bluuebunny/crossref_metadata_2025 huggingface dataset:
The Gamma Secretase Inhibitor MRK-003 Attenuates Pancreatic Cancer Growth in Preclinical Models
Authors: Mizuma Masamichi , Rasheed Zeshaan A. , Yabuuchi Shinichi , Omura Noriyuki , Campbell Nathaniel R. , de Wilde Roeland F. , De Oliveira Elizabeth , Zhang Qing , Puig Oscar , Matsui William , Hidalgo Manuel , Maitra Anirban , Rajeshkumar N.V.
Published: July 2012

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy, with most patients facing an adverse clinical outcome. Aberrant Notch pathway activation has been implicated in the initiation and progression of PDAC, specifically the aggressive phenotype of the disease. We used a panel of human PDAC cell lines as well as patient-derived PDAC xenografts to determine whether pharmacologic targeting of Notch pathway could inhibit PDAC growth and potentiate gemcitabine sensitivity. MRK-003, a potent and selective γ-secretase inhibitor, treatment resulted in the downregulation of nuclear Notch1 intracellular domain, inhibition of anchorage-independent growth, and reduction of tumor-initiating cells capable of extensive self-renewal. Pretreatment of PDAC cells with MRK-003 in cell culture significantly inhibited the subsequent engraftment in immunocompromised mice. MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) PDAC xenografts. A combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared with gemcitabine in 4 of 9 (44%) PDAC xenografts, reduced tumor cell proliferation, and induced both apoptosis and intratumoral necrosis. Gene expression analysis of untreated tumors indicated that upregulation of NF-κB pathway components was predictive of sensitivity to MRK-003, whereas upregulation in B-cell receptor signaling and nuclear factor erythroid-derived 2-like 2 pathway correlated with response to the combination of MRK-003 with gemcitabine. Our findings strengthen the rationale for small-molecule inhibition of Notch signaling as a therapeutic strategy in PDAC. Mol Cancer Ther; 11(9); 1999–2009. ©2012 AACR.
Targeted Expression of BikDD Eliminates Breast Cancer with Virtually No Toxicity in Noninvasive Imaging Models
Authors: Xie Xinhua , Li Laisheng , Xiao Xiangsheng , Guo Jiaoli , Kong Yanan , Wu Minqing , Liu Wanli , Gao Guoquan , Hsu Jennifer L. , Wei Weidong , Hung Mien-Chie , Xie Xiaoming
Published: July 2012

Breast cancer is a major public health problem all over the world, and the current treatment strategies are not potent enough for some patients, especially those with triple-negative breast cancer. Therefore, novel and more effective treatments are critically needed. Of the current methods, targeted therapy, which not only retains cancer-specific expression but also limits toxicity, is a new strategy for treating cancers. In this study, we found that the human telomerase reverse transcriptase (hTERT; T) promoter also possesses high target specificity in breast cancer. Moreover, we developed a versatile T-based breast cancer–specific promoter VISA (VP16-Gal4-WPRE integrated systemic amplifier) composite (T-VISA) to target transgene expression in breast tumors, which has stronger activity comparable or higher than that of the cytomegalovirus promoter in cancer cells. Thereafter, targeted expression of BikDD (a mutant form of proapoptotic gene Bik) through the T-VISA platform in breast cancer initiated robust antitumor effects and prolonged survival in multiple xenograft and syngeneic orthotopic mouse models of breast tumors with virtually no toxicity in intact mice. Thus, these findings show that our T-VISA-BikDD nanoparticles effectively and safely eradicate breast cancer in vitro and in vivo and are worthy of development in clinical trials treating breast cancer. Mol Cancer Ther; 11(9); 1915–24. ©2012 AACR.
Intrathecal Treatment with the Anti-Phosphorylcholine Monoclonal Antibody TEPC-15 Decreases Neuronal Damage in Experimental Pneumococcal Meningitis
Authors: Gerber Joachim , Redlich Sandra , Ribes Sandra , Tauber Simone C. , Schmidt Holger , Nau Roland
Published: July 2012

Background: Neuronal injury in pneumococcal meningitis is a consequence of microglial activation and direct toxicity by bacterial products and systemic inflammation. Methods: The treatment effect of the TEPC-15 antibody recognizing teichoic and lipoteichoic acids was investigated in murine microglial cells and in a rabbit model of pneumococcal meningitis. Results: In vitro, the TEPC-15 antibody recognizing teichoic and lipoteichoic acids increased Streptococcus pneumoniae phagocytosis by murine microglial cells. In rabbit ceftriaxone-treated S. pneumoniae meningitis, intracisternal TEPC-15 reduced the density of apoptotic neurons in the hippocampal dentate gyrus (116 ± 70 vs. 221 ± 132/mm2; p = 0.03). Cerebrospinal fluid inflammatory parameters (protein, lactate, leukocytes, prostaglandins) were not reduced in TEPC-15-treated rabbits. Conclusion: Intracisternal treatment with the TEPC-15 antibody reduced neuronal damage probably by promoting rapid phagocytosis of bacterial products.
Cognitive-Behavioral Therapy for Pathological Gambling in Parkinson’s Disease: A Pilot Controlled Study
Authors: Jiménez-Murcia Susana , Bove Francesca Isabella , Israel Mimi , Steiger Howard , Fernández-Aranda Fernando , Álvarez-Moya Eva , Granero Roser , Penelo Eva , Vergé Begoña , Aymamí Maria-Neus , Santamaría Juan José , Gómez-Peña Mónica , Moragas Laura , Savvidou Lamprini G. , Menchón José Manuel
Published: July 2012

