bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB-72: Rapid detection and profiling of breast cancer cells in blood applied to arrays of carbon nanotube thin film biosensors
Authors: Panchapakesan Balaji , Velasco Vanessa , Jing Rui-Yan , Talati Pooja , Zibelli Allison M. , Wickstrom Eric
Published: February 2011

Breast cancer is the most frequently diagnosed cancer in women. Developing breast cancers shed transformed cells into the blood. More malignant breast cancer cells appear in the blood at later stages. Early detection of circulating breast cancer cells might improve diagnosis of early breast cancer and ultimately might reduce deaths from breast cancer. We hypothesized that nanotube-antibody arrays could detect circulating human breast cancer cells in a drop of blood. Breast cancer cell surfaces show high levels of insulin-like growth factor 1 receptor (IGF1R), human epidermal growth factor receptor 1 (Her1, EGFR), and Her2 (Erb-B2, neu), among others. We have previously demonstrated antibody-specific nanodevice detection of ER+/Her2- MCF7 and ER+/Her2+ BT474 breast cancer cells suspended in a physiological buffer, and in fresh human blood. We discovered significant changes in conductance of single wall carbon nanotube-monoclonal antibody nanodevices upon exposure to human breast cancer cells in 2-5 microliter drops of physiological buffer or fresh donor blood. The nanodevices detected the cancer cells within 60 seconds and stabilized by five minutes. Control cells did not change nanodevice conductance. Breast cancer cells did not perturb the conductance of nanodevices with adsorbed anti-PSMA or nonspecific antibodies. Hence, the conductance change required a specific antigen-antibody complex between the live, intact breast cancer cell and the nanotube surface in blood. We postulate that sensing of breast cancer cell binding is due to cooperative stress on the surface of the nanotubes due to cellular binding to multiple antibodies. The stress on the nanotube is then thought to change its electron transport properties. Five microliter drops of blood from patients with metastatic breast cancer changed nanodevice conductance similarly to 10-100 MCF7 cells. Comparable circulating tumor cell numbers were obtained from 7.5 mL blood draws from the same patients analyzed by EpCAM bead capture and anti-cytokeratin staining. Single wall carbon nanotube-monoclonal antibody nanodevices provide the simplest and quickest method for direct detection of live cancer cells circulating in blood. Supported by a grant from the Breast Cancer Alliance.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-72.
Abstract LB-73: Nuclear S100A4 is a novel prognostic marker in colorectal cancer
Authors: Boye Kjetil , Nesland Jahn M. , Sandstad Berit , Mælandsmo Gunhild M. , Flatmark Kjersti
Published: February 2011

Background and Aims: Current staging classifications in colorectal cancer are not able to accurately predict patient outcome, and the need for novel prognostic markers is evident. S100A4 is a Ca2+-binding protein which promotes metastasis in several tumor types, and the aim of the present study was to investigate the prognostic impact of S100A4 expression in colorectal cancer.

Methods:

242 patients with curatively resected adenocarcinoma of the colon or rectum were prospectively included in the study at the time of surgery. S100A4 expression was analyzed by immunohistochemistry, and associations with clinicopathological variables and patient outcome were investigated.

Results: Nuclear expression of S100A4 was observed in 29% and cytoplasmic expression was observed in 64% of the tumors. In univariate analysis, nuclear S100A4 was a significant predictor of metastasis-free (P= .006) and overall survival (P= .01), whereas cytoplasmic S100A4 was not associated with patient outcome. In multivariate analysis, nuclear localization was associated with metastasis-free (P= .03) and overall survival (P= .02). Interestingly, the prognostic impact was largely confined to TNM stage II, and stage II patients with tumors expressing nuclear S100A4 had a similar prognosis as stage III patients.

Conclusions: Nuclear expression of S100A4 is a novel prognostic marker in colorectal cancer, and the prognostic value in TNM stage II suggests that nuclear S100A4 could be used in the stratification of stage II patients for adjuvant treatment.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-73.
Abstract LB-81: Purification and characterization of a human urinary compound with potent anticancer activity
Authors: Antakly Tony , Chen Ling , Lafaille Francine , Toma Emil , Menezes José , Emwas Abdul-Hamid , Brox Alan
Published: February 2011

Historically, the urine, considered as a blood filtrate has been recognized as a source of medicinal products and important constituents of widely used drugs. However, various molecules in human urine such as growth factors, hormones, and their metabolites have not yet been thoroughly characterized. A group of low molecular weight compounds named HIP's (HCG-like Inhibitory Proteins), was discovered in our laboratories while investigating the hormonal regulation of a skin cancer, Kaposi's sarcoma (KS). Following extraction from the urine of pregnant women, HIP was found to inhibit the growth and kill KS cancer cells by apoptosis both in vitro and in vivo. Initial results following intralesional injection with HIP, revealed a marked reduction in the number of neoplastic cells in the tumor. We are presently testing this product in clinical trials on KS patients in a double blind placebo controlled study. Preliminary results reveal HIP to be safe and well tolerated with no adverse or unexpected reactions. More recently, two other tumors types were demonstrated to be sensitive to HIP and are under further investigation. Following the use of gene microarrays and RT-PCR, the principal target genes for HIP were identified as belonging to a growth factor receptor family. Further purification and biochemical characterization is underway using proteomics and NMR spectroscopy. Overall, the present studies further establish HIP as a urinary compound with potent anti-cancer activity.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-81.
Abstract LB-88: Transient exposure to low-dose decitabine and azacytidine reprograms cancer cells to produce a prolonged antitumor response
Authors: Tsai Hsing-Chen , Van Neste Leander , Li Huili , Cai Yi , Robert Carine , Shin James J. , Pappou Emmanouil , Yen Ray-Whay , Minn IL , Ahuja Nita , Brock Malcolm V. , Rassool Feyruz V. , Jang Yoon-Young , Sharkis Saul J. , Matsui William , Zahnow Cynthia A. , Baylin Stephen B.
Published: February 2011

