bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Cavitation: Impact on Objective Response Evaluation in Trials of Angiogenesis Inhibitors in Non–Small-Cell Lung Cancer
Authors: Crabb Simon J. , Patsios Demetris , Sauerbrei Eric , Ellis Peter M. , Arnold Andrew , Goss Glenwood , Leighl Natasha B. , Shepherd Frances A. , Powers Jean , Seymour Lesley , Laurie Scott A. 
Published: December 2008

Purpose We have observed cavitation of lesions in clinical trials of an angiogenesis inhibitor combined with chemotherapy for non–small-cell lung cancer (NSCLC). We hypothesized that cavitation might alter response assessment in such clinical trials. Patients and Methods We performed a retrospective radiologic review of patients with NSCLC enrolled onto three National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trials of platinum-based chemotherapy with or without a small-molecule angiogenesis inhibitor (vascular endothelial growth factor receptor inhibitor [VEGFRI]). Response was assessed both by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and a novel alternate method in which the longest diameter of any cavity was subtracted from the overall longest diameter of that lesion to measure target lesions. Rates of cavitation were documented. Results Marked cavitation of pulmonary lesions was seen in 24% of 33 patients treated with VEGFRI combined with platinum-based chemotherapy but in none of 18 patients treated with platinum-based chemotherapy alone. Use of the alternate method for response assessment resulted in an alteration of response assessment, time to best response, duration of response, and time of disease progression in a minority of patients compared with RECIST. Conclusion Cavitation of target and nontarget lesions is common in NSCLC patients treated with VEGFRIs and platinum-based chemotherapy. Impact on response and time to event outcomes occurred but seems to be less common. Response assessment might be improved by incorporating cavitation into volume assessment for target lesions, potentially altering outcomes of key efficacy parameters in clinical trials. This should be prospectively assessed in clinical trials of angiogenesis inhibitors.
The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report
Authors: Cohn Susan L. , Pearson Andrew D.J. , London Wendy B. , Monclair Tom , Ambros Peter F. , Brodeur Garrett M. , Faldum Andreas , Hero Barbara , Iehara Tomoko , Machin David , Mosseri Veronique , Simon Thorsten , Garaventa Alberto , Castel Victoria , Matthay Katherine K. 
Published: December 2008

Purpose Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Patients and Methods The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors. Results Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to ≤ 85%, ≥ 50% to ≤ 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively. Conclusion By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.
Prognostic Significance of Serum S100B Protein in High-Risk Surgically Resected Melanoma Patients Participating in Intergroup Trial ECOG 1694
Authors: Tarhini Ahmad A. , Stuckert Joseph , Lee Sandra , Sander Cindy , Kirkwood John M. 
Published: December 2008

Purpose We evaluated adjuvant trial E1694 to more precisely define the prognostic significance of serum S100B in patients with high-risk resected melanoma. Patients and Methods Sera from 670 E1694 patients banked at baseline and three additional time points were tested for S100B protein using chemiluminescence. Results S100B testing results showed that the higher the S100B level is, the higher the risk of relapse and death, regardless of the cutoff value. Univariate analysis showed that baseline S100B ≥ 0.15 μg/L is significantly correlated with overall survival (OS; P = .01). Multivariate analysis was performed adjusting for significant prognostic factors (ulceration and lymph node status) and treatment. Baseline S100B was a significant prognostic factor for survival (hazard ratio = 1.39; 95% CI, 1.01 to 1.92; P = .043). S100B values measured at later time points over 1 year were also demonstrated to be significant prognostic factors for relapse-free survival (RFS) and OS. Lower S100B values at baseline and during follow-up were associated with longer survival. A changing S100B from low at baseline to high on follow-up seemed to be associated with the worst RFS and OS. Conclusion For patients with high-risk surgically resected melanoma, a high baseline or increasing serum S100B is an independent prognostic marker of risk for mortality that may allow us to refine the application of adjuvant therapy in the future.
Sensitivity to Input Variability of the Adjuvant! Online Breast Cancer Prognostic Model
Authors: Ozanne Elissa M. , Braithwaite Dejana , Sepucha Karen , Moore Dan , Esserman Laura , Belkora Jeffrey 
Published: December 2008

