bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multistage Association Study Identifies a Breast Cancer Genetic Locus atNCOA7
Authors: Higginbotham Kathryn S.P. , Breyer Joan P. , Bradley Kevin M. , Schuyler Peggy A. , Plummer W. Dale , Freudenthal Marcia E. , Trentham-Dietz Amy , Newcomb Polly A. , Sanders Melinda E. , Page David L. , Parl Fritz F. , Egan Kathleen M. , Dupont William D. , Smith Jeffrey R.
Published: May 2011

Estrogen metabolism and growth factor signaling pathway genes play key roles in breast cancer development. We evaluated associations between breast cancer and tagging single-nucleotide polymorphisms (SNP) of 107 candidate genes of these pathways using single allele- and haplotype-based tests. We first sought concordance of associations between two study populations: the Nashville Breast Cohort (NBC; 510 cases, 988 controls), and the Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer study (1,145 cases, 1,142 controls). Findings across the two study populations were concordant at tagging SNPs of six genes, and at previously published SNPs of FGFR2. We sought further replication of results for EGFR, NCOA7, and FGFR2 in the independent Collaborative Breast Cancer Study (CBCS; 1,552 cases, 1,185 controls). Associations at NCOA7 and FGFR2 replicated across all three studies. The association at NCOA7 on 6q22.32, detected by a haplotype spanning the initial protein-coding exon (5′-rs9375411, rs11967627, rs549438, rs529858, rs490361, rs17708107-3′), has not been previously reported. The haplotype had a significant inverse association with breast cancer in each study [ORHet: 0.69 (NBC), 0.76 (CGEMS), 0.79 (CBCS)], and a meta-analysis ORHet of 0.75 (95% CI, 0.65–0.87, P = 1.4 × 10−4) in the combined study populations. The haplotype frequency was 0.07 among cases, and 0.09 among controls; homozygotes were infrequent and each ORHom was not significant. NCOA7 encodes a nuclear receptor coactivator that interacts with estrogen receptor α to modulate its activity. These observations provide consistent evidence that genetic variants at the NCOA7 locus may confer a reduced risk of breast cancer. Cancer Res; 71(11); 3881–8. ©2011 AACR.
Physical Activity after Diagnosis and Risk of Prostate Cancer Progression: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor
Authors: Richman Erin L. , Kenfield Stacey A. , Stampfer Meir J. , Paciorek Alan , Carroll Peter R. , Chan June M.
Published: May 2011

Vigorous activity after diagnosis was recently reported to be inversely associated with prostate cancer–specific mortality. However, men with metastatic disease may decrease their activity due to their disease; thus, a causal interpretation is uncertain. We therefore prospectively examined vigorous activity and brisk walking after diagnosis in relation to risk of prostate cancer progression, an outcome less susceptible to reverse causation, among 1,455 men diagnosed with clinically localized prostate cancer. Cox proportional hazards regression was used to examine vigorous activity, nonvigorous activity, walking duration, and walking pace after diagnosis and risk of prostate cancer progression. We observed 117 events (45 biochemical recurrences, 66 secondary treatments, 3 bone metastases, 3 prostate cancer deaths) during 2,750 person-years. Walking accounted for nearly half of all activity. Men who walked briskly for 3 h/wk or more had a 57% lower rate of progression than men who walked at an easy pace for less than 3 h/wk (HR = 0.43; 95% CI: 0.21–0.91; P = 0.03). Walking pace was associated with decreased risk of progression independent of duration (HR brisk vs. easy pace = 0.52; 95% CI: 0.29–0.91; Ptrend = 0.01). Few men engaged in vigorous activity, but there was a suggestive inverse association (HR ≥3 h/wk vs. none = 0.63; 95% CI: 0.32–1.23; Ptrend = 0.17). Walking duration and total nonvigorous activity were not associated with risk of progression independent of pace or vigorous activity, respectively. Brisk walking after diagnosis may inhibit or delay prostate cancer progression among men diagnosed with clinically localized prostate cancer. Cancer Res; 71(11); 3889–95. ©2011 AACR.
Evolved Tumor Suppression: Why Are We So Good at Not Getting Cancer?
Authors: DeGregori James
Published: May 2011

The law of natural selection can be used to understand cancer development at the level of species as well as at the level of cells and tissues. Through this perspective, I seek to explain: (i) Why the lack of sufficient selective pressure to prevent cancers in old age helps explain the exponential increase in cancer incidence in the elderly. (ii) Why the evolution of long-lived animals necessitated the acquisition of potent tumor suppressive mechanisms. (iii) How the requirement to prevent inappropriate somatic cell expansion and cancer has constrained developmental and tissue architectural modalities. (iv) How the evolution of well-adapted stem cells with complex niche requirements has conferred resistance to oncogenic mutations, as phenotype-altering genetic change is almost always disadvantageous within a well-adapted cell population. (v) How the impairment of stem cell fitness, as occurs in old age, can promote selection for adaptive mutations and cancer initiation. (vi) Why differential maintenance of stem cell fitness may explain how different vertebrate species with enormous differences in life span and body size similarly avoid cancer through reproductive years. Cancer Res; 71(11); 3739–44. ©2011 AACR.
Roles of Sildenafil in Enhancing Drug Sensitivity in Cancer
Authors: Shi Zhi , Tiwari Amit K. , Patel Atish S. , Fu Li-Wu , Chen Zhe-Sheng
Published: May 2011

