bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indications for a ceftriaxone dosing regimen in Japanese paediatric patients using population pharmacokinetic/pharmacodynamic analysis and simulation
Authors: Iida Satofumi , Kawanishi Takehiko , Hayashi Masahiro 
Published: December 2010

Abstract

Objectives
The objective of this study was to build a ceftriaxone population pharmacokinetic model for Japanese paediatric patients and to examine the dosing regimen of ceftriaxone based on pharmacokinetic/pharmacodynamic (PK/PD) analysis.

Methods
The population pharmacokinetic analysis using NONMEM was based on published serum concentrations of ceftriaxone. A Monte Carlo simulation was examined to evaluate the time above the minimum inhibitory concentration (TAM) in 20 and 60 mg/kg body weight dose regimen using the population pharmacokinetic parameters.

Key findings
The time course of the serum concentration of ceftriaxone in paediatric patients was fitted to a two-compartment model and body weight was incorporated to pharmacokinetic parameters as the covariate. Based on the percent TAM estimated from the final population pharmacokinetic model and the minimum inhibitory concentration (MIC) of ceftriaxone in 2004, we have predicted that the once daily administration of 20 mg/kg ceftriaxone would be effective on various infecting organisms.

Conclusions
A population pharmacokinetic model of ceftriaxone was built for Japanese paediatric patients based on the available data. The estimated PK/PD result confirmed the appropriateness of once daily dose of 20 mg/kg. In some patients for whom no efficacy was observed at 20 mg/kg, an increase to 60 mg/kg may be required.
Imbalanced K+ and Ca2+ subthreshold interactions contribute to increased hypothalamic presympathetic neuronal excitability in hypertensive rats
Authors: Sonner P. M. , Lee S. , Ryu P. D. , Lee S. Y. , Stern J. E. 
Published: December 2010

Non‐technical summaryDespite the importance of brain‐mediated sympathetic activation in the morbidity and mortality of patients with high blood pressure, the precise cellular mechanisms involved remain largely unknown. We show that an imbalanced interaction between two opposing currents mediated by potassium (IA) and calcium (IT) channels occurs in sympathetic‐related hypothalamic neurons in hypertensive rats. We show that this imbalance contributes to enhanced membrane excitability and firing activity in this neuronal population. Knowledge of how these opposing ion channels interact in normal and disease states increases our understanding of underlying brain mechanisms contributing to the high blood pressure condition.
A trans‐spinal loop between neurones in the reticular formation and in the cerebellum
Authors: Hammar I. , Krutki P. , Drzymala‐Celichowska H. , Nilsson E. , Jankowska E. 
Published: December 2010

Non‐technical summaryVoluntary limb movements are initiated in the brain but the neurones responsible for activating the muscles (motoneurones and interneurones) are located in the spinal cord. The spinal cord also contains neurones that provide the brain, and especially the cerebellum, with continuous information on effects of the descending commands. We show that one population of such neurones provide the cerebellum with information on how likely the brain's commands (mediated by descending reticulospinal neurones) are to be executed as planned, depending on the degree of inhibition of motoneurones. They may therefore play an important role in preventing errors in activation of motoneurones and thereby help the brain to correct its signals to the spinal cord before such errors have been committed.
FKS2
Mutations Associated with Decreased Echinocandin Susceptibility of
Candida glabrata
following Anidulafungin Therapy
Authors: Costa-de-Oliveira Sofia , Marcos Miranda Isabel , Silva Raquel M. , Pinto e Silva Ana , Rocha Rita , Amorim António , Gonçalves Rodrigues Acácio , Pina-Vaz Cidália 
Published: December 2010

ABSTRACT

This is the first case report of
Candida glabrata
-disseminated candidiasis describing the acquisition of echinocandin resistance following anidulafungin treatment. The initial isolates recovered were susceptible to echinocandins. However, during 27 days of anidulafungin treatment, two resistant strains were isolated (from the blood and peritoneal fluid). The resistant peritoneal fluid isolate exhibited a Ser663Pro mutation in position 1987 of
FKS2
HS1 (hot spot 1), whereas the resistant blood isolate displayed a phenylalanine deletion (Phe659).
Three Residues in HIV-1 Matrix Contribute to Protease Inhibitor Susceptibility and Replication Capacity
Authors: Parry Chris M. , Kolli Madhavi , Myers Richard E. , Cane Patricia A. , Schiffer Celia , Pillay Deenan 
Published: December 2010

