bluuebunny/crossref_metadata_2025 huggingface dataset:
Activations of TRPA1 and P2X receptors are important in ROS-mediated stimulation of capsaicin-sensitive lung vagal afferents by cigarette smoke in rats
Authors: Lin You Shuei , Hsu Chun-Chun , Bien Mauo-Ying , Hsu Hui-Chi , Weng Hsu-Ting , Kou Yu Ru
Published: February 2010

Capsaicin-sensitive lung vagal afferents (CSLVAs) are important in detecting pulmonary reactive oxygen species (ROS). We investigated the mechanisms underlying the stimulation of CSLVAs by inhaled cigarette smoke (CS) in 216 anesthetized rats. In spontaneously breathing rats, CS evoked a CSLVA-mediated reflex bradypnea that was prevented by N-acetyl-l-cysteine (NAC; an antioxidant), HC-030031 [a transient receptor potential ankyrin 1 (TRPA1) receptor antagonist], and iso-pyridoxalphosphate-6-azophenyl-2′,5′-disulfonate ( iso-PPADS; a P2X receptor antagonist). In paralyzed, artificially ventilated rats, CS evoked an increase in CSLVA fiber activity (ΔFA) that was abolished by NAC and was attenuated by HC-030031, iso-PPADS, indomethacin (Indo; a cyclooxygenase inhibitor), and a combination of apyrase and adenosine deaminase (ADA) (ATP scavengers); the response to CS was reduced to 11.7 ± 4.0%, 39.5 ± 10.0%, 52.9 ± 14.4%, 68.7 ± 10.1%, and 47.2 ± 12.9% of control, respectively. The suppressive effect on this afferent response was not improved by a combination of HC-030031 and Indo (ΔFA = 39.5 ± 10.1% of control) compared with that induced by HC-030031 alone. In contrast, the suppressive effect was enhanced by a combination of HC-030031 and apyrase+ADA (ΔFA = 5.3 ± 4.9% of control) or a combination of iso-PPADS and Indo (ΔFA = 23.3 ± 7.7% of control) compared with that induced by HC-030031 alone or iso-PPADS alone. This afferent response was not altered by the vehicles for these drugs. These results suggest that activations of TRPA1 receptors by cyclooxygenase metabolites and P2X receptors by ATP are both necessary for the ROS-mediated stimulation of CSLVA fibers by CS in rats.
Reaction time to peripheral visual stimuli during exercise under hypoxia
Authors: Ando Soichi , Yamada Yosuke , Kokubu Masahiro
Published: February 2010

The purpose of this study was to test the hypothesis that decrease in cerebral oxygenation compromises an individual's ability to respond to peripheral visual stimuli during exercise. We measured the simple reaction time (RT) to peripheral visual stimuli at rest and during and after cycling at three different workloads [40%, 60%, and 80% peak oxygen uptake (V̇o2)] under either normoxia [inspired fraction of oxygen (FiO2) = 0.21] or normobaric hypoxia (FiO2= 0.16). Peripheral visual stimuli were presented at 10° to either the right or the left of the midpoint of the eyes. Cerebral oxygenation was monitored during the RT measurement over the right frontal cortex with near-infrared spectroscopy. We used the premotor component of RT (premotor time) to assess effects of exercise on the central process. The premotor time was significantly longer during exercise at 80% peak V̇o2(normoxia: 214.2 ± 33.0 ms, hypoxia: 221.5 ± 30.1 ms) relative to that at rest (normoxia: 201.0 ± 27.2 ms, hypoxia: 202.9 ± 29.7 ms) ( P < 0.01). Under normoxia, cerebral oxygenation gradually increased up to 60% peak V̇o2and then decreased to the resting level at 80% peak V̇o2. Under hypoxia, cerebral oxygenation progressively decreased as exercise workload increased. We found a strong correlation between increase in premotor time and decrease in cerebral oxygenation ( r2= 0.89, P < 0.01), suggesting that increase in premotor time during exercise is associated with decrease in cerebral oxygenation. Accordingly, exercise at high altitude may compromise visual perceptual performance.
High-intensity exercise training in mice with cardiomyocyte-specific disruption of Serca2
Authors: Ericsson Madelene , Andersson Kristin B. , Amundsen Brage H. , Torp Sverre H. , Sjaastad Ivar , Christensen Geir , Sejersted Ole M. , Ellingsen Øyvind
Published: February 2010

Several lines of evidence indicate that the sarco(endo)plasmic reticulum ATPase type 2 (SERCA2) is essential for maintaining myocardial calcium handling and cardiac pump function. Hence, a reduction in SERCA2 abundance is expected to reduce work performance and maximal oxygen uptake (V̇o2max) and to limit the response to exercise training. To test this hypothesis, we compared V̇o2max and exercise capacity in mice with cardiac disruption of Serca2 (SERCA2 KO) with control mice (SERCA2 FF). We also determined whether the effects on V̇o2max and exercise capacity could be modified by high-intensity aerobic exercise training. Treadmill running at 85–90% of V̇o2max started 2 wk after Serca2 gene disruption and continued for 4 wk. V̇o2max and maximal running speed were measured weekly in a metabolic chamber. Cardiac function was assessed by echocardiography during light anesthesia. In sedentary SERCA2 KO mice, the aerobic capacity was reduced by 50% and running speed by 28%, whereas trained SERCA2 KO mice were able to maintain maximal running speed despite a 36% decrease in V̇o2max. In SERCA2 FF mice, both V̇o2max and maximal running speed increased by training, while no changes occurred in the sedentary group. Left ventricle dimensions remained unchanged by training in both genotypes. In contrast, training induced right ventricle hypertrophy in SERCA2 KO mice. In conclusion, the SERCA2 protein is essential for sustaining cardiac pump function and exercise capacity. Nevertheless, SERCA2 KO mice were able to maintain maximal running speed in response to exercise training despite a large decrease in V̇o2max.
Central and peripheral contributions to neuromuscular fatigue induced by a 24-h treadmill run
Authors: Martin Vincent , Kerhervé Hugo , Messonnier Laurent A. , Banfi Jean-Claude , Geyssant André , Bonnefoy Regis , Féasson Léonard , Millet Guillaume Y.
Published: February 2010

