bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system
Authors: Zhu X. R. , Poenisch F. , Lii M. , Sawakuchi G. O. , Titt U. , Bues M. , Song X. , Zhang X. , Li Y. , Ciangaru G. , Li H. , Taylor M. B. , Suzuki K. , Mohan R. , Gillin M. T. , Sahoo N. 
Published: April 2013

Purpose:To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS).Methods:The input data required by the TPS included in‐air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC‐generated IDDs were converted to units of Gy mm2/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel‐plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field‐specific measurements.Results:We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012 with acceptable agreement between TPS calculated and measured dose distributions. However, the current dose model still has limitations in predicting field size dependence of doses at some intermediate depths of proton beams with high energies.Conclusions:We have commissioned a DG fluence model for clinical use. It is demonstrated that the DG fluence model is significantly more accurate than the SG fluence model. However, some deficiencies in modeling the low‐dose envelope in the current dose algorithm still exist. Further improvements to the current dose algorithm are needed. The method presented here should be useful for commissioning pencil beam dose algorithms in new versions of TPS in the future.
Prevalence and Characteristics of the Epidemic Multiresistant Escherichia coli ST131 Clonal Group among Extended-Spectrum Beta-Lactamase-Producing E. coli Isolates in Copenhagen, Denmark
Authors: Olesen Bente , Hansen Dennis S. , Nilsson Frida , Frimodt-Møller Jakob , Leihof Rikke Fleron , Struve Carsten , Scheutz Flemming , Johnston Brian , Krogfelt Karen A. , Johnson James R. 
Published: April 2013

ABSTRACT

We report the characteristics of 115 extended-spectrum beta-lactamase (ESBL)-producing
Escherichia coli
clinical isolates, from 115 unique Danish patients, over a 1-year study interval (1 October 2008 to 30 September 2009). Forty-four (38%) of the ESBL isolates represented sequence type 131 (ST13)1, from phylogenetic group B2. The remaining 71 isolates were from phylogenetic groups D (27%), A (22%), B1 (10%), and B2 (3%). Serogroup O25 ST131 isolates (
n
= 42; 95% of ST131) comprised 7 different K antigens, whereas two ST131 isolates were O16:K100:H5. Compared to non-ST131 isolates, ST131 isolates were associated positively with CTX-M-15 and negatively with CTX-M-1 and CTX-M-14. They also were associated positively with 11 virulence genes, including
afa
and
dra
(Dr family adhesins), the F10
papA
allele (P fimbria variant),
fimH
(type 1 fimbriae),
fyuA
(yersiniabactin receptor),
iha
(adhesin siderophore),
iutA
(aerobactin receptor),
kpsM
II (group 2 capsules),
malX
(pathogenicity island marker),
ompT
(outer membrane protease),
sat
(secreted autotransporter toxin), and
usp
(uropathogenicity-specific protein) and negatively with
hra
(heat-resistant agglutinin) and
iroN
(salmochelin receptor). The consensus virulence gene profile (>90% prevalence) of the ST131 isolates included
fimH
,
fyuA
,
malX
, and
usp
(100% each),
ompT
and the F10
papA
allele (95% each), and
kpsM
II and
iutA
(93% each). ST131 isolates were also positively associated with community acquisition, extraintestinal pathogenic
E. coli
(ExPEC) status, and the O25, K100, and H4 antigens. Thus, among ESBL
E. coli
isolates in Copenhagen, ST131 was the most prevalent clonal group, was community associated, and exhibited distinctive and comparatively extensive virulence profiles, plus a greater variety of capsular antigens than reported previously.
Comparison of Typing Methods with a New Procedure Based on Sequence Characterization for Salmonella Serovar Prediction
Authors: Ranieri Matthew L. , Shi Chunlei , Moreno Switt Andrea I. , den Bakker Henk C. , Wiedmann Martin 
Published: April 2013

