An analysis of variance type method to describe and compare steady states in clinical data

Identifying and comparing different steady states is an important task for clinical decision making. Data from unequal sources, comprising diverse patient status information, have to be interpreted. In order to compare results an expressive representation is the key. In this contribution we suggest a criterion to calculate a context-sensitive value based on variance analysis and discuss its advantages and limitations referring to a clinical data example obtained during anesthesia. Different drug plasma target levels of the anesthetic propofol were preset to reach and maintain clinically desirable steady state conditions with target controlled infusion (TCI). At the same time systolic blood pressure was monitored, depth of anesthesia was recorded using the bispectral index (BIS) and propofol plasma concentrations were determined in venous blood samples. The presented analysis of variance (ANOVA) is used to quantify how accurately steady states can be monitored and compared using the three methods of measurement.

In vitro drug causality assessment in Stevens-Johnson syndrome - alternatives for lymphocyte transformation test

BACKGROUND Patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are often exposed simultaneously to a few potentially culprit drugs. However, both the standard lymphocyte transformation tests (LTT) with proliferation as the assay end-point as well as skin tests, if done, are often negative. OBJECTIVE As provocation tests are considered too dangerous, there is an urgent need to identify the relevant drug in SJS/TEN and to improve sensitivity of tests able to identify the causative drug. METHODS Fifteen patients with SJS/TEN with the ALDEN score ≥ 6 and 18 drug-exposed controls were included. Peripheral blood mononuclear cells (PBMC) were isolated and cultured under defined conditions with drugs. LTT was compared to the following end-points: cytokine levels in cell culture supernatant, number of granzyme B secreting cells by ELISpot and intracellular staining for granulysin and IFNγ in CD3(+) CD4(+), CD3(+) CD8(+) and NKp46(+) cells. To further enhance sensitivity, the effect of IL-7/IL-15 pre-incubation of PBMC was evaluated. RESULTS Lymphocyte transformation tests was positive in only 4/15 patients (sensitivity 27%, CI: 8-55%). Similarly, with granzyme B-ELISpot culprit drugs were positive in 5/15 patients (sensitivity 33%, CI: 12-62%). The expression of granulysin was significantly induced in NKp46(+) and CD3(+) CD4(+) cells (sensitivity 40%, CI: 16-68% and 53%, CI: 27-79% respectively). Cytokine production could be demonstrated in 38%, CI: 14-68% and 43%, CI: 18-71% of patients for IL-2 and IL-5, respectively, and in 55%, CI: 23-83% for IFNγ. Pre-incubation with IL-7/IL-15 enhanced drug-specific response only in a few patients. Specificities of tested assays were in the range of 95 (CI: 80-99%)-100% (CI: 90-100%). CONCLUSIONS AND CLINICAL RELEVANCE Granulysin expression in CD3(+) CD4(+) , Granzyme B-ELISpot and IFNγ production considered together provided a sensitivity of 80% (CI: 52-96%) and specificity of 95% (80-99%). Thus, this study demonstrated that combining different assays may be a feasible approach to identify the causative drug of SJS/TEN reactions; however, confirmation on another group of patients is necessary.

Variance estimation in ranked set sampling using a concomitant variable

We propose a nonparametric variance estimator when ranked set sampling (RSS) and judgment post stratification (JPS) are applied by measuring a concomitant variable. Our proposed estimator is obtained by conditioning on observed concomitant values and using nonparametric kernel regression.

Serum Testosterone Levels and Symptom-Based Depression Subtypes in Men

The main objective of this preliminary study was to further clarify the association between testosterone (T) levels and depression by investigating symptom-based depression subtypes in a sample of 64 men. The data were taken from the ZInEP epidemiology survey. Gonadal hormones of a melancholic (n  = 25) and an atypical (n = 14) depression subtype, derived from latent class analysis, were compared with those of healthy controls (n  = 18). Serum T was assayed using an enzyme-linked immunosorbent assay procedure. Analysis of variance, analysis of covariance, non-parametrical tests, and generalized linear regression models were performed to examine group differences. The atypical depressive subtype showed significantly lower T levels compared with the melancholic depressives. While accumulative evidence indicates that, beyond psychosocial characteristics, the melancholic and atypical depressive subtypes are also distinguishable by biological correlates, the current study expanded this knowledge to include gonadal hormones. Further longitudinal research is warranted to disclose causality by linking the multiple processes in pathogenesis of depression.

An exploratory analysis of variance and volatility in epileptic electroencephalograms

The electroencephalogram (EEG) is a physiological time series that measures electrical activity at different locations in the brain, and plays an important role in epilepsy research. Exploring the variance and/or volatility may yield insights for seizure prediction, seizure detection and seizure propagation/dynamics.^ Maximal Overlap Discrete Wavelet Transforms (MODWTs) and ARMA-GARCH models were used to determine variance and volatility characteristics of 66 channels for different states of an epileptic EEG – sleep, awake, sleep-to-awake and seizure. The wavelet variances, changes in wavelet variances and volatility half-lives for the four states were compared for possible differences between seizure and non-seizure channels.^ The half-lives of two of the three seizure channels were found to be shorter than all of the non-seizure channels, based on 95% CIs for the pre-seizure and awake signals. No discernible patterns were found the wavelet variances of the change points for the different signals. ^

Oxygen variance and meridional oxygen supply in the Tropical North East Atlantic oxygen minimum zone