This experiment investigated the fatigue induced by a 24-h running exercise (24TR) and particularly aimed at testing the hypothesis that the central component would be the main mechanism responsible for neuromuscular fatigue. Neuromuscular function evaluation was performed before, every 4 h during, and at the end of the 24TR on 12 experienced ultramarathon runners. It consisted of a determination of the maximal voluntary contractions (MVC) of the knee extensors (KE) and plantar flexors (PF), the maximal voluntary activation (%VA) of the KE and PF, and the maximal compound muscle action potential amplitude (Mmax) on the soleus and vastus lateralis. Tetanic stimulations also were delivered to evaluate the presence of low-frequency fatigue and the KE maximal muscle force production ability. Strength loss occurred throughout the exercise, with large changes observed after 24TR in MVC for both the KE and PF muscles (−40.9 ± 17.0 and −30.3 ± 12.5%, respectively; P < 0.001) together with marked reductions of %VA (−33.0 ± 21.8 and −14.8 ± 18.9%, respectively; P < 0.001). A reduction of Mmax amplitude was observed only on soleus, and no low-frequency fatigue was observed for any muscle group. Finally, KE maximal force production ability was reduced to a moderate extent at the end of the 24TR (−10.2%; P < 0.001), but these alterations were highly variable ( ± 15.7%). These results suggest that central factors are mainly responsible for the large maximal muscle torque reduction after ultraendurance running, especially on the KE muscles. Neural drive reduction may have contributed to the relative preservation of peripheral function and also affected the evolution of the running speed during the 24TR.
Effects of Bevacizumab on Apoptosis, Na+-K+-Adenosine Triphosphatase and Zonula Occludens 1 Expression on Cultured Corneal Endothelial Cells
Authors: Yoeruek Efdal , Tatar Olcay , Spitzer Martin S. , Saygili Oguzhan , Biedermann Tilo , Bartz-Schmidt Karl U. , Thaler Sebastian , Szurman Peter
Published: February 2010

Background: This laboratory study was undertaken to investigate the influence of bevacizumab on apoptosis, Na+-K+-adenosine triphosphatase (Na+-K+-ATPase) and zonula occludens 1 (ZO-1) expression on cultured human corneal endothelial cells (HCECs). Methods: Annexin V binding combined with propidium iodide (PI) costaining was used to distinguish viable, early and late apoptotic cells. Immunolocalization of ZO-1 and Na+-K+-ATPase was performed to analyze intercellular cell integrity after exposure to 5.0 mg/ml bevacizumab for 24 h. Results: No significant induction of apoptosis or necrosis was seen in HCECs after exposure to 5.0 mg/ml bevacizumab (p = 0.689, p = 0.516, respectively). The mean number of annexin-V-FITC- and PI-positive cells did not change significantly. Additionally, no significant changes in expression were detectable, neither for ZO-1 nor for Na+-K+-ATPase in comparison with the control. For ZO-1, 70.0% of the cells stained intensely, 24.7% stained moderately, and 5.3% stained weakly in the control group. After exposure to 5.0 mg bevacizumab, only minor changes were observable: 68.8% stained intensely, 25.4% moderately and 5.8% weakly (p = 0.524). For Na+-K+-ATPase, 19.3% of the cells stained intensely, 59.4% moderately, and 21.3% weakly in the control group. After exposure to 5.0 mg bevacizumab, again only minor changes were observable in the expression pattern: 18.2% stained intensely, 60.3% moderately and 21.5% weakly. The changes were not significant compared with the control (p = 0.492). Conclusions: Bevacizumab, at concentrations used clinically, did not induce apoptosis or necrosis in HCECs in vitro. Additionally, no alteration of ZO-1 or Na+/K+-ATPase expression was detected after exposure to 5.0 mg/ml bevacizumab for 24 h.
Measures of Disease Frequency: Prevalence and Incidence
Authors: Noordzij Marlies , Dekker Friedo W. , Zoccali Carmine , Jager Kitty J.
Published: February 2010

To describe how often a disease or another health event occurs in a population, different measures of disease frequency can be used. The prevalence reflects the number of existing cases of a disease. In contrast to the prevalence, the incidence reflects the number of new cases of disease and can be reported as a risk or as an incidence rate. Prevalence and incidence are used for different purposes and to answer different research questions. In this article, we discuss the different measures of disease frequency and we explain when to apply which measure.
Pro-atherothrombotic effects of leptin in human coronary endothelial cells
Authors: Angri Valeria , Rosa Salvatore De , Calì Gaetano , Petrillo Gianluca , Maresca Fabio , D’Ascoli Greta-Luana , Maietta Paola , Brevetti Linda , Chiariello Massimo , Cirillo Plinio
Published: February 2010

