bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Efficacy and Safety of Oritavancin Front-Loaded Dosing Regimens to Daily Dosing: an Analysis of the SIMPLIFI Trial
Authors: Dunbar Lala M. , Milata Joe , McClure Ty , Wasilewski Margaret M. ,   the SIMPLIFI Study Team
Published: May 2011

ABSTRACT

Oritavancin is a novel lipoglycopeptide with demonstrated effectiveness against complicated skin and skin structure infections (cSSSI) caused by Gram-positive pathogens, including those caused by methicillin-resistant
Staphylococcus aureus
(MRSA). The pharmacokinetic and pharmacodynamic profile of oritavancin is favorable for single or infrequent dosing. A phase 2, multicenter, randomized, double-blind, parallel, active-comparator study (ClinicalTrials.gov identifier, NCT00514527) of single and infrequent dosing of intravenous (i.v.) oritavancin for the treatment of cSSSI caused by Gram-positive pathogens (wound infections, major abscess, and cellulitis) was undertaken to evaluate the noninferiority of front-loaded dosing regimens compared to a daily-dosing regimen. A total of 302 patients ≥18 years of age were randomized equally to one of three oritavancin treatment groups, receiving either a daily dose (200 mg) administered for 3 to 7 days, a single dose (1,200 mg), or an infrequent dose (800-mg dose, with the option for an additional 400 mg on day 5). The primary efficacy was defined as a clinical response in clinically evaluable (CE) patients assessed at days 21 to 29 (test of cure [TOC]). The cure rates in the CE population were 72.4% (55/76) in the daily-dose group, 81.5% (66/81) in the 1,200-mg-single-dose group, and 77.5% (55/71) in the infrequent-dose group. In patients with MRSA at baseline, the cure rates were 78.3% (18/23), 73.0% (27/37), and 87.0% (20/23) in the daily-, 1,200-mg-single-, and infrequent-dose groups, respectively; however, the study was not powered to assess outcomes in the MRSA subpopulation, and given the heterogeneity of the types of infection and the small sample size, these do not suggest any true differences in efficacy rates for these pathogens. The frequencies of adverse events were similar among treatment groups. The results of this study show that single- and infrequent-dosing schedules of oritavancin were as efficacious as daily administration and had a similar safety profile in treating cSSSI caused by Gram-positive pathogens, including MRSA.
Antimicrobial Resistance in Urinary Tract Pathogens in Canada from 2007 to 2009: CANWARD Surveillance Study
Authors: Karlowsky James A. , Lagacé-Wiens Philippe R. S. , Simner Patricia J. , DeCorby Melanie R. , Adam Heather J. , Walkty Andrew , Hoban Daryl J. , Zhanel George G. 
Published: May 2011

ABSTRACT

From January 2007 to December 2009, an annual Canadian national surveillance study (CANWARD) tested 2,943 urinary culture pathogens for antimicrobial susceptibilities according to Clinical and Laboratory Standards Institute guidelines. The most frequently isolated urinary pathogens were as follows (number of isolates, percentage of all isolates):
Escherichia coli
(1,581, 54%), enterococci (410, 14%),
Klebsiella pneumoniae
(274, 9%),
Proteus mirabilis
(122, 4%),
Pseudomonas aeruginosa
(100, 3%), and
Staphylococcus aureus
(80, 3%). The rates of susceptibility to trimethoprim-sulfamethoxazole (SXT) were 78, 86, 84, and 93%, respectively, for
E. coli
,
K. pneumoniae
,
P. mirabilis
, and
S. aureus
. The rates of susceptibility to nitrofurantoin were 96, 97, 33, and 100%, respectively, for
E. coli
, enterococci,
K. pneumoniae
, and
S. aureus
. The rates of susceptibility to ciprofloxacin were 81, 40, 86, 81, 66, and 41%, respectively, for
E. coli
, enterococci,
K. pneumoniae
,
P. mirabilis
,
P. aeruginosa
, and
S. aureus
. Statistical analysis of resistance rates (resistant plus intermediate isolates) by year for
E. coli
over the 3-year study period demonstrated that increased resistance rates occurred only for amoxicillin-clavulanate (from 1.8 to 6.6%;
P
< 0.001) and for SXT (from 18.6 to 24.3%;
P
= 0.02). For isolates of
E. coli
, in a multivariate logistic regression model, hospital location was independently associated with resistance to ciprofloxacin (
P
= 0.026) with higher rates of resistance observed in inpatient areas (medical, surgical, and intensive care unit wards). Increased age was also associated with resistance to ciprofloxacin (
P
< 0.001) and with resistance to two or more commonly prescribed oral agents (amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and SXT) (
P
= 0.005). We conclude that frequently prescribed empirical agents for urinary tract infections, such as SXT and ciprofloxacin, demonstrate lowered
in vitro
susceptibilities when tested against recent clinical isolates.
Five-Minute Exposure to Caspofungin Results in Prolonged Postantifungal Effects and Eliminates the Paradoxical Growth of Candida albicans
Authors: Shields Ryan K. , Nguyen M. Hong , Press Ellen G. , Clancy Cornelius J. 
Published: May 2011