Reversing abnormal promoter DNA hypermethylation to induce expression of abnormally silenced genes is an attractive cancer therapeutic strategy. The DNA methylation inhibitors, decitabine (5-aza-2′-deoxycytidine) and azacytidine (5-azacytidine), have proven clinically effective against hematological neoplasms especially with use of low, minimally toxic, doses. While, experimentally, high doses of these drugs induce DNA damage and cytotoxicity, the prolonged time for patient responses does not suggest acute tumor cell lysis. We now separate, for these drugs, cytotoxic effects at high doses from cellular reprogramming effects at low nanomolar doses. These latter subsequently reduce tumorigenicity of human leukemia and solid tumor cells, and for leukemia cells, blunt long term self-renewal. We correlate these effects with sustained, genome wide, promoter DNA de-methylation and gene re-expression, and an anti-tumor reprogramming of multiple central cancer pathways which regulate cell cycle entry, mitosis, proliferation, apoptosis, and dependence upon anaerobic glycolysis. Thus, decitabine and azacytidine represent drugs that can, at low nanomolar doses, simultaneously reverse major cancer pathways each of which are the focus of intense drug targeting efforts. This suggests these drugs are broadly applicable to cancer management.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-88.
Abstract LB-90: Sox17 antagonizes Wnt/ß-catenin signaling pathway in HCC
Authors: Guo Mingzhou , Jia Yan , Yang Yunsheng
Published: February 2011

Background: SRY-box containing gene 17 (Sox17) is a candidate tumor suppressor gene, which is indispensable for the embryonic development by antagonizing the canonical Wnt/ß-catenin signaling pathway. We investigated the function and epigenetic regulation of Sox17 in human hepatocellular carcinoma (HCC).

Methods: Methylation and expression of Sox17 were analyzed in 62 HCC tissues and HCC cell lines by MSP and RT-PCR. Inhibitory effects of Sox17 in Wnt/ß-catenin pathway was detected by IHC and luciferase reporter assay. Function as tumor suppressor gene was tested via colony formation assay.

Results: Methylation of Sox17 promoter region occurs in 82.26% of HCC tissues and is associated with nucleus location of -catenin. Restoration of Sox17 in HepG2 cells inhibits colony formation and ß-catenin/TCF-dependent transcription with the presence of HMG box.

Conclusions: Sox17 negatively regulates canonical Wnt/ß-catenin signaling pathway, and inhibits human HCC cells growth through epigenetic mechanism.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-90.
Comparison of Bronchoalveolar Lavage and Mini-Bronchoalveolar Lavage in the Diagnosis of Pneumonia in Immunocompromised Patients
Authors: Tasbakan M. Sezai , Gurgun Alev , Basoglu Ozen K. , Ekren Pervin K. , Pullukcu Husnu , Bacakoglu Feza
Published: February 2011

Background: Pneumonia is a major cause of morbidity and mortality in immunocompromised patients. Bronchoalveolar lavage (BAL) is commonly used to help diagnose and characterize pneumonia in these patients. Mini-BAL is a less-invasive, less-costly and less-cumbersome diagnostic tool than BAL. Objectives: In this study, we compared the diagnostic value of BAL and mini-BAL in the evaluation of pneumonia in immunocompromised patients with respiratory failure. Methods: Sixty-four respiratory samples were collected from 32 immunocompromised patients admitted to our respiratory intensive care unit with a clinical diagnosis of pneumonia and respiratory failure requiring invasive mechanical ventilation. A single BAL sample and a single mini-BAL sample were collected from each patient. Samples were examined for bacteriologic, mycologic, mycobacteriologic, and viral organisms. Results: The mean age of the patients was 56.0 ± 14.4 years. Of the 32 BAL samples, bacterial isolates were detected in 11 patients (34.4%) and on the other hand bacterial isolates were detected in 10 patients (31.3%) of the mini-BAL samples. Fungal isolates were detected in 11 patients (34.4%) from BAL samples and 13 patients (40.6%) from mini-BAL samples. Our analysis demonstrated a strong positive correlation between the results of BAL and mini-BAL testing (r = 0.850 and r = 0.821, respectively). Conclusion: In this study, we demonstrated a strong correlation between the isolation rates of bacteria and fungi in BAL and mini-BAL samples obtained from immunocompromised patients with pneumonia and respiratory failure. The data strongly support the use of mini-BAL sampling in such patients as a less-invasive, less-costly and simpler alternative to traditional BAL.
Cytosolic Phospholipase A
2
α Contributes to Blood Pressure Increases and Endothelial Dysfunction Under Chronic NO Inhibition
Authors: Tanaka Kohei , Yamamoto Yasutaka , Ogino Kazuhide , Tsujimoto Shunsuke , Saito Motoaki , Uozumi Naonori , Shimizu Takao , Hisatome Ichiro
Published: February 2011

Objective—

Nitric oxide (NO) is an important modulator of cardiovascular function. In this study, we examined whether cytosolic phospholipase A
2
α (cPLA
2
α), an initial enzyme in the arachidonic acid pathway, is involved in blood pressure (BP) elevation in a murine model of chronic NO inhibition.

