bluuebunny/crossref_metadata_2025 huggingface dataset:
A Meta-Analysis of Enteral Nutrition and Total Parenteral Nutrition in Patients with Acute Pancreatitis
Authors: Quan Heming , Wang Xingpeng , Guo Chuanyong
Published: June 2011

Objective. To analyze the effect of total parenteral nutrition (TPN) and enteral nutrition (EN) in patients with acute pancreatitis.Methods. Randomized controlled trials of TPN and EN in patients with acute pancreatitis were searched in NCBI and CBM databases and The Cochrane Controlled Trials Register. Six studies were enrolled into the analysis, and the details about the trial designs, characters of the subjects, results of the studies were reviewed by two independent authors and analyzed by STATA 11.0 software.Results. Compared with TPN, EN was associated with a significantly lower incidence of pancreatic infection complications (RR=0.556, 95% CI 0.436∼0.709,P=.000), MOF (RR=0.395, 95% CI 0.272∼0.573,P=.003), surgical interventions (RR=0.556, 95% CI 0.436∼0.709,P=.000), and mortality (RR=0.426, 95% CI 0.238∼0.764,P=.167). There was no statistic significance in non-pancreatitis-related complications (RR=0.853, 95% CI 0.490∼1.483,P=.017). However, EN had a significantly higher incidence of non-infection-related complications (RR=2.697, 95% CI 1.947∼3.735,P=.994).Conclusion. EN could be the preferred nutrition feeding method in patients with acute pancreatitis.
BK Virus in Kidney Transplant Recipients: The Influence of Immunosuppression
Authors: Barraclough Katherine A. , Isbel Nicole M. , Staatz Christine E. , Johnson David W.
Published: June 2011

The incidence of BK virus infection in kidney transplant recipients has increased over recent decades, coincident with the use of more potent immunosuppression. More importantly, posttransplant BK virus replication has emerged as an important cause of graft damage and subsequent graft loss. Immunosuppression has been accepted as a major risk for BK virus replication. However, the specific contribution of individual immunosuppressive medications to this risk has not been well established. The purpose of this paper is to provide an overview of the recent literature on the influence of the various immunosuppressant drugs and drug combinations on posttransplant BK virus replication. Evidence supporting the various immunosuppression reduction strategies utilised in the management of BK virus will also be briefly discussed.
Pulsed Current‐Voltage‐Induced Perturbations of a Premixed Propane/Air Flame
Authors: Schmidt Jacob. B. , Ganguly Biswa. N.
Published: June 2011

The effect of millisecond wide sub‐breakdown pulsed voltage‐current induced flow perturbation has been measured in premixed laminar atmospheric pressure propane/air flame. The flame equivalence ratios were varied from 0.8 to 1.2 with the flow speeds near 1.1 meter/second. Spatio‐temporal flame structure changes were observed through collection of CH (A‐X) and OH (A‐X) chemiluminescence and simultaneous spontaneous Raman scattering from N2. This optical collection scheme allows us to obtain a strong correlation between the measured gas temperature and the chemiluminescence intensity, verifying that chemiluminescence images provide accurate measurements of flame reaction zone structure modifications. The experimental results suggest that the flame perturbation is caused by ionic wind originating only from the radial positive space‐charge distribution in/near the cathode fall. A net momentum transfer acts along the annular space discharge distribution in the reaction zone at or near the cathode fall which modifies the flow field near the cathodic burner head. This radially inward directed body force appears to enhance mixing similar to a swirl induced modification of the flame structure. The flame fluidic response exhibit a strong dependence on the voltage pulse width ≤10 millisecond.
Location Discovery Based on Fuzzy Geometry in Passive Sensor Networks
Authors: Wang Rui , Cao Wenming , Wan Wanggen
Published: June 2011

Location discovery with uncertainty using passive sensor networks in the nation's power grid is known to be challenging, due to the massive scale and inherent complexity. For bearings-only target localization in passive sensor networks, the approach of fuzzy geometry is introduced to investigate the fuzzy measurability for a moving target inR2space. The fuzzy analytical bias expressions and the geometrical constraints are derived for bearings-only target localization. The interplay between fuzzy geometry of target localization and the fuzzy estimation bias for the case of fuzzy linear observer trajectory is analyzed in detail in sensor networks, which can realize the 3-dimensional localization including fuzzy estimate position and velocity of the target by measuring the fuzzy azimuth angles at intervals of fixed time. Simulation results show that the resulting estimate position outperforms the traditional least squares approach for localization with uncertainty.
Strategies for Regenerating Striatal Neurons in the Adult Brain by Using Endogenous Neural Stem Cells
Authors: Nakaguchi Kanako , Masuda Hiroshi , Kaneko Naoko , Sawamoto Kazunobu
Published: June 2011

Currently, there is no effective treatment for the marked neuronal loss caused by neurodegenerative diseases, such as Huntington's disease (HD) or ischemic stroke. However, recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ) of the adult mammalian brain, including the human brain. Because some of these new neurons migrate to the injured striatum and differentiate into mature neurons, such new neurons may be able to replace degenerated neurons and improve or repair neurological deficits. To establish a neuroregenerative therapy using this endogenous system, endogenous regulatory mechanisms that can be co-opted for efficient regenerative interventions must be understood, along with any potential drawbacks. Here, we review current knowledge on the generation of new neurons in the adult brain and discuss their potential for use in replacing striatal neurons lost to neurodegenerative diseases, including HD, and to ischemic stroke.
Photocatalytic Degradation of Phenol Using ImmobilizedTiO2Nanotube Photocatalysts
Authors: Wong Chung Leng , Tan Yong Nian , Mohamed Abdul Rahman
Published: June 2011

