bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use and Interpretation of Competing Risks Regression Models
Authors: Dignam James J. , Zhang Qiang , Kocherginsky Masha
Published: January 2012

Purpose: Competing risks observations, in which patients are subject to a number of potential failure events, are a feature of most clinical cancer studies. With competing risks, several modeling approaches are available to evaluate the relationship of covariates to cause-specific failures. We discuss the use and interpretation of commonly used competing risks regression models.

Experimental Design: For competing risks analysis, the influence of covariate can be evaluated in relation to cause-specific hazard or on the cumulative incidence of the failure types. We present simulation studies to illustrate how covariate effects differ between these approaches. We then show the implications of model choice in an example from a Radiation Therapy Oncology Group (RTOG) clinical trial for prostate cancer.

Results: The simulation studies illustrate that, depending on the relationship of a covariate to both the failure type of principal interest and the competing failure type, different models can result in substantially different effects. For example, a covariate that has no direct influence on the hazard of a primary event can still be significantly associated with the cumulative probability of that event, if the covariate influences the hazard of a competing event. This is a logical consequence of a fundamental difference between the model formulations. The example from RTOG similarly shows differences in the influence of age and tumor grade depending on the endpoint and the model type used.

Conclusions: Competing risks regression modeling requires that one considers the specific question of interest and subsequent choice of the best model to address it. Clin Cancer Res; 18(8); 2301–8. ©2012 AACR.
Overexpression of GDF5 through an Adenovirus Vector Stimulates Osteogenesis of Human Mesenchymal Stem Cells in vitro and in vivo
Authors: Cheng Xiangjun , Yang Tianfu , Meng Wentong , Liu Hao , Zhang Ting , Shi Rui
Published: January 2012

The use of stem cells combined with gene therapy could be an important way to facilitate bone regeneration. In this study, the aim was to investigate the potential of growth and differentiation factor-5 (GDF5) to genetically manipulate human mesenchymal stem cells (hMSCs) for bone regeneration. Recombinant adenovirus Ad-GDF5 and Ad-GFP were constructed and identified, and the titer of both were determined. Third-passage hMSCs were infected with adenovirus, and the expression of GDF5 was confirmed by detection of GFP-positive cells, GDF5 mRNA levels, Western blotting, and enzyme-linked immunosorbent assay (ELISA). hMSCs at passage 3 were divided into four groups: (1) an experimental group infected with Ad-GDF5, (2) a positive control group cultured with osteogenic differentiation medium, (3) a control group infected with Ad-GFP cultured with standard medium, and (4) a blank control group cultured with standard medium. Evaluation of cell morphology and proliferation, analysis of the expression of genes related to osteogenic differentiation, von Kossa staining, and immunofluorescent staining of collagen I were used to investigate the osteogenesis of cells among the groups. After culturing the cells for 2 days under each corresponding condition, the cells were detached and subcutaneously injected into the backs of nude mice to evaluate bone formation. Samples were collected for histological staining, protein Western blotting, and micro-computer tomography. When infected with Ad-GDF5, hMSCs could overexpress GDF5 for a prolonged period in vitro and reach a concentration of 160 ng/ml. Cells infected with Ad-GDF5 or cultured in osteogenic medium displayed osteogenic differentiation based on their histological and cellular properties and on their gene and protein expression patterns. Furthermore, Ad-GDF5 showed a better ability to upregulate the expression of collagen I, alkaline phosphatase, and osteocalcin mRNA than the osteogenic medium. Furthermore, Ad-GDF5 expression was associated with enhanced bone formation in vivo. Our findings suggest that hMSCs infected with Ad-GDF5 can differentiate in an osteogenic direction and may be a promising cell source for bone regeneration.
Combining Nilotinib and Imatinib Improves the Outcome of Imatinib-Resistant Blast Phase CML
Authors: Zhu Guang-rong , Ji Ou , Ji Jian-min , Zhang Ya-cheng , Wu Yu , Yu Hui , Jiang Peng-Jun , Shen Qun
Published: January 2012

Imatinib resistance is an important hurdle in the treatment of chronic myeloid leukemia (CML), and CML patients with this drug resistance are often given a dismal prognosis. In this case report, an imatinib-refractory blast phase CML patient was treated with a combination of imatinib and nilotinib. A complete hematologic response was achieved within 3 months, the drug combination was well tolerated, and there was a relatively long bone-marrow complete remission. These results suggest that combining imatinib and nilotinib treatment may improve the outcome of imatinib-resistant CML patients in the blast phase. We hypothesize regarding the possible mechanism for the effectiveness of the drug combination by reviewing the recent literature.
Effects of Morphine and Midazolam on Sleep-Wake Cycling in Amplitude-Integrated Electroencephalography in Post-Surgical Neonates ≥32 Weeks of Gestational Age
Authors: Olischar Monika , Davidson Andrew J. , Lee Katherine J. , Hunt Rod W.
Published: January 2012

