bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focal adhesion kinase contributes to proliferative potential of ErbB2 mammary tumour cells but is dispensable for ErbB2 mammary tumour induction in vivo
Authors: Lahlou Hicham , Sanguin-Gendreau Virginie , Frame Margaret C , Muller William J 
Published: February 2012

Abstract
Introduction
Activation of focal adhesion kinase (FAK) is hypothesized to play an important role in the pathogenesis of human breast cancer.

Methods
To directly evaluate the role of FAK in mammary tumour progression, we have used a conditional FAK mouse model and mouse mammary tumour virus (MMTV)-driven Cre recombinase strain to inactivate FAK in the mammary epithelium of a transgenic mouse model of ErbB2 breast cancer.

Results
Although mammary epithelial disruption of FAK in this model resulted in both a delay in onset and a decrease in the number of neoplastic lesions, mammary tumours occurred in 100% of virgin female mice. All of the tumours and derived metastases that developed were proficient for FAK due to the absence of Cre recombinase expression. The hyperplastic epithelia where Cre-mediated recombination of FAK could be detected exhibited a profound proliferative defect. Consistent with these observations, disruption of FAK in established tumour cells resulted in reduced tumour growth that was associated with impaired proliferation. To avoid the selection for FAK-proficient ErbB2 tumour epithelia through escape of Cre-mediated recombination, we next intercrossed the FAK conditional mice with a separate MMTV-driven ErbB2 strain that co-expressed ErbB2 and Cre recombinase on the same transcriptional unit.

Conclusions
While a delay in tumour induction was noted, FAK-deficient tumours arose in 100% of female animals indicating that FAK is dispensable for ErbB2 tumour initiation. In addition, the FAK-null ErbB2 tumours retained their metastatic potential. We further demonstrated that the FAK-related Pyk2 kinase is still expressed in these tumours and is associated with its downstream regulator p130Cas. These observations indicate that Pyk2 can functionally substitute for FAK in ErbB2 mammary tumour progression.
Changes in Cardiac Biomarkers During Doxorubicin Treatment of Pediatric Patients With High-Risk Acute Lymphoblastic Leukemia: Associations With Long-Term Echocardiographic Outcomes
Authors: Lipshultz Steven E. , Miller Tracie L. , Scully Rebecca E. , Lipsitz Stuart R. , Rifai Nader , Silverman Lewis B. , Colan Steven D. , Neuberg Donna S. , Dahlberg Suzanne E. , Henkel Jacqueline M. , Asselin Barbara L. , Athale Uma H. , Clavell Luis A. , Laverdière Caroline , Michon Bruno , Schorin Marshall A. , Sallan Stephen E. 
Published: February 2012

Purpose Doxorubicin causes cardiac injury and cardiomyopathy in children with acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might help individualize treatment by immediately identifying cardiac injury and cardiomyopathy. Patients and Methods Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C-reactive protein (hsCRP; inflammatory biomarker) were obtained before, during, and after treatment. Results cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP levels were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment (P = .07). The percentage of children with increased hsCRP levels did not differ between groups at any time. In the first 90 days of treatment, detectable increases in cTnT were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness 4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01). Increases in hsCRP were not associated with any echocardiographic variables. Conclusion cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity in children with high-risk ALL. Definitive validation studies are required to fully establish their range of clinical utility.
First-SIGNAL: First-Line Single-Agent Iressa Versus Gemcitabine and Cisplatin Trial in Never-Smokers With Adenocarcinoma of the Lung
Authors: Han Ji-Youn , Park Keunchil , Kim Sang-We , Lee Dae Ho , Kim Hyae Young , Kim Heung Tae , Ahn Myung Ju , Yun Tak , Ahn Jin Seok , Suh Cheolwon , Lee Jung-Shin , Yoon Sung Jin , Han Jong Hee , Lee Jae Won , Jo Sook Jung , Lee Jin Soo 
Published: February 2012

