bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Analysis Reveals the Molecular Heterogeneity of Ovarian Clear Cell Carcinomas
Authors: Tan David S.P. , Iravani Marjan , McCluggage W. Glenn , Lambros Maryou B.K. , Milanezi Fernanda , Mackay Alan , Gourley Charles , Geyer Felipe C. , Vatcheva Radost , Millar Joanne , Thomas Karen , Natrajan Rachael , Savage Kay , Fenwick Kerry , Williams Alistair , Jameson Charles , El-Bahrawy Mona , Gore Martin E. , Gabra Hani , Kaye Stanley B. , Ashworth Alan , Reis-Filho Jorge S.
Published: March 2011

Purpose: Ovarian clear cell carcinomas (OCCC) are a drug-resistant and aggressive type of epithelial ovarian cancer. We analyzed the molecular genetic profiles of OCCCs to determine whether distinct genomic subgroups of OCCCs exist.

Experimental design: Fifty pure primary OCCCs were subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). Unsupervised hierarchical clustering using Ward's linkage analysis was performed to identify genomic subgroups of OCCCs. Survival analysis was performed using Kaplan–Meier method and log-rank test. Cox-regression analysis was used to identify independent predictors of outcome. Differentially amplified regions between genomic subgroups of OCCCs were identified using a multi-Fisher's exact test.

Results: Hierarchical cluster analysis revealed two distinct clusters of OCCCs with different clinical outcomes. Patients from cluster-1 had a significantly shorter median progression-free survival (PFS) than those from cluster-2 (11 vs. 65 months, P = 0.009), although estimates for ovarian cancer–specific survival (OCS) did not reach statistical significance (P = 0.065). In multivariate analysis, suboptimal debulking surgery and genomic cluster were independently prognostic for PFS. Recurrently amplified genomic regions with a significantly higher prevalence in cluster-1 than cluster-2 OCCCs were identified and validated. HER2 gene amplification and protein overexpression was observed in 14% of OCCCs, suggesting that this may constitute a potential therapeutic target for a subgroup of these tumors.

Conclusions: OCCCs constitute a heterogeneous disease at the genomic level despite having similar histological features. The pattern of genomic aberrations in subgroups of OCCCs is of clinical significance. We have identified recurrently amplified regions that may harbor potential therapeutic targets for subgroups of OCCCs. Clin Cancer Res; 17(6); 1521–34. ©2011 AACR.
Role of ERK-BIM and STAT3-Survivin Signaling Pathways in ALK Inhibitor–Induced Apoptosis in EML4-ALK–Positive Lung Cancer
Authors: Takezawa Ken , Okamoto Isamu , Nishio Kazuto , Jänne Pasi A. , Nakagawa Kazuhiko
Published: March 2011

Purpose: EML4-ALK (echinoderm microtubule-associated protein–like 4 anaplastic lymphoma kinase) was recently identified as a transforming fusion gene in non–small cell lung cancer. The purpose of the present study was to characterize the mechanism of malignant transformation by EML4-ALK.

Experimental Design: We established NIH 3T3 cells that stably express variant 1 or 3 of EML4-ALK and examined the signaling molecules that function downstream of EML4-ALK.

Results: Forced expression of EML4-ALK induced marked activation of extracellular signal–regulated kinase (ERK) and STAT3, but not that of AKT. Inhibition of ERK or STAT3 signaling resulted in substantial attenuation of the proliferation of cells expressing either variant of EML4-ALK, suggesting that these signaling pathways function downstream of EML4-ALK in lung cancer cells. The specific ALK inhibitor TAE684 induced apoptosis that was accompanied both by upregulation of BIM, a proapoptotic member of the Bcl-2 family, and by downregulation of survivin, a member of the inhibitor of apoptosis protein (IAP) family, in EML4-ALK–expressing NIH 3T3 cells as well as in H3122 human lung cancer cells harboring endogenous EML4-ALK. Depletion of BIM and overexpression of survivin each inhibited TAE684-induced apoptosis, suggesting that both upregulation of BIM and downregulation of survivin contribute to TAE684-induced apoptosis in EML4-ALK–positive lung cancer cells. Furthermore, BIM and survivin expression was found to be independently regulated by ERK and STAT3 signaling pathways, respectively.

Conclusions: ALK inhibitor–induced apoptosis is mediated both by BIM upregulation resulting from inhibition of ERK signaling as well as by survivin downregulation resulting from inhibition of STAT3 signaling in EML4-ALK–positive lung cancer cells. Clin Cancer Res; 17(8); 2140–8. ©2011 AACR.
Genomic Loss ofmiR-486Regulates Tumor Progression and theOLFM4Antiapoptotic Factor in Gastric Cancer
Authors: Oh Hue-Kian , Tan Angie Lay-Keng , Das Kakoli , Ooi Chia-Huey , Deng Nian-Tao , Tan Iain BeeHuat , Beillard Emmanuel , Lee Julian , Ramnarayanan Kalpana , Rha Sun-Young , Palanisamy Nallasivam , Voorhoeve P. Mathijs , Tan Patrick
Published: March 2011

Purpose: MicroRNAs (miRNA) play pivotal oncogenic and tumor-suppressor roles in several human cancers. We sought to discover novel tumor-suppressor miRNAs in gastric cancer (GC).

Experimental Design: Using Agilent miRNA microarrays, we compared miRNA expression profiles of 40 primary gastric tumors and 40 gastric normal tissues, identifying miRNAs significantly downregulated in gastric tumors.

