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Familial syndrome patterns in schizophrenia, schizoaffective disorder, mania, and depression.

A major problem with studies in the field of quantitative genetics is that of phenotypical heterogeneity. In particular, such heterogeneities show up in psychiatric investigations: index cases often tend to display more severe forms of disorders than the respective affected relatives. The principal goal of the present investigation was to test the phenotypical equivalence of the two populations of index cases and their affected relatives. Our analyses were based on 269 hospitalized patients with functional psychoses and 350 affected first degree relatives. As opposed to the majority of earlier investigations in which phenotypes were uniquely defined by diagnoses, phenotypes were represented in this study by a list of 22 psychiatric syndromes. Accordingly, multivariate statistical procedures were applied to analyze the intrinsic properties of the empirical lists. The results showed that typical syndrome patterns clearly appeared in both populations and that the phenotypical equivalence of the corresponding population sample sets lay between satisfactory and good. Furthermore, it was possible to select phenotypically homogeneous and reproducible subsets on the basis of the 22 syndromes. These subgroups can be used as basic material to study the genetic modes via current models from quantitative genetics. Nevertheless, our analyses revealed no clear breeding true of either affective disorders or schizophrenia.

Bipolar Disorder↗

Pharmacogenetics of phenylethylamine: determination of heritability and genetic transmission of locomotor effects in recombinant inbred strains of mice.

beta-Phenylethylamine (PEA) is an amphetamine-like compound that is postulated to be a possible endogenous psychotogen. We studied locomotor response to PEA in two inbred progenitor strains of mice (C57BL/6 By and BALB/c By), their reciprocal F1 hybrids (B6CF1 and CB6F1), and seven recombinant inbred strains (CXBD, CXBE, CXBG, CXBH, CXBI, CXGJ, and CXBK). Univariate and multivariate statistical analyses were done. Heritability of the response to PEA was 82%. The strain distribution pattern was suggestive of the inheritance of the trait through a single major gene locus.

Animals↗

Depression among Puerto Ricans in New York City: the Hispanic Health and Nutrition Examination Survey.

This study was conducted to analyze determinants of depression among Puerto Ricans by replicating and expanding earlier studies of depression among Cuban Americans and Mexican Americans. Data from the Hispanic Health and Nutrition Examination Survey, 1982-1984, were employed to examine depression and associated characteristics among Puerto Ricans. We utilized descriptive and multivariate statistics to examine the Center for Epidemiologic Studies Depression Scale (CES-D)-assessed depressive symptomatology and the DSM-III/DIS specification of major depression. The findings indicated that CES-D-assessed depressive symptomatology among Puerto Ricans was associated with female gender, disrupted marital status, poor health, and lower socioeconomic status as indicated by low education, low household income, age, and unemployment. For both 6-month and 1-month DIS major depression, age, disrupted marital status, and income of less than $5,000 were significant risk factors. For 6-month DIS major depression, never married persons had a higher risk for depression. For 1-month diagnoses, writing Spanish better than English was associated with lower risk. In general, our findings for Puerto Ricans were similar to studies of depression among other Hispanic groups. We remained unable to explain the relatively extreme levels of depression among Puerto Ricans in New York, though several probable explanations are elaborated. We emphasized the general need to expand the range of research designs and current risk models in epidemiology in an effort to capture the complexity of psychosocial and cultural processes relevant to psychological distress.

Acculturation↗

Taxonomy of Penicillium nalgiovense isolates from mould-fermented sausages.

A large number of Penicillium nalgiovense isolates from mould fermented sausages and the ex type culture were examined for characters of morphology, physiology and production of secondary metabolites. To separate biotypes within the P. nalgiovense species, the data obtained were evaluated using multivariate statistical methods. The macromorphological characters of the ex type culture and isolates from meat products appeared to be distinctive. The ex type culture is characterized by a brown reverse on both Czapek yeast extract and malt extract agar while the isolates from meat products have a yellow to orange reverse. Proteolytic and/or lipolytic activity was demonstrated by 75% of the examined cultures and all of them demonstrated ability to utilize lactate as sole carbon source. Growth on creatine sucrose agar was very inhibited and acid production was absent or very weak. TLC analysis showed production of three unknown secondary metabolites that constituted the characteristic profile. HPLC analysis showed production of only three known secondary metabolites; chrysogine (96%), nalgiolaxin and nalgiovensin (9%). The ex type culture produced nalgiolaxin and nalgiovensin but not chrysogine. The chemometric evaluation showed that P. nalgiovense isolates from meat products from a homogenous species, which can not be divided into biotypes. The only indication of grouping, beside a separation of the ex type culture, was related to the conidium colour (white, turquoise or grey green). The examined P. nalgiovense isolates showed some resemblance (morphologically and chemically) to P. chrysogenum.

