bluuebunny/crossref_metadata_2025 huggingface dataset:
Control System Analysis and Design Via the “Second Method” of Lyapunov: II—Discrete-Time Systems
Authors: Kalman R. E. , Bertram J. E.
Published: November 2011

The second method of Lyapunov is applied to the study of discrete-time (sampled-data) systems. With minor variations, the discussion parallels that of the companion paper on continuous-time systems. Theorems are stated in full but motivation, proofs, examples, and so on, are given only when they differ materially from their counterparts in the continuous-time case.
Use of the Moire´ Effect to Measure Plastic Strains
Authors: Vinckier A. , Dechaene R.
Published: November 2011

A method is described which should prove useful in the study of strain distribution in a metallic member during plastic deformation. Regularly spaced lines are drawn on a test specimen of interest and on a glass plate. After exposure to strain the part is photographed through the grid of lines on the glass. The strain distortion on the part results in an interference pattern from which the amount of plastic deformation may be calculated.
Steady Creep of a Tube Under Combined Bending and Internal Pressure
Authors: Finnie Iain
Published: November 2011

It is shown that for a tube in bending the steady-state bending creep rate may be greatly increased by the addition of internal pressure. If the maximum bending stress is small compared to the pressure stress, a very simple expression is obtained for the ratio of bending creep rates with and without internal pressure. Experiments on lead tubes show good agreement with the theory.
The Response of a Pressure-Sensing System
Authors: Benedict R. P.
Published: November 2011

A first-order, first-degree, linear expression is developed to describe the transient behavior of a practical pressure-sensing system. The development is in terms of usual fluid-flow parameters. An experiment is described whereby the transient behavior is determined for a variety of pressure-sensing systems. Experimental uncertainties are determined. Comparisons are drawn between several published expressions, the proposed linear expression, and the experimental data reported herein, to indicate the validity of the proposed expression. Selected references to related work are given.
Incidence and Deviation-Angle Correlations for Compressor Cascades
Authors: Lieblein Seymour
Published: November 2011

An analysis is presented for the variation of low-speed, minimum-loss, incidence angle and deviation angle for compressor-cascade blades. The aerodynamics governing the behavior of these angles is discussed, and the principal influencing parameters are established. A single general relation is obtained for predicting these angles for conventional sections such as the British C-series blades, the double circular-arc blade, and the NACA 65-series blades when the latter blade sections are expressed in terms of an equivalent circular-arc chamber line. The specific constants associated with each blade shape are derived from the available data.
A Study of Boundary-Layer Characteristics of Turbomachine Blade Rows and Their Relation to Over-All Blade Loss
Authors: Stewart Warner L. , Whitney Warren J. , Wong Robert Y.
Published: November 2011

This paper presents the results of a number of investigations concerned with the boundary-layer characteristics of turbomachine blade rows and their relation to the over-all blade loss. It is demonstrated how the over-all blade loss can be obtained from the momentum boundary-layer thickness. The momentum boundary-layer thickness is in turn shown to be correlated by flow Reynolds number and total blade surface diffusion. By assuming Zweifel’s form of blade-loading diagram the total blade surface diffusion parameter can be determined as a function of blade solidity and reaction across the blade row. Thus, this type of loss analysis enables an approximate predetermination of the over-all blade row loss as derived from fundamental boundary-layer concepts. In addition, it shows the effect on over-all blade loss of varying such design features as solidity and reaction.
Heat-Transfer Characteristics of Hot-Film Sensing Element Used in Flow Measurement
Authors: Ling S. C.
Published: November 2011

The static and dynamic heat-transfer characteristics of several forms of hot-film element, used in flow measurement, are herein presented. These characteristics are defined in terms of external heat-transfer resistance and internal heat-transfer impedance, and from these terms the frequency response of a probe element is derived.
The Quadrant Edge Orifice—A Fluid Meter for Low Reynolds Numbers
Authors: Bogema M. , Monkmeyer P. L.
Published: November 2011

Tests have been conducted to determine the usefulness of the quadrant edge orifice as a fluid-metering device for low Reynolds number flow. As a result of numerous laboratory tests to determine the behavior of the discharge coefficient with changing Reynolds number, the following are discussed: The range of constant discharge coefficient, reproducibility of orifice plates, diameter ratio effects, upstream roughness effects, reinstallation effects, and effects of pressure tap location.
Control of Oil Whip Frequency Ratio
Authors: Hull E. H.
Published: November 2011

Experiments described in this paper show that a rotatable intermediate sleeve in a journal bearing will change the average oil film velocity and hence can be made to control oil whip frequency. This device should allow oil whip frequency control of shafts running at two or more times their critical speed.
An Effect of Air Content on the Occurrence of Cavitation
Authors: Holl J. W.
Published: November 2011

The simultaneous occurrence of vaporous and gaseous cavitation on hydrofoils is considered. The experimental results show that gaseous cavitation occurs at much higher ambient pressures than that for the vaporous cavitation resulting in desinent-cavitation numbers twice the minimum-pressure coefficient of the hydrofoil. The analysis indicates that the difference between the desinent-cavitation number for the gaseous cavitation and that for the vaporous cavitation is proportional to the dissolved air content and inversely proportional to the square of the velocity.
Charging effects during focused electron beam induced deposition of silicon oxide
Authors: de Boer Sanne K. , van Dorp Willem F. , De Hosson Jeff Th. M.
Published: November 2011

