Prospective determination of imipenem concentration of the plasma of critically-ill children

ABSTRACT Imipenem plasma-concentrations were measured in 19 critically-ill children (median 0.8 year, range 0.02-12.9 years). Wide inter-individual variations (2-4x at peak and >10x at through concentrations) resulted in unpredictable plasma-levels in several children. To avoid subtherapeutic drug levels we recommend at least 100 mg/kg/day of imipenem-cilastatin in critically-ill children requiring such therapy.

Small, stable shuttle vectors based on the minimal pVS1 replicon for use in gram-negative, plant-associated bacteria.

The minimal replicon of the Pseudomonas plasmid pVS1 was genetically defined and combined with the Escherichia coli p15A replicon, to provide a series of new, oligocopy cloning vectors (5.3 to 8.3 kb). Recombinant plasmids derived from these vectors were stable in growing and nongrowing cells of root-colonizing P. fluorescens strains incubated under different environmental conditions for more than 1 month.

Organic and Nitrogen Fertilization of Soil under ‘Syrah’ Grapevine: Effects on Soil Chemical Properties and Nitrate Concentration

ABSTRACT Viticulture is an activity of great social and economic importance in the lower-middle region of the São Francisco River valley in northeastern Brazil. In this region, the fertility of soils under vineyards is generally poor. To assess the effects of organic and nitrogen fertilization on chemical properties and nitrate concentrations in an Argissolo Vermelho-Amarelo (Typic Plinthustalf), a field experiment was carried out in Petrolina, Pernambuco, on Syrah grapevines. Treatments consisted of two rates of organic fertilizer (0 and 30 m3 ha-1) and five N rates (0, 10, 20, 40, and 80 kg ha-1), in a randomized block design arranged in split plots, with five replications. The organic fertilizer levels represented the main plots and the N levels, the subplots. The source of N was urea and the source of organic fertilizer was goat manure. Irrigation was applied through a drip system and N by fertigation. At the end of the third growing season, soil chemical properties were determined and nitrate concentration in the soil solution (extracted by porous cups) was determined. Organic fertilization increased organic matter, pH, EC, P, K, Ca, Mg, Mn, sum of bases, base saturation, and CEC, but decreased exchangeable Cu concentration in the soil by complexation of Cu in the organic matter. Organic fertilization raised the nitrate concentration in the 0.20-0.40 m soil layer, making it leachable. Nitrate concentration in the soil increased as N rates increased, up to more than 300 mg kg-1 in soil and nearly 800 mg L-1 in the soil solution, becoming prone to leaching losses.

Extraction and concentration of vapors from fire debris for forensic purposes: evaluation of the use of Radiello Passive Air Sampler

The Radiello Passive Air Sampler is one of the latest innovations developed for the sampling of pollutants in the air by passive headspace. It has been reported that its properties allow an enhanced sensitivity, reproducibility and adsorption capacity. It therefore appears to be of interest in the extraction of potential residues of ignitable liquids present in fire debris when arson is suspected. A theoretical approach and several laboratory tests have made it possible to precisely characterize in a forensic perspective the potential of the device in extracting and concentrating the vapors of ignitable liquids found in fire debris. Despite some advantages, the Radiello device appears to be less efficient than traditional axial symmetry samplers.

The geographical concentration of industry across Spanish Regions, 1856-1995

New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later

Minimal analytical characterisation of engineered nanomaterials need for hazard assessment in biological matrices