ABSTRACT

Other than cleavage site mutations, there is little data on specific positions within Gag that impact on HIV protease inhibitor susceptibility. We have recently shown that non-cleavage site mutations in
gag
, particularly within matrix protein can restore replication capacity and further reduce protease inhibitor drug susceptibility when coexpressed with a drug-resistant (mutant) protease. The matrix protein of this patient-derived virus was studied in order to identify specific changes responsible for this phenotype. Three amino acid changes in matrix (R76K, Y79F, and T81A) had an impact on replication capacity as well as drug susceptibility. Introduction of these three changes into wild-type (WT) matrix resulted in an increase in the replication capacity of the protease mutant virus to a level similar to that achieved by all the changes within the mutant matrix and part of the capsid protein. Pairs of changes to wild-type matrix led to an increased replication capacity of the protease mutant (although less than with all three changes). Having only these three changes to matrix in a wild-type virus (with wild-type protease) resulted in a 5- to 7-fold change in protease inhibitor 50% effective concentration (EC
50
). Individual changes did not have as great an effect on replication capacity or drug susceptibility, demonstrating an interaction between these positions, also confirmed by sequence covariation analysis. Molecular modeling predicts that each of the three mutations would result in a loss of hydrogen bonds within α-helix-4 of matrix, leading to the hypothesis that more flexibility within this region or altered matrix structure would account for our findings.
In Vitro
Activity and
In Vivo
Efficacy of Anidulafungin in Murine Infections by
Aspergillus flavus
Authors: Calvo Enrique , Pastor F. Javier , Mayayo Emilio , Salas Valentina , Guarro Josep 
Published: December 2010

ABSTRACT

Anidulafungin (AFG) showed high activity against 27 strains of
Aspergillus flavus
by use of broth microdilution and disk diffusion methods. This drug was effective
in vivo
in a murine model of disseminated infection with five isolates tested. AFG was able to prolong survival and reduce tissue burden of infected mice but not able to reduce galactomannan serum concentrations. The AFG serum levels were above the corresponding minimum effective concentrations (MEC) for all of the strains tested.
Interleukin-17 Contributes to Generation of Th1 Immunity and Neutrophil Recruitment duringChlamydia muridarumGenital Tract Infection but Is Not Required for Macrophage Influx or Normal Resolution of Infection
Authors: Scurlock Amy M. , Frazer Lauren C. , Andrews Charles W. , O'Connell Catherine M. , Foote Isaac P. , Bailey Sarabeth L. , Chandra-Kuntal Kumar , Kolls Jay K. , Darville Toni 
Published: December 2010

ABSTRACTInterleukin 17 (IL-17) contributes to development of Th1 immunity and neutrophil influx duringChlamydia muridarumpulmonary infection, but its role duringC. muridarumgenital tract infection has not been described. We detected similar numbers ofChlamydia-specific Th17 and Th1 cells in iliac nodes of wild-type mice early during genitalC. muridaruminfection, while Th1 cells predominated later.il17ra−/−mice exhibited a reduced chlamydia-specific Th1 response in draining iliac nodes and decreased local IFN-γ production. Neutrophil influx into the genital tract was also decreased. However,il17ra−/−mice resolved infection normally, and no difference in pathology was observed compared to the wild type. Macrophage influx and tumor necrosis factor alpha (TNF-α) production were increased inil17ra−/−mice, providing a compensatory mechanism to effectively control chlamydial genital tract infection despite a reduced Th1 response. Inifnγ−/−mice, a marked increase in cellular infiltrates and chronic pathology was associated with an increased Th17 response. Although neutralization of IL-17 inifnγ−/−mice decreased neutrophil influx, macrophage infiltration remained intact and the bacterial burden was not increased. Collectively, these results indicate that IL-17 contributes to the generation of Th1 immunity and neutrophil recruitment but is not required for macrophage influx or normal resolution ofC. muridarumgenital infection. These data highlight the redundant immune mechanisms operative at this mucosal site and the importance of examining site-specific responses to mucosal pathogens.
LiDAR basics for natural resource mapping applications
Authors: Giglierano James D. 
Published: December 2010