Adipocytes are nowadays recognised as cells able to produce and secrete a large variety of active substances termed adipokines, which exert direct effects on vascular cells. Among these adipokines, leptin has been proposed to play a role in the pathophysiology of acute coronary syndromes, as well as in increasing cardiovascular risk. At the moment, however, the mechanisms linking leptin to cardiovascular disease are not completely understood. This study investigates the effects of leptin, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk or measurable in patients with acute coronary syndromes, on tissue factor (TF) and cellular adhesion molecules (CAMs) expression in human coronary endothelial cells (HCAECs). We demonstrate that leptin induces transcription of mRNA for TF and CAMs by real-time PCR. In addition, we show that this adipokine promotes surface expression of TF and CAMs that are functionally active since we observed increased procoagulant activity and leukocyte adhesion on cell surface. Leptin effects appear modulated by eNOS-production of oxygen free radicals through the activation of the transcription factor, nuclear factor(NF)-κB, since L-NAME, Superoxide Dismutase and NF-κB inhibitors suppressed CAMs and TF expression. Data of the present study, although in vitro, indicate that leptin may exert direct effects on human coronary endothelial cells by promoting CAMs and TF expression and support the hypothesis that this adipokines, besides being involved in the pathophysiology of obesity, might play a relevant role as an active mediator linking obesity to cardiovascular disease.
The direct thrombin inhibitor argatroban effectively prevents cardiac catheter thrombosis in vitro
Authors: Kaeberich Anja , Maegdefessel Lars , Buerke Michael , Busshardt Marese , Schubert Sebastian , Russ Martin , Plehn Alexander , Ebelt Henning , Werdan Karl , Schlitt Axel , Raaz Uwe
Published: February 2010

The direct thrombin inhibitor argatroban offers some significant advantages over unfractionated heparin (UFH) and is recommended as an alternative anticoagulant during percutaneous coronary interventions (PCI). The impact of argatroban on cardiac catheter thrombosis – a severe potential complication of PCI – has not been systematically studied yet. The aim of the present study was to test in vitro the hypothesis that argatroban is equivalent to the more established anticoagulants UFH and enoxaparin in preventing catheter thrombus formation. Blood pretreated with the anticoagulants of interest was continuously circulated through a guiding catheter by using a roller pump for a maximum experimental period of 60 minutes. In an alternate model, coagulation was mechanically induced by a magnetic stirrer. Coagulation parameters, overall thrombus weight and electron microscopic features (deposits of platelets and fibrin on the catheter surface) were quantified as endpoints. Argatroban (administered as bolus or continuous in-fusion), UFH (bolus), and enoxaparin (bolus) significantly reduced catheter thrombus formation compared to untreated controls. Here, neither overall thrombus weight nor platelet/fibrin deposition was different among the specific anticoagulants. Declining ACT (activated clotting time) levels – which were found in the argatroban bolus group – could be prevented by continuous infusion. In magnetic stirrer-induced coagulation, thrombus weight was lower following bolus treatment with UFH and enoxaparin compared to argatroban. These data suggest that the potential for argatroban in preventing catheter thrombosis is comparable to that of UFH and enoxaparin. However, the anticoagula-tory efficacy varied, depending on the model of coagulation activation, which demonstrates the necessity for specific testing.
Altered reference ranges for protein C and protein S during early pregnancy: Implications for the diagnosis of protein C and protein S deficiency during pregnancy
Authors: Ignjatovic Vera , Monagle Paul , Walker Susan , Higgins John , Brennecke Shaun , Said Joanne
Published: February 2010

Protein S, protein C and antithrombin are important regulators of coagulation. While deficiencies of these proteins have been linked to adverse pregnancy outcomes, testing for these deficiencies during pregnancy is limited by the use of non-pregnant reference ranges and a limited understanding of the changes that occur during pregnancy. Although several small studies have previously reported on the activity of these proteins during pregnancy, potentially important changes have been overlooked by continuing to compare the activity during pregnancy with non-pregnant reference ranges. In the current study, we investigated the activity of protein S, protein C and antithrombin during the first half of pregnancy in 440 otherwise asymptomatic women who went on to have uncomplicated singleton pregnancies. Consistent with previous studies, we found that antithrombin activity remained unchanged, while protein S activity decreased significantly to a mean level of 46%. We did not observe a progressive decrease in protein S during the second trimester as several studies have suggested previously. In contrast, we observed a potentially biologically significant increase in protein C activity throughout the first 22 weeks of pregnancy. Given the physiological role of protein C, we postulate that this increase may play a role in maintaining early pregnancy through both an anticoagulant and an inflammatory regulation pathway.
Circulating bactericidal/permeability-increasing protein (BPI) is associated with serum lipids and endothelial function
Authors: Esteve Eduardo , Castro Antoni , Moreno Jose Maria , Vendrell Joan , Ricart Wifredo , Fernández-Real José Manuel
Published: February 2010