ABSTRACT

We studied the impact of brief caspofungin exposures on postantifungal effects (PAFEs) and paradoxical effects for five
Candida albicans
isolates. In time-kill studies, caspofungin at 4× and 16× the MIC resulted in significant killing of all isolates. Caspofungin at 8 μg/ml resulted in lower levels of killing, and paradoxical effects were evident with 4 isolates. Caspofungin exposures of 5 to 60 min caused prolonged, concentration-dependent killing that approached or exceeded the results seen with time-kill experiments and eliminated paradoxical growth.
Fate of Mutation Rate Depends on
agr
Locus Expression during Oxacillin-Mediated Heterogeneous-Homogeneous Selection in Methicillin-Resistant Staphylococcus aureus Clinical Strains
Authors: Plata Konrad B. , Rosato Roberto R. , Rosato Adriana E. 
Published: May 2011

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) strains are characterized by a heterogeneous expression of resistance. We have previously shown in clinical oxacillin-susceptible,
mecA-
positive MRSA strains that selection from a very heterogeneous (HeR) to highly homogeneous (HoR) resistant phenotype was mediated by acquisition of mutations through an oxacillin-induced SOS response. In the present study, we used a spotted DNA microarray to evaluate differential gene expression during HeR-HoR selection and found increased expression of the
agr
two-component regulatory system. We hypothesized that increased expression of
agr
represents a mechanistically relevant component of this process. We demonstrated that inactivation of
agr
during the HeR-HoR selection process results in a significant increase in mutation rate; these effects were reversed by complementing the
agr
mutant. Furthermore, we found that extemporal ectopic expression of
agr
and, more specifically, RNAII in
agr
-null mutant HeR cells suppressed mutation frequency and the capacity of these cells to undergo the HeR-HoR selection. These findings sustain the concept that increased expression of
agr
during HeR-HoR selection plays a critical role in regulating the β-lactam-induced increased mutation rate in very heterogeneous MRSA strains. Moreover, they indicate that a temporally controlled increase in
agr
expression is required to tightly modulate SOS-mediated mutation rates, which then allows for full expression of oxacillin homogeneous resistance in very heterogeneous clinical MRSA strains.
The Antibiotic Dehydrophos Is Converted to a Toxic Pyruvate Analog by Peptide Bond Cleavage in Salmonella enterica
Authors: Circello Benjamin T. , Miller Charles G. , Lee Jin-Hee , van der Donk Wilfred A. , Metcalf William W. 
Published: May 2011

ABSTRACT

The metabolic processing of dehydrophos, a broad-spectrum peptide antibiotic containing an unusual vinyl-phosphonate moiety, was examined by using a panel of
Salmonella enterica
mutants deficient in peptide uptake and catabolism. Dehydrophos bioactivity is lost in
opp
tpp
double mutants, demonstrating a requirement for uptake via nonspecific oligopeptide permeases. Dehydrophos bioactivity is also abolished in a quadruple
Salmonella
mutant lacking the genes encoding peptidases A, B, D, and N, showing that hydrolysis of the peptide bond is required for activity.
31
P nuclear magnetic resonance spectroscopy was used to assess the fate of dehydrophos following
in vitro
digestion of the antibiotic with purified PepA. The results suggest that the initial product of peptidase processing is 1-aminovinyl-phosphonate
O
-methyl ester. This phosphonate analogue of dehydroalanine undergoes rearrangement to the more stable imine, followed by spontaneous hydrolysis to yield
O
-methyl-acetylphosphonate, a structural analogue of pyruvate. This compound is a known inhibitor of pyruvate dehydrogenase and pyruvate oxidase and is probably the active species responsible for dehydrophos bioactivity.
Immunomodulatory and Protective Roles of Quorum-Sensing Signaling Molecules
N
-Acyl Homoserine Lactones during Infection of Mice with Aeromonas hydrophila
Authors: Khajanchi Bijay K. , Kirtley Michelle L. , Brackman Sheri M. , Chopra Ashok K. 
Published: May 2011

