Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis.

OBJECTIVE In a phase 3 trial, recombinant human activated protein C (drotrecogin alfa [activated]) significantly reduced mortality in adult patients with severe sepsis. We have now performed a preliminary analysis of the safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in pediatric patients with severe sepsis. DESIGN AND SETTING Open-label, nonrandomized, sequential, 2-part study conducted in 11 medical centers in the United States and United Kingdom. PATIENTS Eighty-three pediatric patients with severe sepsis aged term newborn (>or=38 weeks' gestation) to <18 years old. INTERVENTION In part 1, drotrecogin alfa (activated) was administered as escalating doses of 6, 12, 24, and 36 micro g/kg per hour for 6 hours for each patient (n = 21). In part 2, drotrecogin alfa (activated) was infused at a rate of 24 micro g/kg per hour for 96 hours in 62 patients. MAIN OUTCOME MEASURES Plasma clearance, plasma concentration, D-dimer, protein C, and antithrombin levels were measured, and adverse events were monitored. RESULTS The trial enrolled 83 pediatric patients with severe sepsis, aged term newborn (>or=38 weeks' gestation) to <18 years. In part 1, a dose of 24 micro g/kg per hour produced steady-state plasma concentrations of activated protein C similar to those attained in equivalently dosed adult severe sepsis patients. For all pediatric patients dosed at 24 micro g/kg per hour, the median weight-normalized clearance was 0.45 L/hour/kg and the median steady-state concentration was 51.3 ng/mL. The mean plasma half-life was 30 minutes. Weight-normalized clearance in pediatric and adult patients did not differ significantly with age or weight. D-dimer levels decreased 26% from baseline to end of infusion. Baseline levels of protein C and antithrombin increased 79% and 24%, respectively, over the 96-hour treatment period in part 2. The incidence of serious bleeding during infusion and during the entire study period was 2.4% and 4.8%, respectively. CONCLUSIONS Pediatric patients with severe sepsis manifest sepsis-induced coagulopathy including protein C deficiency comparable to that seen in adults with severe sepsis. The pharmacokinetics, pharmacodynamic effects, and safety profile of drotrecogin alfa (activated) in pediatric patients are similar to those previously published for adult patients. A large, phase 3, randomized, placebo-controlled study is ongoing to confirm these results and formally assess the safety and efficacy of drotrecogin alfa (activated) in children.
Language and Culture in Medieval Britain: The French of England c. 1100-c. 1500

With co-editors: CAROLYN COLLETTE, MARYANNE KOWALESKI, LINNE MOONEY, AD PUTTER, and DAVID TROTTER England was more widely and enduringly francophone in the middle ages than many standard accounts of its history, culture and language allow. The development of French in England, whether known as 'Anglo-Norman' or 'Anglo-French', is deeply interwoven both with medieval English and with the spectrum of Frenches, insular and continental, used within and outside the realm. As the language of nearly a thousand literary texts, of much administration, and of many professions and occupations, the French of England needs more attention than it has so far received. The essays in this volume form a new cultural history focussed round, but not confined to, the presence and interactions of French speakers, writers, readers, texts and documents in England from the eleventh to the later fifteenth century. Taking the French of England into account does not simply add new material to our existing narratives of medieval English culture, but changes them, restoring a multi-vocal, multi-cultural medieval England in all its complexity, and opening up fresh agendas for study and exploration. Contributors: HENRY BAINTON, MICHAEL BENNETT, JULIA BOFFEY, RICHARD BRITNELL, CAROLYN COLLETTE, GODFRIED CROENEN, HELEN DEEMING, STEPHANIE DOWNES, MARTHA DRIVER, MONICA H. GREEN, RICHARD INGHAM, REBECCA JUNE, MARYANNE KOWALESKI, PIERRE KUNSTMANN, FRANCOISE H. M. LE SAUX, SERGE LUSIGNAN, TIM WILLIAM MACHAN, JULIA MARVIN, BRIAN MERRILEES, RUTH NISSE, MARILYN OLIVA, W. MARK ORMROD, HEATHER PAGAN, LAURIE POSTLEWATE, JEAN-PASCAL POUZET, AD PUTTER, GEOFF RECTOR, DELBERT RUSSELL, THEA SUMMERFIELD, ANDREW TAYLOR, DAVID TROTTER, ELIZABETH M. TYLER, NICHOLAS WATSON, JOCELYN WOGAN-BROWNE, ROBERT F. YEAGER
Electrical functionalization of thermoplastic materials by cold active atmospheric plasma technology