PurposeGefitinib has shown high response rate and improved progression-free survival (PFS) in never-smokers with lung adenocarcinoma (NSLAs). We compared efficacy of gefitinib with gemcitabine and cisplatin (GP) chemotherapy in this group of patients as first-line therapy.Patients and MethodsIn this randomized phase III trial, a total of 313 Korean never-smokers with stage IIIB or IV lung adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ function were randomly assigned to receive either gefitinib (250 mg daily) or GP chemotherapy (gemcitabine 1,250 mg/m2on days 1 and 8; cisplatin 80 mg/m2on day 1 every 3 weeks, for up to nine courses). The primary objective was to demonstrate better overall survival (OS) for gefitinib compared with GP in chemotherapy-naive NSLAs.ResultsThree hundred nine patients were analyzed per protocol (gefitinib arm, n = 159; GP arm, n = 150). Gefitinib did not show better OS compared with GP (hazard ratio [HR], 0.932; 95% CI, 0.716 to 1.213; P = .604; median OS, 22.3 v 22.9 months, respectively). The 1-year PFS rates were 16.7% with gefitinib and 2.8% with GP (HR, 1.198; 95% CI, 0.944 to 1.520). Response rates were 55% with gefitinib and 46% with GP (P = .101). Myelosuppression, renal insufficiency, and fatigue were more common in the GP arm, but skin toxicities and liver dysfunction were more common in the gefitinib arm. Two patients (1.3%) in the gefitinib arm developed interstitial lung disease and died.ConclusionGefitinib failed to demonstrate superior OS compared with GP as first-line therapy for NSLAs.
Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987
Authors: Bellmunt Joaquim , von der Maase Hans , Mead Graham M. , Skoneczna Iwona , De Santis Maria , Daugaard Gedske , Boehle Andreas , Chevreau Christine , Paz-Ares Luis , Laufman Leslie R. , Winquist Eric , Raghavan Derek , Marreaud Sandrine , Collette Sandra , Sylvester Richard , de Wit Ronald 
Published: February 2012

Purpose The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival. Patients and Methods We conducted a randomized phase III study to compare paclitaxel/cisplatin/gemcitabine (PCG) with GC in patients with locally advanced or metastatic urothelial carcinoma. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate, and toxicity. Results From 2001 to 2004, 626 patients were randomly assigned; 312 patients were assigned to PCG, and 314 patients were assigned to GC. After a median follow-up of 4.6 years, the median OS was 15.8 months on PCG versus 12.7 months on GC (hazard ratio [HR], 0.85; P = .075). OS in the subgroup of all eligible patients was significantly longer on PCG (3.2 months; HR, 0.82; P = .03), as was the case in patients with bladder primary tumors. PFS was not significantly longer on PCG (HR, 0.87; P = .11). Overall response rate was 55.5% on PCG and 43.6% on GC (P = .0031). Both treatments were well tolerated, with more thrombocytopenia and bleeding on GC than PCG (11.4% v 6.8%, respectively; P = .05) and more febrile neutropenia on PCG than GC (13.2% v 4.3%, respectively; P < .001). Conclusion The addition of paclitaxel to GC provides a higher response rate and a 3.1-month survival benefit that did not reach statistical significance. Novel approaches will be required to obtain major improvements in survival of incurable urothelial cancer.
Book Reviews
Authors: Rand Graham K. 
Published: February 2012

In Book Reviews, we review an extensive and diverse range of books. They cover theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems. In addition, we include books in other fields that emphasize technical applications. The editor will be pleased to receive an e-mail from those willing to review a book, with an indication of specific areas of interest. If you are aware of a specific book that you would like to review, or that you think should be reviewed, please contact the editor. The following books are reviewed in this issue of Interfaces, 42(1), January–February 2012: Profiles in Operations Research: Pioneers and Innovators, Arjang A. Assad and Saul I. Gass, eds.; Operations Rules: Delivering Customer Value through Flexible Operations, David Simchi-Levi; Service Parts Management: Demand Forecasting and Inventory Control, Nezih Altay and Lewis A. Litteral, eds.; Linear Programming Sensitivity Analysis and Related Topics, Marie-France Derhy; Artificial Ants: From Collective Intelligence to Real-life Optimization and Beyond, Nicolas Monmarche, Frederic Guinand, and Patrick Siarry, eds.
Closing the Gaps in Pediatric Laboratory Reference Intervals: A CALIPER Database of 40 Biochemical Markers in a Healthy and Multiethnic Population of Children
Authors: Colantonio David A , Kyriakopoulou Lianna , Chan Man Khun , Daly Caitlin H , Brinc Davor , Venner Allison A , Pasic Maria D , Armbruster David , Adeli Khosrow 
Published: February 2012

