Pattern Detection in Intensive Care Monitoring Time Series with Autoregressive Models: Influence of the Model Order

The detection of patterns in monitoring data of vital signs is of great importance for adequate bedside decision support in critical care. Currently used alarm systems, which are based on fixed thresholds and independency assumptions, are not satisfactory in clinical practice. Time series techniques such as AR‐models consider autocorrelations within the series, which can be used for pattern recognition in the data. For practical applications in intensive care the data analysis has to be automated. An important issue is the suitable choice of the model order which is difficult to accomplish online. In a comparative case‐study we analyzed 34564 univariate time series of hemodynamic variables in critically ill patients by autoregressive models of different orders and compared the results of pattern detection. AR(2)‐models seem to be most suitable for the detection of clinically relevant patterns, thus affirming that treating the data as independent leads to false alarms. Moreover, using AR(2)‐models affords only short estimation periods. These findings for pattern detection in intensive care data are of medical importance as they justify a preselection of a model order, easing further automated statistical online analysis.     

Morphology of the adhesive tail tips of carphodactyline geckos (Reptilia: Diplodactylidae)

Members of the carphodactyline gekkonoid genera Naultinus, Hoplodactylus, Bavayia, Eurydactylodes, Rhacodactylus, and Pseudothecadactylus possess tails that are both prehensile and adhesive. In New Caledonian and Australian species of this group, the adhesive apparatus forms a discrete and grossly observable scansorial pad. The caudal scansorial system appears to show a phylogenetic trend towards increasing complexity. The caudal scansors closely parallel the subdigital scansors in surface morphology and bear branched setae and mechanoreceptive sensillae. Internal morphology also resembles that of the toe, although a tendinous system is absent and the mechanism of pressurization of the vascular network of the tail tip remains unclear. Despite obvious differences in basic organization of tails and toes, the caudal and digital scansors in these taxa appear to be iterative homologues of one another. J. Morphol. 235:41–58, 1998. © 1998 Wiley-Liss, Inc.     

Protein phosphatase 2A in stretch-induced endothelial cell proliferation

We previously proposed that activation of protein kinase C is a key mechanism for control of cell growth enhanced by cyclic strain [Rosales and Sumpio (1992): Surgery 112:459–466]. Here we examined protein phosphatase 1 and 2A activity in bovine aortic endothelial cells exposed to cyclic strain. Protein phosphatase 2A activity in the cytosol was decreased by 36.1% in response to cyclic strain for 60 min, whereas the activity in the membrane did not change. Treatment with low concentration (0.1 nM) of okadaic acid enhanced proliferation of both static and stretched endothelial cells in 10% fetal bovine serum. These data suggest that protein phosphatase 2A acts as a growth suppressor and cyclic strain may enhance cellular proliferation by inhibiting protein phosphatase 2A as well as stimulating protein kinase C. © 1996 Wiley-Liss, Inc.     

Mechanisms of suicidal erythrocyte death.

Erythrocyte injury such as osmotic shock, oxidative stress or energy depletion stimulates the formation of prostaglandin E2 through activation of cyclooxygenase which in turn activates a Ca2+ permeable cation channel. Increasing cytosolic Ca2+ concentrations activate Ca2+ sensitive K+ channels leading to hyperpolarization, subsequent loss of KCl and (further) cell shrinkage. Ca2+ further stimulates a scramblase shifting phosphatidylserine from the inner to the outer cell membrane. The scramblase is sensitized for the effects of Ca2+ by ceramide which is formed by a sphingomyelinase following several stressors including osmotic shock. The sphingomyelinase is activated by platelet activating factor PAF which is released by activation of phospholipase A2. Phosphatidylserine at the erythrocyte surface is recognised by macrophages which engulf and degrade the affected cells. Moreover, phosphatidylserine exposing erythrocytes may adhere to the vascular wall and thus interfere with microcirculation. Erythrocyte shrinkage and phosphatidylserine exposure ('eryptosis') mimic features of apoptosis in nucleated cells which however, involves several mechanisms lacking in erythrocytes. In kidney medulla, exposure time is usually too short to induce eryptosis despite high osmolarity. Beyond that high Cl- concentrations inhibit the cation channel and high urea concentrations the sphingomyelinase. Eryptosis is inhibited by erythropoietin which thus extends the life span of circulating erythrocytes. Several conditions trigger premature eryptosis thus favouring the development of anemia. On the other hand, eryptosis may be a mechanism of defective erythrocytes to escape hemolysis. Beyond their significance for erythrocyte survival and death the mechanisms involved in 'eryptosis' may similarly contribute to apoptosis of nucleated cells.     

Individual Distinctiveness and Possible Function of Song Parts of Short-toed Treecreepers (Certhia brachydactyla). Evidence from Multivariate Song Analysis

Sonagram analyses of short-toed treecreeper (= STT) song by use of discriminant analysis revealed consistent individuality in the songs predominantly sung by each male (P-songs). The P-songs had been digitized and over 30 song variables were used in the analysis to separate different individuals. In the end, 7 of these variables were needed for a correct classification of 100% of the 203 P-songs recorded of 39 individuals in 1986. Most of these variables were derived from the first part of the song. A similar analysis with data from 1987 showed that by use of all variables with unskewed distribution complete discrimination of all 271 P-songs of 47 individuals ensued. The reduction of variables to the 10 most important led to the correct classifications of 99.5%. Using the 7 best discriminators of the 1986 data set 94.2% of the 1987 data were correctly classified, thus confirming the 1986 results. Wrong assignments were mainly due to P-songs from second or third recording dates which in some cases could not be separated from other P-songs of the same males by the analysis. Further analysis of the data showed that although the most important discriminators were found in the first part of the song, the combination of all characters of the end part would also allow for a virtually complete discrimination of individuals. The song features of STT P-song are so distinctive that territory holders should have no difficulties in separating individuals (e.g. neighbours from strangers). Corresponding playback experiments have yet to be carried out on STT.     