ABSTRACT

As the development of molecular serotyping approaches is critical for
Salmonella
spp., which include >2,600 serovars, we performed an initial evaluation of the ability to identify
Salmonella
serovars using (i) different molecular subtyping methods and (ii) a newly implemented combined PCR- and sequencing-based approach that directly targets O- and H-antigen-encoding genes. Initial testing was performed using 46 isolates that represent the top 40
Salmonella
serovars isolated from human and nonhuman sources, as reported by the U.S. Centers for Disease Control and Prevention and the World Health Organization. Multilocus sequence typing (MLST) was able to accurately predict the serovars for 42/46 isolates and showed the best ability to predict serovars among the subtyping methods tested. Pulsed-field gel electrophoresis (PFGE), ribotyping, and repetitive extragenic palindromic sequence-based PCR (rep-PCR) were able to accurately predict the serovars for 35/46, 34/46, and 30/46 isolates, respectively. Among the methods,
S. enterica
subsp.
enterica
serovars 4,5,12:i:−, Typhimurium, and Typhimurium var. 5− were frequently not classified correctly, which is consistent with their close phylogenetic relationship. To develop a PCR- and sequence-based serotyping approach, we integrated available data sources to implement a combination PCR-based O-antigen screening and sequencing of internal
fliC
and
fljB
fragments. This approach correctly identified the serovars for 42/46 isolates in the initial set representing the most common
Salmonella
serovars, as well as for 54/63 isolates representing less common
Salmonella
serovars. Our study not only indicates that different molecular approaches show the potential to allow for rapid serovar classification of
Salmonella
isolates, but it also provides data that can help with the selection of molecular serotyping methods to be used by different laboratories.
Serum Arginase, a Biomarker of Treatment Efficacy in Human African Trypanosomiasis
Authors: Nzoumbou-Boko Romaric , Dethoua Mariette , Gabriel Fréderic , Buguet Alain , Cespuglio Raymond , Courtois Pierrette , Daulouède Sylvie , Bouteille Bernard , Ngampo Stéphane , Mpandzou Ghislain , Semballa Silla , Vincendeau Philippe 
Published: April 2013

ABSTRACT

Arginase serum levels were increased in human African trypanosomiasis patients and returned to control values after treatment. Arginase hydrolyzes
l
-arginine to
l
-ornithine, which is essential for parasite growth. Moreover,
l
-arginine depletion impairs immune functions. Arginase may be considered as a biomarker for treatment efficacy.
Different Distributions of Epstein-Barr Virus Early and Late Gene Transcripts within Viral Replication Compartments
Authors: Sugimoto Atsuko , Sato Yoshitaka , Kanda Teru , Murata Takayuki , Narita Yohei , Kawashima Daisuke , Kimura Hiroshi , Tsurumi Tatsuya 
Published: April 2013

ABSTRACT
Productive replication of the Epstein-Barr virus (EBV) occurs in discrete sites in nuclei, called replication compartments, where viral genome DNA synthesis and transcription take place. The replication compartments include subnuclear domains, designated BMRF1 cores, which are highly enriched in the BMRF1 protein. During viral lytic replication, newly synthesized viral DNA genomes are organized around and then stored inside BMRF1 cores. Here, we examined spatial distribution of viral early and late gene mRNAs within replication compartments using confocal laser scanning microscopy and three-dimensional surface reconstruction imaging. EBV early mRNAs were mainly located outside the BMRF1 cores, while viral late mRNAs were identified inside, corresponding well with the fact that late gene transcription is dependent on viral DNA replication. From these results, we speculate that sites for viral early and late gene transcription are separated with reference to BMRF1 cores.
Geomorphology in legal affairs of the Binghamton, New York, metropolitan area
Authors: Coates Donald R. 
Published: April 2013

The Binghamton area provides many examples of the interface between scientists and land managers. In this paper I use case histories to document the role of the geomorphologist in the decision-making process. Disastrous Binghamton floods in 1935 to 1936 produced a Federal response through the newly enacted Flood Control Act of 1936. Accordingly, the U.S. Corps of Engineers built the only two dams in the Susquehanna Basin, constructed miles of flood walls, and channelized parts of the Susquehanna and Chenango Rivers. Additional geomorphic engineering resulted from Public Law 566 (1954), which enabled the Soil Conservation Service to complete 17 of 22 dam projects. Other Federal laws have financed the Riverbanks Improvement Program of Broome County, New York, and led to municipal ordinances that prohibit new occupancy in flood plains.
Four-lane roads built under the Federal Interstate Highway Program have altered the Binghamton landscape and have led to much litigation. Lands were condemned that contained gravel deposits, water supplies of contiguous properties have been affected, and proper environmental statements are missing in several design plans. The impact statement clause of the National Environmental Policy Act of 1969 was used by a group of preservationists to halt construction of two I-88 projects. Unfortunately, the work stoppage is causing accelerated erosion of unprotected hillslopes and roadbeds and greater environmental damage than if construction had continued. It is important that the urbanization process receive attention from geomorphologists who can aid in minimizing man-made terrain destruction.
A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non–Small Cell Lung Cancer
Authors: Socinski Mark A. , Goldman Jonathan , El-Hariry Iman , Koczywas Marianna , Vukovic Vojo , Horn Leora , Paschold Eugene , Salgia Ravi , West Howard , Sequist Lecia V. , Bonomi Philip , Brahmer Julie , Chen Lin-Chi , Sandler Alan , Belani Chandra P. , Webb Timothy , Harper Harry , Huberman Mark , Ramalingam Suresh , Wong Kwok-Kin , Teofilovici Florentina , Guo Wei , Shapiro Geoffrey I. 
Published: April 2013

