bluuebunny/crossref_metadata_2025 huggingface dataset:
Single nucleotide polymorphisms in the human Na+-dicarboxylate cotransporter affect transport activity and protein expression
Authors: Pajor Ana M. , Sun Nina N.
Published: October 2010

The sodium-coupled transport of citric acid cycle intermediates in the intestine and kidney is mediated by the Na+-dicarboxylate cotransporter, NaDC1. In the kidney, NaDC1 plays an important role in regulating succinate and citrate concentrations in the urine, which may have physiological consequences including the development of kidney stones. In the present study, the impact of nonsynonymous single nucleotide polymorphisms (SNPs) on NaDC1 expression and function was characterized using the COS-7 cell heterologous expression system. The I550V variant had an increased sensitivity to lithium inhibition although there were no significant effects on protein abundance. The L44F variant had no significant effects on expression or function. The membrane protein abundance of the M45L, V117I, and F254L variants was decreased, with corresponding decreases in transport activity. The A310P variant had decreased protein abundance as well as a change in substrate selectivity. The P385S variant had a large decrease in succinate transport Vmax, as well as altered substrate selectivity, and a change in the protein glycosylation pattern. The most damaging variant was V477M, which had decreased affinity for both succinate and sodium. The V477M variant also exhibited stimulation by lithium, indicating a change in the high-affinity cation binding site. We conclude that most of the naturally occurring nonsynonymous SNPs affect protein processing of NaDC1, and several also affect functional properties. All of these mutations are predicted to decrease transport activity in vivo, which would result in decreased intestinal and renal absorption of citric acid cycle intermediates.
Effect of blood pressure on vascular hemodynamics in acute tachycardia
Authors: Zheng Hai , Huo Yunlong , Svendsen Mark , Kassab Ghassan S.
Published: October 2010

Paroxysmal supraventricular tachycardia is accompanied by hypotension, which can affect vascular hemodynamics. Here, we hypothesized that a fall in blood flow as a result of hypotension has a larger effect on hemodynamics in medium-sized peripheral arteries compared with increased pulsatility in rapid pacing. To test this hypothesis, we experimentally and theoretically investigated hemodynamic changes in femoral, carotid, and subclavian arteries at heart rates of 95–170 beats/min after acute pacing. The arterial pressure, blood flow, and other hemodynamic parameters remained statistically unchanged for heart rates ≤135 beats/min. Systemic pressure and flow velocities, however, showed an abrupt decrease, resulting in larger alteration of hemodynamic parameters for heart rates ≥155 beats/min after pacing (initial period) and then recovered close to baseline after several minutes of pacing (recovery period). During the initial period, the pressure dropped from 88 mmHg (baseline) to 44 mmHg, and the flow velocity decreased to about one-third of baseline at heart rate of 170 beats/min. A hemodynamic analysis showed a velocity profile with a near-wall retrograde flow or a fully reversed flow during the initial period, which vanished at the recovery period. It was concluded that the initial fall of blood flow due to pressure drop led to transient flow reversal and negative wall shear stress because this phenomena was not observed at the recovery period. This study underscores the significant effects of hypotension on vascular hemodynamics, which may have relevance to physiology and chronic pathophysiology in paroxysmal supraventricular tachycardia.
Intermuscular force transmission between human plantarflexor muscles in vivo
Authors: Bojsen-Møller Jens , Schwartz Sidse , Kalliokoski Kari K. , Finni Taija , Magnusson S. Peter
Published: October 2010

The exact mechanical function of synergist muscles within a human limb in vivo is not well described. Recent studies indicate the existence of a mechanical interaction between muscle actuators that may have functional significance and further play a role for injury mechanisms. The purpose of the present study was to investigate if intermuscular force transmission occurs within and between human plantarflexor muscles in vivo. Seven subjects performed four types of either active contractile tasks or passive joint manipulations: passive knee extension, voluntary isometric plantarflexion, voluntary isometric hallux flexion, passive hallux extension, and selective percutaneous stimulation of the gastrocnemius medialis (MG). In each experiment plantar- and hallux flexion force and corresponding EMG activity were sampled. During all tasks ultrasonography was applied at proximal and distal sites to assess task-induced tissue displacement (which is assumed to represent loading) for the plantarflexor muscles [MG, soleus (SOL), and flexor hallucis longus (FHL)]. Selective MG stimulation and passive knee extension resulted in displacement of both the MG and SOL muscles. Minimal displacement of the triceps surae muscles was seen during passive hallux extension. Large interindividual differences with respect to deep plantarflexor activation during voluntary contractions were observed. The present results suggest that force may be transmitted between the triceps surae muscles in vivo, while only limited evidence was provided for the occurrence of force transfer between the triceps surae and the deeper-lying FHL.
Metabolic Profiling Detects Field Effects in Nondysplastic Tissue from Esophageal Cancer Patients
Authors: Yakoub Danny , Keun Hector C. , Goldin Robert , Hanna George B.
Published: October 2010