The phenomenon of multidrug resistance (MDR) has decreased the hope for successful cancer chemotherapy. The ATP-binding cassette (ABC) transporter superfamily is the largest transmembrane family. The overexpression of ABC transporters is a major determinant of MDR in cancer cells both in vitro and in vivo. Unfortunately, until recently, most of the strategies used to surmount ABC-transporter–mediated MDR have had limited success. An ideal modulator of MDR would be one that has a low liability to induce toxicity and alter the pharmacokinetic profile of antineoplastic drugs. Sildenafil, an inhibitor of cGMP-specific phosphodiesterase type 5, was found to significantly reverse ABC-transporter–mediated MDR. Our results indicate that sildenafil has differential inhibitory effects on ABC transporters: It significantly decreases the efflux activity of ABCB1 and ABCG2, but has no significant effects on ABCC1. Emerging evidence indicates that sildenafil and other phosphodiesterase type 5 inhibitors may enhance the sensitivity of certain types of cancer to standard chemotherapeutic drugs. Cancer Res; 71(11); 3735–8. ©2011 AACR.
An Epigenetic Marker Panel for Detection of Lung Cancer Using Cell-Free Serum DNA
Authors: Begum Shahnaz , Brait Mariana , Dasgupta Santanu , Ostrow Kimberly L. , Zahurak Marianna , Carvalho André L. , Califano Joseph A. , Goodman Steven N. , Westra William H. , Hoque Mohammad Obaidul , Sidransky David
Published: May 2011

Purpose: We investigated the feasibility of detecting aberrant DNA methylation of some novel and known genes in the serum of lung cancer patients.

Experimental Design: To determine the analytic sensitivity, we examined the tumor and the matched serum DNA for aberrant methylation of 15 gene promoters from 10 patients with primary lung tumors by using quantitative methylation-specific PCR. We then tested this 15-gene set to identify the more useful DNA methylation changes in the serum of a limited number of lung cancer patients and controls. In an independent set, we tested the six most promising genes (APC, CDH1, MGMT, DCC, RASSF1A, and AIM1) for further elucidation of the diagnostic application of this panel of markers.

Results: Promoter hypermethylation of at least one of the genes studied was detected in all 10 lung primary tumors. In majority of cases, aberrant methylation in serum DNA was accompanied by methylation in the matched tumor samples. In the independent set, using a single gene that had 100% specificity (DCC), 35.5% (95% CI: 25–47) of the 76 lung cancer patients were correctly identified. For patients without methylated DCC, addition of a logistic regression score that was based on the five remaining genes improved sensitivity from 35.5% to 75% (95% CI: 64–84) but decreased the specificity from 100% to 73% (95% CI: 54–88).

Conclusion: This approach needs to be evaluated in a larger test set to determine the role of this gene set in early detection and surveillance of lung cancer. Clin Cancer Res; 17(13); 4494–503. ©2011 AACR.
Genetic Aberrations Leading to MAPK Pathway Activation Mediate Oncogene-Induced Senescence in Sporadic Pilocytic Astrocytomas
Authors: Jacob Karine , Quang-Khuong Dongh-Anh , Jones David T.W. , Witt Hendrik , Lambert Sally , Albrecht Steffen , Witt Olaf , Vezina Catherine , Shirinian Margret , Faury Damien , Garami Miklos , Hauser Peter , Klekner Almos , Bognar Laszlo , Farmer Jean-Pierre , Montes Jose-Luis , Atkinson Jeffrey , Hawkins Cynthia , Korshunov Andrey , Collins V. Peter , Pfister Stefan M. , Tabori Uri , Jabado Nada
Published: May 2011

Purpose: Oncogenic BRAF/Ras or NF1 loss can potentially trigger oncogene-induced senescence (OIS) through activation of the mitogen-activated protein kinase (MAPK) pathway. Somatic genetic abnormalities affecting this pathway occur in the majority of pilocytic astrocytomas (PA), the most prevalent brain neoplasm in children. We investigated whether OIS is induced in PA.

Experimental Design: We tested expression of established senescence markers in three independent cohorts of sporadic PA. We also assessed for OIS in vitro, using forced expression of wild-type and V600E-mutant BRAF in two astrocytic cell lines: human telomerase reverse transcriptase (hTERT)-immortalized astrocytes and fetal astrocytes.

Results: Our results indicate that PAs are senescent as evidenced by marked senescence-associated acidic β-galactosidase activity, low KI-67 index, and induction of p16INK4a but not p53 in the majority of 52 PA samples (46 of 52; 88.5%). Overexpression of a number of senescence-associated genes [CDKN2A (p16), CDKN1A (p21), CEBPB, GADD45A, and IGFBP7] was shown at the mRNA level in two independent PA tumor series. In vitro, sustained activation of wild-type or mutant BRAF induced OIS in both astrocytic cell lines. Loss of p16INK4a in immortalized astrocytes abrogated OIS, indicative of the role of this pathway in mediating this phenomenon in astrocytes. OIS is a mechanism of tumor suppression that restricts the progression of benign tumors. We show that it is triggered in PAs through p16INK4a pathway induction following aberrant MAPK activation.