TiO2nanotubes immobilized on silica gel were used in the photocatalytic degradation of phenol in a batch reactor. The highest rate of photocatalytic activity was observed when the ratios of TiO2nanotubes: silica gel: colloidal silica were 3 : 2 : 20. The optimal air flow rate for phenol degradation was 0.3 L/min while pH 3 was optimal for the reaction medium. Decreasing the initial phenol concentration led to an increase in phenol degradation efficiency due to more hydroxyl radicals being presented on the catalyst surface. Immobilized TiO2nanotubes showed higher photocatalytic activity than that of the pure TiO2which only achieved 87% degradation. Compared with pure TiO2, the immobilized TiO2nanotubes benefited from a larger specific surface area and a low recombination rate of photogenerated electron-hole pairs. After three operating cycles, the decrease in photocatalytic activity of the immobilized TiO2nanotubes was slight, indicating that the immobilized TiO2nanotubes have excellent stability and reusability.
The Utility of 2,2′-Bipyrimidine in Lanthanide Chemistry: From Materials Synthesis to Structural and Physical Properties
Authors: Zucchi Gaël
Published: June 2011

This paper reviews the recent investigations undertaken on the use of 2,2′-bipyrimidine (bpm) as a ligand for designing molecular complexes as well as polymeric lanthanide materials. A special emphasis is put on the ability of this polydentate neutral ligand to yield compounds of various dimensionalities, to act as a connector between these large ions, and influence their emissive and magnetic properties. This ligand can adopt a terminal or a bridging coordination mode with lanthanide ions, thus generating a wealth of frameworks of various topologies with the 4felements. The main focus of this review is to show the originality brought by bpm in lanthanide structural chemistry and solid-state photophysics and magnetism.
Exact Solution for the Time‐Dependent Temperature Field in Dry Grinding: Application to Segmental Wheels
Authors: González-Santander J. L. , Valdés Placeres J. M. , Isidro J. M.
Published: June 2011

We present a closed analytical solution for the time evolution of the temperature field in dry grinding for any time‐dependent friction profile between the grinding wheel and the workpiece. We base our solution in the framework of the Samara‐Valencia model Skuratov et al., 2007, solving the integral equation posed for the case of dry grinding. We apply our solution to segmental wheels that produce an intermittent friction over the workpiece surface.
For the same grinding parameters, we plot the temperature fields of up‐ and downgrinding, showing that they are quite different from each other.
Thermodynamical Restrictions and Wave Propagation for a Class ofFractional Order Viscoelastic Rods
Authors: Atanacković Teodor M. , Konjik Sanja , Oparnica Ljubica , Zorica Dušan
Published: June 2011

We discuss thermodynamical restrictions for a linear constitutive equation containing fractional derivatives of stress and strain of different orders. Such an equation generalizes several known models. The restrictions on coefficients are derived by using entropy inequality for isothermal processes. In addition, we study waves in a rod of finite length modelled by a linear fractional constitutive equation. In particular, we examine stress relaxation and creep and compare results with the quasistatic analysis.
Positive Feedback Loop Between PI3K-Akt-mTORC1 Signaling and the Lipogenic Pathway Boosts Akt Signaling: Induction of the Lipogenic Pathway by a Melanoma Antigen
Authors: Yamauchi Yoshio , Furukawa Keiko , Hamamura Kazunori , Furukawa Koichi
Published: June 2011

The lipogenic phenotype is a metabolic hallmark of cancer cells. Sterol regulatory element–binding proteins (SREBP) are key transcriptional factors to regulate biosynthesis of cholesterol and fatty acids. It has been poorly understood how the lipogenic phenotype in cancer cells is regulated and how it augments their malignant properties. Here we describe roles of the melanoma antigen ganglioside GD3 and phosphatidylinositol 3-kinase (PI3K)-Akt-mTOR complex 1 (mTORC1) signaling in the regulation of SREBP activity, cholesterol biosynthesis, and the integrity of lipid rafts in human melanoma cells. GD3 expression induced the activation of both SREBP-1 and SREBP-2. Consequently, HMG-CoA reductase expression and cholesterol biosynthesis increased. The activation of the SREBP pathway was independent of the oncogenic BRAF mutation. On the other hand, it was regulated by PI3K-Akt-mTORC1 signaling in human melanoma cells. Disruption of the signaling pathway resulted in the reduction of cholesterol in lipid rafts. Inhibition of the SREBP pathway attenuated Akt activation in lipid rafts and suppressed the growth of human melanoma cells in vitro and in vivo. These results suggest that PI3K-Akt-mTORC1 signaling is important for the integrity of lipid rafts by regulating SREBP activation and subsequent cholesterogenesis. We thus propose a positive feedback circuit in which PI3K-Akt-mTORC1-SREBP signaling boosts Akt signaling in human melanoma cells expressing GD3. Cancer Res; 71(14); 4989–97. ©2011 AACR.
Notch Signaling Activated by Replication Stress–Induced Expression of Midkine Drives Epithelial–Mesenchymal Transition and Chemoresistance in Pancreatic Cancer
Authors: Güngör Cenap , Zander Hilke , Effenberger Katharina E. , Vashist Yogesh K. , Kalinina Tatyana , Izbicki Jakob R. , Yekebas Emre , Bockhorn Maximilian
Published: June 2011

