bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated size‐specific CT dose monitoring program: Assessing variability in CT dose
Authors: Christianson Olav , Li Xiang , Frush Donald , Samei Ehsan 
Published: November 2012

Purpose:The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size‐specific radiation dose monitoring program for CT and used this program to assess variability in size‐adjusted effective dose from CT imaging.Methods:The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k‐factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose‐length product. The patientˈs thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size‐adjusted effective dose (EDadj). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one‐month period and to analyze the variability in EDadj between scanner models and across institutions.Results:No significant difference was found between computer measurements of patient thickness and observer measurements (p = 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in EDadj that differed by up to 44% from effective dose estimates that were not adjusted by patient size. Additionally, considerable differences were noted in EDadj distributions between scanners, with scanners employing iterative reconstruction exhibiting significantly lower EDadj (range: 9%–64%). Finally, a significant difference (up to 59%) in EDadj distributions was observed between institutions, indicating the potential for dose reduction.Conclusions:The authors developed a robust automated size‐specific radiation dose monitoring program for CT. Using this program, significant differences in EDadj were observed between scanner models and across institutions. This new dose monitoring program offers a unique tool for improving quality assurance and standardization both within and across institutions.
Quantitative 90Y image reconstruction in PET
Authors: Willowson Kathy , Forwood Nicholas , Jakoby Bjoern W. , Smith Anne M. , Bailey Dale L. 
Published: November 2012

Purpose:Positron emission tomography (PET) imaging is increasingly used to confirm localization of90Y microspheres in the treatment of liver cancer. The aim of this work was to evaluate the quantification of 90Y PET data on a current generation time‐of‐flight extended axial field‐of‐view PET/CT camera.Methods:The International Electrotechnical Commission (IEC) body phantom was used to image six spheres of varying diameters containing a high concentration of90Y solution in a lower concentration background. Multiple PET studies were acquired of the phantom over a number of days during decay. The effect of reconstruction parameters in OSEM was evaluated both qualitatively and quantitatively. Expected values of total phantom activity, hot‐sphere, and background concentration were compared to measured values from the reconstructed data as well as misplaced events in a cold insert. The partial volume effect was measured and the effects of time‐of‐flight during reconstruction on hot contrast recovery and background variability were evaluated according to NEMA‐NU2‐2007 protocol, and compared to that for 18F. The method was applied to a patient study following radioembolization to estimate actual implanted radioactivity.Results:Increasing the number of OSEM iterations visually deteriorated image data and resulted in a larger overall difference of hot concentration measures when considering both count high and count poor data. The average difference between measured and true total activity and background concentration was found to be +5% and +5%, respectively. Measured hot‐sphere concentration was linear across all datasets, and while estimated to be within error of expected values, was consistently underestimated by an average of 23%, 12%, and 8%, when using a CT‐derived, 50% threshold‐derived, and 70% threshold‐derived volume of interest, respectively. Partial volume effects were evident in all but the largest sphere, following an expected relationship between object size and recovery coefficient, inferior to that of18F. Time‐of‐flight improved contrast of hot‐spheres but resulted in a deterioration of background variability, following a similar trend to that seen with 18F. The patient data estimated a total implanted activity of 1643 MBq, compared to the intended dose of 1780 MBq, with a difference most likely due to residual and error in the initial dose calibration.Conclusions:Quantitative90Y PET with a state‐of‐the‐art PET/CT scanner with time‐of‐flight and standard corrections for photon interactions demonstrates consistent and acceptable measures of total activity and radionuclide concentration across a range of realistic count statistics. The method is suitable for measuring the radioactivity delivered at the time of 90Y therapy with the potential for absorbed dose calculation.
The Therapeutic Effect of Tigecycline, Unlike That of Ceftazidime, Is Not Influenced by whether the Klebsiella pneumoniae Strain Produces Extended-Spectrum β-Lactamases in Experimental Pneumonia in Rats
Authors: Goessens Wil H. F. , Mouton Johan W. , ten Kate Marian T. , Sörgel Fritz , Kinzig Martina , Bakker-Woudenberg Irma A. J. M. 
Published: November 2012