Chromatography, High Pressure Liquid↗

Generality of test-session observations to kindergarteners' classroom behavior.

Test observations are integral components in the comprehensive assessment of children's academic talents and personal adjustment. They are used to validate standardized test scores obtained during test sessions and to draw inferences about children's general pattern of learning and social adjustment. Unfortunately, little empirical justification exists for extending inferences beyond the confines of test sessions. This issue was examined with 155 kindergarten children using the Stanford Binet Observation Schedule (SBOS), a popular instrument for the summative integration of test-session observations. Children's ratings on the SBOS were used to estimate teacher-observed behavior on the Guide to the Child's Learning Style (GCLS). SBOS and GCLS scores were subjected to independent principal components analyses with varimax rotation and, thereafter, to a joint canonical variance analysis. Weighted factor composites from two SBOS dimensions constituted the predictor data set and three GCLS dimensions the criterion data set. Although multivariate statistical significance was achieved (lambda = .834, F(6,200) = 3.18, p less than .005), cannonical redundancy showed merely 9.4% of classroom behavior predictable from test-session. Results are examined in light of research on the situational specificity of behavior.

Achievement↗

[Prediction of local recurrences after surgery of carcinoma of the middle reticulum (author's transl)].

On the basis of completely and exactly documented follow-up data of 237 patients on whom carcinomas of the middle rectum were resected for cure, a multivariate statistical model was developed and the corresponding parameters were calculated. With this model the individual risk of local recurrences can be estimated after anterior resection with a small margin of clearance (11-30 mm on the fresh specimen without stretching), after anterior resection with a wide margin of clearance (more than 30 mm), and after excision of the rectum. Seven prognostic factors are taken into consideration that can be determined pre- and intraoperatively. Estimations of the risk of local recurrences on the basis of observed and documented follow-up data can be used as decisive factor for differential indication between restorative and excisional surgery on future patients. After anterior resection the risk of local recurrences is calculated according to macroscopic findings on the specimen and to frozen section histology. If the risks in anterior resection and excision are approximately equal, the resection is ended by anastomosis; otherwise the operation will be extended to excision of the rectum. This statistical model enables the surgeon to select the proper operative procedure for each individual situation (histology- and stage-adapted surgery).

Humans↗

Characteristics of users of syringe vending machines in Berlin.

Vending machines providing sterile injection equipment are part of the AIDS prevention measures for injecting drug users (IDU) in Berlin. A study was carried out to assess characteristics (history of iv drug use, frequency of use of the machines, contact with counselling units for IDU, attitudes towards the machines, HIV serostatus) in users of syringe vending machines. Of the 313 individuals surveyed, 77% reported using the vending machines regularly (more than four times a week). Compared to other studies of IDU in Berlin (eg at syringe exchange programmes) the users of the vending machines had a significantly shorter history of iv drug use. Overall, 72% of the IDU had had contacts at some time with specialised agencies for counselling on drug abuse and AIDS; however, only 33% had such contacts currently. Sixty-five percent of the IDU commented critically on the machines or made suggestions for improvement; 18% had experienced that the machines did not always work well, 14% called for more machines. HIV seroprevalence based on self-reported test results (N = 252) was 20%. In multivariate statistical analysis positive HIV serostatus was associated with site of interview, longer history of intravenous drug use, and current contact with counselling agencies. Despite the ready availability of syringes and needles, 25% of the participants reported borrowing injection equipment from other IDU in the previous six months. This proportion was significantly higher in IDU younger than 25 years (39%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

The risks of reoperation for prosthetic valve dysfunction.