Results: Among the top 80 miRNAs differentially expressed between gastric tumors and normals (false discovery rate < 0.01), we identified hsa-miR-486 (miR-486) as a significantly downregulated miRNA in primary GCs and GC cell lines. Restoration of miR-486 expression in GC cell lines (YCC3, SCH and AGS) caused suppression of several pro-oncogenic traits, whereas conversely inhibiting miR-486 expression in YCC6 GC cells enhanced cellular proliferation. Array-CGH analysis of 106 primary GCs revealed genomic loss of the miR-486 locus in approximately 25% to 30% of GCs, including two tumors with focal genomic losses specifically deleting miR-486, consistent with miR-486 playing a tumor-suppressive role. Bioinformatic analysis identified the secreted antiapoptotic glycoprotein OLFM4 as a potential miR-486 target. Restoring miR-486 expression in GC cells decreased endogenous OLFM4 transcript and protein levels, and also inhibited expression of luciferase reporters containing an OLFM4 3′ untranslated region with predicted miR-486 binding sites. Supporting the biological relevance of OLFM4 as a miR-486 target, proliferation in GC cells was also significantly reduced by OLFM4 silencing.

Conclusions: miR-486 may function as a novel tumor-suppressor miRNA in GC. Its antioncogenic activity may involve the direct targeting and inhibition of OLFM4. Clin Cancer Res; 17(9); 2657–67. ©2011 AACR.
Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of TH-302, a Hypoxia-Activated Prodrug, in Patients with Advanced Solid Malignancies
Authors: Weiss Glen J. , Infante Jeffrey R. , Chiorean E. Gabriela , Borad Mitesh J. , Bendell Johanna C. , Molina Julian R. , Tibes Raoul , Ramanathan Ramesh K. , Lewandowski Karen , Jones Suzanne F. , Lacouture Mario E. , Langmuir Virginia K. , Lee Hank , Kroll Stew , Burris Howard A.
Published: March 2011

Purpose: The objectives of this phase 1, first-in-human study were to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary activity of the hypoxia-activated prodrug TH-302 in patients with advanced solid tumors.

Experimental Design: TH-302 was administered intravenously over 30 to 60 minutes in two regimens: three times weekly dosing followed by 1 week off (arm A) and every 3-week dosing (arm B).

Results: Fifty-seven patients enrolled (arm A: N = 37 and arm B: N = 20). The TH-302 dose was escalated from 7.5 to 670 mg/m2 in arm A and from 670 to 940 mg/m2 in arm B. The most common adverse events were nausea, skin rash, fatigue, and vomiting. Hematologic toxicity was mild and limited. Grade 3 skin and mucosal toxicities were dose limiting at 670 mg/m2 in arm A; the MTD was 575 mg/m2. In arm B, grade 3 fatigue and grade 3 vaginitis/proctitis were dose limiting at 940 mg/m2; the MTD was 670 mg/m2. Plasma concentrations of TH-302 and the active metabolite Br-IPM (brominated version of isophosphoramide mustard) increased proportionally with dose. Two partial responses were noted in patients with metastatic small cell lung cancer (SCLC) and melanoma in arm A at 480 and 670 mg/m2. Stable disease was observed in arms A and B in 18 and 9 patients, respectively.

Conclusions: The MTD of TH-302 was 575 mg/m2 weekly and 670 mg/m2 every 3 weeks. Skin and mucosal toxicities were DLTs. On the basis of responses in metastatic melanoma and SCLC, further investigations in these indications were initiated. Clin Cancer Res; 17(9); 2997–3004. ©2011 AACR.
Isolated Renal Artery Thrombosis because of Blunt Trauma Abdomen: Report of a Case with Review of the Literature
Authors: Singh Onkar , Gupta Shilpi Singh , Sharma Dhiraj , Lahoti Brijesh Kumar , Mathur Raj Kumar
Published: March 2011

Background: Isolated renal trauma in case of blunt trauma abdomen (BTA) is not common. Renal artery occlusion by thrombosis in such cases is seen very rarely. These cases had been traditionally treated by early nephrectomy, but nowadays, renal preservation is considered whenever possible. Treatment options to do so are being developed. Methods: Recently we came across one such case of isolated unilateral renal artery thrombosis (RAT) because of BTA. Relevant literature especially on various therapeutic techniques has been critically reviewed briefly along with case presentation. Results: Isolated blunt traumatic RAT has an incidence of less than 1%. Only about 400 cases have been reported. It must be diagnosed and treated as soon as possible to avoid progressive permanent loss of renal function. Contrast-enhanced CT scanning is the preferred modality for evaluation and follow-up of RAT. Conservative treatment is reserved for unilateral cases. For bilateral cases and when RAT occurs in a solitary kidney, revascularization either surgically or more preferably by less invasive percutaneous techniques has been recommended. Conclusion: Renal arterial thrombosis because of blunt abdominal trauma is still an underreported entity, treatment for which has not yet been established. Both early nephrectomy and delayed revascularization are not justified treatment options.
Inhibition of Rho-Kinase Abrogates Migration of Human Transitional Cell Carcinoma Cells: Results of an in vitro Study
Authors: vom Dorp Frank , Sanders Harald , Boergermann Christof , Lümmen Gerd , Rübben Herbert , Jakobs Karl H. , Schmidt Martina
Published: March 2011

