bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Pharmacokinetics of Artemether, Lumefantrine, and Their Respective Metabolites in Papua New Guinean Children with Uncomplicated Malaria
Authors: Salman Sam , Page-Sharp Madhu , Griffin Susan , Kose Kaye , Siba Peter M. , Ilett Kenneth F. , Mueller Ivo , Davis Timothy M. E. 
Published: August 2011

ABSTRACT

There are sparse published data relating to the pharmacokinetic properties of artemether, lumefantrine, and their active metabolites in children, especially desbutyl-lumefantrine. We studied 13 Papua New Guinean children aged 5 to 10 years with uncomplicated malaria who received the six recommended doses of artemether (1.7 mg/kg of body weight) plus lumefantrine (10 mg/kg), given with fat over 3 days. Intensive blood sampling was carried out over 42 days. Plasma artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine were assayed using liquid chromatography-mass spectrometry or high-performance liquid chromatography. Multicompartmental pharmacokinetic models for a drug plus its metabolite were developed using a population approach that included plasma artemether and dihydroartemisinin concentrations below the limit of quantitation. Although artemether bioavailability was variable and its clearance increased by 67.8% with each dose, the median areas under the plasma concentration-time curve from 0 h to infinity (AUC
0-∞
s) for artemether and dihydroartemisinin (3,063 and 2,839 μg·h/liter, respectively) were similar to those reported previously in adults with malaria. For lumefantrine, the median AUC
0–∞
(459,980 μg·h/liter) was also similar to that in adults with malaria. These data support the higher dose recommended for children weighing 15 to 35 kg (35% higher than that for a 50-kg adult) but question the recommendation for a lower dose in children weighing 12.5 to 15 kg. The median desbutyl-lumefantrine/lumefantrine ratio in the children in our study was 1.13%, within the range reported for adults and higher at later time points because of the longer desbutyl-lumefantrine terminal elimination half-life. A combined desbutyl-lumefantrine and lumefantrine AUC
0–∞
weighted on
in vitro
antimalarial activity was inversely associated with recurrent parasitemia, suggesting that both the parent drug and the metabolite contribute to the treatment outcome of artemether-lumefantrine.
Survey of Antimicrobial Resistance in Clinical Burkholderia pseudomallei Isolates over Two Decades in Northeast Thailand
Authors: Wuthiekanun Vanaporn , Amornchai Premjit , Saiprom Natnaree , Chantratita Narisara , Chierakul Wirongrong , Koh Gavin C. K. W. , Chaowagul Wipada , Day Nicholas P. J. , Limmathurotsakul Direk , Peacock Sharon J. 
Published: August 2011

ABSTRACT

A 21-year survey conducted in northeast Thailand of antimicrobial resistance to parenteral antimicrobial drugs used to treat melioidosis identified 24/4,021 (0.6%) patients with one or more isolates resistant to ceftazidime (
n
= 8), amoxicillin-clavulanic acid (
n
= 4), or both drugs (
n
= 12). Two cases were identified at admission, and the remainder were detected a median of 15 days after starting antimicrobial therapy. Resistance to carbapenem drugs was not detected. These findings support the current prescribing recommendations for melioidosis.
Comparative Analysis of EspF Variants in Inhibition of Escherichia coli Phagocytosis by Macrophages and Inhibition of E. coli Translocation through Human- and Bovine-Derived M Cells
Authors: Tahoun Amin , Siszler Gabriella , Spears Kevin , McAteer Sean , Tree Jai , Paxton Edith , Gillespie Trudi L. , Martinez-Argudo Isabel , Jepson Mark A. , Shaw Darren J. , Koegl Manfred , Haas Juergen , Gally David L. , Mahajan Arvind 
Published: August 2011