Methods and Results—

cPLA
2
α gene–deficient mice (cPLA
2
α−/−) and wild-type mice (WT) were administered the NO synthesis inhibitor
N
ω
-nitro-
l
-arginine methyl ester (
l
-NAME) for 4 weeks. Before treatment, BP was comparable in both groups; it increased significantly in the WT but not in the cPLA
2
α−/− after treatment. Bone marrow transplantation experiments showed that cPLA
2
α in blood cells and plasma eicosanoid concentrations were not involved in BP elevation by
l
-NAME treatment. Activation of cPLA
2
α and subsequent production of eicosanoids in the aortic endothelium but not in aortic smooth muscle cell, heart, or kidney was observed after
l
-NAME treatment. Aortic ring assays revealed that endothelial function was comparable in both groups of mice before treatment.
l
-NAME treatment disturbed endothelial function in WT but not in cPLA
2
α−/−.

Conclusion—

These results suggest that endothelial cPLA
2
α may play a principal role in
l
-NAME-induced hypertension and may be a target molecule for maintaining endothelial function under NO inhibition.
The Transcription Factor E74-Like Factor Controls Quiescence of Endothelial Cells and Their Resistance to Myeloablative Treatments in Bone Marrow
Authors: Sivina Mariela , Yamada Takeshi , Park Chun Shik , Puppi Monica , Coskun Suleyman , Hirschi Karen , Lacorazza H. Daniel
Published: February 2011

Objective—

The regeneration of the hematopoietic system in bone marrow after chemotherapy depends on a balance between the quiescence and proliferation of lineage-specific progenitor cells. Even though the vascular network in bone is damaged by cytoablation, the transcriptional control of quiescence in endothelial cells is not well known. In this study, we investigated the role of the transcription factor E74-like factor (ELF4) in the proliferation of endothelial cells in bone marrow.

Methods and Results—

Loss-of-function models were used to study the role of ELF4 in human and murine endothelial cells. ELF4 promotes cell cycle entry by activating cyclin-dependent kinase-4 in human umbilical vein endothelial cells.
Elf4
-null mice exhibited enhanced recovery of bone marrow CD45
−
CD31
+
endothelial cells and sinusoidal blood vessels following administration of 5-fluorouracil.

Conclusion—

Loss of ELF4 leads to increased quiescence in bone marrow endothelial cells by the deregulation of cyclin-dependent kinase-4 expression and to enhanced regeneration of sinusoidal blood vessels.
Plasma Biomarkers That Reflect Determinants of Matrix Composition Identify the Presence of Left Ventricular Hypertrophy and Diastolic Heart Failure
Authors: Zile Michael R. , DeSantis Stacia M. , Baicu Catalin F. , Stroud Robert E. , Thompson Sheila B. , McClure Catherine D. , Mehurg Shannon M. , Spinale Francis G.
Published: February 2011

Background—

Chronic pressure overload (such as arterial hypertension) may cause left ventricular (LV) remodeling, alterations in cardiac function, and the development of diastolic heart failure. Changes in the composition of the myocardial extracellular matrix may contribute to the development of pressure-overload–induced LV remodeling. We hypothesized that a specific pattern of plasma biomarker expression that reflected changes in these pathophysiological mechanisms would have diagnostic application to identify (1) patients who have development of LV hypertrophy (LVH) and (2) patients with LVH who have development of diastolic heart failure.

Methods and Results—

Plasma concentration of 17 biomarkers (matrix metalloproteinase [MMP]-1, -2, -3, -7, -8, and -9; tissue inhibitors -1, -2, -3, and -4;
N
-terminal propeptide of brain natriuretic peptide (NT-proBNP); cardiotrophin; osteopontin; soluble receptor for advanced glycation end products; collagen I teleopeptide; collagen I NT-proBNP; and collagen III
N
-terminal propetide [PIIINP]), an echocardiogram, and 6-minute hall walk were performed on 241 referent control subjects, 144 patients with LVH but no evidence of heart failure, and 61 patients with LVH and diastolic heart failure (DHF). A plasma multibiomarker panel consisting of increased MMP-7, MMP-9, TIMP-1, PIIINP, and NT-proBNP predicted the presence of LVH with an area under the curve of 0.80. A plasma multibiomarker panel consisting of increased MMP-2, TIMP-4, PIIINP, and decreased MMP-8 predicted the presence of DHF with an area under the curve of 0.79. These multibiomarker panels performed better than any single biomarker including NT-proBNP and better than using clinical covariates alone (area under the curve, 0.73 for LVH and 0.68 for DHF).

Conclusions—

Plasma biomarkers reflecting changes in extracellular matrix fibrillar collagen homeostasis, combined into a multibiomarker panel, have discriminative value in identifying the presence of structural remodeling (LVH) and clinical disease (DHF).
Cardiac Resynchronization Therapy Reduces the Risk of Cardiac Events in Patients With Diabetes Enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT)
Authors: Martin David T. , McNitt Scott , Nesto Richard W. , Rutter Martin K. , Moss Arthur J.
Published: February 2011

Background—

Data are limited regarding whether the presence of diabetes mellitus (DM) influences the benefit of cardiac resynchronization with defibrillator therapy (CRT-D) in heart failure (HF) patients.