Objectives: The main objective of this study was to compare the clinical characteristics and differences in response to treatment of two groups of pathological gamblers: with comorbid Parkinson’s disease (PG + PD) and without (PG – PD). Methods: Clinical and psychopathological profiles and response to cognitive-behavioral treatment were assessed in 15 PG + PD and 45 PG – PD individuals consulting a specialized hospital Unit. Results: Statistically significant differences were observed between the two groups on a series of clinical variables. PG + PD patients were older and presented later onset of problematic gambling behaviors, lower alcohol consumption and higher bingo playing than PG – PD patients. No significant differences were noted in psychopathology except for lower measures of hostility in the PG + PD group. No statistical differences were detected between groups in terms of response to treatment. Conclusion: These results may provide guidance for obtaining accurate diagnostic information in pathological gamblers by properly identifying patients with specific needs that may be targeted with treatment.
GLIS1 rs797906: An Increased Risk Factor for Late-Onset Parkinson’s Disease in the Han Chinese Population
Authors: Song Wei , Chen Yong Ping , Huang Rui , Chen Ke , Pan Ping Lei , Li Jianpeng , Yang Yuan , Shang Hui-Fang
Published: July 2012

Background: Single nucleotide polymorphism (SNP) rs797906 of the GLIS family zinc finger 1 (GLIS1) gene has been linked to a risk of Parkinson’s disease (PD) in genome-wide association studies of Caucasian populations. Methods: A total of 380 unrelated Han patients with PD from the Department of Neurology, West China Hospital of Sichuan University, and 275 unrelated Han Chinese healthy controls (HC) from the same region were included. rs797906 SNP was genotyped using Sequenom iPLEX Assay technology. Results: No significant differences were found in the genotype and allele frequencies for rs797906 between the PD and HC groups. There were no significant differences in genotype frequencies between early-onset PD and HC groups and between late-onset PD and HC groups. The frequency of allele ‘A’ for rs797906 in the late-onset PD group was significantly higher than that in the HC group (p = 0.046, OR 1.2726, 95% CI 1.0039–1.6132). Moreover, the frequency of allele ‘A’ in the late-onset PD group was significantly higher than that in the early-onset PD group (p = 0.001). Conclusion: We have found that allele ‘A’ of rs797906 SNP increases the risk for late-onset PD in the Han Chinese population. More associated studies with larger numbers of participants are needed to confirm the present findings.
Sacral Mesh Pullout Strength Based on Suture Location for Sacrocolpopexy
Authors: Shippey Stuart , Sutter Edward , Belkoff Stephen M. , Gutman Robert , Chen Chi Chiung Grace
Published: July 2012

Background: We sought to compare the pullout strengths of the sacral end of the sacrocolpopexy mesh when attached using one suture at the first versus second sacral vertebral level (S1 vs. S2) in female cadaveric pelvises. Methods: The sacral vertebrae were isolated in 9 unembalmed female cadavers, and segments of polypropylene mesh were attached to the sacrum using stitches at either the S1 or S2 level. The free end of the mesh was pulled at a constant rate. Maximum tension prior to system failure was recorded for each specimen. Suture pullout strengths between the two groups were compared using the two-sample Wilcoxon rank-sum test. Results: In all but one specimen, failure of the system occurred at the point of suture attachment to the anterior longitudinal ligament. Among the nine specimens, median pullout strengths were 7.49 lb (interquartile range 7.95) at S1 and 3.15 lb (interquartile range 2.975) at S2 (p = 0.028). Conclusion: The pullout strength of sutures used to attach the sacrocolpopexy mesh to the sacrum is significantly higher at the S1 level than at the S2 level.
Prognostic Aspects, Survival Rate, and Predisposing Risk Factors in Patients with Fournier’s Gangrene and Necrotizing Soft Tissue Infections: Evaluation of Clinical Outcome of 55 Patients
Authors: Martinschek A. , Evers B. , Lampl L. , Gerngroß H. , Schmidt R. , Sparwasser C.
Published: July 2012

