bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Pseudo-Staphylococcal Cassette Chromosome
mec
Element (ΨSCC
mec
57395
) in Methicillin-Resistant Staphylococcus pseudintermedius CC45
Authors: Perreten Vincent , Chanchaithong Pattrarat , Prapasarakul Nuvee , Rossano Alexandra , Blum Shlomo E. , Elad Daniel , Schwendener Sybille 
Published: August 2013

ABSTRACT

Genetic characterization of methicillin-resistant
Staphylococcus pseudintermedius
(MRSP) from Thailand and Israel revealed the presence of a predominant atypical clonal lineage which was not typeable by SmaI-PFGE and SCC
mec
typing. All the atypical isolates (
n
= 34) belonged to CC45 (30 ST45 and 2 ST179 isolates, 1 ST57 isolate, and 1 ST85 isolate). The isolates originated from healthy and diseased dogs and cats, as well as from the environment of one clinic. Cfr9I–pulsed-field gel electrophoresis (Cfr9I-PFGE) and
dru
typing permitted the further distinction of CC45 isolates from the two different countries. Microarray analysis identified genes that confer resistance to β-lactams (
mecA
;
blaZ
), aminoglycosides [
aac(6′)-Ie–aph(2′)-Ia
;
aph(3′)-III
;
ant(6)-Ia
], macrolides and lincosamides [
erm
(B)], tetracyclines [
tet
(M)], trimethoprim [
dfr
(G)], streptothricin (
sat4
), and chloramphenicol (
cat
pC221
). Fluoroquinolone resistance was attributed to specific amino acid substitutions, i.e., Ser84Leu in GyrA and Ser80Ile and Asp84Asn in GrlA. A novel pseudo-staphylococcal cassette chromosome (ΨSCC
mec
57395
) element was identified in MRSP strain 57395 (sequence type ST45) by whole-genome sequencing. The 12,282-bp ΨSCC
mec
57395
element contained a class C1
mec
gene complex but no
ccr
genes. In addition to the methicillin resistance gene
mecA
, ΨSCC
mec
57395
also carried determinants of resistance to heavy metals, such as arsenic, cadmium, and copper. Bsu36I restriction analysis of the ΨSCC
mec
57395
element amplified by long-range PCR revealed the presence of ΨSCC
mec
57395
in the 33 additional isolates of MRSP CC45. The ΨSCC
mec
57395
element represents a new class of SCC
mec
and has been identified in MRSP of CC45, which is a predominant clonal lineage in Israel and Thailand.
Nested Case-Control Study of the Emergence of Tigecycline Resistance in Multidrug-Resistant Klebsiella pneumoniae
Authors: Nigo Masayuki , Cevallos Catalina Salinas , Woods Krystina , Flores Vicente Maco , Francis Gweneth , Perlman David C. , Revuelta Manuel , Mildvan Donna , Waldron Mary , Gomez Tessa , Koshy Sanjana , Jodlowski Tomasz , Riley William , Ruhe Jörg J. 
Published: August 2013

ABSTRACT

We performed a nested case-control study (ratio of 1:4) on the emergence of tigecycline-resistant multidrug-resistant
Klebsiella pneumoniae
(TR-MDRKP) isolates among patients who initially presented with a tigecycline-susceptible MDRKP isolate. Out of 260 patients, 24 (9%) had a subsequent clinical culture positive for a TR-MDRKP isolate within the 90-day follow-up period. On logistic regression analyses, receipt of tigecycline (adjusted odds ratio [OR], 5.06; 95% confidence interval [CI], 1.80 to 14.23;
P
= 0.002) was the only independent predictor of subsequent isolation of a TR strain.
A Novel FexA Variant from a Canine Staphylococcus pseudintermedius Isolate That Does Not Confer Florfenicol Resistance
Authors: Gómez-Sanz Elena , Kadlec Kristina , Feßler Andrea T. , Zarazaga Myriam , Torres Carmen , Schwarz Stefan 
Published: August 2013

ABSTRACT

Transposon Tn
558
integrated in the chromosomal
radC
gene was detected for the first time in
Staphylococus pseudintermedius
. It carried a novel
fexA
variant (
fexAv
) that confers only chloramphenicol resistance. The exporter FexAv exhibited two amino acid substitutions, Gly33Ala and Ala37Val, both of which seem to be important for substrate recognition. Site-directed mutagenesis that reverted the mutated base pairs to those present in the original
fexA
gene restored the chloramphenicol-plus-florfenicol resistance phenotype.
Comparison between the EUCAST Procedure and the Etest for Determination of the Susceptibility of Candida Species Isolates to Micafungin
Authors: Marcos-Zambrano Laura Judith , Escribano Pilar , Rueda Cristina , Zaragoza Óscar , Bouza Emilio , Guinea Jesús 
Published: August 2013