A retrospective study was conducted on 124 patients who underwent re-replacement of previously implanted prosthetic heart valves for structural valve failure, prosthetic valve endocarditis, periprosthetic leak, a thrombosed valve, hemolysis, or prophylactic removal. In total, 85% of the explanted valves were bioprostheses, and 70% of the newly implanted valves were mechanical valves. The overall operative mortality rate was 8.1%, being 3.2% of 95 single valve recipients and 25.0% of 28 double valve recipients (P < 0.001). The overall mortality rate dropped from 13.6% of 66 patients before 1988, to 1.7% of 58 patients encountered in the last 3 years (P < 0.02). Since 1988, a third of the patients have undergone reoperation without homologous blood transfusion. A univariate analysis revealed eight operative risk factors, namely: higher values of preoperative blood urea nitrogen or total bilirubin, double valve replacement at the redo operation, NYHA class IV, urgency of reoperation, a duration of implantation of less than 3 months, reoperation in the earlier period of this study, and reexploration for bleeding or cardiac tamponade after re-replacement surgery. A multivariate statistical analysis demonstrated that preoperative blood urea nitrogen, urgency of reoperation, double valve replacement, and the duration of implantation were independent risk factors. Thus, we recommend that surgery be performed early, before the occurrence of other organ failure induced by congestive heart failure due to any form of valve dysfunction.

Adolescent↗

Results of a Program to Control Phosphorus Discharges from Dairy Operations in South-Central Florida, USA

During 1987-1992, a mandatory program to control phosphorus discharges was implemented at dairy operations located to the north of Lake Okeechobee, Florida, USA. Thirty of 48 dairies participated in this program and implemented best management practices (BMPs), which included the construction of intensive animal waste management systems. Eighteen dairies closed their milk-producing operations under a government-funded buyout program. In this paper, we compare trends in runoff total phosphorus (TP) concentrations among the dairies that remained active and implemented BMPs. A central feature of the dairy waste management system is the high intensity area (HIA), defined as the milking barn and adjacent vegetation-free land, encircled by a drainage ditch and dike. Animal waste from the HIA is diverted into anaerobic lagoons and storage ponds, from which water is periodically removed and used for irrigation of field crops. The impacts of BMP construction on runoff TP concentrations were immediate and, in most cases, dramatic. Average TP concentrations declined significantly (P<0.001), from 9.0 to 1.2 mg TP liter-1 at dairies in one basin (Lower Kissimmee River), and from 2.6 to 1.0 mg TP liter-1 in another (Taylor Creek/Nubbin Slough). Some sites experienced greater declines in TP than others. To elucidate possible causes for the difference in response, a multivariate statistical model was utilized. Independent variables included soil pH, soil drainage characteristics, spodic horizon depth, and the areas of different BMP components (pasture, HIA, spray fields). The analysis significantly separated dairies with the highest and lowest runoff TP concentrations. Lowest TP occurred at dairies having particular soil characteristic (shallow spodic horizon) and certain BMP features (large HIA and small heard pastures).

Journal Article↗

GABAergic neurons in the barrel cortex of the mouse: an analysis using neuronal archetypes.

We describe the morphological types of glutamic acid decarboxylase (GAD) immunoreactive cells in the barrel cortex of the mouse. A method is introduced and applied, which combines qualitative and quantitative criteria to classify these cells through the use of multivariate statistics. With the aid of an interactive computer microscope, 2010 GAD-positive neurons were harvested. Each cell was assigned to one of a set of qualitatively defined classes (archetypes) and further characterized by various morphometric parameters. Through the statistical analysis, new sets of hierarchically ordered archetypes were inferred; these served to classify cells which, due to lack of morphological detail, were unclassifiable using qualitative criteria only. We here report on the characteristics of eight archetypes of GAD-positive neurons, distinguished by means of their size, shape, and orientation and the distribution of their cell bodies over the cortical layers. Some archetypes were observed mostly in the upper layers of the cortex (group I triangular and group I horizontal fusiform cells), others mostly in the lower layers (group II triangular and group II horizontal fusiform cells). Bulb and vertical fusiform, as well as vertical star and horizontal star cells, were present throughout the entire cortical thickness. The star cells formed the two most frequent archetypes. This classification constitutes a baseline which we currently use to elucidate whether differences exist in the birthdates among the GABAergic archetypes within each layer of the mouse barrel cortex.