ABSTRACT

The EspF protein is secreted by the type III secretion system of enteropathogenic and enterohemorrhagic
Escherichia coli
(EPEC and EHEC, respectively). EspF sequences differ between EHEC O157:H7, EHEC O26:H11, and EPEC O127:H6 in terms of the number of SH3-binding polyproline-rich repeats and specific residues in these regions, as well as residues in the amino domain involved in cellular localization. EspF
O127
is important for the inhibition of phagocytosis by EPEC and also limits EPEC translocation through antigen-sampling cells (M cells). EspF
O127
has been shown to have effects on cellular organelle function and interacts with several host proteins, including N-WASP and sorting nexin 9 (SNX9). In this study, we compared the capacities of different
espF
alleles to inhibit (i) bacterial phagocytosis by macrophages, (ii) translocation through an M-cell coculture system, and (iii) uptake by and translocation through cultured bovine epithelial cells. The
espF
gene from
E. coli
serotype O157 (
espF
O157
) allele was significantly less effective at inhibiting phagocytosis and also had reduced capacity to inhibit
E. coli
translocation through a human-derived
in vitro
M-cell coculture system in comparison to
espF
O127
and
espF
O26
. In contrast,
espF
O157
was the most effective allele at restricting bacterial uptake into and translocation through primary epithelial cells cultured from the bovine terminal rectum, the predominant colonization site of EHEC O157 in cattle and a site containing M-like cells. Although LUMIER binding assays demonstrated differences in the interactions of the EspF variants with SNX9 and N-WASP, we propose that other, as-yet-uncharacterized interactions contribute to the host-based variation in EspF activity demonstrated here.
Necessary and Sufficient Role for T Helper Cells To Prevent Fungal Dissemination in Allergic Lung Disease
Authors: Porter Paul C. , Roberts Luz , Fields Anna , Knight Morgan , Qian Yuping , Delclos George L. , Han Shuhua , Kheradmand Farrah , Corry David B. 
Published: August 2011

ABSTRACTMucosal immune responses to fungal infection range from T helper type 2 (Th2) cell-directed allergic inflammation to Th1-predominant neutrophilic inflammation, but the mechanisms directing these divergent mucosal immune outcomes and the role of T cells in host defense against mucosal fungal infections are not known. Here we examined the mouse mucosal immune responses to 12 filamentous environmental fungal species over a broad range of exposure doses and determined the requirement of T cells for host defense. For all tested fungi, low-grade conidium exposures induced Th2- and eosinophil-predominant allergic lung disease, whereas higher exposures led to rapid conversion to neutrophil- and Th1 cell-predominant inflammation, a phenomenon we term immune phenotype switching. All fungal exposure doses were further linked to the secretion of interleukin-17A (IL-17A). Fungal infections withCurvularia lunataandAspergillus fumigatuswere typically confined to the airway during allergic inflammation but became locally invasive and disseminated to the brain at higher conidium challenge doses, in association with predominant Th1 responses. Fungal dissemination occurred at relatively low challenge doses with the conidia ofAspergillus fumigatusadministered to recombinase activating gene 1 (Rag-1)-deficient mice, which lack B and T cells, but B cell-deficient μMT mice and T helper cell-reconstituted Rag-1-deficient mice were comparable to wild-type mice in preventing fungal dissemination. Our findings demonstrate that Th2 cell-predominant allergic responses followed by immune phenotype switching and fungal dissemination are highly predictable outcomes with progressive fungal infectious burdens and that T helper cell responses are protective against lethal fungal dissemination.
The Photobacterium damselae subsp. damselae Hemolysins Damselysin and HlyA Are Encoded within a New Virulence Plasmid
Authors: Rivas Amable J. , Balado Miguel , Lemos Manuel L. , Osorio Carlos R. 
Published: August 2011

ABSTRACT

Photobacterium damselae
subsp.
damselae
(formerly
Vibrio damsela
) is a marine bacterium that causes infections and fatal disease in a wide range of marine animals and in humans. Highly hemolytic strains produce damselysin (Dly), a cytolysin encoded by the
dly
gene that is lethal for mice and has hemolytic activity. We found that Dly is encoded in the highly hemolytic strain RM-71 within a 153,429-bp conjugative plasmid that we dubbed pPHDD1. In addition to Dly, pPHDD1 also encodes a homologue of the pore-forming toxin HlyA. We found a direct correlation between presence of pPHDD1 and a strong hemolytic phenotype in a collection of
P. damselae
subsp.
damselae
isolates. Hemolysis was strongly reduced in a double
dly hlyA
mutant, demonstrating the role of the two pPHDD1-encoded genes in hemolysis. Interestingly, although single
hlyA
and
dly
mutants showed different levels of hemolysis reduction depending on the erythrocyte source, hemolysis was not abolished in any of the single mutants, suggesting that the hemolytic phenotype is the result of the additive effect of Dly and HlyA. We found that pPHDD1-encoded
dly
and
hlyA
genes are necessary for full virulence for mice and fish. Our results suggest that pPHDD1 can be considered as a driving force for the emergence of a highly hemolytic lineage of
P. damselae
subsp.
damselae
.
Protective Role of Naturally Occurring Interleukin-17A-Producing γδ T Cells in the Lung at the Early Stage of Systemic Candidiasis in Mice
Authors: Dejima Takashi , Shibata Kensuke , Yamada Hisakata , Hara Hiromitsu , Iwakura Yoichiro , Naito Seiji , Yoshikai Yasunobu 
Published: August 2011

