bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Platelet Factor 4 Is an Independent Predictor of Survival and Venous Thromboembolism in Patients with Pancreatic Adenocarcinoma
Authors: Poruk Katherine E. , Firpo Matthew A. , Huerter Luke M. , Scaife Courtney L. , Emerson Lyska L. , Boucher Kenneth M. , Jones Kimberly A. , Mulvihill Sean J.
Published: October 2010

Background: Improved diagnostic, predictive, and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed. Platelet factor 4 (PF4) has been proposed as a diagnostic biomarker for PDAC. We assessed the diagnostic and prognostic potential of serum PF4 levels in PDAC patients.

Methods: Serum PF4 levels were determined by enzyme-linked immunosorbent assay in an initial cohort of 62 PDAC patients, 62 healthy control subjects, and 34 chronic pancreatitis patients. A second validation set consisted of 71 PDAC patients. Linear regression models were used to relate PF4 to class, gender, age, stage, platelet count, and diagnosis. Survival analyses were done using univariate and multivariate Cox models.

Results: In the initial cohort, serum PF4 levels distinguished PDAC from chronic pancreatitis patients (P = 0.011), but not from healthy control subjects (P = 0.624). In PDAC patients, high serum PF4 level significantly predicted decreased survival independent of all covariates examined (P < 0.01). The prognostic relationship of serum PF4 levels remained significant in the validation set. Venous thromboembolism (VTE) occurred in 20% of the 133 PDAC patients. The VTE risk was higher in subjects with elevated PF4 levels (P = 0.009).

Conclusions: Serum PF4 is shown for the first time to be prognostic for survival in PDAC patients. High PF4 is associated with an increased risk for the development of VTE.

Impact: Serum PF4 levels may be useful for patient stratification and for directing treatment options in patients with pancreatic cancer including anticoagulation prophylaxis. The relationship between high PF4 levels and poorer outcomes requires further study. Cancer Epidemiol Biomarkers Prev; 19(10); 2605–10. ©2010 AACR.
Reproductive Factors and Exogenous Hormone Use in Relation to Risk of Glioma and Meningioma in a Large European Cohort Study
Authors: Michaud Dominique S. , Gallo Valentina , Schlehofer Brigitte , Tjønneland Anne , Olsen Anja , Overvad Kim , Dahm Christina C. , Kaaks Rudolf , Lukanova Annekatrin , Boeing Heiner , Schütze Madlen , Trichopoulou Antonia , Bamia Christina , Kyrozis Andreas , Sacerdote Carlotta , Agnoli Claudia , Palli Domenico , Tumino Rosario , Mattiello Amalia , Bueno-de-Mesquita H. Bas , Ros Martine M. , Peeters Petra H. M. , van Gils Carla H. , Lund Eiliv , Bakken Kjersti , Gram Inger T. , Barricarte Aurelio , Navarro Carmen , Dorronsoro Miren , Sánchez Maria José , Rodríguez Laudina , Duell Eric J. , Hallmans Göran , Melin Beatrice S. , Manjer Jonas , Borgquist Signe , Khaw Kay-Tee , Wareham Nick , Allen Naomi E. , Tsilidis Konstantinos K. , Romieu Isabelle , Rinaldi Sabina , Vineis Paolo , Riboli Elio
Published: October 2010

Background: The etiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and the risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods: After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma cases were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (95% CI).

Results: No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR, 3.61; 95% CI, 1.75-7.46).

Conclusion: Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, seems to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation.

Impact: Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements. Cancer Epidemiol Biomarkers Prev; 19(10); 2562–9. ©2010 AACR.
Cruciferous Vegetable Intake and Lung Cancer Risk: A Nested Case-Control Study Matched on Cigarette Smoking
Authors: Lam Tram Kim , Ruczinski Ingo , Helzlsouer Kathy J. , Shugart Yin Yao , Caulfield Laura E. , Alberg Anthony J.
Published: October 2010

Background: Due predominantly to cigarette smoking, lung cancer is the leading cancer-related cause of death worldwide. Cruciferous vegetables may reduce lung cancer risk. The association between intake of cruciferous vegetables and lung cancer risk was investigated in the CLUE II study, a community-based cohort established in 1989.

Methods: We matched 274 incident cases of lung cancer diagnosed from 1990 to 2005 to 1,089 cancer-free controls on age, sex, and cigarette smoking. Dietary information was collected at baseline. Multivariable odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression.

Results: Intake of cruciferous vegetables was inversely associated with lung cancer risk (highest-versus-lowest fourth: OR Q4vsQ1, 0. 57; 95% CI, 0.38-0.85; P-trend = 0.01). The inverse associations held true for former smokers (ORQ4vsQ1, 0.49; 95% CI, 0.27-0.92; P-trend = 0.05) and current smokers (ORQ4vsQ1, 0.52; 95% CI, 0.29-0.95; P-trend = 0.02).

Conclusions: After carefully controlling for cigarette smoking, higher intake of cruciferous vegetable was associated with lower risk of lung cancer.