Purpose Adjuvant! Online ( www.adjuvantonline.org ) is a software model that predicts the benefit of adjuvant therapy for women with early-stage breast cancer. The model has been validated, is widely consulted, and has been shown to influence patient choices in the clinical setting. Adjuvant! requires the clinician to input patient age, tumor size, grade, hormone receptor status, number of positive lymph nodes, and comorbidity level. Because comorbidity is strongly and independently associated with survival, this study tested the hypothesis that Adjuvant! predictions would be sensitive to comorbidity inputs. Methods Investigators used single-variable deterministic sensitivity analysis to evaluate the effect of varying each input of the model independently for three representative case examples based on National Comprehensive Cancer Network guidelines (NCCN). The main outcome of interest was 10-year mortality prediction. Results The analyses show that Adjuvant!'s 10-year mortality predictions are most sensitive to patients’ comorbidity levels and the extent of nodal involvement for the cases, particularly among older women. Comorbidity was the most influential input except in younger women, aged 40 years. Conclusion The Adjuvant! model is sensitive to patient comorbidity, and impact on the model outputs are significant enough that they are likely to affect physician recommendations and patients’ treatment choices. For example, incorrect assessments of comorbidities could lead physicians to overtreat or undertreat a patient who is in a gray zone relative to the NCCN guidelines. These results point to the importance of accurately assessing comorbidities in patients with breast cancer when using Adjuvant! and highlight the need for a standardized process of comorbidity ascertainment.
Significance of MYCN Amplification in International Neuroblastoma Staging System Stage 1 and 2 Neuroblastoma: A Report From the International Neuroblastoma Risk Group Database
Authors: Bagatell Rochelle , Beck-Popovic Maja , London Wendy B. , Zhang Yang , Pearson Andrew D.J. , Matthay Katherine K. , Monclair Tom , Ambros Peter F. , Cohn Susan L. 
Published: December 2008

Purpose Treatment of patients with localized neuroblastoma with unfavorable biologic features is controversial. To evaluate the outcome of children with low-stage MYCN-amplified neuroblastoma and develop a rational treatment strategy, data from the International Neuroblastoma Risk Group (INRG) database were analyzed. Patients and Methods The database is comprised of 8,800 patients. Of these, 2,660 patients (30%) had low-stage (International Neuroblastoma Staging System stages 1 and 2) neuroblastoma, known MYCN status, and available follow-up data. Eighty-seven of these patients (3%) had MYCN amplified tumors. Results Patients with MYCN-amplified, low-stage tumors had less favorable event-free survival (EFS) and overall survival (OS) than did patients with nonamplified tumors (53% ± 8% and 72% ± 7% v 90% ± 1% and 98% ± 1%, respectively). EFS and OS were statistically significantly higher for patients whose tumors were hyperdiploid rather than diploid (EFS, 82% ± 20% v 37% ± 21%; P = .0069; OS, 94% ± 11% v 54% ± 15%; P = .0056, respectively). No other variable had prognostic significance. Initial treatment consisted of surgery alone for 29 (33%) of 87 patients. Details of additional therapy were unknown for 14 patients. Twenty-two patients (25%) underwent surgery and moderate-intensity chemotherapy; another 22 underwent surgery, intensive chemotherapy, and radiation therapy. Nine of the latter 22 underwent stem cell transplantation. Survival in patients who received transplantation did not differ from survival in those who did not receive transplantation. Conclusion Among patients with low-stage, MYCN-amplified neuroblastoma, outcomes of patients with hyperdiploid tumors were statistically, significantly better than those with diploid tumors. The data suggest that tumor cell ploidy could potentially be used to identify candidates for reductions in therapy. Further study of MYCN-amplified, low-stage neuroblastoma is warranted.
Engineering at the interface revisited
Authors: Gebeshuber I C 
Published: December 2008