Bactericidal/permeability-increasing protein (BPI), a major constituent of neutrophils that possesses anti-inflammatory properties, shows a structure similar to some proteins implicated in lipid metabolism. We evaluated circulating BPI as a biomarker of endothelial function and lipid metabolism. Circulating BPI concentrations (ELISA) and serum lipids were measured in 202 Caucasian non-smoking men. In a subgroup of 91 consecutive subjects brachial vascular reactivity (high resolution external ultrasound) was assessed. Plasma BPI concentrations were positively associated with total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) (r= 0.203, 0.204 and 0.18; all p<0.05, respectively). In a multiple linear regression analysis, BPI levels were independent contributors to the variance of HDL-C, total cholesterol and LDL-cholesterol after adjusting for age, body mass index and glucose tolerance status. Plasma BPI concentration correlated positively with endothelium-dependent vasodilatation (r=0.277; p<0.05) and HDL-C (r=0.36; p<0.05) in subjects with normal glucose tolerance. In conclusion, circulating BPI could constitute a biomarker of lipid metabolism in subjects with normal glucose tolerance and could help to identify those subjects with preserved endothelial function.
Magnetic resonance imaging to determine the incidence of brain ischaemia in patients with β-thalassaemia intermedia
Authors: Bagheri Hadi , Rastgu Fatemeh , Rachmilewitz Eliezer , Karimi Mehran
Published: February 2010

One complication in patients with β-thalassaemia who had prolonged survival is chronic hypercoagulable state, which results in thromboembolic events involving major organs including the brain. We determined the prevalence of microthrombosis in the brain in an asymptomatic subgroup of patients with β-thalassaemia intermedia (TI) who had undergone splenectomy. This retrospective review included 200 patients with TI diagnosed on the basis of blood count, haemoglobin (Hb) electrophoresis and clinical data. Their ages ranged from 18 to 34 years, 19 (63.3%) were women and 11 (36.7%) were men. We selected 30 patients at random who fulfilled the inclusion criteria: Hb concentration >7 g/dl), splenectomy and platelet count >500,000/ml. Their mean Hb concentration was 8.4 g/dl and their mean ferritin concentration was 519 ng/ml. Magnetic resonance imaging (MRI) was done in every patient, and the findings were interpreted by an expert neuroradiologist. Imaging studies showed pathological findings in 28% of the patients. Six had changes in the white matter suggestive of ischaemia and two had evidence of small infarctions. Conclusion: 1) In this small subset of patients diagnostic magnetic resonance imaging to monitor early asymptomatic or subclinical vascular damage in the brain can be considered when they reach the age of 20 years, and repeated every 3–5 years. 2) Treatment with antiplatelet aggregants is suggested in patients with documented asymptomatic brain ischaemia. 3) These results require confirmation in a larger group of similar patients with other types of thalassaemia who are multitransfused or have an intact spleen.
Intranasal Immunization With an Apolipoprotein B-100 Fusion Protein Induces Antigen-Specific Regulatory T Cells and Reduces Atherosclerosis
Authors: Klingenberg Roland , Lebens Michael , Hermansson Andreas , Fredrikson Gunilla Nordin , Strodthoff Daniela , Rudling Mats , Ketelhuth Daniel F.J. , Gerdes Norbert , Holmgren Jan , Nilsson Jan , Hansson Göran K.
Published: February 2010

Objective—

Atherosclerosis is an inflammatory disease. Autoimmune responses to low-density lipoproteins (LDL) contribute to its progression, whereas immunization with LDL may induce atheroprotective or proatherogenic responses. The objective of this study was to develop an atheroprotective vaccine by targeting a peptide of the LDL protein constituent apolipoprotein B-100 (apoB-100) to the nasal mucosa to induce a protective mucosal immune response.

Methods and Results—

A peptide comprising amino acids 3136 to 3155 of apoB-100 (p210) was fused to the B subunit of cholera toxin (CTB), which binds to a ganglioside on mucosal epithelia. The effect of nasal administration of the p210-CTB fusion protein on atherogenesis was compared with that of an ovalbumin peptide fused to CTB and with untreated controls. Immunization with p210-CTB for 12 weeks caused a 35% reduction in aortic lesion size in
Apoe
−/−
mice. This effect was accompanied by induction of regulatory T cells that markedly suppressed effector T cells rechallenged with apoB-100 and increased numbers of interleukin (IL)-10
+
CD4
+
T cells. Furthermore, a peptide-specific antibody response was observed. Atheroprotection was also documented in
apoe
−/−
mice lacking functional transforming growth factor-β receptors on T cells.

Conclusion—

Nasal administration of an apoB-100 peptide fused to CTB attenuates atherosclerosis and induces regulatory Tr1 cells that inhibit T effector responses to apoB-100.
AMPKα2 Deletion Causes Aberrant Expression and Activation of NAD(P)H Oxidase and Consequent Endothelial Dysfunction In Vivo
Authors: Wang Shuangxi , Zhang Miao , Liang Bin , Xu Jian , Xie Zhonglin , Liu Chao , Viollet Benoit , Yan Daoguang , Zou Ming-Hui
Published: February 2010

Rational
:

AMP-activated protein kinase (AMPK) is an energy sensor and ubiquitously expressed in vascular cells. Recent studies suggest that AMPK activation improves endothelial function by counteracting oxidative stress in endothelial cells. How AMPK suppresses oxidative stress remains to be established.

Objective
:

The aim of this study is to examine the effects of AMPK in regulating NAD(P)H oxidase, oxidative stress, and endothelial function.