Plasmadust® is a new technology using cold active plasma for additive metallization of different substrate materials. For electronics production, in particular Molded Interconnect Devices (MID), thermoplastic materials can be structured with copper as power electronic conductive pattern. The main advantages of Plasmadust® are the controllable process temperature range between about 90°C and 180°C, the good adhesion of the metallization, the fast process speed of about 100 mm/s and the fast growing conductor tracks with about 15 microns thickness per cycle. Plate specimens were made of PA, a thermoplastic commonly used in automotive applications, with different process parameters. Conductor tracks applied onto the substrates consist of one line with different electrical and mechanical properties according to the process temperature and process speed. Additionally, the thickness and the width of the conductor track depend on the process parameters. The setting of the process speed turns out to be an important influence on the thickness and roughness of the conductor track that can be achieved on thermoplastic substrates. The investigated combination of thermoplastic and copper shows a constant bonding performance during thermal shock testing for 1000 cycles in the range of -40°C and +125°C. An exposure to humidity heat (85% r.h / 85°C) for 500 h has only marginal effects on the adhesion of the printed structures on the thermoplastic substrates, too. This highly promising results provide the base for further investigations to achieve a sufficient ampacity related to standard chemical PCB metallization processes.
Contenido en alcaloides en semillas de poblaciones naturales de raigrás inglés del norte de España infectadas con los hongos endofitos "Neotyphodium"

Se analizo el contenido en los alcaloides lolitreno B y ergovalina en semillas de 21 poblaciones naturales de raigras ingles (Lolium perenne L. )del norte de Espana, infectadas con los hongos endofitos Neotyphodium. El nivel de infeccion medio fue de 40, 1 %, variando desde el 8 al 80 %, estando el 62 %de las poblaciones por debajo del nivel del 50 %de infeccion. El contenido medio del alcaloide lolitreno B fue de 1, 1 ppm, variando de 0, 0 a 7, 1 ppm, mientras que el contenido medio del alcaloide ergovalina fue de 13, 5 ppm, variando de 1, 0 a 36, 2 ppm. Se estudiaron las relaciones entre el nivel de infeccion y el contenido en alcaloides mediante las correlaciones de Spearman. Se encontraron correlaciones estadisticamente significativas entre el porcentaje de infeccion y el contenido en ergovalina (r =0, 59)a un nivel de significacion del 1 %. Las concentraciones mas altas de lolitreno B ydeergovalina se consideran suficientes para inducir los sindromes del «ryegrass staggers »y la «festucosis », pero debido a la diversidad de especies pratenses en los prados naturales del norte de Espana es poco probable que aparezcan estos desordenes. Sin embargo, en pastos con gran abundancia de raigras ingles infectado con hongos endofitos seria conveniente evitar que el ganado pastase las plantas espigadas, debido a que es en las semillas donde las concentraciones de alcaloides son mas altas.
399 MUTATIONS OF F110 AND C126 OF THE FORMYL PEPTIDE RECEPTOR INTERFERE WITH G-PROTEIN COUPLING AND CHEMOTAXIS.

BACKGROUND Localized aggressive periodontitis (LAgP) is a disease characterized by rapid loss of alveolar bone in teeth of otherwise healthy patients. Neutrophils from LAgP patients have been shown to exhibit diminished chemotaxis and low levels of formyl peptide receptor (FPR) surface expression. A recent study has associated LAgP with 2 polymorphisms in the FPR: 110Phe-->Ser and 126Cys-->Trp. METHODS We transfected Chinese hamster ovary cells with wtFPR, FPR-110Phe-->Ser, FPR-126Cys-->Trp, or FPR-110Phe-->Ala and determined their surface expression of FPR, their ligand binding affinity, their G-protein coupling, and their chemotaxis toward N-formyl-methionyl-leucyl-phenylalanine (FMLP). RESULTS FPR-110Phe-->Ser mutants failed to show any significant surface expression or chemotaxis toward FMLP. FPR-126Cys-->Trp mutants exhibited slightly lower than normal binding affinity, markedly lower G-protein coupling response, and markedly lower chemotaxis toward FMLP than that observed with wtFPR. We also analyzed another FPR-Phe110 mutant, FPR-110Phe-->Ala, to ascertain what the effect of mutating this residue might be in a mutant that could be expressed on the cell surface. The FPR-110Phe-->Ala mutant demonstrated markedly lower surface expression, normal ligand binding affinity, markedly lower G-protein coupling, and markedly lower chemotaxis toward FMLP. CONCLUSIONS Our data substantiate the hypothesis that the chemotactic defects observed in LAgP patients are due at least in part to molecular alterations in the FPR. The FPR-110Phe-->Ser polymorphism appears to be more defective than the FPR-126Cys-->Trp polymorphism, indicating that patients with the former polymorphism might be expected to exhibit a more severe form of aggressive periodontitis.
Television watching and risk of childhood obesity: a meta-analysis.

