bluuebunny/crossref_metadata_2025 huggingface dataset:
The Form of the Solutions and Periodicity of Some Systems of Difference Equations
Authors: Mansour M. , El-Dessoky M. M. , Elsayed E. M.
Published: August 2012

This paper is devoted to get the form of the solutions and the periodic nature of the following systems of rational difference equations xn+1 = xn−5/(−1 + xn−5yn−2),   yn+1 = yn−5/(±1 ± yn−5xn−2), where the initial conditions are real numbers.
On Some Lacunary Almost Convergent Double Sequence Spaces and Banach Limits
Authors: Başarır Metin , Konca Şükran
Published: August 2012

The object of this paper is to introduce some new sequence spaces
related with the concept of lacunary strong almost convergence for double sequences and also to characterize these spaces through sublinear functionals that
both dominate and generate Banach limits and to establish some inclusion
relations.
A Hybrid Multiobjective Evolutionary Approach for Flexible Job‐Shop Scheduling Problems
Authors: Xiong Jian , Tan Xu , Yang Ke-wei , Xing Li-ning , Chen Ying-wu
Published: August 2012

This paper addresses multiobjective flexible job‐shop scheduling problem (FJSP) with three simultaneously considered objectives: minimizing makespan, minimizing total workload, and minimizing maximal workload. A hybrid multiobjective evolutionary approach (H‐MOEA) is developed to solve the problem. According to the characteristic of FJSP, a modified crowding distance measure is introduced to maintain the diversity of individuals. In the proposed H‐MOEA, well‐designed chromosome representation and genetic operators are developed for FJSP. Moreover, a local search procedure based on critical path theory is incorporated in H‐MOEA to improve the convergence ability of the algorithm. Experiment results on several well‐known benchmark instances demonstrate the efficiency and stability of the proposed algorithm. The comparison with other recently published approaches validates that H‐MOEA can obtain Pareto‐optimal solutions with better quality and/or diversity.
A Mixed Prediction Model of Ground Subsidence for Civil Infrastructures on Soft Ground
Authors: Kobayashi Kiyoshi , Kaito Kiyoyuki
Published: August 2012

The estimation of ground subsidence processes is an important subject for the asset management of civil infrastructures on soft ground, such as airport facilities. In the planning and design stage, there exist many uncertainties in geotechnical conditions, and it is impossible to estimate the ground subsidence process by deterministic methods. In this paper, the sets of sample paths designating ground subsidence processes are generated by use of a one‐dimensional consolidation model incorporating inhomogeneous ground subsidence. Given the sample paths, the mixed subsidence model is presented to describe the probabilistic structure behind the sample paths. The mixed model can be updated by the Bayesian methods based upon the newly obtained monitoring data. Concretely speaking, in order to estimate the updating models, Markov Chain Monte Calro method, which is the frontier technique in Bayesian statistics, is applied. Through a case study, this paper discussed the applicability of the proposed method and illustrated its possible application and future works.
Prevention of LPS-Induced Acute Lung Injury in Mice by Progranulin
Authors: Guo Zhongliang , Li Qinchuan , Han Yang , Liang Yongjie , Xu Zengguang , Ren Tao
Published: August 2012

The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, few therapeutic strategies for clinical ARDS have emerged. Here we carefully evaluated the effect of progranulin (PGRN) in treatment of ARDS using the murine model of lipopolysaccharide (LPS)-induced ALI. We reported that administration of PGRN maintained the body weight and survival of ALI mice. We revealed that administration of PGRN significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in bronchoalveolar lavage (BAL) fluid. Furthermore, administration of PGRN resulted in remarkable reversal of LPS-induced increases in lung permeability as assessed by reductions in total protein, albumin, and IgM in BAL fluid. Consistently, we revealed a significant reduction of histopathology changes of lung in mice received PGRN treatment. Finally, we showed that PGRN/TNFR2 interaction was crucial for the protective effect of PGRN on the LPS-induced ALI. Our findings strongly demonstrated that PGRN could effectively ameliorate the LPS-induced ALI in mice, suggesting a potential application for PGRN-based therapy to treat clinical ARDS.
ROS in AgingCaenorhabditis elegans: Damage or Signaling?
Authors: Back Patricia , Braeckman Bart P. , Matthijssens Filip
Published: August 2012

Many insights into the mechanisms and signaling pathways underlying aging have resulted from research on the nematodeCaenorhabditis elegans. In this paper, we discuss the recent findings that emerged using this model organism concerning the role of reactive oxygen species (ROS) in the aging process. The accrual of oxidative stress and damage has been the predominant mechanistic explanation for the process of aging for many years, but reviewing the recent studies inC. eleganscalls this theory into question. Thus, it becomes more and more evident that ROS are not merely toxic byproducts of the oxidative metabolism. Rather it seems more likely that tightly controlled concentrations of ROS and fluctuations in redox potential are important mediators of signaling processes. We therefore discuss some theories that explain how redox signaling may be involved in aging and provide some examples of ROS functions and signaling inC. elegansmetabolism. To understand the role of ROS and the redox status in physiology, stress response, development, and aging, there is a rising need for accurate and reversiblein vivodetection. Therefore, we comment on some methods of ROS and redox detection with emphasis on the implementation of genetically encoded biosensors inC. elegans.
International Market Orientation and Management Capabilities as Determinants of the New Ventures’ International Behaviour
Authors: Monferrer Diego , Blesa Andreu , Ripollés María
Published: August 2012