Three publications from Part C which strongly influenced the development of the field of lubrication in human joints are revisited and their impact on the field is outlined. Furthermore, the impact of the Journal of Mechanical Engineering Science on the field of lubrication and wear in living and artificial human joints is analysed. ‘Analysis of “boosted lubrication” in human joints’ by Duncan Dowson, Anthony Unsworth, and Verna Wright appeared in 1970, ‘The lubrication of porous elastic solids with reference to the functioning of human joints’ by Gordon R. Higginson and Roger Norman was published in 1974, and ‘Engineering at the interface’ by Duncan Dowson addressed the audience in 1992.
Maximizing the lowest eigenvalue of a constrained affine sum with application to the optimal design of structures and vibrating systems
Authors: Ram Y M , Krishna S G 
Published: December 2008

This article deals with the problem of maximizing the lowest eigenvalue of an affine sum of symmetric matrices subject to a constraint. It is shown that by the repeated use of eliminants, the problem may be reduced in a systematic manner to that of finding the roots of certain polynomials. However, the process of finding the analytical solution is tedious. Therefore, a Newton iterative method, which solves the problem numerically, is developed. To demonstrate the results, the Lagrange problem of determining the shape of the strongest column is formulated in the discrete model setting and solved by using the developed method. The design problem of finding the mass distribution in a vibratory system that optimizes its extreme natural frequencies is also given.
Simulation of traction curving for active yaw — force steered bogies in locomotives
Authors: Simson S A , Cole C 
Published: December 2008

Steering bogies and actively steered bogies are subjected to increasing interest. Self-steering bogies have been used in large numbers of hauling locomotives primarily in the USA to reduce flange wear and improve adhesion. However, the steering performance of self-steering bogies is reported to deteriorate under traction. This article compares several bogie types and proposes a new design of steering bogie featuring forced steering combined with control of the bogie yaw movement or actuated yaw forced steered bogie (AY-FS). The bogie stability of a force steered bogie is improved by yaw actuation using a negative derivative control of the bogie yaw misalignment. An additional benefit of the bogie design is that actuators and control sensors for the AY-FS bogie can be mounted on the vehicle body rather than on the bogie frame. The article presents simulation results for a yaw actuated force steered bogie under traction curving conditions. The AY-FS bogie is compared with rigid and force steered bogies and is shown to give superior performance at high traction adhesion levels during curving. The curving performance improvements achieved depend on the curvature, lateral forces on the vehicle, the traction load, and the rail friction. The greatest curving performance advantages occur in tighter curvatures with high traction loads and low rail friction and with high lateral forces to the inside rail such as would result from coupler loads on pulling locomotives.
Bainitic steel grade for solid wheels: metallurgical, mechanical, and in-service testing
Authors: Gianni A , Ghidini A , Karlsson T , Ekberg A 
Published: December 2008

Bainitic steel grades generally have superior rolling contact and thermal fatigue resistances, but poorer wear characteristics when compared with ‘conventional’ pearlitic steel wheels. To improve the wear characteristics, the manufacturing process of bainitic materials needs to be carefully controlled. In this article, the manufacturing process of the ‘MICRALOS’ bainitic steel grade has been described. The main focus is on metallurgical testing activities performed in order to compare the new steel grade with standard pearlitic steels and to predict the service behaviour of the solid bainitic wheels. Further, on-going field tests on the iron ore line between Luleå and Narvik have been reported, with details about measurement methods and results. The performance of the wheels is reviewed and compared with the current scientific knowledge of bainitic steel grades and the deterioration of heavy haul wheels. Finally, benefits of and challenges for bainitic wheels in general and for the MICRALOS grade wheels in particular will be discussed.
Finite Element Analysis of the Proximal Femur and Hip Fracture Risk in Older Men
Authors: Orwoll Eric S , Marshall Lynn M , Nielson Carrie M , Cummings Steven R , Lapidus Jodi , Cauley Jane A , Ensrud Kristine , Lane Nancy , Hoffmann Paul R , Kopperdahl David L , Keaveny Tony M 
Published: December 2008