ABSTRACT

The efficacies of tigecycline and ceftazidime against fatal pneumonia in rats caused by an extended-spectrum β-lactamase (ESBL)-positive
Klebsiella pneumoniae
strain or its wild-type (WT) progenitor were compared. Ceftazidime at 12.5 or 50 mg/kg of body weight twice daily (b.i.d.) was effective (50% or 100% rat survival) in pneumonia caused by the WT isolate but unsuccessful (100% rat mortality) in pneumonia caused by the ESBL-positive variant. In contrast, tigecycline at 6.25, 12.5, or 25 mg/kg b.i.d. showed dosage-dependent efficacy up to 100% rat survival irrespective of the ESBL character of the infecting organism.
Evaluation of an Expanded Microarray for Detecting Antibiotic Resistance Genes in a Broad Range of Gram-Negative Bacterial Pathogens
Authors: Card Roderick , Zhang Jiancheng , Das Priya , Cook Charlotte , Woodford Neil , Anjum Muna F. 
Published: November 2012

ABSTRACT
A microarray capable of detecting genes for resistance to 75 clinically relevant antibiotics encompassing 19 different antimicrobial classes was tested on 132 Gram-negative bacteria. Microarray-positive results correlated >91% with antimicrobial resistance phenotypes, assessed using British Society for Antimicrobial Chemotherapy clinical breakpoints; the overall test specificity was >83%. Microarray-positive results without a corresponding resistance phenotype matched 94% with PCR results, indicating accurate detection of genes present in the respective bacteria by microarray when expression was low or absent and, hence, undetectable by susceptibility testing. The low sensitivity and negative predictive values of the microarray results for identifying resistance to some antimicrobial resistance classes are likely due to the limited number of resistance genes present on the current microarray for those antimicrobial agents or to mutation-based resistance mechanisms. With regular updates, this microarray can be used for clinical diagnostics to help accurate therapeutic options to be taken following infection with multiple-antibiotic-resistant Gram-negative bacteria and prevent treatment failure.
Genotypic and Phenotypic Analyses of Hepatitis C Virus from Patients Treated with JTK-853 in a Three-Day Monotherapy
Authors: Ogura Naoki , Toyonaga Yukiyo , Ando Izuru , Hirahara Kunihiro , Shibata Tsutomu , Turcanu Gabriela , Pai Sudhakar , Yee Kan , Gerhardt Barbara , Rodriguez-Torres Maribel , Noguchi Toru 
Published: November 2012

ABSTRACT

JTK-853, a palm site-binding NS5B nonnucleoside polymerase inhibitor, shows antiviral activity
in vitro
and in hepatitis C virus (HCV)-infected patients. Here, we report the results of genotypic and phenotypic analyses of resistant variants in 24 HCV genotype 1-infected patients who received JTK-853 (800, 1,200, or 1,600 mg twice daily or 1,200 mg three times daily) in a 3-day monotherapy. Viral resistance in NS5B was investigated using HCV RNA isolated from serum specimens from the patients. At the end of treatment (EOT) with JTK-853, the amino acid substitutions M414T (methionine [M] in position 414 at baseline was replaced with threonine [T] at EOT), C445R (cysteine [C] in position 445 at baseline was replaced with arginine [R] at EOT), Y448C/H (tyrosine [Y] in position 448 at baseline was replaced with cysteine [C] or histidine [H] at EOT), and L466F (leucine [L] in position 466 at baseline was replaced with phenylalanine [F] at EOT), which are known to be typical resistant variants of nonnucleoside polymerase inhibitors, were observed in a clonal sequencing analysis. These substitutions were also selected by a treatment with JTK-853
in vitro
, and the 50% effective concentration of JTK-853 in the M414T-, C445F-, Y448H-, and L466V-harboring replicons attenuated the susceptibility by 44-, 5-, 6-, and 21-fold, respectively, compared with that in the wild-type replicon (Con1). These findings suggest that amino acid substitutions of M414T, C445R, Y448C/H, and L466F are thought to be viral resistance mutations in HCV-infected patients receiving JTK-853 in a 3-day monotherapy.
Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and Reduces
In Vivo
Pathogenicity
Authors: Kato Ilka Tiemy , Prates Renato Araujo , Sabino Caetano Padial , Fuchs Beth Burgwyn , Tegos George P. , Mylonakis Eleftherios , Hamblin Michael R. , Ribeiro Martha Simões 
Published: November 2012