The main research objectives of this paper are the analysis of the influence of international market orientation and the management capabilities derived from that orientation on international new ventures’ (INVs) behavior. Foreign market geographical diversification and the commitment involved in entry modes are considered to reflect this international behavior. Thus existing International Entrepreneurship literature is developed by analyzing the behavior of INVs explaining and testing how international market orientation and management capabilities affect geographical diversification and the commitment involved in entry modes. The empirical study confirms this influence.
The Use of Cubic Splines in the Numerical Solution of Fractional Differential Equations
Authors: Zahra W. K. , Elkholy S. M.
Published: August 2012

Fractional calculus became a vital tool in describing many phenomena appeared in physics, chemistry as well as engineering fields. Analytical solution of many applications, where the fractional differential equations appear, cannot be established. Therefore, cubic polynomial spline-function-based method combined with shooting method is considered to find approximate solution for a class of fractional boundary value problems (FBVPs). Convergence analysis of the method is considered. Some illustrative examples are presented.
Subarachnoid versus General Anesthesia in Penile Prosthetic Implantation: Outcomes Analyses
Authors: Henry Gerard D. , Saccà Antonino , Eisenhart Elizabeth , Cleves Mario A. , Kramer Andrew C.
Published: August 2012

The leading patient complaint during the perioperative period for penile prosthesis implantation is postoperative pain, while emesis and urticaria also affect the procedure’s perceived success. In analyzing surgical outcomes, assessment of the anesthetic for postoperative pain and side effects should be included. This paper retrospectively reviews 90 consecutive, primary inflatable penile prosthetic operations performed by a single surgeon at one private medical center. Fifty-seven patients were included in final analysis. Patients who had more than one procedure that day or who used chronic pain medication were excluded. The type and amount of each drug used for each respective side effect (within the first 24 hours after procedure) were compared to determine relative benefit. Twenty patients received general anesthesia (denoted herein as “GA”) and 37 received spinal (or also known as subarachnoid) anesthesia (denoted herein as “SA”). Patients receiving GA had significantly greater (P<0.0001) occurrence and amount of intravenous pain treatment than those receiving SA. Patients with SA required less intravenous pain medication and less treatment for nausea/emesis.
The Solution of a Coupled Nonlinear System Arising in a Three-Dimensional Rotating Flow Using Spline Method
Authors: Pandya Jigisha U.
Published: August 2012

The behavior of the non-linear-coupled systems arising in axially symmetric hydromagnetics flow between two horizontal plates in a rotating system is analyzed, where the lower is a stretching sheet and upper is a porous solid plate. The equations of conservation of mass and momentum are transformed to a system of coupled nonlinear ordinary differential equations. These equations for the velocity field are solved numerically by using quintic spline collocation method. To solve the nonlinear equation, quasilinearization technique has been used. The numerical results are presented through graphs, in which the effects of viscosity, through flow, magnetic flux, and rotational velocity on velocity field are discussed.
Recursive Feature Selection with Significant Variables of Support Vectors
Authors: Tsai Chen-An , Huang Chien-Hsun , Chang Ching-Wei , Chen Chun-Houh
Published: August 2012

The development of DNA microarray makes researchers screen thousands of genes simultaneously and it also helps determine high- and low-expression level genes in normal and disease tissues. Selecting relevant genes for cancer classification is an important issue. Most of the gene selection methods use univariate ranking criteria and arbitrarily choose a threshold to choose genes. However, the parameter setting may not be compatible to the selected classification algorithms. In this paper, we propose a new gene selection method (SVM-t) based on the use oft-statistics embedded in support vector machine. We compared the performance to two similar SVM-based methods: SVM recursive feature elimination (SVMRFE) and recursive support vector machine (RSVM). The three methods were compared based on extensive simulation experiments and analyses of two published microarray datasets. In the simulation experiments, we found that the proposed method is more robust in selecting informative genes than SVMRFE and RSVM and capable to attain good classification performance when the variations of informative and noninformative genes are different. In the analysis of two microarray datasets, the proposed method yields better performance in identifying fewer genes with good prediction accuracy, compared to SVMRFE and RSVM.
The Common C49620T Polymorphism in the Sulfonylurea Receptor Gene SUR1 (ABCC8) in Patients with Gestational Diabetes and Subsequent Glucose Metabolism Abnormalities
Authors: Molęda Piotr , Bińczak-Kuleta Agnieszka , Homa Katarzyna , Safranow Krzysztof , Celewicz Zbigniew , Syrenicz Anhelli , Stefański Adam , Fronczyk Aneta , Majkowska Lilianna
Published: August 2012