ABSTRACT

Aeromonas hydrophila
leads to both intestinal and extraintestinal infections in animals and humans, and the underlying mechanisms leading to mortality are largely unknown. By using a septicemic mouse model of infection, we showed that animals challenged with
A. hydrophila
die because of kidney and liver damage, hypoglycemia, and thrombocytopenia. Pretreatment of animals with quorum-sensing-associated signaling molecules
N
-acyl homoserine lactones (AHLs), such as butanoyl and hexanoyl homoserine lactones (C
4
- and C
6
-HSLs), as well as
N
-3-oxododecanoyl (3-oxo-C
12
)-HSL, prevented clinical sequelae, resulting in increased survivability of mice. Since little is known as to how different AHLs modulate the immune response during infection, we treated mice with the above AHLs prior to lethal
A. hydrophila
infection. When we compared results in such animals to those in controls, the treated animals exhibited a significantly reduced bacterial load in the blood and other mouse organs, as well as various levels of cytokines/chemokines. Importantly, neutrophil numbers were significantly elevated in the blood of C
6
-HSL-treated mice compared to those in animals given phosphate-buffered saline and then infected with the bacteria. These findings coincided with the fact that neutropenic animals were more susceptible to
A. hydrophila
infection than normal mice. Our data suggested that neutrophils quickly cleared bacteria by either phagocytosis or possibly another mechanism(s) during infection. In a parallel study, we indeed showed that other predominant immune cells inflicted during
A. hydrophila
infections, such as murine macrophages, when they were pretreated with AHLs, rapidly phagocytosed bacteria, whereas untreated cells phagocytosed fewer bacteria. This study is the first to report that AHL pretreatment modulates the innate immune response in mice and enhances their survivability during
A. hydrophila
infection.
Iron-Regulated Lysis of Recombinant Escherichia coli in Host Releases Protective Antigen and Confers Biological Containment
Authors: Guan Lingyu , Mu Wei , Champeimont Jonathan , Wang Qiyao , Wu Haizhen , Xiao Jingfan , Lubitz Werner , Zhang Yuanxing , Liu Qin 
Published: May 2011

ABSTRACT

The use of a recombinant bacterial vector vaccine is an attractive vaccination strategy to induce an immune response to a carried protective antigen. The superiorities of live bacterial vectors include mimicry of a natural infection, intrinsic adjuvant properties, and the potential for administration by mucosal routes.
Escherichia coli
is a simple and efficient vector system for production of exogenous proteins. In addition, many strains are nonpathogenic and avirulent, making it a good candidate for use in recombinant vaccine design. In this study, we screened 23 different iron-regulated promoters in an
E. coli
BL21(DE3) vector and found one, P
viuB
, with characteristics suitable for our use. We fused P
viuB
with lysis gene
E
, establishing an
in vivo
inducible lysis circuit. The resulting
in vivo
lysis circuit was introduced into a strain also carrying an IPTG (isopropyl-β-
d
-thiogalactopyranoside)-inducible P
T7
-controlled protein synthesis circuit, forming a novel
E. coli
-based protein delivery system. The recombinant
E. coli
produced a large amount of antigen
in vitro
and could deliver the antigen into zebrafish after vaccination via injection. The strain subsequently lysed in response to the iron-limiting signal
in vivo
, implementing antigen release and biological containment. The
gapA
gene, encoding the protective antigen GAPDH (glyceraldehyde-3-phosphate dehydrogenase) from the fish pathogen
Aeromonas hydrophila
LSA34, was introduced into the
E. coli
-based protein delivery system, and the resultant recombinant vector vaccine was evaluated in turbot (
Scophtalmus maximus
). Over 80% of the vaccinated fish survived challenge with
A. hydrophila
LSA34, suggesting that the
E. coli
-based antigen delivery system has great potential in bacterial vector vaccine applications.
The association between sedentary leisure and physical activity in middle-aged adults
Authors: Burton Nicola W , Khan Asaduzzaman , Brown Wendy J , Turrell Gavin 
Published: May 2011