ABSTRACTInterleukin-17A (IL-17A)-producing γδ T cells differentiate in the fetal thymus and reside in the peripheral tissues, such as the lungs of naïve adult mice. We show here that naturally occurring γδ T cells play a protective role in the lung at a very early stage after systemic infection withCandida albicans.Selective depletion of neutrophils byin vivoadministration of anti-Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the lung than in the kidney 24 h after intravenous infection withC. albicans.Rapid and transient production of IL-23 was detected in the lung at 12 h, preceding IL-17A production and the influx of neutrophils, which reached a peak at 24 h after infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils concurrently with impaired fungal clearance in the lung after infection. The major source of IL-17A was the γδ T cell population in the lung, and Cδ KO mice showed little IL-17A production and reduced neutrophil infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for IL-17A production by γδ T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing γδ T cells in the first line of host defense againstC. albicansinfection.
Decline of meticillin-resistantStaphylococcus aureusin Oxfordshire hospitals is strain-specific and preceded infection-control intensification
Authors: Wyllie David H , Walker A Sarah , Miller Ruth , Moore Catrin , Williamson Susan R , Schlackow Iryna , Finney John M , O'Connor Lily , Peto Tim E A , Crook Derrick W 
Published: August 2011

BackgroundIn the past, strains ofStaphylococcus aureushave evolved, expanded, made a marked clinical impact and then disappeared over several years. Faced with rising meticillin-resistantS aureus(MRSA) rates, UK government-supported infection control interventions were rolled out in Oxford Radcliffe Hospitals NHS Trust from 2006 onwards.MethodsUsing an electronic Database, the authors identified isolation of MRS among 611 434 hospital inpatients admitted to acute hospitals in Oxford, UK, 1 April 1998 to 30 June 2010. Isolation rates were modelled using segmented negative binomial regression for three groups of isolates: from blood cultures, from samples suggesting invasion (eg, cerebrospinal fluid, joint fluid, pus samples) and from surface swabs (eg, from wounds).FindingsMRSA isolation rates rose rapidly from 1998 to the end of 2003 (annual increase from blood cultures 23%, 95% CI 16% to 30%), and then declined. The decline accelerated from mid-2006 onwards (annual decrease post-2006 38% from blood cultures, 95% CI 29% to 45%, p=0.003 vs previous decline). Rates of meticillin-sensitiveS aureuschanged little by comparison, with no evidence for declines 2006 onward (p=0.40); by 2010, sensitiveS aureuswas far more common than MRSA (blood cultures: 2.9 vs 0.25; invasive samples 14.7 vs 2.0 per 10 000 bedstays). Interestingly, trends in isolation of erythromycin-sensitive and resistant MRSA differed. Erythromycin-sensitive strains rose significantly faster (eg, from blood cultures p=0.002), and declined significantly more slowly (p=0.002), than erythromycin-resistant strains (global p<0.0001). Bacterial typing suggests this reflects differential spread of two major UK MRSA strains (ST22/36), ST36 having declined markedly 2006–2010, with ST22 becoming the dominant MRSA strain.ConclusionsMRSA isolation rates were falling before recent intensification of infection-control measures. This, together with strain-specific changes in MRSA isolation, strongly suggests that incompletely understood biological factors are responsible for the much recent variation in MRSA isolation. A major, mainly meticillin-sensitive,S aureusburden remains.
Joint analysis of multiple biomarkers for identifying type 2 diabetes in middle-aged and older Chinese: a cross-sectional study
Authors: Wu Hongyu , Yu Zhijie , Qi Qibin , Li Huaixing , Sun Qi , Lin Xu 
Published: August 2011

