bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Pharmacokinetics and Safety of Voriconazole Intravenous-to-Oral Switch in Immunocompromised Children and Healthy Adults
Authors: Driscoll Timothy A. , Yu Lolie C. , Frangoul Haydar , Krance Robert A. , Nemecek Eneida , Blumer Jeffrey , Arrieta Antonio , Graham Michael L. , Bradfield Scott M. , Baruch Alice , Liu Ping 
Published: October 2011

ABSTRACT

Voriconazole pharmacokinetics are not well characterized in children despite prior studies. To assess the appropriate pediatric dosing, a study was conducted in 40 immunocompromised children aged 2 to <12 years to evaluate the pharmacokinetics and safety of voriconazole following intravenous (IV)-to-oral (PO) switch regimens based on a previous population pharmacokinetic modeling: 7 mg/kg IV every 12 h (q12h) and 200 mg PO q12h. Area under the curve over the 12-h dosing interval (AUC
0–12
) was calculated using the noncompartmental method and compared to that for adults receiving approved dosing regimens (6→4 mg/kg IV q12h, 200 mg PO q12h). On average, the AUC
0–12
in children receiving 7 mg/kg IV q12h on day 1 and at IV steady state were 7.85 and 21.4 μg·h/ml, respectively, and approximately 44% and 40% lower, respectively, than those for adults at 6→4 mg/kg IV q12h. Large intersubject variability was observed. At steady state during oral treatment (200 mg q12h), children had higher average exposure than adults, with much larger intersubject variability. The exposure achieved with oral dosing in children tended to decrease as weight and age increased. The most common treatment-related adverse events were transient elevated liver function tests. No clear threshold of voriconazole exposure was identified that would predict the occurrence of treatment-related hepatic events. Overall, voriconazole IV doses higher than 7 mg/kg are needed in children to closely match adult exposures, and a weight-based oral dose may be more appropriate for children than a fixed dose. Safety of voriconazole in children was consistent with the known safety profile of voriconazole.
Differences in Efficacy and Cytokine Profiles following Echinocandin or Liposomal Amphotericin B Monotherapy or Combination Therapy for Murine Pulmonary or Systemic Aspergillus flavus Infections
Authors: Olson J. A. , Schwartz J. , Hahka D. , George A. , Proffitt R. T. , Adler-Moore J. P. 
Published: October 2011

ABSTRACT

Given the recent increase in aspergillosis caused by species other than
Aspergillus fumigatus
, micafungin, caspofungin, and liposomal amphotericin B (L-AmBi) were investigated as monotherapy or combination therapy for murine systemic or pulmonary
Aspergillus flavus
infection. Treatment for 3 or 6 days was begun at 24 h (intravenous [i.v.], 2.8 × 10
4
conidia) or 2 h (intranasal, 4.1 × 10
6
to 6.75 × 10
6
conidia) postchallenge as follows: 5 or 10 mg/kg L-AmBi, 10 mg/kg caspofungin, 15 mg/kg micafungin, L-AmBi plus echinocandin, L-AmBi on days 1 to 3 and echinocandin on days 4 to 6, or echinocandin on days 1 to 3 and L-AmBi on days 4 to 6. Mice were monitored for survival, fungal burden, serum or tissue cytokines, and lung histopathology. In the systemic infection, micafungin or caspofungin was more effective than L-AmBi in prolonging survival (
P
< 0.05), and L-AmBi was associated with significantly elevated serum levels of interleukin-6 (IL-6), macrophage inflammatory protein 1α (MIP-1α), and IL-12 (
P
< 0.05). In contrast, L-AmBi was significantly more effective than the echinocandins in reducing fungal growth in most tissues (
P
< 0.05). Concomitant therapies produced significantly enhanced survival, reduction in fungal burden, and low levels of proinflammatory cytokines, while antagonism was seen with some sequential regimens. In comparison, in the pulmonary infection, L-AmBi was significantly better (
P
< 0.05) than caspofungin or the combination of L-AmBi and caspofungin in prolonging survival and reducing lung fungal burden. Caspofungin stimulated high lung levels of IL-1α, tumor necrosis factor alpha (TNF-α), and IL-6, with extensive tissue damage. In summary, systemic
A flavus
infection was treated effectively with L-AmBi plus micafungin or caspofungin provided that the drugs were administered concomitantly and not sequentially, while pulmonary
A. flavus
infection responded well to L-AmBi but not to caspofungin.
Bacteremia Due to Extended-Spectrum-β-Lactamase-Producing Aeromonas spp. at a Medical Center in Southern Taiwan
Authors: Wu Chi-Jung , Chuang Yin-Ching , Lee Mei-Feng , Lee Chin-Chi , Lee Hsin-Chun , Lee Nan-Yao , Chang Chia-Ming , Chen Po-Lin , Lin Yu-Tzu , Yan Jing-Jou , Ko Wen-Chien 
Published: October 2011