Objective: To determine predisposing or prognostic factors and mortality rates of patients with Fournier’s gangrene compared to other necrotizing soft tissue infections (NSTI). Material and Methods: Data of 55 intensive care patients (1981–2010) with NSTI were evaluated. Data were collected prospectively. Results: 43.4% of the patients were in septic condition and 27.3% were hemodynamically unstable. Half of the patients showed predisposing factors (52.7%). The lower extremity (63.2%), abdomen (30.9%), and perineum (14.5%) were most affected. Polymicrobial infections were frequent (65.5%, mean 2.8, range: 1–4). The mortality rate was 16.4% (n = 9). An increase was shown for diabetes mellitus (20%), cardiac insufficiency (22.3%), septic condition at presentation (33.3%), abdominal affection (47.1%), and hemodynamic instability (46.7%). Comparing survivors and nonsurvivors, statistical significance was seen with age (p < 0.001), septic condition at admission (p < 0.001), hemodynamic instability (p < 0.001), low blood pressure (p < 0.001), and abdominal affection (p < 0.001). In laboratory findings, an increase of creatine kinase (p < 0.001) and lactate (p < 0.001) and a decrease of antithrombin III (p < 0.007) and the Quick value (p < 0.01) proved to be significant. Conclusion: Patients with Fournier’s gangrene do not differ in all aspects from those with other NSTI. Successful treatment consists of immediate surgical debridement, broad-spectrum antibiotic treatment, and critical care management. Supportive hyperbaric oxygen therapy should be considered.
Umbilical Artery Intima-Media and Wall Thickness in Infants of Diabetic Mothers
Authors: Sarikabadayi Yusuf Unal , Aydemir Ozge , Kanmaz Gozde , Aydemir Cumhur , Oguz Serife Suna , Erdeve Omer , Eyi Elif Gul Yapar , Zergeroglu Sema , Dilmen Ugur
Published: July 2012

Background: Large for gestational age (LAG) neonates who had been exposed to an intrauterine environment of either diabetes or maternal obesity are at increased risk of developing the metabolic syndrome. This can be explained by exposure to high glucose and insulin levels in utero which alter fetal adaptation and programming. Objectives: The aim of the study was to evaluate the onset of preclinical atherosclerosis in utero. Methods: We measured umbilical artery wall thickness (ruWT) in the third trimester by obstetric ultrasound and umbilical artery intima-media thickness (uIMT) in pathologic specimens of umbilical cords obtained shortly after delivery and investigated the relation between these measurements and serum insulin level and C-peptide level in cord blood and assessed insulin resistance with the homeostasis model assessment of insulin resistance (HOMA-IR) in infants of diabetic mothers (IDMs), i.e. the study group, which was divided into a large for gestational age group (LGA)-IDM group and an appropriate for gestational age group (AGA)-IDM group and compared with a control group. Results: The LGA-IDM group had significantly higher insulin (p < 0.001), C-peptide (p = 0.018) and HOMA-IR levels (p < 0.001) compared with the AGA-IDM and control groups. The LGA-IDM group had significantly larger ruWT (p = 0.013) and uIMT (p < 0.001) compared with the AGA-IDM and the control groups. The LGA-IDM group had increased uIMT and ruWT that correlated with the severity of maternal hyperglycemia. Conclusions: Measurement of ruWT in the third trimester is feasible, reproducible and strongly correlated with pathological serum insulin, C-peptide in cord blood and HOMA-IR levels.
A Case Series of 130 Neonates with Congenital Syphilis: Preterm Neonates Had More Clinical Evidences of Infection than Term Neonates
Authors: Zhou Qinhua , Wang Laishuan , Chen Chao , Cao Yun , Yan Weili , Zhou Wenhao
Published: July 2012

Background: The early clinical manifestations of congenital syphilis (CS) vary from asymptomatic to florid lesions, involving multisystem damage. But little is known about the differences of early clinical features between preterm and term neonates with CS. Objectives: To compare the clinical characteristics between preterm and term neonates with CS and analyze the possible underlying reasons for the differences. Methods: Consecutive medical charts of infants at risk for CS from January 1999 to December 2009 were retrospectively reviewed. Neonates with positive 19S-IgM in serum were included in the study. Results: Among the 1,670 cases at risk for CS, 130 neonatal cases with positive 19S-IgM in serum were included in the analysis, including 58 preterm ones and 72 full-term ones. Compared with term neonates with CS, preterm ones were more likely to have characteristic skin rash (36.2 vs. 9.7%, p < 0.001), hepatomegaly (51.7 vs. 25%, p = 0.02), splenomegaly (32.8 vs. 15.4%, p = 0.02), PRP titer ≥1:8 (96.6 vs. 70.8%, p < 0.001), thrombocytopenia (43.1 vs. 23.6%, p = 0.018), elevated CRP (65.5 vs. 36.5%, p = 0.002), and abnormal long bone X-ray results (94.6 vs. 68.1%, p < 0.001). Fewer mothers of preterm neonates with CS received treatment for syphilis (15.5 vs. 40.3%, p = 0.003). The rate of withdrawal of care was higher in preterm neonates with CS (31 vs.12.5%, p = 0.036). Conclusions: Preterm neonates with CS had more clinical evidences and suffered more than term ones.
Heart Rate Reduction by Ivabradine Improves Aortic Compliance in Apolipoprotein E-Deficient Mice
Authors: Custodis Florian , Fries Peter , Müller Andreas , Stamm Christoph , Grube Markus , Kroemer Heyo K. , Böhm Michael , Laufs Ulrich
Published: July 2012

