributing to falls would be important in decreasing fall risk and reducing length of stay.

Accidental Falls↗
PubMed1989

Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis.

The natural history of primary sclerosing cholangitis was assessed in 174 patients; 37 were asymptomatic and 137 had symptoms related to underlying liver disease. At the time of diagnosis, the mean age was 39.9 years, 66% of the primary sclerosing cholangitis patients were male and 71% had associated inflammatory bowel disease, most commonly chronic ulcerative colitis. Long-term follow-up (mean: 6.0 years; range: 2.7 to 15.5 years) was available in all patients. During follow-up, 59 (34%) of the patients died: 55 in the symptomatic group and four in the asymptomatic group. Median survival from the time of diagnosis of primary sclerosing cholangitis at the Mayo Clinic was 11.9 years. Survival in the asymptomatic group was significantly decreased compared with that in a control population matched for age, race and sex. Multivariate analysis (Cox proportional hazards regression modeling) revealed that age, serum bilirubin concentration, blood hemoglobin concentration, presence or absence of inflammatory bowel disease and histologic stage on liver biopsy were independent predictors of high risk of dying. The development of a multivariate statistical survival model is a major step in identifying individual primary sclerosing cholangitis patients at low, moderate and high risk of dying. Such models will be useful for stratifying patients in therapeutic trials, in patient counseling and in patient selection and timing of liver transplantation.

Adult↗
PubMed1997

The application of image analysis and neural network technology to the study of large-cell liver-cell dysplasia and hepatocellular carcinoma.

Liver cell dysplasia (LCD) is considered a preneoplastic lesion, whose characterization and differentiation from hepatocellular carcinoma (HCC) and from the reactive changes seen in cirrhosis has been controversial. We studied 12 cases of LCD (large cell type) with image analysis techniques (IA) and compared the findings with those of HCC (n = 40), and a spectrum of non-neoplastic hepatic lesions including normal liver and cirrhosis (n = 49). A minimum of 200 Feulgen-stained nuclei were measured from each lesion with the CAS 200 image analysis system. The data were collected with the aid of CellSheet software. Thirty-four variables were measured, including geometric, textural, and photometric nuclear features and DNA ploidy. The data were analyzed with multivariate statistics and a backpropagation neural network (NN). Stepwise statistical analysis selected 22 variables that were statistically significant in the three groups with P values <.05. Various NN architectures were developed using these variables. The best NN architecture included a sigmoidal transfer function, 14 input, 16 hidden, and 3 output neurons. It trained to completion after 8,887 runs using 90% of the lesions. This NN yielded a 100% cross-validation rate for unknown cases. These data support the concept of LCD (large cell type) as a lesion that can be objectively distinguished from HCC and non-neoplastic liver. Our study also demonstrates the potential usefulness of IA for the evaluation of difficult histopathological problems.

Carcinoma, Hepatocellular↗
PubMed1989

A case-control study of diet and breast cancer in Argentina.

A case-control study of breast cancer was carried out in La Plata, Argentina, where the incidence of the disease is comparable to the highest rates recorded worldwide. One hundred and fifty incident cases were identified through major hospitals. For each case, a hospital control, matched by age and hospital, and a neighbourhood control, matched by residential area and age, were also chosen. Cases and controls were interviewed to obtain information on past diet, as well as demographic and socio-economic characteristics, reproductive and menstrual history and other potential breast-cancer risk factors. The dietary information was obtained from questions on the consumption of specific food items and information on portion sizes from an earlier study was used to estimate intake of calories and selected nutrients. There was a substantial excess energy intake among cases as compared to both control groups, which was present across all 3 major macronutrients which contribute to total calories. Among the food groups, the consumption of eggs was a risk factor for breast cancer, and whole-milk products and green leafy vegetables were protective. After adjusting for the calorie difference in multivariate statistical analyses of nutrients, fibre and beta-carotene consumption were weakly protective. The results are discussed with reference to possible methodological difficulties and previous studies of diet and breast cancer.

Argentina↗
PubMed1985

Characteristic views of E. coli and B. stearothermophilus 30S ribosomal subunits in the electron microscope.

Large sets of electron microscopic images of the 30S ribosomal subunits of Bacillus stearothermophilus (914 molecules) and Escherichia coli (422 molecules) were analysed with image processing techniques. Using computer alignment and a new multivariate statistical classification scheme, three predominant views of the subunit were found for both species. These views, which together account for approximately 90% of the population of images, were determined to a reproducible resolution of up to 1.7 nm, thus elucidating many new structural details. The angular spread of the molecular orientations around the three main stable positions is remarkably small (less than 8 degrees). Some of the current models for the small ribosomal subunit are incompatible with our new results.