BACKGROUND Over the last few decades, there has been a worldwide epidemic of childhood obesity. An important step in successful prevention in paediatrics is the identification of modifiable risk factors of childhood obesity. Many studies have evaluated the associations between television (TV) watching and childhood obesity but yielded inconsistent results. METHODS To help elucidate the role of TV watching, PubMed and Embase databases were searched for published studies on associations between TV watching and childhood obesity. Random-effects models and dose-response meta-analyses were used to pool study results. RESULTS Fourteen cross-sectional studies with 24 reports containing 106 169 subjects were included in the meta-analysis. Subgroup analyses were conducted by the available characteristics of studies and participants. The multivariable-adjusted overall OR of the childhood obesity for the highest vs. the lowest time of TV watching was 1.47 [95% confidence interval (95% CI): 1.33-1.62]. A linear dose-response relationship was also found for TV watching and childhood obesity (P < 0.001), and the risk increased by 13% for each 1 h/day increment in TV watching. Subgroup analysis showed a basically consistent result with the overall analysis. The association is observed in both boys and girls (for boys, OR 1.30, 95% CI 1.16-1.45; for girls, OR 1.26, 95% CI 1.11-1.41). CONCLUSIONS our meta-analysis suggested that increased TV watching is associated with increased risk of childhood obesity. And restricting TV time and other sedentary behaviour of children may be an important public health strategy to prevent childhood obesity.
Evidence of a role for the INK4 family of cyclin‐dependent kinase inhibitors in ovarian granulosa cell tumors

Granulosa cell tumors (GCTs) of the ovary are relatively rare and account for <5% of all ovarian cancers. The molecular pathogenesis of these tumors is not well understood. We tested the hypothesis that cyclin‐dependent kinase inhibitors, specifically the inhibitors of the cyclin‐dependent kinase 4 (INK4) family, are targets for altered gene expression in GCTs. The status of RB1, INK4A, INK4B, INK4C, INK4D, and ARF in 13 adult and 2 juvenile ovarian GCTs was determined by reverse transcription–polymerase chain reaction of total RNA and exon‐specific sequencing of genomic DNA. Tumors showing loss of INK4A expression were assayed further by exon‐deletion analysis and methylation‐specific PCR. None of the juvenile tumors demonstrated altered expression, but 7/12 (58%) adult GCTs lacked expression of INK4A, INK4B, or both. In one of these cases, we noted a homozygous deletion of the INK4A locus, and in the remaining tumors we found hypermethylation of the promoter region, a mechanism that can lead to gene inactivation. These data support a role for the INK4 family of CDK inhibitors in the biology of GCTs. © 2002 Wiley‐Liss, Inc.
Early functional development of interneurons in the zebrafish olfactory bulb

In the adult olfactory bulb (OB) of vertebrates, local GABAergic interneurons (INs) mediate recurrent and lateral inhibition between the principal neurons of the OB, the mitral cells (MCs), and play pivotal roles in the processing of odor‐evoked activity patterns. The properties and functions of INs in the developing OB are, however, not well understood. We studied the functional development of INs in the OB of living zebrafish larvae 3–6 days postfertilization using anatomical techniques and in‐vivo two‐photon Ca2+ imaging. We identified MCs and INs by cell‐type‐specific expression of transgenic fluorescent markers and found that the IN : MC ratio was lower than in the adult fish. Moreover, the fraction of INs responding with Ca2+ signals to a set of natural odors was substantially lower than in adults. Odors of different chemical classes evoked overlapping patterns of Ca2+ signals that were concentrated in the center of the IN layer. The GABAA receptor agonists GABA and muscimol strongly suppressed odor responses, whereas a GABAA receptor antagonist enhanced responses and altered the spatial distribution of odor‐evoked activity. These results indicate that IN odor responses at early developmental stages are sparse and exhibit no obvious chemotopic organization. Nevertheless, GABAergic signaling is already inhibitory at early stages of OB development and strongly influences odor‐evoked activity patterns. Hence, INs already participate in the processing of odor information at very early stages of OB development even though the majority of INs emerge only at later stages.
Multi‐scale dynamics and rheology of mantle flow with plates