The safe and responsible development of engineered nanomaterials (ENM), nanotechnology-based materials and products, together with the definition of regulatory measures and implementation of "nano"-legislation in Europe require a widely supported scientific basis and sufficient high quality data upon which to base decisions. At the very core of such a scientific basis is a general agreement on key issues related to risk assessment of ENMs which encompass the key parameters to characterise ENMs, appropriate methods of analysis and best approach to express the effect of ENMs in widely accepted dose response toxicity tests. The following major conclusions were drawn: Due to high batch variability of ENMs characteristics of commercially available and to a lesser degree laboratory made ENMs it is not possible to make general statements regarding the toxicity resulting from exposure to ENMs. 1) Concomitant with using the OECD priority list of ENMs, other criteria for selection of ENMs like relevance for mechanistic (scientific) studies or risk assessment-based studies, widespread availability (and thus high expected volumes of use) or consumer concern (route of consumer exposure depending on application) could be helpful. The OECD priority list is focussing on validity of OECD tests. Therefore source material will be first in scope for testing. However for risk assessment it is much more relevant to have toxicity data from material as present in products/matrices to which men and environment are be exposed. 2) For most, if not all characteristics of ENMs, standardized methods analytical methods, though not necessarily validated, are available. Generally these methods are only able to determine one single characteristic and some of them can be rather expensive. Practically, it is currently not feasible to fully characterise ENMs. Many techniques that are available to measure the same nanomaterial characteristic produce contrasting results (e.g. reported sizes of ENMs). It was recommended that at least two complementary techniques should be employed to determine a metric of ENMs. The first great challenge is to prioritise metrics which are relevant in the assessment of biological dose response relations and to develop analytical methods for characterising ENMs in biological matrices. It was generally agreed that one metric is not sufficient to describe fully ENMs. 3) Characterisation of ENMs in biological matrices starts with sample preparation. It was concluded that there currently is no standard approach/protocol for sample preparation to control agglomeration/aggregation and (re)dispersion. It was recommended harmonization should be initiated and that exchange of protocols should take place. The precise methods used to disperse ENMs should be specifically, yet succinctly described within the experimental section of a publication. 4) ENMs need to be characterised in the matrix as it is presented to the test system (in vitro/ in vivo). 5) Alternative approaches (e.g. biological or in silico systems) for the characterisation of ENMS are simply not possible with the current knowledge. Contributors: Iseult Lynch, Hans Marvin, Kenneth Dawson, Markus Berges, Diane Braguer, Hugh J. Byrne, Alan Casey, Gordon Chambers, Martin Clift, Giuliano Elia1, Teresa F. Fernandes, Lise Fjellsbø, Peter Hatto, Lucienne Juillerat, Christoph Klein, Wolfgang Kreyling, Carmen Nickel1, and Vicki Stone.

Growth rate of fractal copper electrodeposits: Potential and concentration effects

Experiments are reported on fractal copper electrodeposits. An electrochemical cell was designed in order to obtain a potentiostatic control on the quasi-two-dimensional electrodeposition process. The aim was focused on the analysis of the growth rate of the electrodeposited phase, in particular its dependence on the electrode potential and electrolyte concentration.

Calmodulin-dependent protein kinase IV during T-cell development.

In a primary cell culture system of fetal rat brain, the calmodulin-dependent protein-kinase IV (CaMKIV) could be induced by the thyroid hormone T3 in a time- and concentration-dependent manner, provided the tissue was excised not later than day 15 of gestation (E15) (Krebs et al., J. Biol. Chem. 271, 11055, 1996). We report here that in the fetal thymus CaMKIV could not be detected earlier than day 16 of gestation and that the expression of this enzyme was fully upregulated at day 18. In mouse fetal thymus organ culture (FTOC) of day 14 embryonic thymus, CaMKIV could not be detected, even after several days of culture if a minimal culture medium lacking fetal calf serum was used. However, after addition of fetal calf serum to the culture medium the expression of CaMKIV could be specifically induced. Furthermore, it could also be shown that during T-cell development in the adult murine thymus the expression of CaMKIV was tightly regulated. Taken together, these results demonstrate that the expression of CaMKIV, an enzyme involved in the regulation of Ca(2+)-dependent gene expression, is itself under stringent regulatory control during tissue development.

The geographical concentration of industry across Spanish Regions, 1856-1995

New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later

Misleading tacrolimus concentration value in blood taken from a catheter used for tacrolimus administration.

