bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I and Pharmacokinetic Study of Sunitinib in Pediatric Patients with Refractory Solid Tumors: A Children's Oncology Group Study
Authors: DuBois Steven G. , Shusterman Suzanne , Ingle Ashish M. , Ahern Charlotte H. , Reid Joel M. , Wu Bing , Baruchel Sylvain , Glade-Bender Julia , Ivy Percy , Grier Holcombe E. , Adamson Peter C. , Blaney Susan M. 
Published: June 2011

Abstract
Purpose: Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor. The purpose of this study was to determine the recommended phase 2 dose, pharmacokinetics, pharmacodynamic effects, and preliminary antitumor activity of sunitinib in a pediatric population.
Experimental Design: Patients who were 2 to 21 years of age with refractory solid tumors were eligible if they had measurable or evaluable disease and met baseline organ function requirements. Patients received sunitinib once daily for 28 days followed by a 14-day break between each cycle. Dose levels of 15 and 20 mg/m2/d were evaluated, with dose escalation based on a 3 + 3 design. Sunitinib pharmacokinetics and biomarkers of angiogenesis were also evaluated during the first cycle.
Results: Twenty-three patients were treated (median age 13.9 years; range, 3.9–20.6 years). The most common toxicities were neutropenia, thrombocytopenia, elevated liver transaminases, gastrointestinal symptoms, and fatigue. Two patients developed dose-limiting reductions in cardiac ejection fraction prompting a protocol amendment to exclude patients with previous exposure to anthracyclines or cardiac radiation. In patients without these cardiac risk factors, the maximum tolerated dose (MTD) was 15 mg/m2/d. Steady-state plasma concentrations were reached by day 7. No objective responses were observed. Four patients with sarcoma and glioma had stable disease for 2 to 9 cycles.
Conclusions: Cardiac toxicity precluded determination of a recommended dose for pediatric patients with previous anthracycline or cardiac radiation exposure. The MTD of sunitinib for patients without risk factors for cardiac toxicity is 15 mg/m2/d for 28 days followed by a 14-day break. Clin Cancer Res; 17(15); 5113–22. ©2011 AACR.
Combinatorial Effects of Lapatinib and Rapamycin in Triple-Negative Breast Cancer Cells
Authors: Liu Tongrui , Yacoub Rami , Taliaferro-Smith LaTonia D. , Sun Shi-Yong , Graham Tisheeka R. , Dolan Ryan , Lobo Christine , Tighiouart Mourad , Yang Lily , Adams Amy , O'Regan Ruth M. 
Published: June 2011

Abstract
Triple-negative breast cancers, which lack estrogen receptor, progesterone receptor, and HER2/neu overexpression, account for approximately 15% of breast cancers, but occur more commonly in African Americans. The poor survival outcomes seen with triple-negative breast cancers patients are, in part, due to a lack of therapeutic targets. Epidermal growth factor receptor (EGFR) is overexpressed in 50% of triple-negative breast cancers, but EGFR inhibitors have not been effective in patients with metastatic breast cancers. However, mTOR inhibition has been shown to reverse resistance to EGFR inhibitors. We examined the combination effects of mTOR inhibition with EGFR inhibition in triple-negative breast cancer in vitro and in vivo. The combination of EGFR inhibition by using lapatinib and mTOR inhibition with rapamycin resulted in significantly greater cytotoxicity than the single agents alone and these effects were synergistic in vitro. The combination of rapamycin and lapatinib significantly decreased growth of triple-negative breast cancers in vivo compared with either agent alone. EGFR inhibition abrogated the expression of rapamycin-induced activated Akt in triple-negative breast cancer cells in vitro. The combination of EGFR and mTOR inhibition resulted in increased apoptosis in some, but not all, triple-negative cell lines, and these apoptotic effects correlated with a decrease in activated eukaryotic translation initiation factor (eIF4E). These results suggest that mTOR inhibitors could sensitize a subset of triple-negative breast cancers to EGFR inhibitors. Given the paucity of effective targeted agents in triple-negative breast cancers, these results warrant further evaluation. Mol Cancer Ther; 10(8); 1460–9. ©2011 AACR.
Dynamically Shaped Magnetic Fields
Authors: Gang Eli S. , Nguyen Bich Lien , Shachar Yehoshua , Farkas Leslie , Farkas Laszlo , Marx Bruce , Johnson David , Fishbein Michael C. , Gaudio Carlo , Kim Steven J. 
Published: June 2011