Methods and Results—

The effect of CRT-D was evaluated in 1817 patients who were enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Patients were minimally symptomatic (New York Heart Association class I or II), with ejection fraction ≤0.30 and QRS ≥130 ms. We used Cox regression to determine hazard ratio (HR) of CRT-D versus implantable cardioverter-defibrillator (ICD) therapy for the risk of HF event or death, whichever came first (MADIT-CRT primary end point), in DM (n=552) and non-DM (n=1265) patients. Compared with the non-DM patients, those with DM had more coronary risk factors. During an average follow-up of 2.4 years, DM patients had significantly more primary end point events than non-DM patients (26.6% versus 18%,
P
<0.001). CRT-D was associated with a significant reduction in risk of primary end point in both DM (HR=0.56,
P
<0.001) and non-DM patients (HR=0.67,
P
=0.003). Compared with non-DM patients, CRT-D:ICD HRs in DM patients were lower in the total population, and in subgroups with ischemic cardiomyopathy (0.63 versus 0.64), nonischemic cardiomyopathy (0.39 versus 0.73), and left bundle-branch block (0.36 versus 0.50). There were no significant differences in ventricular remodeling, arrhythmia events, or device-related complications between DM and non-DM patients.

Conclusions—

Patients with diabetes, left ventricular dysfunction, mildly symptomatic HF, and wide QRS complex derive similar benefit from CRT-D compared with patients without diabetes.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00180271.
Human Atherosclerotic Plaque Alternative Macrophages Display Low Cholesterol Handling but High Phagocytosis Because of Distinct Activities of the PPARγ and LXRα Pathways
Authors: Chinetti-Gbaguidi Giulia , Baron Morgane , Bouhlel Mohamed Amine , Vanhoutte Jonathan , Copin Corinne , Sebti Yasmine , Derudas Bruno , Mayi Thérèse , Bories Gael , Tailleux Anne , Haulon Stephane , Zawadzki Christophe , Jude Brigitte , Staels Bart
Published: February 2011

Rationale:

A crucial step in atherogenesis is the infiltration of the subendothelial space of large arteries by monocytes where they differentiate into macrophages and transform into lipid-loaded foam cells. Macrophages are heterogeneous cells that adapt their response to environmental cytokines. Th1 cytokines promote monocyte differentiation into M1 macrophages, whereas Th2 cytokines trigger an “alternative” M2 phenotype.

Objective:

We previously reported the presence of CD68
+
mannose receptor (MR)
+
M2 macrophages in human atherosclerotic plaques. However, the function of these plaque CD68
+
MR
+
macrophages is still unknown.

Methods and Results:

Histological analysis revealed that CD68
+
MR
+
macrophages locate far from the lipid core of the plaque and contain smaller lipid droplets compared to CD68
+
MR
−
macrophages. Interleukin (IL)-4–polarized CD68
+
MR
+
macrophages display a reduced capacity to handle and efflux cellular cholesterol because of low expression levels of the nuclear receptor liver x receptor (LXR)α and its target genes, ABCA1 and apolipoprotein E, attributable to the high 15-lipoxygenase activity in CD68
+
MR
+
macrophages. By contrast, CD68
+
MR
+
macrophages highly express opsonins and receptors involved in phagocytosis, resulting in high phagocytic activity. In M2 macrophages, peroxisome proliferator-activated receptor (PPAR)γ activation enhances the phagocytic but not the cholesterol trafficking pathways.

Conclusions:

These data identify a distinct macrophage subpopulation with a low susceptibility to become foam cells but high phagocytic activity resulting from different regulatory activities of the PPARγ-LXRα pathways.
Distinct Effects of Tissue-Type Plasminogen Activator and SMTP-7 on Cerebrovascular Inflammation Following Thrombolytic Reperfusion
Authors: Miyazaki Takuro , Kimura Yuji , Ohata Hisayuki , Hashimoto Terumasa , Shibata Keita , Hasumi Keiji , Honda Kazuo
Published: February 2011

Background and Purpose—

Thrombolysis therapy using tissue-type plasminogen activator (t-PA) is occasionally accompanied by harmful outcomes, including intracerebral hemorrhage. We have reported that Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a candidate thrombolytic drug, has excellent therapeutic effect on cerebral infarction in embolic stroke model in mice; however, little is known regarding whether this agent influences cerebrovascular inflammation following thrombolytic reperfusion. The current study aimed to compare the effects of recombinant t-PA (rt-PA) and SMTP-7 on cerebrovascular inflammation.

Methods—

The impact of rt-PA- and SMTP-7-induced thrombolytic reperfusion on leukocyte dynamics was investigated in a photochemically induced thrombotic middle cerebral artery occlusion (tMCAo) model in mice.

Results—

Both rt-PA and SMTP-7 administration in tMCAo mice (each 10 mg/kg) resulted in thrombolytic reperfusion. The SMTP-7-administered mice showed relatively mild rolling and attachment of leukocytes to the vascular wall in the middle cerebral vein, with weak peroxynitrite reactions and proinflammatory gene expression (IL-1β, TNF-α, ICAM-1, and VCAM-1); thus, a small infarct volume compared with rt-PA-administered mice. In vitro study suggested that rt-PA at 20 μg/mL, but not SMTP-7 at a similar concentration, promotes cytokine-induced reactive oxygen species generation in cultured endothelial cells; moreover, SMTP-7 suppressed cytokine-induced VCAM-1 induction in the cells and leukocyte/ endothelial cell adhesions.