The incidence of pancreatic ductal adenocarcinoma (PDAC) nearly equals its mortality rate, partly because most PDACs are intrinsically chemoresistant and thus largely untreatable. It was found recently that chemoresistant PDAC cells overexpress the Notch-2 receptor and have undergone epithelial–mesenchymal transition (EMT). In this study, we show that these two phenotypes are interrelated by expression of Midkine (MK), a heparin-binding growth factor that is widely overexpressed in chemoresistant PDAC. Gemcitabine, the front-line chemotherapy used in PDAC treatment, induced MK expression in a dose-dependent manner, and its RNAi-mediated depletion was associated with sensitization to gemcitabine treatment. We identified an interaction between the Notch-2 receptor and MK in PDAC cells. MK–Notch-2 interaction activated Notch signaling, induced EMT, upregulated NF-κB, and increased chemoresistance. Taken together, our findings define an important pathway of chemoresistance in PDAC and suggest novel strategies for its clinical attack. Cancer Res; 71(14); 5009–19. ©2011 AACR.
Prediagnostic Serum Levels of Cytokines and Other Immune Markers and Risk of Non-Hodgkin Lymphoma
Authors: Purdue Mark P. , Lan Qing , Bagni Rachel , Hocking William G. , Baris Dalsu , Reding Douglas J. , Rothman Nathaniel
Published: June 2011

Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), it is unclear whether subclinical immune system function influences lymphomagenesis. To address this question, we conducted a nested case–control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate whether circulating levels of cytokines and other immune markers are associated with future risk of NHL. Selected cytokines [interleukin (IL)-4, IL-6, IL-10, and TNF-α] and other immune markers [soluble TNF receptor 1 (sTNF-R1), sTNF-R2, C-reactive protein, and sCD27] were measured in prediagnostic serum specimens from 297 incident NHL cases and 297 individually matched controls. ORs and 95% confidence intervals (CI) relating quartiles of analyte concentration to NHL risk were calculated by using conditional logistic regression. Statistically significant associations with increased NHL risk were observed for elevated serum levels of sTNF-R1 (quartile 4 vs. quartile 1: OR = 1.7, 95% CI: 1.1–2.8; Ptrend = 0.02) and sCD27 (OR = 5.3, 95% CI: 2.9–9.4; Ptrend < 0.0001). These associations remained in analyses of cases diagnosed longer than 6 years following blood collection (sTNF-R1: OR = 2.1, 95% CI: 1.0–4.0, Ptrend = 0.01; sCD27: OR = 4.1, 95% CI: 1.9–8.5, Ptrend = 0.0001). Elevated levels of IL-10, TNF-α and sTNF-R2 were also significantly associated with increased risk of NHL overall; however, these associations weakened with increasing time from blood collection to case diagnosis and were null for cases diagnosed longer than 6 years postcollection. Our findings for sTNF-R1 and sCD27, possible markers for inflammatory and B-cell stimulatory states, respectively, support a role for subclinical inflammation and chronic B-cell stimulation in lymphomagenesis. Cancer Res; 71(14); 4898–907. ©2011 AACR.
Genetic Variations in Multiple Drug Action Pathways and Survival in Advanced Stage Non–Small Cell Lung Cancer Treated with Chemotherapy
Authors: Li Yafei , Sun Zhifu , Cunningham Julie M. , Aubry Marie C. , Wampfler Jason A. , Croghan Gary A. , Johnson Cassandra , Wu Danli , Aakre Jeremiah A. , Molina Julian , Wang Liewei , Pankratz V. Shane , Yang Ping
Published: June 2011

Purpose: Variations in genes related to biological activity of anticancer drugs could influence treatment responses and lung cancer prognosis. Genetic variants in four biological pathways, that is, glutathione metabolism, DNA repair, cell cycle, and epidermal growth factor receptor (EGFR), were systematically investigated to examine their association with survival in advanced stage non–small cell lung cancer (NSCLC) treated with chemotherapy.

Experimental Design: A total of 894 tagging single-nucleotide polymorphisms (SNP) in 70 genes from the four pathways were genotyped and analyzed in a 1,076-patient cohort. Association with overall survival was analyzed at SNP and whole-gene levels within all patients and major chemotherapy agent combination groups.

Results: A poorer overall survival was observed in patients with genetic variations in GSS (glutathione pathway) and MAP3K1 (EGFR pathway; HR = 1.45; 95% CI = 1.20–1.77 and HR = 1.25; 95% CI = 1.05–1.50, respectively). In the stratified analysis on patients receiving platinum plus taxane treatment, we observed a hazardous effect on overall survival by the MAP3K1 variant (HR = 1.38; 95% CI = 1.11–1.72) and a protective effect by RAF1 (HR = 0.64; 95% CI = 0.50–0.82) in the EGFR pathway. In patients receiving platinum plus gemcitabine treatment, RAF1 and GPX5 (glutathione pathway) genetic variations showed protective effects on survival (HR = 0.54; 95% CI = 0.38–0.77; HR = 0.67; 95% CI = 0.52–0.85, respectively); in contrast, NRAS (EGFR pathway) and GPX7 (glutathione pathway) variations showed hazardous effects on overall survival (HR = 1.91; 95% CI = 1.30–2.80; HR = 1.83; 95% CI = 1.27–2.63, respectively). All genes that harbored these significant SNPs remained significant by whole-gene analysis.