The variable rate of missed cancer in endoscopic biopsies and lack of other biomarkers reduce the effectiveness of surveillance programs in esophageal cancer. Based on the “field cancerization” hypothesis that tumors arise within a transformed field with an altered biochemical phenotype, we sought to test if metabolic profiling could differentiate between histologically normal tissue from individuals with and without esophageal cancer. Thirty-five patients with esophageal adenocarcinoma and 52 age-matched controls participated in the study. Using 1H magic angle spinning–nuclear magnetic resonance spectroscopy of intact tissue, we generated metabolic profiles of tumor tissue, proximal histologically normal mucosa from cancer patients (PHINOM), and proximal histologically normal mucosa from a control group. Using multivariate regression and receiver-operator characteristic analysis, we identified a panel of metabolites discriminating malignant and histologically normal tissues from cancer patients and from that of controls. Whereas 26% and 12% of the spectral profile regions were uniquely discriminating tumor or control tissue, respectively, 5% of the profile exhibited a significant progressive change in signal intensity from controls to PHINOM to tumor. Regions identified were assigned to phosphocholine (PC), glutamate (Glu), myo-inositol, adenosine-containing compounds, uridine-containing compounds, and inosine. In particular, the PC/Glu ratio in histologically normal tissue signified the presence of esophageal cancer (n = 123; area under the curve, 0.84; P < 0.001). In conclusion, our findings support the hypothesis of the presence of metabonomic field effects in esophageal cancer, even in non-Barrett's segments. This indicates that metabolic profiling of tissue can potentially play a role in the surveillance of cancer by reporting on the phenotypic consequences of field cancerization. Cancer Res; 70(22); 9129–36. ©2010 AACR.
Sorafenib Overcomes TRAIL Resistance of Hepatocellular Carcinoma Cells through the Inhibition of STAT3
Authors: Chen Kuen-Feng , Tai Wei-Tien , Liu Tsung-Hao , Huang Hsiang-Po , Lin Yu-Chin , Shiau Chung-Wai , Li Pui-Kai , Chen Pei-Jer , Cheng Ann-Lii
Published: October 2010

Purpose: Recombinant tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising antitumor agent. However, many hepatocellular carcinoma (HCC) cells show resistance to TRAIL-induced apoptosis. Here, we report that sorafenib improves the antitumor effect of TRAIL-related agents in resistant HCC.

Experimental Design: HCC cell lines (PLC5, Huh-7, Hep3B, and Sk-Hep1) were treated with sorafenib and/or TRAIL-related agents (TRAIL or LBY135) and analyzed in terms of apoptosis and signal transduction. In vivo efficacy was determined in nude mice with PLC5 xenografts.

Results: Sorafenib, the only approved drug for HCC, sensitizes resistant HCC cells to an agonistic DR5 antibody (LBY135) and TRAIL-induced apoptosis in TRAIL-resistant HCC cells. We found that STAT3 played a significant role in mediating TRAIL sensitization. Our data showed that sorafenib downregulated phospho-STAT3 (pSTAT3) and subsequently reduced the expression levels of STAT3-related proteins (Mcl-1, survivin, and cyclin D1) in a dose- and time-dependent manner in TRAIL-treated HCC cells. Knockdown of STAT3 by RNA interference overcame apoptotic resistance to TRAIL in HCC cells, and ectopic expression of STAT3 in HCC cells abolished the TRAIL-sensitizing effect of sorafenib. Moreover, SHP-1 inhibitor reversed downregulation of pSTAT3 and apoptosis induced by sorafenib, and silencing of SHP-1 by RNA interference abolished the effects of sorafenib on pSTAT3. Notably, sorafenib increased SHP-1 activity in PLC5 cells. Finally, sorafenib plus LBY135 significantly suppressed PLC5 xenograft tumor growth.

Conclusions: Sorafenib sensitizes resistant HCC cells to TRAIL-induced apoptosis at clinical achievable concentrations, and this effect is mediated via the inhibition of STAT3. Clin Cancer Res; 16(21); 5189–99. ©2010 AACR.
Oral thrombostatin FM19 inhibits prostate cancer
Authors: Nieman Marvin , LaRusch Gretchen , Fang Chao , Zhou Yihua , Schmaier Alvin
Published: October 2010

Thrombin stimulates proliferation, invasion and metastasis by cleaving protease-activated receptor 1 (PAR1) on human prostate cancer cells. Current direct thrombin inhibitors pose risks for bleeding in the cancer patients. We have developed an oral reversible direct thrombin inhibitor called FM19. FM19 inhibits thrombin-induced calcium mobilisation of PC3 cells with an IC50 of 15 μM with a 95% confidence interval of 7.3–31.6 μM. Thrombin stimulation increases PC3 cell invasion threefold from 27.1 ± 11.4 to 66 ± 11.6. FM19 or bivalirudin reduces cell invasion at ≥0.1 μM (p≤0.02). After inoculation with PC3 cells, nude mice were treated with oral FM19 at 3 mg/ml in the drinking water. The treated mice did not have long bleeding times and only a 1.4-fold increase in their thrombin clotting time. However, with treatment, the mice have a reduced rate of tumour growth 0.26 ± 0.17 fold change/day vs. 0.55 ± 0.35 for untreated (p = 0.038), reduced fold change in tumour size 5.3 ± 0.47 to 8.9 ± 1.8 (untreated) (p=0.048), and reduced overall tumour weight 0.5 ± 0.31 g vs. 0.82 ± 0.32 g (untreated) (p=0.04). On microscopic examination, FM19 treatment reduces the number of large vessels in the tumours from 4.6 ± 2.1 per high-powered field in untreated samples to 1.4 ± 1.4 in treated samples (p≤0.04). These studies show FM19 reduces prostate tumour growth in vivo at a concentration below that needed for anticoagulation. These data suggest novel opportunities for oral direct thrombin inhibitors in cancer therapy.
Biological and clinical response to desmopressin (DDAVP) in a retrospective cohort study of children with low von Willebrand factor levels and bleeding history
Authors: Meschengieser Susana , Woods Adriana , Chuit Roberto , Turdó Karina , Blanco Alicia , Lazzari María , Sánchez-Luceros Analía
Published: October 2010