Background: Impaired vascular compliance is associated with cardiovascular mortality. The effects of heart rate on vascular compliance are unclear. Therefore, we characterized effects of heart rate reduction (HRR) by I(f) current inhibition on aortic compliance and underlying molecular mechanisms in apolipoprotein E-deficient (ApoE–/–) mice. Methods: ApoE–/– mice fed a high-cholesterol diet and wild-type (WT) mice were treated with ivabradine (20 mg/kg/d) or vehicle for 6 weeks. Compliance of the ascending aorta was evaluated by MRI. Results: Ivabradine reduced heart rate by 113 ± 31 bpm (∼19%) in WT mice and by 133 ± 6 bpm (∼23%) in ApoE–/– mice. Compared to WT controls, ApoE–/– mice exhibited reduced distensibility and circumferential strain. HRR by ivabradine increased distensibility and circumferential strain in ApoE–/– mice but did not affect both parameters in WT mice. Ivabradine reduced aortic protein and mRNA expression of the angiotensin II type 1 (AT1) receptor and reduced rac1-GTPase activity in ApoE–/– mice. Moreover, membrane translocation of p47phox was inhibited. In ApoE–/– mice, HRR induced anti-inflammatory effects by reduction of aortic mRNA expression of IL-6, TNF-alpha and TGF-beta. Conclusion: HRR by ivabradine improves vascular compliance in ApoE–/– mice. Contributing mechanisms include downregulation of the AT1 receptor, attenuation of oxidative stress and modulation of inflammatory cytokine expression.
Clearance of Fetuin-A–Containing Calciprotein Particles Is Mediated by Scavenger Receptor-A
Authors: Herrmann Marietta , Schäfer Cora , Heiss Alexander , Gräber Steffen , Kinkeldey Anne , Büscher Andrea , Schmitt Martin M.N. , Bornemann Jörg , Nimmerjahn Falk , Herrmann Martin , Helming Laura , Gordon Siamon , Jahnen-Dechent Willi
Published: July 2012

Rationale:

Fetuin-A is a liver-derived plasma protein involved in the regulation of calcified matrix metabolism. Biochemical studies showed that fetuin-A is essential for the formation of protein-mineral complexes, called calciprotein particles (CPPs). CPPs must be cleared from circulation to prevent local deposition and pathological calcification.

Objective:

We studied CPP clearance in mice and in cell culture to identify the tissues, cells, and receptors involved in the clearance.

Methods and Results:

In mice, fetuin-A–containing CPPs were rapidly cleared by the reticuloendothelial system, namely Kupffer cells of the liver and marginal zone macrophages of the spleen. Macrophages from scavenger receptor-AI/II (SR-A)-deficient mice cleared CPPs less efficiently than macrophages from wild-type mice, suggesting that SR-AI/II is involved in CPP binding and endocytosis. Accordingly, we found reduced clearance of CPPs in SR-A/MARCO–deficient mice.

Conclusions:

We could demonstrate that fetuin-A–containing CPPs facilitate the clearance of mineral debris by macrophages via SR-A. Since the same receptor also contributes to the uptake of modified low-density lipoprotein particles in atherosclerosis, defective endocytosis of both types of particle may impinge on lipid as well as mineral debris clearance in calcifying atherosclerosis.
Apelin Enhances Cardiac Neovascularization After Myocardial Infarction by Recruiting Aplnr+ Circulating Cells
Authors: Tempel Dennie , de Boer Martine , van Deel Elza D. , Haasdijk Remco A. , Duncker Dirk J. , Cheng Caroline , Schulte-Merker Stefan , Duckers Henricus J.
Published: July 2012

Rationale:

Neovascularization stimulated by local or recruited stem cells after ischemia is a key process that salvages damaged tissue and shows similarities with embryonic vascularization. Apelin receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular development. However, the role of apelin signaling in stem cell recruitment after ischemia is unknown.

Objective:

To investigate the role of apelin signaling in recruitment after ischemia.

Methods and Results:

Aplnr was specifically expressed in circulating cKit+/Flk1+ cells but not in circulating Sca1+/Flk1+ and Lin+ cells. cKit+/Flk1+/Aplnr+ cells increased significantly early after myocardial ischemia but not after hind limb ischemia, indicative of an important role for apelin/Aplnr in cell recruitment during the nascent biological repair response after myocardial damage. In line with this finding, apelin expression was upregulated in the infarcted myocardium. Injection of apelin into the ischemic myocardium resulted in accelerated and increased recruitment of cKit+/Flk1+/Aplnr+ cells to the heart. Recruited Aplnr+/cKit+/Flk1+ cells promoted neovascularization in the peri-infarct area by paracrine activity rather than active transdifferentiation, resulting into cardioprotection as indicated by diminished scar formation and improved residual cardiac function. Aplnr knockdown in the bone marrow resulted in aggravation of myocardial ischemia–associated damage, which could not be rescued by apelin.