Aim. The aim of this study is to investigate the relationship between the common C49620T polymorphism in the sulfonylurea receptor (SUR1) gene and glucose metabolism,β-cell secretory function and insulin resistance in women with a history of gestational diabetes (GDM).Material and Methods. Study group included 199 women, diagnosed GDM within the last 5–12 years and control group of comparable 50 women in whom GDM was excluded during pregnancy. Blood glucose and insulin levels were measured during oral glucose tolerance test. Indices of insulin resistance (HOMA-IR) andβ-cell function (HOMA %B) were calculated. In all patients, the C49620T polymorphism in intron 15 of the SUR1 gene was determined.Results. The distribution of the studied polymorphism in the two groups did not differ from each other (χ2= 0.34,P=0.8425). No association between the distribution of polymorphisms and coexisting glucose metabolism disorders (χ2= 7,13,P=0,3043) was found. No association was also observed between the polymorphism and HOMA %B or HOMA-IR.Conclusions. The polymorphism C49620T in the SUR1 gene is not associated with insulin resistance and/or insulin secretion in women with a history of GDM and does not affect the development of GDM, or the development of glucose intolerance in the studied population.
On a Family of High‐Order Iterative Methods under Kantorovich Conditions and Some Applications
Authors: Amat S. , Bermúdez C. , Busquier S. , Legaz M. J. , Plaza S.
Published: August 2012

This paper is devoted to the study of a class of high‐order iterative
methods for nonlinear equations on Banach spaces. An analysis of
the convergence under Kantorovich‐type conditions is proposed. Some
numerical experiments, where the analyzed methods present better behavior
than some classical schemes, are presented. These applications
include the approximation of some quadratic and integral equations.
Pituitary Apoplexy Associated with Endocrine Stimulation Test: Endocrine Stimulation Test, Treatment, and Outcome
Authors: Yamamoto Takahiro , Yano Shigetoshi , Kuroda Jun-ichiro , Hasegawa Yu , Hide Takuichiro , Kuratsu Jun-ichi
Published: August 2012

Pituitary apoplexy is a rare clinical syndrome attributable to hemorrhage or hemorrhagic infarction of pituitary tumors or pituitary glands. The features of pituitary apoplexy associated with the endocrine stimulation test remain to be elucidated and the importance of surgical treatment has not been discussed enough. We report two rare patients who were treated successfully by endoscopic endonasal transsphenoidal surgery within several hours after onset of pituitary apoplexy associated with the endocrine stimulation test. Their postoperative course was uneventful. We reviewed earlier reports on this clinical entity, document its features especially as related to the endocrine stimulation test, discuss the significance of immediate surgical treatment, and present our treatment outcomes. Performing only conservative treatment is not recommended. We suggest that the necessity of endocrine stimulation test should be assessed on a case-by-case basis and in patients subjected to the test, and neurosurgical support should be sought.
Global Attractivity of a Higher‐Order Difference Equation
Authors: Abo-Zeid R.
Published: August 2012

The aim of this work is to investigate the global stability, periodic nature, oscillation, and the boundedness of all admissible solutions of the difference equation where A, B, C are positive real numbers and l, r, k are nonnegative integers, such that l ≤ k.
On Upper and Lower -Continuous Multifunctions
Authors: Boonpok Chawalit
Published: August 2012

A new class of multifunctions, called upper (lower) -continuous multifunctions, has been defined and studied. Some characterizations and several properties concerning upper (lower) -continuous multifunctions are obtained. The relationships between upper (lower) -continuous multifunctions and some known concepts are also discussed.
Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction fromCaryocar brasilienseCamb. Leaves in Rat Thoracic Aorta
Authors: Oliveira Lais Moraes de , Rodrigues Aline Gabriela , Silva Elaine Fernanda da , Cerqueira Letícia Bonancio , Castro Carlos Henrique , Pedrino Gustavo Rodrigues , Carvalho Maria Helena Catelli de , Pontarolo Roberto , Costa Elson Alves , Campos Francinete Ramos , Filgueira Fernando Paranaiba , Ghedini Paulo César
Published: August 2012

Caryocar brasilienseCamb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) ofC. brasilienseleaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal thatC. brasiliensepossesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway.
Vaccination with Enzymatically Cleaved GPI-Anchored Proteins fromSchistosoma mansoniInduces Protection against Challenge Infection
Authors: Martins Vicente P. , Pinheiro Carina S. , Figueiredo Barbara C. P. , Assis Natan R. G. , Morais Suellen B. , Caliari Marcelo V. , Azevedo Vasco , Castro-Borges William , Wilson R. Alan , Oliveira Sergio C.
Published: August 2012

The flatwormSchistosoma mansoniis a blood fluke parasite that causes schistosomiasis, a debilitating disease that occurs throughout the developing world. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control schistosomiasis is through immunization with an antischistosomiasis vaccine combined with drug treatment. In the search for potential vaccine candidates, numerous tegument antigens have been assessed. As the major interface between parasite and mammalian host, the tegument plays crucial roles in the establishment and further course of schistosomiasis. Herein, we evaluated the potential of a GPI fraction, containing representative molecules located on the outer surface of adult worms, as vaccine candidate. Immunization of mice with GPI-anchored proteins induced a mixed Th1/Th2 type of immune response with production of IFN-γand TNF-α, and low levels of IL-5 into the supernatant of splenocyte cultures. The protection engendered by this vaccination protocol was confirmed by 42% reduction in worm burden, 45% reduction in eggs per gram of hepatic tissue, 29% reduction in the number of granulomas per area, and 53% reduction in the granuloma fibrosis. Taken together, the data herein support the potential of surface-exposed GPI-anchored antigens from theS. mansonitegument as vaccine candidate.
Fabrication and Evaluation of Large Area Mo/Si Soft X-Ray Multilayer Mirrors at Indus SR Facilities
Authors: Rao P. N. , Nayak Maheswar , Lodha G. S. , Rai S. K. , Srivastava A. K. , Modi M. H. , Sagdeo A.
Published: August 2012