Escherichia coli↗
PubMed1993

The portal protein of bacteriophage SPP1: a DNA pump with 13-fold symmetry.

Electron microscopy in combination with image processing is a powerful method for obtaining structural information on non-crystallized biological macromolecules at the 10-50 A resolution level. The processing of noisy microscopical images requires advanced data processing methodologies in which one must carefully avoid the introduction of any form of bias into the data set. Using a novel multivariate statistical approach to the analysis of symmetry, we studied the structure of the bacteriophage SPP1 portal protein oligomer. This portal structure, ubiquitous in icosahedral bacteriophages which package dsDNA, is located at the site of symmetry mismatch between a 5-fold vertex of the icosahedral shell and the 6-fold symmetric (helical) tail. From previous studies such 'head-to-tail connector' structures were generally accepted to be homododecamers assembled in a 12-fold symmetric ring around a central channel. Using a new analysis methodology we have found that the phage SPP1 portal structure exhibits 13-fold cyclical symmetry: a new point group organization for oligomeric proteins. A model for the DNA packaging mechanism by 13-fold symmetric portal protein assemblies is presented which attributes a coherent functional meaning to their unusual symmetry.

Biological Transport↗
PubMedDate not supplied

A multivariable analysis of factors governing the steady-state pharmacokinetics of valproic acid in 52 young epileptics.

A number of factors have been implicated in the interpatient variability of valproic acid (VPA) pharmacokinetics. These include patient age, concurrent anticonvulsant therapy, and dosage of VPA. In the clinical setting, it is important to determine which of these variables exert a major effect on the observed differences in VPA disposition. Accordingly, we analyzed the data from 52 young epileptic patients using multivariate statistical methods. Concurrent anticonvulsant therapy was the major determinant of VPA clearance in this patient population. The half-life of VPA was significantly related to age, but volume of distribution and clearance were not. The dosage of VPA affected the volume of distribution of VPA but not the half-life or clearance of this drug. These results provide a more rational understanding of VPA pharmacokinetics in the clinical setting and have implications for the monitoring and manipulation of VPA therapy in the epileptic population.

Adolescent↗
PubMed2005

Ontogeny, phylogeny, and morphology in anuran larvae: morphometric analysis of cranial development and evolution in Rana tadpoles (Anura: Ranidae).

Comparative studies of chondrocranial morphology in larval anurans are typically qualitative in nature, focusing primarily on discrete variation or gross differences in the size or shape of individual structures. Detailed data on chondrocranial allometry are currently limited to only two species, Rana sylvatica and Bufo americanus. This study uses geometric morphometric and multivariate statistical analyses to examine interspecific variation in both larval chondrocranial shape and patterns of ontogenetic allometry among six species of Rana. Variation is interpreted within the context of hypothesized phylogenetic relationships among these species. Canonical variates analyses of geometric morphometric datasets indicate that species can be clearly discriminated based on chondrocranial shape, even when whole ontogenies are included in the analysis. Ordinations and cluster analyses based on chondrocranial shape data indicate the presence of three primary groupings (R. sylvatica; R. catesbeiana + R. clamitans; and R. palustris + R. pipiens + R. sphenocephala), and patterns of similarity closely reflect phylogenetic relationships. Analysis of chondrocranial allometry reveals that some patterns are conserved across all species (e.g., most measurements scale with negative allometry, those associated with the posterior palatoquadrate tend to scale with isometry or positive allometry). Ontogenetic scaling along similar allometric trajectories, lateral transpositions of individual trajectories, and variable allometric relationships all contribute to shape differences among species. Overall patterns of similarity among ontogenetic trajectories also strongly reflect phylogenetic relationships. Thus, this study demonstrates a tight link between ontogeny, phylogeny, and morphology, and highlights the importance of including both ontogenetic and phylogenetic data in studies of chondrocranial evolution in larval anurans.

Animals↗
PubMed1989

Histochemical classification of neck and limb muscle fibers in a turtle, Pseudemys scripta: a study using microphotometry and cluster analysis techniques.