Conclusions:

We conclude that apelin functions as a new and potent chemoattractant for circulating cKit+/Flk1+/Aplnr+ cells during early myocardial repair, providing myocardial protection against ischemic damage by improving neovascularization via paracine action.
Optimal Antihypertensive Level for Improvement of Coronary Microvascular Dysfunction
Authors: Mizuno Reiko , Fujimoto Shinichi , Saito Yoshihiko , Okamoto Yasuyuki
Published: July 2012

Recently, coronary microvascular function was documented to be impaired even in patients with prehypertension. However, the impact of antihypertensive level on improvement of coronary microvascular dysfunction in hypertensive patients remains to be established. We investigated the optimal blood pressure achieved with treatment of antihypertensive agents for improvement of coronary microvascular dysfunction in hypertensive patients. We prospectively studied 108 untreated hypertensive patients. All patients were treated with antihypertensive agents for approximately 12 months. Coronary flow reserve (CFR) was measured before and after treatment. The patients were divided into hypertensive, prehypertensive, and normal groups based on their average blood pressure during the treatment period. Pretreatment CFR was similar among all groups. CFR increased significantly in the normal group during the treatment period, but decreased significantly in the prehypertensive and hypertensive groups. This decrease was significantly greater in the hypertensive group than in the prehypertensive group. Multivariate analysis showed lowering blood pressure to normal level to be an independent determinant of improvement in CFR. The normal group was divided into normal-higher and normal-lower subgroups based on their average diastolic blood pressure during the treatment period. Increase in CFR was significantly greater in the normal-higher group than in the normal-lower group. These findings indicate that lowering blood pressure to a normal level is necessary to improve coronary microvascular dysfunction in hypertensive patients. Furthermore, raising diastolic blood pressure to a higher level within normal range has the most beneficial effect. However, as this study is based on observational design, it may have several limitations.
Association Between Annual Visit-to-Visit Blood Pressure Variability and Stroke in Postmenopausal Women
Authors: Shimbo Daichi , Newman Jonathan D. , Aragaki Aaron K. , LaMonte Michael J. , Bavry Anthony A. , Allison Matthew , Manson JoAnn E. , Wassertheil-Smoller Sylvia
Published: July 2012

Accumulating evidence suggests that increased visit-to-visit variability (VVV) of blood pressure is associated with stroke. No study has examined the association between VVV of blood pressure and stroke in postmenopausal women, and scarce data exist as to whether this relation is independent of the temporal trend of blood pressure. We examined the association of VVV of blood pressure with stroke in 58228 postmenopausal women enrolled in the Women's Health Initiative. Duplicate blood pressure readings, which were averaged, were taken at baseline and at each annual visit. VVV was defined as the SD for the participant's mean systolic blood pressure (SBP) across visits (SD) and about the participant's regression line with SBP regressed across visits (SDreg). Over a median follow-up of 5.4 years, 997 strokes occurred. In an adjusted model including mean SBP over time, the hazard ratios (95% CI) of stroke for higher quartiles of SD of SBP compared with the lowest quartile (referent) were 1.39 (1.03–1.89) for quartile 2, 1.52 (1.13–2.03) for quartile 3, and 1.72 (1.28–2.32) for quartile 4 (
P
trend <0.001). The relation was similar for SDreg of SBP quartiles in a model that additionally adjusted for the temporal trend in SBP (
P
trend <0.001). The associations did not differ by stroke type (ischemic versus hemorrhagic). There was a significant interaction between mean SBP and SDreg on stroke with the strongest association seen below 120 mmHg. In postmenopausal women, greater VVV of SBP was associated with increased risk of stroke, particularly in the lowest range of mean SBP.
Vascular Function and the Role of Oxidative Stress in Heart Failure, Heart Transplant, and Beyond
Authors: Witman Melissa A.H. , Fjeldstad Anette S. , McDaniel John , Ives Stephen J. , Zhao Jia , Barrett-O'Keefe Zachary , Nativi Jose N. , Stehlik Josef , Wray D. Walter , Richardson Russell S.
Published: July 2012

Using flow-mediated vasodilation (FMD), reactive hyperemia, and an acute oral antioxidant cocktail (AOC; vitamins C and E and α-lipoic acid), this study aimed to provide greater insight into altered vascular function and the role of oxidative stress in chronic heart failure patients with reduced ejection fraction (HFrEF) and at several time points beyond heart transplantation (HTx). A total of 61 age-matched subjects (12 healthy controls, 14 New York Heart Association class II and III HFrEF, and 35 HTx recipients [<3 years post-HTx, 5–10 years post-HTx, and >14 years post-HTx]) ingested either placebo (PL) or an AOC before FMD and reactive hyperemia testing of the brachial artery. Vascular function, as measured by FMD, was not different among the controls (6.8±1.9%), recent <3-year post-HTx group (8.1±1.2%), and the 5- to 10-year post-HTx group (5.5±1.0%). However, PL FMD was lower in the HFrEF (4.5±0.7%) and in the >14-year post-HTx group (2.9±0.8%). The AOC increased plasma ascorbate levels in all of the groups but only increased FMD in the controls (PL, 6.8±1.9%; AOC, 9.2±1.0%) and >14-year post-HTx recipients (PL, 2.9±0.8%; AOC, 4.5±1.3%). There were no differences in reactive hyperemia in any of the groups with PL or AOC. This cross-sectional study reveals that, compared with controls, vascular function is blunted in HFrEF, is similar soon after HTx, but is decreased with greater time post-HTx with free radicals implicated in this progression.
Association of Pulse Pressure With New-Onset Atrial Fibrillation in Patients With Hypertension and Left Ventricular Hypertrophy
Authors: Larstorp Anne Cecilie K. , Ariansen Inger , Gjesdal Knut , Olsen Michael H. , Ibsen Hans , Devereux Richard B. , Okin Peter M. , Dahlöf Björn , Kjeldsen Sverre E. , Wachtell Kristian
Published: July 2012