ABSTRACT

We compared the ability of the EUCAST EDef 7.2 and the Etest to detect the susceptibility to micafungin of 160
Candida
and non-
Candida
clinical isolates. Agreement was higher when Etest MICs were obtained after 24 h of incubation; essential agreement was 90%, and categorical agreement was >90%. False susceptibility was seen only for
Candida krusei
(10%), and false resistance was observed in 6% of the isolates, ranging from 2.6% (
C. glabrata
) to 13% (
C. albicans
).
Impact of Reduced Vancomycin MIC on Clinical Outcomes of Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Park So-Youn , Oh In-Hwan , Lee Hee-Joo , Ihm Chun-Gyoo , Son Jun Seong , Lee Mi Suk , Kim Mi-Na 
Published: August 2013

ABSTRACT

Vancomycin has been a key antibiotic agent for the treatment of methicillin-resistant
Staphylococcus aureus
(MRSA) infections. However, little is known about the relationship between vancomycin MIC values at the higher end of the susceptibility range and clinical outcomes. The aim of this study was to determine the impact of MRSA bacteremia on clinical outcomes in patients with a vancomycin MIC near the upper limit of the susceptible range. Patients with MRSA bacteremia were divided into a high-vancomycin-MIC group (2 μg/ml) and a low-vancomycin-MIC group (≤1.0 μg/ml). We examined the relationship between MIC, genotype, primary source of bacteremia, and mortality. Ninety-four patients with MRSA bacteremia, including 31 with a high vancomycin MIC and 63 with a low MIC were analyzed. There was no significant difference between the presence of
agr
dysfunction and SCC
mec
type between the two groups. A higher vancomycin MIC was not found to be associated with mortality. In contrast, high-risk bloodstream infection sources (hazard ratio [HR], 4.63; 95% confidence interval [CI] = 1.24 to 17.33) and bacterial eradication after treatment (HR, 0.06; 95% CI = 0.02 to 0.17), irrespective of vancomycin MIC, were predictors of all-cause 30-day mortality. Our study suggests that a high-risk source of bacteremia is likely to be associated with unfavorable clinical outcomes, but a high vancomycin MIC in a susceptible range, as well as genotype characteristics, are not associated with mortality.
Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, against Hospital and Community Pathogens
Authors: Sutcliffe J. A. , O'Brien W. , Fyfe C. , Grossman T. H. 
Published: August 2013

ABSTRACT

Eravacycline (TP-434 or 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline) is a novel fluorocycline that was evaluated for antimicrobial activity against panels of recently isolated aerobic and anaerobic Gram-negative and Gram-positive bacteria. Eravacycline showed potent broad-spectrum activity against 90% of the isolates (MIC
90
) in each panel at concentrations ranging from ≤0.008 to 2 μg/ml for all species panels except those of
Pseudomonas aeruginosa
and
Burkholderia cenocepacia
(MIC
90
values of 32 μg/ml for both organisms). The antibacterial activity of eravacycline was minimally affected by expression of tetracycline-specific efflux and ribosomal protection mechanisms in clinical isolates. Furthermore, eravacycline was active against multidrug-resistant bacteria, including those expressing extended-spectrum β-lactamases and mechanisms conferring resistance to other classes of antibiotics, including carbapenem resistance. Eravacycline has the potential to be a promising new intravenous (i.v.)/oral antibiotic for the empirical treatment of complicated hospital/health care infections and moderate-to-severe community-acquired infections.
Plasma Concentrations of Isoniazid and Rifampin Are Decreased in Adult Pulmonary Tuberculosis Patients with Diabetes Mellitus
Authors: Babalik Aylin , Ulus Ismail Hakki , Bakirci Nadi , Kuyucu Tulin , Arpag Huseyin , Dagyildizi Lale , Capaner Esen 
Published: August 2013