Introduction: Migration of cells involves a complex signaling network. The aim of the present study was to elucidate the impact of Rho-kinase (ROK) on G protein-coupled receptor-induced migration of human transitional cell carcinoma cells in an in vitro experimental setting. Materials and Methods: Intracellular calcium concentration ([Ca2+]i) was measured with the indicator dye Fura-2 in response to lysophosphatidic acid, thrombin and sphingosine-1-phosphate. Phospholipase C activity was determined in myo-[3H]inositol- (0.5 µCi/ml) labeled cells. Migration was performed using a Boyden chamber. Transient transfection of a dominant-negative mutant of ROK was done with calcium phosphate. For staining of actin filaments, tetramethylrhodamine isothiocyanate-conjugated phalloidin was used. Results: Lysophosphatidic acid, thrombin and sphingosine-1-phosphate cause increases in [Ca2+]i, cellular responses being accompanied by an enhancement of phospholipase C activity and sensitive to the Gi inhibitor pertussis toxin. Agonists potently stimulated migration of T24 and J82 cells. Inhibition of Rho proteins by Clostridium difficile toxin B abrogated cell migration. Inhibition of ROK using HA1077 and Y-27632 mimicked the properties of toxin B. Expression of a ROK mutant drastically reduced migration. Conclusions: G protein-coupled receptors potently stimulated cell migration in T24 and J82 cells. Rho proteins and ROK play a pivotal role in this signaling cascade. Rho and ROK may be putative targets for new therapy options in bladder cancer.
Large Fetal Goiter due to Placental Passage of Maternal Antithyroperoxidase Antibodies
Authors: Vico Irene , Molina Francisca S. , Alarcón-Blanco Pedro , Durán Santiago , Azumendi Guillermo
Published: March 2011

We report a case of fetal goiter in a pregnant woman with Graves-Basedow disease. It was diagnosed in the third trimester by a routine ultrasound, and the cordocentesis verified increased levels of thyroxine (T4) and increased autoantibodies (antithyroperoxidase antibodies) that were also increased in maternal blood. Fetal goiter got smaller on the follow-up scans, and the newborn presented hypothyroidism. Current notions on the diagnosis and management of fetal goiter are briefly discussed.
Fournier’s Gangrene, a Urologic and Surgical Emergency: Presentation of a Multi-Institutional Experience with 45 Cases
Authors: Koukouras Dimitrios , Kallidonis Panagiotis , Panagopoulos Constantinos , Al-Aown Abhulrahman , Athanasopoulos Anastasios , Rigopoulos Christos , Fokaefs Eleftherios , Stolzenburg Jens-Uwe , Perimenis Petros , Liatsikos Evangelos
Published: March 2011

Objective: To review multi-institutional, multidisciplinary experience in the management of Fournier’s gangrene (FG) in an attempt to identify etiologic parameters as well as to propose methods of efficient management. Patients and Methods: Retrospective chart review of 45 patients diagnosed with FG and treated in three departments (general surgery and urology departments) was performed. Results: Average patient age was 50 ± 15.8 (range 33–81) years. Five female and 40 male patients. Seven patients deceased due to the disease. In 26 and 6 cases, perianal or ischiorectal abscess was present, respectively. These abscesses were extending up to the level of rectovesical/Douglas pouch in 12 cases. Abscesses in the scrotum and perineum were revealed in 10 and 6 cases, respectively. A fistula to the rectum and 8 sinuses to the skin were observed. Colostomy was performed in 25 cases, diverting cystostomy in 17, and orchidectomy in 12 cases. In 18 patients (40%) repeat debridement was deemed necessary. Three patients required more than 3 debridement procedures. Average hospitalization time was 15.7 ± 11.6 (range 4–40) days. Conclusion: FG is a life-threatening form of necrotizing soft tissue infection. The disease is unpredictable and the currently proposed methods for prognosis are promising but still questionable.
Acquired Chiari I Malformation in a Child with Corrected Diastematomyelia Disappeared after Thickened Filum Division
Authors: Sgouros S.
Published: March 2011

Introduction: In recent years there has been renewed interest in the relation between Chiari I malformation and spinal cord tethering. Case Report: A 3-year-old girl presented with right leg pain. At spinal MR scan there was diastematomyelia with a bony peg at L1 and syringomyelia at T10–11. She had a surgical repair of the diastematomyelia without filum division. Symptoms settled postoperatively. A few months later she started displaying weakness in the right leg and loss of bulkiness of the right calf. A new MR scan showed a new Chiari I malformation, which was not present in the preoperative MR scan. The syringomyelia cavity was smaller. There was low-ending conus medullaris at L3 and a thickened filum. The filum was divided 15 months after the first operation. At MR scan obtained 18 months after filum division, the previously noted acquired Chiari I malformation had disappeared. Discussion: There is no obvious explanation for the formation of acquired Chiari I malformation and its disappearance after filum division. Recently, there has been description of patients with Chiari I malformation and normal posterior fossa volume, who were treated with filum division, and their Chiari malformation regressed without craniovertebral decompression surgery. Nevertheless, it is difficult to explain how traction on the lowest aspect of the spinal cord could lead to herniation of the cerebellar tonsils through the foramen magnum.
Outcomes Associated with Carotid Pseudo-Occlusion
Authors: Ogata Toshiyasu , Yasaka Masahiro , Kanazawa Yuka , Wakugawa Yoshiyuki , Inoue Tooru , Yasumori Kotaro , Kitazono Takanari , Okada Yasushi
Published: March 2011