Previous studies have found pulse pressure (PP), a marker of arterial stiffness, to be an independent predictor of atrial fibrillation (AF) in general and hypertensive populations. We examined whether PP predicted new-onset AF in comparison with other blood pressure components in the Losartan Intervention For Endpoint reduction in hypertension study, a double-blind, randomized (losartan versus atenolol), parallel-group study, including 9193 patients with hypertension and electrocardiographic left ventricular hypertrophy. In 8810 patients with neither a history of AF nor AF at baseline, Minnesota coding of electrocardiograms confirmed new-onset AF in 353 patients (4.0%) during mean 4.9 years of follow-up. In multivariate Cox regression analyses, baseline and in-treatment PP and baseline and in-treatment systolic blood pressure predicted new-onset AF, independent of baseline age, height, weight, and Framingham Risk Score; sex, race, and treatment allocation; and in-treatment heart rate and Cornell product. PP was the strongest single blood pressure predictor of new-onset AF determined by the decrease in the −2 Log likelihood statistic, in comparison with systolic blood pressure, diastolic blood pressure, and mean arterial pressure. When evaluated in the same model, the predictive effect of systolic and diastolic blood pressures together was similar to that of PP. In this population of patients with hypertension and left ventricular hypertrophy, PP was the strongest single blood pressure predictor of new-onset AF, independent of other risk factors.
Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human Hypertension
Authors: Schillaci Giuseppe , Bilo Grzegorz , Pucci Giacomo , Laurent Stéphane , Macquin-Mavier Isabelle , Boutouyrie Pierre , Battista Francesca , Settimi Laura , Desamericq Gaëlle , Dolbeau Guillaume , Faini Andrea , Salvi Paolo , Mannarino Elmo , Parati Gianfranco
Published: July 2012

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP,
r
=0.17/0.19/0.13; weighted SD of 24-hour SBP,
r
=0.21; ARV,
r
=0.26; all
P
<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all
P
<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.
Essential Factors for the Development of a Residency Global Health Track
Authors: Campagna Ann M. , St. Clair Nicole E. , Gladding Sophia P. , Wagner Sabrina M. , John Chandy C.
Published: July 2012

Objective

There is increasing awareness of the importance of global health (GH) residency education but little guidance on what departmental, financial, and human resource support is required to develop a GH track. The authors aimed to identify essential factors and major obstacles to the development of a GH track.

Methods

A survey assessing curriculum, support, and factors considered essential to or obstacles to successful development of a GH track was sent to 24 GH education directors within pediatric residencies.

Results

In all, 19 programs (79%) completed the survey, and 6 factors were identified as essential for developing and sustaining a GH track by ≥95% of all GH education directors: supportive residency program director, resident commitment, supportive department chair, protected resident elective time, dedicated budget, and GH faculty with protected time.

Conclusions

Residency programs aiming to start a GH track should start by assessing the availability and sustainability of these identified essential factors within their program.
Chest Pain in Young Patients in an Office Setting
Authors: Cohn Herbert E. , Arnold Lucy W.
Published: July 2012

This study determined the incidence of cardiac diagnoses demonstrably related to chest pain in young patients and determined whether those with exertional chest pain were more likely to have a cardiac diagnosis. It evaluated the course of patients with chest pain after pediatric cardiology evaluation regarding interventions, outcomes, and additional test burden. This was a retrospective study of 203 patients with an office pediatric cardiology assessment of chest pain from January 2000 through December 2004. Fifteen patients (7.4%) had cardiac diagnoses, 5 (2.5%) had cardiac diagnoses demonstrably related to their chest pain complaints (arrhythmias, mitral valve prolapse), and none had ischemia. Exertional chest pain, in this study, did not increase the risk of having a cardiac diagnosis. Following evaluation, 80% of patients did not return for complaints of chest pain. Ten percent had 2 or more additional visits to any medical site for chest pain but no additional cardiac diagnoses were found.
Impact of Blue Force Tracking on Combat Identification Judgments
Authors: Bryant David J. , Smith David G.
Published: July 2012

Objective:

We examined the effectiveness of blue force tracking (BFT) decision support for dismounted infantry soldiers.