Background: Studies of children who undergo major non-cardiac surgery in the neonatal period are needed so that subsequent abnormal neurodevelopment can be better understood. Objective:It was the aim of our study to describe the influence of analgesic and sedative medication on the predominant background pattern and the development of sleep-wake cycling (SWC), as measured on amplitude-integrated electroencephalography (aEEG), in newborn infants born ≥32 weeks’ gestation after major non-cardiac surgery. Methods:This prospective study included infants ≥32+0 weeks’ gestation admitted to the Neonatal Intensive Care Unit at The Royal Children’s Hospital in Melbourne who were undergoing major non-cardiac surgery. Data on morphine and midazolam given after surgery were recorded and the BrainZ Monitor was applied post-operatively. The maximum levels of morphine and midazolam were assessed as predictors of time to aEEG outcomes using linear regression. Results: Forty-seven eligible infants were included. Emergence of SWC was observed at a mean of 13 h after surgery. The maximum dose of morphine or midazolam was not predictive of time to either any or developed SWC. Conclusions: Despite high doses of morphine and midazolam, SWC was observed on aEEG in neonates ≥32 weeks’ gestational age soon after major non-cardiac surgery. The aEEG background pattern was not affected by the maximum dose of either morphine or midazolam.
Radiographic Response of Brain Metastasis after Linear Accelerator Radiosurgery
Authors: Rahman Maryam , Cox J. Bridger , Chi Yueh-Yun , Carter Jamal H. , Friedman William A.
Published: January 2012

Background: Radiographic response of brain metastasis to stereotactic radiosurgery (SRS) over time has not been well characterized. Being able to predict SRS-induced changes in tumor size over time may allow improved counseling of patients and potentially earlier recognition of poor response to SRS. Objective: To quantify the rate of change in size of metastatic brain tumors after treatment with a linear accelerator (LINAC) SRS. Methods: We performed a retrospective analysis of patients with single metastatic brain tumors treated with LINAC SRS at the University of Florida between 1992 and 2009 who had at least one MRI after treatment. A total of 218 patients with 406 follow-up MRI scans were included in the study. Tumor area was calculated by measuring the largest tumor area on axial imaging and using the equation for area of an ellipse. Primary outcome was percent change in tumor size. The contribution of several factors including gender, primary tumor histology, synchronous or asynchronous presentation, prior treatment, primary tumor control, and SRS dose were examined using multivariate analysis. Results: Mean patient age was 58.3 years (range 4–86), and 48.6% of patients were female. Sixty-three percent of patients had primary tumor control and 70.6% had asynchronous presentation of their brain metastases. SRS peripheral dose range was 1,000–2,250 cGy with a median of 1,750 cGy. The mean percent size change was –22.6% with a mean rate of change of –7.0% per month. The median percent change was –49.7% with a median rate of change of –8.8% per month. The median follow-up was 4.8 months (range 0.3–52.5). Female gender and melanoma histology were found to be significant predictors of an increase in tumor size. Lack of previous surgical resection was a significant predictor of a decrease in tumor size after SRS. Other factors tested with multivariate analysis, including age, synchronicity of presentation, dose, dose volume, Karnofsky performance score, and primary tumor control, were not significant in predicting tumor size change after SRS. Conclusion: In this study, brain metastases decreased in size by a median of 50% for a median follow-up of 4.8 months after SRS. The overall rate of decrease was 9% per month after treatment with SRS. Melanoma histology was a predictor of poor tumor control.
Analysis of p16CDKN2A Methylation and HPV-16 Infection in Oral Mucosal Dysplasia
Authors: Fonseca-Silva Thiago , Farias Lucyana Conceição , Cardoso Claudio Marcelo , de Souza Ludmilla Regina , de Carvalho Fraga Carlos Alberto , de Oliveira Marcos Vinícius Macedo , Barros Lucas Oliveira , Alves Lucas Rodrigues , De-Paula Alfredo Maurício Batista , Marques-Silva Luciano , Gomez Ricardo Santiago , Guimarães André Luiz Sena
Published: January 2012

Objective: The purpose of this study was to investigate the relationship between p16CDKN2A methylation and epithelial dysplasia (ED). We also evaluated the expressions of proteins related to methylation (DNMT3B and DNMT1). Finally, we tested whether HPV-16/18 or the dmt3b (C46359T) polymorphism is associated with p16CDKN2A methylation status. Methods: To test the hypothesis, a case-control study with 72 (control, n = 24; ED, n = 48) tissue samples from subjects was performed. Methylation-specific PCR, RFLP, and immunohistochemical analyses were performed to evaluate p16CDKN2A methylation status, dmt3b (C46359T) genotyping, and protein levels, respectively. Results: The methylation of p16CDKN2A and HPV-16 was associated with ED gradation (p = 0.001 and 0.002, respectively). In addition, most HPV-16-positive samples (77.8%) exhibited p16CDKN2A methylation; however, changes in DNMT3B and DNMT1 protein levels were not observed in HPV-positive samples. Neither HPV-18 nor the dmt3b polymorphism was associated with p16CDKN2A methylation. Conclusions: There is an association between the presence of HPV-16 in ED and the occurrence of p16CDKN2A methylation. Both variables are also associated with ED development, but further studies are necessary to clarify if they operate independently and if they have any impact on OD malignization.
Imaging in Prostate Cancer Staging: Present Role and Future Perspectives
Authors: Pinto Francesco , Totaro Angelo , Palermo Giuseppe , Calarco Alessandro , Sacco Emilio , D’Addessi Alessandro , Racioppi Marco , Valentini AnnaLia , Gui Benedetta , Bassi PierFrancesco
Published: January 2012