Purpose: We tested the hypothesis that patients with carotid pseudo-occlusion (PO) have a different prognosis from those with carotid artery stenosis (CS) without PO. Materials and Methods: 500 patients were examined for CS by cerebral angiography; those with severe CS ≧70% (CS group) or with PO (PO group) were enrolled in this study. The primary endpoint was defined as the combined endpoint of the occurrence of stroke, myocardial infarction, or death. Patients without any events were censored at 60 months. We followed patients for the occurrence and date of primary endpoints and compared clinical characteristics and outcomes between the PO group and the CS group. Results: We enrolled 337 patients (281 men, 56 women, mean age: 70.4 years, mean follow-up period: 32.0 months), of whom 303 (89.9%) were allocated to the CS group while 34 (10.1%) were allocated to the PO group. The rate of diabetes mellitus in the PO group (55.9%) tended to be higher than in the CS group (39.9%). According to Kaplan-Meier analysis, the PO group suffered from the primary outcome more frequently than the CS group. The occurrence of the primary outcome was also associated with older age, peripheral arterial disease and a history of myocardial infarction. Multivariate analysis indicated that patients in the PO group had a significantly poorer outcome compared with those in the CS group (p = 0.013). Conclusion: Patients in the PO group more frequently had neurological and cardiac events or died compared with those in the CS group.
Autosomal Recessive Bestrophinopathy: New Observations on the Retinal Phenotype – Clinical and Molecular Report of an Italian Family
Authors: Guerriero S. , Preising M.N. , Ciccolella N. , Causio F. , Lorenz B. , Fischetto R.
Published: March 2011

Purpose: To describe the genotype and phenotype in a 9-year-old boy with bilateral retinopathy. Methods: The patient, his healthy (by history) nonconsanguineous parents and his sister were examined by best-corrected visual acuity, matrix frequency doubling technology, monocular static field analysis, fundus autofluorescence imaging, optical coherence tomography, Ganzfeld electroretinography (ERG), pattern ERG, multifocal ERG, electro-oculography and genotyping of the BEST1 gene. Results: The patient presented with an Arden ratio of 1.25, an unremarkable ERG and fluorescent yellow deposits distributed throughout the fundus suggestive of autosomal recessive bestrophinopathy (ARB). Genotyping revealed a homozygous nonsense mutation in BEST1 (p.R200X). The parents and the sister, who were heterozygous mutation carriers, presented with normal ophthalmological function. Conclusions: ARB is a rare retinal disorder. We contribute a novel patient report indicative of ARB, assessed by clinical examination and confirmed by genotyping of BEST1, to the short list of ARB cases in the literature.
Ethnic Variations in Acute Ischemic Stroke: Findings from the National Acute Stroke Israeli Survey (NASIS)
Authors: Gross B. , Feldman-Idov Y. , Molshatzki N. , Azrilin O. , Goldbourt U. , Bornstein N.M. , Tanne D. ,   for the National Acute Stroke Israeli Survey Study Group
Published: March 2011

Background: We intended to determine ethnic differences in the characteristics, management and outcome of acute ischemic stroke between the Israeli Arab and Jewish populations. Methods: A national survey was conducted in 2004 at all 28 hospitals in Israel. Information on demographics, transportation, risk factors, clinical presentation, stroke severity, type and subtype, management and clinical outcome was obtained. Mortality during the 36 months after hospitalization was assessed by matching with national mortality data. Results: Of the 1,540 patients, 169 (11%) were Arabs and 1,371 (89%) were Jews. The mean age of Arab patients was 9 years younger than in Jewish patients (63 ± 11 vs. 72 ± 12 years). Also, Arabs were more likely to be obese (OR = 1.72; 95% CI: 1.19–2.50) and have diabetes (OR = 1.41; 95% CI: 1.01–1.96), while Jews were more likely to have dyslipidemia (OR = 1.56; 95% CI: 1.11–2.17). A greater percentage of the Arab patients arrived at the hospital independently (OR = 3.85; 95% CI: 2.56–5.56) and were less likely to arrive within 3 h of symptom onset (OR = 2.33; 95% CI: 1.39–3.85). Arabs suffered increased rates of lacunar stroke (OR = 1.67; 95% CI: 1.14–2.43) and were discharged home more often (OR = 2.40; 95% CI: 1.35–4.25). No differences in severity of stroke, management, complications, disability or mortality were found between the 2 groups. Conclusions: The unique characteristics of the Arab and Jewish populations should be considered when planning stroke-care services and culturally oriented public education programs.
Endothelial Nox4 NADPH Oxidase Enhances Vasodilatation and Reduces Blood Pressure In Vivo
Authors: Ray Robin , Murdoch Colin E. , Wang Minshu , Santos Celio X. , Zhang Min , Alom-Ruiz Sara , Anilkumar Narayana , Ouattara Alexandre , Cave Alison C. , Walker Simon J. , Grieve David J. , Charles Rebecca L. , Eaton Philip , Brewer Alison C. , Shah Ajay M.
Published: March 2011

Objective—

Increased reactive oxygen species (ROS) production is involved in the pathophysiology of endothelial dysfunction. NADPH oxidase-4 (Nox4) is a ROS-generating enzyme expressed in the endothelium, levels of which increase in pathological settings. Recent studies indicate that it generates predominantly hydrogen peroxide (H
2
O
2
), but its role in vivo remains unclear.

Methods and Results—

We generated transgenic mice with endothelium-targeted Nox4 overexpression (Tg) to study the in vivo role of Nox4. Tg demonstrated significantly greater acetylcholine- or histamine-induced vasodilatation than wild-type littermates. This resulted from increased H
2
O
2
production and H
2
O
2
-induced hyperpolarization but not altered nitric oxide bioactivity. Tg had lower systemic blood pressure than wild-type littermates, which was normalized by antioxidants.