AbstractBACKGROUNDPediatric healthcare is critically dependent on the availability of accurate and precise laboratory biomarkers of pediatric disease, and on the availability of reference intervals to allow appropriate clinical interpretation. The development and growth of children profoundly influence normal circulating concentrations of biochemical markers and thus the respective reference intervals. There are currently substantial gaps in our knowledge of the influences of age, sex, and ethnicity on reference intervals. We report a comprehensive covariate-stratified reference interval database established from a healthy, nonhospitalized, and multiethnic pediatric population.METHODSHealthy children and adolescents (n = 2188, newborn to 18 years of age) were recruited from a multiethnic population with informed parental consent and were assessed from completed questionnaires and according to defined exclusion criteria. Whole-blood samples were collected for establishing age- and sex-stratified reference intervals for 40 serum biochemical markers (serum chemistry, enzymes, lipids, proteins) on the Abbott ARCHITECT c8000 analyzer.RESULTSReference intervals were generated according to CLSI C28-A3 statistical guidelines. Caucasians, East Asians, and South Asian participants were evaluated with respect to the influence of ethnicity, and statistically significant differences were observed for 7 specific biomarkers.CONCLUSIONSThe establishment of a new comprehensive database of pediatric reference intervals is part of the Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER). It should assist laboratorians and pediatricians in interpreting test results more accurately and thereby lead to improved diagnosis of childhood diseases and reduced patient risk. The database will also be of global benefit once reference intervals are validated in transference studies with other analytical platforms and local populations, as recommended by the CLSI.
Functional Difficulties and Health Conditions Among Children With Special Health Needs
Authors: Lollar Donald J. , Hartzell Marilyn Sue , Evans Mary Ann 
Published: February 2012

OBJECTIVES:
To describe the functional difficulties of children with special health needs and to demonstrate the shared and unique contributions in predicting health outcomes and informing therapeutic interventions, policies, and research by using data from the 2005–2006 National Survey of Children With Special Health Care Needs.

RESULTS:
Children with special health care needs experience an array of health conditions and functional difficulties that are interrelated. Although health conditions tend not to change, the characteristics of functional difficulties are subject to changes over time with age or as a result of interventions. Descriptive data highlight common functional difficulties across health conditions. Multiple regression analyses support both health conditions and functional difficulties predicting (1) health services, such as emergency department visits, (2) personal limitations such as impairment of daily activities and school absences, and (3) family impact, stopping or reducing work. Functional difficulties were, however, the stronger predictor for all outcomes except school absences.

CONCLUSIONS:
The results support the utility of expanding measures of children with special health care needs to include functional difficulties in survey research, as well as clinical and public health practice. Systematic inclusion of functional difficulties will inform policy development, program planning, outcome assessment, and resource allocation for this vulnerable population. A focus on functional difficulties facilitates stronger coordination of services across sectors including physical health, mental health, education, and other social services to improve the health and well-being for these children and youth.
What the Orphan Drug Act Has Done Lately for Children With Rare Diseases: A 10-Year Analysis
Authors: Thorat Chandana , Xu Kui , Freeman Scott N. , Bonnel Renan A. , Joseph Francesca , Phillips M. Ian , Imoisili Menfo A. 
Published: February 2012

OBJECTIVES:
The 1983 US Orphan Drug Act (ODA) provided incentives to stimulate treatment product development for patients with rare disease. This article highlights a decade of ODA contributions to this goal for children with RDs.