This paper concentrates on focused electron beam induced deposition of silicon oxide. Silicon oxide pillars are written using 2, 4, 6, 8, 10-pentamethyl-cyclopenta-siloxane (PMCPS) as precursor. It is observed that branching of the pillar occurs above a minimum pillar height. The branching is attributed to charging of the deposit by the electron beam. The branching can be suppressed by introducing water into the chamber together with PMCPS. At the same time, the cointroduction of water results in a higher growth rate, which is found to be specific to PMCPS.
In Vivo
Comparison of CXA-101 (FR264205) with and without Tazobactam versus Piperacillin-Tazobactam Using Human Simulated Exposures against Phenotypically Diverse Gram-Negative Organisms
Authors: Bulik Catharine C. , Tessier Pamela R. , Keel Rebecca A. , Sutherland Christina A. , Nicolau David P.
Published: November 2011

CXA-101 is a novel antipseudomonal cephalosporin with enhanced activity against Gram-negative organisms displaying various resistance mechanisms. This study evaluates the efficacy of exposures approximating human percent free time above the MIC (%fT > MIC) of CXA-101 with or without tazobactam and piperacillin-tazobactam (TZP) against target Gram-negative organisms, including those expressing extended-spectrum β-lactamases (ESBLs). Sixteen clinical Gram-negative isolates (6
Pseudomonas aeruginosa
isolates [piperacillin-tazobactam MIC range, 8 to 64 μg/ml], 4
Escherichia coli
isolates (2 ESBL and 2 non-ESBL expressing), and 4
Klebsiella pneumoniae
isolates (3 ESBL and 1 non-ESBL expressing) were used in an immunocompetent murine thigh infection model. After infection, groups of mice were administered doses of CXA-101 with or without tazobactam (2:1) designed to approximate the %fT > MIC observed in humans given 1 g of CXA-101 with or without tazobactam every 8 h as a 1-h infusion. As a comparison, groups of mice were administered piperacillin-tazobactam doses designed to approximate the %fT > MIC observed in humans given 4.5 g piperacillin-tazobactam every 6 h as a 30-min infusion. Predicted piperacillin-tazobactam %fT > MIC exposures of greater than 40% resulted in static to >1 log decreases in CFU in non-ESBL-expressing organisms with MICs of ≤32 μg/ml after 24 h of therapy. Predicted CXA-101 with or without tazobactam %fT > MIC exposures of ≥37.5% resulted in 1- to 3-log-unit decreases in CFU in non-ESBL-expressing organisms, with MICs of ≤16 μg/ml after 24 h of therapy. With regard to the ESBL-expressing organisms, the inhibitor combinations showed enhanced CFU decreases versus CXA-101 alone. Due to enhanced
in vitro
potency and resultant increased
in vivo
exposure, CXA-101 produced statistically significant reductions in CFU in 9 isolates compared with piperacillin-tazobactam. The addition of tazobactam to CXA-101 produced significant reductions in CFU for 7 isolates compared with piperacillin-tazobactam. Overall, human simulated exposures of CXA-101 with or without tazobactam demonstrated improved efficacy versus piperacillin-tazobactam.
The
spiFEG
Locus in Streptococcus infantarius subsp. infantarius BAA-102 Confers Protection against Nisin U
Authors: Draper Lorraine A. , Tagg John R. , Hill Colin , Cotter Paul D. , Ross R. Paul
Published: November 2011

Nisin U is a member of the extended nisin family of lantibiotics. Here we identify the presence of nisin U immunity gene homologues in
Streptococcus infantarius
subsp.
infantarius
BAA-102. Heterologous expression of these genes in
Lactococcus lactis
subsp.
cremoris
HP confers protection to nisin U and other members of the nisin family, thereby establishing that the recently identified phenomenon of resistance through immune mimicry also occurs with respect to nisin.
Experiential and rational decision making: a survey to determine how emergency physicians make clinical decisions
Authors: Calder Lisa A , Forster Alan J , Stiell Ian G , Carr Laura K , Brehaut Jamie C , Perry Jeffrey J , Vaillancourt Christian , Croskerry Patrick
Published: November 2011

Background

Dual-process psychological theories argue that clinical decision making is achieved through a combination of experiential (fast and intuitive) and rational (slower and systematic) cognitive processes.

Objective

To determine whether emergency physicians perceived their clinical decisions in general to be more experiential or rational and how this compared with other physicians.

Methods

A validated psychometric tool, the Rational Experiential Inventory (REI-40), was sent through postal mail to all emergency physicians registered with the College of Physicians and Surgeons of Ontario, according to their website in November 2009. Forty statements were ranked on a Likert scale from 1 (Definitely False) to 5 (Definitely True). An initial survey was sent out, followed by reminder cards and a second survey to non-respondents. Analysis included descriptive statistics, Student t tests, analysis of variance and comparison of mean scores with those of cardiologists from New Zealand.