Background:

Technologies to support combat identification (CID) are rapidly evolving and may be deployable to dismounted soldiers in the future. BFT systems are designed to mitigate the risk of fratricide by supplying positional information regarding friendly units to enhance situation awareness.

Method:

Participants played the role of a dismounted infantry soldier in a first-person perspective gaming environment and made engagement decisions for a series of simulated targets, half of which were enemies and half of which were friends.

Results:

Participants performed better overall when they were able to use a BFT system than when they performed the task without assistance. When a 10-s latency was added to the updating of position information in the BFT, participants made significantly more false alarms (engaged a friendly target) regardless of whether they knew about the latency.

Conclusion:

The results indicate the promise of a personal BFT device to reduce the likelihood of fratricide by dismounted infantry soldiers. The results, however, also indicate that the effectiveness of such a device can be dramatically reduced when it does not provide real-time data.

Application:

Potential applications of this research include development of performance standards for BFT devices and assessment of decision support for dismounted soldiers.
Overexcitabilities and Giftedness Research
Authors: Mendaglio Sal
Published: July 2012

There has been an increase in publications of quantitative research studies investigating overexcitabilities (OEs) and giftedness. On one hand, increased interest in OEs bodes well for the dissemination of Dabrowski’s theory of positive disintegration (TPD), from which OEs are derived. On the other hand, recent research raises concerns regarding the assumptions underlying the research methods in common use. This article argues that the assumptions regarding OEs and their relationship to giftedness evident in recent research run counter to Dabrowskian theorizing. Due to the uniqueness and coherence of TPD, the article concludes by noting the need for a paradigm shift when researchers investigate TPD concepts such as OE.
Perceived Economic Strain and Psychological Well-Being
Authors: Uçanok Zehra , Güre Ayş en
Published: July 2012

This study primarily aims to explore the association between perceived economic strain, parent-adolescent relational qualities and psychological well-being and to investigate the dyadic parental relationships during early adolescence. A total of 414 adolescents between the ages of 10 and 14 (M= 12.58, SD = .90) from three different socioeconomic status groups were included. Adolescents from low socioeconomic status families reported more parental conflict and in terms of dyadic relations, both boys and girls perceive more positive communication and less conflict with their fathers. Our findings have shown that the quality of adolescents’ relationships with parents partially mediate the association between perceived economic strain and psychological well-being. Although findings related to dyadic relations indicated more positive relationships with fathers than with mothers, it seems that the mediational role of maternal outcome is relatively more powerful on the association between perceived economic strain and the life satisfaction and self-worth of Turkish adolescents.
Predicting Achievement in Mathematics in Adolescent Students
Authors: Levpušček Melita Puklek , Zupančič Maja , Sočan Gregor
Published: July 2012

The study examined individual factors and social factors that influence adolescent students’ achievement in mathematics. The predictive model suggested direct positive effects of student intelligence, self-rated openness and parental education on achievement in mathematics, whereas direct effects of extraversion on measures of achievement were negative. Indirect positive effects of intelligence, self-rated conscientiousness, student-perceived mathematics teacher’s press for understanding and mastery goal, and a negative effect of student-rated parental academic pressure on course achievement were mediated through the students’ self-efficacy in mathematics. The findings highlight the important role that individual differences in ability and personality, as well as student perceptions of parent and teacher academically related variables, play in the students’ performance in mathematics.
The Use of Team-Based Learning as an Approach to Increased Engagement and Learning for Marketing Students
Authors: Chad Paul
Published: July 2012

Marketing educators are often faced with poor preclass preparation by students, declining student interest in attending classes as the semester progresses, and student complaints regarding previous bad experiences with team assessment activities. Team-based learning (TBL) is an innovative teaching strategy using semiformalized guidelines aimed to enhance student engagement and improve teamwork and, hence, overcome the typical problems faced by educators. This case study examines the first-time use of TBL in a postgraduate marketing subject at an Australian university. The results indicate that the TBL innovation has a positive influence on student engagement and offers opportunities to assist learning. The study concludes that TBL is an effective teaching process enabling educators to offer students enhanced and stimulating learning experiences. The case study contributes to the marketing education literature by assessing the first-time TBL experience of students and educator. Key issues addressed are student engagement, opportunities for learning, and the benefits of teamwork in preparing students for the workforce. Significantly, the research also offers practical advice for marketing educators desirous of developing and implementing effective and engaging pedagogy via TBL.
Building a Metrics-Enabled Marketing Curriculum
Authors: Pilling Bruce K. , Rigdon Edward E. , Brightman Harvey J.
Published: July 2012