The diagnosis and management of von Willebrand disease (VWD) in paediatrics is challenging. Our aim was to review patient’s characteristics related to biological and clinical response to DDAVP in children with low von Willebrand factor (VWF) levels and bleeding history from a single institution. We included a retrospective cohort of 221 children (median age 11 years; 137 females): 27 type 1 (VWF levels within 15–30 IU dL-1) and 194 possible type 1 (VWF levels within 31–49 IU dL-1). The DDAVP infusion-test was performed in 214/221 children, 93.4% of whom showed good response. Patients with type 1 were at higher risk of DDAVP-test failure: 9/26 (34.6%) vs. 18/188 (9.6%) with possible type 1 (RR 3.44, 1.75–6.79; p= 0.002, Fisher’s exact test). In 68 children, the clinical response to DDAVP was evaluated 87 times: i) to stop bleeding: menorrhagia (13), mucocutaneous (12), haemarthrosis (1); and ii) to prevent surgical bleeding: adenotonsillectomy (17), major (15) and minor surgery (10); and dental procedures (19). No major adverse events or bleeding were observed. The treatment was effective with one single dose of DDAVP in almost all patients, without antifibrinolytic or local therapy, except in a girl with severe haemorrhage during menarche who required replacement therapy. In conclusion, patients with VWD type 1 were at higher risk of no response to DDAVP infusion-test. In this series, one dose of DDAVP proved effective and safe for children with VWD. Since this is a safe, effective and affordable therapy, we consider that a wider use should be promoted, especially in developing countries.
The effect of initiating combined antiretroviral therapy on endothelial cell activation and coagulation markers in South African HIV-infected individuals
Authors: van Gorp Eric C. M. , Meijers Joost C. M. , Cate Hugo ten , Jacobson Barry F. , Jong Eefje , Louw Susan
Published: October 2010

An increased incidence of venous thromboembolism (VTE) is observed in human immunodeficiency virus (HIV)-infected patients. Only a limited number of studies described the effect of combined antiretroviral therapy (cART) on coagulation markers. In a prospective cohort study in cART-naive South African HIV-infected individuals the effect of initiating cART on markers of endothelial cell activation, coagulation and natural anticoagulation was studied. These markers were compared to the reference ranges for an HIV-uninfected control population recruited from hospital staff. A venous ultrasound of both legs was performed to detect asymptomatic deep venous thrombosis (DVT). A total number of 123 HIV-infected participants were included. The patients were predominantly black and severely immuno-compromised. The CD4 cell count increased and the HIV viral load decreased significantly after the initiation of cART (p<0.001). The median follow-up period was 7.2 (± 1.6) months. Laboratory testing before and after initiation of cART was completed by 86 patients. Before initiating cART significantly elevated von Willebrand factor and D-dimer levels, increased activated protein C sensitivity ratio (APCsr) and decreased total and free protein S and protein C levels were observed compared to HIV-negative controls. At follow-up all markers, except APCsr, improved towards the normal range for controls without showing complete normalisation. In a subgroup of 57 patients no asymptomatic DVT was found. Compared to the controls, abnormal levels of coagulation markers were observed in HIV-infected individuals before and after the initiation of cART. Most markers improved after starting cART, but remained significantly different from the controls, indicating a persistent disturbed haemostatic balance.
Safety of thrombolysis in cerebral venous thrombosis
Authors: Squizzato Alessandro , Gianni Monica , De Lodovici Maria , Venco Achille , Paciaroni Maurizio , Crowther Mark , Ageno Walter , Dentali Francesco
Published: October 2010

Several small series have suggested the efficacy of thrombolysis in patients with cerebral vein thrombosis (CVT). However, since no randomised controlled trials have compared the use of thrombolysis with anticoagulant treatment in these patients, the risk to benefit ratio of this approach remains uncertain. The aim of this study is therefore to assess the safety of thrombolysis in CVT estimating mortality and major bleeding complications. MEDLINE and EMBASE databases were searched up to June 2010. Two reviewers performed study selection independently. Studies providing data on mortality and/or on the incidence of major bleeding complications were potentially eligible for the study. Two reviewers independently extracted data on study and population characteristics, type, dose and administration route of thrombolytic treatment; use and dose of concomitant heparin. Weighted mean proportion of the mortality rate and of the rate of major and non-major bleeding complications were calculated. Fifteen studies for a total of 156 patients were included. Twelve patients died after thrombolysis (weighted mean 9.2%; 95% CI 4.3, 15.7%) and 15 patients had a major bleeding complication (weighted mean 9.8%; 95% CI 5.3, 15.6%). Twelve haemorrhages were intracranial (weighted mean 7.6%; 95% CI 3.5, 13.1%), and seven of these patients died (58.3%; 95% CI 32.0, 80.7%). Our results suggest that thrombolysis is associated with a nonnegligible incidence of major bleeding complications, including intracranial bleeding potentially affecting patients outcome. Future studies are necessary to evaluate the safety of thrombolysis in comparison to more conservative strategies.
Inconsistencies in the planning of the duration of anticoagulation among outpatients with acute deep-vein thrombosis
Authors: Willenberg Torsten , Banyai Martin , Frank Ulrich , Baldi Thomas , Amann-Vesti Beatrice , Baumgartner Iris , Spirk David , Husmann Marc , Kucher Nils
Published: October 2010