Abstract
Purpose: Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated patients with non–small cell lung cancer (NSCLC).
Experimental Design: Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m2 ganetespib by intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until disease progression. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies.
Results: Ninety-nine patients with a median of 2 prior systemic therapies were enrolled; 98 were assigned to cohort A (n = 15), B (n = 17), or C (n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively. Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n = 1) or PCR-based assays (n = 3), in crizotinib-naïve patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The most common AEs were diarrhea, fatigue, nausea, and anorexia.
Conclusions: Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement. Clin Cancer Res; 19(11); 3068–77. ©2013 AACR.
Evaluation of Food Effect on Pharmacokinetics of Vismodegib in Advanced Solid Tumor Patients
Authors: Sharma Manish R. , Karrison Theodore G. , Kell Bethany , Wu Kehua , Turcich Michelle , Geary David , Kang Soonmo P. , Takebe Naoko , Graham Richard A. , Maitland Michael L. , Schilsky Richard L. , Ratain Mark J. , Cohen Ezra E.W. 
Published: April 2013

Abstract
Purpose: Vismodegib, an orally bioavailable small-molecule Smoothened inhibitor, is approved for treatment of advanced basal cell carcinoma (BCC). We conducted a pharmacokinetic study of vismodegib in patients with advanced solid tumors to explore the effects of food on drug exposure.
Experimental Design: In part I, patients were randomized to fasting overnight (FO), a high fat meal (HF), or a low fat meal (LF) before a single dose of vismodegib 150 mg. Plasma concentrations of vismodegib were determined by a validated liquid chromatography-tandem mass spectrometry assay. Primary endpoints were Cmax and area under the curve (AUC0–168). In part II, patients randomized to FO or HF in part I took vismodegib 150 mg daily after fasting; those randomized to LF took it after a meal. Primary endpoints after two weeks were Cmax and AUC0–24.
Results: Sixty (22 FO, 20 HF, 18 LF) and 52 (25 fasting, 27 fed) patients were evaluable for primary endpoints in parts I and II, respectively. Mean Cmax and AUC0–168 after a single dose were higher in HF than FO patients [ratios of geometric means (90% CI) = 1.75 (1.30, 2.34) and 1.74 (1.25, 2.42), respectively]. There were no significant differences in Cmax or AUC0–24 between fasting and fed groups after daily dosing. The frequencies of drug-related toxicities were similar in both groups.
Conclusions: A HF meal increases plasma exposure to a single dose of vismodegib, but there are no pharmacokinetic or safety differences between fasting and fed groups at steady-state. Vismodegib may be taken with or without food for daily dosing. Clin Cancer Res; 19(11); 3059–67. ©2013 AACR.
Human Breast Tissue Disposition and Bioactivity of Limonene in Women with Early-Stage Breast Cancer
Authors: Miller Jessica A. , Lang Julie E. , Ley Michele , Nagle Ray , Hsu Chiu-Hsieh , Thompson Patricia A. , Cordova Catherine , Waer Amy , Chow H-H. Sherry 
Published: April 2013

AbstractLimonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment. Cancer Prev Res; 6(6); 577–84. ©2013 AACR.
Use of Dabigatran for Periprocedural Anticoagulation in Patients Undergoing Catheter Ablation for Atrial Fibrillation
Authors: Bassiouny Mohamed , Saliba Walid , Rickard John , Shao Mingyuan , Sey Albert , Diab Mariam , Martin David O. , Hussein Ayman , Khoury Maurice , Abi-Saleh Bernard , Alam Samir , Sengupta Jay , Borek P. Peter , Baranowski Bryan , Niebauer Mark , Callahan Thomas , Varma Niraj , Chung Mina , Tchou Patrick J. , Kanj Mohamed , Dresing Thomas , Lindsay Bruce D. , Wazni Oussama 
Published: April 2013

Background—
Pulmonary vein isolation (PVI) for atrial fibrillation is associated with a transient increased risk of thromboembolic and hemorrhagic events. We hypothesized that dabigatran can be safely used as an alternative to continuous warfarin for the periprocedural anticoagulation in PVI.