Large area Mo/Si multilayer (ML) mirrors with high reflectivity are fabricated using magnetron sputtering deposition system. Thin film growth is optimized for film roughness, density, and interface quality by changing process parameters through fabrication of thin films. Mo/Si MLs are fabricated with varying thickness ratio, number of layer pairs, and periodicity from 0.3 to 0.45, 5 to 65, and 40 to 100 Å, respectively. The samples are characterized using hard X-ray reflectivity and transmission electron microscopy. Soft X-ray performance tests of MLs are done by soft X-ray reflectivity using Indus-1 synchrotron radiation. ML coating with thickness errors of ~0.03% per layer and interface roughness in the range of 2 to 5 Å has been realized. The lateral variation of the periodicity is controlled within 0.5 Å over the  mm2 area of the plane substrate by using substrate motion and appropriate masking arrangement. Maximum variation of periodicity from run to run is less than 0.5 Å. Peak reflectivity of ~63% at wavelength of ~127 Å is achieved for incident angle of 71 degree.
The Pancreas Cancer Microenvironment
Authors: Feig Christine , Gopinathan Aarthi , Neesse Albrecht , Chan Derek S. , Cook Natalie , Tuveson David A.
Published: August 2012

Pancreatic ductal adenocarcinoma (PDA) is a common and lethal malignancy resulting in more than 250,000 deaths per year worldwide. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for patients with PDA to date. One contributing factor to the failure of systemic therapies may be the abundant tumor stromal content that is the characteristic of PDA. The PDA stroma, aptly termed the tumor microenvironment, occupies the majority of the tumor mass, and consists of a dynamic assortment of extracellular matrix components and nonneoplastic cells including fibroblastic, vascular, and immune cells. Recent work has revealed that the PDA stroma supports tumor growth and promotes metastasis and simultaneously serves as a physical barrier to drug delivery. Accordingly, methods that alter stromal composition or function, for instance interference with the vasculature via Notch/Hedgehog pathway inhibition or relief of vascular compression by hyaluronidase, are under active investigation. Here, we will review our current understanding of the PDA tumor microenvironment, and highlight opportunities for further exploration that may benefit patients. Clin Cancer Res; 18(16); 4266–76. ©2012 AACR.
A Phase I Dose-Finding Trial of Recombinant Interleukin-21 and Rituximab in Relapsed and Refractory Low Grade B-cell Lymphoproliferative Disorders
Authors: Timmerman John M. , Byrd John C. , Andorsky David J. , Yamada Reiko E. , Kramer Janet , Muthusamy Natarajan , Hunder Naomi , Pagel John M.
Published: August 2012

Purpose: We conducted a phase I study to determine the safety, maximum-tolerated dose (MTD), and efficacy of weekly bolus recombinant human interleukin-21 (rIL-21) plus rituximab in patients with indolent B-cell malignancies.

Experimental Design: One week after a lead-in rituximab dose, cohorts of three patients were treated with 30, 100, or 150 μg/kg rIL-21 weekly for four weeks, concurrent with four weekly doses of rituximab. Patients with stable disease or better were eligible for a second course of therapy.

Results: Twenty-one patients with relapsed small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL, n = 11), follicular lymphoma (n = 9), or marginal zone lymphoma (n = 1) were enrolled, with 19 completing at least one course of therapy. The MTD for rIL-21 was 100 μg/kg, based on observed toxicities including nausea, vomiting, diarrhea, hypotension, edema, and hypophosphatemia. Clinical responses were seen in 8 of 19 evaluable patients (42%; 3 CR/CRu, 5 PR), with 4 of longer duration than the patient's previous response to rituximab-based treatment (median 9 months vs. 3 months).

Conclusions: Outpatient therapy of indolent B-cell malignancies with rituximab and weekly rIL-21 was well tolerated and clinically active, with durable complete remissions in a small subset of patients. Additional studies of rIL-21 and anti-CD20 antibodies in lymphoma and SLL/CLL are warranted. Clin Cancer Res; 18(20); 5752–60. ©2012 AACR.
Macrophages Promote Fibroblast Growth Factor Receptor-Driven Tumor Cell Migration and Invasion in a Cxcr2-Dependent Manner
Authors: Bohrer Laura R. , Schwertfeger Kathryn L.
Published: August 2012