Three-month anticoagulation is recommended to treat provoked or first distal deep-vein thrombosis (DVT), and indefinite-duration anticoagulation should be considered for patients with unprovoked proximal, un-provoked recurrent, or cancer-associated DVT. In the prospective Out-patient Treatment of Deep Vein Thrombosis in Switzerland (OTIS-DVT) Registry of 502 patients with acute objectively confirmed lower extremity DVT (59% provoked or first distal DVT; 41% unprovoked proximal, unprovoked recurrent, or cancer-associated DVT) from 53 private practices and 11 hospitals, we investigated the planned duration of anticoagulation at the time of treatment initiation. The decision to administer limited-duration anticoagulation therapy was made in 343 (68%) patients with a median duration of 107 (interquartile range 91–182) days for provoked or first distal DVT, and 182 (interquartile range 111–184) days for unprovoked proximal, unprovoked recurrent, or cancer-associated DVT. Among patients with provoked or first distal DVT, anticoagulation was recommended for <3 months in 11%, ≥3 months in 63%, and for an indefinite period in 26%. Among patients with unprovoked proximal, unprovoked recurrent, or cancer-associated DVT, anticoagulation was recommended for <6 months in 22%, 6–12 months in 38%, and for an indefinite period in 40%. Overall, there was more frequent planning of indefinite-duration therapy from hospital physicians as compared with private practice physicians (39% vs. 28%; p=0.019). Considerable inconsistency in planning the duration of anticoagulation therapy mandates an improvement in risk stratification of outpatients with acute DVT.
Loss of MicroRNAs in Neural Crest Leads to Cardiovascular Syndromes Resembling Human Congenital Heart Defects
Authors: Huang Zhan-Peng , Chen Jian-Fu , Regan Jenna N. , Maguire Colin T. , Tang Ru-Hang , Dong Xiu Rong , Majesky Mark W. , Wang Da-Zhi
Published: October 2010

Objective—

Congenital heart defects represent the most common human birth defects. Even though the genetic cause of these syndromes has been linked to candidate genes, the underlying molecular mechanisms are still largely unknown. Disturbance of neural crest cell (NCC) migration into the derivatives of the pharyngeal arches and pouches can account for many of the developmental defects. The goal of this study was to investigate the function of microRNA (miRNA) in NCCs and the cardiovascular system.

Methods and Results—

We deleted Dicer from the NCC lineage and showed that Dicer conditional mutants exhibit severe defects in multiple craniofacial and cardiovascular structures, many of which are observed in human neuro-craniofacial-cardiac syndrome patients. We found that cranial NCCs require Dicer for their survival and that deletion of Dicer led to massive cell death and complete loss of NCC-derived craniofacial structures. In contrast, Dicer and miRNAs were not essential for the survival of cardiac NCCs. However, the migration and patterning of these cells were impaired in Dicer knockout mice, resulting in a spectrum of cardiovascular abnormalities, including type B interrupted aortic arch, double-outlet right ventricle, and ventricular septal defect. We showed that Dicer loss of function was, at least in part, mediated by miRNA-21 (miR-21) and miRNA-181a (miR-181a), which in turn repressed the protein level of Sprouty 2, an inhibitor of Erk1/2 signaling.

Conclusion—

Our results uncovered a central role for Dicer and miRNAs in NCC survival, migration, and patterning in craniofacial and cardiovascular development which, when mutated, lead to congenital neuro-craniofacial-cardiac defects.
Circulating Proprotein Convertase Subtilisin Kexin Type 9 Has a Diurnal Rhythm Synchronous With Cholesterol Synthesis and Is Reduced by Fasting in Humans
Authors: Persson Lena , Cao Guoqing , Ståhle Lars , Sjöberg Beatrice G. , Troutt Jason S. , Konrad Robert J. , Gälman Cecilia , Wallén Håkan , Eriksson Mats , Hafström Ingiäld , Lind Suzanne , Dahlin Maria , Åmark Per , Angelin Bo , Rudling Mats
Published: October 2010

Objective—

To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes.

Methods and Results—

We monitored circulating PCSK9 in a set of dynamic human experiments and could show that serum PCSK9 levels display a diurnal rhythm that closely parallels that of cholesterol synthesis, measured as serum lathosterol. In contrast to these marked diurnal changes in cholesterol metabolism, serum low-density lipoprotein (LDL) cholesterol levels remained stable during the diurnal cycle. Depletion of liver cholesterol by treatment with the bile acid–binding resin, cholestyramine, abolished the diurnal rhythms of both PCSK9 and lathosterol. Fasting (>18 hours) strongly reduced circulating PCSK9 and lathosterol levels, whereas serum LDL levels remained unchanged. Growth hormone, known to be increased during fasting in humans, reduced circulating PCSK9 in parallel to LDL cholesterol levels.

Conclusion—

Throughout the day, and in response to fasting and cholesterol depletion, circulating PCSK9 displays marked variation, presumably related to oscillations in hepatic cholesterol that modify its activity in parallel with cholesterol synthesis. In addition to this sterol-mediated regulation, additional effects on LDL receptors may be mediated by hormones directly influencing PCSK9.
Protein Kinase Cδ Deficiency Accelerates Neointimal Lesions of Mouse Injured Artery Involving Delayed Reendothelialization and Vasohibin-1 Accumulation
Authors: Bai Xue , Margariti Andriana , Hu Yanhua , Sato Yasufumi , Zeng Lingfang , Ivetic Aleksandar , Habi Ouassila , Mason Justin C. , Wang Xian , Xu Qingbo
Published: October 2010

Objective—

To use protein kinase C (PKC) δ–knockout mice to investigate the role of PKCδ in lesion development and to understand the underlying mechanism of the vascular disease.