ABSTRACT

Plasma isoniazid and rifampin concentrations, but not pyrazinamide and ethambutol concentrations, were decreased by about 50% (
P
< 0.05) in diabetic pulmonary tuberculosis patients. The prevalences of subnormal plasma isoniazid, rifampin, pyrazinamide, and ethambutol concentrations were 49% or 100% (
P
< 0.01), 66% or 100% (
P
< 0.05), 30% or 50% (
P
= 0.198), and 32% or 21% (
P
= 0.742) in nondiabetic or diabetic tuberculosis patients, respectively. These data show that plasma concentrations of isoniazid and rifampin were greatly reduced in diabetic tuberculosis patients.
In Vivo
Emergence of Colistin Resistance in Klebsiella pneumoniae Producing KPC-Type Carbapenemases Mediated by Insertional Inactivation of the PhoQ/PhoP
mgrB
Regulator
Authors: Cannatelli Antonio , D'Andrea Marco Maria , Giani Tommaso , Di Pilato Vincenzo , Arena Fabio , Ambretti Simone , Gaibani Paolo , Rossolini Gian Maria 
Published: August 2013

ABSTRACT

Colistin is one of the few agents that retain activity against extensively drug-resistant strains of
Klebsiella pneumoniae
producing KPC-type carbapenemases (KPC-KP). However, resistance to colistin is increasingly reported among KPC-KP. Comparative genomic analysis of a pair of sequential KPC-KP isolates from the same patient including a colistin-susceptible isolate (KKBO-1) and a colistin-resistant isolate (KKBO-4) selected after colistin exposure revealed that insertional inactivation of the
mgrB
gene, encoding a negative regulator of the PhoQ/PhoP signaling system, is a genetic mechanism for acquired colistin resistance. The role of
mgrB
inactivation in acquired colistin resistance was confirmed by complementation experiments with wild-type
mgrB
, which restored colistin susceptibility in KKBO-4, and by construction of an
mgrB
deletion mutant from KKBO-1, which exhibited a colistin-resistant phenotype. Insertional
mgrB
inactivation was also detected in 60% of colistin-resistant mutants selected from KKBO-1
in vitro
, following plating on colistin-containing medium, confirming the role (although not unique) of this mechanism in the emergence of acquired colistin resistance. In colistin-resistant mutants carrying insertional inactivation or deletion of the
mgrB
gene, upregulated transcription of
phoP
,
phoQ
, and
pmrK
(which is part of the
pmrHFIJKLM
operon) was detected. These findings confirmed the MgrB regulatory role in
K. pneumoniae
and were in agreement with the known association between upregulation of the PhoQ/PhoP system and activation of the
pmrHFIJKLM
operon, which eventually leads to resistance to polymyxins by modification of the lipopolysaccharide target.
A Novel C5a-Derived Immunobiotic Peptide Reduces Streptococcus agalactiae Colonization through Targeted Bacterial Killing
Authors: Cavaco Courtney K. , Patras Kathryn A. , Zlamal Jaime E. , Thoman Marilyn L. , Morgan Edward L. , Sanderson Sam D. , Doran Kelly S. 
Published: August 2013

ABSTRACTStreptococcus agalactiae(group BStreptococcus[GBS]) is a Gram-positive bacterium that colonizes the cervicovaginal tract in approximately 25% of healthy women. Although colonization is asymptomatic, GBS can be vertically transmitted to newborns peripartum, causing severe disease such as pneumonia and meningitis. Current prophylaxis, consisting of late gestation screening and intrapartum antibiotics, has failed to completely prevent transmission, and GBS remains a leading cause of neonatal sepsis and meningitis in the United States. Lack of an effective vaccine and emerging antibiotic resistance necessitate exploring novel therapeutic strategies. We have employed a host-directed immunomodulatory therapy using a novel peptide, known as EP67, derived from the C-terminal region of human complement component C5a. Previously, we have demonstratedin vivothat EP67 engagement of the C5a receptor (CD88) effectively limits staphylococcal infection by promoting cytokine release and neutrophil infiltration. Here, using our established mouse model of GBS vaginal colonization, we observed that EP67 treatment results in rapid clearance of GBS from the murine vagina. However, this was not dependent on functional neutrophil recruitment or CD88 signaling, as EP67 treatment reduced the vaginal bacterial load in mice lacking CD88 or the major neutrophil receptor CXCr2. Interestingly, we found that EP67 inhibits GBS growthin vitroandin vivoand that antibacterial activity was specific toStreptococcusspecies. Our work establishes that EP67-mediated clearance of GBS is likely due to direct bacterial killing rather than to enhanced immune stimulation. We conclude that EP67 may have potential as a therapeutic to control GBS vaginal colonization.
CD38 Controls the Innate Immune Response against Listeria monocytogenes
Authors: Lischke Timo , Heesch Kira , Schumacher Valéa , Schneider Michael , Haag Friedrich , Koch-Nolte Friedrich , Mittrücker Hans-Willi 
Published: August 2013