We have attempted to develop an objective, semiquantitative classification of fiber types in turtle neck and limb muscle using microphotometry and multivariate statistical techniques. We first stained serial sections for myosin adenosine triphosphatase (ATPase) (with acid and alkaline preincubation and without preincubation), NADH-diaphorase, and two glycolysis-associated markers, alpha-glycerophosphate dehydrogenase (alpha-GPDH) and glycogen phosphorylase A (GPA). This allowed us to characterize individual muscle fibers in terms of their contraction speed and metabolic properties. Next we used microphotometry to measure the optical density of the reaction product in each fiber, and we subjected the resulting optical density matrix to cluster and discriminant function analyses in order to assign fibers to groups (fiber types) and to determine which stains contribute most to the distinction between groups. As a control, we processed a well characterized mammalian muscle (rat sternomastoid) simultaneously. Our results suggest that both neck and limb muscle in Pseudemys can best be described as falling into three groups: 1) slow oxidative (SO) fibers; 2) fast oxidative glycolytic (FOG) fibers, with relatively high oxidative and glycolytic capacities; and 3) fast glycolytic (Fg) fibers, with low oxidative, low/intermediate alpha-GPDH, and high GPA activities. These three fiber types differ from like-named types in rat muscle both in the pH lability of their myosins and in their metabolic profiles.

Animals↗
PubMed2007

Inhibitors of glutamate transport modulate distinct patterns in brain metabolism.

High affinity uptake of glutamate plays a major role in the termination of excitatory neurotransmission. Identification of the ramifications of transporter function is essential to understand the diseases in which defective excitatory amino acid transporters (EAAT) have been implicated. In this work we incubated Guinea pig cortical tissue slices with [3-(13)C]pyruvate and major currently available glutamate uptake inhibitors and studied the resultant metabolic sequelae by (13)C and (1)H NMR spectroscopy using a multivariate statistical approach. Perturbation of glutamate uptake produced significant effects on metabolic flux through the Krebs cycle, and on glutamate/glutamine cycling rates, with this effect accounting for 76% of the variation in the total data set. The effects of all inhibitors were separable from each other along three major principal components. The competitive inhibitor L-CCG III ((2S,1'S,2'R)-2-carboxycyclopropyl)glycine) differed most from the other inhibitors, showing negative weightings on both the first and second principal components, whereas the EAAT2-specific inhibitor dihydrokainate (DHK) showed metabolic patterns similar to that of anti-endo-3,4-methanopyrolidine dicarboxylate but separate from those of DL-threo-beta-benzyloxyaspartate (TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (L-tPDC). This indicates that different inhibition mechanisms or different colocalisation of the separate transporter subtypes with glutamate receptors can produce significantly different metabolic and functional outcomes for the brain.

Animals↗
PubMed1979

Individualizing gentamicin dosage regimens in burn patients with gram-negative septicemia: a cost--benefit analysis.

Services provided by a clinical pharmacokinetics laboratory were evaluated in terms of an accepted cost--benefit model, and a model to evaluate clinical services provided by the pharmacist is presented. A retrospective study was conducted to evaluate the impact, in terms of patient outcomes, of individualizing gentamicin dosage regimens in severely burned patients. Analysis was conducted using multivariate statistical techniques and appropriate nonparametric and parametric tests to determine significant differences. This analysis provided the necessary data to quantify the impact of the pharmacokinetic service. The findings suggest that significant differences do exist in comparing individually dosed patients against those who were not, based upon discriminant and multiple regression analyses and/or nonparametric tests. Furthermore, the results will be useful for insurance companies, third-party payers, and government agencies in deciding which innovative clinical services should be reimbursed.

Burns↗
PubMed1995

Molecular topology and quantum chemical descriptors in the study of reversed-phase liquid chromatography. Hydrogen-bonding behavior of chalcones and flavanones.

The reversed-phase liquid chromatographic hydrophobicity parameters (log K'w and S) of several chalcones and flavanones were determined with methanol:water mobile phases of different compositions and with trace quantities of n-decylamine and 1-octanol added to the eluent to minimize the silanophilic interactions present in alkylsilane-bonded phases. It has been reported that qualitative hydrogen bonding information can be obtained from the relationship between S and log K'w determined with these chromatographic conditions. To quantitatively describe the hydrogen-bonding discrimination effects observed for the compounds under study, the parameter delta was defined as follows: delta(s-log kw) = S-log K'w. With topological and molecular orbital calculations, several molecular descriptors were computed for test compounds, and multivariate statistical techniques were used to examine the informative value of the parameter proposed. The results obtained indicate that delta(s-log Kw) encodes structural information mainly related to the molecular polarity and the ability of compounds to participate in hydrogen-bonding interactions. Similar structural information was also obtained for delta(s-log Kw) values of 31 structurally dissimilar compounds.