Conclusions: OIS may account for the slow growth pattern in PA, the lack of progression to higher-grade astrocytomas, and the high overall survival of affected patients. Clin Cancer Res; 17(14); 4650–60. ©2011 AACR.
Inhibiting the mTOR Pathway Synergistically Enhances Cytotoxicity in Ovarian Cancer Cells Induced by Etoposide through Upregulation of c-Jun
Authors: Itamochi Hiroaki , Oishi Tetsuro , Shimada Muneaki , Sato Shinya , Uegaki Kazunori , Naniwa Jun , Sato Seiya , Nonaka Michiko , Terakawa Naoki , Kigawa Junzo , Harada Tasuku
Published: May 2011

Purpose: The mTOR pathway is thought to be a central regulator of proliferation and survival of cells. Rapamycin and its analogs are undergoing clinical trials in patients with epithelial ovarian cancer. This study aimed to assess the potential to use rapamycin and anticancer agents in combination for first- and second-line chemotherapy to treat ovarian cancer.

Experimental Design: We used six ovarian serous adenocarcinoma cell lines (KF, KOC-2S, SHIN-3, SK-OV-3, TU-OS-3, and TU-OS-4) in this study. We treated the cells with rapamycin and anticancer agents, then assessed cell viability, apoptosis, and the expression of protein in apoptotic pathways and molecules downstream of the mTOR signaling pathways. We also investigated the effect of these drug combinations on survival in nude mouse xenograft models.

Results: Synergistic effects were observed in five cell lines from the combination of etoposide and rapamycin. However, we observed antagonistic effects when rapamycin was combined with gemcitabine, cisplatin, or paclitaxel on more than two cell lines. Rapamycin dramatically enhanced apoptosis induced by etoposide and the expression of cleaved caspase 9. This effect was associated with upregulation of phosphorylated c-Jun and downregulation of Bcl-xL. The synergistic interaction of rapamycin and etoposide was lower when the c-Jun pathway was suppressed by a c-Jun N-terminal kinase inhibitor (SP600125). Finally, treating nude mice with rapamycin and etoposide significantly prolonged survival in the model mice with ovarian cancer xenografts.

Conclusions: Chemotherapy with rapamycin and etoposide combined is worth exploring as a treatment modality for women with epithelial ovarian cancer. Clin Cancer Res; 17(14); 4742–50. ©2011 AACR.
Dual Targeting of Tumor Angiogenesis and Chemotherapy by Endostatin–Cytosine Deaminase–Uracil Phosphoribosyltransferase
Authors: Chen Chun-Te , Yamaguchi Hirohito , Lee Hong-Jen , Du Yi , Lee Heng-Huan , Xia Weiya , Yu Wen-Hsuan , Hsu Jennifer L. , Yen Chia-Jui , Sun Hui-Lung , Wang Yan , Yeh Edward T.H. , Hortobagyi Gabriel N. , Hung Mien-Chie
Published: May 2011

Several antiangiogenic drugs targeting VEGF/VEGF receptor (VEGFR) that were approved by the Food and Drug Administration for many cancer types, including colorectal and lung cancer, can effectively reduce tumor growth. However, targeting the VEGF signaling pathway will probably influence the normal function of endothelial cells in maintaining homeostasis and can cause unwanted adverse effects. Indeed, emerging experimental evidence suggests that VEGF-targeting therapy induced less tumor cell–specific cytotoxicity, allowing residual cells to become more resistant and eventually develop a more malignant phenotype. We report an antitumor therapeutic EndoCD fusion protein developed by linking endostatin (Endo) to cytosine deaminase and uracil phosphoribosyltransferase (CD). Specifically, Endo possesses tumor antiangiogenesis activity that targets tumor endothelial cells, followed by CD, which converts the nontoxic prodrug 5-fluorocytosine (5-FC) to the cytotoxic antitumor drug 5-fluorouracil (5-FU) in the local tumor area. Moreover, selective targeting of tumor sites allows an increasing local intratumoral concentration of 5-FU, thus providing high levels of cytotoxic activity. We showed that treatment with EndoCD plus 5-FC, compared with bevacizumab plus 5-FU treatment, significantly increased the 5-FU concentration around tumor sites and suppressed tumor growth and metastasis in human breast and colorectal orthotropic animal models. In addition, in contrast to treatment with bevacizumab/5-FU, EndoCD/5-FC did not induce cardiotoxicity leading to heart failure in mice after long-term treatment. Our results showed that, compared with currently used antiangiogenic drugs, EndoCD possesses potent anticancer activity with virtually no toxic effects and does not increase tumor invasion or metastasis. Together, these findings suggest that EndoCD/5-FC could become an alternative option for future antiangiogenesis therapy. Mol Cancer Ther; 10(8); 1327–36. ©2011 AACR.
A Model Investigation of Aerosol-Induced Changes in Boreal Winter Extratropical Circulation
Authors: Ming Y. , Ramaswamy V. , Chen Gang
Published: May 2011

The authors examine the key characteristics of the boreal winter extratropical circulation changes in response to anthropogenic aerosols, simulated with a coupled atmosphere–slab ocean general circulation model. The zonal-mean response features a pronounced equatorward shift of the Northern Hemisphere subtropical jet owing to the midlatitude aerosol cooling. The circulation changes also show strong zonal asymmetry. In particular, the cooling is more concentrated over the North Pacific than over the North Atlantic despite similar regional forcings. With the help of an idealized model, the authors demonstrate that the zonally asymmetrical response is linked tightly to the stationary Rossby waves excited by the anomalous diabatic heating over the tropical east Pacific. The altered wave pattern leads to a southeastward shift of the Aleutian low (and associated changes in winds and precipitation), while leaving the North Atlantic circulation relatively unchanged.