Methods and Results
:

The markers of oxidative stress, NAD(P)H oxidase subunit expression (gp91
phox
, p47
phox
, p67
phox
, NOX1 to -4), NAD(P)H oxidase–mediated superoxide production, 26S proteasome activity, IκBα degradation, and nuclear translocation of nuclear factor (NF)-κB (p50 and p65) were examined in cultured human umbilical vein endothelial cells and mouse aortas isolated from AMPKα2 deficient mice. Compared to the wild type, acetylcholine-induced endothelium-dependent relaxation was significantly impaired in parallel with increased production of oxidants in AMPKα2
−/−
mice. Further, pretreatment of aorta with either superoxide dismutase (SOD) or tempol or apocynin significantly improved acetylcholine-induced endothelium-dependent relaxation in AMPKα2
−/−
mice. Analysis of aortic endothelial cells from AMPKα2
−/−
mice and human umbilical vein endothelial cells expressing dominant negative AMPK or AMPKα2-specific siRNA revealed that loss of AMPK activity increased NAD(P)H oxidase subunit expression (gp91
phox
, p47
phox
, p67
phox
, NOX1 and -4), NAD(P)H oxidase–mediated superoxide production, 26S proteasome activity, IκBα degradation, and nuclear translocation of NF-κB (p50 and p65), whereas AMPK activation by AICAR or overexpression of constitutively active AMPK had the opposite effect. Consistently, we found that genetic deletion of AMPKα2 in low-density lipoprotein receptor knockout (LDLr
−/−
) strain markedly increased 26S proteasome activity, IκB degradation, NF-κB transactivation, NAD(P)H oxidase subunit overexpression, oxidative stress, and endothelial dysfunction, all of which were largely suppressed by chronic administration of MG132, a potent cell permeable proteasome inhibitor.

Conclusions
:

We conclude that AMPKα2 functions as a physiological suppressor of NAD(P)H oxidase and ROS production in endothelial cells. In this way, AMPK maintains the nonatherogenic and noninflammatory phenotype of endothelial cells.
Inotropic Response of Cardiac Ventricular Myocytes to β-Adrenergic Stimulation With Isoproterenol Exhibits Diurnal Variation
Authors: Collins Helen E. , Rodrigo Glenn C.
Published: February 2010

Rationale
:

Although >10% of cardiac gene expression displays diurnal variations, little is known of their impact on excitation–contraction coupling.

Objective
:

To determine whether the time of day affects excitation–contraction coupling in rat ventricles.

Methods and Results
:

Left ventricular myocytes were isolated from rat hearts at 2 opposing time points, corresponding to the animals resting or active periods. Basal contraction and [Ca
2+
]
i
was significantly greater in myocytes isolated during the resting versus active periods (cell shortening 12.4±0.3 versus 11.0±0.2%;
P
<0.05 and systolic [Ca
2+
]
i
422±12 versus 341±9 nmol/L;
P
<0.01. This corresponded to a greater sarcoplasmic reticulum (SR) Ca
2+
load (672±20 versus 551±13 nmol/L
P
<0.001). The increase in systolic [Ca
2+
]
i
in response to isoproterenol (>3 nmol/L) was also significantly greater in resting versus active period myocytes, reflecting a greater SR Ca
2+
load at this time. This diurnal variation in response of Ca
2+
-homeostasis to isoproterenol translated to a greater incidence of arrhythmic activity in resting period myocytes. Inhibition of neuronal NO synthase during stimulation with isoproterenol, further increased systolic [Ca
2+
]
i
and the percentage of arrhythmic myocytes, but this effect was significantly greater in active period versus resting period myocytes. Quantitative RT-PCR analysis revealed a 2.65-fold increase in neuronal NO synthase mRNA levels in active over resting period myocytes (
P
<0.05).

Conclusions
:

The threshold for the development of arrhythmic activity in response to isoproterenol is higher during the active period of the rat. We suggest this reflects a reduction in SR Ca
2+
loading and a diurnal variation in neuronal NO synthase signaling.
Advances in Genomic Analysis of Stroke
Authors: Lanktree Matthew B. , Dichgans Martin , Hegele Robert A.
Published: February 2010

As a result of technological advances, the genomic analysis of stroke has shifted from candidate gene association studies to genome-wide association studies (GWAS). Agnostic GWAS evaluate up to 90% of common genetic variation in a single experiment, creating an improved framework for identifying novel genetic leads for biochemical and cellular mechanisms underlying stroke. Given the ubiquity of the GWAS approach, it has become essential for stroke researchers and clinicians to be able to interpret GWAS results. Thus, we review the basic elements of design, methods, presentation, and interpretation of GWAS in the context of stroke research. In 8 recent stroke GWAS reports, no single locus has been identified in 2 GWAS at a genome-wide level of significance. Additionally, no significant association signal between stroke and a locus with previous evidence from candidate gene studies of stroke has been identified yet. Some caveats of the approach and future directions for stroke genomics are discussed, including the use of intermediate phenotypes, Mendelian randomization, phenomics, and deep resequencing. Intelligent, appropriately powered, multidisciplinary studies incorporating knowledge from clinical medicine, epidemiology, genetics, and molecular biology will be required to fully characterize the genomic contributors to stroke.
Ultraearly Thrombolysis in Acute Ischemic Stroke Is Associated With Better Outcome and Lower Mortality
Authors: Strbian Daniel , Soinne Lauri , Sairanen Tiina , Häppölä Olli , Lindsberg Perttu J. , Tatlisumak Turgut , Kaste Markku
Published: February 2010

Background and Purpose—

Pooled analysis of major placebo-controlled trials suggests that the earlier thrombolysis is given after ischemic stroke, the better the outcome. We report a single-center assessment of the effect of ultraearly thrombolysis on the outcome of our patients.