Fundamental issues in our understanding of plate and mantle dynamics remain unresolved, including the rheology and state of stress of plates and slabs; the coupling between plates, slabs and mantle; and the flow around slabs. To address these questions, models of global mantle flow with plates are computed using adaptive finite elements, and compared to a variety of observational constraints. The dynamically consistent instantaneous models include a composite rheology with yielding, and incorporate details of the thermal buoyancy field. Around plate boundaries, the local resolution is 1 km, which allows us to study highly detailed features in a globally consistent framework. Models that best fit plateness criteria and plate motion data have strong slabs with high stresses. We find a strong dependence of global plate motions, trench rollback, net rotation, plateness, and strain rate on the stress exponent in the nonlinear viscosity; the yield stress is found to be important only if it is smaller than the ambient convective stress. Due to strong coupling between plates, slabs, and the surrounding mantle, the presence of lower mantle anomalies affect plate motions. The flow in and around slabs, microplate motion, and trench rollback are intimately linked to the amount of yielding in the subducting slab hinge, slab morphology, and the presence of high viscosity structures in the lower mantle beneath the slab.
Classification of clouds sampled at the puy de Dôme (France) based on 10 yr of monitoring of their physicochemical properties

Abstract. Long-term monitoring of the chemical composition of clouds (73 cloud events representing 199 individual samples) sampled at the puy de Dome (pdD) station (France) was performed between 2001 and 2011. Physicochemical parameters, as well as the concentrations of the major organic and inorganic constituents, were measured and analyzed by multicomponent statistical analysis. Along with the corresponding back-trajectory plots, this allowed for distinguishing four different categories of air masses reaching the summit of the pdD: polluted, continental, marine and highly marine. The statistical analysis led to the determination of criteria (concentrations of inorganic compounds, pH) that differentiate each category of air masses. Highly marine clouds exhibited high concentrations of Na+ and Cl−; the marine category presented lower concentration of ions but more elevated pH. Finally, the two remaining clusters were classified as "continental" and "polluted"; these clusters had the second-highest and highest levels of NH4+, NO3−, and SO24−, respectively. This unique data set of cloud chemical composition is then discussed as a function of this classification. Total organic carbon (TOC) is significantly higher in polluted air masses than in the other categories, which suggests additional anthropogenic sources. Concentrations of carboxylic acids and carbonyls represent around 10% of the organic matter in all categories of air masses and are studied for their relative importance. Iron concentrations are significantly higher for polluted air masses and iron is mainly present in its oxidation state (+II) in all categories of air masses. Finally, H2O2 concentrations are much more varied in marine and highly marine clouds than in polluted clouds, which are characterized by the lowest average concentration of H2O2. This data set provides concentration ranges of main inorganic and organic compounds for modeling purposes on multiphase cloud chemistry.
Tissue distribution and persistence of arthritogenic and non-arthritogenic Eubacterium cell walls.

OBJECTIVE To study the tissue distribution and persistence of arthritogenic and non-arthritogenic Eubacterium cell walls (CWs), using arthritogenic Eubacterium aerofaciens and non-arthritogenic Eubacterium limosum. METHODS Eubacterium aerofaciens or Eubacterium limosum CW was injected into Lewis rats intraperitoneally. Inflammatory changes in the synovium and periarticular tissues were graded histologically. On days 14, 28 and 56 after the injection, the presence of CW in the liver, spleen, mesenteric lymph nodes and synovium was studied by indirect immunofluorescence. In parallel, CW-derived muramic acid in the liver and spleen was measured by gas chromatography-mass spectrometry. In addition, serum TNF-alpha, IL-1 beta and IL-10 concentrations were determined by ELISA. RESULTS Systemic injection of Eubacterium aerofaciens CW, but not of Eubacterium limosum CW, resulted in chronic arthritis. Both E. aerofaciens and E. limosum CWs were observed in the liver and spleen at all of the time points studied. In addition, Eubacterium limosum CW was present in non-arthritic synovium on day 14. It was not, however, detected in the synovium or lymph nodes on days 28 and 56, in clear contrast to the rats injected with E. aerofaciens CW. According to the analysis by gas chromatography-mass spectrometry, non-arthritogenic E. limosum CW had accumulated in the liver cells on days 14 and 28 after the injection to a greater extent than arthritogenic E. aerofaciens CW, leading to a lesser distribution in the other organs. A weak trend was observed suggesting that the production of TNF-alpha and IL-1 beta, but not of IL-10, is stimulated better by arthritogenic CW than by non-arthritogenic CW. CONCLUSION Our results indicate that non-arthritogenic CWs are handled by the rat's defence mechanisms in a different way than arthritogenic CWs. The tissue distribution and persistence of CWs play a role in arthritogenicity, but additional factors must exist to determine why the CWs of certain bacteria are arthritogenic and those of others are not.
Noncontact, high-resolution ultrasonic imaging of wood samples using coded chirp waveforms