Methods and Results—

PKCδ functions as a signal transducer mediating several essential functions of cell proliferation and apoptosis. However, the effect of PKCδ on neointimal formation in wire-injured vessels is unknown. Three weeks after wire injury of femoral arteries, neointimal lesions were significantly increased in PKCδ
−/−
mice compared with PKCδ
+/+
animals. Immunohistochemical staining revealed that total numbers of smooth muscle cells and macrophages in the lesions of PKCδ
−/−
mice were markedly elevated without changing the ratio of these 2 cell types. To further elucidate the mechanisms of PKCδ-mediated increase in the lesion, an in vivo endothelial migration model was established to evaluate endothelial wound healing after wire injury. Data showed that reendothelialization of the injured vessel was markedly delayed in PKCδ
−/−
mice; this coincided with more severe intimal hyperplasia. Migration of endothelial cells cultivated from cardiac tissue was markedly reduced in the absence of PKCδ, whereas no difference in proliferation or apoptosis was detected. Inhibition of PKCδ activity or protein expression by small hairpin RNA (shRNA) in cultured endothelial cells confirmed the defective migratory phenotype. Interestingly, vasohibin-1, an antiangiogenesis protein, was elevated in endothelial cells derived from PKCδ
−/−
mice, which was mainly because of delayed protein degradation mediated by PKCδ. Downregulation of vasohibin-1 restored the migration rate of PKCδ
−/−
endothelial cells to a similar level as PKCδ
+/+
cells.

Conclusion—

PKCδ deficiency enhances neointimal formation, which is associated with delayed reendothelialization and involves increased cellular vasohibin-1 accumulation.
Paracrine Stimulation of Endothelial Cell Motility and Angiogenesis by Platelet-Derived Deoxyribose-1-Phosphate
Authors: Pula Giordano , Garonna Elena , Dunn Warwick B. , Hirano Michio , Pizzorno Giuseppe , Campanella Michelangelo , Schwartz Edward L. , el Kouni Mahmoud H. , Wheeler-Jones Caroline P.D.
Published: October 2010

Objective—

Micromolar concentrations of the proangiogenic metabolite deoxyribose-1-phosphate (dRP) were detected in platelet supernatants by mass spectrometry. In this study, we assessed whether the release of dRP by platelets stimulates endothelial cell migration and angiogenesis.

Methods and Results—

Protein-free supernatants from thrombin-stimulated platelets increased human umbilical vein endothelial cell migratory activity in transmigration and monolayer repair assays. This phenomenon was ablated by genetic silencing of dRP-generating uridine phosphorylase (UP) and thymidine phosphorylase (TP) or pharmacological inhibition of UP and restored by exogenous dRP. The stimulation of endothelial cell migration by platelet-derived dRP correlated with upregulation of integrin β
3
, which was induced in a reactive oxygen species–dependent manner, and was mediated by the activity of the integrin heterodimer α
v
β
3
. The physiological relevance of dRP release by platelets was confirmed in a chick chorioallantoic membrane assay, where the presence of this metabolite in platelet supernatants strongly induced capillary formation.

Conclusion—

Platelet-derived dRP stimulates endothelial cell migration by upregulating integrin β
3
in a reactive oxygen species–dependent manner. As demonstrated by our in vivo experiments, this novel paracrine regulatory pathway is likely to play an important role in the stimulation of angiogenesis by platelets.
Characterization of Degenerative Mitral Valve Disease Using Morphologic Analysis of Real-Time Three-Dimensional Echocardiographic Images
Authors: Chandra Sonal , Salgo Ivan S. , Sugeng Lissa , Weinert Lynn , Tsang Wendy , Takeuchi Masaaki , Spencer Kirk T. , O'Connor Anne , Cardinale Michael , Settlemier Scott , Mor-Avi Victor , Lang Roberto M.
Published: October 2010

Background—

Presurgical planning of mitral valve (MV) repair in patients with Barlow disease (BD) and fibroelastic deficiency (FED) is challenging because of the inability to assess accurately the complexity of MV prolapse. We hypothesized that the etiology of degenerative MV disease (DMVD) could be objectively and accurately ascertained using parameters of MV geometry obtained by morphological analysis of real-time 3D echocardiographic (RT3DE) images.

Methods and Results—

Seventy-seven patients underwent transesophageal RT3DE study: 57 patients with DMVD studied intraoperatively (28 BD, 29 FED classified during surgery) and 20 patients with normal MV who were used as control subjects (NL). MVQ software (Philips) was used to measure parameters of annular dimensions and geometry and leaflet surface area, including billowing volume and height. The Student
t
test and multinomial logistic regression was performed to identify parameters best differentiating DMVD patients from normal as well as FED from BD. Morphological analysis in the DMVD group revealed a progressive increase in multiple parameters from NL to FED to BD, allowing for accurate diagnosis of these entities. The strongest predictors of the presence of DMVD included billowing height and volume. Three-dimensional billowing height with a cutoff value of 1.0 mm differentiated DMVD from NL without overlap, and billowing volume with a cutoff value 1.15 mL differentiated between FED and BD without overlap.