ABSTRACT

Although extended-spectrum-β-lactamase (ESBL)-producing aeromonads have been increasingly reported in recent years, most of them were isolates from case reports or environmental isolates. To investigate the prevalence of ESBL producers among
Aeromonas
blood isolates and the genes encoding ESBLs, consecutive nonduplicate
Aeromonas
blood isolates collected at a medical center in southern Taiwan from March 2004 to December 2008 were studied. The ESBL phenotypes were examined by clavulanate combination disk test and the cefepime-clavulanate ESBL Etest. The presence of ESBL-encoding genes, including
bla
TEM
,
bla
PER
,
bla
CTX-M
, and
bla
SHV
genes, was evaluated by PCR and sequence analysis. The results showed that 4 (2.6%) of 156
Aeromonas
blood isolates, 1
Aeromonas hydrophila
isolate and 3
Aeromonas caviae
isolates, expressed an ESBL-producing phenotype. The ESBL gene in two
A. caviae
isolates was
bla
PER-3
, which was located in both chromosomes and plasmids, as demonstrated by Southern hybridization. Of four patients with ESBL-producing
Aeromonas
bacteremia, two presented with catheter-related phlebitis and the other two with primary bacteremia. Three patients had been treated with initial noncarbapenem β-lactams for 5 to 10 days, and all survived. In conclusion, ESBL producers exist among
Aeromonas
blood isolates, and clinical suspicion of ESBL production should be raised in treating infections due to cefotaxime-resistant
Aeromonas
isolates.
Cyclopropyl Carboxamides, a Chemically Novel Class of Antimalarial Agents Identified in a Phenotypic Screen
Authors: Sanz Laura M. , Jiménez-Díaz M. Belen , Crespo Benigno , De-Cozar Cristina , Almela M. Jesus , Angulo-Barturen Iñigo , Castañeda Pablo , Ibañez Javier , Fernández Esther Pilar , Ferrer Santiago , Herreros Esperanza , Lozano Sonia , Martínez María Santos , Rueda Lourdes , Burrows Jeremy N. , García-Bustos Jose F. , Gamo Francisco-Javier 
Published: October 2011

ABSTRACT

Malaria is one of the deadliest infectious diseases in the world, with the eukaryotic parasite
Plasmodium falciparum
causing the most severe form of the disease. Discovery of new classes of antimalarial drugs has become an urgent task to counteract the increasing problem of drug resistance. Screening directly for compounds able to inhibit parasite growth
in
vitro
is one of the main approaches the malaria research community is now pursuing for the identification of novel antimalarial drug leads. Very recently, thousands of compounds with potent activity against the parasite
P. falciparum
have been identified and information about their molecular descriptors, antiplasmodial potency, and cytotoxicity is publicly available. Now the challenges are how to identify the most promising chemotypes for further development and how best to progress these compounds through a lead optimization program to generate antimalarial drug candidates. We report here the first chemical series to be characterized from one of those screenings, a completely novel chemical class with the generic name cyclopropyl carboxamides that has never before been described as having antimalarial or other pharmacological activities. Cyclopropyl carboxamides are potent inhibitors of drug-sensitive and -resistant strains of
P. falciparum
in
vitro
and show
in
vivo
oral efficacy in malaria mouse models. In the present work, we describe the biological characterization of this chemical family, showing that inhibition of their still unknown target has very favorable pharmacological consequences but the compounds themselves seem to select for resistance at a high frequency.
First Face Composite-Tissue Transplant Recipient Successfully Treated for Cytomegalovirus Infection with Preemptive Valganciclovir Treatment
Authors: BenMarzouk-Hidalgo O. J. , Cordero E. , Gómez-Cía T. , Sánchez M. , González-Padilla J. D. , Infante-Cossio P. , Sicilia-Castro D. , Hernández-Guisado J. M. , Pérez-Romero P. 
Published: October 2011