Results

The response rate in this study was 46.9% (434/925). The respondents' median age was 41–50 years; they were mostly men (72.6%) and most had more than 10 years of clinical experience (66.8%). The mean REI-40 rational scores were higher than the experiential scores (3.93/5 (SD 0.35) vs 3.33/5 (SD 0.49), p<0.0001), similar to the mean scores of cardiologists from New Zealand (mean rational 3.93/5, mean experiential 3.05/5). The mean experiential scores were significantly higher for female respondents than for male respondents (3.40/5 (SD 0.49) vs 3.30/5 (SD 0.48), p=0.003).

Conclusions

Overall, emergency physicians favoured rational decision making rather than experiential decision making; however, female emergency physicians had higher experiential scores than male emergency physicians. This has important implications for future knowledge translation and decision support efforts among emergency physicians.
Introgressive hybridization among major Columbia River Chinook salmon (Oncorhynchus tshawytscha) lineages within the Klickitat River due to hatchery practices
Authors: Hess Jon E. , Matala Andrew P. , Zendt Joseph S. , Frederiksen Chris R. , Sharp Bill , Narum Shawn R.
Published: November 2011

Major lineages of anadromous salmonids show resilience to natural introgressive hybridization; however, Klickitat River spring-run Chinook salmon (KRSC, Oncorhynchus tshawytscha ) have an enigmatic origin because of their intermediate genetic and geographic relationship among Columbia River Chinook salmon lineages. We used computer simulations to evaluate four anthropogenic and natural processes as likely causes of the apparent introgressed genetic composition of KRSC: recent admixture (∼5 generations), historical admixture (>200 generations), isolation-by-distance gene flow, and natural selection. We also genotyped 2413 fish (32 collections) across 96 single nucleotide polymorphism loci to clarify the relationship of KRSC among the three major Columbia River lineages (Lower Columbia and interior ocean- and stream-types) and to quantify introgression among collections. Between 1980 and 2000, we observed a decline of pure interior stream-type individuals in the KRSC collections. This temporal shift in genetic composition was coincident with relevant changes in hatchery practices. Based on results from the simulations and time-series samples, a recent and anthropogenically caused admixture was most likely responsible for introgression of KRSC. Potential long-term negative effects of introgression may require some form of mitigation.
Genetic diversity of the Bambara groundnut (Vigna subterranea(L.) Verdc.) as assessed by SSR markers
Authors: Somta P. , Chankaew S. , Rungnoi O. , Srinives P.
Published: November 2011

Bambara groundnut ( Vigna subterranea (L.) Verdc.) is an important African legume crop. In this study, a collection consisting of 240 accessions was analyzed using 22 simple sequence repeat (SSR) markers. In total, 166 alleles were detected, with a mean of 7.59 alleles per locus. Allelic and gene diversities were higher in the west African and Cameroon/Nigeria regions with 6.68 and 6.18 alleles per locus, and 0.601 and 0.571, respectively. The genetic distance showed high similarity between west African and Cameroon/Nigeria accessions. Principal coordinate analyses and neighbor-joining analysis consistently revealed that the majority of west African accessions were grouped with Cameroon/Nigeria accessions, but they were differentiated from east African, central African, and southeast Asian accessions. Population structure analysis showed that two subpopulations existed, and most of the east African accessions were restricted to one subpopulation with some Cameroon/Nigeria accessions, whereas most of the west African accessions were associated with most of the Cameroon/Nigeria accessions in the other subpopulation. Comparison with SSR analysis of other Vigna cultigens, i.e., cultivated azuki bean ( Vigna angularis ) and mungbean ( Vigna radiata ), reveals that the mean gene diversity of Bambara groundnut was lower than azuki bean but higher than mungbean.
Ecosystem management and forestry planning in Labrador: how does Aboriginal involvement affect management plans?
Authors: Wyatt Stephen , Merrill Stephanie , Natcher David
Published: November 2011

Aboriginal peoples are increasingly being invited to participate in sustainable forest management processes as a means of including their knowledge, values, and concerns. However, it is justifiable to ask if this participation does lead to changes in forest management plans and to outcomes in management activities. We review four forest management plans over 10 years (1999–2009) in Labrador, Canada, to determine if increasing involvement by the Aboriginal Innu Nation has led to changes in plan content. We also compare these plans with three plans from another forest management district where there is no Innu presence and with two provincial forest strategies . Analysis shows that Labrador plans prepared since 2000, when the Innu and the provincial government established a collaborative process, are different from all other plans reviewed. Four principal characteristics distinguish these plans: a structure based around ecological, cultural, and economic landscapes, a network of cultural and ecological protected areas, increased attention to social and cultural values, and greater emphasis on research and monitoring. This suggests that Innu involvement has in fact influenced the contents of these plans, developing an innovative approach to implementing ecosystem management and demonstrating the utility of involving Aboriginal peoples in forest management planning processes.
A Dynamic Inflammatory Cytokine Network in the Human Ovarian Cancer Microenvironment
Authors: Kulbe Hagen , Chakravarty Probir , Leinster D. Andrew , Charles Kellie A. , Kwong Joseph , Thompson Richard G. , Coward Jermaine I. , Schioppa Tiziana , Robinson Stephen C. , Gallagher William M. , Galletta Laura , Salako Michael A. , Smyth John F. , Hagemann Thorsten , Brennan Donal J. , Bowtell David D. , Balkwill Frances R.
Published: November 2011