Aniline Compounds↗
PubMed2003

PLS-ANN based classification model for oral submucous fibrosis and oral carcinogenesis.

BACKGROUND AND OBJECTIVES: For effective management of oral neoplasia, autofluorescence spectroscopy was conducted on patients with different characteristics of oral lesions in vivo. This study tested the possibility of using a multivariate statistical algorithm to differentiate human oral premalignant and malignant lesions from benign lesions or normal oral mucosa. STUDY DESIGN/MATERIALS AND METHODS: A fiber optics-based fluorospectrometer was used to measure the autofluorescence spectra from healthy volunteers (NOM) and patients with oral lesions of submucous fibrosis (OSF), epithelial hyperkeratosis (EH), epithelial dysplasia (ED), and squamous cell carcinoma (SCC). A partial least-squares and artificial neural network (PLS-ANN) classification algorithm was used to characterize these oral lesions to discriminate premalignant (ED) and malignant (SCC) tissues from "benign" (NOM, OSF, and EH) tissues. RESULTS: The normalized and centerized spectra of the different kinds of samples showed similar but divergent patterns. Our PLS-ANN classification algorithm could differentiate "premalignant and malignant" tissues from "benign" tissues with a sensitivity of 81%, a specificity of 96%, and a positive predictive value of 88%. CONCLUSIONS: We conclude that the PLS-ANN classification algorithm based on autofluorescence spectroscopy at 330-nm excitation is useful for in vivo diagnosis of OSF as well as oral premalignant and malignant lesions.

Algorithms↗
PubMed2000

Antidepressant treatment for depression: total charges and therapy duration*

BACKGROUND: The economic costs of depression are significant, both the direct medical costs of care and the indirect costs of lost productivity. Empirical studies of antidepressant cost-effectiveness suggest that the use of selective serotonin reuptake inhibitors (SSRIs) may be no more costly than tricyclic antidepressants (TCAs), will improve tolerability, and is associated with longer therapy duration. However the success of depression care usually involves multiple factors, including source of care, type of care, and patient characteristics, in addition to drug choice. The cost-effective mix of antidepressant therapy components is unclear. AIMS OF THE STUDY: Our study evaluates cost and antidepressant-continuity outcomes for depressed patients receiving antidepressant therapy. Specifically, we determined the impact of provider choice for initial care, concurrent psychotherapy, and choice of SSRI versus TCA-based pharmacotherapies on the joint outcome of low treatment cost and continuous antidepressant therapy. METHODS: A database of private health insurance claims identifies 2678 patients who received both a diagnosis of depression and a prescription for an antidepressant during 1990-1994. Patients each fall into one of four groups according to whether their health care charges are high versus low (using the median value as the break point) and by whether their antidepressant usage pattern is continuous versus having discontinued pharmacotherapy early (filling fewer than six prescriptions). A bivariate probit model controlling for patient characteristics, co-morbidities, type of depression and concurrent treatment is the primary multivariate statistical vehicle for the cost-effective treatment situation. RESULTS: SSRIs substantially reduce the incidence of patients discontinuing pharmacotherapy while leaving charges largely unchanged. The relative effectiveness of SSRIs in depression treatment is independent of the patient's personal characteristics and dominates the consequences of other treatment dimensions such as seeing a mental health specialist and receiving concurrent psychotherapy. Initial provider specialty is irrelevant to the continuity of pharmacotherapy, and concurrent psychotherapy creates a tradeoff through reduced pharmacotherapy interruption with higher costs. DISCUSSION: Longer therapy duration is associated with SSRI-based pharmacotherapy (relative to TCA-based pharmacotherapy) and with concurrent psychotherapy. High cost is associated with concurrent psychotherapy and choice of a specialty provider for initial care. In our study cost-effective care includes SSRI-based pharmacotherapy initiated with a non-specialty provider. Previous treatment history and other unobserved factors that might affect antidepressant choice are not included in our model. IMPLICATIONS FOR HEALTH CARE PROVISION: The decision to use an SSRI-based pharmacotherapy need not consider carefully the patient's personal characteristics. Shifting depressed patients' pharmacotherapy away from TCAs to SSRIs has the effect of improving outcomes by lowering the incidence of discontinuation of pharmacotherapy while leaving largely unchanged the likelihood of having high overall health care charges. Targeted use of concurrent psychotherapy may be additionally cost-effective. IMPLICATIONS FOR HEALTH POLICIES: The interaction of various components of depression care can alter the cost-effectiveness of antidepressant therapy. Our results demonstrate a role for the non-specialty provider in initiating care and support increased use of SSRIs as first-line therapy for depression as a way of providing cost-effective care that is consistent with APA guidelines for continuous antidepressant treatment. IMPLICATIONS FOR FURTHER RESEARCH: Further research that improves our understanding of how decisions regarding provider choice, concurrent psychotherapy, and drug choice are made will improve our understanding of the effects treatment choices on the cost-effectiveness of depression care. We have suggested that targeted concurrent psychotherapy may prove to be cost-effective; research to determine groups most likely to benefit from the additional treatment would further enable clinicians and healthcare policy makers to form a consensus regarding a model for treating depression.