Despite recent improvements in detection and treatment, prostate cancer continues to be the most common malignancy and the second leading cause of cancer-related mortality. Thus, although survival rate continues to improve, prostate cancer remains a compelling medical health problem. The major goal of prostate cancer imaging in the next decade will be more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information in order to plan the most appropriate therapeutic strategy. No consensus exists regarding the use of imaging for evaluating primary prostate cancer. However, conventional and functional imaging are expanding their role in detection and local staging and, moreover, functional imaging is becoming of great importance in oncologic management and monitoring of therapy response. This review presents a multidisciplinary perspective on the role of conventional and functional imaging methods in prostate cancer staging.
Prenatal Stress Produces Sexually Dimorphic and Regionally Specific Changes in Gene Expression in Hippocampus and Frontal Cortex of Developing Rat Offspring
Authors: Mychasiuk Richelle , Gibb Robbin , Kolb Bryan
Published: January 2012

Prenatal stress has been known to induce structural changes in the brain and lead to negative psychological well-being. To further understanding of the mechanisms that underlie these effects, whole genome microarray analysis was used to analyze gene expression changes in the developing brain. Epigenetic changes in the hippocampus and frontal cortex of offspring exposed to stress during gestation were investigated. Biological process ontology and pathway analysis was used to increase understanding of the changes produced in response to prenatal stress. The study identified over 700 genes in the frontal cortex and hippocampus that are differentially expressed following prenatal stress. The epigenetic changes demonstrate sex-dependent and region-specific profiles, exhibiting very little overlap between sexes and brain area. Frontal cortex changes were largely related to neurotransmitter function, whereas hippocampal changes were more prominent in females and concentrated around growth factors. These findings have important implications for generalized intervention strategies using a single methodology for all individuals.
Accuracy of Sonographic Fetal Weight Estimation within 14 Days of Delivery in a Jordanian Population Using Hadlock Formula 1
Authors: Basha Asma S. , Abu-Khader Ilham B. , Qutishat Rawan M. , Amarin Zouhair O.
Published: January 2012

Objectives: To assess the accuracy of sonographic fetal weight estimation within 14 days of delivery in a Jordanian population using Hadlock formula 1 in the third trimester. Materials and Methods: Estimated fetal weights and actual fetal weights data were collected from the medical records of pregnant women who had undergone sonographic fetal weight estimation within 14 days of delivery over the period of March 2008 to June 2010. The analysis included 409 Jordanian women; 6 of them had twins, so the study involved estimation of 415 fetal weights, and these were compared to the actual recorded neonatal weights. Using Hadlock formula 1, we compared the estimations with the infants’ actual birth weights. The data were analyzed in 2 groups: within 7 days and 8–14 days. Results: The mean estimated fetal weight was 3,133 ± 475 g (range 1,343–4,420 g). The mean actual birth weight was 3,179 ± 450 g (range 1,300–4,450 g). The mean absolute percentage of error of ultrasound fetal weight estimation for all infants was 6.5%; however, it was 6.1 and 8.2% if the fetus was delivered within 7 days or 8–14 days of sonography, respectively. Overall, 78.8% of fetal weight estimations were within 10% of actual birth weight; however it was 81.3 and 69.9% if the fetus was delivered within 7 days or from 8–14 days of sonography, respectively. Conclusion: The use of Hadlock formula 1 for sonographic fetal weight estimations in Jordanian women showed acceptable results relative to the actual neonatal weight at birth. However, fetal weight estimation was more reliable when performed within 7 days of delivery.
Glomerular Expression of Hydrogen Peroxide-Inducible Clone-5 in Human and Rat Progressive Mesangial Proliferative Glomerulonephritis
Authors: Suga Kenichi , Kondo Shuji , Matsuura Sato , Kinoshita Yukiko , Urushihara Maki , Kagami Shoji
Published: January 2012

Background/Aims: Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor-β1 (TGF-β1)- and hydrogen peroxide (H2O2)-inducible focal adhesion protein that may be necessary for maintaining the myofibroblastic phenotype in pathological scar formation. To investigate the involvement of Hic-5 in the pathogenesis of glomerulonephritis (GN), we examined the glomerular expression of Hic-5 in human and rat GN as well as the regulation of Hic-5 by TGF-β1 in vitro. Methods and Results: Immunohistochemical analyses showed that the expression of Hic-5 was increased in mesangial cells (MCs) in human mesangial proliferative GN. Hic-5 expression was significantly correlated not only with the levels of α-smooth muscle actin (α-SMA) and TGF-β1, the accumulation of extracellular matrix, and the number of glomerular cells, but also with the urinary protein level in patients with GN. Glomerular Hic-5 expression increased in parallel with α-SMA expression in a rat model of mesangial proliferative GN. Combined therapy with an angiotensin type I receptor blocker and an antioxidant in this model improved the histology and the expression of Hic-5 and α-SMA. TGF-β1 upregulated Hic-5 and α-SMA protein levels in human cultured MCs. Conclusion: Our findings suggest that Hic-5 is involved in changes in the MC phenotype to produce abnormal extracellular matrix remodeling in GN.
Design and Validation of a Specific Scavenger Receptor Class AI Binding Peptide for Targeting the Inflammatory Atherosclerotic Plaque
Authors: Segers Filip M.E. , Yu Haixiang , Molenaar Tom J.M. , Prince Perry , Tanaka Toshiki , van Berkel Theo J.C. , Biessen Erik A.L.
Published: January 2012

Objective—

Scavenger receptor A (SR-A) is abundantly expressed by macrophage and plays a critical role in foam cell formation and atherogenesis. In search of selective SR-AI antagonists, we have used affinity selection of a phage displayed peptide library on the synthetic extracellular domain of SR-AI.