Constitutive production of inflammatory cytokines is a characteristic of many human malignant cell lines; however, the in vitro and in vivo interdependence of these cytokines, and their significance to the human cancer microenvironment, are both poorly understood. Here, we describe for the first time how three key cytokine/chemokine mediators of cancer-related inflammation, TNF, CXCL12, and interleukin 6, are involved in an autocrine cytokine network, the “TNF network,” in human ovarian cancer. We show that this network has paracrine actions on angiogenesis, infiltration of myeloid cells, and NOTCH signaling in both murine xenografts and human ovarian tumor biopsies. Neutralizing antibodies or siRNA to individual members of this TNF network reduced angiogenesis, myeloid cell infiltration, and experimental peritoneal ovarian tumor growth. The dependency of network genes on TNF was shown by their downregulation in tumor cells from patients with advanced ovarian cancer following the infusion of anti-TNF antibodies. Together, the findings define a network of inflammatory cytokine interactions that are crucial to tumor growth and validate this network as a key therapeutic target in ovarian cancer. Cancer Res; 72(1); 66–75. ©2011 AACR.
Multiple Myeloma Mesenchymal Stem Cells: Characterization, Origin, and Tumor-Promoting Effects
Authors: Reagan Michaela R. , Ghobrial Irene M.
Published: November 2011

Hematologic malignancies rely heavily on support from host cells through a number of well-documented mechanisms. Host cells, specifically mesenchymal stem cells (MSC), support tumor cell growth, metastasis, survival, bone marrow colonization, and evasion of the immune system. In multiple myeloma, similar to solid tumors, supporting cells have typically been considered healthy host cells. However, recent evidence reveals that many MSCs derived from patients with multiple myeloma (MM-MSC) show significant defects compared with MSCs from nondiseased donors (ND-MSC). These abnormalities range from differences in gene and protein expression to allelic abnormalities and can initiate after less than 1 day of coculture with myeloma cells or persist for months, perhaps years, after removal from myeloma influence. Alterations in MM-MSC function contribute to disease progression and provide new therapeutic targets. However, before the scientific community can capitalize on the distinctions between MM-MSCs and ND-MSCs, a number of confusions must be clarified, as we have done in this review, including the origin(s) of MM-MSCs, identification and characterization of MM-MSCs, and downstream effects and feedback circuits that support cancer progression. Further advances require more genetic analysis of MM-MSCs and disease models that accurately represent MSC-MM cell interactions. Clin Cancer Res; 18(2); 342–9. ©2011 AACR.
Activation of Androgen Receptor, Lipogenesis, and Oxidative Stress Converged by SREBP-1 Is Responsible for Regulating Growth and Progression of Prostate Cancer Cells
Authors: Huang Wen-Chin , Li Xiangyan , Liu Jian , Lin Jentai , Chung Leland W.K.
Published: November 2011

We previously reported that sterol regulatory element-binding protein-1 (SREBP-1) is involved in the transcriptional regulation of androgen receptor (AR) and formation of fatty acid through altered expression of fatty acid synthase (FASN). In this article, we provide a new finding that SREBP-1 induced oxidative stress in prostate cancer cells through increased production of reactive oxygen species (ROS) and expression of NADPH oxidase 5 (Nox5). We have shown that (i) expression of SREBP-1 protein is positively associated with the clinical Gleason grades in human prostate cancer; (ii) genetic overexpression or knockdown of SREBP-1 in prostate cancer cells resulted in corresponding increased or decreased AR, FASN and Nox5 expression, fatty acid and lipid droplet accumulation, and ROS generation; and (iii) SREBP-1 induces and promotes the growth, migration, invasion, and castration-resistant progression of prostate cancer cells in vitro and in vivo. Our data show a novel molecular mechanism by which SREBP-1 promotes prostate cancer growth and progression through alterations in the concerted intracellular metabolic and signaling networks involving AR, lipogenesis, and ROS in prostate cancer cells. Mol Cancer Res; 10(1); 133–42. ©2011 AACR.
High-Throughput Detection of Actionable Genomic Alterations in Clinical Tumor Samples by Targeted, Massively Parallel Sequencing
Authors: Wagle Nikhil , Berger Michael F. , Davis Matthew J. , Blumenstiel Brendan , DeFelice Matthew , Pochanard Panisa , Ducar Matthew , Van Hummelen Paul , MacConaill Laura E. , Hahn William C. , Meyerson Matthew , Gabriel Stacey B. , Garraway Levi A.
Published: November 2011

Knowledge of “actionable” somatic genomic alterations present in each tumor (e.g., point mutations, small insertions/deletions, and copy-number alterations that direct therapeutic options) should facilitate individualized approaches to cancer treatment. However, clinical implementation of systematic genomic profiling has rarely been achieved beyond limited numbers of oncogene point mutations. To address this challenge, we utilized a targeted, massively parallel sequencing approach to detect tumor genomic alterations in formalin-fixed, paraffin-embedded (FFPE) tumor samples. Nearly 400-fold mean sequence coverage was achieved, and single-nucleotide sequence variants, small insertions/deletions, and chromosomal copynumber alterations were detected simultaneously with high accuracy compared with other methods in clinical use. Putatively actionable genomic alterations, including those that predict sensitivity or resistance to established and experimental therapies, were detected in each tumor sample tested. Thus, targeted deep sequencing of clinical tumor material may enable mutation-driven clinical trials and, ultimately, “personalized” cancer treatment.

