bluuebunny/crossref_metadata_2025_split huggingface dataset:
A COMPARISON OF ORDER‐RELEASE AND DISPATCH RULES FOR THE DYNAMIC WEIGHTED EARLY/TARDY PROBLEM
Authors: ROHLEDER THOMAS R. , SCUDDER GARY 
Published: July 2010

The early/tardy problem is one of the most vexing pieces of the complex production scheduling decision process. So far most of the research has been on single‐machine environments. Hence, we considered the weighted early/tardy scheduling problem in a simulated dynamic multimachine job shop. We analyzed controlled job‐release and dispatch rules using time and cost information at a variety of stationary and nonstationary utilization rates, due‐date allowances, and early/tardy cost levels. We found a newly developed method for controlling the release for all job operations using early/tardy cost information, superior to other release mechanisms overall in both our stationary and nonstationary analyses. We found immediate release useful at many high utilization conditions and a gateway‐only release method best in many low utilization conditions. A modified version of a single‐machine early/tardy dispatch method was clearly superior to the dispatch rules for almost all the simulated shop conditions.
The Modern Call Center: A Multi‐Disciplinary Perspective on Operations Management Research
Authors: Aksin Zeynep , Armony Mor , Mehrotra Vijay 
Published: July 2010

Call centers are an increasingly important part of today's business world, employing millions of agents across the globe and serving as a primary customer‐facing channel for firms in many different industries. Call centers have been a fertile area for operations management researchers in several domains, including forecasting, capacity planning, queueing, and personnel scheduling. In addition, as telecommunications and information technology have advanced over the past several years, the operational challenges faced by call center managers have become more complicated. Issues associated with human resources management, sales, and marketing have also become increasingly relevant to call center operations and associated academic research. In this paper, we provide a survey of the recent literature on call center operations management. Along with traditional research areas, we pay special attention to new management challenges that have been caused by emerging technologies, to behavioral issues associated with both call center agents and customers, and to the interface between call center operations and sales and marketing. We identify a handful of broad themes for future investigation while also pointing out several very specific research opportunities.
Genetic Factors Associated with Elevated Carbapenem Resistance in KPC-Producing
Klebsiella pneumoniae
Authors: Kitchel Brandon , Rasheed J. Kamile , Endimiani Andrea , Hujer Andrea M. , Anderson Karen F. , Bonomo Robert A. , Patel Jean B. 
Published: July 2010

ABSTRACT

In the United States, the most prevalent mechanism of carbapenem resistance among
Enterobacteriaceae
is the production of a
Klebsiella pneumoniae
carbapenemase (KPC). KPC-producing isolates often exhibit a range of carbapenem MICs. To better understand the factors that contribute to overall carbapenem resistance, we analyzed 27 KPC-producing
K. pneumoniae
isolates with different levels of carbapenem resistance, 11 with low-level (i.e., meropenem or imipenem MIC ≤ 4 μg/ml), 2 with intermediate-level (i.e., meropenem and imipenem MIC = 8 μg/ml), and 14 with high-level (i.e., imipenem or meropenem MIC ≥ 16 μg/ml) carbapenem resistance, that were received from throughout the United States. Among 14 isolates that exhibited high-level carbapenem resistance, Western blot analysis indicated that 10 produced an elevated amount of KPC. These isolates either contained an increased
bla
KPC
gene copy number (
n
= 3) or had deletions directly upstream of the
bla
KPC
gene (
n
= 7). Four additional isolates lacked elevated KPC production but had high-level carbapenem resistance. Porin sequencing analysis identified 22 isolates potentially lacking a functional OmpK35 and three isolates potentially lacking a functional OmpK36. The highest carbapenem MICs were found in two isolates that lacked both functioning porins and produced elevated amounts of KPC. The 11 isolates with low-level carbapenem resistance contained neither an upstream deletion nor increased
bla
KPC
copy number. These results suggest that both
bla
KPC
copy number and deletions in the upstream genetic environment affect the level of KPC production and may contribute to high-level carbapenem resistance in KPC-producing
K. pneumoniae
, particularly when coupled with OmpK36 porin loss.
Phase 2a Study of the CCR5 Monoclonal Antibody PRO 140 Administered Intravenously to HIV-Infected Adults
Authors: Jacobson Jeffrey M. , Lalezari Jacob P. , Thompson Melanie A. , Fichtenbaum Carl J. , Saag Michael S. , Zingman Barry S. , D'Ambrosio Paul , Stambler Nancy , Rotshteyn Yakov , Marozsan Andre J. , Maddon Paul J. , Morris Stephen A. , Olson William C. 
Published: July 2010