ABSTRACT

Little is known about cytomegalovirus (CMV) infection after face transplantation, since only two of the 11 cases of face transplantation reported worldwide have documented a CMV infection after transplantation. Herein, we present the first report of a composite-tissue face allotransplant recipient at high risk for CMV infection (D
+
/R
−
[CMV serpositive donor positive/CMV seronegative receptor]) undergoing preemptive treatment. Preemptive treatment was safe and effective for controlling CMV infection and thus promoting early acquisition of a CMV-specific immune response that protected the patient from late-onset CMV disease.
PhoQ Mutations Promote Lipid A Modification and Polymyxin Resistance of Pseudomonas aeruginosa Found in Colistin-Treated Cystic Fibrosis Patients
Authors: Miller Amanda K. , Brannon Mark K. , Stevens Laurel , Johansen Helle Krogh , Selgrade Sara E. , Miller Samuel I. , Høiby Niels , Moskowitz Samuel M. 
Published: October 2011

ABSTRACT

Pseudomonas aeruginosa
can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of polymyxin resistance (MICs of 8 to 64 mg/liter) in laboratory and clinical strains of this organism. To explore the role of PhoPQ in high-level clinical polymyxin resistance,
P. aeruginosa
strains with colistin MICs > 512 mg/liter that had been isolated from cystic fibrosis patients treated with inhaled colistin (polymyxin E) were analyzed. Probable loss-of-function
phoQ
alleles found in these cystic fibrosis strains conferred resistance to polymyxin. Partial and complete suppressor mutations in
phoP
were identified in some cystic fibrosis strains with resistance-conferring
phoQ
mutations, suggesting that additional loci can be involved in polymyxin resistance in
P. aeruginosa
. Disruption of chromosomal
phoQ
in the presence of an intact
phoP
allele stimulated 4-amino-
l
-arabinose addition to lipid A and induced transcription from the promoter of the
pmrH
(
arnB
) operon, consistent with the known role of this lipid A modification in polymyxin resistance. These results indicate that
phoQ
loss-of-function mutations can contribute to high-level polymyxin resistance in clinical strains of
P. aeruginosa
.
Role of the Yersinia pestis Ail Protein in Preventing a Protective Polymorphonuclear Leukocyte Response during Bubonic Plague
Authors: Hinnebusch B. Joseph , Jarrett Clayton O. , Callison Julie A. , Gardner Donald , Buchanan Susan K. , Plano Gregory V. 
Published: October 2011

ABSTRACT

The ability of
Yersinia pestis
to forestall the mammalian innate immune response is a fundamental aspect of plague pathogenesis. In this study, we examined the effect of Ail, a 17-kDa outer membrane protein that protects
Y. pestis
against complement-mediated lysis, on bubonic plague pathogenesis in mice and rats. The
Y. pestis ail
mutant was attenuated for virulence in both rodent models. The attenuation was greater in rats than in mice, which correlates with the ability of normal rat serum, but not mouse serum, to kill
ail
-negative
Y. pestis in vitro
. Intradermal infection with the
ail
mutant resulted in an atypical, subacute form of bubonic plague associated with extensive recruitment of polymorphonuclear leukocytes (PMN or neutrophils) to the site of infection in the draining lymph node and the formation of large purulent abscesses that contained the bacteria. Systemic spread and mortality were greatly attenuated, however, and a productive adaptive immune response was generated after high-dose challenge, as evidenced by high serum antibody levels against
Y. pestis
F1 antigen. The
Y. pestis
Ail protein is an important bubonic plague virulence factor that inhibits the innate immune response, in particular the recruitment of a protective PMN response to the infected lymph node.
Educational level and HIV disease progression before and after the introduction of HAART: a cohort study in 989 HIV seroconverters in Spain
Authors: Monge Susana , Jarrín Inmaculada , Pérez-Hoyos Santiago , Ferreros Inmaculada , García-Olalla Patricia , Muga Roberto , Del Romero Jorge , Belda Josefina , Castilla Jesús , Bolúmar Francisco , Del Amo Julia ,   on behalf of GEMES
Published: October 2011