Significance: Despite the rapid proliferation of targeted therapeutic agents, systematic methods to profile clinically relevant tumor genomic alterations remain underdeveloped. We describe a sequencing-based approach to identifying genomic alterations in FFPE tumor samples. These studies affirm the feasibility and clinical utility of targeted sequencing in the oncology arena and provide a foundation for genomics-based stratification of cancer patients. Cancer Discovery; 2(1); 82–93. ©2011 AACR.

Read the Commentary on this article by Corless and Spellman, p. 23

This article is highlighted in the In This Issue feature, p. 1
Differential Hemodynamic Effects of Levosimendan in a Porcine Model of Neonatal Hypoxia-Reoxygenation
Authors: Esch J. , Joynt C. , Manouchehri N. , Lee T.F. , Li Y.-Q. , Bigam D. , Vento M. , Cheung P.-Y.
Published: November 2011

Background: Neonatal asphyxia can be complicated by myocardial dysfunction with secondary alterations in pulmonary and regional hemodynamics. Levosimendan is a calcium-sensitizing inotrope that may support cardiac output, but little is known regarding its differential hemodynamic effects in asphyxiated neonates. Methods: Mixed breed piglets (1–4 days old, weight 1.6–2.3 kg) were acutely instrumented. Normocapnic alveolar hypoxia (10–15% oxygen) was induced for 2 h, followed by reoxygenation with 100% (1 h) and then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer’s lactate 10 ml/kg), either levosimendan (0.1 or 0.2 µg/kg/min) or D5W (placebo) was infused for 2 h in a blinded, block-randomized fashion (n = 7–8/group). The systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics were compared. Results: At 0.1 and 0.2 µg/kg/min, levosimendan significantly increased cardiac output (121 and 123% of pretreatment, respectively) and heart rate, and decreased systemic vascular resistance without causing hypotension. Pulmonary arterial pressure and estimated pulmonary vascular resistance were significantly increased from pretreatment baseline in 0.1 but not 0.2 µg/kg/min levosimendan. Levosimendan infusion had no effects on regional hemodynamics. Myocardial efficiency but not oxygen consumption increased with 0.1 µg/kg/min levosimendan without significant effects on plasma troponin and myocardial lactate levels. Conclusions: In newborn piglets following hypoxia-reoxygenation injury, levosimendan improves cardiac output but has no marked effects in carotid, superior mesenteric and renal perfusion. It appears that various doses of levosimendan increase the cardiac output through different mechanisms. Further investigations are needed to examine the effectiveness of levosimendan as a cardiovascular supportive therapy either alone or in conjunction with other inotropes in asphyxiated neonates.
Stopping Renin-Angiotensin System Inhibitors in Chronic Kidney Disease: Predictors of Response
Authors: Gonçalves Anderson Roman , Khwaja Arif , Ahmed Aimune K. , El Kossi Mohsen , El Nahas Meguid
Published: November 2011

Background/Aims: Renin-angiotensin system (RAS) inhibitors are considered first-line agents for hypertensive patients with progressive chronic kidney disease (CKD). In a previous study, we showed that stopping RAS inhibitors increased estimated glomerular filtration rate (eGFR) in a significant number of advanced CKD patients. The present study tries to address who would benefit and whether this benefit is predictable. Methods: Forty-three CKD stage 4 patients had RAS inhibitors stopped and were followed for at least 24 months. Compared outcome groups were ‘alive’, ‘renal replacement therapy (RRT)’ or ‘died’. Improvement in eGFR was used in a receiver-operating characteristic curve and finds the best predictor for surviving without RRT. Results: Patients who survived without RRT were all hypertensive and had a higher eGFR increment after stopping the drugs. Those with eGFR improvement ≧5 ml/min/1.73 m2 were the most likely to survive long term without RRT (log-rank test, p = 0.03). They had a significant increment in blood pressure that correlated with eGFR improvement (r = 0.403, p = 0.013). Conclusion: A significant increase in eGFR after stopping RAS inhibitors suggests that long-term survival without RRT is more likely. Our findings question the universal preemptive indication of RAS inhibitors in advanced CKD and suggest that they can be safely stopped, at least in some patients.
The GABAA Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome
Authors: Olmos-Serrano Jose Luis , Corbin Joshua G. , Burns Mark P.
Published: November 2011