Abstract
LiDAR elevation data is becoming widely available for use by many non-engineering mapping specialists such as geologists, soil scientists and planners. Understanding the basics of LiDAR data acquisition is essential to using the data effectively in mapping applications, including how vegetation affects the vertical accuracy of LiDAR. Tools are available for mapping specialists to process raw LiDAR data into useful GIS products so they do not have to rely on vendor supplied products.
Monitoring coastal change using terrestrial LiDAR
Authors: Hobbs P. R. N. , Gibson A. , Jones L. , Pennington C. , Jenkins G. , Pearson S. , Freeborough K. 
Published: December 2010

Abstract
The paper describes recent applications by the British Geological Survey (BGS) of the technique of mobile terrestrial Light Detection And Ranging (LiDAR) surveying to monitor various geomorphological changes on English coasts and estuaries. These include cliff recession, landslides and flood defences, and are usually sited at remote locations undergoing dynamic processes with no fixed reference points. Advantages, disadvantages and some practical problems are discussed. The role of GPS in laser scanning is described.
Digital elevation models for research: UK datasets, copyright and derived products
Authors: Smith M. J. 
Published: December 2010

Abstract
The UK is served by a wide range of digital elevation models (DEMs) that have a variety of technical specifications from several different vendors. The abundance of data presents researchers with a complex range of choices dependent upon their application (and therefore ‘fitness-for-purpose’) and desired use of intellectual property rights (IPR). This paper explores current DEM datasets of the UK and presents their use within the context of claimed copyright and IPR. In particular, responsibilities placed upon grant holders for the lodgement of research outputs by UK Research Councils places new emphasis upon data access, derived data and data re-use. The complex interplay of rights between research output stakeholders (data suppliers, data creators, data users) presents a difficult scenario for both data repositories and data depositors.
Refinement of ASTER digital elevation models using SRTM data for an environmental study in China
Authors: Nightingale M. R. A. , Morgan G. L. K. 
Published: December 2010

Abstract
This paper presents a simple but effective method to improve Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) digital elevation models (DEMs). Digital elevation models are an important component of geomorphological modelling so their integrity is vital to achieve reliable results. For this investigation the relative ASTER DEM produced from an automated cross-correlation algorithm was not considered accurate enough, so 3 arcsecond (90 m) Shuttle Radar Topography Mission (SRTM) data were used to modulate the ASTER DEM.
The method presented in this paper allows the SRTM to enforce vertical control on the relative ASTER DEM whilst attempting to maintain the ASTER DEM's 30 m spatial resolution. The process is fast and efficient, and can be applied to other DEMs. There is, however, a compromise since the fusion process, involving the averaging of the values, does potentially mean that some of the detail in the original 30 m ASTER DEM will be lost.
Analysis of the T-Cell Receptor Repertoires of Tumor-Infiltrating Conventional and Regulatory T Cells Reveals No Evidence for Conversion in Carcinogen-Induced Tumors
Authors: Hindley James P. , Ferreira Cristina , Jones Emma , Lauder Sarah N. , Ladell Kristin , Wynn Katherine K. , Betts Gareth J. , Singh Yogesh , Price David A. , Godkin Andrew J. , Dyson Julian , Gallimore Awen 
Published: December 2010