Conclusion: Common genetic variations in genes of EGFR and glutathione pathways may be associated with overall survival among patients with advanced stage NSCLC treated with platinum, taxane, and/or gemicitabine combinations. Clin Cancer Res; 17(11); 3830–40. ©2011 AACR.
Prognostic and Predictive Role of Lactate Dehydrogenase 5 Expression in Colorectal Cancer Patients Treated with PTK787/ZK 222584 (Vatalanib) Antiangiogenic Therapy
Authors: Koukourakis Michael I. , Giatromanolaki Alexandra , Sivridis Efthimios , Gatter Kevin C. , Trarbach Tanja , Folprecht Gunnar , Shi Michael M. , Lebwohl David , Jalava Tarja , Laurent Dirk , Meinhardt Gerold , Harris Adrian L.
Published: June 2011

Purpose: The Colorectal Oral Novel therapy For the Inhibition of angiogenesis and Retarding of Metastases (CONFIRM)-randomized trials, investigating the role of the VEGF-receptor inhibitor PTK787/ZK 222584 (vatalanib) in colorectal cancer (FOLFOX 4 ± vatalanib), showed some benefit in patients with high serum lactate dehydrogenase (LDH) levels. Here, we investigated the expression of LDH5 (encoded entirely by the LDHA gene, regulated by the hypoxia inducible factors) in cancer tissues from patients recruited in the CONFIRM trials and relationship to response.

Experimental Design: Paraffin-embedded materials from 179 patients recruited in the CONFIRM trials were analyzed by immunohistochemistry for the expression of the LDH5 protein. Correlations with serum LDH, response, and survival were assessed.

Results: A significant association of tumor burden and of poor performance status (PS) with serum LDH was noted. Poor PS and high tumor LDH5 expression predicted for poor response rates. High tissue LDH5 was related to poor progression-free survival (PFS) only in the placebo group of patients, whereas the addition of vatalanib seemed to improved response and PFS in this subgroup. High serum LDH levels were linked with significantly poorer overall survival, which however was not sustained in multivariate analysis.

Conclusions: Serum LDH and tissue LDH5 levels are complementary features that help to characterize the activity of LDH in colorectal cancer and have a potent value in predicting response to chemotherapy. The addition of vatalanib diminished the impact of LDH expression on the prognosis of patients. Clin Cancer Res; 17(14); 4892–900. ©2011 AACR.
In Vivo Activity of Combined PI3K/mTOR and MEK Inhibition in a KrasG12D;Pten Deletion Mouse Model of Ovarian Cancer
Authors: Kinross Kathryn M. , Brown Daniel V. , Kleinschmidt Margarete , Jackson Susan , Christensen James , Cullinane Carleen , Hicks Rodney J. , Johnstone Ricky W. , McArthur Grant A.
Published: June 2011

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is commonly dysregulated in human cancer, making it an attractive target for novel anticancer therapeutics. We have used a mouse model of ovarian cancer generated by KrasG12D activation and Pten deletion in the ovarian surface epithelium for the preclinical assessment of a novel PI3K/mTOR inhibitor PF-04691502. To enable higher throughput studies, we developed an orthotopic primary transplant model from these mice and evaluated therapeutic response to PF-04691502 using small-animal ultrasound and FDG-PET imaging. PF-04691502 inhibited tumor growth at 7 days by 72% ± 9. FDG-PET imaging revealed that PF-04691502 reduced glucose metabolism dramatically, suggesting FDG-PET may be exploited as an imaging biomarker of target inhibition by PF-04691502. Tissue biomarkers of PI3K/mTOR pathway activity, p-AKT (S473), and p-RPS6 (S240/244), were also dramatically inhibited following PF-04691502 treatment. However, as a single agent, PF-04691502 did not induce tumor regression and the long-term efficacy was limited, with tumor proliferation continuing in the presence of drug treatment. We hypothesized that tumor progression was because of concomitant activation of the mitogen-activated protein kinase pathway downstream of KrasG12D expression promoting cell survival and that the therapeutic effect of PF-04691502 would be enhanced by combinatory inhibition of MEK using PD-0325901. This combination induced striking tumor regression, apoptosis associated with upregulation of Bim and downregulation of Mcl-1, and greatly improved duration of survival. These data suggest that contemporaneous MEK inhibition enhances the cytotoxicity associated with abrogation of PI3K/mTOR signaling, converting tumor growth inhibition to tumor regression in a mouse model of ovarian cancer driven by PTEN loss and mutant K-Ras. Mol Cancer Ther; 10(8); 1440–9. ©2011 AACR.
Clonal Structure of Carcinogen-Induced Intestinal Tumors in Mice
Authors: Thliveris Andrew T. , Clipson Linda , White Alanna , Waggoner Jesse , Plesh Lauren , Skinner Bridget L. , Zahm Christopher D. , Sullivan Ruth , Dove William F. , Newton Michael A. , Halberg Richard B.
Published: June 2011

Previous studies have shown that intestinal tumors from ApcMin/+ (Min) mice and familial adenomatous polyposis (FAP) patients are often polyclonal. We sought to determine whether polyclonality is unique to tumors arising from hereditary predispositions or, instead, is a common feature of intestinal tumorigenesis in other pathways to tumorigenesis. Ethylnitrosourea-induced intestinal tumors from mice wild type at the Apc locus and chimeric for the Rosa26 lineage marker were analyzed. Many were overtly polyclonal, being composed of a mixture of Rosa26+ and Rosa26− neoplastic cells. Statistical analyses revealed that polyclonality could be explained by interactions between two initiated clones separated by a very short distance. The frequency of overtly polyclonal tumors and the range of interactions estimated in this model are similar to those observed when analyzing familial tumors from Min mice. Thus, polyclonality does not depend on the familial pathway to tumorigenesis. Interactions between two initiated clones might provide a selective advantage during the early stages of intestinal tumorigenesis. Cancer Prev Res; 4(6); 916–23. ©2011 AACR.
Cancer Interception
Authors: Blackburn Elizabeth H.
Published: June 2011