Impact: The observed inverse association coupled with accumulating evidence suggests that intake of cruciferous vegetables is inversely associated with lung cancer risk, and this association seems to hold true beyond the confounding effects of cigarette smoking. Cancer Epidemiol Biomarkers Prev; 19(10); 2534–40. ©2010 AACR.
High-Throughput Simultaneous Analysis of Five Urinary Metabolites of Areca Nut and Tobacco Alkaloids by Isotope-Dilution Liquid Chromatography-Tandem Mass Spectrometry with On-Line Solid-Phase Extraction
Authors: Hu Chiung-Wen , Chang Yan-Zin , Wang Hsiao-Wen , Chao Mu-Rong
Published: October 2010

Background: Areca nut and tobacco are commonly used drugs worldwide and have been frequently used in combination. We describe the use of on-line solid-phase extraction and isotope-dilution liquid chromatography-tandem mass spectrometry for the simultaneous measurement of five major urinary metabolites of both areca nut and tobacco alkaloids, namely, arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine.

Methods: Automated purification of urine was accomplished with a column-switching device. After the addition of deuterium-labeled internal standards, urine samples were directly analyzed within 13 minutes. This method was applied to measure urinary metabolites in 90 healthy subjects to assess areca nut/tobacco exposure. Urinary time course of arecoline, arecaidine, and N-methylnipecotic acid was investigated in five healthy nonchewers after oral administration of areca nut water extracts.

Results: The limits of detection were 0.016 to 0.553 ng/mL. Interday and intraday imprecision were <10%. Mean recoveries of five metabolites in urine were 97% to 114%. Mean urinary concentrations of arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine in regular areca nut chewers also smokers were 23.9, 5,816, 1,298, 2,635, and 1,406 ng/mg creatinine, respectively. Time course study revealed that after administration of areca nuts extracts, the major urinary metabolite was arecaidine with a half-life of 4.3 hours, followed by N-methylnipecotic acid with a half-life of 7.9 hours, and very low levels of arecoline with a half-life of 0.97 hour.

Conclusions: This on-line solid-phase extraction liquid chromatography-tandem mass spectrometry method firstly provides high-throughput direct analysis of five urinary metabolites of areca nut/tobacco alkaloids.

Impact: This method may facilitate the research into the oncogenic effects of areca nut/tobacco exposure. Cancer Epidemiol Biomarkers Prev; 19(10); 2570–81. ©2010 AACR.
Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
Authors: Bianco-Miotto Tina , Chiam Karen , Buchanan Grant , Jindal Shalini , Day Tanya K. , Thomas Mervyn , Pickering Marie A. , O'Loughlin Melissa A. , Ryan Natalie K. , Raymond Wendy A. , Horvath Lisa G. , Kench James G. , Stricker Phillip D. , Marshall Villis R. , Sutherland Robert L. , Henshall Susan M. , Gerald William L. , Scher Howard I. , Risbridger Gail P. , Clements Judith A. , Butler Lisa M. , Tilley Wayne D. , Horsfall David J. , Ricciardelli Carmela
Published: October 2010

Background: Epigenetic alterations are common in prostate cancer, yet how these modifications contribute to carcinogenesis is poorly understood. We investigated whether specific histone modifications are prognostic for prostate cancer relapse, and whether the expression of epigenetic genes is altered in prostate tumorigenesis.

Methods: Global levels of histone H3 lysine-18 acetylation (H3K18Ac) and histone H3 lysine-4 dimethylation (H3K4diMe) were assessed immunohistochemically in a prostate cancer cohort of 279 cases. Epigenetic gene expression was investigated in silico by analysis of microarray data from 23 primary prostate cancers (8 with biochemical recurrence and 15 without) and 7 metastatic lesions.

Results: H3K18Ac and H3K4diMe are independent predictors of relapse-free survival, with high global levels associated with a 1.71-fold (P < 0.0001) and 1.80-fold (P = 0.006) increased risk of tumor recurrence, respectively. High levels of both histone modifications were associated with a 3-fold increased risk of relapse (P < 0.0001). Epigenetic gene expression profiling identified a candidate gene signature (DNMT3A, MBD4, MLL2, MLL3, NSD1, and SRCAP), which significantly discriminated nonmalignant from prostate tumor tissue (P = 0.0063) in an independent cohort.

Conclusions: This study has established the importance of histone modifications in predicting prostate cancer relapse and has identified an epigenetic gene signature associated with prostate tumorigenesis.

Impact: Our findings suggest that targeting the epigenetic enzymes specifically involved in a particular solid tumor may be a more effective approach. Moreover, testing for aberrant expression of epigenetic genes such as those identified in this study may be beneficial in predicting individual patient response to epigenetic therapies. Cancer Epidemiol Biomarkers Prev; 19(10); 2611–22. ©2010 AACR.
EML4-ALK Fusion Gene Assessment Using Metastatic Lymph Node Samples Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
Authors: Sakairi Yuichi , Nakajima Takahiro , Yasufuku Kazuhiro , Ikebe Dai , Kageyama Hajime , Soda Manabu , Takeuchi Kengo , Itami Makiko , Iizasa Toshihiko , Yoshino Ichiro , Mano Hiroyuki , Kimura Hideki
Published: October 2010

Purpose: Anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes for non–small cell lung cancers (NSCLC). Several ALK inhibitors have been developed, and are now being evaluated in ALK-positive NSCLC. The feasibility of detecting ALK fusion genes in samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was determined. The clinicopathologic characteristics of ALK-positive lung cancer were also analyzed.