ABSTRACT

CD38, adenosine-5′-diphosphate-ribosyl cyclase 1, is a multifunctional enzyme, expressed on a wide variety of cell types. CD38 has been assigned diverse functions, including generation of calcium-mobilizing metabolites, cell activation, and chemotaxis. Using a murine
Listeria monocytogenes
infection model, we found that CD38 knockout (KO) mice were highly susceptible to infection. Enhanced susceptibility was already evident within 3 days of infection, suggesting a function of CD38 in the innate immune response. CD38 was expressed on neutrophils and inflammatory monocytes, and especially inflammatory monocytes further upregulated CD38 during infection. Absence of CD38 caused alterations of the migration pattern of both cell types to sites of infection. We observed impaired accumulation of cells in the spleen but surprisingly similar or even higher accumulation of cells in the liver. CD38 KO and wild-type mice showed similar changes in the composition of neutrophils and inflammatory monocytes in blood and bone marrow, indicating that mobilization of these cells from the bone marrow was CD38 independent.
In vitro
, macrophages of CD38 KO mice were less efficient in uptake of listeria but still able to kill the bacteria. Dendritic cells also displayed enhanced CD38 expression following infection. However, absence of CD38 did not impair the capacity of mice to prime CD8
+
T cells against
L. monocytogenes
, and CD38 KO mice could efficiently control secondary listeria infection. In conclusion, our results demonstrate an essential role for CD38 in the innate immune response against
L. monocytogenes
.
Choosing a model to predict hospital admission: an observational study of new variants of predictive models for case finding
Authors: Billings John , Georghiou Theo , Blunt Ian , Bardsley Martin 
Published: August 2013

ObjectivesTo test the performance of new variants of models to identify people at risk of an emergency hospital admission. We compared (1) the impact of using alternative data sources (hospital inpatient, A&E, outpatient and general practitioner (GP) electronic medical records) (2) the effects of local calibration on the performance of the models and (3) the choice of population denominators.DesignMultivariate logistic regressions using person-level data adding each data set sequentially to test value of additional variables and denominators.Setting5 Primary Care Trusts within England.Participants1 836 099 people aged 18–95 registered with GPs on 31 July 2009.Main outcome measuresModels to predict hospital admission and readmission were compared in terms of the positive predictive value and sensitivity for various risk strata and with the receiver operating curve C statistic.ResultsThe addition of each data set showed moderate improvement in the number of patients identified with little or no loss of positive predictive value. However, even with inclusion of GP electronic medical record information, the algorithms identified only a small number of patients with no emergency hospital admissions in the previous 2 years. The model pooled across all sites performed almost as well as the models calibrated to local data from just one site. Using population denominators from GP registers led to better case finding.ConclusionsThese models provide a basis for wider application in the National Health Service. Each of the models examined produces reasonably robust performance and offers some predictive value. The addition of more complex data adds some value, but we were unable to conclude that pooled models performed less well than those in individual sites. Choices about model should be linked to the intervention design. Characteristics of patients identified by the algorithms provide useful information in the design/costing of intervention strategies to improve care coordination/outcomes for these patients.
Are interventions to reduce interruptions and errors during medication administration effective?: a systematic review
Authors: Raban Magdalena Z , Westbrook Johanna I 
Published: August 2013

BackgroundMedication administration errors are frequent and lead to patient harm. Interruptions during medication administration have been implicated as a potential contributory factor.ObjectiveTo assess evidence of the effectiveness of interventions aimed at reducing interruptions during medication administration on interruption and medication administration error rates.MethodsIn September 2012 we searched MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Effective Practice and Organisation of Care Group reviews, Google and Google Scholar, and hand searched references of included articles. Intervention studies reporting quantitative data based on direct observations of at least one outcome (interruptions, or medication administration errors) were included.ResultsTen studies, eight from North America and two from Europe, met the inclusion criteria. Five measured significant changes in interruption rates pre and post interventions. Four found a significant reduction and one an increase. Three studies measured changes in medication administration error rates and showed reductions, but all implemented multiple interventions beyond those targeted at reducing interruptions. No study used a controlled design pre and post. Definitions for key outcome indicators were reported in only four studies. Only one study reported κ scores for inter-rater reliability and none of the multi-ward studies accounted for clustering in their analyses.ConclusionsThere is weak evidence of the effectiveness of interventions to significantly reduce interruption rates and very limited evidence of their effectiveness to reduce medication administration errors. Policy makers should proceed with great caution in implementing such interventions until controlled trials confirm their value. Research is also required to better understand the complex relationship between interruptions and error to support intervention design.
A framework for application guidance in virtual memory systems
Authors: Jantz Michael R. , Strickland Carl , Kumar Karthik , Dimitrov Martin , Doshi Kshitij A. 
Published: August 2013