Despite the rich circulation changes, the variations in the extratropical meridional latent heat transport are controlled strongly by the dependence of atmospheric moisture content on temperature. This suggests that one can project reliably the changes in extratropical zonal-mean precipitation solely from the global-mean temperature change, even without a good knowledge of the detailed circulation changes caused by aerosols. On the other hand, such knowledge is indispensable for understanding zonally asymmetrical (regional) precipitation changes.
The Relationship between the North Atlantic Jet and Tropical Convection over the Indian and Western Pacific Oceans
Authors: Yuan Jiacan , Feldstein Steven B. , Lee Sukyoung , Tan Benkui
Published: May 2011

Boreal winter jet variability over the North Atlantic is investigated using 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40) data, where the variability is defined by the first EOF of the zonal wind on seven vertical levels. The principal component time series of this EOF is referred to as the jet index. A pattern correlation analysis indicates that the jet index more accurately describes intraseasonal North Atlantic zonal wind variability than does the North Atlantic Oscillation (NAO). A series of composite calculations of the jet index based on events of intraseasonal convective precipitation over the tropical Indian and western Pacific Oceans reveals the following statistically significant relationships: 1) negative jet events lead enhanced Indian Ocean precipitation, 2) positive jet events lag enhanced Indian Ocean precipitation, 3) positive jet events lead enhanced western Pacific Ocean precipitation, and 4) negative jet events lag enhanced western Pacific Ocean precipitation. These intraseasonal relationships are found to be linked through the circumglobal teleconnection pattern (CTP). Implications of the sign of the CTP being opposite to that of the jet index suggest that relationships 1 and 3 may arise from cold air surges associated with the CTP over these oceans. On interdecadal time scales, a much greater increase in the frequency of precipitation events from 1958 to 1979 (P1) to 1980 to 2001 (P2) was found for the Indian Ocean relative to the western Pacific Ocean. This observation, combined with relationships 2 and 4, leads to the suggestion that this change in the frequency of intraseasonal Indian Ocean precipitation events may make an important contribution to the excitation of interdecadal variability of the North Atlantic jet.
Further discussion of indigenization in social work: A response to Gray and Coates
Authors: Yunong Huang , Xiong Zhang
Published: May 2011

This article responds to Gray’s (2010) and Gray and Coates’ (2010) responses to A Reflection on Indigenization Discourse in Social Work ( Huang and Zhang, 2008 ), and presents further discussion of indigenization in social work. We indicate that it is an inherent professional requirement for social workers to use different ways to understand local contexts and to do locally relevant research and practice. We extend to address some points of indigenization from the Chinese perspective. The problems with the emphasis on culture in indigenization are also discussed. It is suggested that indigenization is likely to bring harm to social work.
Strain energy release rate assessment in mode I delamination of foam core sandwich composites by acoustic emission
Authors: Hajikhani Milad , Ahmadi Mehdi , Farjpour Mehdi , Oskouei Amir Refahi , Sharifi Amir
Published: May 2011

In sandwich structures, delamination along the interface between the face sheet and the core is one of the most common failure modes, and it is often referred to as the adherent or adhesive interface in adhesively bonded joints. The three modes of fracture achieved for delamination are modes I, II, and III, in which mode I is the most critical. Delamination depends on stacking sequence, material properties, the production process, and so on, which are measured by mode I interlaminar fracture energy ( GIc). In this study, the double cantilever beam test is used to simulate mode I interlaminar fracture and damage evolution through the acoustic emission (AE) method. Based on AE events and the mechanical properties of sandwich composites, the mode I interlaminar fracture toughness, GIc, is investigated. The influence of in-plane fiber orientation on the fracture behavior of interfaces is studied and compared with other techniques in ASTM. Consequently, the presented method of employing AEs to obtain GIc was determined to be successful.
Classical micromechanics modeling of nanocomposites with carbon nanofibers and interphase
Authors: Yu Jaesang , Lacy Thomas E. , Toghiani Hossein , Pittman Charles U. , Hwang Youngkeun
Published: May 2011

A micromechanics parametric study was performed to investigate the effect of carbon nanofiber morphology (i.e. hollow vs. solid cross-section), nanofiber waviness, and both nanofiber–resin interphase properties and dimensions on bulk nanocomposite elastic moduli. Mori–Tanaka and self-consistent models were developed for composites containing heterogeneities with multilayered coatings. For a given nanofiber axial force–displacement relationship, the elastic modulus for hollow nanofibers can significantly exceed that for solid nanofibers resulting in notable differences in bulk nanocomposite properties. In addition, the development of a nanofiber–resin interphase had a notable effect on the bulk elastic moduli. Consistent with results from the literature, small degrees of nanofiber waviness resulted in a significant decrease in effective composite properties.
Determination of the fracture process zone under Mode I fracture in glass fiber composites
Authors: Tsouvalis Nicholas G. , Anyfantis Konstantinos N.
Published: May 2011