METHODS:
An internal US Food and Drug Administration database was the information source for orphan designations, marketing approvals, and prevalence numbers for 2000 to 2009. Product categorization was based on the disease age of onset for which they received designation. Category 1 products were for diseases with onset exclusively in Childhood; Category 2 products were for diseases with onset at any age; and Category 3 products were for diseases with adult onset only. Disease prevalence distributions were analyzed by using population intervals of 20 000.

RESULTS:
From 2000 to 2009, 1138 orphan drugs were designated and 148 received marketing approval, of which 38 (26%) were for pediatric diseases. The proportion of approvals for pediatric products increased from 17.5% (10 of 57) in the first half of the decade, to 30.8% (28 of 91) in the second. More products received designation and marketing approval for pediatric diseases with prevalence numbers fewer than 20 000 than for any other prevalence subgroup. The median disease prevalence for all pediatric orphan designations that received marketing approval was 8972. Among the pediatric orphan drug approvals categorized by therapeutic class, the endocrine/metabolic drugs had the largest representation (39%).

CONCLUSIONS:
The ODA incentives have led to increased product availability for RDs overall, with an increasing number of marketing approvals for children this past decade.
Self-Referral and Serious Illness in Children With Fever
Authors: van Ierland Yvette , Seiger Nienke , van Veen Mirjam , van Meurs Alfred H. J. , Ruige Madelon , Oostenbrink Rianne , Moll Henriëtte A. 
Published: February 2012

OBJECTIVE:The goal of this study was to evaluate parents’ capability to assess their febrile child’s severity of illness and decision to present to the emergency department. We compared children referred by a general practitioner (GP) with those self-referred on the basis of illness-severity markers.METHODS:This was a cross-sectional observational study conducted at the emergency departments of a university and a teaching hospital. GP-referred or self-referred children with fever (aged &lt;16 years) who presented to the emergency department (2006–2008) were included. Markers for severity of illness were urgency according to the Manchester Triage System, diagnostic interventions, therapeutic interventions, and follow-up. Associations between markers and referral type were assessed by using logistic regression analysis. Subgroup analyses were performed for patients with the most common presenting problems that accompanied the fever (ie, dyspnea, gastrointestinal complaints, neurologic symptoms, fever without specific symptoms).RESULTS:Thirty-eight percent of 4609 children were referred by their GP and 62% were self-referred. GP-referred children were classified as high urgency (immediate/very urgent categories) in 46% of the cases and self-referrals in 45%. Forty-three percent of GP referrals versus 27% of self-referrals needed extensive diagnostic intervention, intravenous medication/aerosol treatment, hospitalization, or a combination of these (odds ratio: 2.0 [95% confidence interval: 1.75–2.27]). In all subgroups, high urgency was not associated with referral type. GP-referred and self-referred children with dyspnea had similar frequencies of illness-severity markers.CONCLUSIONS:Although febrile self-referred children were less severely ill than GP-referred children, many parents properly judged and acted on the severity of their child’s illness. To avoid delayed or missed diagnoses, recommendations regarding interventions that would discourage self-referral to the emergency department should be reconsidered.
Effect of Microalloying Elements (B, Nb, V and Ti) on the Strain Hardening Behavior of High-Manganese TWIP Steels.
Authors: Reyes-Calderón F. , Mejía I. , Cabrera J.M. 
Published: February 2012

ABSTRACTThe present research work analyses the influence of microalloying elements (B, Nb, V and Ti) on the tensile strength and the strain hardening behavior of a high-manganese TWIP steel. The analysis was carried out by means of true stress-true strain curves derived from uniaxial tension tests. The work hardening exponent was determined by using the Hollomon and differential Crussard-Jaoul models. Metallographic characterization was carried out to determine the metallurgical changes associated with n values. The results indicate that the Hollomon analysis results in strain hardening exponent values up to 0.46. On the other hand, the differential Crussard-Jaoul analysis establishes a clear distinction of n value for two stages of plastic deformation which are determined by a sharp slope change in the plot of ln(dσ/dε)-lnε.
Principles of Hand Fracture Management
Authors: Haughton DN , Jordan D , Malahias M , Hindocha S , Khan W 
Published: February 2012