Methods and Results—

Phage selection led to an almost 1,000-fold enrichment of SR-AI binding phage, which bound avidly to human THP-1 cells. A 15-mer corresponding to the peptide insert of the major SR-AI binding phage (PP1) displaced phage binding to SR-AI. Peptides, docked to a streptavidin scaffold, were effectively internalized by macrophages in an SR-AI-dependent manner. The enriched phage pool and streptavidin bound PP1 exhibited marked uptake by hepatic macrophages in mice. Importantly, PP1 significantly increased streptavidin as well as particulate accumulation in advanced aortic plaques, and in particular intraplaque macrophage, of apolipoprotein E
−/−
mice.

Conclusion—

We have identified a novel peptide antagonist selective for SR-AI; this antagonist could be a valuable tool in SR-AI targeted imaging of atherosclerotic lesions.
TGF-β1 Downregulates AT1 Receptor Expression via PKC-δ-Mediated Sp1 Dissociation From KLF4 and Smad-Mediated PPAR-γ Association With KLF4
Authors: Zhang Xin-hua , Zheng Bin , Gu Chun , Fu Jian-ran , Wen Jin-kun
Published: January 2012

Objective—

Cardiovascular effects of angiotensin II are primarily mediated via the angiotensin II type 1 receptor (AT1R). Krüppel-like factor 4 (KLF4), a transcription factor that binds to the transforming growth factor (TGF)-β control element (TCE), regulates a variety of receptor expression in vascular smooth muscle cells. In the present study, we investigated the mechanisms of TGF-β-mediated KLF4 regulation of AT1R expression.

Methods and Results—

Coimmunoprecipitation, chromatin immunoprecipitation, and luciferase assays were performed, with the results suggesting that Sp1 forms a complex with KLF4 bound to the TCE of the AT1R promoter and cooperatively activates AT1R transcription in vascular smooth muscle cells under basal conditions. On activation of TGF-β1 signaling, Sp1 is dissociated from the KLF4-Sp1 complex through PKC-δ-mediated KLF4 phosphorylation at Thr401, downregulating AT1R expression. Simultaneously, TGF-β1 facilitates KLF4-PPAR–γ complex formation and its binding to the TCE of the AT1R promoter through Smad-mediated KLF4 phosphorylation at Ser470, subsequently leading to inhibition of AT1R transcription.

Conclusion—

KLF4 functions as a protein platform that is able to bind to the TCE of the AT1R promoter. On activation of TGF-β signaling, KLF4 mediates Sp1 dissociation from, and PPAR-γ association with, the AT1R promoter, leading to downregulation of AT1R expression in VSMCs.
Extrinsic Notch Ligand Delta-Like 1 Regulates Tip Cell Selection and Vascular Branching Morphogenesis
Authors: Napp L.C. , Augustynik M. , Paesler F. , Krishnasamy K. , Woiterski J. , Limbourg A. , Bauersachs J. , Drexler H. , Le Noble F. , Limbourg F.P.
Published: January 2012

Rationale:

In developing blood vessels, single endothelial cells (ECs) specialize into tip cells that sense vascular endothelial growth factor (VEGF) and contribute to vessel sprouting and branch formation. Tip cell differentiation is inhibited through lateral Notch signaling between ECs, which is controlled by Notch ligands expressed in vessel sprouts. The contribution of the Notch ligand Delta-like (Dll) 1 herein is unknown.

Objective:

To investigate the role of Dll1 in vascular morphogenesis and tip cell formation in the mouse retina.

Methods and Results:

Mice with heterozygous deletion of Dll1 had fewer tip cells during angiogenic sprouting of the superficial vascular plexus but also showed impaired vessel branching into deeper retinal layers and impaired deep plexus angiogenesis. Interestingly, the formation of vertical branches was also guided by filopodia-extending ECs located at the tip of branches, consistent with tip cells, which emerged from established vessels to form a secondary plexus within the deeper neuronal cell layers. During both phases of vascular patterning, Dll1 was not expressed in ECs but in the superficial neuronal layer in close contact with expanding vessels, where Dll1 expression coincided with tip cell formation in a spatiotemporal manner. In vitro, culture of ECs on DLL1 induced essential tip cell genes, including Dll4, VEGF receptor 3, and ephrin-B2, and stimulated VEGF responsiveness and vascular network formation.

Conclusions:

Dll1 acts as an extrinsic cue involved in tip cell selection, which directs vessel sprouting and branch formation.
Association of Plasma Phospholipid Long-Chain Omega-3 Fatty Acids With Incident Atrial Fibrillation in Older Adults
Authors: Wu Jason H.Y. , Lemaitre Rozenn N. , King Irena B. , Song Xiaoling , Sacks Frank M. , Rimm Eric B. , Heckbert Susan R. , Siscovick David S. , Mozaffarian Dariush
Published: January 2012

Background—

Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may reduce the risk of atrial fibrillation (AF). Prior studies evaluating fish or n-3 PUFA consumption from dietary questionnaires and incident AF have been conflicting. Circulating levels of n-3 PUFAs provide an objective measurement of exposure.

Methods and Results—

Among 3326 US men and women ≥65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992–2006). In multivariable Cox models adjusted for other risk factors, the relative risk in the top versus lowest quartile of total n-3 PUFAs (eicosapentaenoic acid+docosapentaenoic acid+docosahexaenoic acid) levels was 0.71 (95% confidence interval, 0.57–0.89;
P
for trend=0.004) and of DHA levels was 0.77 (95% confidence interval, 0.62–0.96;
P
for trend=0.01). Eicosapentaenoic acid and docosapentaenoic acid levels were not significantly associated with incident AF. Evaluated nonparametrically, both total n-3 PUFAs and docosahexaenoic acid showed graded and linear inverse associations with incidence of AF. Adjustment for intervening events such as heart failure or myocardial infarction during follow-up did not appreciably alter results.