ObjectiveIdentifying individuals with high risk of type 2 diabetes is important. To evaluate discriminatory ability of multiple biomarkers for type 2 diabetes in a Chinese population.MethodsPlasma adiponectin, plasminogen activator inhibitor-1, retinol-binding protein 4, resistin, C-reactive protein, interleukin 6 (IL-6), tumour necrosis factor α receptor 2 and ferritin were measured in a population-based sample of 3189 Chinese (1419 men and 1770 women) aged 50–70 years. A weighted biomarkers risk score (BRS) was developed based on the strength of associations of these biomarkers with type 2 diabetes. The discriminatory ability was tested by the area under receiver operating characteristics curve (AUC).ResultsAdiponectin, plasminogen activator inhibitor-1, IL-6 and ferritin were independently associated with the prevalence of type 2 diabetes, and they were used to calculate the biomarkers risk score (BRS). After adjustment for the confounding factors, the ORs for type 2 diabetes and impaired fasting glucose with each point increment of BRS were 1.28 (95% CI 1.22 to 1.34) and 1.16 (1.12 to 1.20), respectively. Compared with those in the lowest quintile of the BRS, the participants in the highest quintile have an OR (95% CI) of 6.67 (4.21 to 10.55) for type 2 diabetes. The area under the curve for the BRS and conventional risk factors alone was 0.73 and 0.76, respectively, and substantially increased to 0.81 after combining both BRS and conventional risk factors (p<0.001).ConclusionsThese data suggest that combining multiple biomarkers and conventional risk factors might substantially enhance the ability to identify individuals with type 2 diabetes. More prospective data are warranted to confirm this observation.
The clinician’s response to a report of an incidental pulmonary embolism detected on multidetector CT
Authors: Franklin James M , Rahman Najib , Gleeson Fergus V 
Published: August 2011

ABSTRACT

Background
The prevalence of incidental pulmonary emboli (PE) detected on contrast enhanced CT performed for other reasons is approximately 2.5%. The treatment decisions based upon the discovery of incidental PE have been less well reported. The purpose of this study was to report the clinician’s response to, and consequences of, the finding of incidental PE on contrast enhanced CT.

Methods
Retrospective cohort study. Patients with incidental PE detected on a contrast enhanced CT were retrospectively identified at a single institution between 1 January 2009 and 31 December 2009. Case note review was performed to assess clinicians' responses to this finding. Patients with synchronous venous thromboembolism, unrecognised symptoms or factors preventing response assessment were excluded from this analysis. Patient and PE characteristics, treatment, and outcomes related to treatment and non-treatment were recorded.

Results
There were 73 patients with incidental PE: 52 were in the proximal pulmonary arteries and 21 were distal. 16 patients were excluded from the treatment analysis. 52 of 57 (91.2%) patients were treated with therapeutic anticoagulation. There were 2 (3.8%) serious adverse events related to treatment. 5 (8.8%) patients were not treated; 2 (40%) developed recurrent venous thromboembolism. Treatment of incidental PE was not significantly associated with patient age, PE risk factors or PE location. A smaller proportion of single incidental PE were treated than multiple incidental PE (p=0.047).

Conclusion
There is morbidity associated with both treatment and non-treatment of incidental PE. However, despite the uncertainty about the natural history and clinical significance of incidental PE, the majority of patients at the authors' institution received prompt anticoagulation.
Improving STI counselling services of non-formal providers in Bangladesh: testing an alternative strategy: Table 1
Authors: Sarma Haribondhu , Oliveras Elizabeth 
Published: August 2011