Conclusions—

Morphological analysis as a form of decision support in assessing MV billowing revealed significant quantifiable differences between NL, FED, and BD patients, allowing accurate classification of the etiology of MV prolapse and determination of the anticipated complexity of repair.
Prognostic Value of Coronary Computed Tomographic Angiography in Comparison With Calcium Scoring and Clinical Risk Scores
Authors: Hadamitzky Martin , Distler Roland , Meyer Tanja , Hein Franziska , Kastrati Adnan , Martinoff Stefan , Schömig Albert , Hausleiter Jörg
Published: October 2010

Background—

Several studies have demonstrated a high accuracy of coronary computed tomography angiography (CCTA) for detection of obstructive coronary artery disease (CAD), whereas some studies have also shown a good prediction of cardiac events. However, it remains to be proven whether CCTA is better predictive of events than conventional risk scores or calcium scoring. Therefore, we compared CCTA with calcium scoring and clinical risk scores for the ability to predict cardiac events.

Methods and Results—

Patients (n=2223) with suspected CAD undergoing CCTA were followed up for a median of 28 months. The end point was the occurrence of cardiac events (cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and coronary revascularization later than 90 days after CCTA). Patients with obstructive CAD had a significantly higher event rate (2.9% per year; 95% confidence interval, 2.1 to 4.0) than those without obstructive CAD, having an event rate 0.3% per year (95% confidence interval, 0.1 to 0.5; hazard ratio, 13.5; 95% confidence interval, 6.7 to 27.2;
P
<0.001). CCTA had significant incremental predictive value when compared with calcium scoring, both with scores assessing the degree of stenosis (
P
<0.001) and with scores assessing the number of diseased coronary segments (
P
=0.027).

Conclusions—

In patients with suspected CAD, CCTA not only detects coronary stenosis but also improves prediction of cardiac events over and above conventional risk scores and calcium scoring. This may result in a reclassification of cardiovascular risk in a substantial proportion of patients.
Hemorrhagic Manifestations of Reversible Cerebral Vasoconstriction Syndrome
Authors: Ducros Anne , Fiedler Ursula , Porcher Raphael , Boukobza Monique , Stapf Christian , Bousser Marie-Germaine
Published: October 2010

Background and Purpose—

Reversible cerebral vasoconstriction syndrome (RCVS), characterized by severe headaches and reversible constriction of cerebral arteries, may be associated with ischemic and hemorrhagic strokes. The aim of this study was to describe the frequency, patterns, and risk factors of intracranial hemorrhages in RCVS.

Methods—

We analyzed prospective data on 89 consecutive patients with RCVS, of which 8 were postpartum and 46 used vasoactive substances. Standard bivariate and multivariate statistical tests were applied to compare patients with and without hemorrhage.

Results—

Thirty patients (34%), of which 5 were postpartum and 12 used vasoactive substances, developed at least 1 type of intracranial hemorrhage, including cortical subarachnoid (n=27), intracerebral (n=11), and subdural hemorrhage (n=2). Patients with hemorrhage had an older age (46.6 versus 41.6 years,
P
=0.049) and were more frequently females (90% versus 51%,
P
=0.0017) or were migrainers (43% versus 19%,
P
=0.022) than those without hemorrhage. Multivariate testing identified 2 independent risk factors of hemorrhage in RCVS: female gender (OR, 4.05; 95% CI, 1.46 to 11.2) and migraine (OR, 2.34; 95% CI, 1.06 to 5.18). Patients with hemorrhage had a greater risk of persistent focal deficits (30% versus 2%,
P
=0.0002), cerebral infarction (13% versus 2%,
P
=0.039), posterior reversible encephalopathy syndrome (17% versus 3%,
P
=0.041) at the acute stage, and of inability to resume normal activities at 6 months (27% versus 0%,
P
<0.0001).

Conclusion—

In RCVS, women and migrainers seem to be at higher risk of intracranial hemorrhage. Overall, intracranial hemorrhages are frequent in RCVS and are associated with a more severe clinical spectrum.
Improving Stroke Prevention in the French West Indies
Authors: Kelly-Irving Michelle , Mulot Stéphanie , Inamo Jocelyn , Ruidavets Jean-Bernard , Atallah André , Lang Thierry
Published: October 2010

Background and Purpose—

We sought to evaluate lay knowledge and understanding of cardiovascular diseases in the French West Indies.

Methods—

In 2007, a cross-sectional study of 1005 randomly selected men and women (54%) age 25 to 74 years from Guadeloupe and stratified by sex, age, and region was established to ascertain the population’s knowledge and awareness of chronic diseases. Questions were asked about the respondent’s knowledge of cardiovascular risk factors as well as their opinions and beliefs about measures to prevent these diseases.

Results—

Knowledge about stroke prevention in this sample was lower than for heart disease, with 69% of women and 65% of men reporting that precautions can be taken to avoid a stroke versus 84% and 77%, respectively, for heart disease. “Avoid stress” was the most commonly cited stroke prevention measure, with 35% of women and 27% of men reporting it. The first spontaneous item cited for heart disease prevention was “physical exercise or sport,” reported by 47% of women and 45% of men. We hypothesize that knowledge of stroke and stroke risk factors is poor in Guadeloupe or that it reflects culturally adapted health promotion messages from doctors.

