bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognosis in Patients With Sentinel Node–Positive Melanoma Is Accurately Defined by the Combined Rotterdam Tumor Load and Dewar Topography Criteria
Authors: van der Ploeg Augustinus P.T. , van Akkooi Alexander C.J. , Rutkowski Piotr , Nowecki Zbigniew I. , Michej Wanda , Mitra Angana , Newton-Bishop Julia A. , Cook Martin , van der Ploeg Iris M.C. , Nieweg Omgo E. , van den Hout Mari F.C.M. , van Leeuwen Paul A.M. , Voit Christiane A. , Cataldo Francesco , Testori Alessandro , Robert Caroline , Hoekstra Harald J. , Verhoef Cornelis , Spatz Alain , Eggermont Alexander M.M. 
Published: April 2011

Purpose Prognosis in patients with sentinel node (SN) –positive melanoma correlates with several characteristics of the metastases in the SN such as size and site. These factors reflect biologic behavior and may separate out patients who may or may not need additional locoregional and/or systemic therapy. Patients and Methods Between 1993 and 2008, 1,080 patients (509 women and 571 men) were diagnosed with tumor burden in the SN in nine European Organisation for Research and Treatment of Cancer (EORTC) melanoma group centers. In total, 1,009 patients (93%) underwent completion lymph node dissection (CLND). Median Breslow thickness was 3.00 mm. The median follow-up time was 37 months. Tumor load and tumor site were reclassified in all nodes by the Rotterdam criteria for size and in 88% by the Dewar criteria for topography. Results Patients with submicrometastases (< 0.1 mm in diameter) were shown to have an estimated 5-year overall survival rate of 91% and a low nonsentinel node (NSN) positivity rate of 9%. This is comparable to the rate in SN-negative patients. The strongest predictive parameter for NSN positivity and prognostic parameter for survival was the Rotterdam-Dewar Combined (RDC) criteria. Patients with submicrometastases that were present in the subcapsular area only, had an NSN positivity rate of 2% and an estimated 5- and 10-year melanoma-specific survival (MSS) of 95%. Conclusion Patients with metastases < 0.1 mm, especially when present in the subcapsular area only, may be overtreated by a routine CLND and have an MSS that is indistinguishable from that of SN-negative patients. Thus the RDC criteria provide a rational basis for decision making in the absence of conclusions provided by randomized controlled trials.
Cytoplasmic Poly(Adenosine Diphosphate–Ribose) Polymerase Expression Is Predictive and Prognostic in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy
Authors: von Minckwitz Gunter , Müller Berit Maria , Loibl Sibylle , Budczies Jan , Hanusch Claus , Darb-Esfahani Silvia , Hilfrich Jörn , Weiss Erich , Huober Jens , Blohmer Jens Uwe , du Bois Andreas , Zahm Dirk-Michael , Khandan Fariba , Hoffmann Gerald , Gerber Bernd , Eidtmann Holger , Fend Falko , Dietel Manfred , Mehta Keyur , Denkert Carsten 
Published: April 2011