The hand is essential in humans for physical manipulation of their surrounding environment. Allowing the ability to grasp, and differentiated from other animals by an opposing thumb, the main functions include both fine and gross motor skills as well as being a key tool for sensing and understanding the immediate surroundings of their owner.Hand fractures are the most common fractures presenting at both accident and emergency and within orthopaedic clinics. Appropriate evaluation at first presentation, as well as during their management, can significantly prevent both morbidity and disability to a patient. These decisions are dependant on a wide range of factors including age, hand dominance, occupation and co-morbidities.A fracture is best described as a soft tissue injury with an associated bony injury. Despite this being the case, this paper intends to deal mainly with the bone injury and aims to discuss both the timing, as well as the methods available, of hand fracture management.
A note on the extent of two subclasses of star countable spaces
Authors: Yu Zuoming 
Published: February 2012

Abstract
We prove that every Tychonoff strongly monotonically monolithic star countable space is Lindelöf, which solves a question posed by O.T. Alas et al. We also use this result to generalize a metrization theorem for strongly monotonically monolithic spaces. At the end of this paper, we study the extent of star countable spaces with k-in-countable bases, k ∈ ℤ.
Formation of dioxospiroindene[1,3]thiazine and thioxoindeno[2,1-d]imidazolone derivatives from alkenylidene-hydrazinecarbothioamides
Authors: Hassan Alaa , Nour El-Din Ahmed , Abdel-Latif Fathy , Mostafa Sara , Bräse Stefan 
Published: February 2012

AbstractThe reaction of (substituted) alkenylidene-hydrazinecarbothioamides with 2-(1,3-dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile led to the formation of 1,3-dioxospiroindene[1,3]-thiazine and thioxoindeno[2,1-d]imidazolone derivatives in modest yields. In addition, 1,3-dihydroxyindan-2-ylidenepropanedinitrile was found. Explanations of these conversions involving nucleophilic reactions and condensations are presented.
Some Tauberian conditions for Cesàro summability method
Authors: Çanak İbrahi̇m , Totur Ümi̇t 
Published: February 2012

Abstract
Let u = (u
n) be a sequence of real numbers whose generator sequence is Cesàro summable to a finite number. We prove that (u
n) is slowly oscillating if the sequence of Cesàro means of (ω
n(m−1)(u)) is increasing and the following two conditions are hold: $$\begin{gathered}
\left( {\lambda - 1} \right)\mathop {\lim \sup }\limits_n \left( {\frac{1}
{{\left[ {\lambda n} \right] - n}}\sum\limits_{k = n + 1}^{\left[ {\lambda n} \right]} {\left( {\omega _k^{\left( m \right)} \left( u \right)} \right)^q } } \right)^{\frac{1}
{q}} = o\left( 1 \right), \lambda \to 1^ + , q > 1, \hfill \\
\left( {1 - \lambda } \right)\mathop {\lim \sup }\limits_n \left( {\frac{1}
{{n - \left[ {\lambda n} \right]}}\sum\limits_{k = \left[ {\lambda n} \right] + 1}^n {\left( {\omega _k^{\left( m \right)} \left( u \right)} \right)^q } } \right)^{\frac{1}
{q}} = o\left( 1 \right), \lambda \to 1^ - , q > 1, \hfill \\
\end{gathered}$$ where (ω
n(m) (u)) is the general control modulo of the oscillatory behavior of integer order m ≥ 1 of a sequence (u
n) defined in [DİK, F.: Tauberian theorems for convergence and subsequential convergence with moderately oscillatory behavior, Math. Morav. 5, (2001), 19–56] and [λn] denotes the integer part of λn.
Some common fixed point theorems for hybrid pairs of maps without the completeness assumption
Authors: Imdad M. , Ahmed M. 
Published: February 2012

Abstract
Motivated by some recent works due to Singh and Kumar and Ahmed, the main result of Imdad and Ali is generalized and improved by removing the completeness assumption besides weakening the quasi-coincidentally commuting property of the involved hybrid pair to S-weak commutativity. Some illustrative examples are also furnished to support the genuineness of our extension besides deriving some related results.