Conclusions—

Knowledge and awareness were found to be lower for stroke than for heart diseases. Changes in health promotion strategies are required in the French West Indies to improve the population’s overall awareness of these diseases and to narrow the gap between knowledge and practice.
Signatures of Nonlinear Dynamics in an Idealized Atmospheric Model
Authors: Kondrashov Dmitri , Kravtsov Sergey , Ghil Michael
Published: October 2010

Signatures of nonlinear dynamics are analyzed by studying the phase-space tendencies of a global baroclinic, quasigeostrophic, three-level (QG3) model with topography. Nonlinear, stochastic, low-order prototypes of the full QG3 model are constructed in the phase space of this model’s empirical orthogonal functions using the empirical model reduction (EMR) approach. The phase-space tendencies of the EMR models closely match the full QG3 model’s tendencies. The component of these tendencies that is not linearly parameterizable is shown to be dominated by the interactions between “resolved” modes rather than by multiplicative “noise” associated with unresolved modes. The method of defining the leading resolved modes and the interactions between them plays a key role in understanding the nature of the QG3 model’s dynamics, whether linear or nonlinear, deterministic or stochastic.
Automatic Minimum and Maximum Alarm Thresholds for Quality Control
Authors: Hasu Vesa , Aaltonen Ari
Published: October 2010

Automated quality control is a necessity for meteorological measurement networks because of an ever-increasing number of measurements. One of the basic quality control tests is to check that the observations fall into a range of acceptable values. This paper proposes an algorithm for the automatic determination of maximum and minimum thresholds for such a test. The automated algorithm results in more statistically justified thresholds compared to the operator-fed values, which some quality control systems normally use. The suggested algorithm is a tuning-free method for the determination of daily minimum and maximum limits. The basis of the algorithm is, first, to collect the essential statistics of observations during their annual cycle and, second, to use these statistics to determine the acceptable observation range. This paper introduces a semirecursive version with lower computational requirements and discusses additional algorithmic details. The algorithm is demonstrated through numerical examples, which show that limits converge to satisfactory values in a few years.
Instrumental Music Education Students’ Perceptions of Tensions Experienced During Their Undergraduate Degree
Authors: Conway Colleen , Eros John , Pellegrino Kristen , West Chad
Published: October 2010

In response to recent concern regarding music education major retention and as an effort to contribute to the “lives of teachers” scholarship in music education, the primary research question for this study was: How do undergraduate students describe their lived experiences within the instrumental music education community? Data included a questionnaire from sophomore, junior, and senior undergraduate students ( N = 34); researcher journals; 12 undergraduate student interviews; an undergraduate student focus group; and 6 study team meetings. What the authors learned from this inquiry is organized by the following themes: (a) participants perceive themselves as “different” from other music students; (b) participants perceive music education to be “different” within the music school; and (c) participants’ musician/ teacher identity changed throughout their experience.
The Influence of Social Intelligence on Effective Music Teaching
Authors: Juchniewicz Jay
Published: October 2010

The purpose of this study was to investigate the influence of social intelligence on effective music teaching. Forty teachers from “exemplary programs” and “more challenging programs” across band, chorus, orchestra, and general public school music programs were administered the Interpersonal Perception Task—15 (IPT-15). In addition, 84 external evaluators viewed teaching excerpts of 12 “exemplary” and “challenged” teachers and rated the (a) overall effectiveness and (b) main attribute that influenced their evaluations of each teaching excerpt. Results indicated no significant differences between the IPT-15 scores of “exemplary” teachers and “challenged” teachers.The external evaluators rated teachers identified as “exemplary” significantly higher than they rated teachers labeled as “challenged.” The majority of attributes influencing external evaluators’ ratings of overall teacher effectiveness were social, constituting more than 85% of all responses. All teachers who demonstrated effective social skills were perceived as effective teachers. Effective communication skills were the most frequently cited attributes for “exemplary” teachers, whereas ineffective classroom management was the most listed attribute for why teachers were rated ineffective.
Exploring the Relationship Between Social Support and Job Burnout Among Correctional Staff
Authors: Lambert Eric G. , Altheimer Irshad , Hogan Nancy L.
Published: October 2010

This study examined the relationship between social support and burnout among correctional staff at a private midwestern correctional facility for juveniles tried as adults. Research on correctional staff burnout often calls for social support to help combat the problem; however, there has been no published research on whether different types of social support influence the different dimensions of job burnout. As such, the analyses examined the effects of family-and-friends support, coworker support, management support, and supervisor support on emotional exhaustion, depersonalization, and ineffectiveness. The results revealed that different types of social support influenced different dimensions of burnout. Each dimension of job burnout was influenced by at least one type of social support. Furthermore, the effects of some types of social support were unique to specific dimensions of job burnout, and none of the types combined to influence any dimension of job burnout in a uniform manner. The results point to the need to develop different forms of social support to deal with the different dimensions of burnout.
Criminal Trajectories and Risk Factors in a Canadian Sample of Offenders
Authors: Ward Ashley K. , Day David M. , Bevc Irene , Ye Sun  , Rosenthal Jeffrey S. , Duchesne Thierry
Published: October 2010