Experimental Design: From April 2008 to July 2009, NSCLC cases with hilar/mediastinal lymph node metastases detected by EBUS-TBNA were enrolled. Positive expression of ALK fusion protein was determined using immunohistochemistry, and ALK gene rearrangements were further examined to verify the translocation between ALK and partner genes using fluorescent in situ hybridization and reverse transcription-PCR. Direct sequencing of PCR products was performed to identify ALK fusion variants.

Results: One hundred and nine cases were eligible for the analysis using re-sliced samples. Screening of these specimens with immunohistochemistry revealed ALK positivity in seven cases (6.4%), all of which possessed echinoderm microtubule–associated protein-like 4–ALK fusion genes as detected by fluorescent in situ hybridization and reverse transcription-PCR. All ALK-positive cases had an adenocarcinoma histology and possessed no EGFR mutations. Compared with ALK-negative cases, ALK-positive cases were more likely to have smaller primary tumors (P < 0.05), to occur at a younger age (<60 years; P < 0.05), and to occur in never/light smokers (smoking index < 400; P < 0.01). Mucin production was frequently observed in ALK-positive adenocarcinomas (29.4%; P < 0.01).

Conclusions: EBUS-TBNA is a practical and feasible method for obtaining tissue from mediastinal and hilar lymph nodes that can be subjected to multimodal analysis of ALK fusion genes in NSCLC. Clin Cancer Res; 16(20); 4938–45. ©2010 AACR.
Simultaneous Blockade of Multiple Immune System Inhibitory Checkpoints Enhances Antitumor Activity Mediated by Interleukin-15 in a Murine Metastatic Colon Carcinoma Model
Authors: Yu Ping , Steel Jason C. , Zhang Meili , Morris John C. , Waldmann Thomas A.
Published: October 2010

Purpose: Interleukin 15 (IL-15) is a promising cytokine for immunotherapy of cancer due to its ability to stimulate the immunity of natural killer, B, and T cells. Its effectiveness, however, may be limited by inhibitory checkpoints and pathways that can attenuate immune responses. Finding strategies to abrogate these negative regulators and enhance the efficacy of IL-15 is a critical challenge.

Experimental Design: In a preclinical study, we evaluated IL-15 combined with antibodies to block the negative immune regulators cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death ligand 1 (PD-L1) in a metastatic murine CT26 colon carcinoma model.

Results: IL-15 treatment resulted in a significant prolongation of survival in mice with metastatic tumor. Administration of IL-15, however, also increased expression of PD-1 on the surface of CD8+ T cells including CD8+CD44high memory phenotype T cells. Moreover, IL-15 also increased the secretion of the immunosuppressive cytokine, IL-10. Combining IL-15 with anti-PD-L1 and anti-CTLA-4 (multiple immune checkpoint blockade) exhibited greater CTL killing and IFNγ secretion. Moreover, this combination resulted in a significant reduction in surface expression of PD-1 on CD8+ T cells, a decrease in IL-10 secretion, and led to significantly longer survival of tumor-bearing animals compared with mice treated with IL-15 alone or combined singularly with anti-PD-L1 or anti-CTLA-4.

Conclusions: Combining the immune stimulatory properties of IL-15 with the simultaneous removal of 2 critical immune system inhibitory checkpoints, we showed enhancement of immune responses leading to increased antitumor activity. Clin Cancer Res; 16(24); 6019–28. ©2010 AACR.
The Tissue Is the Issue: Personalized Medicine for Non-Small Cell Lung Cancer
Authors: Hirsch Fred R. , Wynes Murry W. , Gandara David R. , Bunn Paul A.
Published: October 2010

The development of molecular markers is crucial for improving therapy in advanced non-small cell lung cancer (NSCLC). Here, we review perspectives of biomarker-driven personalized therapy in NSCLC, with particular reference to the detection of EML4-ALK gene rearrangements. Different molecular assays, validation, and clinical application to different types of tissue specimens are discussed. Clin Cancer Res; 16(20); 4909–11. ©2010 AACR.
CADPE Inhibits PMA-Stimulated Gastric Carcinoma Cell Invasion and Matrix Metalloproteinase-9 Expression by FAK/MEK/ERK–Mediated AP-1 Activation
Authors: Han Honghui , Du Bing , Pan Xinhua , Liu Junchen , Zhao Qufei , Lian Xiaoyuan , Qian Min , Liu Mingyao
Published: October 2010