Abstract
Low areal BMD (aBMD) is associated with increased risk of hip fracture, but many hip fractures occur in persons without low aBMD. Finite element (FE) analysis of QCT scans provides a measure of hip strength. We studied the association of FE measures with risk of hip fracture in older men. A prospective case-cohort study of all first hip fractures (n = 40) and a random sample (n = 210) of nonfracture cases from 3549 community-dwelling men ≥65 yr of age used baseline QCT scans of the hip (mean follow-up, 5.6 yr). Analyses included FE measures of strength and load-to-strength ratio and BMD by DXA. Hazard ratios (HRs) for hip fracture were estimated with proportional hazards regression. Both femoral strength (HR per SD change = 13.1; 95% CI: 3.9–43.5) and the load-to-strength ratio (HR = 4.0; 95% CI: 2.7–6.0) were strongly associated with hip fracture risk, as was aBMD as measured by DXA (HR = 5.1; 95% CI: 2.8–9.2). After adjusting for age, BMI, and study site, the associations remained significant (femoral strength HR = 6.5, 95% CI: 2.3–18.3; load-to-strength ratio HR = 4.3, 95% CI: 2.5–7.4; aBMD HR = 4.4, 95% CI: 2.1–9.1). When adjusted additionally for aBMD, the load-to-strength ratio remained significantly associated with fracture (HR = 3.1, 95% CI: 1.6–6.1). These results provide insight into hip fracture etiology and demonstrate the ability of FE-based biomechanical analysis of QCT scans to prospectively predict hip fractures in men.
Single-Dose, Randomized, Double-Blind, Placebo-Controlled Study of ACE-011 (ActRIIA-IgG1) in Postmenopausal Women
Authors: Ruckle Jon , Jacobs Mark , Kramer William , Pearsall Amelia E , Kumar Ravindra , Underwood Kathryn W , Seehra Jasbir , Yang Yijun , Condon Carolyn H , Sherman Matthew L 
Published: December 2008

Abstract
The effects of ACE-011 on safety, pharmacokinetics, and bone biomarkers were evaluated in healthy, postmenopausal women. Our data indicate that ACE-011 results in a sustained increase in biomarkers of bone formation and reduction in markers of bone resorption. The activin type IIA receptor (ActRIIA) is the high-affinity receptor for activin. ACE-011 is a dimeric fusion protein consisting of the extracellular domain of the human ActRIIA linked to the Fc portion of human IgG1. ACE-011 binds to activin, preventing activin from binding endogenous receptors. A randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and tolerability of ACE-011. Forty-eight healthy, postmenopausal women were randomized to receive either a single dose of ACE-011 or placebo and were followed for 4 mo. Dose levels ranged from 0.01 to 3.0 mg/kg intravenously and from 0.03 to 0.1 mg/kg subcutaneously. Safety and pharmacokinetic (PK) analyses and the biological activity of ACE-011, as assessed by markers of bone turnover, and follicle stimulating hormone (FSH) levels were measured. No serious adverse events (AEs) were reported. AEs were generally mild and transient. The PK of ACE-011 was linear over the dose range studied, with a mean half-life of 24–32 days. The absorption after subcutaneous dosing was essentially complete. ACE-011 caused a rapid and sustained dose-dependent increase in serum levels of bone-specific alkaline phosphatase (BSALP) and a dose-dependent decrease in C-terminal type 1 collagen telopeptide (CTX) and TRACP-5b levels. There was also a dose-dependent decrease in serum FSH levels consistent with inhibition of activin. ACE-011 is a novel agent with biological evidence of both an increase in bone formation and a decrease in bone resorption. ACE-011 may be an effective therapy in a variety of diseases involving bone loss.
FGF2 Stimulation of the Pyrophosphate-Generating Enzyme, PC-1, in Pre-Osteoblast Cells Is Mediated by RUNX2
Authors: Hatch Nan E , Li Yan , Franceschi Renny T 
Published: December 2008