Silver and Gold Nanoparticles Exposure to In Vitro Cultured Retina – Studies on Nanoparticle Internalization,Apoptosis, Oxidative Stress,Glial- and Microglial Activity

The complex network of neuronal cells in the retina makes it a potential target of neuronal toxicity – a risk factor for visual loss. With growing use of nanoparticles (NPs) in commercial and medical applications, including ophthalmology, there is a need for reliable models for early prediction of NP toxicity in the eye and retina. Metal NPs, such as gold and silver, gain much of attention in the ophthalmology community due to their potential to cross the barriers of the eye. Here, NP uptake and signs of toxicity were investigated after exposure to 20 and 80 nm Ag- and AuNPs, using an in vitro tissue culture model of the mouse retina. The model offers long-term preservation of retinal cell types, numbers and morphology and is a controlled system for delivery of NPs, using serum-free defined culture medium. AgNO₃-treatment was used as control for toxicity caused by silver ions. These end-points were studied; gross morphological organization, glial activity, microglial activity, level of apoptosis and oxidative stress, which are all well described as signs of insult to neural tissue. TEM analysis demonstrated cellular- and nuclear uptake of all NP types in all neuronal layers of the retina. Htx-eosin staining showed morphological disruption of the normal complex layered retinal structure, vacuole formation and pyknotic cells after exposure to all Ag- and AuNPs. Significantly higher numbers of apoptotic cells as well as an increased number of oxidative stressed cells demonstrated NP-related neuronal toxicity. NPs also caused increased glial staining and microglial cell activation, typical hallmarks of neural tissue insult. This study demonstrates that low concentrations of 20 and 80 nm sized Ag- and AuNPs have adverse effects on the retina, using an organotypic retina culture model. Our results motivate careful assessment of candidate NP, metallic or-non-metallic, to be used in neural systems for therapeutic approaches.     

Influence of organically or conventionally produced wheat on health, performance and mycotoxin residues in tissues and bile of growing pigs

From 1999-2001 three different varieties of wheat [Contur (susceptible to Fusarium), Batis and Petrus (less susceptible to Fusarium)] were cultivated under organic and conventional conditions in order to determine mycotoxin burden. Soil quality, preceding crop and weather conditions were comparable in the different production systems. The wheat batches were analysed for moulds, and the contents of zearalenone (ZEN) and deoxynivalenol (DON). Feeding trials were carried out with growing pigs (n = 96; average initial live weight 22.2 +/- 1.5 kg [mean +/- SD]) to examine a possible influence on the animal performance and on mycotoxin residues. The data recorded were clinical conditions, performance, biochemical and hematological data. Residues of ZEN, alpha- and beta-zearalenol (ZEL) and of DON were determined in bile, liver and muscle after slaughtering. Conventionally cultivated wheat was more frequently contaminated with Fusarium and contained more frequently ZEN and DON in higher concentrations than the organically produced wheat. Hematological and biochemical parameters of pigs fed with organically cultivated diets were not different from those of conventionally fed pigs. Pigs fed with organically produced wheat showed a slightly higher daily weight gain, but a lower carcass yield than the conventionally fed animals. The highest residues of DON and total-ZEN (ZEN + alpha-ZEL + beta-ZEL) were found in bile. Bile samples of organically fed pigs contained lower concentrations of total-ZEN than those of conventionally fed pigs. Altogether, these data suggest that wheat from an organic farming does not have higher mycotoxin-contamination than wheat from the conventional farming system.     

Susceptibility to neoplastic and non-neoplastic pulmonary diseases in mice: genetic similarities

Chronic inflammation predisposes toward many types of cancer. Chronic bronchitis and asthma, for example, heighten the risk of lung cancer. Exactly which inflammatory mediators (e.g., oxidant species and growth factors) and lung wound repair processes (e.g., proangiogenic factors) enhance pulmonary neoplastic development is not clear. One approach to uncover the most relevant biochemical and physiological pathways is to identify genes underlying susceptibilities to inflammation and to cancer development at the same anatomic site. Mice develop lung adenocarcinomas similar in histology, molecular characteristics, and histogenesis to this most common human lung cancer subtype. Over two dozen loci, called Pas or pulmonary adenoma susceptibility, Par or pulmonary adenoma resistance, and Sluc or susceptibility to lung cancer genes, regulate differential lung tumor susceptibility among inbred mouse strains as assigned by QTL (quantitative trait locus) mapping. Chromosomal sites that determine responsiveness to proinflammatory pneumotoxicants such as ozone (O3), particulates, and hyperoxia have also been mapped in mice. For example, susceptibility QTLs have been identified on chromosomes 17 and 11 for O3-induced inflammation (Inf1, Inf2), O3-induced acute lung injury (Aliq3, Aliq1), and sulfate-associated particulates. Sites within the human and mouse genomes for asthma and COPD phenotypes have also been delineated. It is of great interest that several susceptibility loci for mouse lung neoplasia also contain susceptibility genes for toxicant-induced lung injury and inflammation and are homologous to several human asthma loci. These QTLs are described herein, candidate genes are suggested within these sites, and experimental evidence that inflammation enhances lung tumor development is provided.