A common perception is that cancer risk reduction is passive, such as not smoking. However, advances in the understanding of cancer biology and in cancer treatment modalities suggest that it is now timely to consider anew cancer risk reduction by active, including pharmacologic, approaches. Risk avoidance approaches are certainly important, but other approaches are important as well, as exemplified by the irony that most new lung cancers occur in former smokers, or current avoiders. Cancer interception is the active way of combating cancer and carcinogenesis at earlier and earlier stages. A great challenge is to educate people that the development of cancers, like heart disease, typically takes years and accordingly can potentially be intercepted with risk-reducing agents in the same way that advanced cancers can be treated with drugs or that cardiovascular disease can be intercepted with antihypertensive and other risk-reducing drugs. The cancer biology behind cancer interception is increasingly solid. For example, hedgehog pathway studies of mutations in the patched homolog 1 (PTCH1) gene, which constitutively activates Smoothened (SMO), led to development of an oral SMO inhibitor active in advanced basal cell carcinoma and which, in very high-risk Gorlin syndrome patients (germ line PTCH1 mutation), is nearly completely clinically effective in intercepting basal cell neoplasia. Also, the oral immunomodulator lenalidomide, first found to be active in advanced, relapsed multiple myeloma, was highly effective in intercepting the precursor stage, high-risk smoldering multiple myeloma from progressing. These are but two exciting, recent examples of the many advances in cancer research that have created an optimal time to discover and implement cancer interception. The multifaceted roles of telomere maintenance in both fueling advanced cancers and, at early stages, keeping them at bay, also highlight how the growing knowledge of cancer biology opens avenues for cancer interception. Emerging molecular techniques, including next-generation sequencing platforms, that account for a large part of the remarkable recent advances in cancer biology are now being applied to interception of premalignancy. Keeping the medical community and public at large informed about possibilities for actively intercepting cancer will be important for gaining acceptance of this increasingly powerful approach to lessening the cancer burden. Cancer Prev Res; 4(6); 787–92. ©2011 AACR.
Altered Histology Provides a Positive Clinical Signal in the Bronchial Epithelium
Authors: Szabo Eva
Published: June 2011

The history of lung cancer chemoprevention trials has been uniformly disappointing in that the large phase III studies showed no effect or harm in actively smoking participants, and smaller phase II studies have also been negative. In this issue of the journal (beginning on page 793), Keith and colleagues report their randomized, placebo-controlled trial of the oral prostacyclin analogue iloprost, the first trial to show an improvement in bronchial histology (i.e., regression), which occurred in former, but not current, smokers with sputum atypia. This Perspective discusses the strength of the clinical signal provided by this observation and its implications for further drug development. Cancer Prev Res; 4(6); 775–8. ©2011 AACR.
Response Gene to Complement 32 Promotes Vascular Lesion Formation Through Stimulation of Smooth Muscle Cell Proliferation and Migration
Authors: Wang Jia-Ning , Shi Ning , Xie Wei-Bing , Guo Xia , Chen Shi-You
Published: June 2011

Objective—

The objectives of this study were to determine the role of response gene to complement 32 (RGC-32) in vascular lesion formation after experimental angioplasty and to explore the underlying mechanisms.

Methods and Results—

Using a rat carotid artery balloon-injury model, we documented for the first time that neointima formation was closely associated with a significantly increased expression of RGC-32 protein. Short hairpin RNA knockdown of RGC-32 via adenovirus-mediated gene delivery dramatically inhibited the lesion formation by 62% as compared with control groups 14 days after injury. Conversely, RGC-32 overexpression significantly promoted the neointima formation by 33%. Gain- and loss-of-function studies in primary culture of rat aortic smooth muscle cells (RASMCs) indicated that RGC-32 is essential for both the proliferation and migration of RASMCs. RGC-32 induced RASMC proliferation by enhancing p34
CDC2
activity. RGC-32 stimulated the migration of RASMC by inducing focal adhesion contact and stress fiber formation. These effects were caused by the enhanced rho kinase II-α activity due to RGC-32-induced downregulation of Rad GTPase.

Conclusion—

RGC-32 plays an important role in vascular lesion formation following vascular injury. Increased RGC-32 expression in vascular injury appears to be a novel mechanism underlying the migration and proliferation of vascular smooth muscle cells. Therefore, targeting RGC-32 is a potential therapeutic strategy for the prevention of vascular remodeling in proliferative vascular diseases.
A Cost–Utility Analysis of Mechanical Thrombectomy as an Adjunct to Intravenous Tissue-Type Plasminogen Activator for Acute Large-Vessel Ischemic Stroke
Authors: Kim Anthony S. , Nguyen-Huynh Mai , Johnston S. Claiborne
Published: June 2011

Background and Purpose—

Mechanical thrombectomy has the potential to improve recanalization rates and outcomes for patients with ischemic stroke, but potential gains could be offset by procedural complications and costs. We evaluated the cost and utility of combined intravenous (IV) tissue-type plasminogen activator (tPA) and mechanical thrombectomy compared to IV tPA alone for acute large-vessel ischemic stroke.

Methods—

We constructed a decision tree for a hypothetical 68-year-old with a large-vessel ischemic stroke who is eligible for IV tPA. The interventional strategy was IV tPA, a cerebral angiogram, and mechanical thrombectomy and thrombolysis if indicated. Recanalization, hemorrhage complications, and outcomes for the interventional strategy were from the Multi-MERCI study. The medical strategy was IV tPA using inputs from a comprehensive systematic review. Costs were estimated from Medicare reimbursements. We modeled lifetime costs and utilities for disability using a Markov model and Monte-Carlo multivariable sensitivity analysis.