Abstract
Pyrophosphate is an established inhibitor of hydroxyapatite deposition and crystal growth, yet when hydrolyzed into phosphate, it becomes a substrate for hydroxyapatite deposition. Pyrophosphate-generating enzyme (PC-1), Ank, and tissue nonspecific alkaline phosphatase (Tnap) are three factors that regulate extracellular pyrophosphate levels through its generation, transport, and hydrolysis. We previously showed that fibroblast growth factor 2 (FGF2) induces PC-1 and Ank while inhibiting Tnap expression and mineralization in MC3T3E1(C4) calvarial pre-osteoblast cells. In this study, we showed similar FGF2 regulation of these genes in primary pre-osteoblast cultures. In contrast to Ank and Tnap that are regulated by FGF2 in multiple cell types, we found regulation of PC-1 to be selective to pre-osteoblastic cells and to require the osteoblast-related transcription factor, Runx2. Specifically, FGF2 was unable to induce PC-1 expression in Runx2-negative nonbone cells or in calvarial cells from Runx2-deficient mice. Transfection of these cells with a Runx2 expression vector restored FGF2 responsiveness. FGF2 was also shown to stimulate recruitment of Runx2 to the endogenous PC-1 promoter in MC3T3E1(C4) cells, as measured by chromatin immunoprecipitation. Taken together, our results establish that FGF2 is a specific inducer of PC-1 in pre-osteoblast cells and that FGF2 induces PC-1 expression through a mechanism involving Runx2.
Water-Manometer Tensiometers Installed and Read from the Land Surface
Authors: Oaksford ET 
Published: December 2008

Abstract
Soil-moisture tension has been measured beneath an artificial-recharge basin in Suffolk County, Long Island, N.Y., with water-manometer tensiometers that can be installed and read from the land surface. The manometer-tensiometer unit is buried at the desired depth, and soil-moisture tension is measured from the land surface with a simple wire probe and electrical circuit that detect the level of water in the manometer. The water manometer is more sensitive than other common methods for determining unsaturated pressure head or soil-moisture tension over small ranges and is most helpful in situations where small changes in soil-moisture tension can reflect significant changes in hydraulic conductivity. Although the configuration may not be appropriate for installation at great depth (&gt; 6 m) or in extremely coarse or fine soils, it provides rapid, reliable measurement of soil-moisture tension.
Testing of Geotechnical Fabric for Use as Reinforcement
Authors: Haliburton TA , Anglin CC , Lawmaster JD 
Published: December 2008

Abstract
Twenty-seven commercially available petrochemical-based geotechnical fabrics, both woven and nonwoven, and one fiberglass fabric were evaluated for suitability as reinforcement in an embankment test section to be constructed on soft foundation at Pinto Pass in Mobile Harbor, Ala. by the U.S. Army Corps of Engineers Mobile District. All fabrics were subjected to initial testing in uniaxial tension and fabrics meeting or exceeding established strength criteria were subjected to additional testing to determine creep behavior, soil-fabric frictional resistance, and the effects of immersion and water absorption on developed tensile strength. The effects of specimen width and testing strain rate on uniaxial tension test results were also investigated.
Four woven geotechnical fabrics plus the woven fiberglass fabric were found to meet or exceed required tensile strength criteria: Nicolon 66475, Nicolon 66186, Polyfilter-X, Advance Type I, and Bay Mills 196-380-000 (fiberglass). Both Nicolon materials were found to have minimal creep tendency and strength loss after soaking. Polyfilter-X was found to have moderate creep tendencies and high strength loss upon soaking, while Advance Type I was found to have high creep tendencies and moderate strength loss upon soaking. Bay Mills 196-380-000 had zero creep tendency and was not tested for soaking strength loss. Minimum soil-fabric frictional resistance for all five fabrics approximated soil-alone behavior for a loose relative density condition.