AbstractA significant enrichment of CD4+Foxp3+ T cells (regulatory T cells, Treg) is frequently observed in murine and human carcinomas. As Tregs can limit effective antitumor immune responses, thereby promoting tumor progression, it is important that the mechanisms underpinning intratumoral accumulation of Tregs are identified. Because of evidence gathered mostly in vitro, the conversion of conventional T cells (Tconv) into Tregs has been proposed as one such mechanism. We assessed the contribution of conversion in vivo by analyzing the TCR (T-cell receptor) repertoires of Tconvs and Tregs in carcinogen-induced tumors in mice. Our results indicate that the TCR repertoires of Tregs and Tconvs within tumor-infiltrating lymphocytes (TIL) are largely distinct. Indeed, the cell population with the greatest degree of repertoire similarity with tumor-infiltrating Tregs was the Treg population from the tumor-draining lymph node. These findings demonstrate that conversion of Tconvs does not contribute significantly to the accumulation of tumor-infiltrating Tregs; rather, Tconvs and Tregs arise from different populations with unique TCR repertoires. Enrichment of Tregs within TILs most likely, therefore, reflects differences in the way that Tregs and Tconvs are influenced by the tumor microenvironment. Elucidating the nature of these influences may indicate how the balance between tumor-infiltrating Tregs and Tconvs can be manipulated for therapeutic purposes. Cancer Res; 71(3); 736–46. ©2010 AACR.
Serial Glycosylated Hemoglobin Levels and Risk of Colorectal Neoplasia among Patients with Type 2 Diabetes Mellitus
Authors: Yang Yu-Xiao , Habel Laurel A. , Capra Angela M. , Achacoso Ninah S. , Quesenberry Charles P. , Ferrara Assiamira , Levin Theodore R. , Lewis James D. 
Published: December 2010

Abstract
Background: Hyperglycemia may increase the risk of colorectal neoplasia by serving as an energy source for neoplastic growth. We sought to determine whether glycemic control measured by serial hemoglobin A1c (HbA1c) was associated with the risk of colorectal adenoma.
Methods: Among a cohort of patients with type 2 diabetes mellitus who received health care within the Kaiser Permanente Northern California from 1994 to 2005, we conducted 2 case–control analyses. Cases had at least 1 colorectal adenoma identified at either colonoscopy (analysis 1) or sigmoidoscopy (analysis 2). Controls had no colorectal neoplasia identified at the corresponding endoscopic examination. Serial HbA1c levels between the cases and the controls were compared using a longitudinal model.
Results: Case–control analysis 1 included 4,248 patients, of whom 1,296 (31%) had at least 1 adenoma. The adjusted mean HbA1c levels among those without any adenomas was 8.20% versus 8.26% among those with at least 1 adenoma, a difference of 0.06% (95% CI = −0.02 to 0.14, P = 0.16). Case–control analysis 2 included 9,813 patients, of whom 951 (10%) had at least 1 distal adenoma. The adjusted mean HbA1c levels among those without any distal adenomas was 8.32% versus 8.37% among those with at least 1 distal adenoma, a difference of 0.05% (95% CI = −00.04 to 0.14, P = 0.25). The results were similar for advanced adenomas.
Conclusions: Glycemic control was not associated with the risk of colorectal adenoma among diabetic persons.
Impact: These results would suggest that glycemic control is unlikely to confound the reported association between diabetes medications and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(12); 3027–36. ©2010 AACR.
Polymorphisms inside MicroRNAs and MicroRNA Target Sites Predict Clinical Outcomes in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy
Authors: Bao Bo-Ying , Pao Jiunn-Bey , Huang Chun-Nung , Pu Yeong-Shiau , Chang Ta-Yuan , Lan Yu-Hsuan , Lu Te-Ling , Lee Hong-Zin , Juang Shin-Hun , Chen Lu-Min , Hsieh Chi-Jeng , Huang Shu-Pin 
Published: December 2010