Results—

For the baseline scenario, the recanalization rate was 72.9% for the interventional strategy and 46.2% for the medical strategy. For the interventional strategy, the symptomatic hemorrhage rate was 8.6% with recanalization and 15.4% without. For the medical strategy, the corresponding rates were 3.6% and 13.3%, respectively. The interventional strategy was cost-effective in 97.6% of simulations (incremental cost-effectiveness ratio $16 001/quality-adjusted life year; 95% CI, $2736–$39 232).

Conclusions—

Based on observational data, the combination of IV tPA and mechanical thrombectomy for large-vessel ischemic stroke appears to be cost-effective compared to IV tPA alone. These findings require additional validation with randomized trial data.
Severity of Intraventricular Extension Correlates With Level of Admission Glucose After Intracerebral Hemorrhage
Authors: Appelboom Geoffrey , Piazza Matthew A. , Hwang Brian Y. , Carpenter Amanda , Bruce Samuel S. , Mayer Stephan , Connolly E. Sander
Published: June 2011

Background and Purpose—

Hyperglycemia after spontaneous intracerebral hemorrhage (ICH) is associated with poor outcome, but the pathophysiology of ICH-induced glucose dysregulation remains unclear. We sought to identify clinical and radiographic parameters of ICH that are associated with admission hyperglycemia.

Methods—

Patients admitted to the Columbia University Medical Center Neurological Intensive Care Unit with spontaneous ICH between January 2009 and September 2010 were prospectively enrolled in the ICH Outcomes Project. Clinical, radiographic, and laboratory data were collected prospectively. Receiver operating characteristic analysis was used to identify the glucose level with optimal sensitivity and specificity for in-hospital mortality. Logistic and linear regression analyses were used to identify independent predictors of outcome measures where appropriate.

Results—

One hundred four patients admitted during the study period were included in the analysis. Mean admission glucose level was 8.23±3.15 mmol/L (3.83 to 18.89 mmol/L) and 23.2% had a history of diabetes mellitus. Admission glucose was significantly associated with discharge (
P
=0.003) and 3-month mortality (
P
=0.002). Critical hyperglycemia defined at 10 mmol/L independently predicted discharge mortality (
P
=0.027; OR, 4.381; 95% CI, 1.186 to 16.174) and 3-month mortality (
P
=0.011; OR, 10.95; 95% CI, 1.886 to 62.41). Admission intraventricular extension score (
P
=0.038; OR, 1.117; 95% CI, 1.043 to 1.197) and diabetes mellitus (
P
=0.002; OR, 5.530; 95% CI, 1.833 to 16.689) were independent predictors of critical hyperglycemia. The intraventricular extension score (B=0.115,
P
=0.001) linearly correlated with admission glucose level (
R
=0.612,
P
=0.001) after adjusting for other clinical variables.

Conclusions—

Admission hyperglycemia after spontaneous ICH is associated with poor outcome and potentially related to the presence and severity of intraventricular extension.
Impact of White Matter Lesions on Physical Functioning and Fall Risk in Older People
Authors: Zheng Jacqueline J.J. , Delbaere Kim , Close Jacqueline C.T. , Sachdev Perminder S. , Lord Stephen R.
Published: June 2011

Background and Purpose—

White matter lesions (WMLs) are common findings on neuroimaging in older people. This review systematically evaluates the published literature on the associations between WMLs and balance, gait, mobility, and falls in older people.

Methods—

Studies were identified with searches of the MEDLINE databases. Articles reporting associations between WMLs and balance, gait, mobility, and falls in older people in cross-sectional and longitudinal studies were included.

Results—

Thirty-one articles reporting data from 19 studies met the inclusion criteria. There were consistent findings from both cross-sectional and longitudinal studies indicating greater WML volumes are associated with impaired balance, slower gait, and reduced mobility. Most studies addressing regional WML distributions have reported that WMHs in the frontal lobe and periventricular regions show the strongest relationships with balance, gait, and mobility impairments. In relation to falls, a threshold effect was apparent in that only those with severe WML volumes were found to be at increased risk of falling.

Conclusions—

The findings of this systematic review indicate that WMLs are common and are significantly associated with impaired balance, gait, mobility, and falls in older people. In many studies, however, impaired mobility and increased fall risk are only evident in people who have the most severe degree of WMLs.
Reliability and Validity of Bilateral Ankle Accelerometer Algorithms for Activity Recognition and Walking Speed After Stroke
Authors: Dobkin Bruce H. , Xu Xiaoyu , Batalin Maxim , Thomas Seth , Kaiser William
Published: June 2011

Background and Purpose—

Outcome measures of mobility for large stroke trials are limited to timed walks for short distances in a laboratory, step counters and ordinal scales of disability and quality of life. Continuous monitoring and outcome measurements of the type and quantity of activity in the community would provide direct data about daily performance, including compliance with exercise and skills practice during routine care and clinical trials.

Methods—

Twelve adults with impaired ambulation from hemiparetic stroke and 6 healthy controls wore triaxial accelerometers on their ankles. Walking speed for repeated outdoor walks was determined by machine-learning algorithms and compared to a stopwatch calculation of speed for distances not known to the algorithm. The reliability of recognizing walking, exercise, and cycling by the algorithms was compared to activity logs.