Purpose Poly(adenosine diphosphate–ribose) polymerase (PARP) plays a key role in DNA repair and cellular stress response. Inhibitors of PARP show promising clinical activity in metastatic, triple-negative or BRCA-mutated breast cancer. Patients and Methods We investigated cytoplasmic PARP (cPARP) and nuclear PARP (nPARP) expression by immunohistochemistry in 638 pretreatment biopsies from patients on the GeparTrio study and evaluated its predictive and prognostic value after neoadjuvant anthracycline/taxane-based chemotherapy. Results cPARP expression was high in 23.7%, intermediate in 50.9%, and negative in 25.4% of tumors. High cPARP expression was significantly correlated with nonlobular histology (P < .001), undifferentiated grade (P < .001), positive nodal status (P = .049), and negative hormone receptor (HR) status (P < .001) but not with human epidermal growth factor receptor 2 (HER2) status. Expression was high in 35.5% of triple-negative tumors, 24.6% of HER2-positive tumors, and 18.0% of HR-positive/HER2-negative tumors (P < .001). Pathologic complete response (pCR) rates were 26.5%, 19.1%, and 8.0% in patients with high, intermediate, or negative expression, respectively (P < .001). This predictive effect was most prominent in HR-positive tumors (P = .035) or HER2-negative tumors (P < .001). High cPARP expression was a negative, but not independent, prognostic factor for disease-free survival (DFS; P = .0025) and overall survival (OS; P = .0022). cPARP expression was highly prognostic in patients without a pCR (DFS, P < .001; OS, P < .001) and in patients with HR-positive tumors (DFS, P < .001; OS, P < .001). No such correlations were found for nPARP expression. Conclusion High cPARP expression correlates with aggressive tumor pattern and predicts high sensitivity to neoadjuvant taxane/anthracycline-based chemotherapy but also unfavorable long-term prognosis. As a potential target for PARP inhibitors, cPARP-positive breast cancer might become a new, clinically relevant entity.
Phase II Study of the Mitogen-Activated Protein Kinase 1/2 Inhibitor Selumetinib in Patients With Advanced Hepatocellular Carcinoma
Authors: O'Neil Bert H. , Goff Laura W. , Kauh John Sae Wook , Strosberg Jonathan R. , Bekaii-Saab Tanios S. , Lee Ruey-min , Kazi Aslamuzzaman , Moore Dominic T. , Learoyd Maria , Lush Richard M. , Sebti Said M. , Sullivan Daniel M. 
Published: April 2011

Purpose Hepatocellular carcinoma (HCC) is a common and deadly malignancy with few systemic therapy options. The RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is activated in approximately 50% to 60% of HCCs and represents a potential target for therapy. Selumetinib is an orally available inhibitor of MEK tyrosine kinase activity. Patients and Methods Patients with locally advanced or metastatic HCC who had not been treated with prior systemic therapy were enrolled on to the study. Patients were treated with selumetinib at its recommended phase II dose of 100 mg twice per day continuously. Cycle length was 21 days. Imaging was performed every two cycles. Biopsies were obtained at baseline and at steady-state in a subset of patients, and pharmacokinetic (PK) analysis was performed on all patients. Results Nineteen patients were enrolled, 17 of whom were evaluable for response. Most (82%) had Child-Pugh A cirrhosis. Toxicity was in line with other studies of selumetinib in noncirrhotic patients. PK parameters were also comparable to those in noncirrhotic patients. No radiographic response was observed in this group, and the study was stopped at the interim analysis. Of 11 patients with elevated α-fetoprotein, three (27%) had decreases of 50% or more. Median time to progression was 8 weeks. Inhibition of ERK phosphorylation was demonstrated by Western blotting. Conclusion In this study of selumetinib for patients with HCC, no radiographic responses were seen and time to progression was short, which suggests minimal single-agent activity despite evidence of suppression of target activation.
Multi-Institutional Phase II Study of Selumetinib in Patients With Metastatic Biliary Cancers
Authors: Bekaii-Saab Tanios , Phelps Mitch A. , Li Xiaobai , Saji Motoyasu , Goff Laura , Kauh John Sae Wook , O'Neil Bert H. , Balsom Stephanie , Balint Catherine , Liersemann Ryan , Vasko Vasily V. , Bloomston Mark , Marsh William , Doyle L. Austin , Ellison Gilian , Grever Michael , Ringel Matthew D. , Villalona-Calero Miguel A. 
Published: April 2011