Conclusions—

In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF. These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF.
Pyruvate Protects the Brain Against Ischemia–Reperfusion Injury by Activating the Erythropoietin Signaling Pathway
Authors: Ryou Myoung-Gwi , Liu Ran , Ren Ming , Sun Jie , Mallet Robert T. , Yang Shao-Hua
Published: January 2012

Background and Purpose—

Pyruvate is known to be cytoprotective through antioxidant and anti-inflammatory mechanisms. We tested the hypothesis that pyruvate protects the brain against ischemia–reperfusion injury by inducing endogenous erythropoietin (EPO) expression.

Methods—

Pyruvate's protective effect was evaluated in C6 glioma cells and HT22 neuronal cells subjected to transient oxygen glucose deprivation. Cell viability (calcein AM assay) and expression of hypoxia-inducible factor-1α, EPO, Akt and Erk (immunoblot), and EPO receptor (reverse transcription–polymerase chain reaction) were analyzed. Transient focal cerebral ischemia in rats was induced by 2 hours middle cerebral artery occlusion followed by 24 hours reperfusion. Pyruvate or saline was infused from 60 minutes occlusion until 30 minutes reperfusion. Lesion volume and DNA fragmentation were assessed by 2,3,5-triphenyltetrazolium staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, respectively. Immunoblots were conducted to determine cerebral EPO contents.

Results—

Pyruvate increased cell viability, hypoxia-inducible factor-1α, EPO, and Akt phosphorylation. Small interfering RNA suppression of hypoxia-inducible factor-1α and EPO abolished pyruvate-induced cytoprotection. In the rat stroke model, pyruvate reduced lesion volume by 84% and DNA fragmentation by 77% versus controls; increased EPO content paralleled these cerebroprotective actions of pyruvate.

Conclusions—

Pyruvate activation of the hypoxia-inducible factor-1α–EPO signaling cascade in neurons and glia could protect the brain from ischemia–reperfusion injury.
Lumbar Drainage of Cerebrospinal Fluid After Aneurysmal Subarachnoid Hemorrhage
Authors: Al-Tamimi Yahia Z. , Bhargava Deepti , Feltbower Richard G. , Hall Gregory , Goddard Anthony J.P. , Quinn Audrey C. , Ross Stuart A.
Published: January 2012

Background and Purpose—

A single-center prospective randomized controlled trial has been conducted to determine if lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage reduces the prevalence of delayed ischemic neurological deficit and improves clinical outcome.

Methods—

Patients with World Federation of Neurological Surgeons Grade 1 to 3 aneurysmal subarachnoid hemorrhage and modified Fisher Grades 2, 3, 4, and 3+4 were randomized to either the study group of standard therapy plus insertion of a lumbar drain or the control group of standard therapy alone. The primary outcome measure was the prevalence of delayed ischemic neurological deficit.

Results—

Two hundred ten patients with aneurysmal subarachnoid hemorrhage (166 female, 44 male; median age, 54 years; interquartile range, 45–62 years) were recruited into the control (n=105) and study (n=105) groups of the trial. World Federation of Neurological Surgeons grade was: 1 (n=139), 2 (n=60), and 3 (n=11); Fisher grade was: 2 (n=87), 3 (n=85), and 4 (n=38). The prevalence of delayed ischemic neurological deficit was 35.2% and 21.0% in the control and study groups, respectively (
P
=0.021). The prevalence of a modified Rankin Scale score of 4, 5, or 6 at Day 10 and 6 months, respectively, was 62.5% and 18.6% in the control group and 44.8% and 19.8% in the study group (
P
=0.009 and 0.83, respectively).

Conclusions—

Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage has been shown to reduce the prevalence of delayed ischemic neurological deficit and improve early clinical outcome but failed to improve outcome at 6 months after aneurysmal subarachnoid hemorrhage.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT00842049.
Flow Diverters at and Beyond the Level of the Circle of Willis for the Treatment of Intracranial Aneurysms
Authors: Pistocchi Silvia , Blanc Raphaël , Bartolini Bruno , Piotin Michel
Published: January 2012

Background and Purpose—

Flow Diverters (FD) are a new emerging therapy for intracranial aneurysms. Initial reports focused on the treatment of proximally located aneurysms. We report our experience with FDs in the treatment of aneurysms at and beyond the circle of Willis.

Methods—

We treated 30 aneurysms at and beyond the circle of Willis with FDs (silk and pipeline). Aneurysms were treated with FDs alone in 73.3% (22/30) and with FDs and coils in 23.3% (7/30). One procedure was converted in parent vessel occlusion.

Results—

Thirty aneurysms (21/30, 70.0% saccular; 7/30, 23.3% fusiform; 2/30, 6.7% blister-like; sizes 1.2–19.6, mean 6.8 mm) were treated in 26 patients (17 women, 9 men; mean age, 49 years) during 27 procedures. Access site complication was noted in 3.7% (1/27). Reversible neurological complications were noted in 7.4% (2/27), permanent neurological complication in 3.7% (1/27). There was no mortality. No aneurysms bled or rebled after treatment. Aneurysms treated with FDs alone were significantly smaller than those treated with FDs and coils (5.7 and 10.0 mm, respectively;
P
=0.0174). Immediate angiographic occlusion was achieved in 18.2% (4/22) with FDs alone, in 0.0% (0/7) with FDs and coils. Twenty-four aneurysms (80.0%) had been followed (mean, 13 months). Fifteen of 19 aneurysms (78.9%) treated with FDs against 4 of 4 of aneurysms (100%) treated with FDs and coils were occluded. There was no angiographic recurrence of initially totally occluded aneurysms.