Hyperactivity, hypersensitivity to auditory stimuli, and exaggerated fear are common behavioral abnormalities observed in individuals with fragile X syndrome (FXS), a neurodevelopmental disorder that is the most common genetic cause of autism. Evidence from studies of the Fmr1 knockout (KO) mouse model of FXS supports the notion that impaired GABAergic transmission in different brain regions such as the amygdala, striatum or cerebral cortex is central to FXS behavioral abnormalities. This suggests that the GABAergic system might be an intriguing target to ameliorate some of the phenotypes in FXS. Our recent work revealed that THIP (gaboxadol), a GABAA receptor agonist, can restore principal neuron excitability deficits in the Fmr1 KO amygdala, suggesting that THIP may also restore some of the key behavioral abnormalities in Fmr1 KO mice. Here, we reveal that THIP significantly attenuated hyperactivity in Fmr1 KO mice, and reduced prepulse inhibition in a volume-dependent manner. In contrast, THIP did not reverse the deficits in cued fear or startle response. Thus, this study shows that enhancing GABAergic transmission can correct specific behavioral phenotypes of the Fmr1 KO mouse further supporting that targeting the GABAergic system, and specifically tonic inhibition, might be important for correcting or ameliorating some key behaviors in FXS.
Adjuvant Hepatic Arterial Infusional Chemotherapy with 5-Fluorouracil and Cisplatin after Curative Resection of Hepatocellular Carcinoma
Authors: Kim Do Young , Ahn Sang Hoon , Kim Seung Up , Choi Sae Byeol , Lee Kwang-Hun , Park Mi Sook , Park Jun Yong , Lee Do Yun , Han Kwang-Hyub , Kim Kyung Sik
Published: November 2011

Objectives: We investigated whether adjuvant hepatic arterial infusional chemotherapy (HAIC) with 5-fluorouracil (5-FU) and cisplatin reduces the recurrence of hepatocellular carcinoma (HCC) after curative resection. Methods: Between January 2006 and December 2008, 31 HCC patients received four cycles of adjuvant HAIC with 5-FU and cisplatin via port system after curative resection. During the same period, 62 patients, who did not take any adjuvant therapy, were selected as controls. Results: Tumor characteristics, such as distribution of TNM stage, pathologic differentiation, portal vein invasion, or microscopic invasion did not differ between control and adjuvant groups. During follow-up, recurrence developed in 11 adjuvant (35.5%) and 24 control patients (38.7%; p = 0.823). Tumor progression after recurrence was the cause of death in 2 adjuvant (28.6%) and 7 control patients (38.8%; p = 0.912). The 2-year recurrence rate was 9.1% in the adjuvant group and 4.2% in the control group, with the median recurrence-free survival time being 10.5 and 7.5 months, respectively (p = 0.324). The 3-year cumulative survival rate was 73.3% in the adjuvant group and 68.3% in the control group (p = 0.355). Conclusion: Adjuvant HAIC with 5-FU and cisplatin did not offer any beneficial effect on the recurrence after curative resection of HCC.
Endocardial Left Ventricular Pacing Improves Cardiac Resynchronization Therapy in Chronic Asynchronous Infarction and Heart Failure Models
Authors: Strik Marc , Rademakers Leonard M. , van Deursen Caroline J.M. , van Hunnik Arne , Kuiper Marion , Klersy Catherine , Auricchio Angelo , Prinzen Frits W.
Published: November 2011

Background—

Studies in canine hearts with acute left bundle branch block (LBBB) showed that endocardial left ventricular (LV) pacing improves the efficacy of cardiac resynchronization therapy (CRT) compared with conventional epicardial LV pacing. The present study explores the efficacy of endocardial CRT in more compromised hearts and the mechanisms of such beneficial effects.

Methods and Results—

Measurements were performed in 22 dogs, 9 with acute LBBB, 7 with chronic LBBB combined with infarction (embolization; LBBB plus myocardial infarction, and concentric remodeling), and 6 with chronic LBBB and heart failure (rapid pacing, LBBB+HF, and eccentric remodeling). A head-to-head comparison was performed of the effects of endocardial and epicardial LV pacing at 8 sites. LV activation times were measured using ≈100 endocardial and epicardial electrodes and noncontact mapping. Pump function was assessed from right ventricular and LV pressures. Endocardial CRT resulted in better electric resynchronization than epicardial CRT in all models, although the benefit was larger in concentrically remodeled LBBB plus myocardial infarction than in eccentrically remodeled LBBB+HF hearts (19% versus 10%). In LBBB and LBBB+HF animals, endocardial conduction was ≈50% faster than epicardial conduction; in all models, transmural impulse conduction was ≈25% faster when pacing from the endocardium than from the epicardium. Hemodynamic effects were congruent with electric effects.

Conclusions—

Endocardial CRT improves electric synchrony of activation and LV pump function compared with conventional epicardial CRT in compromised canine LBBB hearts. This benefit can be explained by a shorter path length along the endocardium and by faster circumferential and transmural impulse conduction during endocardial LV pacing.
Frailty Is Independently Associated With Short-Term Outcomes for Elderly Patients With Non–ST-Segment Elevation Myocardial Infarction
Authors: Ekerstad Niklas , Swahn Eva , Janzon Magnus , Alfredsson Joakim , Löfmark Rurik , Lindenberger Marcus , Carlsson Per
Published: November 2011

Background—

For the large and growing population of elderly patients with cardiovascular disease, it is important to identify clinically relevant measures of biological age and their contribution to risk. Frailty is an emerging concept in medicine denoting increased vulnerability and decreased physiological reserves. We analyzed the manner in which the variable frailty predicts short-term outcomes for elderly non–ST-segment elevation myocardial infarction patients.