Results—

A high correlation was found between stopwatch-measured outdoor walking speed and algorithm-calculated speed (Pearson coefficient, 0.98;
P
=0.001) and for repeated measures of algorithm-derived walking speed (
P
=0.01). Bouts of walking >5 steps, variations in walking speed, cycling, stair climbing, and leg exercises were correctly identified during a day in the community. Compared to healthy subjects, those with stroke were, as expected, more sedentary and slower, and their gait revealed high paretic-to-unaffected leg swing ratios.

Conclusions—

Test–retest reliability and concurrent and construct validity are high for activity pattern-recognition Bayesian algorithms developed from inertial sensors. This ratio scale data can provide real-world monitoring and outcome measurements of lower extremity activities and walking speed for stroke and rehabilitation studies.
Isentropic Slopes, Downgradient Eddy Fluxes, and the Extratropical Atmospheric Circulation Response to Tropical Tropospheric Heating
Authors: Butler Amy H. , Thompson David W. J. , Birner Thomas
Published: June 2011

Climate change experiments run on Intergovernmental Panel on Climate Change (IPCC)–class numerical models consistently suggest that increasing concentrations of greenhouse gases will lead to a poleward shift of the midlatitude jets and their associated eddy fluxes of heat and potential vorticity (PV). Experiments run on idealized models suggest that the poleward contraction of the jets can be traced to the effects of increased latent heating and thus locally enhanced warming in the tropical troposphere. Here the authors provide new insights into the dynamics of the circulation response to tropical tropospheric heating using transient experiments in an idealized general circulation model.

It is argued that the response of the midlatitude jets to tropical heating is driven fundamentally by 1) the projection of the heating onto the meridional slope of the lower tropospheric isentropic surfaces, and 2) a diffusive model of the eddy fluxes of heat and PV. In the lower and middle troposphere, regions where the meridional slope of the isentropes (i.e., the baroclinicity) is increased are marked by anomalously poleward eddy fluxes of heat, and vice versa. Near the tropopause, regions where the meridional gradients in PV are increased are characterized by anomalously equatorward eddy fluxes of PV, and vice versa. The barotropic component of the response is shown to be closely approximated by the changes in the lower-level heat fluxes. As such, the changes in the eddy fluxes of momentum near the tropopause appear to be driven primarily by the changes in wave generation in the lower troposphere.
Ice in Clouds Experiment—Layer Clouds. Part I: Ice Growth Rates Derived from Lenticular Wave Cloud Penetrations
Authors: Heymsfield Andrew J. , Field Paul R. , Bailey Matt , Rogers Dave , Stith Jeffrey , Twohy Cynthia , Wang Zhien , Haimov Samuel
Published: June 2011

Lenticular wave clouds are used as a natural laboratory to estimate the linear and mass growth rates of ice particles at temperatures from −20° to −32°C and to characterize the apparent rate of ice nucleation at water saturation at a nearly constant temperature. Data are acquired from 139 liquid cloud penetrations flown approximately along or against the wind direction. A mean linear ice growth rate of about 1.4 μm s−1, relatively independent of particle size (in the range 100–400 μm) and temperature is deduced. Using the particle size distributions measured along the wind direction, the rate of increase in the ice water content (IWC) is calculated from the measured particle size distributions using theory and from those distributions by assuming different ice particle densities; the IWC is too small to be measured. Very low ice effective densities, <0.1 g cm−3, are needed to account for the observed rate of increase in the IWC and the unexpectedly high linear growth rate.

Using data from multiple penetrations through a narrow (along wind) and thin wave cloud with relatively flat airflow streamlines, growth rate calculations are used to estimate where the ice particles originate and whether the ice is nucleated in a narrow band or over an extended period of time. The calculations are consistent with the expectation that the ice formation occurs near the leading cloud edge, presumably through a condensation–freezing process. The observed ice concentration increase along the wind is more likely due to a variation in ice growth rates than to prolonged ice nucleation.
Spectrally Invariant Approximation within Atmospheric Radiative Transfer
Authors: Marshak A. , Knyazikhin Y. , Chiu J. C. , Wiscombe W. J.
Published: June 2011

Certain algebraic combinations of single scattering albedo and solar radiation reflected from, or transmitted through, vegetation canopies do not vary with wavelength. These “spectrally invariant relationships” are the consequence of wavelength independence of the extinction coefficient and scattering phase function in vegetation. In general, this wavelength independence does not hold in the atmosphere, but in cloud-dominated atmospheres the total extinction and total scattering phase function vary only weakly with wavelength. This paper identifies the atmospheric conditions under which the spectrally invariant approximation can accurately describe the extinction and scattering properties of cloudy atmospheres. The validity of the assumptions and the accuracy of the approximation are tested with 1D radiative transfer calculations using publicly available radiative transfer models: Discrete Ordinate Radiative Transfer (DISORT) and Santa Barbara DISORT Atmospheric Radiative Transfer (SBDART). It is shown for cloudy atmospheres with cloud optical depth above 3, and for spectral intervals that exclude strong water vapor absorption, that the spectrally invariant relationships found in vegetation canopy radiative transfer are valid to better than 5%. The physics behind this phenomenon, its mathematical basis, and possible applications to remote sensing and climate are discussed.
Evaluation of WRF Parameterizations for Climate Studies over Southern Spain Using a Multistep Regionalization
Authors: Argüeso Daniel , Hidalgo-Muñoz José M. , Gámiz-Fortis Sonia R. , Esteban-Parra María Jesús , Dudhia Jimy , Castro-Díez Yolanda
Published: June 2011

This paper evaluates the Weather Research and Forecasting model (WRF) sensitivity to eight different combinations of cumulus, microphysics, and planetary boundary layer (PBL) parameterization schemes over a topographically complex region in southern Spain (Andalusia) for the period 1990–99. The WRF configuration consisted of a 10-km-resolution domain nested in a coarser domain driven by 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40) data, with spectral nudging above the PBL employed over the latter domain. The model outputs have been compared at different time scales with an observational dataset that comprises 438 rain gauges and 152 temperature stations with records of both daily maximum and minimum temperatures. To reduce the “representation error,” the validation with observations has been performed using a multistep regionalization that distinguishes five precipitation regions and four temperature regions.