ObjectivesTo analyse the effect of educational level on the progression from HIV seroconversion to highly active antiretroviral therapy (HAART) requirement, HAART initiation, AIDS and death from any cause at different periods of the HIV epidemic in Spain.MethodsOpen, prospective, multicentre cohort of HIV seroconverters set up in 1983. The risk of progression was calculated by the multiple decrements method. Effect of educational level was estimated by Fine and Gray model, adjusting for sex, HIV transmission category, age and method to estimate seroconversion. Calendar period was introduced as a variable that could change over time (<1997; 1997–2003; >2003).ResultsUp to 2009, 989 HIV seroconverters with information on educational level were identified. Some 52% and 48% had a low and a high educational level respectively. Persons with higher education had 32% lower risk of death (HR: 0.68; 95% CI 0.45 to 1.03). Regarding progression to AIDS, educational level had no effect in the pre-HAART era (HR: 1.47; 95% CI 0.91 to 2.38), but did show an effect in the period 1997–2003 (HR: 0.58; 95% CI 0.34 to 0.99), which was accentuated after 2004 (HR: 0.26; 95% CI 0.10 to 0.68). No difference was found in time to HAART requirement or initiation.ConclusionsResults suggest that, despite similar access to HAART, persons with low educational level are at increased risk of HIV disease progression, highlighting the impact of social inequities on health. The availability of more effective treatments over time will strengthen the protective effect of higher education on the development of AIDS.
Prevalence and factors associated with HSV-2 and hepatitis B infections among truck drivers crossing the southern Brazilian border
Authors: Pinho Adriana A , Chinaglia Magda , Lippman Sheri A , Reingold Arthur , Diaz Ricardo Sobhie , Sucupira Maria Cecilia , Page Kimberly , Díaz Juan 
Published: October 2011

ObjectivesThe authors estimate the prevalence of HIV, syphilis, hepatitis B virus (HBV) and herpes simplex virus type-2 (HSV-2) infection and correlates of HBV and HSV-2 infection among truck drivers crossing the southern Brazilian border at Foz do Iguaçu.MethodsBetween October 2003 and March 2005, 1945 truck drivers were sampled while accessing voluntary counselling and testing services; 1833 (94.2%) were tested for HIV (ELISA and confirmatory immunofluorescence assay) and syphilis (non-treponemal (VDRL) and treponemal tests (FTA-ABS)). From these, 799 stored sera were tested for HSV-2 (type-specific ELISA test for detection of IgG) and HBV (core antibodies (anti-HBc) with positives tested for surface antigen (HBsAg)). The authors estimate HIV, syphilis, HSV-2 and HBV prevalence and determine socio-demographic and behavioural correlates of HSV-2 infection and HBV exposure.ResultsHIV prevalence was 0.3% (95% CI 0.1 to 0.6) and syphilis 4.5% (95% CI 3.6 to 5.4). Among those tested for HBV and HSV-2, 32.3% (95% CI 28.9 to 35.6) had serological evidence of exposure to HBV and 26.6% (95% CI 23.5 to 29.7) tested positive for HSV-2. Factors independently associated with HBV exposure included increasing age, Brazilian nationality and unprotected anal sex. Increasing age and reporting an unknown number of lifetime partners were associated with HSV-2 infection.ConclusionsIn this sample of truck drivers in southern Brazil, HIV prevalence was lower than national population estimates; exposure to HBV was higher than population estimates, while per cent positive for HSV-2 was similar to population estimates. The low prevalence of HIV in truck drivers indicates prevention successes; however, future HIV prevention programming should incorporate HBV vaccination and sexually transmitted infection prevention.
Competition and coexistence among short-grass grazers in the Hluhluwe-iMfolozi Park, South Africa
Authors: Arsenault Randal , Owen-Smith Norman 
Published: October 2011

Coexistence among grazing ungulates has been related to differences in grass height and grassland types selected, underlain by morphological distinctions. Nevertheless, resource competition may arise when smaller species depress grass height below that suitable for larger species, whereas competition may be counteracted by facilitation when larger species increase the extent of high-quality grassland available. We investigated resource-use overlap between white rhinoceros ( Ceratotherium simum (Burchell, 1817)), blue wildebeest ( Connochaetes taurinus (Burchell, 1823)), and Burchell’s zebra (Equus burchelli (Gray, 1824)) in the Hluhluwe-iMfolozi Park in South Africa. We recorded the grassland type favoured, grass species utilized, grass height grazed, and greenness selected during the dry seasons of 2 years. Blue wildebeest shifted their grazing away from lawn grassland in the drier year, whereas Burchell’s zebra favoured lawn grassland only in the relatively wet year. White rhinoceros concentrated their feeding on lawn grassland throughout the dry seasons of both years, and favoured shorter grass than the other two grazers. Species characterizing grazing lawns contributed relatively more to the grass used by white rhinoceros in the drier year. Resource competition was potentially ameliorated by widened availability of lawn grassland promoted by white rhinoceros grazing. This counterbalancing of feeding competition and habitat facilitation enables the coexistence of these grazers despite similar food requirements.
Timing analysis for a composable mode switch
Authors: Hang Yin , Hansson Hans 
Published: October 2011