Metastasis is one of the main causes of death for patients with malignant tumors. Aberrant expression of matrix metalloproteinase-9 (MMP-9) has been implicated in the invasion and metastasis of various cancer cells. Here, we found that caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) could inhibit the migration and invasion of human gastric carcinoma cells in Transwell migration assays. To understand the underlying mechanism, we showed that CADPE significantly inhibited phorbol 12-myristate 13-acetate (PMA)–induced increases in MMP-9 expression and activity in a dose-dependent manner. The inhibitory effect of CADPE on MMP-9 expression correlated well with the suppression of MMP-9 promoter activity and the reduction of MMP-9 mRNA. Reporter gene assay and electrophoretic mobility shift assay showed that CADPE inhibited MMP-9 expression by suppressing the activation of the nuclear transcription factor activator protein-1 (AP-1) and c-Fos, but not NF-κB. Moreover, CADPE inhibited PMA-induced phosphorylation of protein kinases involved in AP-1 activation, such as focal adhesion kinase (FAK), mitogen-activated protein kinase/extracellular signal–regulated kinase (ERK) kinase (MEK), and ERK1/2, whereas CADPE had little effect on the phosphorylation of p38 and c-jun NH2-terminal kinase. Taken together, our findings indicate that CADPE could be a unique antitumor agent that specifically inhibits MMP-9 activity by targeting the activation of FAK/MEK/ERK protein kinases and AP-1 transcription factor. Mol Cancer Res; 8(11); 1477–88. ©2010 AACR.
A Mouse Model for Human Anal Cancer
Authors: Stelzer Marie K. , Pitot Henry C. , Liem Amy , Schweizer Johannes , Mahoney Charles , Lambert Paul F.
Published: October 2010

Human anal cancers are associated with high-risk human papillomaviruses (HPV) that cause other anogenital cancers and head and neck cancers. As with other cancers, HPV16 is the most common high-risk HPV in anal cancers. We describe the generation and characterization of a mouse model for human anal cancer. This model makes use of K14E6 and K14E7 transgenic mice in which the HPV16 E6 and E7 genes are directed in their expression to stratified squamous epithelia. HPV16 E6 and E7 possess oncogenic properties including, but not limited to, their capacity to inactivate the cellular tumor suppressors p53 and pRb, respectively. Both E6 and E7 were found to be functionally expressed in the anal epithelia of K14E6/K14E7 transgenic mice. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. Nearly 50% of DMBA-treated HPV16 E6/E7 transgenic mice showed overt signs of tumors, whereas none of the like-treated nontransgenic mice showed tumors. Histopathologic analyses confirmed that the HPV16 transgenic mice were increased in their susceptibility to anal cancers and precancerous lesions. Biomarker analyses demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in HPV-positive precursors to human anal cancer. This is the first mouse model for investigating the contributions of viral and cellular factors in anal carcinogenesis, and should provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer. Cancer Prev Res; 3(12); 1534–41. ©2010 AACR.
Low Hemoglobin A1c and Risk of All-Cause Mortality Among US Adults Without Diabetes
Authors: Carson April P. , Fox Caroline S. , McGuire Darren K. , Levitan Emily B. , Laclaustra Martin , Mann Devin M. , Muntner Paul
Published: October 2010

Background—

Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c.

Methods and Results—

National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76).

Conclusions—

In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.
Conjuring Unity: The Politics of the Crowd and the Poetics of the Candidate
Authors: Brown Robert E.
Published: October 2010

Although the rhetorical gifts of Barack Obama have been copiously examined, considerably less attention has been paid to one of the principal actors in political campaigns: the crowd. This critical analysis examines the nature and influence of the crowd as a political actor in the Obama campaign. Drawing on dramaturgical theory and literary history, the article also considers how a candidate’s strategic performance of his or her political self can be understood within the legacy of American romantic and transcendental conceptions of the self and its mystical and sacramental relationship to the crowd.
Aging and Bone
Authors: Boskey A.L. , Coleman R.
Published: October 2010

Bones provide mechanical and protective function, while also serving as housing for marrow and a site for regulation of calcium ion homeostasis. The properties of bones do not remain constant with age; rather, they change throughout life, in some cases improving in function, but in others, function deteriorates. Here we review the modifications in the mechanical function and shape of bones, the bone cells, the matrix they produce, and the mineral that is deposited on this matrix, while presenting recent theories about the factors leading to these changes.
The Role of Bacteria in the Caries Process
Authors: Takahashi N. , Nyvad B.
Published: October 2010

Dental biofilms produce acids from carbohydrates that result in caries. According to the extended caries ecological hypothesis, the caries process consists of 3 reversible stages. The microflora on clinically sound enamel surfaces contains mainly non-mutans streptococci and Actinomyces, in which acidification is mild and infrequent. This is compatible with equilibrium of the demineralization/remineralization balance or shifts the mineral balance toward net mineral gain (dynamic stability stage). When sugar is supplied frequently, acidification becomes moderate and frequent. This may enhance the acidogenicity and acidurance of the non-mutans bacteria adaptively. In addition, more aciduric strains, such as ‘low-pH’ non-mutans streptococci, may increase selectively. These microbial acid-induced adaptation and selection processes may, over time, shift the demineralization/remineralization balance toward net mineral loss, leading to initiation/progression of dental caries (acidogenic stage). Under severe and prolonged acidic conditions, more aciduric bacteria become dominant through acid-induced selection by temporary acid-impairment and acid-inhibition of growth (aciduric stage). At this stage, mutans streptococci and lactobacilli as well as aciduric strains of non-mutans streptococci, Actinomyces, bifidobacteria, and yeasts may become dominant. Many acidogenic and aciduric bacteria are involved in caries. Environmental acidification is the main determinant of the phenotypic and genotypic changes that occur in the microflora during caries.
Fluoride’s Effects on the Formation of Teeth and Bones, and the Influence of Genetics
Authors: Everett E.T.
Published: October 2010