Purpose Biliary cancers (BCs) carry a poor prognosis, but targeting the RAS/RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is of significance. Selumetinib is an inhibitor of MEK1/2, so this trial was designed to determine the safety and efficacy of selumetinib in BC. Patients and Methods This was a multi-institutional phase II study of selumetinib at 100 mg given orally twice per day to patients with advanced BC. The primary end point was response rate. All patients were required to provide tissue before enrolling. The levels of phosphorylated ERK (pERK) and AKT (pAKT) were assessed by immunohistochemistry. Tumors were genotyped for the presence of BRAF- and/or RAS-activating mutations. Results Twenty-eight eligible patients with a median age of 55.6 years were enrolled. Thirty-nine percent of patients had received one prior systemic therapy. Three patients (12%) had a confirmed objective response. Another 17 patients (68%) experienced stable disease (SD), 14 of whom (56%) experienced prolonged SD (> 16 weeks). Patients gained an average nonfluid weight of 8.6 pounds. Median progression-free survival was 3.7 months (95% CI, 3.5 to 4.9) and median overall survival was 9.8 months (95% CI, 5.97 to not available). Toxicities were mild, with rash (90%) and xerostomia (54%) being most frequent. Only one patient experienced grade 4 toxicity (fatigue). All patients had tissue available for analysis. No BRAF V600E mutations were found. Two patients with short-lived SD had KRAS mutations. Absence of pERK staining was associated with lack of response. Conclusion Selumetinib displays interesting activity and acceptable tolerability in patients with metastatic BC. Our results warrant further evaluation of selumetinib in patients with metastatic BC.
Biological Variation and Reference Change Value of High-Sensitivity Troponin T in Healthy Individuals during Short and Intermediate Follow-up Periods
Authors: Frankenstein Lutz , Wu Alan HB , Hallermayer Klaus , Wians Frank H , Giannitsis Evangelos , Katus Hugo A 
Published: April 2011

BACKGROUND
Acute myocardial infarction is defined by a troponin concentration &gt;99th percentile with an acute increase and/or decrease, the magnitude of which has not yet been well defined. To aid the interpretation of changes in cardiac troponin concentration, we sought to establish biological variation and reference change values (RCVs) by applying both the normal and lognormal approaches for cardiac troponin T (cTnT) sampled at hourly and weekly intervals in healthy individuals and measured on the Roche E 170 and Elecsys® 2010 automated platforms.

METHODS
High-sensitivity cTnT (hsTnT) was measured at baseline, and after 1, 2, 3, and 4 h and after 1, 2, 3, and 4 weeks in 20 and 17 healthy individuals, respectively. A healthy status was established by physical examination, MRI analysis at rest and during dobutamine stress, lung function testing, and blood sample testing.

RESULTS
Hourly total and within-individual CVs were 18% and 15%, respectively, for the E 170 assay, and 24% and 21%, respectively, for the Elecsys 2010 assay. Weekly total and within-individual CVs for these assays were 32% and 31%, respectively, for the E 170 assay, and 32% and 30%, respectively, for the Elecsys 2010 assay. The RCVs for the E 170 and Elecsys 2010 assays were ±46% and ±62% (hourly), respectively, and ±87% and ±86% (weekly), respectively. The corresponding lognormal values were +64%/−39% and +90%/−47% (hourly), and +138%/−58% and +135%/−58% (weekly).

CONCLUSIONS
RCVs appear attractive for interpreting hsTnT results. The short-term biological variation of hsTnT is low but becomes somewhat more important at intermediate sampling intervals. Knowledge of this variation is important for interpreting results from patients in whom cTnT values increase from low concentrations.
Centrifuge Test to Assess the Seismic Compression of Partially Saturated Sand Layers
Authors: Ghayoomi Majid , McCartney John , Ko Hon-Yim 
Published: April 2011

Abstract
A new testing approach for characterization of the response of partially saturated sand layers to cyclic loading is described in this paper. The approach involves basal shaking of a soil specimen within a laminar container using a hydraulic servo-controlled shake table in a geotechnical centrifuge. Infiltration of water was used to control the profiles of matric suction and degree of saturation, and thus the effective stress state, in the partially saturated sand layer during centrifugation. At steady state infiltration, relatively uniform profiles of degree of saturation and matric suction developed with depth in the sand layer. By varying the infiltration rate, different initial unsaturated conditions were obtained for cyclic testing. Instrumentation was incorporated into the setup to measure the accelerations induced in the shake table and soil profile, surface settlements, volumetric water content profiles, and pore water pressure. Cyclic tests were performed on sand layers having degrees of saturation ranging from 0.00 to 0.55 to assess the impact of effective stress on the layer’s deformation response. A nonlinear trend was observed in the variation of surface settlement with degree of saturation, with a minimum value obtained for sand having a degree of saturation of 0.28. This trend is consistent with the relationship between small strain shear modulus and degree of saturation for this sand.
Evaluation of Bias for Two Charpy Impact Machines with the Same Instrumented Striker
Authors: McCowan Chris N. , Lucon Enrico , Santoyo Raymond L. 
Published: April 2011