ObjectiveThe authors conducted this study to assess the effectiveness of using a public health detailing approach by medical representatives of a private pharmaceutical company to disseminate sexually transmitted infection (STI) counselling information to non-formal providers (NFPs) to improve their STI counselling services.MethodsAn intervention was developed that included developing STI counselling guidelines and training medical representatives to disseminate the counselling guidelines to NFPs. To assess the effectiveness of this intervention, the authors conducted 67 mystery client visits to compare the counselling provided by NFPs in intervention areas with counselling provided in areas where the intervention was not implemented.ResultsA significantly higher proportion (p<0.05) of mystery clients in the intervention area received advice that was consistent with the national STI counselling guidelines compared with the mystery clients in the control area. No mystery clients in the control area were told to use condoms while the STI lasts compared with 44% (95% CI 28% to 62%) in the intervention area. Likewise, more than twice as many clients in the intervention area were advised not to visit sex workers (53% vs 23%; p=0.014).ConclusionPublic health detailing of medical representatives is a feasible mechanism to improve STI counselling services of NFPs in Bangladesh. Private sector companies provide a potential avenue for reaching the vast number of NFPs with basic information that they can share with their clients. The immediate improvements seen in this study suggest the strong potential of public health detailing as a training tool for NFPs.
The monte carlo database system
Authors: Jampani Ravi , Xu Fei , Wu Mingxi , Perez Luis , Jermaine Chris , Haas Peter J. 
Published: August 2011

The application of stochastic models and analysis techniques to large datasets is now commonplace. Unfortunately, in practice this usually means extracting data from a database system into an external tool (such as SAS, R, Arena, or Matlab), and then running the analysis there. This extract-and-model paradigm is typically error-prone, slow, does not support fine-grained modeling, and discourages what-if and sensitivity analyses.
In this article we describe MCDB, a database system that permits a wide spectrum of stochastic models to be used in conjunction with the data stored in a large database, without ever extracting the data. MCDB facilitates in-database execution of tasks such as risk assessment, prediction, and imputation of missing data, as well as management of errors due to data integration, information extraction, and privacy-preserving data anonymization. MCDB allows a user to define “random” relations whose contents are determined by stochastic models. The models can then be queried using standard SQL. Monte Carlo techniques are used to analyze the probability distribution of the result of an SQL query over random relations. Novel “tuple-bundle” processing techniques can effectively control the Monte Carlo overhead, as shown in our experiments.
Perceptual considerations for motion blur rendering
Authors: Navarro Fernando , Castillo Susana , Serón Francisco J. , Gutierrez Diego 
Published: August 2011

Motion blur is a frequent requirement for the rendering of high-quality animated images. However, the computational resources involved are usually higher than those for images that have not been temporally antialiased. In this article we study the influence of high-level properties such as object material and speed, shutter time, and antialiasing level. Based on scenes containing variations of these parameters, we design different psychophysical experiments to determine how influential they are in the perception of image quality.This work gives insights on the effects these parameters have and exposes certain situations where motion blurred stimuli may be indistinguishable from a gold standard. As an immediate practical application, images of similar quality can be produced while the computing requirements are reduced.Algorithmic efforts have traditionally been focused on finding new improved methods to alleviate sampling artifacts by steering computation to the most important dimensions of the rendering equation. Concurrently, rendering algorithms can take advantage of certain perceptual limits to simplify and optimize computations. To our knowledge, none of them has identified nor used these limits in the rendering of motion blur. This work can be considered a first step in that direction.
Spectroscopy Methods and Applications of the Tor Vergata Laser‐Plasma Facility Driven by GW‐Level Laser System
Authors: Francucci M. , Gaudio P. , Martellucci S. , Richetta M. 
Published: August 2011

A review focused on plasma induced on solid target by GW‐level pulsed laser source is presented. A description of the Tor Vergata laser‐plasma source (TVLPS), at the Tor Vergata University in Rome, is given. Such a facility uses a 1
GW, tabletop, multistage Nd:YAG/Glass laser system, delivering infrared (IR) pulses with nanosecond width and 1064 nm wavelength (TEM00 mode). Its applications are discussed providing: wide analysis of IR → soft X‐ray conversion efficiency (1.3–1.55 keV); measures and modeling of line emission in soft X‐ray spectra, such as those from zinc plasma near Ne‐like Zn XXI and from barium plasma near Ni‐like Ba XXIX. Particular attention is devoted to high‐n dielectronic Rydberg satellites for finding a useful diagnostic tool for plasma conditions. Dependence of plasma spectra on laser parameters is shown. Finally, microradiography applications are presented for thin biological samples. Images permit to visualize specific structures and detect bioaccumulation sites due to contamination from pollutants.