Methods—

Between January 2003, and December 2008, a total of 878 patients with ischemic stroke received thrombolysis within 4.5 hours from the symptom onset at the Helsinki University Central Hospital. Using univariate methods and multivariable logistic regression, we assessed the association between onset-to-treatment time (OTT) and favorable 3-month outcome (modified Rankin Scale 0 to 2).

Results—

Median age was 70.5 years, median OTT 115 minutes, and median National Institutes of Health Stroke Scale (NIHSS) on admission 9. After adjustment for baseline stroke severity, more patients with OTT <70 minutes had a favorable outcome than those with OTT ≥70 minutes. Specifically, OR of 5.15 (1.50 to 27.5) was for the patients with NIHSS 7 to 12, and 2.74 (1.26 to 5.90) for those with NIHSS ≥13. Of the patients with OTT ≤90 minutes, those with NIHSS 7 to 12 had an OR of 1.72 (1.00 to 2.96) for a favorable outcome, and those with NIHSS ≥13 had lower mortality than the ones with OTT >90 minutes (16.4% versus 29.5%;
P
=0.01). Multivariable model showed an association of better outcome with lower baseline glucose level, younger age, lower baseline NIHSS, and OTT <70 minutes.

Conclusions—

Ultraearly thrombolysis was associated with better outcome of our patients with stroke with moderate or severe symptoms. The earlier the treatment was given, the higher the likelihood of favorable outcome.
Five-Year Outcome of a Stroke Cohort in Martinique, French West Indies
Authors: Chausson Nicolas , Olindo Stéphane , Cabre Philippe , Saint-Vil Martine , Smadja Didier
Published: February 2010

Background and Purpose—

Limited information exists on stroke among black populations outside the United States and United Kingdom. Part 1 of the Etude Réalisée en Martinique et Centrée sur l’Incidence des Accidents vasculaires cérebraux (ERMANCIA) provided strong epidemiologic data on the incidence of first-ever stroke in a black Caribbean population and showed a 40% greater incidence of stroke in Martinique than in continental France. In ERMANCIA part 2, we evaluated the long-term outcomes of our cohort.

Methods—

Survivors of a first stroke from this prospective, community-based, stroke incidence study were reassessed at 5 years according to standardized procedures and criteria, including the modified Rankin scale, Barthel Index, Montgomery-Asberg Depression-Rating Scale, Mini-Mental State Examination, treatment compliance, and blood pressure control.

Results—

Of the 293 survivors of the original 580 (50.5%) patients who were still alive 5 years after stroke, 262 (89.4%) were assessed. Among these survivors, 66.4% were functionally independent and 43% were completely autonomous for activities of daily living, but 25.8% were depressed and 58.9% were cognitively impaired. Only 50 of 170 (29.4%) of the hypertensive patients achieved their target blood pressure.

Conclusions—

These results highlight the very poor blood pressure control and the very high rate of cognitive impairment in Martinican patients after stroke. As a consequence, a poststroke prevention network was established in Martinique.
‘Al Pie De La Letra’
Authors: Ovbiagele Bruce
Published: February 2010

Background and Purpose—

Ethnic minorities are at higher stroke risk than non-Hispanic whites yet are less likely to have optimal vascular risk factor control. There is a need to develop culturally sensitive strategies for enhancing vascular risk reduction in minority patients with stroke. This study aimed to develop a postdischarge report card to boost treatment adherence among elderly Spanish-speaking patients with stroke within an urban health system.

Methods—

This study included a total of 13 Spanish-only speaking participants aged ≥60 years discharged from a local government hospital in Los Angeles within 18 months of an index ischemic stroke and 6 caregivers engaged in focus groups and interviews. Structured interviews were conducted with 11 care providers and 9 administrators at the hospital. Framework analysis examined the data and elicited themes to adapt a pre-existing patient report card tool.

Results—

Spontaneously using the same phrase, “Al pie de la letra,” several participants expressed a need to follow medical instructions accurately to prevent recurrent stroke and identified barriers/facilitators for doing so. They made comments about the pre-existing report card, advising several changes, including the clarification of phrases, and written instructions to explain the need for the card and how to fill it out. The providers and administrators recommended avenues for successfully using the card at the hospital. A new report card was created that incorporated all major perspectives.

Conclusions—

Crafting a culturally sensitive tool for promoting treatment adherence in elderly Spanish-only-speaking patients with stroke within an urban health system using a participatory methodology is feasible. The efficacy of this new report card should be tested in a randomized controlled trial.
The Fact and Fiction of Cotton Mather's Correspondence with German Pietist August Hermann Francke
Authors: Splitter Wolfgang
Published: February 2010

Carefully reevaluating the available sources, this essay sheds new light on Cotton Mather's correspondence with German Pietist August Hermann Francke. Far from being a model of early modern cross-Atlantic intellectual exchange, theirs was just an intermittent, limited contact that, for many reasons, failed to grow into a mutually stimulating discourse.
Boswell at the Breakfast Table
Authors: Dowling William C.
Published: February 2010

Oliver Wendell Holmes's The Autocrat of the Breakfast Table is subtitled “Every Man His Own Boswell”: a declaration not only of Holmes's admiration for Samuel Johnson but of his urgent sense of Johnson's London circle as embodying intellectual values still sadly lacking in an America ruled by crude economic individualism.
Breathing the “Free Aire of the New World”: The Influence of the New England Way on the Gathering of Congregational Churches in Old England, 1640–1660
Authors: Young Ralph F.
Published: February 2010