Abstract
Two Charpy machines were used to test NIST verification specimens at three energy levels: low energy (∼15 J at −40°C), high energy (∼100 J at −40°C), and super-high energy (∼240 J at room temperature). The study evaluates the differences observed for the bias between two impact machines and the variation in test data for instrumented versus non-instrumented impact tests. The machines used for testing were of very similar design, and all tests were performed with the same instrumented striker (switched between machines). After testing, the raw force/time data were used for the analyses, without correcting instrumented data by matching absorbed energies measured by the machine encoder (KV) and calculated under the force/deflection test record (Wt). The characteristic forces at general yield (Fgy) and the maximum forces (Fm) were determined in accordance with ASTM E2298-09 from the instrumented impact record that was used to calculate the total impact energy (Wt). The findings show the following: (1) one machine consistently produced higher absorbed energy values than the other machine; (2) the variation in Wt is significantly lower than the variation in absorbed energy measured in the non-instrumented test (KV) for a given machine and energy level; (3) the relative differences between KV and Wt increased with increasing absorbed energy levels; (4) variations in maximum force are lower than variations in absorbed energy values; (5) instrumented data indicate that the variation in the curves is very small up to maximum force, and that differences in absorbed energy mainly occur during fracture propagation (post-maximum force data); (6) data from these two independent measures of absorbed energy indicate that scatter is due primarily to material variability; and (7) the bias between the two machines is significantly reduced when the same striker is used for testing.
Multi-Parameter Monitoring System für Hydraulische Flüssigkeiten
Authors: Paul Sumit , Legner Wolfgang , Hackner Angelika , Baumbach Volker , Müller Gerhard 
Published: April 2011

Zusammenfassung
Es wird ein miniaturisiertes Messsystem für hydraulische Flüssigkeiten vorgestellt. Das System besteht aus zwei Teilen: (i) einem opto-chemischen Sensor, der die Stärke und die energetische Lage der O-H Absorption in der Umgebung von 3500 cm−1 detektiert, und (ii) einem Partikelsensor, der auf einem Lichtschrankenprinzip beruht. Der erste Sensor misst den Wasser- und den Säuregehalt und der zweite die Anzahl fester Teilchen in der Flüssigkeit.
Messung der Strömungsverteilung am Austritt der Bipolarplatten eines Brennstoffzellen-Stacks
Authors: Klinner Joachim , Willert Christian , Schneider Armin , Mack-Gardner André 
Published: April 2011

Zusammenfassung
Es werden zwei experimentelle Ansätze vorgestellt, um die Strömungsverteilung eines luftdurchströmten 8–12 KW Brennstoffzellen-Stacks unter realistischen Massenströmen nahe am anodenseitigen Austritt zu erfassen. Mit Hilfe einer Visualisierungstechnik kann die Eindringtiefe der Freistrahlen in das Sammelleitungsgebiet dargestellt werden. Durch Anwendung von zweikomponentiger Particle Image Velocimetry (2C-PIV) wird das Geschwindigkeitsfeld in der gesamten Höhe des Stacks hochaufgelöst gemessen. Neben der Implementierung des experimentellen Setups wird auf die PIV Datenauswertung eingegangen.
Micro-Particle-Image-Velocimetry zur Bestimmung der Geschwindigkeiten in einem Koronargefäß mit Stent
Authors: Quosdorf Daniel , Brede Martin , Leder Alfred , Lootz Daniel , Martin Heiner , Schmitz Klaus-Peter 
Published: April 2011