PURPOSE: A misleading blood tacrolimus concentration (BTC) value caused by the contamination of a central venous catheter previously used for tacrolimus administration is described. SUMMARY: A 59-year-old woman with severe chronic obstructive pulmonary disease successfully underwent double lung transplantation. In the intensive care unit, she received a continuous i.v. infusion of tacrolimus from days 1 to 5 after transplantation through the distal lumen of a polyurethane triple-lumen central venous catheter. The catheter lumen was flushed twice a day with 0.9% sodium chloride injection. The proximal lumen was used for blood sampling after being flushed; the first 10 mL of blood was discarded. BTCs determined in whole blood one, four, and five days after transplantation were within the therapeutic range of 5-15 ng/mL. On day five the patient was transferred to the thoracic surgery ward and was switched to oral tacrolimus 1.5 mg twice daily. The BTC on day 6 was unexpectedly high at 134.5 ng/mL. The patient's clinical status was normal, and no signs of tacrolimus toxicity were observed. On day 7, blood samples were drawn from a peripheral vein and simultaneously through the central venous catheter. Although the central venous catheter had not been exposed to tacrolimus during the preceding two days, it yielded blood with a BTC eight times higher than the BTC in blood from the peripheral vein (41.4 ng/mL versus 5.1 ng/mL). CONCLUSION: The collection of blood from a central venous catheter lumen that had been used for tacrolimus administration resulted in a BTC about eight times higher than what was measured in peripheral blood.

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients.

BACKGROUND: We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. Materials and methods: World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS: Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION: These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

Linear relations between writhe and minimal crossing number in Conway families of ideal knots and links

We showed earlier how to predict the writhe of any rational knot or link in its ideal geometric configuration, or equivalently the average of the 3D writhe over statistical ensembles of random configurations of a given knot or link (Cerf and Stasiak 2000 Proc. Natl Acad. Sci. USA 97 3795). There is no general relation between the minimal crossing number of a knot and the writhe of its ideal geometric configuration. However, within individual families of knots linear relations between minimal crossing number and writhe were observed (Katritch et al 1996 Nature 384 142). Here we present a method that allows us to express the writhe as a linear function of the minimal crossing number within Conway families of knots and links in their ideal configuration. The slope of the lines and the shift between any two lines with the same

CYP3A7, CYP3A5, CYP3A4, and ABCB1 genetic polymorphisms, cyclosporine concentration, and dose requirement in transplant recipients.

Cyclosporine is a substrate of cytochrome P450 (CYP) 3A and of the transporter ABCB1, for which polymorphisms have been described. In particular, CYP3A5 *3/*3 genotype results in the absence of CYP3A5 activity, whereas CYP3A7 *1/*1C genotype results in high CYP3A7 expression in adults. Log-transformed dose-adjusted cyclosporine trough concentration and daily dose per weight were compared 1, 3, 6, and 12 months after transplantation between CYP3A and ABCB1 genotypes in 73 renal (n = 64) or lung (n = 9) transplant recipients. CYP3A5 expressors (*1/*3 genotype; n = 8-10) presented significantly lower dose-adjusted cyclosporine trough concentrations (P < 0.05) and required significantly higher daily doses per weight (P < 0.01) than the nonexpressors (*3/*3 genotype; n = 55-59) 1, 3, 6, and 12 months after transplantation. In addition, 7 days after transplantation, more CYP3A5 expressors had uncorrected trough cyclosporine concentration below the target concentration of 200 ng/mL than the nonexpressors (odds ratio = 7.2; 95% confidence interval = 1.4-37.3; P = 0.009). CYP3A4 rs4646437C>T influenced cyclosporine kinetics, the T carriers requiring higher cyclosporine dose. CYP3A7*1C carriers required a 1.4-fold to 1.6-fold higher cyclosporine daily dose during the first year after transplantation (P < 0.05). In conclusion, CYP3A4, CYP3A5, and CYP3A7 polymorphisms affect cyclosporine metabolism, and therefore, their genotyping could be useful, in association with therapeutic drug monitoring, to prospectively optimize cyclosporine prescription in transplant recipients. The administration of a CYP3A genotype-dependent cyclosporine starting dose should therefore be tested prospectively in a randomized controlled clinical trial to assess whether it leads to an improvement of the patients outcome after transplantation, with adequate immunosuppression and decreased toxicity.