Abstract
Purpose: Recent evidence indicates that small noncoding RNA molecules, known as microRNAs (miRNAs), are involved in cancer initiation and progression. We hypothesized that genetic variations in miRNAs and miRNA target sites could be associated with the efficacy of androgen-deprivation therapy (ADT) in men with prostate cancer.
Experimental Design: We systematically evaluated 61 common single nucleotide polymorphisms (SNPs) inside miRNAs and miRNA target sites in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan–Meier analysis and Cox regression model.
Results: Four, seven, and four SNPs were significantly associated with disease progression, PCSM, and ACM, respectively, after ADT in univariate analysis. KIF3C rs6728684, CDON rs3737336, and IFI30 rs1045747 genotypes remained as significant predictors for disease progression; KIF3C rs6728684, PALLD rs1071738, GABRA1 rs998754, and SYT9 rs4351800 remained as significant predictors for PCSM; and SYT9 rs4351800 remained as a significant predictor for ACM in multivariate models that included clinicopathologic predictors. Moreover, strong combined genotype effects on disease progression and PCSM were also observed. Patients with a greater number of unfavorable genotypes had a shorter time to progression and worse prostate cancer-specific survival during ADT (P for trend &lt; 0.001).
Conclusion: SNPs inside miRNAs and miRNA target sites have a potential value to improve outcome prediction in prostate cancer patients receiving ADT. Clin Cancer Res; 17(4); 1–9. ©2010 AACR.
Improvements in Shortwave Bulk Scattering and Absorption Models for the Remote Sensing of Ice Clouds
Authors: Baum Bryan A. , Yang Ping , Heymsfield Andrew J. , Schmitt Carl G. , Xie Yu , Bansemer Aaron , Hu Yong-Xiang , Zhang Zhibo 
Published: December 2010

AbstractThis study summarizes recent improvements in the development of bulk scattering/absorption models at solar wavelengths. The approach combines microphysical measurements from various field campaigns with single-scattering properties for nine habits including droxtals, plates, solid/hollow columns, solid/hollow bullet rosettes, and several types of aggregates. Microphysical measurements are incorporated from a number of recent field campaigns in both the Northern and Southern Hemisphere. A set of 12 815 particle size distributions is used for which Tcld ≤ −40°C. The ice water content in the microphysical data spans six orders of magnitude. For evaluation, a library of ice-particle single-scattering properties is employed for 101 wavelengths between 0.4 and 2.24 μm. The library includes the full phase matrix as well as properties for smooth, moderately roughened, and severely roughened particles. Habit mixtures are developed for generalized cirrus, midlatitude cirrus, and deep tropical convection. The single-scattering properties are integrated over particle size and wavelength using an assumed habit mixture to develop bulk scattering and absorption properties. In comparison with global Cloud Aerosol Lidar with Orthogonal Polarization (CALIOP) data, models built with severely roughened particles compare best for all habit mixtures. The assumption of smooth particles provided the largest departure from CALIOP measurements. The use of roughened rather than smooth particles to infer optical thickness and effective diameter from satellite imagery such as the Moderate Resolution Imaging Spectroradiometer (MODIS) will result in a decrease in optical thickness and an increase in particle size.
Response-Guided Induction Therapy in Pediatric Acute Myeloid Leukemia With Excellent Remission Rate
Authors: Abrahamsson Jonas , Forestier Erik , Heldrup Jesper , Jahnukainen Kirsi , Jónsson Ólafur G. , Lausen Birgitte , Palle Josefine , Zeller Bernward , Hasle Henrik 
Published: December 2010

Purpose To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course. Patients and Methods All Nordic children with AML younger than 15 years (n = 151) were treated on the Nordic Society for Pediatric Hematology and Oncology (NOPHO) AML 2004 protocol. After the first course of idarubicin, cytarabine, etoposide, and 6-thioguanin, patients with good response were allowed hematologic recovery before the second course, whereas patients with a poor (≥ 15% blasts) or intermediate (5% to 14.9% blasts) were recommended to proceed immediately with therapy. Patients not in remission after the second course received fludarabine, cytarabine, and granulocyte colony-stimulating factor. Poor responders received allogeneic stem-cell transplantation (SCT) as consolidation. Results Seventy-four percent of patients had good response, 17% had intermediate response, and 7% had poor response after the first course. The overall remission frequency was 97.4%, with 92% in remission after the second course. The rate of induction death was 1.3%. Patients with an intermediate response had a lower event-free survival of 35% compared with good (61%) and poor responders (82%). Conclusion The NOPHO-AML 2004 induction strategy gives an excellent remission rate with low toxic mortality in an unselected population. Outcome is worse in patients with intermediate response but may be improved by intensifying consolidation in this group using SCT.