Animals↗

Evolution of the amino acid substitution in the mammalian myoglobin gene.

Multivariate statistical analyses were applied to 16 physical and chemical properties of amino acids. Four of these properties; volume, polarity, isoelectric point (charge), and hydrophobicity were found to explain adequately 96% of the total variance of amino acid attributes. Using these four quantitative measures of amino acid properties, a structural discriminate function in the form of a weighted difference sum of squares equation was developed. The discriminate function is weighted by the location of each particular residue within a given tertiary structure and yields a numerical discriminate or difference value for the replacement of these residues by different amino acids. This resulting discriminate value represents an expression of the perturbation in the local positional environment of a protein when an amino acid substitution occurs. With the use of this structural discriminate function, a residue by residue comparison of the known mammalian myoglobin sequences was carried out in an attempt to elucidate the positions of possible deviations from the known tertiary structure of sperm whale myoglobin. Only 11 of the 153 residue positions in myoglobin demonstrated possible structural deviations. From this analysis, indices of difference were calculated for all amino acid exchanges between the various myoglobins. All comparisons yielded indices of difference that were considerably lower than would be expected if mutations had been fixed at random, even if the organization of the genetic code is taken into consideration. On the basis of these results, it is inferred that some form of selection has acted in the evolution of mammalian myoglobins to favor amino acid substitutions that are compatible with the retention of the original conformation of the protein.

Amino Acid Sequence↗

Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma.

The purpose of this study was to determine immunological parameters in the peripheral blood that correlate with the clinical effect of interleukin-2 (IL-2) in patients with metastatic renal cell cancer. A group of 26 patients with metastatic renal cell cancer underwent IL-2 treatment using a 36-day schedule with continuous intravenous IL-2 infusion (3 x 10(6) units m-2 day-1) administered from days 1 to 5 and days 12 to 16. The white blood cell count and the absolute and relative number of neutrophils, lymphocytes, eosinophils and monocytes were recorded six times in peripheral blood during the treatment. Also the blood counts of T cell and NK cell subsets and cells expressing the T cell activation markers IL-2R alpha and VLA-1 were measured. The lymphokine-activated killer (LAK) cell cytotoxicity was measured either with or without additional in vitro stimulation by IL-2. Multivariate statistical analysis showed that the clinical responses were related to the administered dose of IL-2, to a low number of blood cells expressing IL-2 receptors and to a reduction in the blood monocyte count (P less than 0.05).

Adult↗

Progesterone receptor activity and relapse-free survival in patients with primary breast cancer: the role of adjuvant chemotherapy.

The prognostic significance of progesterone receptor activity (PgR) with regard to the estimated relapse-free survival (RFS) was studied in 350 one-center patients with primary breast cancer. All receptor assays were performed in one laboratory; PgR levels greater than 10 fmol/mg protein were considered positive. Univariate as well as multivariate statistical analyses were used to examine the prognostic significance of several variables. Eighty-nine of the 350 patients received adjuvant CMF chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil). The median observation period was 69 months (range 12-125 months). In the group of 261 patients who did not receive adjuvant CMF, the PgR-status lacked prognostic significance; only the lymph node status significantly affected the RFS (p less than 0.00001). In contrast, in the CMF-treated group of patients, the PgR-status was the most powerful predictor of recurrence (p less than 0.001). Premenopausal CMF-treated patients with PgR+ tumors had a significantly longer RFS than those with PgR- tumors (p less than 0.02). The present data urge the need for a reappraisal of the prognostic significance of PgR and of the mechanism of action of adjuvant chemotherapy in primary breast cancer.

Analysis of Variance↗

Nuclear DNA content and prognosis in human breast cancer: a static cytophotometric study.

Nuclear DNA content was measured by static cytophotometry in smears from breast carcinomas from 80 women, and the results were correlated with other prognostic variables and survival using multivariate statistical analysis. 49% of patients had diploid tumors and 51% hyperdiploid tumors. There was a strong correlation between DNA ploidy and axillary lymph node status, tumor size, ER status, and short term survival (median follow-up 40 months). Of all parameters measured, ploidy showed the strongest correlation with survival, and was a significant prognostic indicator even when other prognostic factors were taken into account.