This study provides a simple yet effective procedure for the characterization of the fracture process zone (FPZ) developing in the interface of unidirectional laminates under Mode I delamination fracture. Double cantilever beam (DCB) coupons have been manufactured and tested. Three data reduction schemes available in the literature have been utilized for the calculation of the energy release rate (ERR) magnitude as a function of crack extension and the corresponding R-curves have been constructed. The R-curves were then reconstructed in terms of the experimentally registered pre-crack tip opening displacement ( δ*) and analytical functions have been used to describe their concatenate trend. The J-integral approach was then applied over the analytical functions to derive the corresponding bridging laws that describe the FPZ. The derived bridging laws were appropriately modified according to three different traction–separation models and implemented into user-developed interface finite elements (UEL) for the simulation of the fracture tests in ABAQUS® commercial software. Comparisons between numerical and experimental results have shown that the proposed straightforward procedure leads to an effective traction–separation law that can be used as a material property of the modeled interface.
It’s the Local Economy, Stupid! Geographic Wealth Dispersion and Conflict Outbreak Location
Authors: Buhaug Halvard , Gleditsch Kristian Skrede , Holtermann Helge , Østby Gudrun , Tollefsen Andreas Forø
Published: May 2011

Income varies considerably within countries and the locations where conflicts emerge are rarely typical or representative for states at large. Yet, most research on conflict has only examined national income averages and neglected spatial variation. The authors argue that civil conflicts are more likely to erupt in areas with low absolute income, even if a country’s gross domestic product (GDP) per capita is not necessarily low, and in areas with large deviations from national averages. The authors test these hypotheses empirically using spatially disaggregated data on the location of conflict outbreaks and per capita income estimates. The authors find that areas with absolute poverty indeed see more outbreaks of conflict, and they find some evidence that inequality increases the risk of conflict. Subnational information can improve on conventional country-based measures and help our understanding of how local features and variation can give rise to mobilization and violence.
Pharmacokinetics of Oral Tonapofylline and Its Acyl‐Glucuronide Metabolite in Patients With Mild and Moderate Hepatic Impairment
Authors: Li Zhaoyang , Gan Liang‐Shang , Marbury Thomas , Lasseter Kenneth C. , Natarajan Amy , Stecher Scott , Wei Dong , Yang Liyu , Freedman Daniel , Deykin Aaron
Published: May 2011

The objective of the study was to evaluate the effect of hepatic impairment on the pharmacokinetics of tonapofylline. Patients with mild or moderate hepatic impairment were enrolled in parallel with demographically matched healthy subjects. All study participants received a single 75‐mg oral tonapofylline capsule. The pharmacokinetic parameters for both tonapofylline and its active metabolite, acyl‐glucuronide (tonapofylline‐AG), were affected by hepatic impairment significantly (P < .1) except for time to peak plasma concentration (tmax), terminal half‐life (t1/2), and apparent volume of distribution based on the terminal phase (Vdz/F). In the mild group, peak plasma concentration (Cmax), area under the time‐concentration curve from time 0 to 48 hours postdose (AUC48h), and from time 0 to infinity (AUCinf) of tonapofylline modestly increased as compared with the control healthy subjects (GMR 1.62, 1.57, and 1.53, respectively). The extent of increase of these parameters for tonapofylline‐AG was more profound than tonapofylline with geometric mean ratio (GMR) ranging from 2.02 to 2.08. Moderate hepatic impairment was also associated with modest increases of Cmax, AUC48h, and AUCinf of tonapofylline (GMR 1.41, 1.98, and 2.08, respectively). Similar to the mild group, the increase of these parameters were higher for tonapofylline‐AG with GMR ranging from 2.80 to 3.86. Single oral 75‐mg tonapofylline was safe and well tolerated in patients with mild or moderate hepatic impairment.
Renal Profiles of Anticoagulants
Authors: Harder Sebastian
Published: May 2011

Anticoagulants are widely used to prevent and treat venous thromboembolism, prevent stroke in atrial fibrillation, and manage acute coronary syndrome. These drugs are often used in elderly patients, who commonly have renal impairment, comorbidities, and polypharmacy. Renal impairment is a risk factor for bleeding and thrombosis during anticoagulant therapy and can influence the balance between the safety and efficacy of such agents. Some of the more established anticoagulants, such as the low‐molecular‐weight heparins, warfarin, and fondaparinux, are contraindicated for use in patients with severe renal impairment. Of the new oral anticoagulants, dabigatran etexilate, rivaroxaban, and apixaban are at the most advanced stages of development. Dabigatran requires dose adjustment in patients with moderate renal impairment and is contraindicated in patients with severe renal impairment. Rivaroxaban can be administered as a fixed dose for the prevention of venous thromboembolism in patients with moderate renal impairment and should be used with caution in patients with severe renal impairment. Apixaban excretion is also partly dependent on renal function, although the impact of renal insufficiency has not been determined. Additional data on the safety of chronic dosing of the newer oral anticoagulants in renal impairment are awaited.
Sociological Writing as Higher-level Thinking
Authors: Massengill Rebekah Peeples
Published: May 2011

Educators agree that developing critical thinking skills is a key goal of college education. While the literature on higher-level thinking emphasizes the significance of writing for developing such skills, teachers often receive little guidance about the kinds of writing assignments that can prove most beneficial for helping students to develop and practice these new forms of thinking. This teaching note describes the course scaffolding surrounding one such assignment in a writing-intensive course, which challenges students to use common course texts to interpret evidence they have found in an outside setting—including TV shows, movies, and newspaper reports. The assignment demonstrates one way that students can be prompted to integrate intentionally the processes of thinking and writing, and it could be implemented across the undergraduate curriculum.
Nutrition Therapy in a Pediatric Intensive Care Unit
Authors: Zamberlan Patrícia , Delgado Artur Figueiredo , Leone Cláudio , Feferbaum Rubens , Okay Thelma Suely
Published: May 2011