ABSTRACTThe anti-CCR5 antibody PRO 140 has shown potent and prolonged antiretroviral activity in subjects infected with CCR5-tropic (R5) HIV-1. Prior studies have examined single intravenous doses ranging up to 5 mg/kg of body weight or up to three subcutaneous doses ranging up to 324 mg. Here we report the results of a randomized, double-blind, placebo-controlled trial that examined the antiviral activity, tolerability, and pharmacokinetics of single 5-mg/kg and 10-mg/kg intravenous infusions of PRO 140 in 31 treated subjects. Eligibility criteria included HIV-1 RNA levels of >5,000 copies/ml, CD4+cell counts of >300/μl, no antiretroviral therapy for ≥12 weeks, and detection of only R5 HIV-1 in the original Trofile assay. Following poststudy testing with an enhanced-sensitivity Trofile assay, one subject treated with 10 mg/kg was reclassified as having dual/mixed-tropic virus at screening, and the data for that subject were censored from efficacy analyses. The mean maximum reduction of the HIV-1 RNA level from the baseline level was 1.8 log10units for both the 5-mg/kg and 10-mg/kg doses (P< 0.0001 relative to placebo). Viral loads reached their nadir at day 12 posttreatment and remained significantly (P< 0.01) reduced through day 29 for both PRO 140 dose groups. Treatment was generally well tolerated, with no dose-limiting toxicity being observed. Peak serum concentrations and overall exposures increased proportionally with dose. In summary, single 5-mg/kg and 10-mg/kg doses of PRO 140 exhibited potent, long-lived antiviral activity and were generally well tolerated. The findings further delineate the safety and antiviral properties of this novel, long-acting antiretroviral agent.
Dissemination of an
Enterococcus
Inc18-Like
vanA
Plasmid Associated with Vancomycin-Resistant
Staphylococcus aureus
Authors: Zhu Wenming , Murray Patrick R. , Huskins W. Charles , Jernigan John A. , McDonald Lawrence C. , Clark Nancye C. , Anderson Karen F. , McDougal Linda K. , Hageman Jeff C. , Olsen-Rasmussen Melissa , Frace Mike , Alangaden George J. , Chenoweth Carol , Zervos Marcus J. , Robinson-Dunn Barbara , Schreckenberger Paul C. , Reller L. Barth , Rudrik James T. , Patel Jean B. 
Published: July 2010

ABSTRACT

Of the 9 vancomycin-resistant
Staphylococcus aureus
(VRSA) cases reported to date in the literature, 7 occurred in Michigan. In 5 of the 7 Michigan VRSA cases, an Inc18-like
vanA
plasmid was identified in the VRSA isolate and/or an associated vancomycin-resistant
Enterococcus
(VRE) isolate from the same patient. This plasmid may play a critical role in the emergence of VRSA. We studied the geographical distribution of the plasmid by testing 1,641 VRE isolates from three separate collections by PCR for plasmid-specific genes
traA
,
repR
, and
vanA
. Isolates from one collection (phase 2) were recovered from surveillance cultures collected in 17 hospitals in 13 states. All VRE isolates from 2 Michigan institutions (
n
= 386) and between 60 and 70 VRE isolates (
n
= 883) from the other hospitals were tested. Fifteen VRE isolates (3.9%) from Michigan were positive for an Inc18-like
vanA
plasmid (9
E. faecalis
[12.5%], 3
E. faecium
[1.0%], 2
E. avium
, and 1
E. raffinosus
). Six VRE isolates (0.6%) from outside Michigan were positive (3
E. faecalis
[2.7%] and 3
E. faecium
[0.4%]). Of all
E. faecalis
isolates tested, 6.0% were positive for the plasmid, compared to 0.6% for
E. faecium
and 3.0% for other spp. Fourteen of the 15 plasmid-positive isolates from Michigan had the same Tn
1546
insertion site location as the VRSA-associated Inc18-like plasmid, whereas 5 of 6 plasmid-positive isolates from outside Michigan differed in this characteristic. Most plasmid-positive
E. faecalis
isolates demonstrated diverse patterns by PFGE, with the exception of three pairs with indistinguishable patterns, suggesting that the plasmid is mobile in nature. Although VRE isolates with the VRSA-associated Inc18-like
vanA
plasmid were more common in Michigan, they remain rare. Periodic surveillance of VRE isolates for the plasmid may be useful in predicting the occurrence of VRSA.
In Vitro
Pharmacokinetic and Pharmacodynamic Evaluation of S-013420 against
Haemophilus influenzae
and
Streptococcus pneumoniae
Authors: Homma Tomoyuki , Hori Toshihiko , Ohshiro Merime , Maki Hideki , Yamano Yoshinori , Shimada Jingoro , Kuwahara Shogo 
Published: July 2010