Age Factors↗

Immunohistochemical reaction to human milk fat globule antibodies and breast cancer differentiation.

Immunohistochemical studies of human breast cancers using human milk fat globule (HMFG) antibodies are divergent regarding the association with histologic differentiation. To clarify this association 392 tumors were assessed using two antibodies, HMFG-1 and HMFG-2. In half the tumors studied the tissue reaction to both antibodies was the same and in 63% the site of reaction was identical. Using both univariate and multivariate statistics, a highly significant association was recorded between membrane staining and well differentiated cancers and cytoplasmic staining and poor differentiation. Well differentiated tumors contained significantly more reactive cells. Complementing these findings was the association between age at diagnosis, tumor stage, and estrogen receptor status and differentiation. It is possible that immunohistochemical analysis with HMFG antibodies will provide better characterization of tumor differentiation than morphologic interpretation.

Antibodies↗

Strategies for analyzing nutritional data for epidemiological purposes--conceptual framework.

The relation between nutritional factors and health investigated in epidemiological studies are often inconsistent. One of the reasons for such findings can be the improper addressing of the multitude of nutritional dimensions in the specific study situation such as physiological individuality of human beings, different living conditions, or numerous interdependencies between nutritional variables. Epidemiological research in nutrition and health should recognize such facts and work with appropriate study models and adequate data analyses. Instead of investigating heterogeneous populations it is advisable to concentrate on specific "types" of people. Under consideration of the study goals such "types" can be compiled according to physiological properties, e.g., cholesterol sensitivity, or biological-constitutional factors such as body build, life-style entities, or other factors. The variety of nutrition factors far beyond the commonly applied nutrient values can be expressed in integrated indices of "food patterns". Such "food patterns" can be derived in many ways. They can be deduced from theories by using specific criteria, but also explored by modern multivariate statistical analyses. The ways leading to "food patterns" are discussed. The ideas presented and discussed in this paper lead to an improved model for research in the field of nutrition and health with integrated indices of "food patterns" as the critical point. It is assumed that using this approach will generate new insight in the relation of nutrition and health, a currently still diffuse research area.

Eating↗

Characteristic views of prokaryotic 50S ribosomal subunits.

Multivariate statistical analysis and classification techniques are powerful tools in sorting noisy electron micrographs of single particles according to their principal features, enabling one to form average images with an enhanced signal-to-noise ratio and a better reproducible resolution. We apply this methodology here to determining the characteristic views of the large (50S) ribosomal subunits from the eubacterium Escherichia coli and the archaebacteria Methanococcus vannielii, Sulfolobus solfataricus, and Halobacterium marismortui. Average images were obtained of the subunit in the common crown and kidney projections, but views of the particle in orientations intermediate between these two extremes were also elucidated for all species. These averages show reproducible detail of up to 2.0 nm resolution, thus enabling the visualization and interspecies comparison of many structural features as a first step toward comparing the actual three-dimensional structures. Our results disprove evolutionary lineages recently postulated on the basis of electron microscopical images of ribosomal subunits.

Archaea↗

Interrelatedness of 5S RNA sequences investigated by correspondence analysis.

Correspondence analysis (a form of multivariate statistics) applied to 74 5S ribosomal RNA sequences indicates that the sequences are interrelated in a systematic, nonrandom fashion. Aligned sequences are represented as vectors in a 5N-dimensional space, where N is the number of base positions in the 5S RNA molecule. Mutually orthogonal directions (called factor axes) along which intersequence variance is greatest are defined in this hyperspace. Projection of the sequences onto planes defined by these factorial directions reveals clustering of species that is suggestive of phylogenetic relationships. For each factorial direction, correspondence analysis points to regions of "importance," i.e., those base positions at which the systematic changes occur that define that particular direction. In effect, the technique provides a rapid determination of group-specific signatures. In several instances, similarities between sequences are indicated that have only recently been inferred from visual base-to-base comparisons. These results suggest that correspondence analysis may provide a valuable starting point from which to uncover the patterns of change underlying the evolution of a macromolecule, such as 5S RNA.

Analysis of Variance↗