Methods and Results—

A total of 999 consecutive patients undergoing PVI were included; 376 patients were on dabigatran (150 mg), and 623 patients were on warfarin with therapeutic international normalized ratio. Dabigatran was held 1 to 2 doses before PVI and restarted at the conclusion of the procedure or as soon as patients were transferred to the nursing floor. Propensity score matching was applied to generate a cohort of 344 patients in each group with balanced baseline data. Total hemorrhagic and thromboembolic complications were similar in both groups, before (3.2% versus 3.9%;
P
=0.59) and after (3.2% versus 4.1%;
P
=0.53) matching. Major hemorrhage occurred in 1.1% versus 1.6% (
P
=0.48) before and 1.2% versus 1.5% (
P
=0.74) after matching in the dabigatran versus warfarin group, respectively. A single thromboembolic event occurred in each of the dabigatran and warfarin groups. Despite higher doses of intraprocedural heparin, the mean activated clotting time was significantly lower in patients who held dabigatran for 1 or 2 doses than those on warfarin.

Conclusions—
Our study found no evidence to suggest a higher risk of thromboembolic or hemorrhagic complications with use of dabigatran for periprocedural anticoagulation in patients undergoing PVI compared with uninterrupted warfarin therapy.
Socialist Values and Cooperation in Brazil’s Landless Rural Workers’ Movement
Authors: Diniz Aldiva Sales , Gilbert Bruce 
Published: April 2013

When the Movimento de Trabalhadores Rurais Sem Terra do Brasil (Movement of Landless Rural Workers’ of Brazil—MST) occupies land and forms autonomous agricultural communities, it aspires to achieve the supremacy of labor over capital and to embody socialist values. However, a policy of organizing production cooperatives on its settlements in the early 1990s was unsuccessful, principally because of a failure fully to respect traditional forms of work and sociability. However, the MST learned from its early mistakes and has since developed elaborate forms of informal and formal cooperation on land that is essentially the common property of a democratic settlement association. It is therefore living up to its socialist objectives and manifesting a real alternative to capitalist work and property relations. Cuando el Movimento de Trabalhadores Rurais Sem Terra do Brasil (MST) ocupa tierra y forma comunidades agrícolas autónomas, aspira a lograr la supremacía del trabajo sobre capital y encarnar valores socialistas. No obstante, una política para organizar cooperativas de producción en sus asentamientos a principios de los 1990 no prosperó, mayormente por la falta de respeto pleno a las formas tradicionales de trabajo y sociabilidad. El MST aprendió de sus errores iniciales y desde entonces ha desarrollado intricadas formas de cooperación informal y formal en tierra que es esencialmente la propiedad común de una asociación de asentamiento democrática. Por lo tanto está haciendo honra a sus objetivos socialistas y demostrando una alternativa concreta a las relaciones capitalistas de trabajo y propiedad.
Effect of sugammadex on rocuronium induced changes in pancreatic mast cells
Authors: Kalkan Yıldıray , Tumkaya Levent , Bostan Habib , Tomak Yakup , Altuner Durdu , Yilmaz Adnan , Erdivanli Başar , Bedir Recep , Yalcin Alper , Turan Alparslan 
Published: April 2013

Mast cells play a vital role in hypersensitivity reactions. Rocuronium is known to cause mast cell mobilization, hypersensitivity, and pancreatitis. The aim of this study was to investigate the effects of sugammadex on pancreatic changes due to rocuronium. A total of 42 Sprague-Dawley male rats were divided into six equal groups to receive either rocuronium 1 mg/kg intravenously (i.v., R group), rocuronium 1 mg/kg + sugammadex 16 mg/kg i.v. (RS16 group), rocuronium 1 mg/kg + sugammadex 96 mg/kg i.v. (RS96 group), sugammadex 16 mg/kg (S16), sugammadex 96 mg/kg i.v. (S96 group), or 0.9% sodium chloride (control group). Sugammadex was administered 5s later following rocuronium. In R group, mast count was higher, and the distribution rate of granules and nuclear changes were different compared with other groups. Distribution rate of granules in groups S16 and S96 were similar to the control group and lower compared with other groups. The amount of mast cells and granule density in groups RS16 and RS96 was lower compared with R group. The amount of mast cells in groups RS16 and RS96 was significantly lower compared with other treatment groups. These results suggest that sugammadex may have an inhibitory effect on mobilization and morphological changes in pancreatic mast cells induced by administration of rocuronium and sugammadex in rats.