ABSTRACT

The pharmacokinetic (PK)/pharmacodynamic (PD) parameters and the antibacterial activity of S-013420, a novel bicyclolide, against
Haemophilus influenzae
and
Streptococcus pneumoniae
, including macrolide-resistant isolates, were investigated using an
in vitro
PD model. Various time-concentration curves were artificially constructed by modifying the PK data obtained in phase I studies. The activity against
H. influenzae
was evaluated using two parameters, that is, the area above the killing curve (AAC) and the viable cell reduction at 24 h. The relationships between the antibacterial activity of S-013420 and the three PK/PD parameters were investigated by fitting the data to the sigmoid maximum effective concentration model. The square of the correlation coefficient (
R
2
) values for AAC versus the area under the concentration-time curve from 0 to 24 h (AUC
0-24
)/MIC, the peak concentration (
C
max
)/MIC, and the cumulative percentage of a 24-h period that the drug concentration exceeded the MIC under steady-state PK conditions (%
T
MIC
) were 0.92, 0.87, and 0.49, respectively. The
R
2
values for viable cell reduction at 24 h versus AUC
0-24
/MIC,
C
max
/MIC, and %
T
MIC
were 0.93, 0.61, and 0.56, respectively. These results demonstrated that AUC
0-24
/MIC is the most significant parameter for evaluation of the antibacterial activity of S-013420. The values of AUC
0-24
/MIC required for maximum and static efficacy were 10.8 and 9.63, respectively, for
H. influenzae
and 16.3 to 22.3 and 4.66 to 9.01, respectively, for
S. pneumoniae
. This analysis is considered useful for determining the AUC value at the infection site, which would be required for efficacy in clinical use.
Role of Arginine Deiminase of
Streptococcus cristatus
in
Porphyromonas gingivalis
Colonization
Authors: Wu Jie , Xie Hua 
Published: July 2010

ABSTRACT

The ability to attach to a variety of oral surfaces is an important characteristic of
Porphyromonas gingivalis
. Previous studies have demonstrated that expression and production of FimA, a major subunit protein of the long fimbriae, is required for
P. gingivalis
colonization. Here we report that a surface protein, arginine deiminase (ArcA) of
Streptococcus cristatus
, represses FimA production and inhibits biofilm formation of
P. gingivalis
. This inhibitory function of ArcA is also observed in the formation of heterotypic
P. gingivalis-Streptococcus gordonii
biofilms.
P. gingivalis
is released from streptococcal substrates in the presence of ArcA, likely due to an inhibition of FimA production. This work suggests that ArcA may have the potential to be a specific antibiofilm agent to fight
P. gingivalis
infections.
Efficacy and Safety of Nemonoxacin versus Levofloxacin for Community-Acquired Pneumonia
Authors: van Rensburg Dirkie J. J. , Perng Reury-Perng , Mitha Ismail H. , Bester Andrè J. , Kasumba Joseph , Wu Ren-Guang , Ho Ming-Lin , Chang Li-Wen , Chung David T. , Chang Yu-Ting , King Chi-Hsin R. , Hsu Ming-Chu 
Published: July 2010

ABSTRACT

Nemonoxacin, a novel nonfluorinated quinolone, exhibits potent
in vitro
and
in vivo
activities against community-acquired pneumonia (CAP) pathogens, including multidrug-resistant
Streptococcus pneumoniae
. Patients with mild to moderate CAP (
n
= 265) were randomized to receive oral nemonoxacin (750 mg or 500 mg) or levofloxacin (500 mg) once daily for 7 days. Clinical responses were determined at the test-of-cure visit in intent-to-treat (ITT), clinical per protocol (PPc), evaluable-ITT, and evaluable-PPc populations. The clinical cure rates for 750 mg nemonoxacin, 500 mg nemonoxacin, and levofloxacin were 89.9%, 87.0%, and 91.1%, respectively, in the evaluable-ITT population; 91.7%, 87.7%, and 90.3%, respectively, in the evaluable-PPc population; 82.6%, 75.3%, and 80.0%, respectively, in the ITT population; and 83.5%, 78.0%, and 82.3%, respectively, in the PPc population. Noninferiority to levofloxacin was demonstrated in both the 750-mg and 500-mg nemonoxacin groups for the evaluable-ITT and evaluable-PPc populations, and also in the 750 mg nemonoxacin group for the ITT and PPc populations. Overall bacteriological success rates were high for all treatment groups in the evaluable-bacteriological ITT population (90.2% in the 750 mg nemonoxacin group, 84.8% in the 500 mg nemonoxacin group, and 92.0% in the levofloxacin group). All three treatments were well tolerated, and no drug-related serious adverse events were observed. Overall, oral nemonoxacin (both 750 mg and 500 mg) administered for 7 days resulted in high clinical and bacteriological success rates in CAP patients. Further, good tolerability and excellent activity against common causative pathogens were demonstrated. Nemonoxacin (750 mg and 500 mg) once daily is as effective and safe as levofloxacin (500 mg) once daily for the treatment of CAP.
Clinical Evaluation of a Dried Blood Spot Assay for Atazanavir
Authors: Van Schooneveld Trevor , Swindells Susan , Nelson Sarah R. , Robbins Brian L. , Moore Ryan , Fletcher Courtney V. 
Published: July 2010