Methods and Results—

Patients aged ≥75 years, with diagnosed non–ST-segment elevation myocardial infarction were included at 3 centers, and clinical data including judgment of frailty were collected prospectively. Frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale. The impact of the comorbid conditions on risk was quantified by the coronary artery disease–specific index. Of 307 patients, 149 (48.5%) were considered frail. By multiple logistic regression, frailty was found to be strongly and independently associated with risk for the primary composite outcome (death from any cause, myocardial reinfarction, revascularization due to ischemia, hospitalization for any cause, major bleeding, stroke/transient ischemic attack, and need for dialysis up to 1 month after inclusion) (odds ratio, 2.2; 95% confidence interval, 1.3–3.7), in-hospital mortality (odds ratio, 4.6; 95% confidence interval, 1.3–16.8), and 1-month mortality (odds ratio, 4.7; 95% confidence interval, 1.7–13.0).

Conclusions—

Frailty is strongly and independently associated with in-hospital mortality, 1-month mortality, prolonged hospital care, and the primary composite outcome. The combined use of frailty and comorbidity may constitute an ultimate risk prediction concept in regard to cardiovascular patients with complex needs.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT01049997.
Carotid Stiffness in Young Adults: A Life-Course Analysis of its Early Determinants
Authors: Ferreira Isabel , van de Laar Roel J. , Prins Martin H. , Twisk Jos W. , Stehouwer Coen D.
Published: November 2011

Cardiovascular risk factors affecting arterial stiffness in adulthood may develop at different critical periods earlier in life. We examined whether the trajectories, from adolescence to young adulthood, of blood pressure, body fatness and fat distribution, blood lipids, cardiorespiratory fitness, and heart rate determined levels of arterial stiffness in young adults. We investigated 373 apparently healthy adults in whom cardiovascular risk factors were repeatedly examined between the ages of 13 and 36 years and carotid stiffness estimates were obtained at the age of 36 years. Differences in the mean levels and the trajectories of risk factors throughout the 24-year longitudinal period between subjects with different levels of carotid stiffness at age 36 years were analyzed with generalized estimating equations. Compared with individuals with less stiff carotid arteries, those with stiffer carotid arteries at the age of 36 years were characterized from ages 13 to 36 years by greater levels of and steeper increases in blood pressure and central fatness, independently of each other and other risk factors. These increases were already present in adolescence, preceded the development of poorer levels of blood lipids, cardiorespiratory fitness, and heart rate, which were evident during adulthood only, and explained to a great extent the deleterious association between these risk factors and carotid stiffness at the age of 36 years. Multiple and intertwined mechanisms involved in the pathogenesis of arterial stiffness have their origins in early life. Blood pressure and central fatness have a pivotal role herein and should be specifically targeted to prevent arterial stiffening and its cardiovascular sequelae.
Vitamin D, Parathyroid Hormone, and Sudden Cardiac Death
Authors: Deo Rajat , Katz Ronit , Shlipak Michael G. , Sotoodehnia Nona , Psaty Bruce M. , Sarnak Mark J. , Fried Linda F. , Chonchol Michel , de Boer Ian H. , Enquobahrie Daniel , Siscovick David , Kestenbaum Bryan
Published: November 2011

Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD ≥20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH ≥65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95% CI: 1.17–4.10];
P
=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease.
Relation Between Blood Pressure and Vascular Events and Mortality in Patients With Manifest Vascular Disease
Authors: Dorresteijn Johannes A.N. , van der Graaf Yolanda , Spiering Wilko , Grobbee Diederick E. , Bots Michiel L. , Visseren Frank L.J.
Published: November 2011

Recent studies have challenged the notion that “lower is better” for blood pressure in relation to vascular events and mortality in patients with vascular disease, whereas practice guidelines currently recommend to lower blood pressure to <130/80 mm Hg. We reassessed this J-curved relationship between blood pressure and cardiovascular events and all-cause mortality in patients with various manifestations of vascular disease. For this purpose, 5788 patients with symptomatic vascular disease enrolled in the Secondary Manifestations of Arterial Disease Study were followed-up for the occurrence of new vascular events (ie, myocardial infarction, stroke, or vascular death) and all-cause mortality. During a median of 5.0 years (interquartile range: 2.6–8.1 years), 788 patients experienced a new vascular event, and 779 died. Overall, the covariate-adjusted relationship between mean baseline systolic, diastolic, or pulse pressure and the occurrence of vascular events followed a J-curve with increased event rates above and below the nadir blood pressure of 143/82 mm Hg. A similar nonlinear relationship was found for diastolic pressure and all-cause mortality. Elevated blood pressure was not associated with increased morbidity and mortality in patients with recently diagnosed coronary artery disease, ≥65 years, and having >60 mm Hg pulse pressure. Importantly, especially in these subgroups, low blood pressure could also be a symptom rather than a cause of disease. Blood pressure level below and above 143/82 mm Hg is, thus, an independent risk factor for recurrent events in patients with manifest vascular disease. Uncertainty of whether this association is causal provides a strong rationale for trials evaluating blood pressure treatment targets.
Plasma Aldosterone Levels and Development of Insulin Resistance
Authors: Kumagai Eita , Adachi Hisashi , Jacobs David R. , Hirai Yuji , Enomoto Mika , Fukami Ako , Otsuka Maki , Kumagae Shun-ichi , Nanjo Yasuki , Yoshikawa Kuniko , Esaki Eishi , Yokoi Kanako , Ogata Kinuka , Kasahara Akiko , Tsukagawa Eri , Ohbu-Murayama Kyoko , Imaizumi Tsutomu
Published: November 2011