Background—
To address some of the shortcomings of existing remote catheter navigation systems (RNS), a new magnetic RNS has been developed that provides real-time navigation of catheters within the beating heart. The initial experience using this novel RNS in animals is described.

Methods and Results—
A real-time, high-speed, closed-loop, magnetic RNS system (Catheter Guidance Control and Imaging) comprises 8 electromagnets that create unique dynamically shaped (“lobed”) magnetic fields around the subject's torso. The real-time reshaping of these magnetic fields produces the appropriate 3D motion or change in direction of a magnetized electrophysiology ablation catheter within the beating heart. The RNS is fully integrated with the Ensite-NavX 3D electroanatomic mapping system (St Jude Medical) and allows for both joystick and automated navigation. Conventional and remote navigational mapping of the left atrium were performed using a 4-mm-tip ablation catheter in 10 pigs. A multielectrode transseptal sheath allowed for additional motion compensation. Linear and circumferential radiofrequency lesion sets were performed; in a subset of cases, selective pulmonary vein isolation was also performed. Recording and fluoroscopic equipments were unaffected by the magnetic fields generated by Catheter Guidance Control and Imaging. Automated mode navigation was highly reproducible (96±8.4% of attempts), accurate (1.9±0.4 mm from target site), and rapid (11.6±3.5 seconds to reach targets). At postmortem examination, radiofrequency lesion depth was 78.5±12.1% of atrial wall thickness.

Conclusions—
A new magnetic RNS using a dynamically shaped magnetic field concept can reproducibly and effectively reach target radiofrequency ablation points within the pig left atrium. Validation of the system in clinical settings is under way.
Signature microRNA Expression Profile of Essential Hypertension and Its Novel Link to Human Cytomegalovirus Infection
Authors: Li Shuqiang , Zhu Jianguo , Zhang Weili , Chen Youren , Zhang Ke , Popescu Laurentiu M. , Ma Xinliang , Bond Lau Wayne , Rong Rong , Yu Xueqing , Wang Bingbing , Li Yafeng , Xiao Chuanshi , Zhang Mingming , Wang Shuyan , Yu Liping , Chen Alex F. , Yang Xinchun , Cai Jun 
Published: June 2011

Background—
Essential hypertension has been recognized as a disease resulting from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in cardiac hypertrophy and heart failure. However, little is known about the roles of miRNAs in essential hypertension.

Methods and Results—

Using microarray-based miRNA expression profiling, we compared the miRNA expressions in plasma samples from 13 hypertensive patients and 5 healthy control subjects. Twenty-seven miRNAs were found to be differentially expressed. The expressions of selected miRNAs (miR-296–5p, let-7e, and a human cytomegalovirus [HCMV]–encoded miRNA, hcmv-miR-UL112) were validated independently in plasma samples from 24 hypertensive patients and 22 control subjects. The absolute expression levels of hcmv-miR-UL112, miR-296–5p, and let-7e were further determined in 127 patients and 67 control subjects (fold changes are 2.5, 0.5, and 1.7 respectively; all
P
<0.0001). Additionally, we demonstrated that interferon regulatory factor 1 is a direct target of hcmv-miR-UL112. Increased HCMV seropositivity and quantitative titers were found in the hypertension group compared with the control group (52.7% versus 30.9%,
P
=0.0005; 1870 versus 54 copies per 1 mL plasma,
P
<0.0001). Seropositivity, log-transformed copies of HCMV, and hcmv-miR-UL112 were independently associated with an increased risk of hypertension (odds ratio, 2.48; 95% confidence interval, 1.48 to 4.15;
P
=0.0005; odds ratio, 1.97; 95% confidence interval, 1.58 to 2.46;
P
<0.0001; and odds ratio, 2.55; 95% confidence interval, 1.98 to 3.27;
P
<0.0001, respectively).