Infiltration of immune cells, specifically macrophages, into the tumor microenvironment has been linked to increased mammary tumor formation and progression. Activation of growth factor receptor signaling pathways within mammary epithelial cells, such as the fibroblast growth factor receptor 1 (FGFR1) pathway, induces recruitment of macrophages to the mammary epithelium. These macrophages promote increased epithelial cell proliferation and angiogenesis. However, the specific mechanisms by which these macrophages are regulated by the preneoplastic epithelial cells and the mechanisms of action of the macrophages within the developing FGFR1-driven tumor microenvironment remain unknown. In this study, we show that activation of inducible FGFR1 in mammary glands leads to decreased activity of the TGFβ/Smad3 pathway in macrophages associated with early stage lesions. Further studies show that macrophages have increased expression of inflammatory chemokines that bind Cxcr2 following exposure to conditioned media from mammary epithelial and tumor cells in which the FGF pathway had been activated. The increase in these ligands is inhibited following activation of the TGFβ pathway, suggesting that decreased TGFβ signaling contributes to the upregulation of these chemokines. Using coculture studies, we further show that macrophages are capable of promoting epithelial and tumor cell migration and invasion through activation of Cxcr2. These results indicate that macrophage-derived Cxcr2 ligands may be important for promoting mammary tumor formation regulated by FGFR signaling. Furthermore, these results suggest that targeting Cxcr2 may represent a novel therapeutic strategy for breast cancers that are associated with high levels of infiltrating macrophages. Mol Cancer Res; 10(10); 1294–305. ©2012 AACR.
Consumption of Nonfat Milk Results in a Less Atherogenic Lipoprotein Profile: A Pilot Study
Authors: Hidaka Hiroya , Takiwaki Masaki , Yamashita Mine , Kawasaki Kenji , Sugano Mitsutoshi , Honda Takayuki
Published: August 2012

Background: An increase in plasma low-density lipoprotein (LDL) is a well-known risk factor in the development of atherosclerosis. Dairy consumption may lower the risk of atherosclerosis; however, studies on the effects of milk on cardiovascular risk factors are still scarce. We were interested in investigating whether the intake of milk improves the atherogenic lipoprotein profile. Aims: We investigated the effects of consuming whole or nonfat milk on plasma lipoprotein composition in healthy Japanese subjects as a pilot study. Methods: Normolipidemic subjects consumed 500 ml of whole milk (whole milk group; n = 7) or nonfat milk (nonfat milk group; n = 7) every day for 2 weeks. Results: The consumption of nonfat milk resulted in a lowering of plasma triglyceride (TG) and phospholipid levels and TG level in high-density lipoprotein (HDL) and increased the plasma apolipoprotein (apo) C-III level. In addition, the TG/cholesterol ratios in HDL and LDL were significantly decreased, and LDL particles became larger. In contrast, the only changes observed following whole milk consumption were increases in the plasma levels of apoC-III and apoE. Conclusions: These findings suggest that consumption of nonfat milk, but not whole milk, may result in a less atherogenic lipoprotein profile, and that the constituents of nonfat milk may improve lipid metabolism.
Renal Replacement Therapy in Patients with Severe Precapillary Pulmonary Hypertension with Acute Right Heart Failure
Authors: Sztrymf Benjamin , Prat Dominique , Jacobs Frédéric M. , Brivet François G. , O'Callaghan Dermot S. , Price Laura C. , Jais Xavier , Sitbon Olivier , Simonneau Gérald , Humbert Marc
Published: August 2012

Background: Renal replacement therapy has been suggested as a therapeutic option in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension. However, there are few data supporting this strategy. Objectives: To describe the clinical course and the prognosis of pulmonary hypertensive patients undergoing renal replacement therapy in the setting of acute right heart failure. Methods: This was a single-center retrospective study over an 11-year period. Data were collected from all patients with chronic precapillary pulmonary hypertension requiring catecholamine infusions for clinical worsening and acute kidney injury that necessitated renal replacement therapy. Results: Fourteen patients were included. At admission, patients had a blood urea of 28.2 mmol/l (22.3-41.2), a creatinine level of 496 µmol/l (304-590), and a mean urine output in the 24 h preceding hospitalization of 200 ml (0-650). Sixty-eight renal replacement therapy sessions were performed, 36 of which were continuous and 32 of which were intermittent. Systemic hypotension occurred in 16/32 intermittent and 16/36 continuous sessions (p = 0.9). Two patients died during a continuous session. The intensive care unit-related, 1-, and 3-month mortality was 46.7, 66.7, and 73.3%, respectively. Conclusion: Renal replacement therapy is feasible in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension but is associated with a poor prognosis. The best modality and timing in this population remain to be defined.
A Phase I Clinical Trial of Irinotecan and Carboplatin in Patients with Extensive Stage Small Cell Lung Cancer
Authors: Crabb Simon J. , Bradbury Jennifer , Nolan Luke , Selman Diana , Muthuramalingam Sethupathi R. , Cave Judith , Johnson Peter W.M. , Ottensmeier Christian
Published: August 2012

Background: Treatment options for small cell lung cancer (SCLC) remain inadequate. Irinotecan has been tested in various combinations with platinum agents but the optimal regimen remains uncertain. We undertook a phase I trial to optimise the dose intensity of a 3-weekly irinotecan/carboplatin combination. Methods: Twenty patients with extensive stage SCLC received intravenous carboplatin at an area under the curve (AUC) of 5 on day 1, and irinotecan in 40–70 mg/m2 dose levels on days 1 and 8, every 21 days, for up to 6 cycles. Results: Dose-limiting toxicity occurred in 1 patient at the 50 mg/m2 irinotecan level (grade 3 diarrhoea) and in 2 patients at 70 mg/m2 (grade 5 neutropenic sepsis; combined grade 4 febrile neutropenia, grade 4 diarrhoea and grade 3 thrombosis). Toxicity patterns were consistent with the expected profile for this combination. The objective response rate was 75% and the median survival was 9.3 months (95% confidence interval 7.5–11.2). Conclusion: Irinotecan 60 mg/m2 on days 1 and 8 combined with carboplatin AUC 5 every 21 days is recommended for phase II evaluation. This regimen has clinical activity, acceptable toxicity and greater dose intensity over those currently tested in phase III trials.
Wolbachia Induced Cytogenetical Effects as Evidenced in Chorthippus parallelus (Orthoptera)
Authors: Sarasa J. , Bernal A. , Fernández-Calvín B. , Bella J.L.
Published: August 2012