Conclusion—

Endothelial Nox4 exerts potentially beneficial effects on vasodilator function and blood pressure that are attributable to H
2
O
2
production. These effects contrast markedly with those reported for Nox1 and Nox2, which involve superoxide-mediated inactivation of nitric oxide. Our results suggest that therapeutic strategies to modulate ROS production in vascular disease may need to separately target individual Nox isoforms.
A Novel Hypoxia-Inducible Spliced Variant of Mitochondrial Death Gene Bnip3 Promotes Survival of Ventricular Myocytes
Authors: Gang Hongying , Hai Yan , Dhingra Rimpy , Gordon Joseph W. , Yurkova Natalia , Aviv Yaron , Li Hongzhao , Aguilar Floribeth , Marshall Aaron , Leygue Etienne , Kirshenbaum Lorrie A.
Published: March 2011

Rationale:

Alternative splicing provides a versatile mechanism by which cells generate proteins with different or even antagonistic properties. Previously, we established hypoxia-inducible death factor Bnip3 as a critical component of the intrinsic death pathway.

Objective:

To investigate alternative splicing of Bnip3 pre-mRNA in postnatal ventricular myocytes during hypoxia.

Methods and Results:

We identify a novel previously unrecognized spliced variant of Bnip3 (Bnip3Δex3) generated by alternative splicing of exon3 exclusively in cardiac myocytes subjected to hypoxia. Sequencing of Bnip3Δex3 revealed a frame shift mutation that terminated transcription up-stream of exon5 and exon6 ablating translation of the BH3-like domain and critical carboxyl-terminal transmembrane domain crucial for mitochondrial localization and cell death. Notably, although the 26-kDa Bnip3 protein (Bnip3FL) encoded by full-length mRNA was localized to mitochondria and provoked cell death, the 8.2-kDa Bnip3Δex3 protein encoded by the truncated spliced mRNA was defective for mitochondrial targeting but interacted with Bnip3FL resulting in less association of Bnip3FL with mitochondria and diminished apoptotic and necrotic cell death. Forced expression of Bnip3FL in cardiac myocytes or Bnip3
−/−
mouse embryonic fibroblasts triggered widespread cell death that was inhibited by coexpression of Bnip3Δex3. Conversely, RNA interference targeted against sequences encompassing the unique exon2-exon4 junction of the Bnip3Δex3 sensitized cardiac myocytes to mitochondrial perturbations and cell death induced by Bnip3FL.

Conclusions:

Given the otherwise lethal consequences of deregulated Bnip3FL expression in postmitotic cells, our findings reveal a novel intrinsic defense mechanism that opposes the mitochondrial defects and cell death of ventricular myocytes that is obligatorily linked and mutually dependent on alternative splicing of Bnip3FL during hypoxia or ischemic stress.
Common Carotid End-Diastolic Velocity and Intima-Media Thickness Jointly Predict Ischemic Stroke in Taiwan
Authors: Chuang Shao-Yuan , Bai Chyi-Huey , Chen Jiunn-Rong , Yeh Wen-Ting , Chen Hsin-Jen , Chiu Hou-Chang , Shiu Ruei-Shiang , Pan Wen-Harn
Published: March 2011

Background and Purpose—

In Asian populations, few studies investigated the association between stroke and common carotid artery intima-media thickness (IMT). Our previous case-control studies showed that low end-diastolic velocity (EDV) in common carotid artery, a potential hemodynamic marker of intracranial resistance, was associated with ischemic stroke. Therefore, we investigated the relationship between both EDV and IMT and incident ischemic stroke in an Asian population.

Methods—

Baseline data from 3175 adults (30 years or older) in the Cardiovascular Diseases Risk Factor Two-Township Study were linked to incidental ischemic stroke status derived from insurance claims and death certificate records. Hazard ratios for risk of ischemic stroke for high IMT and low EDV values measured in common carotid artery were calculated using Cox proportional hazard models.

Results—

With 9.85 years (median) of follow-up, 184 persons had ischemic stroke develop. Compared with the first tertile of IMT, hazard ratios were 2.03 (95% confidence intervals, 1.27–3.25) for the second tertile and 3.87 (95% confidence intervals, 2.36–5.69) for the third tertile. Hazard ratios of EDV were 5.31 (95% confidence intervals, 3.52–7.99; first tertile) and 1.94 (95% confidence intervals, 1.21–3.09; second tertile) compared with the third tertile. The individuals with high IMT and low EDV had >2-fold ischemic stroke risk compared to those with low IMT and high EDV (2.10; 95% confidence intervals, 1.35–3.26) after adjusting for age, sex, and traditional cardiovascular risk.