ABSTRACT

The objective of this study was to evaluate whether
Candida albicans
exhibits altered pathogenicity characteristics following sublethal antimicrobial photodynamic inactivation (APDI) and if such alterations are maintained in the daughter cells.
C. albicans
was exposed to sublethal APDI by using methylene blue (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (λ 660 nm, 75 mW/cm
2
, 9 to 27 J/cm
2
).
In vitro
, we evaluated APDI effects on
C. albicans
growth, germ tube formation, sensitivity to oxidative and osmotic stress, cell wall integrity, and fluconazole susceptibility.
In vivo
, we evaluated
C. albicans
pathogenicity with a mouse model of systemic infection. Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the growth rate and the ability of
C. albicans
to form germ tubes compared to untreated cells (
P
< 0.05). Survival of mice systemically infected with
C. albicans
pretreated with APDI was significantly increased compared to mice infected with untreated yeast (
P
< 0.05). APDI increased
C. albicans
sensitivity to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for fluconazole for
C. albicans
was also reduced following sublethal MB-mediated APDI. However, none of those pathogenic parameters was altered in daughter cells of
C. albicans
submitted to APDI. These data suggest that APDI may inhibit virulence factors and reduce
in vivo
pathogenicity of
C. albicans
. The absence of alterations in daughter cells indicates that APDI effects are transitory. The MIC reduction for fluconazole following APDI suggests that this antifungal could be combined with APDI to treat
C. albicans
infections.
Population Pharmacokinetic-Pharmacodynamic Analysis of Anidulafungin in Adult Patients with Fungal Infections
Authors: Liu Ping 
Published: November 2012

ABSTRACT

To evaluate the exposure-response relationships for efficacy and safety of intravenous anidulafungin in adult patients with fungal infections, a population pharmacokinetic-pharmacodynamic (PK-PD) analysis was performed with data from 262 patients in four phase 2/3 studies. The plasma concentration data were fitted with a previously developed population PK model. Anidulafungin exposures in patients with weight extremities (e.g., 40 kg and 150 kg) were simulated based on the final PK model. Since the patient population, disease status, and efficacy endpoints varied in these studies, the exposure-efficacy relationship was investigated separately for each study using logistic regression as appropriate. Safety data from three studies (
n
= 235) were pooled for analysis, and one study was excluded due to concomitant use of amphotericin B as a study treatment and different disease populations. The analysis showed that the same dosing regimen of anidulafungin can be administered to all patients regardless of body weight. Nonetheless, caution should be taken for patients with extremely high weight (e.g., >150 kg). There was a trend of positive association between anidulafungin exposure and efficacy in patients with esophageal candidiasis or invasive candidiasis, including candidemia (ICC); however, adequate characterization of the effect of anidulafungin exposure on response could not be established due to the relatively small sample size. No threshold value for exposure could be established, since patients with low exposure also achieved successful outcomes (e.g., area under the curve < 40 mg · h/liter in ICC patients). There was no association between anidulafungin exposure and the treatment-related adverse events or all-causality hepatic laboratory abnormalities.
Novel Aminoglycoside 2″-Phosphotransferase Identified in a Gram-Negative Pathogen
Authors: Toth Marta , Frase Hilary , Antunes Nuno T. , Vakulenko Sergei B. 
Published: November 2012