Conclusions—

Relatively mild cerebrovascular inflammation and cerebral infarction in the SMTP-7 mice, compared with in rt-PA mice, is thought to be caused at least in part by direct antioxidative actions of SMTP-7 in ECs.
Home Time Is Extended in Patients With Ischemic Stroke Who Receive Thrombolytic Therapy
Authors: Mishra Nishant K. , Shuaib Ashfaq , Lyden Patrick , Diener Hans-Christoph , Grotta James , Davis Stephen , Davalos Antoni , Ashwood Tim , Wasiewski Warren , Lees Kennedy R.
Published: February 2011

Background and Purpose—

“Home time” (HT) refers to the number of days over the first 90 after stroke onset that a patient spends residing in their own home or a relative's home versus any institutional care. It is an accessible and objective parameter, free from subjective bias, with potential as an outcome measure in acute stroke trials. We sought to validate HT and assess treatment responsiveness using independent data.

Methods—

We estimated HT in the Stroke Acute Ischemic NXY Treatment (SAINT) I neuroprotection trial. We compared outcomes between thrombolyzed (T) and nonthrombolyzed comparators (C) using HT and the modified Rankin Scale. For our primary analysis, we adjusted for baseline covariates that significantly influence HT and in sensitivity analyses considered all variables that differed between groups at baseline. We report ordinal logistic regression and analysis of covariance with 95% CIs. We describe the relationship of HT with baseline National Institutes of Health Stroke Scale and its components and with Day 90 modified Rankin Scale and Barthel Index.

Results—

SAINT I included 1699 patients from 23 countries, of whom 28.7% received alteplase. HT correlated with age, baseline severity, alteplase use, side of ischemic lesion, presence of diabetes, and country of patient enrolment (each
P
<0.05). We found an association between use of alteplase with better adjusted outcomes by either measure (OR for extended HT, 1.36; 95% CI, 1.08 to 1.72;
P
=0.009; analysis of covariance
P
=0.007 with a 5.5-day advantage; OR for more favorable modified Rankin Scale, 1.6; 95% CI, 1.28 to 2.00;
P
<0.0001; Cochran-Mantel-Haenszel
P
=0.046). HT was significantly associated with baseline National Institutes of Health Stroke Scale and each component of the National Institutes of Health Stroke Scale except level of consciousness, dysarthria, and ataxia. HT was significantly associated with Day 90 modified Rankin Scale and Barthel Index.

Conclusions—

HT is a responsive measure for use in multinational acute stroke trials. Its inclusion as a complementary outcome is reasonable. We propose treatment effects are adjusted for age, baseline National Institutes of Health Stroke Scale, side of stroke lesion, country of enrollment, and the presence of diabetes.
Restenosis After Carotid Surgery
Authors: van Lammeren Guus W. , Peeters Wouter , de Vries Jean-Paul P.M. , de Kleijn Dominique P.V. , De Borst Gert-Jan , Pasterkamp Gerard , Moll Frans L.
Published: February 2011

Background and Purpose—

Carotid endarterectomy (CEA) of stable atherosclerotic plaques is associated with an increased risk for restenosis. Patients with transient ischemic attack and patients with and stroke have relatively unstable atherosclerotic plaques. However, carotid plaques stabilize over time after a cerebrovascular event due to plaque repair after rupture. These findings raised 2 questions: (1) Is preoperative clinical presentation related to restenosis after CEA? (2) Does delayed revascularization result in a higher risk for restenosis compared with CEA in the short term after a cerebrovascular event?

Methods—

Between 2002 and 2009, 1203 patients undergoing CEA were included. The impact of clinical presentation on the occurrence of restenosis 1 year after CEA was investigated and corrected for cardiovascular risk factors, medication use, and type of arteriotomy closure. Patency was assessed with standardized duplex ultrasound imaging at 1 year after CEA. Restenosis was defined as recurrent luminal narrowing ≥50% at the endarterectomy site.

Results—

At 1 year of follow-up, restenosis was observed more frequently in asymptomatic patients than in patients with transient ischemic attack and patients with stroke. The adjusted odds ratio (95% CI) for restenosis was 0.56 (0.35 to 0.89) for patients with transient ischemic attack and 0.49 (0.27 to 0.87) for patients with stroke compared with asymptomatic patients. Subgroup analysis showed an increased risk for restenosis if CEA was performed >30 days after stroke (adjusted OR, 2.23; 1.02 to 5.73).

Conclusions—

Asymptomatic patients have an increased risk for restenosis at 1 year after CEA compared with patients with transient ischemic stroke and patients with stroke. CEA within 30 days after stroke is associated with a decreased risk of restenosis, which supports the current strategy for early surgical intervention after stroke.
The Impact of Future Climate Change on TC Intensity and Structure: A Downscaling Approach
Authors: Hill Kevin A. , Lackmann Gary M.
Published: February 2011