Conclusions—

Common carotid IMT and EDV jointly and independently predicted future ischemic stroke in this Taiwanese population. More prospective studies are required in various ethnic groups to understand the significance and implication of the current findings, particularly with respect to EDV.
Preventing Enemy Coalitions: How Wedge Strategies Shape Power Politics
Authors: Crawford Timothy W.
Published: March 2011

States use wedge strategies to prevent hostile alliances from forming or to disperse those that have formed. These strategies can cause power alignments that are otherwise unlikely to occur, and thus have significant consequences for international politics. How do such strategies work and what conditions promote their success? The wedge strategies that are likely to have significant effects use selective accommodation—concessions, compensations, and other inducements—to detach and neutralize potential adversaries. These kinds of strategies play important roles in the statecraft of both defensive and offensive powers. Defenders use selective accommodation to balance against a primary threat by neutralizing lesser ones that might ally with it. Expansionists use selective accommodation to prevent or break up blocking coalitions, which isolates opposing states by inducing potential balancers to buck-pass, bandwagon, or hide. Two cases—Great Britain's defensive attempts to accommodate Italy in the late 1930s and Germany's offensive efforts to accommodate the Soviet Union in 1939—help to demonstrate these arguments. By paying attention to these dynamics, international relations scholars can better understand how balancing works in specific cases, how it manifests more broadly in international politics, and why it sometimes fails in situations where it ought to work well.
Can Regional Climate Models Represent the Indian Monsoon?
Authors: Lucas-Picher Philippe , Christensen Jens H. , Saeed Fahad , Kumar Pankaj , Asharaf Shakeel , Ahrens Bodo , Wiltshire Andrew J. , Jacob Daniela , Hagemann Stefan
Published: March 2011

The ability of four regional climate models (RCMs) to represent the Indian monsoon was verified in a consistent framework for the period 1981–2000 using the 45-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) as lateral boundary forcing data. During the monsoon period, the RCMs are able to capture the spatial distribution of precipitation with a maximum over the central and west coast of India, but with important biases at the regional scale on the east coast of India in Bangladesh and Myanmar. Most models are too warm in the north of India compared to the observations. This has an impact on the simulated mean sea level pressure from the RCMs, being in general too low compared to ERA-40. Those biases perturb the land–sea temperature and pressure contrasts that drive the monsoon dynamics and, as a consequence, lead to an overestimation of wind speed, especially over the sea. The timing of the monsoon onset of the RCMs is in good agreement with the one obtained from observationally based gridded datasets, while the monsoon withdrawal is less well simulated. A Hovmöller diagram representation of the mean annual cycle of precipitation reveals that the meridional motion of the precipitation simulated by the RCMs is comparable to the one observed, but the precipitation amounts and the regional distribution differ substantially between the four RCMs. In summary, the spread at the regional scale between the RCMs indicates that important feedbacks and processes are poorly, or not, taken into account in the state-of-the-art regional climate models.
The Impact of Dropwindsonde Data from the THORPEX Pacific Area Regional Campaign and the NOAA Hurricane Field Program on Tropical Cyclone Forecasts in the Global Forecast System
Authors: Aberson Sim D.
Published: March 2011

Four aircraft released dropwindsondes in and around tropical cyclones in the west Pacific during The Observing System Research and Predictability Experiment (THORPEX) Pacific Area Regional Campaign (T-PARC) in 2008 and the Dropwindsonde Observations for Typhoon Surveillance near the Taiwan Region (DOTSTAR); multiple aircraft concurrently participated in similar missions in the Atlantic. Previous studies have treated each region separately and have focused on the tropical cyclones whose environments were sampled. The large number of missions and tropical cyclones in both regions, and additional tropical cyclones in the east Pacific and Indian Oceans, allows for the global impact of these observations on tropical cyclone track forecasts to be studied.

The study shows that there are unintended global consequences to local changes in initial conditions, in this case due to the assimilation of dropwindsonde data in tropical cyclone environments. These global impacts are mainly due to the spectral nature of the model system. These differences should be small and slightly positive, since improved local initial conditions should lead to small global forecast improvements. However, the impacts on tropical cyclones far removed from the data are shown to be as large and positive as those on the tropical cyclones specifically targeted for improved track forecasts. Causes of this unexpected result are hypothesized, potentially providing operational forecasters tools to identify when large remote impacts from surveillance missions might occur.
Stakeholder Management and Nonparticipation in Controversial Business
Authors: Moura-Leite Rosamaria C. , Padgett Robert C. , Galán José I.
Published: March 2011

The main objective of this research is to provide knowledge on the impact that nonparticipation in controversial business can have on corporate financial performance. Accordingly, the stakeholder theory perspective was adopted and the effect of nonparticipation in controversial business on corporatefinancial performance was tested by using market-based and accounting-based economic measures. In addition, the effect of primary stakeholders’ management activities on corporate financial performance was tested, whereby it can be seen whether this nonparticipation in controversial business reveals a different causal relationship with certain aspects of economic performance.
How Hot Is Your Bottom Line? Linking Carbon and Financial Performance
Authors: Busch Timo , Hoffmann Volker H.
Published: March 2011

This study adds two new perspectives to the long-running debate regarding the linkage between corporate social performance (CSP) and corporate financial performance (CFP): First, we add the aspect of issue materiality and suggest research to put more emphasis on the question of how individual CSP issues can be assumed to systematically influence the business environment from a theoretical point of view. Second, we highlight the measurement level of the underlying data screens as an important determinant of the actual effects of CSP on CFP. Focusing on climate change, we developed a set of questions that cover a firm’s carbon emissions and carbon management strategies. These questions were included in a questionnaire sent out annually to the 2,500 largest companies by market cap within the Dow Jones Global Index by an independent Swiss-based asset management firm. Our results show that when using carbon emissions as an outcome-based measurement, corporate environmental performance pays off. Conversely, when using carbon management as a process-based measurement, we find a negative relationship between corporate environmental performance and CFP.
Forgiveness, amnesty and justice
Authors: Jeffery Renée
Published: March 2011