Fluorides are present in the environment. Excessive systemic exposure to fluorides can lead to disturbances of bone homeostasis (skeletal fluorosis) and enamel development (dental/enamel fluorosis). The severity of dental fluorosis is also dependent upon fluoride dose and the timing and duration of fluoride exposure. Fluoride’s actions on bone cells predominate as anabolic effects both in vitro and in vivo. More recently, fluoride has been shown to induce osteoclastogenesis in mice. Fluorides appear to mediate their actions through the MAPK signaling pathway and can lead to changes in gene expression, cell stress, and cell death. Different strains of inbred mice demonstrate differential physiological responses to ingested fluoride. Genetic studies in mice are capable of identifying and characterizing fluoride-responsive genetic variations. Ultimately, this can lead to the identification of at-risk human populations who are susceptible to the unwanted or potentially adverse effects of fluoride action and to the elucidation of fundamental mechanisms by which fluoride affects biomineralization.
Model Identification and Computer Algebra
Authors: Bollen Kenneth A. , Bauldry Shawn
Published: October 2010

Multiequation models that contain observed or latent variables are common in the social sciences. To determine whether unique parameter values exist for such models, one needs to assess model identification. In practice, analysts rely on empirical checks that evaluate the singularity of the information matrix evaluated at sample estimates of parameters. The discrepancy between estimates and population values, the limitations of numerical assessments of ranks, and the difference between local and global identification make this practice less than perfect. In this article, the authors outline how to use computer algebra systems (CAS) to determine the local and global identification of multiequation models with or without latent variables. They demonstrate a symbolic CAS approach to local identification and develop a CAS approach to obtain explicit algebraic solutions for each of the model parameters. The authors illustrate the procedures with several examples, including a new proof of the identification of a model for handling missing data using auxiliary variables. They present an identification procedure for structural equation models that makes use of CAS and that is a useful complement to current methods.
Clinical Pharmacokinetics of Tonapofylline: Evaluation of Dose Proportionality, Oral Bioavailability, and Gender and Food Effects in Healthy Human Subjects
Authors: Li Zhaoyang , TenHoor Christopher , Marbury Thomas , Swan Suzanne , Ticho Barry , Rogge Mark , Nestorov Ivan
Published: October 2010

Tonapofylline is an antagonist of adenosine A1 receptor being developed for heart failure. In the present studies, pharmacokinetic characteristics, including dose proportionality, bioavailability, and effects of gender and food, were evaluated in healthy subjects receiving single‐dose tonapofylline (0.2–375 mg) in a parallel or crossover design. Following oral administration, tonapofylline concentrations mostly peaked within 3 hours and declined over time in a multiple phasic manner. Based on a power model, dose proportionality of peak concentration (Cmax), area under the time‐concentration curve for all values (AUCall), and area under the time‐concentration curve to infinity (AUCinf) was concluded in a clinical setting. The bioavailability of tonapofylline was 81.2% (90% confidence interval, 70.6%–93.5%). Following intravenous administration, the steady‐state volume of distribution of tonapofylline was estimated to be 756 mL/kg. The total clearance of tonapofylline was low (64.8 mL/h/kg), approximately 5% of hepatic blood flow. The terminal half‐life was variable within groups and ranged from 11.2 to 24.2 hours across the dose range. Female subjects showed significantly higher Cmax, AUCall, and AUCinf than male subjects (P < .05). Food decreased Cmax by approximately 39%, whereas it did not appear to affect AUCall and AUCinf. The intersubject variability of the pharmacokinetic parameters of tonapofylline was generally less than 30%. In these studies, a single dose of tonapofylline was safe and well tolerated.
The Indigenous Movement in Ecuador
Authors: Jameson Kenneth P.
Published: October 2010

The indigenous movement in Ecuador has been among the most successful new social movements in Latin America since the late 1980s. Its success may be attributed to its formulation and persistent advocacy of an alternative to the changing manifestations of the capitalist order—the “plurinational state.” This position has organized and motivated the movement for the past 20 years, in the course of which it has gained access to the center of economic policy for a time and more recently has operated with greater autonomy. The struggle for plurinationalism remains at the core of the indigenous movement’s approach to the current progressive government of President Rafael Correa and provides a distinctly anticapitalist alternative. Though the new constitution embodies elements of the movement’s program, there remain fundamental areas of disagreement on the meaning and realization of the plurinational state.
A Comparison Between Some Generalized Mantel-Haenszel Statistics for Detecting DIF in Data Simulated Under the Graded Response Model
Authors: Fidalgo Ángel M. , Bartram Dave
Published: October 2010

