CC and CXC chemokine levels in children with meningococcal sepsis accurately predict mortality and disease severity

INTRODUCTION: Chemokines are a superfamily of small peptides involved in leukocyte chemotaxis and in the induction of cytokines in a wide range of infectious diseases. Little is known about their role in meningococcal sepsis in children and their relationship with disease severity and outcome. METHODS: Monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP) 1α, growth-related gene product (GRO)-α and interleukin (IL)-8 were measured in 58 children with meningococcal sepsis or septic shock on admission and 24 hours thereafter. Nine patients died. Serum chemokine levels of survivors and nonsurvivors were compared, and the chemokine levels were correlated with prognostic disease severity scores and various laboratory parameters. RESULTS: Extremely high levels of all chemokines were measured in the children's acute-phase sera. These levels were significantly higher in nonsurvivors compared with survivors and in patients with septic shock compared with patients with sepsis (P < 0.0001). The cutoff values of 65,407 pg/ml, 85,427 pg/ml and 460 pg/ml for monocyte chemoattractant protein, for IL-8 and for macrophage inflammatory protein 1α, respectively, all had 100% sensitivity and 94–98% specificity for nonsurvival. Chemokine levels correlated better with disease outcome and severity than tumor necrosis factor (TNF)-α and correlated similarly to interleukin (IL)-6. In available samples 24 hours after admission, a dramatic decrease of chemokine levels was seen. CONCLUSION: Initial-phase serum levels of chemokines in patients with meningococcal sepsis can predict mortality and can correlate strongly with disease severity. Chemokines may play a key role in the pathophysiology of meningococcal disease and are potentially new targets for therapeutic approaches

Biophysical interactions in tropical agroforestry systems

sequential systems, simultaneous systems Abstract. The rate and extent to which biophysical resources are captured and utilized by the components of an agroforestry system are determined by the nature and intensity of interac-tions between the components. The net effect of these interactions is often determined by the influence of the tree component on the other component(s) and/or on the overall system, and is expressed in terms of such quantifiable responses as soil fertility changes, microclimate modification, resource (water, nutrients, and light) availability and utilization, pest and disease incidence, and allelopathy. The paper reviews such manifestations of biophysical interactions in major simultaneous (e.g., hedgerow intercropping and trees on croplands) and sequential (e.g., planted tree fallows) agroforestry systems. In hedgerow intercropping (HI), the hedge/crop interactions are dominated by soil fertility improvement and competition for growth resources. Higher crop yields in HI than in sole cropping are noted mostly in inherently fertile soils in humid and subhumid tropics, and are caused by large fertility improvement relative to the effects of competition. But, yield increases are rare in semiarid tropics and infertile acid soils because fertility improvement does not offse

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

The analysis of EDTA (ethylenediaminetetraacetic acid) in water by HPLC

Abstract niet beschikbaarThis report describes the development of a method for the determination of ethylenediaminetetraacetic aced (EDTA) in various types of water at low mug/L level. After a short sample pretreatment the sample is analyzed using reversedphase ion-pair liquid chromatography. UV absorbance detection is applied at 254 nm. The method is suitable to determine EDTA in surface water, bank filtrate, infiltrated water and fineshed drinking water. The method is simple (short sample pretreatment) and has a low limit of detection (0.8 mug/L). In general, the method provides calibration curves which have good regression characteristics (correlation coefficient > 0.999). 31 samples from several drinking water companies have been analyzed in order to determine the concentration of EDTA.DGM/DWL-

The optimization of a method for the analysis of ditalloq-dimethyl- ammoniumchloride (DTDMAC) in water

This report describes the optimization of a method for the analysis of DTDMAC in water. After a short sample pre-treatment, the sample is injected in a HPLC-system. After separation, ion-pair formation takes place between DTDMAC and DAS, which is a fluorophore. Detection is performed fluorometrically. The method is suitable for the determination of DTDMAC in surface water, bank filtrate, infiltrated water and finished drinking water. The method is simple and sensitive (1.1 mug/L) ; the accuracy is not ideal.DGM/DWB-

The occurrence and behaviour of ditallow-dimethyl-ammoniumchloride (DTDMAC) during drinking water production

Cationic quaternary ammonium compounds are used as fabric softeners. DTDMAC, a technical product with an ecotoxicological risk for aquatic organisms, is the most well known. Ecotoxicological risk values have been determined, followed by an agreement to ban the product from fabric softeners. The quaternary ammonium compounds are highly adsorptive for anionic surfactants, particles and sediments in watersystems. This report describes research on occurrence and behaviour of DTDMAC during drinking water production and gives possible risks for public health. DTDMAC occurs in raw surface water (maximum 30 mug/l), in bankfiltrate (maximum 5 mug/l) and in finished drinking water (maximum 4.3 mug/l ; median 1.7 mug/l). The measured concentrations in drinking water do not give risks for public health. The maximum acceptable value, calculated on the basis of literature data is 0.8 mg/kg food or water. On every sampling point only two measurements were carried out, and therefore effects due to the purification processes can only be interpreted qualitatively. In general, a relatively high concentration of DTDMAC can be decreased easily (bottom passage, conventional purification steps) to a few mug's, but the compound cannot be removed completely even by ozone or activated carbon filtration. In surface water the concentrations are much higher than the negligible risk value (0.5 mug/l) for aquatic ecosystems. The actual concentration given in this report give no reason to continue the research into the meaning of DTDMAC for drinking water supplies.DGM/DWB-