A comprehensive analysis of tropical cyclone (TC) intensity change in a warming climate is undertaken with high-resolution (6- and 2-km grid spacing) idealized simulations using the Weather Research and Forecasting (WRF) model. With the goal of isolating the influence of thermodynamic aspects of climate change on maximum hurricane intensity, an idealized TC is placed within a quiescent, horizontally uniform tropical environment computed from averaged reanalysis data for the tropical Atlantic Ocean. The analyzed tropical environment is used for control simulations. Changes between the periods 1990–99 and 2090–99 are computed using output from 13 GCMs from the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4), for the A1B, A2, and B1 emissions scenarios. These changes are then added to the reanalysis-derived initial and boundary conditions used in the control simulations. Some processes known to impact TC intensity, such as environmental vertical wind shear and sea surface wake cooling, are not considered in this study. Future TC intensity increased for 75 of 78 future simulations using 6-km grid length, with a 9% (~8 hPa) average increase in central surface-pressure deficit. For the 2-km simulations, the average increase was 14% (~14 hPa). The depth of the TC secondary circulation increases in future simulations, consistent with an increase in the height of the freezing level and tropopause. Inner-core precipitation increases of 10%–30% are found for future simulations, with large sensitivity to the emission scenario. The increase in precipitation is consistent with a stronger potential vorticity tower, a warmer eye, and lower central pressure. Enhanced upper-tropospheric warming in the GCM environment is shown to be an important mitigating influence on TC intensity change but is also shown to exhibit large uncertainty in GCM projections.
Evaluation of Biases in JRA-25/JCDAS Precipitation and Their Impact on the Global Terrestrial Carbon Balance
Authors: Saito Makoto , Ito Akihiko , Maksyutov Shamil
Published: February 2011

This study evaluates a modeled precipitation field and examines how its bias affects the modeling of the regional and global terrestrial carbon cycle. Spatial and temporal variations in precipitation produced by the Japanese 25-yr reanalysis (JRA-25)/Japan Meteorological Agency (JMA) Climate Data Assimilation System (JCDAS) were compared with two large-scale observation datasets. JRA-25/JCDAS captures the major distribution patterns of annual precipitation and the features of the seasonal cycle. Notable problems include over- and undersimulated areas of precipitation amount in South America, Africa, and Southeast Asia in the 30°N–30°S domain and a large discrepancy in the number of rainfall days. The latter problem was corrected by using a stochastic model based on the probability of the occurrence of dry and wet day series; the monthly precipitation amount was then scaled by the comparison data. Overall, the corrected precipitation performed well in reproducing the spatial distribution of and temporal variations in total precipitation. Both the corrected and original precipitation data were used to simulate regional and global terrestrial carbon cycles using the prognostic biosphere model Vegetation Integrative Simulator for Trace Gases (VISIT). Following bias correction, the model results showed differences in zonal mean photosynthesis uptake and respiration release ranging from −2.0 to +3.3 Pg C yr−1, compared with the original data. The difference in the global terrestrial net carbon exchange rate was 0.3 Pg C yr−1, reflecting the compensation of coincident increases or decreases in carbon sequestration and respiration loss. At the regional scale, the ecosystem carbon cycle and canopy structure, including seasonal variations in autotrophic and heterotrophic respiration and total biomass, were strongly influenced by the input precipitation data. The results highlight the need for precise precipitation data when estimating the global terrestrial carbon balance.
Gain Affected by the Interior Shape of the Ear Canal
Authors: Yu Jen‐Fang , Chen Yen‐Sheng , Cheng Wei‐De
Published: February 2011

Objective

This study investigated the correlation of gain distribution and the interior shape of the human external ear canal.

Study Design

Cross‐sectional study of gain measurement at the first bend and second bend.

Setting

Chang Gung Memorial Hospital and Chang Gung University.

Subjects and Methods

There were 15 ears in patients aged between 20 and 30 years (8 men/7 women) with normal hearing and middle ears. Stimulus frequencies of 500, 1000, 2000, 3000, and 4000 Hz were based on the standard clinical hearing test. Measurements closer to the tympanic membrane and the positions at the first and second bends were confirmed by using otoscope. Real ear measurement to analyze the canal resonance in human external ears was adopted.

Results

This study found that gain at stimulus frequencies of 4000 Hz was affected by the interior shape of the ear canal (P <. 005), particularly at the first and second bends, whereas gain was only affected by the length of the ear canal for stimulus frequencies of 2000 Hz (P <. 005).

Conclusion

This study found that gain was affected not only by the length of the external auditory canal (EAC) but also by the interior shape of the EAC significantly. The findings of this study may have potential clinical applications in canalplasty and congenital aural atresia surgery and may be used to guide surgeries that attempt to reshape the ear canal to achieve more desirable hearing outcomes.
Massive Facial Trauma following Improvised Explosive Device Blasts in Operation Iraqi Freedom
Authors: Salinas Nathan L. , Brennan Joseph , Gibbons Mark D.
Published: February 2011

Objective

To investigate the association of massive facial trauma with brain and eye injuries, injury severity scores, and blood transfusion utilization.

Study Design

Retrospective study.

Setting

Air Force Theater Hospital, Balad, Iraq.

Subjects and Methods

Retrospective review of US service members injured by improvised explosive devices and treated at the Air Force Theater Hospital in Iraq from October 2004 to September 2007. Massive facial trauma was defined as any injury to the face involving 3 or more facial aesthetic units. The anatomic injury patterns, injury severity scores, and blood transfusion rates of simple and massive facial trauma were compared.

Results

One hundred four patients who sustained facial trauma from improvised explosive device blasts were reviewed, including 29 patients with massive facial trauma. The average injury severity score was 13.9 in the simple facial trauma group and 21.7 in the massive facial trauma group (P =. 006). Sixteen (55%) of the patients in the massive facial trauma group received transfusions compared with only 21 (28%) in the simple facial trauma group (P =. 009). The rate of associated eye injury was 55% in the massive facial trauma group and 27% in the simple facial trauma group (P =. 006). Brain injuries occurred in 48% of the patients with massive facial trauma and 28% of the patients with simple facial trauma (P =. 05).