Background: Nutrition therapy (NT) is essential for the care of critically ill children. Inadequate feeding leads to malnutrition and may increase the patient's risk of morbidity and mortality. The aim of this study was to describe the NT used in a tertiary pediatric intensive care unit (PICU). Methods: The authors evaluated NT administered to 90 consecutive patients who were hospitalized for 7 days in the PICU of Instituto da Criança, Hospital das Clínicas, Universidade de São Paulo, Brazil. NT was established according to the protocol provided by the institution's NT team. NT provided a balance of fluids and nutrients and was monitored with a weekly anthropometric nutrition assessment and an evaluation of complications. Results: NT was initiated, on average, within 72 hours of hospitalization. Most children (80%) received enteral nutrition (EN) therapy; of these, 35% were fed orally and the rest via nasogastric or postpyloric tube. There were gastrointestinal complications in patients (5%) who needed a postpyloric tube. Parenteral nutrition (PN) was used in only 10% of the cases, and the remaining 10% received mixed NT (EN + PN). The average calorie and protein intake was 82 kcal/kg and 2.7 g/kg per day. Arm circumference and triceps skinfold thickness decreased. Conclusions: The use of EN was prevalent in the tertiary PICU, and few clinical complications occurred. There was no statistically significant change in most anthropometric indicators evaluated during hospitalization, which suggests that NT probably helped patients maintain their nutrition status.
Training teachers to support pupils’ listening in class: An evaluation using pupil questionnaires
Authors: Crosskey Liz , Vance Maggie
Published: May 2011

Many children with speech, language and communication needs are educated in mainstream schools. Current policy and practice includes training for school staff in facilitating the development of speaking and listening skills. This study evaluates one such training package that focuses on supporting pupils’ listening skills, delivered in a mainstream primary school. Perceived changes in teacher practice following training were evaluated using a questionnaire completed by pupils. Twenty-seven pupils completed a questionnaire two months prior to the training, immediately preceding the training and three months after the training. Pupils’ responses at the three time points were compared. These suggest positive changes following the training. Pupils were more aware of the specific skills that they needed to practise to develop good listening. They also indicated that school staff were using a wider range of strategies to support listening activities in the classroom.
Explaining the academic achievement at school leaving for pupils with a history of language impairment: Previous academic achievement and literacy skills
Authors: Dockrell Julie E. , Lindsay Geoff , Palikara Olympia
Published: May 2011

The relationships are explored between language and literacy and academic success at 16 years in an English sample of 62 young people with a history of specific language impairment identified at 8 years. Data were available from national assessments at 16 and 14; in addition the pupils had completed a range of standardized tests to examine language, literacy and non-verbal ability at 10 years and 8 months and at 16 years. Concurrent measures of literacy had the highest correlations with academic performance. However, analysis revealed a complex model identifying relationships between academic performance at 16 and previous academic attainments in secondary school (national assessments at 14) and a measure of language (listening to paragraphs, Clinical Evaluation of Language Fundamentals 3 or CELF-RUK; Peers et al., 1999). Standardized measures of literacy, non-verbal ability and listening to paragraphs (CELF-RUK) taken at age 11 accounted for over 50% of the variance in performance on Key Stage 3 (KS3) assessments at 14 in English, maths and science. Current gaps in our understanding of the factors that support successful school performance are discussed.
Disulfide-crosslinked heparin-pluronic nanogels as a redox-sensitive nanocarrier for intracellular protein delivery
Authors: Dai Hai Nguyen  , Jong Hoon Choi  , Yoon Ki Joung  , Ki Dong Park
Published: May 2011

Improving the efficacy of drug delivery via nanocarriers has been a major issue in the field of intravenous delivery. In this study, a polymeric nanogel was developed to enhance the stability, redox responsiveness, and the efficacy for intracellular protein delivery. The thiolated heparin-Pluronic conjugate was self-assembled and oxidized to form a disulfide-crosslinked nanogel network under a diluted aqueous condition. The disulfide-crosslinked heparin-Pluronic (DHP) nanogels with encapsulated RNase A were characterized by in vitro release and cytotoxicity tests depending on the existence of glutathione (GSH). The DHP nanogels exhibited reduced hydrodynamic size, higher encapsulation degree, and augmentable release responding to the GSH concentration. The ctotoxicity data confirmed that DHP nanogels were more effective for the intracellular delivery of RNase A compared to non-crosslinked nanogel.
Synergistic effect of HPMA copolymer-bound doxorubicin and dexamethasone in vivo on mouse lymphomas
Authors: Kostková Hana , Etrych Tomáš , Říhová Blanka , Ulbrich Karel
Published: May 2011