Puritans in England, although engaged in the struggle against Charles I and setting up the Commonwealth under Cromwell closely watched the Puritans of Massachusetts Bay. In demonstrating how the New England Way of church polity influenced the rise of Congregationalism in England, Young details the transatlantic flow of ideas from colony to motherland.
Internet Use and the Concentration of Disadvantage: Glocalization and the Urban Underclass
Authors: Hampton Keith N.
Published: February 2010

This article argues that the literature on digital inequality—in its focus on individual characteristics, behaviors, and outcomes—has overlooked change within the context of where social and civic inequalities are reproduced. This omission is the result of a failure to explore the role of ecological context within the study of the digital divide and the role of communication within the study of collective efficacy. Social cohesion, and an expectation for informal social control at the neighborhood level, is a function of both ecological context and media context. Those embedded within settings where prior media, including the telephone and face-to-face contact, could not overcome contextual barriers to collective action, namely within areas of concentrated disadvantage; may now, as a result of local Internet use, experience reduced social and civic inequality. This article is based on the results of a 3-year naturalistic experiment that examined the use of the Internet for communication at the neighborhood level. It proposes a new measure of collective efficacy — in place of network measures or perceived cohesion — based on the direct observation of communication practices. The analysis includes a model of the ecological characteristics associated with neighborhoods that adopted the Internet as a means of local information exchange, and it provides a comparison of the content of electronic messages exchanged within areas of advantage and those of extreme poverty, unemployment, and racial segregation. Findings suggest that as much as the Internet supports social and civic engagement in areas where it is already likely to be high, it also affords engagement within contexts of extreme disadvantage.
Competing rationalities in the diversity project of the UK judiciary: The politics of assessment centres
Authors: Healy Geraldine , Kirton Gill , Özbilgin Mustafa , Oikelome Franklin
Published: February 2010

Assessment centres (ACs) are increasingly used to recruit highly qualified staff, yet there are few attempts to appraise their introduction from a diversity perspective. This article addresses this gap by exploring the introduction of ACs as a means of increasing the diversity of the judiciary in the UK. It analyses the underpinning politics guiding the processes and subjective experiences of ACs using Weber’s identification of types of rationality and argues that substantive rationalities drive the formal rationality of the AC. The study demonstrates the theoretical value of incorporating diversity into the rationality framework and shows that the design, management and implementation of ACs are shaped by the competing rationalities that surround and imbue judicial work. While ACs may be introduced to demonstrate fair selection practices and challenge the reproduction of unfair discriminatory practices, such formal interventions are inevitably partial and bound by the distinctive institutional context and the societal context of inequalities.
A Modified TSD Specimen for Fracture Toughness Characterization - Fracture Mechanics Analysis and Design
Authors: Berggreen Christian , Carlsson Leif A.
Published: February 2010

The tilted sandwich debond (TSD) specimen has been recognized as a viable candidate for characterization of the face/core fracture resistance. Analysis, however, shows that the range of phase angles that can be realized by altering the tilt angle and other parameters of the test is quite limited. A method to extend the range of mode-mixities of the TSD specimen is to introduce a larger amount of transverse shear by reinforcing the loaded upper face with a stiff metal plate. Analysis shows that this method extends the range of phase angles to a practically useful range. Guidelines on selection of thicknesses of the reinforcement, and design considerations for further modifications are provided.
Cyclic Hysteresis Evolution as a Damage Parameter for Notched Composite Laminates
Authors: Tan T.F. , Dharan C.K.H.
Published: February 2010

In cyclically loaded polymer matrix composites, structural health monitoring is useful for detecting and tracking progressive damage. Existing approaches use stiffness degradation, crack propagation/strain energy change, or dynamic parameters such as frequency response. These approaches, however, depend on prior assumptions of the dominant damage mechanisms. In this study, a new hysteresis-based damage parameter, D′, that is a measure of damage progression and failure is shown to be more sensitive than stiffness degradation and can be determined during cycling without the use of additional instrumentation. D′ was measured for cyclically loaded notched glass fiber laminates and was found to be useful as a measure of damage progression. Cyclic hysteresis strain energy dissipated at each cycle was monitored continuously without interruption. A conventional servo-hydraulic fatigue testing system was modified with the incorporation of new custom code for performing command and data acquisition on a cycle-by-cycle basis. In this fashion, progressive damage at each cycle was determined quantitatively in real time during each test. Hysteresis data were obtained from fatigue tests conducted on notched [0/90] E-glass/epoxy laminates in real time on a cycle-by-cycle basis and used to estimate failure. The damage parameter D′ exhibited an approximately linear increase with cycling followed by an exponential increase just before failure. Modeling this behavior allowed for the prediction of damage progression and residual life as a function of load cycles. Hysteresis-based damage parameters for other material configurations were also calculated and found to give good estimates for the cyclic life.
Cultural Capital in East Asian Educational Systems
Authors: Yamamoto Yoko , Brinton Mary C.
Published: February 2010

Cultural capital has been an important but often elusive concept in the study of educational processes and social class reproduction. The authors suggest that this is partly because a country’s educational system and ways of evaluating students at different educational transitions set the context for the mechanisms through which embodied and objectified cultural capital operate. Moreover, parents in some societies invest in children’s “shadow education” (extracurricular classes or tutoring) at key educational transitions, and it is not clear whether this replaces cultural capital or supplements it. The authors use data from Japan, a country whose educational system depends heavily but not exclusively on standardized examinations, to examine how cultural capital affects students’ progress at three points in the educational process that involve different relative emphasis on examinations and on teachers’ subjective judgment. In this way, the authors clarify the ways that embodied and objectified cultural capital exert effects on educational outcomes.
Local Public Expenditures and Housing Prices
Authors: García Jaume , Montolio Daniel , Raya Josep Maria
Published: February 2010