A noncontact ultrasonic inspection technique has been developed to study the properties of wood samples in air. The system makes use of two broad bandwidth capacitive transducers, combined with signal processing techniques. A coded chirp signal was used in the current application to provide a waveform that could be postprocessed to provide sufficient sensitivity for transmission across samples of wood. It is shown in this paper that the signal-to-noise ratio (SNR) can be greatly improved using two signal recovery techniques, namely pulse compression and swept frequency multiplication (SFM). A simulation of both techniques is presented and compared to experimental data. As seen from the experimental results, it is possible to perform noncontact ultrasonic experiments to extract a range of useful information such as ring density and the presence of microcracks.
Mental retardation in African children attending paediatric neurology clinic of Kenyatta National Hospital, Nairobi, Kenya.

Etude de 89 cas etudies de 1980 a 1981. Les facteurs etiologiques sont des anomalies a la naissance (44%), des infections post-natales (19%), l'epilepsie et des origines congenitales (7% chacune), l'ictere neonatal et la deshydratation severe (3% chacun), un traumatisme (2%) et une cause indeterminee (15%). Les symptomes sont un mauvais developpement physique (56%), des problemes de comportement (24%), de mauvais resultats scolaires (10%) et des problemes de vision (10%)
Blood–Brain Transport of Thiamine Monophosphate in the Rat: A Kinetic Study In Vivo

Abstract: To calculate the kinetic parameters of thiamine monophosphate transport across the rat blood‐brain barrier in vivo, different doses of a [35S]thiamine monophosphate preparation with a specific activity of 14.8 mCi·mmol−1 were injected in the femoral vein and the radioactivity was measured in arterial femoral blood and in the cerebellum, cerebral cortex, pons, and medulla 20 s after the injection. This short experimental time was used to prevent thiamine monophosphate hydrolysis. Thiamine monophosphate was transported into the nervous tissue by a saturable mechanism. The maximal transport rate (Jmax) and the half‐saturation concentration (Km) equaled 27–39 pmol·g−1·min−1 and 2.6–4.8 μM, respectively. When compared with that of thiamine, thiamine monophosphate transport seemed to be characterized by a lower affinity and a lower maximal influx rate. At physiological plasma concentrations, thiamine monophosphate transport rate ranged from 2.06 to 4.90 pmol·g−1· min−1, thus representing a significant component of thiamine supply to nervous tissue.
Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: A review

The purpose of this review is to give an insight into the considerable potential of lecithin organogels (LOs) in the applications meant for topical drug delivery. LOs are clear, thermodynamically stable, viscoelastic, and biocompatible jelly-like phases, chiefly composed of hydrated phospholipids and appropriate organic liquid. These systems are currently of interest to the pharmaceutical scientist because of their structural and functional benefits. Several therapeutic agents have been formulated as LOs for their facilitated transport through topical route (for dermal or transdermal effect), with some very encouraging results. The improved topical drug delivery has mainly been attributed to the biphasic drug solubility, the desired drug partitioning, and the modification of skin barrier function by the organogel components. Being thermodynamically stable, LOs are prepared by spontaneous emulsification and therefore posses prolonged shelf life. The utility of this novel matrix as a topical vehicle has further increased owing to its very low skin irritancy potential. Varied aspects of LOs viz formation, composition, phase behavior, and characterization have been elaborated, including a general discussion on the developmental background. Besides a comprehensive update on the topical applications of lecithin organogels, the review also includes a detailed account on the mechanistics of organogelling.