The practice of forgiveness in processes of conflict resolution and post-conflict justice is confronted by two sets of serious criticisms. First, scholars and practitioners alike have questioned whether or not the fundamentally interpersonal practice of forgiveness can be readily and legitimately transposed to broader socio-political contexts. Second, questions have also been raised concerning the potential for forgiveness, particularly when associated with amnesties, to jeopardize and even circumvent the application of justice in post-conflict contexts. By contrast, supporters argue that forgiveness is not only possible but necessary in politics and, by drawing a distinction between amnesties and forgiveness, and restorative and retributive forms of justice, that forgiveness contributes to the achievement of restorative justice. By analysing the role that forgiveness is playing in bringing almost two decades of conflict between the Lord’s Resistance Army and the Ugandan government to an end, this article demonstrates that a disjuncture exists between the theoretical treatment of forgiveness and the practice of political forgiveness. That is, it demonstrates, contrary to arguments made by both its supporters and critics, that political forgiveness, even when conceived in conjunction with amnesties, may contribute to both restorative and retributive forms of justice.
Competencies and Characteristics for Teaching Gifted Students: A Comparative Study of Beijing and Hong Kong Teachers
Authors: Cheung Hoi Yan , Hui Sammy King Fai
Published: March 2011

This study examines the competencies and characteristics of in-service teachers who teach gifted students. A total of 511 in-service teachers participated in the study, 334 of whom were from Beijing and 177 were from Hong Kong. The scale developed by D. W. Chan was used as the instrument to examine the competencies and characteristics of the teachers. The Beijing in-service teachers gave significantly higher self-ratings for their characteristics and competencies than the Hong Kong in-service teachers. Beijing in-service teachers who taught in schools for the gifted (supernormal schools) gave the highest ratings for all the variables. This study analyzed the reasons behind why teachers in each city would have such ratings on competencies and characteristics for themselves, and why Beijing teachers (especially those who taught in supernormal schools) would have significantly higher ratings than their Hong Kong counterparts.
Towards a professional supervision culture: The development of social work supervision in Aotearoa New Zealand
Authors: O’Donoghue Kieran , Tsui Ming-sum
Published: March 2011

This article reviews the development of social work supervision within New Zealand (NZ) and identifies that supervision in NZ has developed a distinctive professional culture in four respects: recognition and acceptance of plurality and diversity, culturally based approaches, use of the concept of cultural supervision, and commitment to competent social work practice. From the literature reviewed it is asserted that New Zealand’s experience provides valuable insights and learning for supervision internationally.
Effect of isopropanol rinse on adhesion of plasma-treated carbon-fiber reinforced epoxy composites
Authors: Morgan B.A. , Zaldivar R.J. , Kim H.I. , Steckel G.L. , Chaney J.A. , Nokes J.P.
Published: March 2011

In this article, we present a comparative assessment of adhesion in plasma-treated carbon fiber reinforced epoxy specimens subject to a post plasma isopropanol rinse. We find that plasma-treated and rinsed samples have better average adhesion than otherwise comparable unrinsed samples and attribute this finding to removal of a thin layer of ash from the plasma-treated surface. Using SEM, XPS, SIMS, and FTIR as diagnostic techniques, we are able to monitor the effects of the rinse on surface chemical functionalization.
Strengthening of damaged structures with bonded prestressed FRP composites plates: an improved theoretical solution
Authors: Kerboua Bachir , Adda bedia E. , Benmoussat Abderrahim
Published: March 2011

In this article, a closed-form rigorous original solution for interfacial stresses in simply supported beams strengthened with bonded prestressed fiber-reinforced polymer (FRP) plates and subjected to a uniformly distributed load, is developed using an improved new model shear deformation coupled with the prestressed force effect. The main interest of this research puts in evidence a new originality approach theory, taking into account the mechanical load, the shear deformation of adherends, and the prestressed FRP plate model with a new shear lag model, which considers a strength rigidity and resistance of the damaged structures, which is one aspect that has not been taken into account by the previous studies. A parametric study has been conducted on factors such as laminate and adhesive stiffness and the thickness of the laminate and the adhesive, where all of them were found to have a marked effect on the magnitude of maximum shear and normal stress.
Studies on acrylonitrile—butadiene copolymer (NBR) layered silicate composites: mechanical and viscoelastic properties
Authors: Balachandran Meera , Bhagawan S.S.
Published: March 2011

Nanocomposites were obtained from a masterbatch of acrylonitrile—butadiene copolymer (NBR; nitrile rubber) and organomodified layered silicate (nanoclay) prepared in an internal mixer followed by mixing with neat NBR and other compounding ingredients on a two-roll mill. Addition of nanoclay reduced the cure time and the vulcanization kinetics closely fitted a first-order model. The morphology was investigated by X-ray diffraction and transmission electron microscopy. The tensile strength, modulus (M100), and storage modulus (E') increased up to 5-phr nanoclay content and thereafter showed a decline. The effect of temperature and frequency on E' and loss tangent was also investigated.
Saliva/Pathogen Biomarker Signatures and Periodontal Disease Progression
Authors: Kinney J.S. , Morelli T. , Braun T. , Ramseier C.A. , Herr A.E. , Sugai J.V. , Shelburne C.E. , Rayburn L.A. , Singh A.K. , Giannobile W.V.
Published: March 2011