AimThe aim of this study was to examine the association between time spent in sedentary leisure and physical activity level in mid-aged men and women.MethodsData were from the 2007 HABITAT study in Brisbane, Australia. A mail survey sent to 17 000 adults (40–65 years) provided 11 037 responses (68.5%), and 9121 (82.6%) were analysed. Sedentary leisure was quantified as hours/day spent sitting watching television, in home computer use, in general leisure, and overall, on a usual week and weekend day. Physical activity level (no activity, low, recommended, high, very high) included walking, moderate and vigorous activity combined into a measure of MET.min/week. Data were analysed separately for men and women using multilevel multinomial logistic regression with adjustment for sociodemographic and health variables.ResultsThe only significant negative associations were between watching television on a week day and high activity in men (0.91; 0.83–0.98), and home computer use on a weekend day and very high activity in men (0.89; 0.81–0.98). For both men and women, there were significant positive associations between overall sedentary leisure time on a week day and very high activity (men: 1.07, 1.02–1.13; women: 1.10, 1.04–1.16), home computer use on a week day and very high activity (men: 1.11, 1.01–1.22; women: 1.15, 1.04–1.27) and general leisure on a week day and most activity levels.ConclusionsSedentary leisure is mainly independent of physical activity and does not preclude meeting physical activity recommendations.
Effects of aspect and type of competition on the early performance of Nothofagus dombeyi and Nothofagus nervosa in a mixed plantation
Authors: Donoso Pablo J. , Muñoz Ariel A. , Thiers Oscar , Soto Daniel P. , Donoso Claudio 
Published: May 2011

In the Andes of Chile, two valuable Nothofagus tree species coexist (Nothofagus dombeyi (Mirb.) Oerst. and Nothofagus nervosa (Phil.) Krasser). They could provide an opportunity for mixed plantations because of their ecological differences. In a mixed plantation with a checkerboard design on a good site where the two species naturally coexist, we evaluated their performance according to aspect and type of competition. Nothofagus dombeyi had a greater survivorship (90% vs. 65%) and growth (twice in diameter and 20% greater in height). Forking was significantly lower in N. nervosa (23% vs. 70%). Aspect did not significantly affect the performance of N. dombeyi. The north aspect had a significant negative effect on survivorship of N. nervosa, but aspect did not significantly affect growth or forking of this species. The aspect – type of competition interaction was only significant for N. nervosa in diameter and marginally significant in height. The checkerboard design allowed for a clear separation of interspecific and intraspecific competition in this mixed plantation. Interspecific competition favored growth of N. nervosa on the north aspect (facilitation) and was detrimental to N. nervosa on the south aspect (competition). These results have a direct application when planting mixtures of species of complementary ecological characteristics that can increase the value of the plantation.
Augmentation of cellular immune response byIpomoea obscuraand Ipobscurine alkaloid attenuates tumor growth in mice
Authors: Hamsa T.P. , Kuttan Girija 
Published: May 2011

The immune status of the host plays a crucial role in controling the process of carcinogenesis. General or selective activation of various immunocompetent cells and their secretory function to maintain a healthy immune status may help in cancer prophylaxis, as well as therapy. The present study focused on the effect of Ipomoea obscura and Ipobscurine on cell-mediated immune response. In this study we evaluated the effect of I. obscura and an indole alkaloid fraction from I. obscura on effector mechanisms of cell-mediated immune response by analyzing cytotoxic T lymphocyte (CTL) activity, natural killer (NK) cell activity, antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent complement-mediated cytotoxicity (ACC). The effect of I. obscura and Ipobscurine on interleukin-2 (IL-2) and interferon-γ (IFN-γ) levels was also analyzed. In the in vitro and in vivo systems, I. obscura and Ipobscurine treatment augmented cell-mediated immune response by enhancing the killing activity of CTL and NK cells from splenocytes in normal as well as tumor-bearing mice. ADCC and ACC were also enhanced significantly in both normal and tumor-bearing animals after drug administration, compared with untreated control. Administration of I. obscura and Ipobscurine significantly enhanced the production of IL-2 and IFN-γ in normal as well as tumor-bearing animals. This study reveals that both I. obscura and Ipobscurine have the potential to augment immune response through the enhanced secretion of IL-2 and IFN-γ by T cells and thereby inhibit tumor growth and as an alternative medicine for cancer treatment.
THE RECONSTRUCTION OF SATELLITE IMAGES BASED ON FRACTAL INTERPOLATION
Authors: CHEN CHING-JU , CHENG SHU-CHEN , HUANG Y. M. 
Published: May 2011