ABSTRACT

Aminoglycoside 2″-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci. We describe a novel aminoglycoside 2″-phosphotransferase from the Gram-negative pathogen
Campylobacter jejuni
, which shares 78% amino acid sequence identity with the APH(2″)-Ia domain of the bifunctional aminoglycoside-modifying enzyme aminoglycoside (6′) acetyltransferase-Ie/aminoglycoside 2″-phosphotransferase-Ia or AAC(6′)-Ie/APH(2″)-Ia from Gram-positive cocci, which we called APH(2″)-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin, but not to any of the 4,5-disubstituted antibiotics tested. Steady-state kinetic studies demonstrated that GTP, and not ATP, is the preferred cosubstrate for APH(2″)-If. The enzyme phosphorylates the majority of 4,6-disubstituted aminoglycosides with high catalytic efficiencies (
k
cat
/

K
m

= 10
5
to 10
7
M
−1
s
−1
), while the catalytic efficiencies against the 4,6-disubstituted antibiotics amikacin and isepamicin are 1 to 2 orders of magnitude lower, due mainly to the low apparent affinities of these substrates for the enzyme. Both 4,5-disubstituted antibiotics and the atypical aminoglycoside neamine are not substrates of APH(2″)-If, but are inhibitors. The antibiotic susceptibility and substrate profiles of APH(2″)-If are very similar to those of the APH(2″)-Ia phosphotransferase domain of the bifunctional AAC(6′)-Ie/APH(2″)-Ia enzyme.
Low-Density Lipoprotein Cholesterol–Lowering Effects of AMG 145, a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease in Patients With Heterozygous Familial Hypercholesterolemia
Authors: Raal Frederick , Scott Rob , Somaratne Ransi , Bridges Ian , Li Gang , Wasserman Scott M. , Stein Evan A. 
Published: November 2012

Background—
Despite statin treatment, many patients with heterozygous familial hypercholesterolemia do not reach desired low-density lipoprotein cholesterol (LDL-C) targets. AMG 145, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease, demonstrated significant reductions in LDL-C in phase 1 studies. This phase 2, multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluated the efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia patients.

Methods and Results—

Patients with heterozygous familial hypercholesterolemia diagnosed by Simon Broome criteria with LDL-C ≥2.6 mmol/L (100 mg/dL) despite statin therapy with or without ezetimibe were randomized 1:1:1 to AMG 145 350 mg, AMG 145 420 mg, or placebo-administered subcutaneously every 4 weeks. The primary end point was percentage change from baseline in LDL-C at week 12. Of 168 patients randomized, 167 received investigational product and were included in the full analysis set (mean [SD] age, 50 [13] years; 47% female; 89% white; mean [SD] baseline LDL-C, 4.0 [1.1] mmol/L (156 [42] mg/dL)). At week 12, LDL-C reduction measured by preparative ultracentrifugation (least squares mean [standard error (SE)]) was 43 (3)% and 55 (3)% with AMG 145 350 mg and 420 mg, respectively, compared with 1 (3)% increase with placebo (
P
<0.001 for both dose groups). Serious adverse events (not considered treatment-related) occurred in 2 patients on AMG 145.

Conclusions—
AMG 145 administered every 4 weeks yielded rapid and substantial reductions in LDL-C in heterozygous familial hypercholesterolemia patients despite intensive statin use, with or without ezetimibe, with minimal adverse events and good tolerability.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01375751.
Risk Prediction for Adverse Events After Carotid Artery Stenting in Higher Surgical Risk Patients
Authors: Wimmer Neil J. , Yeh Robert W. , Cutlip Donald E. , Mauri Laura 
Published: November 2012

Background and Purpose—
The goal of carotid artery stenting is to decrease the risk of stroke or other adverse events from carotid artery disease. Choosing a treatment strategy requires patient-specific information regarding periprocedural risk of adverse neurologic events. The aim of this study was to predict individual patient risk after carotid artery stenting in patients at higher risk for carotid endarterectomy.

Methods—
Subjects enrolled in the Stenting and Angioplasty with Protection in Patients at High-Risk for Endarterectomy (SAPPHIRE) worldwide study underwent carotid artery stenting with distal protection. Only patients with at least 1 anatomic or comorbid factor associated with elevated surgical risk were included. Preprocedural factors were used to develop a model and integer-based risk score predicting stroke or death within 30 days. The model was calibrated and internally validated using bootstrap resampling.