The cytoplasmic incompatibility induced by the bacterial endosymbiont Wolbachia is attributed to chromatin modification in the sperm of infected individuals and is only ‘rescued’ by infected females after fertilization. Chorthippus parallelus is a grasshopper with 2 subspecies that form a hybrid zone in the Pyrenees in which this Wolbachia-generated cytoplasmic incompatibility has recently been described. The analysis of certain cytogenetic traits (sex chromosome-linked heterochromatic bands, nucleolar organizing region expression, spermatid size and morphology, and number of chiasmata formed) in pure and hybrid Chorthippus parallelus that are infected and not infected by this bacterium indicates that the infection affects some of these traits and, in the case of the spermatids, reveals a synergism between the infection and the hybrid condition. These results are interpreted as being secondary effects of the chromatin modification induced by Wolbachia which thereby support this model of modification/rescue. The possible effects of these cytogenetic variations on affected individuals are also considered.
Targeting the Consequences of the Metabolic Syndrome in the Diabetes Prevention Program
Authors: Goldberg Ronald B. , Mather Kieren
Published: August 2012

This review describes the effect of lifestyle change or metformin compared with standard care on incident type 2 diabetes and cardiometabolic risk factors in the Diabetes Prevention Program and its Outcome Study. The Diabetes Prevention Program was a randomized controlled clinical trial of intensive lifestyle and metformin treatments versus standard care in 3234 subjects at high risk for type 2 diabetes. At baseline, hypertension was present in 28% of subjects, and 53% had metabolic syndrome with considerable variation in risk factors by age, sex, and race. Over 2.8 years, type 2 diabetes incidence fell by 58% and 31% in the lifestyle and metformin groups, respectively, and metabolic syndrome prevalence fell by one-third with lifestyle change but was not reduced by metformin. In placebo- and metformin-treated subjects, the prevalence of hypertension and dyslipidemia increased during the Diabetes Prevention Program, whereas lifestyle intervention slowed these increases significantly. During long-term follow-up using modified interventions, type 2 diabetes incidence decreased to ≈5% per year in all groups. This was accompanied by significant improvement in cardiovascular disease risk factors over time in all treatment groups, in part associated with increasing use of lipid-lowering and antihypertensive medications. Thus a program of lifestyle change significantly reduced type 2 diabetes incidence and metabolic syndrome prevalence in subjects at high risk for type 2 diabetes. Metformin had more modest effects.
Insulin Resistance: Metabolic Mechanisms and Consequences in the Heart
Authors: Abel E. Dale , O’Shea Karen M. , Ramasamy Ravichandran
Published: August 2012

Insulin resistance is a characteristic feature of obesity and type 2 diabetes mellitus and impacts the heart in various ways. Impaired insulin-mediated glucose uptake is a uniformly observed characteristic of the heart in these states, although changes in upstream kinase signaling are variable and dependent on the severity and duration of the associated obesity or diabetes mellitus. The understanding of the physiological and pathophysiological role of insulin resistance in the heart is evolving. To maintain its high energy demands, the heart is capable of using many metabolic substrates. Although insulin signaling may directly regulate cardiac metabolism, its main role is likely the regulation of substrate delivery from the periphery to the heart. In addition to promoting glucose uptake, insulin regulates long-chain fatty acid uptake, protein synthesis, and vascular function in the normal cardiovascular system. Recent advances in understanding the role of metabolic, signaling, and inflammatory pathways in obesity have provided opportunities to better understand the pathophysiology of insulin resistance in the heart. This review will summarize our current understanding of metabolic mechanisms for and consequences of insulin resistance in the heart and will discuss potential new areas for investigating novel mechanisms that contribute to insulin resistance in the heart.
ABO Blood Group and Risk of Coronary Heart Disease in Two Prospective Cohort Studies
Authors: He Meian , Wolpin Brian , Rexrode Kathy , Manson JoAnn E. , Rimm Eric , Hu Frank B. , Qi Lu
Published: August 2012

Objective—

Epidemiological data regarding the association between ABO blood groups and risk of coronary heart disease (CHD) have been inconsistent. We sought to investigate the associations between ABO blood group and CHD risk in prospective cohort studies.

Methods and Results—

Two large, prospective cohort studies (the Nurses’ Health Study [NHS] including 62 073 women and the Health Professionals Follow-up Study [HPFS] including 27 428 men) were conducted with more than 20 years of follow-up (26 years in NHS and 24 years in HPFS). A meta-analysis was performed to summarize the associations from the present study and previous studies. In NHS, during 1 567 144 person-years of follow-up, 2055 participants developed CHD; in HPFS, 2015 participants developed CHD during 517 312 person-years of follow-up. ABO blood group was significantly associated with the risk of developing CHD in both women and men (log-rank test;
P
=0.0048 and 0.0002, respectively). In the combined analysis adjusted for cardiovascular risk factors, compared with participants with blood group O, those with blood groups A, B, or AB were more likely to develop CHD (adjusted hazard ratios [95% CI] for incident CHD were 1.06 [0.99–1.15], 1.15 [1.04–1.26], and 1.23 [1.11–1.36], respectively). Overall, 6.27% of the CHD cases were attributable to inheriting a non-O blood group. Meta-analysis indicated that non-O blood group had higher risk of CHD (relative risk =1.11; 95% CI, 1.05–1.18;
P
=0.001) compared with O blood group.