Conclusions—

Aneurysms at and beyond the circle of Willis are amenable to selective treatment with FDs.
Free Fatty Acids and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage
Authors: Badjatia Neeraj , Seres David , Carpenter Amanda , Schmidt J. Michael , Lee Kiwon , Mayer Stephan A. , Claassen Jan , Connolly E. Sander , Elkind Mitchell S.
Published: January 2012

Background and Purpose—

The purpose of this study was to understand factors related to increases in serum free fatty acid (FFA) levels and association with delayed cerebral ischemia (DCI) after subarachnoid hemorrhage.

Methods—

We performed serial measurement of systemic oxygen consumption by indirect calorimetry and FFA levels by liquid chromatography/mass spectrometry in the first 14 days after ictus in 50 consecutive patients with subarachnoid hemorrhage. Multivariable generalized estimating equation models identified associations with FFA levels in the first 14 days after SAH and Cox proportional hazards model used to identified associations with time to DCI.

Results—

There were 187 measurements in 50 patients with subarachnoid hemorrhage (mean age, 56±14 years old; 66% women) with a median Hunt–Hess score of 3. Adjusting for Hunt–Hess grade and daily caloric intake, n-6 and n-3 FFA levels were both associated with oxygen consumption and the modified Fisher score. Fourteen (28%) patients developed DCI on median postbleed Day 7. The modified Fisher score (
P
=0.01), mean n-6:n-3 FFA ratio (
P
=0.02), and mean oxygen consumption level (
P
=0.04) were higher in patients who developed DCI. In a Cox proportional hazards model, the mean n-6:n-3 FFA ratio (
P
<0.001), younger age (
P
=0.05), and modified Fisher scale (
P
=0.004) were associated with time to DCI.

Conclusions—

Injury severity and oxygen consumption hypermetabolism are associated with higher n-FFA levels and an increased n-6:n-3 FFA ratio is associated with DCI. This may indicate a role for interventions that modulate both oxygen consumption and FFA levels to reduce the occurrence of DCI.
Country Comparisons of Human Stroke Research Since 2001
Authors: Asplund Kjell , Eriksson Marie , Persson Olle
Published: January 2012

Background and Purpose—

This is the first bibliometric comparison between countries of the development of stroke research over time.

Methods—

Clinical and epidemiological articles on stroke published 2001 to mid-2011 were identified in Science Citation Index Expanded. Article fractions, citation fractions, h-index, and international collaboration were calculated using the BibExcel software and adjusted for population size and gross domestic product.

Results—

The United States dominated with 28.7% of the sum of article fractions and 36.2% of the sum of citation fractions. The United States, Japan, the United Kingdom, and Germany together accounted for 52.1% of articles and 61.0% of citations. When adjusted for population size or gross domestic product, several small European countries, together with Israel and Taiwan, ranked the highest. Per population, there was a negative association (
r
=0.60) between burden of stroke (disability-adjusted life-years lost) and number of articles per population. In China, South Korea, and Singapore, the annual growth of stroke articles was more than twice the worldwide average. Whereas multinational collaboration was common within Europe and North America, it was relatively uncommon between Asian countries.

Conclusions—

The Big 4 in scientific literature on stroke, as to both number of articles and citations, are the United States, Japan, the United Kingdom, and Germany. Many small European countries have, in relation to their size, a high scientific production. Several countries with rapidly expanding economies have very fast growth of scientific production on stroke. Our results emphasize the need for stroke research in countries with a high population burden of stroke and they highlight the role of multinational collaboration.
Frontal Infarcts and Anxiety in Stroke
Authors: Tang Wai Kwong , Chen Yangkun , Lu Jinyan , Liang Huajun , Chu Winnie Chiu Wing , Tong Mok Vincent Chung , Ungvari Gabor Sandor , Wong Ka Sing
Published: January 2012

Background and Purpose—

This study examined the association between poststroke anxiety symptoms (PSA) and frontal lobe infarcts.

Methods—

A cohort of 693 patients was recruited. PSA was defined as an anxiety subscale of the Hospital Anxiety and Depression Scale score of 8 or above. The presence and location of infarcts were evaluated with MRI.

Results—

Compared with the non-PSA group, PSA patients were more likely to have right frontal acute infarcts. Right frontal infarcts remained independent predictors of PSA in the multivariate analysis, with an odds ratio of 4.44 (
P
=0.002).