The main objective of this study was to establish the relative efficacy of the generalized Mantel-Haenszel test (GMH) and the Mantel test for detecting large numbers of differential item functioning (DIF) patterns. To this end this study considered a topic not dealt with in the literature to date: the possible differential effect of type of scores assigned to item-response categories on the power and Type I error rate of the Mantel test. For this purpose, a simulation study with data generated under the graded response model was carried out. The results showed that (a) the scoring system used to compute the Mantel test influences its power for detecting DIF and (b) for conditions comparable to those simulated, the GMH may be the best option, given that it is capable of detecting more complex patterns of association than the Mantel test, that is, more types of DIF.
Recommendations for Pathology Peer Review
Authors: Morton Daniel , Sellers Rani S. , Barale-Thomas Erio , Bolon Brad , George Catherine , Hardisty Jerry F. , Irizarry Armando , McKay Jennifer S. , Odin Marielle , Teranishi Munehiro
Published: October 2010

Pathology peer review verifies and improves the accuracy and quality of pathology diagnoses and interpretations. Pathology peer review is recommended when important risk assessment or business decisions are based on nonclinical studies. For pathology peer review conducted before study completion, the peer-review pathologist reviews sufficient slides and pathology data to assist the study pathologist in refining pathology diagnoses and interpretations. Materials to be reviewed are selected by the peer-review pathologist. Consultations with additional experts or a formal (documented) pathology working group may be used to resolve discrepancies. The study pathologist is solely responsible for the content of the final pathology data and report, makes changes resulting from peer-review discussions, initiates the audit trail for microscopic observations after all changes resulting from peer-review have been made, and signs the final pathologist’s report. The peer-review pathologist creates a signed peer-review memo describing the peer-review process and confirming that the study pathologist’s report accurately and appropriately reflects the pathology data. The study pathologist also may sign a statement of consensus. It is not necessary to archive working notes created during the peer-review process.
Ulcerative Typhlocolitis Associated With Helicobacter mastomyrinus in Telomerase-Deficient Mice
Authors: Eaton K. A. , Opp J. S. , Gray B. M. , Bergin I. L. , Young V. B.
Published: October 2010

Telomerase deficiency induces early senescence and defects in proliferating cell populations, but in mice it has not been associated with inflammatory bowel disease. Genetically engineered mice lacking either telomerase reverse transcriptase (TERT) or telomerase RNA were examined for chronic diarrhea and wasting. Affected mice had pasty stools, thickened nondistensible colon walls, and contracted ceca. Histologically, the cecal mucosa was largely replaced by inflammatory infiltrate consisting of plasma cells, neutrophils, lymphocytes, and macrophages with marked widespread fibrosis and ulceration. Remaining epithelium was disorganized and hyperplastic, with multifocal dysplasia. Colonic mucosa was markedly hyperplastic with similar inflammation and epithelial dysplasia. Multifocal adenomatous hyperplasia, but no inflammation, was present in the small intestine. Microaerophilic spiral bacteria with 16S rRNA gene sequences identical to Helicobacter mastomyrinus were isolated from the colon and cecum. Severe granulomatous typhlocolitis without epithelial dysplasia developed in germ-free recombination-activating gene (RAG) knockout (KO) recipients of CD4+ T cells and inoculated with cecal contents from affected TERT KO mice and in specific pathogen-free recipient RAG KO mice and interleukin-10 KO mice inoculated with H mastomyrinus. Typhlocolitis in mice given H mastomyrinus was more severe than in mice given Helicobacter hepaticus. Telomerase-deficient mice are susceptible to helicobacter-associated typhlocolitis. H mastomyrinus causes severe disease in susceptible mouse strains.
Thoracic Mass in a Cynomolgus Macaque (Macaca fascicularis)
Authors: Yamauchi H. , Takai Y. , Yamasaki H. , Fukuda R.
Published: October 2010

A male cynomolgus macaque at the age of 3 years and 11 months suffered sudden cardiac arrest during a surgical operation. This animal had been clinically asymptomatic for 6 months from the acclimatization period to death. At necropsy, a white mass approximately 5 cm in diameter was found at the base of the heart. Histopathologically, the mass consisted of a granuloma with a number of multinucleated giant cells and multiple necrotic foci. Fungal hyphae characterized by parallel cell walls, distinct septa, and branching were observed in the lesion. The granuloma extended into the thoracic lymph nodes and the subepicardium of the left atrium, compressed the bronchioli, and was separated from the pulmonary parenchyma by a thick fibrous layer. The hyphal morphology and results of polymerase chain reaction assays demonstrated that the pathogen was Aspergillus sp.
Scotland: Birthplace of passive revolution?
Authors: Davidson Neil
Published: October 2010