The analysis proves that both cumulus and PBL schemes have a crucial impact on the description of precipitation in Andalusia, whereas no noticeable differences between microphysics options were appreciated. Temperature is described similarly by all the configurations, except for the PBL choice affecting minimum values.

WRF provides a definite improvement over ERA-40 in the climate description in terms of frequency, spatial distribution, and intensity of extreme events. It also captures more accurately the annual cycle and reduces the biases and the RMSE for monthly precipitation, whereas only a minor enhancement of these features was obtained for monthly-mean maximum and minimum temperatures. The results indicate that WRF is able to correctly reproduce Andalusian climate and produces useful added-value information for climate studies.
Seasonal Variation of Surface Temperature Change during the Last Several Decades
Authors: Manabe Syukuro , Ploshay Jeffrey , Lau Ngar-Cheung
Published: June 2011

Using the historical surface temperature dataset compiled by Climatic Research Unit of the University of East Anglia and the Hadley Centre of the United Kingdom, this study examines the seasonal and latitudinal profile of the surface temperature change observed during the last several decades. It reveals that the recent change in zonal-mean surface air temperature is positive at practically all latitudes. In the Northern Hemisphere, the warming increases with increasing latitude and is large in the Arctic Ocean during much of the year except in summer, when it is small. At the Antarctic coast and in the northern part of the circumpolar ocean (near 55°S), where limited data are available, the changes appear to be small during most seasons, though the warming is notable at the coast in winter. However, this warming is much less than the warming over the Arctic Ocean. The seasonal variation of the surface temperature change appears to be broadly consistent with the result from a global warming experiment that was conducted some time ago using a coupled atmosphere–ocean–land model.
Deep Signatures of Southern Tropical Indian Ocean Annual Rossby Waves*
Authors: Johnson Gregory C.
Published: June 2011

The southern tropical Indian Ocean contains a striking forced annual Rossby wave studied previously using satellite altimeter sea surface height data, surface wind fields, expendable bathythermograph ocean temperature data, and models. Here, the deep reach of this wave and its velocity are analyzed using density–depth profiles and 1000-dbar horizontal drift data from Argo. Significant annual cycles in isopycnal vertical displacements and zonal velocity persist to the deepest pressures to which Argo data can be mapped reliably in the region, 1600–1900 dbar. Phase propagation of the annual cycle of the directly measured zonal velocities at 1000 dbar suggests a zonal wavelength of about 6000 km—about the length of the deep basin in which the wave is found—and a westward phase speed of ~0.2 m s−1. Apparent upward phase propagation in isopycnal vertical displacements suggests energy propagation downward into the abyss. This pattern is clearer when accounting for both the potential and kinetic energy of the wave. The largest zonal current associated with this wave has a middepth maximum that decays rapidly up through the pycnocline and less rapidly with increasing depth, suggesting a first-vertical-mode structure. The anomalous zonal volume transport of this annually reversing current is ~27 × 106 m3 s−1 across 80°E in mid-November. The peak zonal velocity of 0.06 m s−1 implies a maximum zonal excursion of about 600 km associated with the wave over an annual cycle.
Assessments of Chinese Fengyun Microwave Temperature Sounder (MWTS) Measurements for Weather and Climate Applications
Authors: Zou X. , Wang X. , Weng F. , Li G.
Published: June 2011

After the successful launches of the first two polar-orbiting satellites in a new Fengyun-3 (FY-3) series, FY-3A/B, into a morning- and afternoon-configured orbit in May 2008 and November 2010, respectively, China will launch its next three polar-orbiting satellites before 2020. The Microwave Temperature Sounder (MWTS) on the FY-3A/B satellites has four channels that have the same channel frequency as channels 3, 5, 7, and 9 of Advanced Microwave Sounding Unit-A (AMSU-A). Thus, the quality of the brightness temperature measurements from the FY-3A MWTS can be assessed using the AMSU-A brightness temperature observations from the NOAA-18 satellite. Overall, MWTS data compare favorably with AMSU-A data in terms of its global bias to NWP simulations. The standard deviations of global MWTS brightness temperatures are slightly larger than those of AMSU-A data. The scan-angle dependence of the brightness temperature bias is found to be symmetric for MWTS channel 3 as well as AMSU-A channel 7, and asymmetric for MWTS channels 2 and 4 and AMSU-A channels 5 and 9; there is a warm (cold) bias located at the beginning (end) of a scan line for all asymmetric channels except for MWTS channel 4. A major difference between the two instruments is that the MWTS biases in channels 3 and 4 are negative in low latitudes and positive in high latitudes, while the AMSU-A biases are negative in all latitudes. A detailed analysis of the data reveals that such a difference is closely related to the difference in the temperature dependence of biases between the two instruments. The AMSU-A biases are independent of the scene temperature, but MWTS biases vary with the earth scene brightness temperature. The root cause of the bias could be a combination of several factors, including solar contamination on its calibration target, detector nonlinearity, and the center frequency drift. This study further demonstrates the utility of a well-calibrated radiometer like AMSU-A for the assessment of a new instrument with NWP fields that are used as inputs to forward radiative transfer simulations.