Aldosterone plays a role in hypertension, and hypertension is prevalent in patients with insulin resistance. Cross-sectional studies have reported that plasma aldosterone levels are higher in patients with insulin resistance. However, it is not known whether plasma aldosterone levels predict the development of insulin resistance. Subjects of the present study were 1235 local residents (490 men and 745 women) who participated in health screenings in Japan in 1999. Plasma aldosterone levels were measured by radioimmunoassay. We investigated the cross-sectional relationship between plasma aldosterone levels and insulin resistance (homeostasis model assessment index ≥1.73 according to the diagnostic criteria used in Japan) in 1088 nondiabetic participants. At the 10-year follow-up, 141 subjects had died, and 260 subjects refused re-examination. We performed a prospective analysis of 564 subjects to predict incident insulin resistance. We found a significant (
P
<0.001) cross-sectional relationship between plasma aldosterone and homeostasis model assessment index at baseline. In the prospective analysis, a significantly higher (
P
<0.05) relative risk (1.71 [95% CI: 1.03–2.84]) was observed in the highest tertile versus lowest tertile of plasma aldosterone for the development of insulin resistance, after adjustment for confounding factors. This 10-year prospective study demonstrated that plasma aldosterone levels predicted the development of insulin resistance in a general population.
Somatosensory Anticipatory Alpha Activity Increases to Suppress Distracting Input
Authors: Haegens Saskia , Luther Lisa , Jensen Ole
Published: November 2011

Effective processing of sensory input in daily life requires attentional selection and amplification of relevant input and, just as importantly, attenuation of irrelevant information. It has been proposed that top–down modulation of oscillatory alpha band activity (8–14 Hz) serves to allocate resources to various regions, depending on task demands. In previous work, we showed that contralateral somatosensory alpha activity decreases to facilitate processing of an anticipated target stimulus in a tactile discrimination task. In the current study, we asked whether somatosensory alpha activity is also modulated when expecting incoming distracting stimuli on the nonattended side. We hypothesized that an ipsilateral increase of alpha to suppress distracters would be required for optimal task performance. We recorded magneto-encephalography while subjects performed a tactile stimulus discrimination task where a cue directed attention either to their left or right hand. Distracters were presented simultaneously to the unattended hand. We found that alpha power contralateral to the attended hand decreased, whereas ipsilateral alpha power increased. In addition, posterior alpha power showed a general increase. Importantly, these three alpha components all contributed to discrimination performance. This study further extends the notion that alpha band activity is involved in shaping the functional architecture of the working brain by determining the engagement and disengagement of specific regions: Contralateral alpha decreases to facilitate stimulus detection, whereas ipsilateral alpha increases when active suppression of distracters is required. Importantly, the ipsilateral alpha increase is crucial for optimal task performance.
Equatorial Planetary Waves and Their Signature in Atmospheric Variability
Authors: Grise Kevin M. , Thompson David W. J.
Published: November 2011

Equatorial planetary waves are a fundamental component of the tropical climate system. Previous studies have examined their structure in the climatological-mean circulation, their role in the climatological-mean momentum balance of the tropics, and their contribution to the climatological-mean upwelling across the tropical tropopause. In this study, the authors focus on the contribution of the equatorial planetary waves to variability in the tropical circulation about its climatological-mean state.

The equatorial planetary waves that dominate the climatological mean exhibit considerable variability on intraseasonal and interannual time scales. Variability in the amplitude of the equatorial planetary waves is associated with a distinct pattern of equatorially symmetric climate variability that also emerges from empirical orthogonal function analysis of various tropical dynamical fields. Variability in the equatorial planetary waves is characterized by variations in 1) convection in the deep tropics, 2) eddy momentum flux convergence and zonal-mean zonal wind in the tropical upper troposphere, 3) the mean meridional circulation of the tropical and subtropical troposphere, 4) temperatures in the tropical lower stratosphere and subtropical troposphere of both hemispheres, and 5) the amplitude of the upper tropospheric anticyclones over the western tropical Pacific Ocean.

It is argued that pulsation of the equatorial planetary waves provides an alternative framework for interpreting the response of the tropical circulation to a range of climate phenomena. Pulsation of the equatorial planetary waves is apparent in association with opposing phases of El Niño–Southern Oscillation and select phases of the Madden–Julian oscillation. Pulsation of the equatorial planetary waves also contributes to variability in measures of the width of the tropical belt.
Does it matter where your manager works? Comparing managerial work mode (traditional, telework, virtual) across subordinate work experiences and outcomes
Authors: Golden Timothy D , Fromen Allan
Published: November 2011

Although research has begun to examine impacts from employee work modes such as teleworking, studies to date have overlooked the impact that managers who work away from the office might have on subordinates. Using a large dataset ( N = 11,059), this study therefore compares three managerial work modes (traditional, telework, virtual work), to investigate differences in subordinate work experiences and outcomes. Results suggest that in comparison to subordinates with managers in a traditional work mode, work experiences and outcomes are generally less positive for subordinates with teleworking managers who spend a portion of the week away from the office, and they are lower as well for subordinates with virtual managers who are away from the office full time. These results differ based on the subordinate’s own work mode and are modest in magnitude. This study suggests a need for further investigation into the effects of managerial work modes on subordinate experiences and outcomes.