This paper estimates a hedonic price model which makes it possible to determine how the price of a unit varies with the set of attributes it possesses, in the Spanish housing market. Concretely, and by means of capitalisation, hedonic price models can be used as an instrument to capture how local public expenditures influence housing prices and, by extension, how homeowners can indirectly receive benefit from local public investment. Using individual data for dwellings from the city of Barcelona (Spain) for the period 1998—2001, it is found that local policies aimed at enhancing the quality of life or the location-specific characteristic of the city of Barcelona have a positive impact on housing values.
On the application of fuzzy predictive control based on multiple models strategy to a tubular heat exchanger system
Authors: Mazinan A.H. , Sadati N.
Published: February 2010

The purpose of the paper presented here is to control the fluid temperature that flows in the inner tube of a tubular heat exchanger system by means of the fluid flow pressure. This system in its present form has a specified range of the coefficients’ variation, while the temperature of the outlet fluid could generally be controlled by either the temperature or the flow of the inlet fluid flowing in the shell tube. The control realization for the system presented is often complicated, because the variation of the system coefficients and the reference signal must be thoroughly covered by the control action. In such a case, the system behaviour must first be represented by the multiple explicit models and then the appropriate control approach needs to be realized based on new techniques. A novel multiple models control strategy using both fuzzy-based predictive control (FPC) and overall fuzzy-based predictive model (OFPM) has been proposed in this paper. Concerning the strategy, the system must be modelled through the multiple OFPMs, while the corresponding FPCs need to be designed based on the model results. Hereinafter, the best OFPM of the system is accurately identified by an intelligent decision mechanism (IDM), as long as the system coefficients are abruptly varied, at each instant of time. Subsequently, the best FPC is chosen by the IDM and therefore its control action is applied to the system. In order to demonstrate the effectiveness of the proposed strategy, simulations are carried out and the corresponding results are compared with those obtained using the well-known single model linear generalized predictive controller (SMLGPC), where the observer polynomial so-called T- polynomial is used to cope with the better disturbance rejection properties. By analysing the proposed control strategy performance in comparison with the SMLGPC, when the system coefficients and the desired set point are abruptly changed, it is easily observed that the new acquired performance is as good as the SMLGPC, where it is well known as a powerful control approach in the linear model-based predictive control family.
Anarchy
Authors: Billow Richard M.
Published: February 2010

Therapists face situations in which individuals, subgroups, or groups cannot or will not tolerate and rebel against truth seeking. Anarchy, a virulent form of rebellion, utilizes excessive and violent projective identification to engulf participants in treatment—destructive enactments. Anarchic members and/or group processes aggressively disturb mental and emotional links within and among individuals through which truth is negotiated and substantiated by experience. Empathy, thinking, language—and the social boundaries of time and space—may be applied deceitfully to undermine truth seeking. The goal is to destroy the particular group, and also, the very idea of group, which is envied and hated. In four case examples, members (including the leaders) lost their confidence and faith in groups to the extent to which they were not protected from anarchy.
The arbitrariness of supermajority rules
Authors: Schwartzberg Melissa
Published: February 2010

There may be good general grounds for the adoption of supermajoritarian thresholds, but no such general arguments can justify the selection of a specific threshold. Although the benefits of supermajority rules, especially in the context of constitutional-amendment procedures, may outweigh the costs of their ex ante indeterminacy, the technically unjustifiable nature of specific thresholds means that those who are disadvantaged under such rules can be given no rational or reasonable explanation for their defeat other than the de facto power of coordination on a threshold. Political theory has a potential remedy in cases in which good reasons are not available, and in which bad reasons (such as the desire to ensure a veto for a powerful minority) might be brought to bear: randomization. If the benefits of supermajority rules are worth the costs of arbitrariness, we may wish to randomize the choice of threshold, though the move to do so may have its own negative consequences.
Wisdom and numbers
Authors: Lagerspetz Eerik
Published: February 2010

There is a permanent tension between the requirements of substantive goodness or wisdom and those of formal legitimacy in public decision-making. This article charts the various attempts to reconcile the two requirements within decision rules. First, the history of decision rules from medieval times to the 19th century is briefly reviewed. Second, it is shown that the most popular contemporary attempt to justify a decision principle in epistemic terms, based on Condorcet’s famous Jury Theorem, does not actually support democracy. Finally, it is argued that the contemporary theorists of deliberative democracy are ultimately struggling with the same old problem as the medieval political theorists. All attempts to combine the two requirements in a systematic way are doomed to fail.
Bullying Perpetration and Victimization in Special Education: A Review of the Literature
Authors: Rose Chad A. , Monda-Amaya Lisa E. , Espelage Dorothy L.
Published: February 2010

Bullying perpetration and victimization have become pervasive problems in American schools. Recent research suggests a causal association between prolonged periods of victimization and overt acts of school violence. These findings are germane to students with disabilities in light of evidence suggesting these students are victimized more often than typically developing peers. The purpose of this review is to provide special educators with an overview of definitions and issues related to bullying perpetration and victimization and to synthesize research on this topic as it pertains to students with disabilities by disability type, personal characteristics, and educational placement. It was concluded that additional research is needed on prevalence and types of bullying, factors related to perpetration or victimization, and appropriate school-based interventions for special needs populations.