Conclusions—
We report for the first time a circulating miRNA profile for hypertensive patients and demonstrate a novel link between HCMV infection and essential hypertension. These findings may reveal important insights into the pathogenesis of essential hypertension.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00420784.
Conducting field research in a primary school setting: Methodological considerations for maximizing response rates, data quality and quantity
Authors: Trapp Georgina , Giles-Corti Billie , Martin Karen , Timperio Anna , Villanueva Karen 
Published: June 2011

Background: Schools are an ideal setting in which to involve children in research. Yet for investigators wishing to work in these settings, there are few method papers providing insights into working efficiently in this setting. Objective: The aim of this paper is to describe the five strategies used to increase response rates, data quality and quantity in the TRansport Environment and Kids (TREK) project. Setting: The TREK project examined the association between neighbourhood urban design and active transport in Grade 5–7 school children ( n = 1480) attending 25 primary schools in metropolitan Perth, Western Australia during 2007. Method: Children completed several survey components during school time (i.e. questionnaire, mapping activity, travel diary and anthropometric measurements) and at home (i.e. pedometer study, parent questionnaire). Results: Overall, 69.4% of schools and 56.6% of children agreed to participate in the study and, of these, 89.9% returned a completed travel diary, 97.8% returned their pedometer and 88.8% of parents returned their questionnaire. These return rates are superior to similar studies. Five strategies appeared important: (1) building positive relationships with key school personnel; (2) child-centred approaches to survey development; (3) comprehensive classroom management techniques to standardize and optimize group sessions; (4) extensive follow-up procedures for collecting survey items; and (5) a specially designed data management/monitoring system. Conclusion: Sharing methodological approaches for obtaining high-quality data will ensure research opportunities within schools are maximized. These methodological issues have implications for planning, budgeting and implementing future research.
Design and verification of fabric surface softness testing system
Authors: Kuo Chung-Feng Jeffrey , Lin Wen-Tsung , Su Te-Li 
Published: June 2011

This study developed a testing system for fabric surface softness based on the sled method. The system is compact, lightweight, portable and convenient to use. The device can be installed on the sueding machine as an on-line real-time testing system for fabric surface softness, thus improving the response efficiency of the process parameters of the sueding machine. Moreover, it can be used to construct a database of these parameters, store different fabric types, process quality requirements and reproduce processing at the same quality, in order to automatically, rapidly and accurately calibrate the parameters. This study applied the Taguchi method on the process parameters of the sueding machine to analyze the interaction between parameters, design the orthogonal array according to actual needs, and process the grinded fabric on-line. It also measured the testing system and plotted the Signal-to-Noise (S/N) ratio response table based on the S/N calculated for the parameter combinations. In the table, the larger S/N ratios represent a better quality characteristic and smaller variation. Hence, the main effect of the control factors and the optimum factor level can be obtained. After determining the optimal combination of process parameters, the process and measuring experiment of the reference group was conducted with these control factors to verify the results. It was proven that the device can obtain the maximum surface softness, and effectively and accurately test the surface softness of finished fabrics.
Bending behavior of multilayered and multidirectional stitched aramid woven fabric structures
Authors: Bilisik Kadir 
Published: June 2011