As far as the bourgeois revolutions were concerned, Antonio Gramsci used the term ‘passive revolution’ to contrast the form taken by the Italian Risorgimento and comparable ‘revolutions from above’ with that of the French Revolution, where the main dynamic had come ‘from below’.1 The key era of passive revolution in this sense lies between 1859 and 1871. From the closing decades of the 17th century, however, a different set of circumstances had already led to a comparable revolution in Scotland which, although little known, is one of the decisive turning points for the transition in Western Europe. The context for this transformation was the global inter-systemic conflict between England and France, in which Scotland was one of the main battlefields. The process had four key moments: first, a subsistence crisis at home and imperial failure abroad, the combined effects of which sent Scottish capitalist development into reverse. Second, and in response to the first, was the Anglo-Scottish Union of 1707, which dissolved the Scottish state while leaving the feudal jurisdictions of the Scottish lords intact. Third, the failure of a French-backed attempt at counter-revolution in 1745—6, which led to the military suppression and juridical abolition of feudal social relations north of the border; and fourth, the imposition of capitalist social relations in the Scottish countryside by an alliance of former feudal landlords, ‘improving’ tenant farmers and Enlightenment intellectuals, who then theorised the entire process in their discussion of ‘civil society’.
The limits of passive revolution
Authors: Callinicos Alex
Published: October 2010

This article addresses what it identifies as the over-extension of the concept of passive revolution in recent writing on international political economy. It traces the evolution of the concept in the Prison Notebooks, where it is rooted in Antonio Gramsci’s development of the Marxist theory of bourgeois revolutions to account for episodes of what he called ‘revolution/restoration’ such as the Italian Risorgimento. But, in his attempt to offer a comprehensive alternative to the great liberal philosopher Benedetto Croce, Gramsci extends the concept to cases such as Mussolini’s fascism. The core meaning common to these uses is that of socio-political processes in which revolution-inducing strains are at once displaced and at least partially fulfilled. In more recent Marxist work, even this meaning is in danger of being lost. The article concludes by seeking to relocate passive revolution within Gramsci’s non-determinist, but still firmly materialist, understanding of Marx’s theory of history.
The continuum of passive revolution
Authors: Morton Adam David
Published: October 2010

‘Some aspects of the Southern question’ (1926) established a strain of thought in Antonio Gramsci’s questioning of conditions of uneven and combined development in Italy, which encompassed complex relations of class stratification, racial domination, colonial rule, the social function of intellectuals, and how best to mobilise against the bourgeois state. This strain of thought was then extended, in his carceral research, through his sustained and wide-ranging historical sociological focus on passive revolution as a condition of modern state formation. This article sets up the importance of passive revolution as a backdrop to approaching passive revolutions of diverse varieties, which is the subject of this wider special issue, stressing ‘approaching’ (as transitive verb) in terms of setting about the task of assessing the theoretical import of passive revolution; and ‘approaching’ (as intransitive verb) in terms of the advance of passive revolutions that are contemporary to us, and those that are in the process of becoming. The continuum of passive revolution is thereby asserted in a historically specific sense, capturing transitions to and transformations of the social relations of capitalist production, rather than as some transhistorical affirmation of intersocietal existence.
Board multimodal vibration control using piezoelectric synchronized switch damping techniques
Authors: Richard Thibaut , Magnet Christophe , Richard Claude , Guyomar Daniel
Published: October 2010

Several types of vibration control using piezoelectric materials exist. The method used here is Synchronized Switching Damping (SSD). It offers several advantages, for example a multimodal damping is achievable without complex circuits. This paper deals with the application of the SSD techniques to the vibration control of a clamped board. An example of possible application is an embedded electronic Printed Circuit Board.

The experimental structure is exposed. A model taking into account the multimodal behaviour of the structure is then developed. After that, two different improvements are presented in order for the SSD techniques to accept a multimodal excitation. Finally, theoretical and experimental results are compared. Both show an attenuation of, respectively, 20 dB, 6 dB and 8 dB on the three first flexion modes of the board simultaneously.
Social Integration and Health Behavioral Change in San Luis, Honduras
Authors: McQuestion Michael J. , Quijano Calle Ana , Drasbek Christopher , Harkins Thomas , Sagastume Lourdes J.
Published: October 2010

This study explores the effects of social integration on behavioral change in the course of an intensive, community-based public health intervention. The intervention trained volunteers and mobilized local organizations to promote 16 key family health practices in rural San Luis, Honduras, during 2004 to 2006. A mixed methods approach is used. Standard household sample surveys were performed in 22 villages before and after the intervention. Eight villages were then resurveyed. A household survey, focus groups, and key informant interviews measured health behaviors and several social structural and psychosocial variables. The villages were then ranked on their mean behavioral and social integration scores. The quantitative and qualitative rankings were in close agreement (Kendall’s coefficient of concordance = .707, p < .001). Behaviors changed most markedly in the villages where respondents participated in local organizations, observed that others performed those behaviors, and depended on their neighbors for support. The results show that social integration conditions health behavioral change. Health interventions can be made more effective by analyzing these features a priori.
Genetic ancestry and lower extremity peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis
Authors: Allison Matthew A , Peralta Carmen A , Wassel Christina L , Aboyans Victor , Arnett Donna K , Cushman Mary , Eng John , Ix Joachim , Rich Stephen S , Criqui Michael H
Published: October 2010

