Once daily dosing of netilmicin in neonatal and pediatric intensive care

OBJECTIVE: To examine a once daily dosing regimen of netilmicin in critically ill neonates and children. DESIGN AND SETTING: Open, prospective study on 81 antibiotic courses in 77 critically ill neonates and children, hospitalized in a multidisciplinary pediatric/neonatal intensive care unit. For combined empiric therapy (aminoglycoside and beta-lactam), netilmicin was given intravenously over 5 min once every 24 h. The dose ranged from 3.5-6 mg/kg, mainly depending upon gestational and postnatal age. Peak levels were determined by immunoassay 30 min after the second dose and trough levels 1 h before the third and fifth dose or after adaptation of dosing. RESULTS: All peak levels (n = 28) were clearly above 12 mumol/l (mean 22, range 13-41 mumol/l). Eighty-nine trough levels were within desired limits (< 4 mumol/l) and 11 (11%) above 4 mumol/l, mostly in conjunction with impaired renal function. CONCLUSIONS: Optimal peak and trough levels of netilmicin can be achieved by once daily dosing, adapted to gestational/postnatal age and renal function.

Drivers of nitrogen leaching from organic layers in Central European beech forests

Background and Aims: The response of forest ecosystems to continuous nitrogen (N) deposition is still uncertain. We investigated imports and exports of dissolved N from mull-type organic layers to identify the controls of N leaching in Central European beech forests under continuous N deposition. Methods: Dissolved N fluxes with throughfall and through mull-type organic layers (litter leachate) were measured continuously in 12 beech forests on calcareous soil in two regions in Germany over three consecutive growing seasons. Results Mean growing season net (i.e. litter leachate – throughfall flux) fluxes of total dissolved N (TDN) from the organic layer were low (2.3 ± 5.6 kg ha −1 ) but varied widely from 12.9 kg ha −1 to –8.3 kg ha −1 . The small increase of dissolved N fluxes during the water passage through mull-type organic layers suggested that high turnover rates coincided with high microbial N assimilation and plant N uptake. Stand basal area had a positive feedback on N fluxes by providing litter for soil organic matter forma- tion. Plant diversity, especially herb diversity, reduced dissolved N fluxes. Soil fauna biomass increased NO3−-N fluxes with litter leachate by stimulating mineralization. Microbial biomass measures were not related to dissolved N fluxes. Conclusions Our results show that dissolved N exports from organic layers contain significant amounts of throughfall-derived N (mainly NO3−-N) that flushes through the organic layer but also highlight that N leaching from organic layers is driven by the complex interplay of plants, animals and microbes. Furthermore, diverse understories reduce N leaching from Central European beech forests.

LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases

BACKGROUND Niemann-Pick type C (NP-C) is a rare progressive neurodegenerative lipid storage disorder with heterogeneous clinical presentation and challenging diagnostic procedures. Recently oxysterols have been reported to be specific biomarkers for NP-C but knowledge on the intra-individual variation and on reference intervals in children and adolescents are lacking. METHODS We established a LC-MS/MS assay to measure Cholestane-3β, 5α, 6β-triol (C-triol) and 7-Ketocholesterol (7-KC) following Steglich esterification. To assess reference intervals and intra-individual variation we determined oxysterols in 148 children and adolescents from 0 to 18 years and repeat measurements in 19 of them. RESULTS The reported method is linear (r>0.99), sensitive (detection limit of 0.03 ng/mL [0.07 nM] for C-triol, and 0.54 ng/mL [1.35 nM] for 7-KC) and precise, with an intra-day imprecision of 4.8% and 4.1%, and an inter-day imprecision of 7.0% and 11.0% for C-triol (28 ng/ml, 67 nM) and 7-KC (32 ng/ml, 80 nM), respectively. Recoveries for 7-KC and C-triol range between 93% and 107%. The upper reference limit obtained for C-triol is 40.4 ng/mL (95% CI: 26.4-61.7 ng/mL, 96.0 nM, 95% CI: 62.8-146.7 nM) and 75.0 ng/mL for 7-KC (95% CI: 55.5-102.5 ng/mL, 187.2 nM, 95% CI: 138.53-255.8 nM), with no age or gender dependency. Both oxysterols have a broad intra-individual variation of 46%±23% for C-triol and 52%±29% for 7-KC. Nevertheless, all Niemann-Pick patients showed increased C-triol levels including Niemann-Pick type A and B patients. CONCLUSIONS The LC-MS/MS assay is a robust assay to quantify C-triol and 7-KC in plasma with well documented reference intervals in children and adolescents to screen for NP-C in the pediatric population. In addition our results suggest that especially the C-triol is a biomarker for all three Niemann-Pick diseases.