Conclusion

There is an association between massive facial trauma higher injury severity scores, higher transfusion rates, and an increased risk for eye and brain injuries.
Amplitude and Strength of Muscle Contraction Are Reduced in Experimental Tears of the Rotator Cuff
Authors: Meyer Dominik C. , Gerber Christian , Von Rechenberg Brigitte , Wirth Stephan H. , Farshad Mazda
Published: February 2011

Background: Chronic tendon tears lead to retraction, fatty infiltration, and atrophy of the respective muscle. These muscle changes are decision-making criteria in rotator cuff tear management.

Purpose: To investigate the functional implications of these morphological changes in a sheep rotator cuff tear model.

Study Design: Controlled laboratory study.

Methods: The authors established chronic retraction of the musculotendinous unit accompanied with fatty infiltration and atrophy of the infraspinatus muscle in 20 sheep. The contractile force and passive tension of the muscle as a function of its length were measured and the active work capacity determined.

Results: After tendon release and chronic retraction (by 5.7 ± 0.9 cm), fatty infiltrated and atrophied infraspinatus muscles (with a density of 22.4 ± 10.4 Hounsfield units [HU] and a cross-sectional area of 65% ± 16% of the contralateral control side) had a mean contractile amplitude and strength of 2.7 ± 0.4 cm and 235 ± 71 N compared with the contralateral control shoulder of 4.1 ± 0.7 cm and 485 ± 78 N ( P < .05), respectively. The mean active work of the muscle was 2.8 ± 0.9 N·m for retracted and 8.8 ± 2.4 N·m for control muscles ( P < .05). The correlation of total active work to fatty infiltration ( r = 0.78, P < .001) was significant.

Conclusion: Chronic tendon tears are associated not only with retraction, fatty infiltration, and atrophy but also with loss of strength and contractile amplitude. The functional changes can only indirectly and approximately be predicted by computed tomography imaging findings.

Clinical Relevance: The current criteria (atrophy, retraction, and fatty infiltration) may help to quantify the structural reparability of a chronically retracted musculotendinous unit after rotator cuff tendon tear but may only approximately predict the remaining function of the muscle.
An Investigation of the Relationship Between Chinese Exporters and U.S. Importers From China’s Perspective
Authors: Dong Shen
Published: February 2011

In marketing relationship literature, the buyer—supplier relationship is often studied from the buyers’ perspective in Western countries. In order to address these two gaps, this study investigated the relationship between Chinese exporters/suppliers and U.S. importers/buyers from the Chinese suppliers’ perspective. Fourteen in-depth interviews were conducted in 2008 and two themes were identified. The first theme, surviving, presented a negative and pessimistic perception between the two parties. The second theme, thriving, presented a positive and optimistic perception. Three conclusions were drawn. First, an x—y diagram presented the overall perceptions of Chinese suppliers on their business relationship with U.S. buyers. Second, this study supported the transition from a power-dominating supplier—buyer relationship to a commitment—trust supplier—buyer relationship in the United States—China trading business. Last, what business partners either side needs to look for when they want to do business with each other was stated. Contributions and limitations were discussed as well.
Soulmates, Best Friends, and Casual Buddies: The Relationship of U.S. College Students to Retailer Brands
Authors: Kim Hye-Young , Yoo Jin Kwon
Published: February 2011

While the idea of brand relationships is a promising new way of thinking about consumer behavior, there has been a lack of reflection regarding its feasibility to accurately represent the way consumers interact with retailer brands. This study examines college students’ relationships with retailer brands based on three interpersonal relationship metaphors (i.e., soulmates, best friends, and casual buddies). Forty five college students participated in the study. Participants were asked to think of retailer brands as ‘‘people’’ with actual thoughts, feelings, and actions. Next, they were asked to write about their relationship with a specific retailer brand. A content analysis was conducted. Findings suggest that even though college students’ relationships with retailer brands do not necessarily share the same richness and depth as their relationships with human partners, they sometimes do behave with retailer brands as if they have a relationship with them. Implications are discussed with suggestions for future research.
Modeling and experimental verification of a variable-stiffness isolation system using a leverage mechanism
Authors: Lu Lyan-Ywan , Chu Shih-Yu , Yeh Shih-Wei , Peng Chih-Hua
Published: February 2011

Recent studies have discovered that conventional isolation systems may incur excessive isolator displacement in a near-fault earthquake with strong long-period wave components. To overcome this problem without jeopardizing isolation efficiency, a novel semi-active isolation system called a Leverage-type Variable Stiffness Isolation System (LVSIS) is realized in this study. By utilizing a simple leverage mechanism, the isolation stiffness of the LVSIS can be easily controlled by adjusting the position of the pivot point on the leverage arm. For accurate analysis, the dynamic equation based on a mathematical model that considers the actual situation of all friction forces within the LVSIS is derived in the study. The mathematical model is then verified experimentally by using a prototype LVSIS tested dynamically on a shaking table. Furthermore, to determine the on-line pivot position of the LVSIS, this study also proposes a semi-active control law whose feedback gain is decided by utilizing a linear active control algorithm, such as the LQR or modal control. By comparing the isolation performance of its uncontrolled passive counterpart, the test results also demonstrate that the LVSIS with the proposed control law is especially effective in suppressing the excessive base displacement induced by a near-fault earthquake.
Must tensor addition be among same-order tensors?
Authors: Warne Debra Polignone , Warne Paul G.
Published: February 2011