Conclusions—

The results suggest that right frontal acute infarcts may play a role in the development of PSA.
Searching for Information in 133 Years of California Snowfall Observations
Authors: Christy John R.
Published: January 2012

Monthly snowfall totals from over 500 stations in California, some of which date back to 1878, are examined. Most data were accessed through the NOAA archive, but several thousand station months of data were separately keyed in from image files of original documents. Over 26 000 of these entries were new relative to the NOAA archive, generally providing data prior to 1920. The stations were then subdivided into 18 regions for the construction of representative time series of each area. There were problems with the basic data—the most difficult with which to deal was the increasing presence of “zero” totals that should have been recorded as “missing.” This and other issues reduce the confidence that the regional time series are representative of true variations and trends, especially for regions with few systematically reporting stations. Interpreting linear trends on time series with infrequent large anomalies of one sign (i.e., heavy snowfall years) and unresolved data issues should be done with caution. For those regions characterized by consistent monitoring and with the most robust statistical reproducibility, no statistically significant trends in their periods of record (up to 133 years) nor in the most recent 50 years are found. This result encompasses the main snowfall region of the western slope of the Sierra Nevada Mountains.
Comparison between GOES-12 Overshooting-Top Detections, WSR-88D Radar Reflectivity, and Severe Storm Reports
Authors: Dworak Richard , Bedka Kristopher , Brunner Jason , Feltz Wayne
Published: January 2012

Studies have found that convective storms with overshooting-top (OT) signatures in weather satellite imagery are often associated with hazardous weather, such as heavy rainfall, tornadoes, damaging winds, and large hail. An objective satellite-based OT detection product has been developed using 11-μm infrared window (IRW) channel brightness temperatures (BTs) for the upcoming R series of the Geostationary Operational Environmental Satellite (GOES-R) Advanced Baseline Imager. In this study, this method is applied to GOES-12 IRW data and the OT detections are compared with radar data, severe storm reports, and severe weather warnings over the eastern United States. The goals of this study are to 1) improve forecaster understanding of satellite OT signatures relative to commonly available radar products, 2) assess OT detection product accuracy, and 3) evaluate the utility of an OT detection product for diagnosing hazardous convective storms. The coevolution of radar-derived products and satellite OT signatures indicates that an OT often corresponds with the highest radar echo top and reflectivity maximum aloft. Validation of OT detections relative to composite reflectivity indicates an algorithm false-alarm ratio of 16%, with OTs within the coldest IRW BT range (<200 K) being the most accurate. A significant IRW BT minimum typically present with an OT is more often associated with heavy precipitation than a region with a spatially uniform BT. Severe weather was often associated with OT detections during the warm season (April–September) and over the southern United States. The severe weather to OT relationship increased by 15% when GOES operated in rapid-scan mode, showing the importance of high temporal resolution for observing and detecting rapidly evolving cloud-top features. Comparison of the earliest OT detection associated with a severe weather report showed that 75% of the cases occur before severe weather and that 42% of collocated severe weather reports had either an OT detected before a severe weather warning or no warning issued at all. The relationships between satellite OT signatures, severe weather, and heavy rainfall shown in this paper suggest that 1) when an OT is detected, the particular storm is likely producing heavy rainfall and/or possibly severe weather; 2) an objective OT detection product can be used to increase situational awareness and forecaster confidence that a given storm is severe; and 3) this product may be particularly useful in regions with insufficient radar coverage.
Tailoring a future overheating risk tool for existing building design practice in domestic and non-domestic sectors
Authors: Gul M , Jenkins DP , Patidar S , Banfill PFG , Menzies G , Gibson G
Published: January 2012

The Low Carbon Futures Project, as part of the Adaptation and Resilience to Climate Change (ARCC) programme, has developed an overheating tool, based on probabilistic UK Climate Projections (UKCP09), to provide design advice for building adaptations in future. For dwellings this tool, initiated by a single simulation, relies on just hourly climate information to predict the internal temperature profile and for a non-domestic building, it includes internal activity profiles to account for lighting, equipment, metabolic gains and air change. To produce a tailored design tool, a qualitative investigation has been carried out to understand current building practices. This investigation shows that the two sectors take a significantly different approach to design, where dynamic building simulation is rare for domestic developments. The diversity of the non-domestic building stock poses different challenges and requires more detail to perform any overheating analysis, with dynamic building simulation playing a key role. The suitability of this tool, and the need to balance complexity and detail with usability and applicability, will be explored for the two sectors, with an approach for implementing this in the future proposed.

Practical application: This paper compares current overheating analyses, as reported through correspondence with practitioners, with a suggested approach for a more detailed future overheating assessment using the latest climate projections. The required steps to bridge the gap between current and possible future design methods are explored for both the domestic and non-domestic sectors, with a prototype tool proposed that has been formulated with the aid of industry feedback. The described project is therefore able to translate complex building and climate science into an approach that is potentially useful for building practitioners.
Human Leukocyte Death After a Preoperative Infusion of Medium/Long‐Chain Triglyceride and Fish Oil Parenteral Emulsions
Authors: Cury‐Boaventura Maria Fernanda , Torrinhas Raquel Susana Matos de Miranda , de Godoy André Borella Pereira , Curi Rui , Waitzberg Dan Linetzky
Published: January 2012