This paper proposes a collaborative approach in which applications can provide guidance to the operating system regarding allocation and recycling of physical memory. The operating system incorporates this guidance to decide which physical page should be used to back a particular virtual page. The key intuition behind this approach is that application software, as a generator of memory accesses, is best equipped to inform the operating system about the relative access rates and overlapping patterns of usage of its own address space. It is also capable of steering its own algorithms in order to keep its dynamic memory footprint under check when there is a need to reduce power or to contain the spillover effects from bursts in demand. Application software, working cooperatively with the operating system, can therefore help the latter schedule memory more effectively and efficiently than when the operating system is forced to act alone without such guidance. It is particularly difficult to achieve power efficiency without application guidance since power expended in memory is a function not merely of the intensity with which memory is accessed in time but also how many physical ranks are affected by an application's memory usage.
Our framework introduces an abstraction called "colors" for the application to communicate its intent to the operating system. We modify the operating system to receive this communication in an efficient way, and to organize physical memory pages into intermediate level grouping structures called "trays" which capture the physically independent access channels and self-refresh domains, so that it can apply this guidance without entangling the application in lower level details of power or bandwidth management.
This paper describes how we re-architect the memory management of a recent Linux kernel to realize a three way collaboration between hardware, supervisory software, and application tasks.
A peta-scalable CPU-GPU algorithm for global atmospheric simulations
Authors: Yang Chao , Xue Wei , Fu Haohuan , Gan Lin , Li Linfeng , Xu Yangtong , Lu Yutong , Sun Jiachang , Yang Guangwen , Zheng Weimin 
Published: August 2013

Developing highly scalable algorithms for global atmospheric modeling is becoming increasingly important as scientists inquire to understand behaviors of the global atmosphere at extreme scales. Nowadays, heterogeneous architecture based on both processors and accelerators is becoming an important solution for large-scale computing. However, large-scale simulation of the global atmosphere brings a severe challenge to the development of highly scalable algorithms that fit well into state-of-the-art heterogeneous systems. Although successes have been made on GPU-accelerated computing in some top-level applications, studies on fully exploiting heterogeneous architectures in global atmospheric modeling are still very less to be seen, due in large part to both the computational difficulties of the mathematical models and the requirement of high accuracy for long term simulations.
In this paper, we propose a peta-scalable hybrid algorithm that is successfully applied in a cubed-sphere shallow-water model in global atmospheric simulations. We employ an adjustable partition between CPUs and GPUs to achieve a balanced utilization of the entire hybrid system, and present a pipe-flow scheme to conduct conflict-free inter-node communication on the cubed-sphere geometry and to maximize communication-computation overlap. Systematic optimizations for multithreading on both GPU and CPU sides are performed to enhance computing throughput and improve memory efficiency. Our experiments demonstrate nearly ideal strong and weak scalabilities on up to 3,750 nodes of the Tianhe-1A. The largest run sustains a performance of 0.8 Pflops in double precision (32% of the peak performance), using 45,000 CPU cores and 3,750 GPUs.
Array dataflow analysis for polyhedral X10 programs
Authors: Yuki Tomofumi , Feautrier Paul , Rajopadhye Sanjay , Saraswat Vijay 
Published: August 2013

This paper addresses the static analysis of an important class of X10 programs, namely those with finish/async parallelism, and affine loops and array reference structure as in the polyhedral model. For such programs our analysis can certify whenever a program is deterministic or flags races.
Our key contributions are (i) adaptation of array dataflow analysis from the polyhedral model to programs with finish/async parallelism, and (ii) use of the array dataflow analysis result to certify determinacy. We distinguish our work from previous approaches by combining the precise statement instance-wise and array element-wise analysis capability of the polyhedral model with finish/async programs that are more expressive than doall parallelism commonly considered in the polyhedral literature. We show that our approach is exact (no false negative/positives) and more precise than previous approaches, but is limited to programs that fit the polyhedral model.