The distribution of the mean oceanic oxygen concentration results from a balance between ventilation and consumption. In the eastern tropical Pacific and Atlantic, this balance creates extended oxygen minimum zones (OMZ) at intermediate depth. Here, we analyze hydrographic and velocity data from shipboard and moored observations, which were taken along the 23°W meridian cutting through the Tropical North East Atlantic (TNEA) OMZ, to study the distribution and generation of oxygen variability. By applying the extended Osborn-Cox model, the respective role of mesoscale stirring and diapycnal mixing in producing enhanced oxygen variability, found at the southern and upper boundary of the OMZ, is quantified. From the well-ventilated equatorial region toward the OMZ core a northward eddy-driven oxygen flux is observed whose divergence corresponds to an oxygen supply of about 2.4 µmol kg-1 year-1 at the OMZ core depth. Above the OMZ core, mesoscale eddies act to redistribute low- and high-oxygen waters associated with westward and eastward currents, respectively. Here, absolute values of the local oxygen supply >10 mmol kg-1 year-1 are found, likely balanced by mean zonal advection. Combining our results with recent studies, a refined oxygen budget for the TNEA OMZ is derived. Eddy-driven meridional oxygen supply contributes more than 50 % of the supply required to balance the estimated oxygen consumption. The oxygen tendency in the OMZ, as given by the multidecadal oxygen decline, is maximum slightly above the OMZ core and represents a substantial imbalance of the oxygen budget reaching about 20 % of the magnitude of the eddy-driven oxygen supply.

Causality Relationships between Total Exports with Agricultural and Manufacturing GDP in Tanzania

This paper, investigates causal relationships among agriculture, manufacturing and export in Tanzania by using time series data for the period between 1970 and 2005. The empirical results show in both sectors there is Granger causality where agriculture causes both exports and manufacturing. Exports also cause both agricultural GDP and manufacturing GDP and any two variables out of three jointly cause the third one. There is also some evidence that manufacturing does not cause export and agriculture. Regarding cointegration, pairwise agricultural GDP and export are cointegrated, export and manufacture are cointegrated. Agriculture and manufacture are cointegrated but they are lag sensitive. However, three variables, manufacturing, export and agriculture both together are cointegrated showing that they share long run relation and this has important economic implications.

Olfactory fMRI Connectivity Analysis Based on Granger Causality with Application in Anosmia Assessment

In this work, we describe hubs organization within the olfactory network with Functional Magnetic Resonance Imaging (fMRI). Granger causality analyses were applied in the supposed regions of interest (ROIs) involved in olfactory tasks, as described in [1]. We aim to get deeper knowledge about the hierarchy of the regions within the olfactory network and to describe which of these regions, in terms of strength of the connectivity, impair in different types of anosmia.

Patterns of variance in stage-structured populations: Evolutionary predictions and ecological implications

Variability in population growth rate is thought to have negative consequences for organism fitness. Theory for matrix population models predicts that variance in population growth rate should be the sum of the variance in each matrix entry times the squared sensitivity term for that matrix entry. I analyzed the stage-specific demography of 30 field populations from 17 published studies for pattern between the variance of a demographic term and its contribution to population growth. There were no instances in which a matrix entry both was highly variable and had a large effect on population growth rate; instead, correlations between estimates of temporal variance in a term and contribution to population growth (sensitivity or elasticity) were overwhelmingly negative. In addition, survivorship or growth sensitivities or elasticities always exceeded those of fecundity, implying that the former two terms always contributed more to population growth rate. These results suggest that variable life history stages tend to contribute relatively little to population growth rates because natural selection may alter life histories to minimize stages with both high sensitivity and high variation.

Age-specific inbreeding depression and components of genetic variance in relation to the evolution of senescence.

Two major theories of the evolution of senescence (mutation accumulation and antagonistic pleiotropy) make different predictions about the relationships between age, inbreeding effects, and the magnitude of genetic variance components of life-history components. We show that, under mutation accumulation, inbreeding decline and three major components of genetic variance are expected to increase with age in randomly mating populations. Under the simplest version of the antagonistic pleiotropy model, no changes in the severity of inbreeding decline, dominance variance, or the genetic variance of chromosomal homozygotes are expected, but additive genetic variance may increase with age. Age-specific survival rates and mating success were measured on virgin males, using lines extracted from a population of Drosophila melanogaster. For both traits, inbreeding decline and several components of genetic variance increase with age. The results are consistent with the mutation accumulation model, but can only be explained by antagonistic pleiotropy if there is a general tendency for an increase with age in the size of allelic effects on these life-history traits.

Does Trait Emotional Intelligence Predict Unique Variance in Early Career Success Beyond IQ and Personality?

In order to determine the contribution of emotional intelligence (EI) to career success, in this study, we analyzed the relationship between trait EI (TEI), general mental ability (GMA), the big five personality traits, and career success indicators, in a sample of 130 graduates who were in the early stages of their careers. Results from hierarchical regression analyses indicated that TEI, and especially its dimension “repair,” has incremental validity in predicting one of the career success indicators (salary) after controlling for GMA and personality. These findings provide support for the use of TEI measures as predictors of career success in the early stage.

Effects of Interspecific Gene Flow on the Phenotypic Variance-Covariance Matrix in Lake Victoria Cichlids

Quantitative genetics theory predicts adaptive evolution to be constrained along evolutionary lines of least resistance. In theory, hybridization and subsequent interspecific gene flow may however rapidly change the evolutionary constraints of a population and eventually change its evolutionary potential, but empirical evidence is still scarce. Using closely related species pairs of Lake Victoria cichlids sampled from four different islands with different levels of interspecific gene flow, we tested for potential effects of introgressive hybridization on phenotypic evolution in wild populations. We found that these effects differed among our study species. Constraints measured as the eccentricity of phenotypic variance-covariance matrices declined significantly with increasing gene flow in the less abundant species for matrices that have a diverged line of least resistance. In contrast we find no such decline for the more abundant species. Overall our results suggest that hybridization can change the underlying phenotypic variance-covariance matrix, potentially increasing the adaptive potential of such populations.