Background: Parenteral lipid emulsions (LEs) can influence leukocyte functions. The authors investigated the effect of 2 LEs on leukocyte death in surgical patients with gastrointestinal cancer. Material and Methods: Twenty‐five patients from a randomized, double‐blind clinical trial (ID: NCT01218841) were randomly included to evaluate leukocyte death after 3 days of preoperative infusion (0.2 g fat/kg/d) of an LE composed equally of medium/long‐chain triglycerides and soybean oil (MCTs/LCTs) or pure fish oil (FO). Blood samples were collected before (t0) and after LE infusion (t1) and on the third postoperative day (t2). Results: After LE infusion (t1 vs t0), MCTs/LCTs did not influence cell death; FO slightly increased the proportion of necrotic lymphocytes (5%). At the postoperative period (t2 vs t0), MCTs/LCTs tripled the proportion of apoptotic lymphocytes; FO maintained the slightly increased proportion of necrotic lymphocytes (7%) and reduced the percentage of apoptotic lymphocytes by 74%. In the postoperative period, MCT/LCT emulsion increased the proportion of apoptotic neutrophils, and FO emulsion did not change any parameter of apoptosis in the neutrophil population. There were no differences in lymphocyte or neutrophil death when MCT/LCT and FO treatments were compared during either preoperative or postoperative periods. MCT/LCTs altered the expression of 12 of 108 genes related to cell death, with both pro‐ and antiapoptotic effects; FO modulated the expression of 7 genes, demonstrating an antiapoptotic effect. Conclusion: In patients with gastrointestinal cancer, preoperative MCT/LCT infusion was associated with postoperative lymphocyte and neutrophil apoptosis. FO has a protective effect on postoperative lymphocyte apoptosis.
Why cosmoipolitanism in a post-secular age? Taylor and Habermas on European vs American exceptionalism
Authors: Bowman Jonathan M.
Published: January 2012

While Taylor and Habermas respectively follow communitarian vs cosmopolitan lines in their political theories, trends in each of their writings on religion in a global context have taken surprising turns toward convergence. However, what both views lack would be a further analytical and normative classification that better captures the pluralistic dimensions of this shared turn. I consider Taylor’s critique of Habermas’ appeals to constitutional patriotism that lead to recanting the exceptionalist thesis attributed to the USA in order to own up to the exceptionalism of European secularity. I then take up the more pragmatic concern of the religion in a global public, using their writings on Islam in the USA and in the EU as a litmus test for the epistemic scope of our respective degrees of Jamesian openness, referring to the inherent potentials for the moral, social and political integration of immigrants and minorities into a more encompassing cosmoipolitanism.
On a universal scale
Authors: Sørensen Asger
Published: January 2012

This article analyses the general economy of Georges Bataille (1897–1962) in relation to political economy. In the first section I present a critical perspective on economy that is necessary in order to appreciate Bataille’s conception of general economy, which is presented in the second section. The general economy is first considered in a macro-perspective, which comprises the whole of the universe, second in a micro-perspective, where the subjective aspect of economy is maintained as non-objectified desire and inner experience. In the third section I turn to the general economy as it was explicitly intended, namely as a political economy. First I argue that the suggestions that Bataille himself presents are apolitical in an ordinary sense of politics, and that this can be shown to be due to some conceptual slides between nature and society and between history and ontology. I then sketch some postmodern attempts to legitimize respectively capitalism and communism, which refer to the general economy, but argue finally that Bataille can escape both, since he maintains the important distinction between need and desire. Although Bataille’s conception of economy thus reminds us of aspects often overlooked by economy in an ordinary sense, it also contains some serious aporias, which means that it cannot constitute the theoretical basis of a new general political economy, as Bataille had hoped.
The Effects of Functional Polymorphisms in the TGFβ1 Gene on Nasopharyngeal Carcinoma Susceptibility
Authors: Hu Sunhong , Zhou Guojin , Zhang Lei , Jiang Huifen , Xiao Mang
Published: January 2012

Objective

Transforming growth factor β1 (TGFβ1) promotes tumor growth and metastasis in the later stage of cancer development. In this study, we explored whether TGFβ1 polymorphisms were associated with increased risk of nasopharyngeal carcinoma (NPC) in a Chinese population.

Design

Case‐control study.

Setting

Hospitals of the Department of Otorhinolaryngology–Head and Neck Surgery.

Subjects and Methods

Two single nucleotide polymorphisms of TGFβ1 gene promoter ‐509C/T (rs1800469) and 869T/C (Leu 10 Pro, rs1800470) at exon 1 were analyzed in 522 NPC patients and 712 age‐ and sex‐matched controls in a Chinese population, using polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) analysis. Functional relevance of the polymorphism was determined by biochemical assays.

Results

The ‐509T allele carriers were associated with a significantly reduced risk of NPC as compared with the noncarriers (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53‐0.89 and OR, 0.50; 95% CI, 0.31‐0.67, respectively). Moreover, ‐509C‐containing TGFβ1 promoter drove an ~1.7‐fold increase in reporter expression, compared with the ‐509T‐containing counterpart in both CNE‐1 and CNE‐2 cell lines. The TGFβ1 ‐509 CC genotype carriers had a higher TGFβ1 mRNA level than the TGFβ1 ‐509TT genotype carriers did (P <. 01). However, no significant association was observed between the 869T/C polymorphism and risk of NPC.

Conclusion

These findings indicate that the ‐509C/T polymorphism in TGFβ1 may play a vital role in mediating individual susceptibility to NPC.
Technology-Supported Performance-Based Feedback for Early Intervention Home Visiting
Authors: Marturana Emily R. , Woods Juliann J.
Published: January 2012

This study was conducted to evaluate the effects of a Distance Mentoring Model (DMM), including performance-based feedback and technology support, on expanding the use of recommended home visiting practices by early interventionists. Data from 18 early interventionists indicated that participation in the DMM approach was associated with increased use of various caregiver coaching strategies and routine contexts. Specifically, participants spent significantly less time in child-focused intervention and more time using specific coaching interactions with the caregiver and child as a dyad after participating in technology-supported, performance-based feedback. All participants reported that they would participate in technology-supported, professional development opportunities again in the future.