Component based software development (CBD) reduces development time and effort by allowing systems to be built from pre-developed reusable components. A classical approach to reduce embedded systems design and run-time complexity is to partition the behavior into a set of major system modes. In supporting system modes in CBD, a key issue is seamless composition of multi-mode components into systems.
In addressing this issue, we have developed a mode switch logic and algorithm for component-based multi-mode systems. In this paper we introduce timing analysis for our composable mode switch.
Learning-based visual saliency computation
Authors: Li Jia 
Published: October 2011

With the rapid development of Internet, the amounts of images and videos are now growing explosively, leading to many new challenges on image/video processing. On one hand, the processing capability of computer is limited and the computational resource should be allocated to the important visual information with high priorities. On the other hand, the analysis results given by computer should be consistent with human cognition. To solve these two problems, this thesis will focus on learning-based visual saliency computation and the main objective can be described as predicting, locating and mining the important visual information that is consistent with human cognition. The main contributions of this thesis can be summarized as follows:
Firstly, this thesis presents a probabilistic multi-task learning approach for computing visual saliency by simultaneously integrating the bottom-up and topdown factors. To the best of our knowledge, it is the first approach that explores the problem of visual saliency computation with the multi-task learning algorithm. In our approach, the bottom-up and the top-down factors are considered simultaneously in a probabilistic framework. In this framework, a bottom-up component simulates the low-level processes in human vision system using multi-scale wavelet decomposition; while a top-down component simulates the high-level processes to bias the competition of the input visual stimuli. Moreover, we propose a multi-task learning algorithm to optimize the models and model fusion strategies for various scenes. Extensive experiments on several datasets show that this approach demonstrates high robustness and effectiveness in computing visual saliency.
Alu in Lynch Syndrome: A Danger SINE?
Authors: Hitchins Megan P. , Burn John 
Published: October 2011

Abstract
Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline loss of a DNA mismatch repair gene. In a significant proportion of cases, loss of function of the MSH2 mismatch repair gene is caused by large heterogeneous deletions involving MSH2 and/or the adjacent EPCAM gene. These deletions usually result from homologous malrecombination events between Alu elements, a family of short interspersed nuclear elements (SINE). Recent recognition that the extent of these deletions influences phenotypic outcome provided new impetus for fine-mapping the breakpoints. In doing so, Pérez-Cabornero and colleagues uncovered new evidence for Alu-mediated ancestral founder deletions within MSH2 in the Spanish Lynch syndrome population (as reported beginning on pages 1546 and 1556 in this issue of the journal). This is the first such finding to date and prompted a revisitation of the role of Alu elements in the causation of Lynch syndrome. Whether Alu density is a danger sign for genomic regions prone to rearrangement and what additional factors may be required to actuate these events remain to be discovered. Cancer Prev Res; 4(10); 1527–30. ©2011 AACR.
Molecular Imaging of Inflammation and Carcinogenesis
Authors: Ostrov David A. , Contag Christopher H. 
Published: October 2011

Abstract
Development of imaging agents that can be used broadly for early detection of neoplasia at various tissue sites and at various stages of disease and that also can assess states of minimal residual disease would have tremendous utility in the diagnosis and management of cancer. In a series of articles culminating with a report in this issue of the journal (beginning on page 1536), Uddin and colleagues show their ability to systemically target the enzyme COX-2 with imaging probes that will serve as agents for early detection, risk assessment, prognosis, and intervention outcome measures. These probes will enable the detection and localization of regions of inflammation and a wide variety of premalignant lesions and cancers, with utility in monitoring the effects of cancer prevention and therapy. Cancer Prev Res; 4(10); 1523–6. ©2011 AACR.