Las subculturas e "ideologías" informáticas, barreras para la educación innovadora sobre tecnologías de la información

Al presentar mi ponencia (1) en un seminario que sobre el tema de este Simposio organizó el CREI meses pasados, dije que el problema global de la educación en informática es un asunto Multidisciplinar, que exige tomar en cuenta simultáneamente por lo menos ocho factores, 1) el retraso del aprendizaje, 2) la complejidad general de las sociedades tecnificadas, 3) la evolución y complejidad de la informática, 4) las insuficiencias intrínsecas multidimensionales de la informática, 5) la presión de la industria informática, 6) el sistema cultural informático predominante, 7) el sistema educativo y, 8) la presión de los especialistas y diletantes. Los cinco primeros factores son universales, es decir, operan indistintamente en cualquier lugar, y los tres últimos son locales. Precisamente, el documento de la ponencia se proponía trazar un marco general del problema,para situarlo en términos lo más alejados posibles del simplismo mecánico habitual, qué no percibe más que una realidad reducida. A posteriori, se vió que el alcance y la densidad del documento habrían requerido más debate y más desarrollo escrito, lo que podía haberse presumido considerando la fuerza de los factores, 3, 5, 6 y 8.

Functional Hierarchy of Simultaneously Expressed Adhesion Receptors: Integrin α2β1 but Not CD44 Mediates MV3 Melanoma Cell Migration and Matrix Reorganization within Three-dimensional Hyaluronan-containing Collagen MatricesV⃞

Haptokinetic cell migration across surfaces is mediated by adhesion receptors including β1 integrins and CD44 providing adhesion to extracellular matrix (ECM) ligands such as collagen and hyaluronan (HA), respectively. Little is known, however, about how such different receptor systems synergize for cell migration through three-dimensionally (3-D) interconnected ECM ligands. In highly motile human MV3 melanoma cells, both β1 integrins and CD44 are abundantly expressed, support migration across collagen and HA, respectively, and are deposited upon migration, whereas only β1 integrins but not CD44 redistribute to focal adhesions. In 3-D collagen lattices in the presence or absence of HA and cross-linking chondroitin sulfate, MV3 cell migration and associated functions such as polarization and matrix reorganization were blocked by anti-β1 and anti-α2 integrin mAbs, whereas mAbs blocking CD44, α3, α5, α6, or αv integrins showed no effect. With use of highly sensitive time-lapse videomicroscopy and computer-assisted cell tracking techniques, promigratory functions of CD44 were excluded. 1) Addition of HA did not increase the migratory cell population or its migration velocity, 2) blocking of the HA-binding Hermes-1 epitope did not affect migration, and 3) impaired migration after blocking or activation of β1 integrins was not restored via CD44. Because α2β1-mediated migration was neither synergized nor replaced by CD44–HA interactions, we conclude that the biophysical properties of 3-D multicomponent ECM impose more restricted molecular functions of adhesion receptors, thereby differing from haptokinetic migration across surfaces.

Circular[s] of information.

Circulars of information, no. 1, 1887; nos. 1-4, 7, 1888; nos. 1,3, 1889; no. 1, 1890; nos. 1, 4-6, 1891; nos. 2-3, 5-6, 1893; nos. 1-2, 1894; nos. 1-3, 1898; nos. 1-3, 1899; nos. 1-4, 1900; nos. 1-4, 1902; nos. 1-3, 1903, are issued also as Contributions of American educational history, nos. [1-]36, respectively.

Joh. Frid. Wilh. de Neumann ... Meditationes juris principum privati, de jure personarum illustrium earumque ministris, praemittitur notitia scriptorum juris principum privati

T.II: De matrimoniis principum commentatio. - T.III: De patria potestate et tutela principum commentatio. - IV: Reale principium jus sive De dominio et servitute, pignore et hypotheca ... - V: De hereditatibus et successionibus principum commentatio. - VI: De pactis et contractibus principum commentatio . - VII: De delictis et poenis principum commentatio. - VIII: De processu judiciario in causis principum commentatio. - IX: Supplementa

Collections of the New Hampshire historical society.

List of members in v. 3, 5-6. 8.

Columbia University contributions to philosophy and psychology.

Volume numbers irregular: v. 14, no. 3 repeated; v. 15, no. 1 omitted; v. 16, no. 1 called v. [blank] no. 4; v. 17, no. 4 called v. 17, no. 3; v. 10, no. 1 [a] called v. 18, no. 1; v. 23 omitted.

Shakespeare-vorträge,

Includes complete German translations of Hamlet, Macbeth, Romeo and Juliet, Othello, King Lear, and Richard III, partial translations of the other plays.

Journal of agriculture: comprising the transactions and the correspondence of the United States Agricultural Society.

The Monthly bulletin, which forms a part of v.6, 1858, has its own numbering, v.1, no. 1-11.