Journal Article↗
PubMed2001

Survival trends of childhood cancer diagnosed during 1970-1994 in Piedmont, Italy: a report from the Childhood Cancer Registry.

BACKGROUND: The Childhood Cancer Registry of Piedmont (CCRP) started its activity in 1967. It is population based and covers the Piedmont Region (population 4,500,000; NW Italy). This article reports on time trends in survival after a childhood cancer diagnosed during 1970-1994. PROCEDURE: During 1970-1994, 2,329 incident cases were registered at CCRP on the basis of histological and/or clinical information, excluding 30 cases reported only by death certificate. Histological or hematological diagnosis was available for 2,067 cases. Vital status was assessed through the offices of the town of residence. At the end of follow-up, 1,202 cases were alive, 1,084 dead and 43 were not traceable. Survival was measured for the major diagnostic groups using both univariate and multivariate statistics. RESULTS: The 5-yr survival rate for acute lymphoblastic leukemia (ALL) improved regularly from 24.7% in 1970-1974 to 81.1% in 1990-1994, for acute nonlymphoblastic leukemia (ANLL) from 0% to 38.1%, for non-Hodgkin lymphoma (NHL) from 25.2% to 67.7%, for tumors of the central nervous system (CNS) (all types) from 33.4% to 75.9% and for Ewing tumor from 0% to 90%. Focusing on survival by period of diagnosis, the highest 5-year survival rate was observed for children diagnosed during 1985-1989 for medulloblastoma, neuroblastoma (NB), retinoblastoma, Wilms tumor, osteosarcoma, and rhabdomyosarcoma and for children diagnosed in 1990-1994 for the remaining sites. The trend over time was statistically significant for ALL, ANLL, NHL, CNS tumors, NB, and osteosarcoma as well as for all malignancies together. CONCLUSIONS: Population-based survival studies are useful complements to clinical studies. Survival results in the present study are similar to those presented for other European countries and the United States. For most types of neoplasm (except CNS) survival probability appears to stabilize 5-10 years after diagnosis.

Adolescent↗
PubMed1988

Prognostic factors in 281 children with nonmetastatic rhabdomyosarcoma (RMS) at diagnosis.

Pretreatment characteristics of 281 children with nonmetastatic rhabdomyosarcoma, included in the registry of the International Society of Pediatric Oncology (SIOP) between January 1975 and December 1983, were examined to study the children's prognosis. The multivariate statistical method (Cox regression model) was used for each of two endpoints: survival time and disease-free time. The three most important predictors for survival time were primary site (p less than .001), clinical stage (p = .009), and sex (p = .020). The best results involved paratesticular and orbital primary sites, regardless of the clinical stage; males fared slightly better than females. These same three factors were also significant predictors for disease-free time.

Adolescent↗
PubMed2003

Novel nonparametric approach to canonical correlation analysis with applications to low CNR functional MRI data.

Detection of activation in functional MRI (fMRI) is often complicated by the low contrast-to-noise ratio (CNR) in the data. The primary source of the difficulty is the fact that for activities that are subtle the signal can be hidden inside the inherent noise in the data. Classical univariate methods based on t-test or F-test are susceptible to noise, as they fail to harness systematic correlations in evoked responses within neighboring voxels. Here the power of a multivariate statistical analysis tool known as canonical correlation analysis (CCA) in fMRI studies is demonstrated where the CNR is low. As a further illustration of the power of the method, a comparative study of CCA and ordinary correlation analysis using simulated data under various noise levels is also performed. A novel nonparametric approach is introduced to calculate the P-values from the distribution of the complicated test statistic. The circumstances under which CCA is a better performer as well as when it is not the case are discussed. As an example, this method is applied to detect hippocampal activation from memory-related tasks.

Adult↗