ABSTRACT

Current procedures for obtaining and measuring plasma concentrations of HIV protease inhibitors (PIs) are technically challenging. Dried blood spot (DBS) assays offer a way to overcome many of the obstacles. We sought to develop a DBS assay for quantitation of the PI atazanavir (ATV) and to compare this method with a previously validated plasma assay. We prospectively enrolled 48 patients with well-controlled HIV disease who had been on ATV for at least 7 days. ATV was quantified from plasma by use of high-performance liquid chromatography (HPLC). A reversed-phase ultrahigh-performance liquid chromatography (UPLC) assay was utilized for DBS samples. The concentrations of ATV quantified in a DBS matrix showed very strong agreement with those measured in plasma (
r
2
= 0.988). The mean difference in ATV concentration between the two methods was −10.8% (95% confidence interval [95% CI], −7.65% to −13.95%), indicating that the DBS method has a slight negative bias. A majority (97.8%) of the differences in concentration between the two assays fell within ±2 standard deviations. ATV concentrations were lower in subjects who had detectable HIV RNA in plasma (mean, 543 ng/ml) than in those with HIV RNA of <50 copies/ml (mean, 1,582 ng/ml) (
P
= 0.03, Wilcoxon rank-sum test). In conclusion, our study demonstrated that ATV quantitation in a DBS matrix is feasible and accurate. DBS use offers a convenient alternative for measuring plasma concentrations of ATV and may have utility in monitoring of drug concentrations in clinical practice and in future studies.
In Vivo
Protection Provided by a Synthetic New Alpha-Galactosyl Ceramide Analog against Bacterial and Viral Infections in Murine Models
Authors: Lin Kun-Hsien , Liang Jian-Jong , Huang Wen-I , Lin-Chu Shao-Ying , Su Ching-Yao , Lee Yi-Ling , Jan Jia-Tsong , Lin Yi-Ling , Cheng Yih-Shyun E. , Wong Chi-Huey 
Published: July 2010

ABSTRACT

Alpha-galactosyl ceramide (α-GalCer) has been known to bind to the CD1d receptor on dendritic cells and activate invariant natural killer T (iNKT) cells, which subsequently secrete T-helper-cell 1 (Th1) and Th2 cytokines, which correlate with anti-infection activity and the prevention of autoimmune diseases, respectively. α-GalCer elicits the secretion of these two cytokines nonselectively, and thus, its effectiveness is limited by the opposing effects of the Th1 and Th2 cytokines. Reported here is the synthesis of a new α-GalCer analog (compound C34), based on the structure of CD1d, with a 4-(4-fluorophenoxy) phenyl undecanoyl modification of the
N
-acyl moiety of α-GalCer. Using several murine bacterial and viral infection models, we demonstrated that C34 has superior antibacterial and antiviral activities in comparison with those of several other Th1-selective glycolipids and that it is most effective by administering it to mice in a prophylactic manner before or shortly after infection.
Pharmacokinetics, Safety, and Tolerability of Voriconazole in Immunocompromised Children
Authors: Walsh Thomas J. , Driscoll Timothy , Milligan Peter A. , Wood Nolan D. , Schlamm Haran , Groll Andreas H. , Jafri Hasan , Arrieta Antonio C. , Klein Nigel J. , Lutsar Irja 
Published: July 2010