This paper gives a concise outline for an extended, multi-dimensional number system from a component perspective. We briefly motivate such a system, sketch the associated algebra and geometry, and conclude with a connection to tensor products that shows it is reasonable, if not desirable, to add tensors of different orders.
What do parents and carers think about routine outcome measures and their use? A focus group study of CAMHS attenders
Authors: Moran Philippa , Kelesidi Katerina , Guglani Sacha , Davidson Sue , Ford Tamsin
Published: February 2011

Currently service user involvement in routine outcomes monitoring has been minimal, particularly in Children’s services. There needs to be a more sustained effort to involve service users because of the valuable information that they could provide for service development and improvement. Focus groups were conducted with service users, including parents, carers and young people from a London CAMHS. Their views were elicited on routine outcomes monitoring in general, three specific approaches and suggestions about what else might be important to capture when measuring outcomes. The focus groups raised a number of issues pertinent to routine outcomes monitoring in general, including the reliability of answers, the need for the measures to reflect more than just a tick-box approach and that different people will have different perspectives. Analysis also focused on feedback about the three specific measures discussed. It is important that service users are involved in the process of outcome measurement, from the development of measures, to their application in therapeutic encounters and in service development. Outcome monitoring needs to become a more collaborative process in order that services are measuring what service users think is important, as most would agree that a service should deliver the outcomes that its users want to see.
The dominant negative β isoform of the glucocorticoid receptor is uniquely expressed in erythroid cells expanded from polycythemia vera patients
Authors: Varricchio Lilian , Masselli Elena , Alfani Elena , Battistini Angela , Migliaccio Giovanni , Vannucchi Alessandro Maria , Zhang Wenyong , Rondelli Damiano , Godbold James , Ghinassi Barbara , Whitsett Carolyn , Hoffman Ronald , Migliaccio Anna Rita
Published: February 2011

Glucocorticoid receptor (GR) agonists increase erythropoiesis in vivo and in vitro. To clarify the effect of the dominant negative GRβ isoform (unable to bind STAT-5) on erythropoiesis, erythroblast (EB) expansion cultures of mononuclear cells from 18 healthy (nondiseased) donors (NDs) and 16 patients with polycythemia vera (PV) were studied. GRβ was expressed in all PV EBs but only in EBs from 1 ND. The A3669G polymorphism, which stabilizes GRβ mRNA, had greater frequency in PV (55%; n = 22; P = .0028) and myelofibrosis (35%; n = 20) patients than in NDs (9%; n = 22) or patients with essential thrombocythemia (6%; n = 15). Dexamethasone stimulation of ND cultures increased the number of immature EBs characterized by low GATA1 and β-globin expression, but PV cultures generated great numbers of immature EBs with low levels of GATA1 and β-globin irrespective of dexamethasone stimulation. In ND EBs, STAT-5 was not phosphorylated after dexamethasone and erythropoietin treatment and did not form transcriptionally active complexes with GRα, whereas in PV EBs, STAT-5 was constitutively phosphorylated, but the formation of GR/STAT-5 complexes was prevented by expression of GRβ. These data indicate that GRβ expression and the presence of A3669G likely contribute to development of erythrocytosis in PV and provide a potential target for identification of novel therapeutic agents.
Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A
Authors: Joyal Jean-Sébastien , Sitaras Nicholas , Binet François , Rivera Jose Carlos , Stahl Andreas , Zaniolo Karine , Shao Zhuo , Polosa Anna , Zhu Tang , Hamel David , Djavari Mikheil , Kunik Dario , Honoré Jean-Claude , Picard Emilie , Zabeida Alexandra , Varma Daya R. , Hickson Gilles , Mancini Joseph , Klagsbrun Michael , Costantino Santiago , Beauséjour Christian , Lachapelle Pierre , Smith Lois E. H. , Chemtob Sylvain , Sapieha Przemyslaw
Published: February 2011

The failure of blood vessels to revascularize ischemic neural tissue represents a significant challenge for vascular biology. Examples include proliferative retinopathies (PRs) such as retinopathy of prematurity and proliferative diabetic retinopathy, which are the leading causes of blindness in children and working-age adults. PRs are characterized by initial microvascular degeneration, followed by a compensatory albeit pathologic hypervascularization mounted by the hypoxic retina attempting to reinstate metabolic equilibrium. Paradoxically, this secondary revascularization fails to grow into the most ischemic regions of the retina. Instead, the new vessels are misdirected toward the vitreous, suggesting that vasorepulsive forces operate in the avascular hypoxic retina. In the present study, we demonstrate that the neuronal guidance cue semaphorin 3A (Sema3A) is secreted by hypoxic neurons in the avascular retina in response to the proinflammatory cytokine IL-1β. Sema3A contributes to vascular decay and later forms a chemical barrier that repels neo-vessels toward the vitreous. Conversely, silencing Sema3A expression enhances normal vascular regeneration within the ischemic retina, thereby diminishing aberrant neovascularization and preserving neuroretinal function. Overcoming the chemical barrier (Sema3A) released by ischemic neurons accelerates the vascular regeneration of neural tissues, which restores metabolic supply and improves retinal function. Our findings may be applicable to other neurovascular ischemic conditions such as stroke.