Using self-report of race/ethnicity, African Americans consistently have a higher prevalence of peripheral artery disease (PAD) compared to other ethnic groups. We aimed to determine the associations between estimated genetic admixture and PAD among African and Hispanic Americans. We studied the association between genetic ancestry and PAD among 1417 African and Hispanic American participants in the Multi-Ethnic Study of Atherosclerosis who were genotyped for ancestry informative markers (AIMs). PAD was defined as an ankle—brachial index (ABI) < 0.90. The overall prevalence of PAD among the 712 self-identified African American subjects was 15.2% and 4.6% among the 705 self-identified Hispanic Americans. A one standard deviation increment in European ancestry was associated with non-significant reductions in the odds for PAD among African (OR: 0.96 [95% CI: 0.78—1.18]) and Hispanic Americans (0.84 [0.58—1.23]), while the same increment in Native American ancestry was significantly associated with a lower odds of PAD in Hispanic Americans (0.56 [0.36—0.96]). Adjustment for demographic variables, field center, cardiovascular disease (CVD) risk factors and inflammatory markers strengthened the odds for European ancestry among African (0.85 [0.66—1.10]) and Hispanic Americans (0.68 [0.41—1.11]). The magnitude of the association for Native American ancestry among Hispanic Americans did not materially change (0.56 [0.29—1.09]). In conclusion, a higher percent Native American ancestry in Hispanics is associated with a lower odds of PAD while in both Hispanics and African Americans, greater European ancestry does not appear to be associated with lower odds for PAD.
Diagnosis of venous thromboembolism: an update
Authors: Bounameaux Henri , Perrier Arnaud , Righini Marc
Published: October 2010

Deep vein thrombosis (DVT) and pulmonary embolism (PE) cannot be diagnosed solely on a clinical basis owing to the lack of sensitivity and specificity of clinical signs and symptoms. Phlebography and pulmonary angiography are invasive and resource-demanding imaging modalities. Because the prevalence of DVT and PE is relatively low (typically 20% or less) among clinically suspected individuals, submitting all of them to imaging would not be cost-effective. Therefore, non-invasive diagnostic algorithms have been developed that include clinical probability assessment and D-dimer measurement. These initial steps allow the selection of patients who require non-invasive imaging: compression ultrasonography in cases of suspected DVT and multidetector computed tomography (CT) angiography in cases of suspected PE. This review gives a critical appraisal of the sequential steps of the diagnostic work-up in suspected DVT or PE.
Improving language production using subtitled similar task videos
Authors: Arslanyilmaz Abdurrahman , Pedersen Susan
Published: October 2010

This study examines the effects of subtitled similar task videos on language production by nonnative speakers (NNSs) in an online task-based language learning (TBLL) environment. Ten NNS—NNS dyads collaboratively completed four communicative tasks, using an online TBLL environment specifically designed for this study and a chat tool in WebCT-Vista. Five dyads were provided with subtitled similar task videos and the remaining five dyads were not. Language production was investigated in terms of fluency, accuracy, and complexity, including lexical and syntactic complexity. The data from the chat-scripts showed that NNSs produced more fluent and more accurate language when provided with the subtitled similar task videos than when they were not provided with them.
Pre-learning low-frequency vocabulary in second language television programmes
Authors: Webb Stuart
Published: October 2010

This study investigated the potential of pre-learning frequently occurring low-frequency vocabulary as a means to increase comprehension of television and incidental vocabulary learning through watching television. Eight television programmes, each representing different television genres, were analysed using the RANGE program to determine the 10 most frequent low-frequency word-families in each programme and the coverage that they represented. The results showed that coverage of the 10 most frequent low-frequency word-families ranged from 0.70% to 3.91%, coverage of the most frequent 3,000 to 3,999 word-families ranged from 0.22% to 2.58%, and coverage of the 4,000 to 4,999 word-families ranged from 0.35% to 1.96%. This result shows the relative value of pre-learning vocabulary in television programmes and provides a strong argument for pre-learning vocabulary. The findings also suggested that if learners knew the most frequent 3,000 word-families and pre-learned low-frequency vocabulary, comprehension and incidental vocabulary learning may increase.
Seeing eye to eye? The academic writing needs of graduate and undergraduate students from students’ and instructors’ perspectives
Authors: Huang Li-Shih
Published: October 2010

This article reports on findings from a research project designed to assess undergraduate and graduate students’ language-learning needs in the context of a new academic language support center at a Canadian university. A total of 432 students of English as an additional language and 93 instructors responded to the questionnaires, which asked them to provide importance ratings of academic language skills, to assess their own or their students’ skill status, and to respond to open-ended questions. This article reports on data collected from the writing section of the study.The findings indicated that there is much overlap in the skill items identified as ‘very important’ between graduate and undergraduate students and instructors. Students’ self-assessments and instructors’ assessments of their students differed dramatically, however. In addition to important pedagogical implications, this study suggests a need to be cautious when interpreting needs assessment results because what instructors or students consider as an important skill to possess may not be what students need to develop.