This study contributed to the criminal trajectory literature using a Canadian-based sample of offenders and examined childhood and adolescent predictors of trajectory group membership. The sample comprised 378 males who had been sentenced as youth, between 1986 and 1996, to one of two open custody facilities in Toronto, Canada. Official criminal records were obtained from late childhood and early adolescence into adulthood for an average follow-up of 12.1 years. Childhood and adolescent predictors reflecting individual, family, peer, and school domains were extracted from client files. Trajectory analysis yielded four groups, labeled moderate rate (MR); low rate (LR); high-rate, adult peaked (HRADL); and high-rate, adolescence peaked (HRADOL). Multinomial regression analyses indicated that risk factors representing the family and peer domains differentiated the MR, HRADL, and HRADOL groups from the LR group. Moreover, whereas both child and adolescent risk factors were associated with the MR, HRADL, and HRADOL groups, only adolescent risk factors were associated with the LR group.
Multidimensional Item Response Theory Parameter Estimation With Nonsimple Structure Items
Authors: Finch Holmes
Published: October 2010

Estimation of multidimensional item response theory (MIRT) model parameters can be carried out using the normal ogive with unweighted least squares estimation with the normal-ogive harmonic analysis robust method (NOHARM) software. Previous simulation research has demonstrated that this approach does yield accurate and efficient estimates of item discrimination and difficulty across a variety of conditions. However, these studies have been limited primarily to the case of simple structure, where each item is associated only with one of the latent traits underlying the data. The current simulation study seeks to extend this earlier work by comparing NOHARM and unidimensional IRT-based estimates of difficulty and discrimination values for items that do not conform to simple structure, that is, are associated with more than one latent trait. The outcomes of interest were relative bias and standard error values for parameter estimates under a variety of conditions, including the degree of nonsimple structure present. Results demonstrate that both bias and standard error tended to be larger for items that do not conform to simple structure than for those that do, but that the degree of such differences was influenced by factors such as correlation between the latent traits, sample size and distribution of the latent trait, among others.
The Effects of Consultation on Individualized Education Program Outcomes for Young Children With Autism: The Collaborative Model for Promoting Competence and Success
Authors: Ruble Lisa A. , Dalrymple Nancy J. , McGrew John H.
Published: October 2010

The effects of a teacher consultation intervention were examined—namely, the collaborative model for promoting competence and success (COMPASS), which was designed to improve objectives of individualized education programs for children with autism. The intervention consists of an initial parent—teacher consultation, followed by four teacher consultations across the school year. Thirty-five teachers and a randomly selected child with autism ( M age = 6.1 years) from each classroom participated. Compared to the nonintervention teacher—child dyads, the intervention teacher—child dyads showed improvements in individualized education program objectives, with a large effect size ( d = 1.51).
Practitioners’ Self-Evaluations of Contrasting Types of Professional Development
Authors: Dunst Carl J. , Raab Melinda
Published: October 2010

The effects of three types of in-service training on practitioners’ self-evaluations of evidence-based preschool classroom practices were evaluated in a study of 255 participants from 26 states. Participants attended either conference presentations or 1-day or 2- to 3-day workshops or received one of two types of intensive in-service training (weeklong institutes or on-site training in the participants’ classrooms). Study participants made self-ratings of the usefulness of the training content and the extent to which the training changed or improved their classroom practices, 1 or 6 months after training. Results show that both types of intensive in-service training are more effective than either conference presentations or workshops and that on-site training is more effective than weeklong institutes in affecting study participants’ judgments of the in-service training. The findings are discussed in terms of the characteristics of in-service training most likely to change or improve preschool classroom practices.
Evaluation of the Battelle Developmental Inventory, 2nd Edition, Screening Test for Use in States’ Child Outcomes Measurement Systems Under the Individuals With Disabilities Education Act
Authors: Elbaum Batya , Gattamorta Karina A. , Penfield Randall D.
Published: October 2010

This study evaluated the Battelle Developmental Inventory, 2nd Edition, Screening Test (BDI-2 ST) for use in states’ child outcomes accountability systems under the Individuals with Disabilities Education Act. Complete Battelle Developmental Inventory, 2nd Edition (BDI-2), assessment data were obtained for 142 children, ages 2 to 62 months, who had been referred for eligibility evaluation for early intervention or preschool special education services. Results of a Rasch measurement analysis provided evidence supporting the reliability and validity of the five domain scores and total BDI-2 ST score. A comparison of children’s classifications as either having or not having a developmental delay based on the BDI-2 ST and the BDI-2 full assessment—using cut scores of 1.0, 1.5, and 2.0 standard deviations below the mean—indicated acceptable sensitivity, specificity, and overall classification accuracy of the BDI-2 ST. Implications of the findings are discussed for accountability reporting and clinical practice.
Who votes in Africa? An examination of electoral participation in 10 African countries
Authors: Kuenzi Michelle , Lambright Gina M. S.
Published: October 2010

The question ‘Who votes in Africa?’ has yet to receive significant attention. We use Afrobarometer survey data to assess the determinants of voting for over 17,000 voting-age adults in 10 African countries. We find that Africans are driven by many of the same forces as their counterparts elsewhere. The agencies of mobilization are important in determining who votes in these countries. Notably, identifying with a political party is one of the most important predictors of voting. Thus, although political parties may have questionable democratic credentials in many African countries, ultimately, political parties serve the function of getting citizens to the polls. Certain attitudes also influence individuals' decisions of whether to vote, including support for democracy. Among the demographic variables, age registers a significant, positive relationship with voting. Interestingly, the study’s findings regarding the socio-economic status (SES) model are contradictory. Educated Africans in these countries are significantly more likely to vote than their less educated counterparts, as the SES model would lead one to expect. Contrary to what one would expect based on the SES model, more impoverished Africans are also significantly more likely to vote than their wealthier counterparts. In addition, the institutional and political context influences individuals' propensities to vote.