Results—

Ten thousand one hundred eighty-six patients were included in the analysis. The overall rate of stroke or death was 3.6% at 30 days after carotid artery stenting. Independent predictors of adverse outcomes were increased age (
P
=0.006), history of stroke (
P
<0.001), history of transient ischemic attack presentation (
P
=0.001), recent (<4 weeks) myocardial infarction (
P
=0.006), dialysis treatment (
P
=0.007), need for cardiac surgery in addition to carotid revascularization (
P
=0.005), a right-sided carotid stenosis (
P
=0.006), a longer carotid plaque (
P
=0.012), the presence of a Type II or III aortic arch (
P
=0.035), and a tortuous carotid arterial system (
P
=0.004). The optimism-adjusted C-statistic was 0.691.

Conclusions—
Commonly collected clinical and anatomic variables can identify patients at high and low risk for stroke or death after carotid artery stenting.
Tropical Precipitation Variability and Convectively Coupled Equatorial Waves on Submonthly Time Scales in Reanalyses and TRMM
Authors: Kim Ji-Eun , Alexander M. Joan 
Published: November 2012

Abstract
Tropical precipitation characteristics are investigated using the Tropical Rainfall Measuring Mission (TRMM) 3-hourly estimates, and the result is compared with five reanalyses including the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-Analysis (ERA-Interim), Modern Era Retrospective Analysis for Research and Applications (MERRA), National Centers for Environmental Prediction (NCEP)–National Center for Atmospheric Research (NCAR) reanalysis (NCEP1), NCEP–U.S. Department of Energy (DOE) reanalysis (NCEP2), and NCEP–Climate Forecast System Reanalysis (CFSR). Precipitation characteristics are evaluated in terms of the mean, convectively coupled equatorial wave activity, frequency characteristics, diurnal cycle, and seasonality of regional precipitation variability associated with submonthly scale waves. Generally the latest reanalyses such as ERA-Interim, MERRA, and CFSR show better performances than NCEP1 and NCEP2. However, all the reanalyses are still different from observations. Besides the positive mean bias in the reanalyses, a spectral analysis revealed that the reanalyses have overreddened spectra with persistent rainfall. MERRA has the most persistent rainfall, and CFSR appears to have the most realistic variability. The diurnal cycle in NCEP1 is extremely exaggerated relative to TRMM. The low-frequency waves with the period longer than 3 days are relatively well represented in ERA-Interim, MERRA, and CFSR, but all the reanalyses have significant deficiencies in representing convectively coupled equatorial waves and variability in the high-frequency range.
Some Three-Dimensional Nonlinear Equatorial Flows
Authors: Constantin Adrian 
Published: November 2012

AbstractThis study presents some explicit exact solutions for nonlinear geophysical ocean waves in the β-plane approximation near the equator. The solutions are provided in Lagrangian coordinates by describing the path of each particle. The unidirectional equatorially trapped waves are symmetric about the equator and propagate eastward above the thermocline and beneath the near-surface layer to which wind effects are confined. At each latitude the flow pattern represents a traveling wave.
Dynamical Potential Energy: A New Approach to Ocean Energetics
Authors: Roquet Fabien 
Published: November 2012

Abstract
The concept of available potential energy is supposed to indicate which part of the potential energy is available to transform into kinetic energy. Yet it is impossible to obtain a unique definition of available potential energy for the real ocean because of nonlinearities of the equation of state, rendering its usefulness largely hypothetical. In this paper, the conservation of energy is first reformulated in terms of horizontal anomalies of density and pressure for a simplified ocean model using the Boussinesq and hydrostatic approximations. This framework introduces the concept of “dynamical potential energy,” defined as the horizontal anomaly of potential energy, to replace available potential energy. Modified conservation equations are derived that make it much simpler to identify oceanic power input by buoyancy and mechanical forces. Closed budgets of energy are presented for idealized circulations obtained with a general circulation model, comparing spatial patterns of power inputs generated by wind and thermal forcings. Finally, a generalization of the framework to compressible fluids is presented, opening the way to applications in atmosphere energetics.