Conclusion—

These data suggest that ABO blood group is significantly associated with CHD risk. Compared with other blood groups, those with the blood type O have moderately lower risk of developing CHD.
Cardiac Resynchronization Therapy in Patients With Permanent Atrial Fibrillation
Authors: Healey Jeff S. , Hohnloser Stefan H. , Exner Derek V. , Birnie David H. , Parkash Ratika , Connolly Stuart J. , Krahn Andrew D. , Simpson Chris S. , Thibault Bernard , Basta Magdy , Philippon Francois , Dorian Paul , Nair Girish M. , Sivakumaran Soori , Yetisir Elizabeth , Wells George A. , Tang Anthony S.L.
Published: August 2012

Background—

Cardiac resynchronization (CRT) prolongs survival in patients with systolic heart failure and QRS prolongation. However, most trials excluded patients with permanent atrial fibrillation.

Methods and Results—

The Resynchronization for Ambulatory Heart Failure Trial (RAFT) randomized patients to an implantable cardioverter defibrillator (ICD) or ICD+CRT, stratified by the presence of permanent atrial fibrillation. Patients with permanent atrial fibrillation were randomized to CRT-ICD (n=114) or ICD (n=115). Patients receiving a CRT-ICD were similar to those receiving an ICD: age (71.6±7.3 versus 70.4±7.7 years), left ventricular ejection fraction (22.9±5.3% versus 22.3±5.1%), and QRS duration (151.0±23.6 versus 153.4±24.7 ms). There was no difference in the primary outcome of death or heart failure hospitalization between those assigned to CRT-ICD versus ICD (hazard ratio, 0.96; 95% CI, 0.65–1.41;
P
=0.82). Cardiovascular death was similar between treatment arms (hazard ratio, 0.97; 95% CI, 0.55–1.71;
P
=0.91); however, there was a trend for fewer heart failure hospitalizations with CRT-ICD (hazard ratio, 0.58; 95% CI, 0.38–1.01;
P
=0.052). The change in 6-minute hall walk duration between baseline and 12 months was not different between treatment arms (CRT-ICD: 19±84 m versus ICD: 16±76 m;
P
=0.88). Patients treated with CRT-ICD showed a trend for a greater improvement in Minnesota Living with Heart Failure score between baseline and 6 months (CRT-ICD: 41±21 to 31±21; ICD: 33±20 to 28±20;
P
=0.057).

Conclusions—

Patients with permanent atrial fibrillation who are otherwise CRT candidates appear to gain minimal benefit from CRT-ICD compared with a standard ICD.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00251251.
Overexpression of Endothelial Nitric Oxide Synthase Prevents Diet-Induced Obesity and Regulates Adipocyte Phenotype
Authors: Sansbury Brian E. , Cummins Timothy D. , Tang Yunan , Hellmann Jason , Holden Candice R. , Harbeson Matthew A. , Chen Yang , Patel Rakesh P. , Spite Matthew , Bhatnagar Aruni , Hill Bradford G.
Published: August 2012

Rationale:

Endothelial dysfunction is a characteristic feature of diabetes and obesity in animal models and humans. Deficits in nitric oxide production by endothelial nitric oxide synthase (eNOS) are associated with insulin resistance, which is exacerbated by high-fat diet. Nevertheless, the metabolic effects of increasing eNOS levels have not been studied.

Objective:

The current study was designed to test whether overexpression of eNOS would prevent diet-induced obesity and insulin resistance.

Methods and Results:

In
db/db
mice and in high-fat diet-fed wild-type C57BL/6J mice, the abundance of eNOS protein in adipose tissue was decreased without significant changes in eNOS levels in skeletal muscle or aorta. Mice overexpressing eNOS (eNOS transgenic mice) were resistant to diet-induced obesity and hyperinsulinemia, although systemic glucose intolerance remained largely unaffected. In comparison with wild-type mice, high-fat diet-fed eNOS transgenic mice displayed a higher metabolic rate and attenuated hypertrophy of white adipocytes. Overexpression of eNOS did not affect food consumption or diet-induced changes in plasma cholesterol or leptin levels, yet plasma triglycerides and fatty acids were decreased. Metabolomic analysis of adipose tissue indicated that eNOS overexpression primarily affected amino acid and lipid metabolism; subpathway analysis suggested changes in fatty acid oxidation. In agreement with these findings, adipose tissue from eNOS transgenic mice showed higher levels of PPAR-
α
and PPAR-
γ
gene expression, elevated abundance of mitochondrial proteins, and a higher rate of oxygen consumption.