The aim of this study was to experimentally determine the bending behavior of developed multilayered and multistitched ballistic structures which could affect the comfort for the wearer. For this reason, the bending rigidity test was conducted on all developed multilayered and multistitched ballistic structures after the impact test. Fabric density and crimp ratio influenced the bending rigidity of single layer fabric. On the other hand, the bending rigidities of multilayered and multistitched ballistic structures depended on the number of fabric layers and stitching directions. Generally, multilayered four directional stitched ballistic structures showed the highest bending rigidity compared to the two and one directional stitching. Multilayered and multistitched ballistic structures showed high bending rigidity compared to multilayered and unstitched ballistic structures. This indicated that the number of stitching directions affected the bending rigidity of the developed ballistic structures. In addition, multilayered and multistitched structures showed a low order of bending curvatures compared to the multilayered unstitched structure. On the other hand, after all structures were impacted by one type of projectile but varied speeds, multistitched structures had low conical depth compared to those of the unstitched structures. This was because stitching increased the bending rigidity of the ballistic structures and reduced the structural deformation to the out-of-plane direction. It could not, however, be easily formed and it could decrease the ballistic comfort to the wearer.
Community-Based Translation of the Diabetes Prevention Program’s Lifestyle Intervention in an Underserved Latino Population
Authors: Ruggiero Laurie , Oros Susan , Choi Young Ku 
Published: June 2011

Purpose The objective was to take prevention from the clinic to the community by including a high-risk group and working with the community to tailor, enhance, deliver, and evaluate a community-based version of the Diabetes Prevention Program’s (DPP) clinic-based lifestyle intervention. Methods This was a nonrandomized prospective study using a single-group design. Study eligibility included a screening glucose value in the normal to prediabetes range with no current diagnosis of diabetes, overweight, not pregnant nor planning to become pregnant during study period, aged 18 to 65, Latino, living in the study target communities, and no reported medical restrictions related to the program goals. A total of 69 individuals participated. The Healthy Living Program (HLP) was based on the DPP’s 1-year intensive lifestyle program, was tailored and enhanced for a Latino community, and was delivered by community health workers. Anthropometric and paper and pencil measures were administered to examine program outcome at 6 months and 12 months. Results In general, results indicate statistically significant improvements in anthropometrics and many behavioral outcomes, particularly at 6 months. Participants demonstrated forward movement through the stages of change during the program. Conclusions Results support the effectiveness of the intervention and show that delivery of the translated version of the DPP’s lifestyle intervention in the community by community residents holds promise as one strategy to reach people at increased risk of developing diabetes. Use of this translation model, including collaboration with community health workers, offers diabetes educators an opportunity to extend their reach into underserved communities.
The International Burden of Migraine Study (IBMS): Study design, methodology, and baseline cohort characteristics
Authors: Payne Krista A , Varon Sepideh F , Kawata Ariane K , Yeomans Karen , Wilcox Teresa K , Manack Aubrey , Buse Dawn C , Lipton Richard B , Goadsby Peter J , Blumenfeld Andrew M 
Published: June 2011

Objective: To describe a survey methodology to evaluate headache characteristics and burden and to present baseline characteristics for the international cohort of survey participants. Methods: A targeted, web-based methodology was used to recruit and survey subjects with migraine in 10 countries. Based on reported symptoms, subjects meeting ICHD-2 criteria for migraine were included; eligible subjects were classified as chronic (≥ 15 headache days per month) or episodic (< 15 headache days per month). Outcomes included sociodemographic and clinical characteristics, resource utilization, disability, health-related quality of life, anxiety, depression and productivity. Results: Of 23,312 survey respondents, 11,897 were eligible and 9715 (81.7%) completed the survey; subjects were 81.5% female; 5.7% ( n = 555) had chronic migraine. Conclusions: This is the first large international cohort of persons with chronic and episodic migraine studied using a web-based approach, a methodology well suited to the study of the burden of migraines.
Time accurate modelling of the secondary air system response to rapid transients
Authors: Gallar L , Calcagni C , Llorens C , Pachidis V 
Published: June 2011