This study discussed the application of a fractal interpolation method in satellite image data reconstruction. It used low-resolution images as the source data for fractal interpolation reconstruction. Using this approach, a high-resolution image can be reconstructed when there is only a low-resolution source image available. The results showed that the high-resolution image data from fractal interpolation can effectively enhance the sharpness of the border contours. Implementing fractal interpolation on an insufficient image resolution image can avoid jagged edges and mosaic when enlarging the image, as well as improve the visibility of object features in the region of interest. The proposed approach can thus be a useful tool in land classification by satellite images.
Human activity analysis
Authors: Aggarwal J.K. , Ryoo M.S. 
Published: May 2011

Human activity recognition is an important area of computer vision research. Its applications include surveillance systems, patient monitoring systems, and a variety of systems that involve interactions between persons and electronic devices such as human-computer interfaces. Most of these applications require an automated recognition of high-level activities, composed of multiple simple (or atomic) actions of persons. This article provides a detailed overview of various state-of-the-art research papers on human activity recognition. We discuss both the methodologies developed for simple human actions and those for high-level activities. An approach-based taxonomy is chosen that compares the advantages and limitations of each approach.
Recognition methodologies for an analysis of the simple actions of a single person are first presented in the article. Space-time volume approaches and sequential approaches that represent and recognize activities directly from input images are discussed. Next, hierarchical recognition methodologies for high-level activities are presented and compared. Statistical approaches, syntactic approaches, and description-based approaches for hierarchical recognition are discussed in the article. In addition, we further discuss the papers on the recognition of human-object interactions and group activities. Public datasets designed for the evaluation of the recognition methodologies are illustrated in our article as well, comparing the methodologies' performances. This review will provide the impetus for future research in more productive areas.
Parallelization libraries
Authors: Bhattacharjee Abhishek , Contreras Gilberto , Martonosi Margaret 
Published: May 2011

Creating efficient, scalable dynamic parallel runtime systems for chip multiprocessors (CMPs) requires understanding the overheads that manifest at high core counts and small task sizes.
In this article, we assess these overheads on Intel's Threading Building Blocks (TBB) and OpenMP. First, we use real hardware and simulations to detail various scheduler and synchronization overheads. We find that these can amount to 47% of TBB benchmark runtime and 80% of OpenMP benchmark runtime. Second, we propose load balancing techniques such as occupancy-based and criticality-guided task stealing, to boost performance.
Overall, our study provides valuable insights for creating robust, scalable runtime libraries.
Differences in Repeating Patterns of Complex Fractionated Left Atrial Electrograms in Longstanding Persistent Atrial Fibrillation as Compared With Paroxysmal Atrial Fibrillation
Authors: Ciaccio Edward J. , Biviano Angelo B. , Whang William , Vest John A. , Gambhir Alok , Einstein Andrew J. , Garan Hasan 
Published: May 2011

Background—
Complex fractionated atrial electrograms (CFAE) are morphologically more uniform in persistent longstanding as compared with paroxysmal atrial fibrillation (AF). It was hypothesized that this may result from a greater degree of repetitiveness in CFAE patterns at disparate left atrial (LA) sites in longstanding AF.

Methods and Results—

CFAEs were obtained from recording sites outside the 4 pulmonary vein (PV) ostia and at a posterior and an anterior LA site during paroxysmal and longstanding persistent AF (10 patients each, 120 sequences total). To quantify repetitiveness in CFAE, the dominant frequency was measured from ensemble spectra using 8.4-second sequences, and repetitiveness was calculated by 2 novel techniques: linear prediction and Fourier reconstruction methods. Lower prediction and reconstruction errors were considered indicative of increasing repetitiveness and decreasing randomness. In patients with paroxysmal AF, CFAE pattern repetitiveness was significantly lower (randomness higher) at antral sites outside PV ostia as compared with LA free wall sites (
P
<0.001). In longstanding AF, repetitiveness increased outside the PV ostia, especially outside the left superior PV ostium, and diminished at the LA free wall sites. The result was that in persistent AF, there were no significant site-specific differences in CFAE repetitiveness at the selected LA locations used in this study. Average dominant frequency magnitude was 5.32±0.29 Hz in paroxysmal AF and higher in longstanding AF, at 6.27±0.13 Hz (
P
<0.001), with the frequency of local activation approaching a common upper bound for all sites.

Conclusions—
In paroxysmal AF, CFAE repetitiveness is low and randomness high outside the PVs, particularly the left superior PV. As evolution to persistent longstanding AF occurs, CFAE repetitiveness becomes more uniformly distributed at disparate sites, possibly signifying an increasing number of drivers from remote PVs.