ABSTRACT
The pharmacokinetics of voriconazole in children receiving 4 mg/kg intravenously (i.v.) demonstrate substantially lower plasma exposures (as defined by area under the concentration-time curve [AUC]) than those in adults receiving the same therapeutic dosage. These differences in pharmacokinetics between children and adults limit accurate prediction of pediatric voriconazole exposure based on adult dosages. We therefore studied the pharmacokinetics and tolerability of higher dosages of an i.v.-to-oral regimen of voriconazole in immunocompromised children aged 2 to <12 years in two dosage cohorts for the prevention of invasive fungal infections. The first cohort received 4 mg/kg i.v. every 12 h (q12h), then 6 mg/kg i.v. q12h, and then 4 mg/kg orally (p.o.) q12h; the second received 6 mg/kg i.v. q12h, then 8 mg/kg i.v. q12h, and then 6 mg/kg p.o. q12h. The mean values for the AUC over the dosing interval (AUCτ) for 4 mg/kg and 6 mg/kg i.v. in cohort 1 were 11,827 and 22,914 ng·h/ml, respectively, whereas the mean AUCτ values for 6 mg/kg and 8 mg/kg i.v. in cohort 2 were 17,249 and 29,776 ng·h/ml, respectively. High interpatient variability was observed. The bioavailability of the oral formulation in children was approximately 65%. The safety profiles were similar in the two cohorts and age groups. The most common treatment-related adverse event was increased gamma glutamyl transpeptidase levels. There was no correlation between adverse events and voriconazole exposure. In summary, voriconazole was tolerated to a similar degree regardless of dosage and age; the mean plasma AUCτ for 8 mg/kg i.v. in children approached that for 4 mg/kg i.v. in adults, thus representing a rationally selected dosage for the pediatric population.
γδ T Cells but Not NK Cells Are Essential for Cell-Mediated Immunity againstPlasmodium chabaudiMalaria
Authors: Weidanz William P. , LaFleur GayeLyn , Brown Andrew , Burns James M. , Gramaglia Irene , van der Heyde Henri C. 
Published: July 2010

ABSTRACTBlood-stagePlasmodium chabaudiinfections are suppressed by antibody-mediated immunity and/or cell-mediated immunity (CMI). To determine the contributions of NK cells and γδ T cells to protective immunity, C57BL/6 (wild-type [WT]) mice and B-cell-deficient (JH−/−) mice were infected withP. chabaudiand depleted of NK cells or γδ T cells with monoclonal antibody. The time courses of parasitemia in NK-cell-depleted WT mice and JH−/−mice were similar to those of control mice, indicating that deficiencies in NK cells, NKT cells, or CD8+T cells had little effect on parasitemia. In contrast, high levels of noncuring parasitemia occurred in JH−/−mice depleted of γδ T cells. Depletion of γδ T cells during chronic parasitemia in B-cell-deficient JH−/−mice resulted in an immediate and marked exacerbation of parasitemia, suggesting that γδ T cells have a direct killing effectin vivoon blood-stage parasites. Cytokine analyses revealed that levels of interleukin-10, gamma interferon (IFN-γ), and macrophage chemoattractant protein 1 (MCP-1) in the sera of γδ T-cell-depleted mice were significantly (P< 0.05) decreased compared to hamster immunoglobulin-injected controls, but these cytokine levels were similar in NK-cell-depleted mice and their controls. The time courses of parasitemia in CCR2−/−and JH−/−× CCR2−/−mice and in their controls were nearly identical, indicating that MCP-1 is not required for the control of parasitemia. Collectively, these data indicate that the suppression of acuteP. chabaudiinfection by CMI is γδ T cell dependent, is independent of NK cells, and may be attributed to the deficient IFN-γ response seen early in γδ T-cell-depleted mice.
The awareness and use of chaperones by patients in an English general practice
Authors: Pydah K L , Howard J 
Published: July 2010

ObjectiveTo ascertain and improve the understanding and use of chaperones among the patients of an English general practice (GP).BackgroundDoctors have long been advised to have a third party present during intimate physical examinations. Little is known about the understanding of the term in the general population in England and the consequences of this for the promotion and use of chaperones in GP. We audited the understanding and use of chaperones in an English GP. The aim of the study was to increase the awareness of the availability of chaperones in our population.MethodsA questionnaire was given randomly to 100 patients attending the GP surgery. Participants were asked about their awareness of and frequency of requesting a chaperone while undergoing intimate examinations. Based on the initial results, a poster was designed for the waiting room to increase awareness. Data were collected with the same questionnaire to see if the new poster altered surgery attendees understanding and likely subsequent use of chaperones.ResultsIn the initial audit, 29% of patients were unaware of the termchaperone, and only one person (1%) had ever requested a chaperone. After the introduction of a specially designed poster, the results showed an improvement in awareness from 71% to 89%, and the likely frequency of using a chaperone increased from 1% to 4%.ConclusionThere is a need to improve the understanding of the general population about chaperones if we are to see greater use of chaperones in GP.