The amount of air drawn by the secondary air system (SAS) from the main gas path, although necessary, impairs the engine performance because it does not contribute to engine thrust. In order to quantify and minimize this pernicious effect, the usual practice is to model the air system with one-dimensional network solvers where the net nodes represent the various components of the system. For usual engine transients, it is sufficient to analyse the system performance with a quasi-steady approach because the time constant of the air system is two orders of magnitude smaller than the turbomachinery characteristic time. Nonetheless, the rapid changes that occur during certain transient or failure scenarios – particularly shaft failure events – call for a different approach to calculate the air system performance and the fluctuations of the turbomachinery endloads. However, there is no such approach available in the open literature to predict the transient response of the system. For steady-state conditions, the differential equations that govern the fluid evolution are not time discretized and thus can be solved in a relatively straightforward fashion. Moreover, unlike during transients, the flow is not supposed to reach sonic conditions anywhere within the network and, more importantly, flow reversal is not expected to occur. The aim of this study is to develop a model for gas turbine SAS dynamics capable of tackling the sudden changes in the flow properties that occur within the system in the rapid transient scenarios. The whole system is initially broken down into a series of chambers of a finite volume connected by pipes that are initially modelled in isolation and then interconnected. The single-component models and their assembly are successfully validated against numerical and experimental data. The resultant modular tool constitutes a baseline into which further improvements and modifications can be integrated in subsequent works. The usefulness of the computational tool is demonstrated through the analysis of the flow evolution within the SAS and the subsequent turbine endload during a shaft failure event.
Hybrid adaptive ascent flight control for a flexible launch vehicle
Authors: LeFevre B D , Jha R 
Published: June 2011

For the purpose of improving trajectory tracking performance of a launch vehicle under adverse flight conditions, this article describes the development of a hybrid adaptive ascent flight control architecture. The hybrid adaptive control approach augments linear feedback signals with contributions from both direct and indirect adaptive control elements. In addition, signal filters are incorporated into the feedback loop to prevent harmful interaction between the flight control system and structural bending modes. The performance of the hybrid adaptive flight controller is compared to that of a typical gain-scheduled linear feedback controller in a high-fidelity Ares I ascent simulator obtained from the NASA Marshall Space Flight Center. Results from simulations which consider nominal flight conditions show that the hybrid adaptive controller is able to maintain a tracking error magnitude that is comparable to or lower than its classical proportional–integral–derivative (PID) counterpart for the vast majority of the ascent phase. However, when a 10 per cent thrust reduction is applied to the first-stage rocket motor, the PID controller experiences significantly elevated error that diverges rapidly at the end of the simulation. In contrast, the hybrid adaptive controller steadily maintains a tracking error magnitude that is frequently 50 per cent or less of the corresponding PID value during the latter stages of ascent.
Effect of vitamin D3 supplementation on peripheral B cell differentiation and isotype switching in patients with multiple sclerosis
Authors: Knippenberg Stephanie , Smolders Joost , Thewissen Mariëlle , Peelen Evelyn , Tervaert Jan Willem Cohen , Hupperts Raymond , Damoiseaux Jan 
Published: June 2011

Background: Vitamin D has been proposed as a promoter of immune homeostasis in multiple sclerosis (MS). During the past decade, the focus of the effects of vitamin D has been on dendritic cells and on T cells. Since there is an increasing interest in the role of B cells in the pathophysiology of MS, we studied the role of vitamin D on B cells in vivo in patients with MS. Objective: We explored the effects of 12 weeks high-dose vitamin D3 supplementation on peripheral B cell differentiation, immunoglobulin production and levels of B cell activating factor (BAFF) in 15 patients with MS. Methods: Circulating B cell subsets were characterized by flow cytometry. Plasma immunoglobulin levels were assessed by nephelometry. Plasma BAFF levels were assessed by enzyme-linked immunosorbent assay (ELISA). Results: Although a significant increase serum 25-hydroxyvitamin D was induced, we found no significant shift in B cell differentiation, isotype switching, or plasma BAFF levels. Conclusion: In patients with MS, supplementation of high doses vitamin D3 does not have substantial effects on phenotypic markers of B cell differentiation in circulating B cells. Future studies may unravel more subtle changes in the B cell compartment, either in the circulation or in the central nervous system.