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer—drug conjugates bearing the antiinflammatory and anti-proliferative drug dexamethasone (DEX) and the anti-cancer drug doxorubicin (DOX) bound to either the polymer carrier separately or in combination, were synthesized. Both the in vitro and in vivo anti-cancer activity on mouse B-cell (38C13) and T-cell (EL4) lymphoma was studied. The conjugates were fairly stable in model buffers at pH 7.4, simulating blood pH, and the drug was released by chemical hydrolysis at pH values based on the endosomal and lysosomal environments in the target cells (pH 5—6). As a control, polymer conjugates containing only a single-drug (DOX or DEX) attached to the HPMA copolymer carrier were synthesized and tested. Contrary to the treatment with either single drug conjugate, where no significant long-term survival was observed, a synergistic effect of the two drugs was manifested in vivo. Treatment of mice bearing B-cell lymphoma 38C13 formulated as a mixture of both single drug-containing conjugates or a as a conjugate with both drugs in combination gave long-term survivors.
Osteogenic activities of MC3T3-E1 cells on heparin-immobilized poly(caprolactone) membranes
Authors: Gümüşderelioğlu Menemşe , Karakeçili Ayşe , Demirtaş T Tolga
Published: May 2011

The aim of this study was to investigate the effects of heparin on the activity of osteoblast-like cells seeded on poly(caprolactone) (PCL) membranes. The membranes were prepared by solvent-casting technique in ~150 µm thickness. Then they were treated with 1,6-hexanediamine solution and functionalized with covalently bound heparin. The morphology, proliferation, and differentiation of MC3T3-E1 preosteoblasts on these membranes were investigated in vitro. The heparin functionalized PCL membranes, compared to non-functionalized membranes, significantly stimulated osteoblast proliferation. The Scanning electron microscope images confirmed the stimulative effect of covalently bound heparin on the osteoblast-like cell proliferation. The alkaline phosphatase and osteocalcin levels for cells proliferated on heparin containing PCL membranes were higher than that of nonfunctionalized membranes.
On-line Consolidation of Commingled Polypropylene/Glass Roving During Filament Winding
Authors: Gennaro R. , Montagna F. , Maffezzoli A. , Fracasso F. , Fracasso S.
Published: May 2011

In this study, the in situ consolidation of polypropylene matrix/glass reinforced rovings was performed combining two heating systems, an infrared oven and a hot air gun, and a roll pressing the commingled roving during hoop winding on a cylindrical mandrel. Process parameters were set up on the basis of a preliminary simulation of the heat transfer along the roving and then comparison of the results with experimental temperature profiles obtained by a noncontact thermometer. Composite samples were cut along the cylinder axis for mechanical characterization. Physical properties, such as density and void content, obtained using different processing conditions, were compared. Electron microscopy was performed in order to assess how processing conditions affect fiber–matrix impregnation.
Mechanical Properties, Morphology, Thermal Performance, Crystallization Behavior, and Kinetics of PP/Microcrystal Cellulose Composites Compatibilized by Two Different Compatibilizers
Authors: Xiuju Z. , Juncai S. , Huajun Y. , Zhidan L. , Shaozao T.
Published: May 2011

Polypropylene (PP)/microcrystalline cellulose (MCC) composites and PP/MCC composites modified by maleic anhydride grafted PP (PP-g-MA) and methyl acrylic acid glycidyl ester grafted PP (PP-g-GMA) respectively were prepared in a twin-screw extruder. The mechanical properties, morphology, and thermal performance were investigated. The nonisothermal crystallization, melting behavior, and nonisothermal crystallization kinetics were investigated by DSC. The results indicated that the addition of MCC had led to the increase of the tensile strength, impact strength, and flexural strength of PP. PP-g-GMA modification was more conducive to the improvement in tensile strength, impact strength, and flexural strength. The three types of PP/MCC composites have higher thermal decomposition temperatures, Vicat softening temperatures, and dimensional stability. Nonisothermal crystallizations of PP/MCC composites were in accordance with tridimensional growth with heterogeneous nucleation. Meanwhile, MCC was acted as the nucleating agent in PP matrix, which increased the crystallization temperature. PP-g-GMA further increased the crystallization temperature while PP-g-MA weakened the heterogeneous nucleation effect of MCC. Avrami equation and Mo method give a satisfactory description of the crystallization kinetics process. The activation energy of crystallization, nucleation constant, and fold surface free energy of PP were markedly reduced in PP/MCC composites and its compatibilized composites. The value of F( T) systematically increased with increasing relative degree of crystallinity. The addition of microcrystalline cellulose has greatly reduced the spherulitic size of PP.
Policy Analytical Capacity in Changing Governance Contexts: A Structural Equation Model (SEM) Study of Contemporary Canadian Policy Work
Authors: Wellstead Adam M. , Stedman Richard C. , Howlett Michael
Published: May 2011

Abstract Governments face many challenges in maintaining effective policymaking capacity as their governance activities alter and change. The emergence of a gap between government aspirations and street-level conditions for policy workers can lead to an increased likelihood of poor policy outcomes. Maintaining strong policy capacity in such public services is a critical factor in avoiding various kinds of policy failures. Very little large-scale empirical research has been dedicated to the study of contemporary policy work, however, making it difficult to evaluate competing claims about the impact of changing conditions on practices of policy analysis. Using data derived from three large-scale surveys of Canadian policy analysts conducted during 2007 to 2008, this article develops and tests several key hypotheses about contemporary policy work and its relationship to policy analytical capacity.
Multi-point and multi-objective optimization design method for industrial axial compressor cascades
Authors: Ju Y P , Zhang C H
Published: May 2011