The purpose of this study was to determine the role of saliva-derived biomarkers and periodontal pathogens during periodontal disease progression (PDP). One hundred human participants were recruited into a 12-month investigation. They were seen bi-monthly for saliva and clinical measures and bi-annually for subtraction radiography, serum and plaque biofilm assessments. Saliva and serum were analyzed with protein arrays for 14 pro-inflammatory and bone turnover markers, while qPCR was used for detection of biofilm. A hierarchical clustering algorithm was used to group study participants based on clinical, microbiological, salivary/serum biomarkers, and PDP. Eighty-three individuals completed the six-month monitoring phase, with 44 exhibiting PDP, while 39 demonstrated stability. Participants assembled into three clusters based on periodontal pathogens, serum and salivary biomarkers. Cluster 1 members displayed high salivary biomarkers and biofilm; 82% of these individuals were undergoing PDP. Cluster 2 members displayed low biofilm and biomarker levels; 78% of these individuals were stable. Cluster 3 members were not discriminated by PDP status; however, cluster stratification followed groups 1 and 2 based on thresholds of salivary biomarkers and biofilm pathogens. The association of cluster membership to PDP was highly significant (p < 0.0002). The use of salivary and biofilm biomarkers offers potential for the identification of PDP or stability (ClinicalTrials.gov number, CT00277745).
Presentation of a virtual power plant environment and its application with combined first-principle and data-driven models intended for the diagnostics of a power plant – Part 1
Authors: Barszcz Tomasz , Czop Piotr
Published: March 2011

This work aims to present and discuss the architecture and application aspects of the Virtual Power Plant (VPP) environment, a tool created for the purpose of modeling, simulation, data management, and visualization of power plant systems. The VPP environment is based on a general-purpose simulation package that provides a framework for incorporating a broad variety of models, ranging from real-time models to detailed models that require off-line execution. The VPP, as a tool, opens up the possibility to develop, test, and validate the feasibility of new software and hardware components within simulated operational scenarios.

The first part of the work presents the architecture of the VPP and briefly describes its main components. The implementation, including necessary simplifications, encapsulation, and integration of sub-models is discussed and illustrated. A feedwater heater model is the main contributor to the performance of the entire simulation model of a power unit. In the first part of this work, the development process of such a model is presented, including necessary simplifications for improving its performance and functionality.
From Hopelessness to Hope
Authors: Cammarota Julio
Published: March 2011

This article reviews the social justice youth development (SJYD) model conceptualized to facilitate and enhance urban youth awareness of their personal potential, community responsibility, and broader humanity. The SJYD requires the healing of youth identities by involving them in social justice activities that counter oppressive conditions preventing healthy self-identification. Data from a school-based organization in Tucson called the Social Justice Education Project (SJEP) describe the objectives and outcomes of the curricula employed by the SJEP. While urban youth engage in social justice activities and become committed agents of change, positive educational and development experiences will emerge.
Local Housing Supply and the Impact of History and Geography
Authors: Meen Geoffrey , Nygaard Christian
Published: March 2011

This paper considers the impact of existing land use patterns on housing supply price elasticities in local areas of England, under existing planning policies. The paper demonstrates that, despite common national planning policies, local supply responses to market pressures vary considerably, because of differences in historical land uses. The study area covers the Thames Gateway and Thames Valley, which lie to the east and west of London respectively. However, whereas the latter is one of the wealthiest areas of England, the former includes some of the highest pockets of deprivation and was a government priority area for increasing housing supply. Due to differences in historical land use and geography, the price elasticity in the least constrained area is approximately six times higher than the most constrained.
Information-Processing Strategies
Authors: Jun Soo Hyun , Holland Stephen
Published: March 2011

In this study, information-processing strategies that travelers use in information judgment and decision making were investigated. The study results indicate that individuals use certain information attributes (i.e., text argument quality, picture attractiveness) in different involvement situations. Low-involved individuals under a strong argument condition focused on picture attractiveness to quickly assess positive or negative values. High-involved individuals focused on both text argument quality and picture attractiveness for comprehensive evaluation. Three rules were revealed for high-involved individuals’ interactive processing because of offsetting, redundancy, and negative-valence effects. Theoretical implications are discussed and marketing implications are suggested based on these findings.
Evaluation of Eslicarbazepine Acetate on Cardiac Repolarization in a Thorough QT/QTc Study
Authors: Vaz‐Da‐Silva Manuel , Nunes Teresa , Almeida Luis , Gutierrez Maria J. , Litwin Jeffrey S. , Soares‐Da‐Silva Patrício
Published: March 2011

This study investigated the effect of eslicarbazepine acetate (ESL) on cardiac repolarization in healthy adult volunteers. A randomized, placebo/active‐controlled, 4‐period crossover study was conducted in 67 participants. In 3 periods, participants received once‐daily doses of ESL 1200 mg, ESL 2400 mg, and placebo for 5 days; in 1 period, participants received placebo on days 1 to 4 and a 400‐mg moxifloxacin single dose on day 5. In each period, 24‐hour 12‐lead Holter monitoring was performed on days −;1 (baseline) and 5. There was no clinically relevant effect of ESL 1200 mg and 2400 mg versus placebo on cardiac depolarization or repolarization as measured by the QRS or QTc intervals, respectively. Mean PR interval increased following ESL 1200 mg and 2400 mg, but there was no participant with a PR interval above the upper limit of the normal range (200 ms). The upper bound of the 95% confidence interval for the placebo‐corrected change from baseline of the individually corrected QT interval (QTcI) following administration of ESL 1200 mg and ESL 2400 mg was <10 ms at every time point. Moxifloxacin caused an increase in QTcI above the 10‐ms threshold for clinical significance at several time points, demonstrating assay sensitivity. It is concluded that administration of ESL 1200 mg and ESL 2400 mg did not induce a clinically significant prolongation of the QTcI interval.