Conclusions:

These findings demonstrate that increased eNOS activity prevents the obesogenic effects of high-fat diet without affecting systemic insulin resistance, in part, by stimulating metabolic activity in adipose tissue.
STIM1 Restores Coronary Endothelial Function in Type 1 Diabetic Mice
Authors: Estrada Irene A. , Donthamsetty Reshma , Debski Patryk , Zhou Meng-Hua , Zhang Shenyuan L. , Yuan Jason X.-J. , Han Wenlong , Makino Ayako
Published: August 2012

Rationale:

The endoplasmic reticulum (ER) is a major intracellular Ca
2+
store in endothelial cells (ECs). The Ca
2+
concentration in the ER greatly contributes to the generation of Ca
2+
signals that regulate endothelial functions. Many proteins, including stromal interaction molecule 1/2 (STIM1/2), Orai1/2/3, and sarcoplasmic/endoplasmic reticulum Ca
2+
-ATPase 3 (SERCA3), are involved in the ER Ca
2+
refilling after store depletion in ECs.

Objective:

This study is designed to examine the role of Ca
2+
in the ER in coronary endothelial dysfunction in diabetes.

Methods and Results:

Mouse coronary ECs (MCECs) isolated from diabetic mice exhibited (1) a significant decrease in the Ca
2+
mobilization from the ER when the cells were treated by SERCA inhibitor, and (2) significant downregulation of STIM1 and SERCA3 protein expression in comparison to the controls. Overexpression of STIM1 restored (1) the increase in cytosolic Ca
2+
concentration due to Ca
2+
leak from the ER in diabetic MCECs, (2) the Ca
2+
concentration in the ER, and (3) endothelium-dependent relaxation that was attenuated in diabetic coronary arteries.

Conclusions:

Impaired ER Ca
2+
refilling in diabetic MCECs, due to the decrease in STIM1 protein expression, attenuates endothelium-dependent relaxation in diabetic coronary arteries, while STIM1 overexpression has a beneficial and therapeutic effect on coronary endothelial dysfunction in diabetes.
A Novel Sonification Strategy for Auditory Display of Heart Rate and Oxygen Saturation Changes in Clinical Settings
Authors: Janata Petr , Edwards William H.
Published: August 2012

Objective:

The aim of this study was development of a sonification scheme to convey deviations in heart rate and oxygen saturation from a desired target level.

Background:

Maintaining physiologic parameters, such as oxygen saturation, within desired ranges, is challenging in many clinical situations. High rates of false positive alarms in clinical settings limit the utility of the alarms that trigger when thresholds are exceeded. Auditory displays that consider the semantic connotations of sounds and the processing limitations of human perception and cognition may improve monitoring.

Method:

Across two experiments, clinical practi-tioners were tested on their ability to (a) discriminate pairs of sounds (two-note discrimination task), (b) infer and discern the intended physiological connotation of each acoustic attribute (name-the-variable task), and (c) categorize the amount of change in an implied physiological variable into three levels of change: none, small, and large (change-magnitude task).

Results:

Considerable variation in performance was observed across the set of practitioners, ranging from near-perfect performance on all tasks, even with no prior exposure to the stimuli, to failure to reach a target accuracy criterion of 87.5% after ~80 min of training. On average, performance was well above chance on the name-the-variable and change-magnitude tasks during initial exposure and reached criterion within ~20 min of training on each task.

Conclusion:

The described sonification strategy may effectively communicate information about current heart rate and oxygen saturation status relative to desired target levels.

Application:

The results can be applied to clinical monitoring settings in which a stream of discrete auditory informational items is indicated.
Disjunctures and diaspora in Kiran Desai’s The Inheritance of Loss
Authors: Sabo Oana
Published: August 2012

In The Inheritance of Loss, Kiran Desai juxtaposes underprivileged diasporic subjects in India and the USA in both the colonial past and the global present, thereby challenging its readers to develop a larger perspective on historical and global power asymmetries and minority struggles for recognition. She uses a fragmentary structure that shifts across time and space to suggest that immigration and diaspora are predicated on a rift between home and host land. I argue that in her novel, diaspora represents both a socio-political formation and a narrative strategy that underscores socio-economic inequalities in the world and invites readers to think critically about immigration and global capitalism. In blending aesthetic and material concerns, Desai departs from theories of diaspora and cosmopolitanism that tend to privilege hybridity and mobility. By narrating the experiences of cross-ethnic diasporas in the context of global capitalism, Desai expands the generic boundaries of Indian diasporic writing in English.
Electromechanical analysis of length-related resistance and contact resistance of conductive knitted fabrics
Authors: Li Li , Liu Song , Ding Feng , Hua Tao , Au Wai Man , Wong Kwok-Shing
Published: August 2012

Conductive fabrics usually exhibit two types of electrical resistance: the length-related resistance and contact resistance. The length-related resistance increases with the applied extensile force, whereas the contact resistance decreases with the contact force. The resistance of conductive knitted fabrics could be modeled by the superposition of the length-related resistance and contact resistance. Three experiments were conducted to investigate the resistance of conductive yarns: two overlapped conduct yarns and conductive knitting stitches under unidirectional extensile forces, respectively; and the corresponding empirical equations were developed. The relationship of the resistance, tensile force, fabric length and width were established. The fitting curves with high coefficient of determinations (>0.94) and low standard errors (<0.18) given by the modeling equations were achieved. Therefore, the proposed model could be used to compute the resistance of the conductive knitting fabrics under unidirectional extension.