Modern aerodynamic optimization design methods for the industrial axial compressor cascade mainly aim at improving both design point and off-design point performance. In this study, a multi-point and multi-objective optimization design method is established for the cascade, particularly aiming at widening the operating range while maintaining good performance at the acceptable expense of computational load. The design objectives are to maximize the static pressure ratio and minimize the total pressure loss coefficient at the design point, and to maximize the operating range for the positive and negative incidences. To alleviate the computational load, a design of experiment (DOE)-based GA–BP-ANN model is constructed to rapidly approximate the cascade aerodynamic performance in the optimization process. The artificial neural network (ANN) is trained by the genetic algorithm (GA) technique and back propagation (BP) algorithm, where the training cascades are sampled by the DOE method and analysed by the computational fluid dynamics method. The multi-objective genetic algorithm is used to search for a series of Pareto-optimum solutions, from which an optimal cascade is found out whose objectives are all better than (ABT) those of the original design. The ABT cascade is characterized by the lower camber and higher turning angle, leading to better aerodynamic performance in a widened operating range. Compared with the original design, the ABT cascade decreases the total pressure loss coefficient by 1.54 per cent, 23.4 per cent, and 7.87 per cent at the incidences of 5°, −9°, and 13°, respectively. The established optimization design method can be extended to the three-dimensional aerodynamic design of axial compressor blade.
Geometrical abstraction of screw compressors for thermodynamic optimization
Authors: Hauser J , Brümmer A
Published: May 2011

The construction and development of different rotor profiles is an important area in connection with the development of screw compressors for specific applications. Geometrical performance figures (using criteria to describe interdependencies of geometrical parameters for screw compressors) for profile optimization are used in order to achieve specific improvements in performance. During this process, rotor profiles and spatial parameters are the main factors. Compared to data derived from the front section of rotor profiles, these figures which also take spatial parameters into account provide a better evaluation of gap conditions and operating efficiency of the compressors under examination.
Bending analysis of moderately thick laminated conical panels with various boundary conditions
Authors: Maleki S , Andakhshideh A , Aghdam M M
Published: May 2011

Bending analysis of moderately thick laminated conical panels with various boundary conditions is presented using the generalized differential quadrature (GDQ) method. Different combinations of clamped, simply supported, and free boundary conditions are considered. General lay up of laminates including symmetric and asymmetric panels is considered. Assuming the effects of shear deformation and initial curvature, the governing partial differential equations (PDEs) of the problem consist of 15 first-order PDEs in terms of unknown displacements, rotations, moments, and forces. Solution domain, governing equations and related boundary conditions are then discretized based on the GDQ technique. Results revealed that convergence of the method is very fast as it provides reasonably accurate results with a relatively small number of grid points. It is also demonstrated that a similar formulation and solution technique can be used to obtain predictions for sector plates by assuming appropriate geometrical parameters. Comparison of the predictions with results of other analytical and numerical methods shows very good agreement. Further results for symmetric and asymmetric laminated conical panels with various boundary conditions are also presented and validated using the commercial finite-element code ABAQUS for future references.
Commodity Prices and Domestic Inflation in India
Authors: Joshi Ajit R. , Acharya Debashis
Published: May 2011

In this article, the relationship between international prices of primary commodities and domestic inflation in India has been explored empirically for the period 1994 to 2007. For this purpose a commodity price index with international price quotations and domestic WPI weights has been constructed. The empirical results show that cointegration between international and domestic prices has grown stronger in the period since 2000. The co-movement is found at both aggregate indices as also the sub-groups viz. fuel and manufactured products. While carrying out this analysis, it was found that it is necessary to use an appropriate index, in order to capture the country-specific exposure, rather than using the aggregate indices published by international agencies, whose coverage and weights may not represent the risks and exposures of specific countries.
Customs Union and Competitiveness of Turkish Exports in the EU Market
Authors: Akkemik K. Ali
Published: May 2011

When Turkey signed the Customs Union (CU) agreement with the EU in 1996 there were doubts about the costs and benefits of the CU with regards to Turkey’s foreign trade and industrial production. Theoretically, the CU helps improve efficiency by stimulating productivity gains in the tradable sectors and via technological gains due to spillover effects. It is of utmost interest to examine whether such expectations were materialized for Turkey. This article examines the changes in major Turkish exports destined to the EU market and determinants of competitiveness using dynamic shift-share analysis for the period 1987–2006. In this method, the competitiveness of Turkish products is examined vis-à-vis her competitors in the EU market. The results of the dynamic shift-share analysis show that Turkey’s competitive position has only partially improved. The results demonstrate that Turkey’s competitive position improved in textiles, iron and steel and automotive exports, and deteriorated in technologically more advanced manufacturing exports. The major determinants of this competitive position are found not to be price-related factors but “real” factors, such as productivity. The article concludes that potential benefits from a customs union have not yet materialized for major Turkish exports.
The Tipping Point
Authors: Dendler David , Edwards Kay L.
Published: May 2011

As a cooperating teacher and university supervisor (respectively), the authors have mentored many general music student teachers and helped them prepare for the job application and interview process. Today, merely having an updated resume, good recommendations, portfolio, and notes from mock interviews is average and minimum. One way to take a proactive approach is to get noticed in an impressive and professional manner while using technology as your closest ally. Creating a “video resume” of teaching excerpts that can be sent electronically along with an application puts a prospective general music teacher at an advantage and can be the “tipping point” to get one the job.