Zusammenfassung
In diesem Beitrag wird ein Micro-Particle-Image-Velocimetry Messaufbau (Micro-PIV) beschrieben, mit dem das dreidimensionale Geschwindigkeitsfeld der Strömung an einem transparenten 1:1 Modell eines originalen koronaren Stents quantitativ bestimmt werden kann. Der Behandlung der koronaren Herzkrankheit durch Stents kommt eine hohe Bedeutung zu. Durch den Stent hervorgerufene Veränderungen der Strömung führen zu unerwünschten Begleiterscheinungen.
Early Onset Neonatal Sepsis: The Burden of Group B Streptococcal and E. coli Disease Continues
Authors: Stoll Barbara J. , Hansen Nellie I. , Sánchez Pablo J. , Faix Roger G. , Poindexter Brenda B. , Van Meurs Krisa P. , Bizzarro Matthew J. , Goldberg Ronald N. , Frantz Ivan D. , Hale Ellen C. , Shankaran Seetha , Kennedy Kathleen , Carlo Waldemar A. , Watterberg Kristi L. , Bell Edward F. , Walsh Michele C. , Schibler Kurt , Laptook Abbot R. , Shane Andi L. , Schrag Stephanie J. , Das Abhik , Higgins Rosemary D. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Published: April 2011

BACKGROUND:
Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen.

OBJECTIVE:
To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers.

METHODS:
Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ≤72 hours plus treatment with antibiotic therapy for ≥5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence.

RESULTS:
Among 396 586 LBs (2006–2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%).

CONCLUSION:
In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge.
Parents' Experiences of Their Children's Presence in Discussions With Physicians About Leukemia
Authors: Young Bridget , Ward Joanne , Salmon Peter , Gravenhorst Katja , Hill Jonathan , Eden Tim 
Published: April 2011

OBJECTIVE:We aimed to examine parents' views regarding their preadolescent child's presence during discussions about serious illnesses.METHODS:In-depth qualitative interviews with parents of children receiving treatment for acute lymphoblastic leukemia were conducted. Parents were sampled from 6 UK treatment centers. Analysis was informed by the constant comparative method and content analysis.RESULTS:We report on interviews with 53 parents (33 mothers, 20 fathers). Parents acknowledged the benefits of communicating openly with children, but few thought that their child's presence in discussions was straightforwardly desirable. They described how their child's presence restricted their own communication with physicians, made concentrating difficult, and interfered with their efforts to care for their child emotionally. Children's presence was particularly difficult when significant issues were being discussed, including prognoses, adverse results, and certain medical procedures. Parents felt that such discussions posed a potential threat to their child, particularly when they had not first had an opportunity to discuss information with the physician separately from the child. In contrast, separate meetings enabled parents to absorb information and to convey it to their child at an appropriate time and in a reassuring way. Some parents experienced difficulties in accessing separate meetings with physicians.CONCLUSIONS:The difficulties parents described could potentially be addressed by extending, beyond the diagnosis period, the practice of sequencing significant information so that it is communicated to parents in separate meetings before being communicated to the child and by periodically exploring with parents what information would be in each child's interests.
Novel Approach to Parental Permission and Child Assent for Research: Improving Comprehension
Authors: O'Lonergan Theresa A. , Forster-Harwood Jeri E. 
Published: April 2011

OBJECTIVE:
The aim of this research was to test a multimedia permission/assent (P/A) process. The overall hypothesis was that children and their parents exposed to a multimedia P/A process would have better comprehension compared with those exposed to a text-based process.

METHODS:
Traditional and multimedia P/A processes were created by using an innovative learning-objective approach. A total of 194 parent-child dyads (children aged 11–14 years) were enrolled: 24 dyads in a prestudy testing P/A components for preference and effect on comprehension and 170 dyads in a randomized trial of a multimedia or paper P/A process for a hypothetical study. Participants were predominantly white and were from a metropolitan area served by a tertiary care pediatric hospital and outpatient facility. Comprehension of 8 essential elements of the P/A process was assessed.

RESULTS:
The majority of prestudy subjects preferred the video version of the dual-energy radiograph absorptiometry description over the animated and paper versions combined (41 of 48 [85%]; P &lt; .0001), and there were similar results for the abdominal ultrasound description (38 of 47 [81%]; P &lt; .0001). Children exposed to the novel process showed significantly better overall comprehension compared with the paper P/A process (P = .0009), and there were highly significant differences in understanding of study procedures (P = .0002) and risks (P &lt; .0001). The parental multimedia group had significantly better overall comprehension (P = .03).

CONCLUSIONS:
Multimedia approaches to the research P/A process may improve overall understanding of research participation for children and parents. Improved understanding of study-specific research components (rather than research rights) may improve overall comprehension.