The lack of analytical preparation of marketing students was a key concern at a large, public university in southeastern United States, leading to the decision to create a new required undergraduate marketing metrics course. This article describes the development of that course, designed specifically to strengthen analytical skills across the marketing curriculum. The process that guided course development is presented. The specific stages in course design are briefly discussed, and the instructional plan and specific teaching strategies are presented. This discussion includes the allocation of instructional time across topics, a description of in-class exercises, a description of hooks for each module, and a focus on establishing the relevance of individual metrics and introducing/reviewing math concepts on a just-in-time basis. Student perceptions of learning and primary trait analysis results are reported, followed by a discussion of challenges encountered and issues surrounding the applicability of the process.
A review of the technological solutions for the treatment of oily sludges from petroleum refineries
Authors: da Silva Leonardo Jordão , Alves Flávia Chaves , de França Francisca Pessôa
Published: July 2012

The activities of the oil industry have several impacts on the environment due to the large amounts of oily wastes that are generated. The oily sludges are a semi-solid material composed by a mixture of clay, silica and iron oxides contaminated with oil, produced water and the chemicals used in the production of oil. Nowadays both the treatment and management of these waste materials is essential to promote sustainable management of exploration and exploitation of natural resources. Biological, physical and chemical processes can be used to reduce environmental contamination by petroleum hydrocarbons to acceptable levels. The choice of treatment method depends on the physical and chemical properties of the waste as well as the availability of facilities to process these wastes. Literature provides some operations for treatment of oily sludges, such as landfilling, incineration, co-processing in clinkerization furnaces, microwave liquefaction, centrifugation, destructive distillation, thermal plasma, low-temperature conversion, incorporation in ceramic materials, development of impermeable materials, encapsulation and biodegradation in land farming, biopiles and bioreactors. The management of the technology to be applied for the treatment of oily wastes is essential to promote proper environmental management, and provide alternative methods to reduce, reuse and recycle the wastes.
The Visuospatial Dimension of Writing
Authors: Olive Thierry , Passerault Jean-Michel
Published: July 2012

The authors suggest that writing should be conceived of not only as a verbal activity but also as a visuospatial activity, in which writers process and construct visuospatial mental representations. After briefly describing research on visuospatial cognition, they look at how cognitive researchers have investigated the visuospatial dimension of the mental representations and processes engaged in writing. First, they show how Hayes’s research integrated the visuospatial dimension of writing. Second, they describe how the written trace can serve as a visual resource. Third, they focus on the visuospatial processes involved in constructing an overall representation of the text and its physical layout. Finally, they review findings on the visuospatial demands that planning places on working memory. All the data and theories presented in this article support the idea that writing is indeed a visuospatial activity.
Can Carpooling Clear the Road and Clean the Air?
Authors: Shewmake Sharon
Published: July 2012

Proponents of High Occupancy Vehicle (HOV) lanes claim the lanes reduce vehicle-trips by encouraging more people to carpool, but the evidence is mixed. This article reviews studies on the impacts of HOV lanes with a focus on behavioral models. This research makes a case for performance measures with direct welfare, congestion, or air pollution effects and focuses on papers that explicitly model carpool formation and allow for induced demand. Papers on individual regions find that HOV lanes may increase or decrease welfare, while more general papers find that the impact of HOV lanes depends on underlying parameters. The Clean Air Act assumes that HOV lanes reduce traffic volume and improve air quality and recommends HOV lanes to areas with poor air quality. This research finds there is no consensus on HOV lane impacts and, that using HOV lanes as a travel control measure may be misguided, but that further research is warranted.
Governors as Economic Problem Solvers
Authors: Taylor Charles D.
Published: July 2012

Despite the important role governors have played in shaping states’ economic development strategies, existing quantitative studies of state economic development policymaking have paid only scant attention to the factors that influence governors’ decisions about economic development policy. This study investigates these factors using a unique data set of gubernatorial economic development proposals generated by content analyzing hundreds of major legislative addresses delivered by governors during the 12-year period from 1995 to 2006. The findings reveal that gubernatorial economic development policymaking is only partially an attempt to solve a state’s economic problems. Economic policy making by governors appears to be driven largely by a desire to compete for new business investment during periods of economic expansion.
Fuzzy compensator design against windup of a magnetic actuator during milling operation
Authors: Lee Rong-Mao , Tsai Nan-Chyuan
Published: July 2012

A fuzzy anti-windup compensator is proposed and applied to the embedded cylindrical-array magnetic actuator to ensure the superior performance of spindle position regulation for milling machines under actuator saturation. Since embedded cylindrical-array magnetic actuator is a type of active magnetic bearing, the supplied coil current and the induced magnetic force are both limited by the maximum current and power output of the active magnetic bearing and the associated amplifier. Once the magnetic actuator is saturated, the required control input cannot be realized by an embedded cylindrical-array magnetic actuator and may lead to drastic tremble of the spindle position. In this work, an anti-windup compensator, based on a fuzzy logic algorithm, is therefore proposed to rectify the control input to an embedded cylindrical-array magnetic actuator. By employing commercial software, MATLAB/Simulink, and signal processing interface, Module DS1104 by dSPACE, the efficacy of the fuzzy anti-windup compensation is practically verified by intensive experiments.
Combustion and emission characteristics of a gasoline–dimethyl ether dual-fuel engine
Authors: Cha Junepyo , Kwon Sangil , Kwon Seokjoo , Park Sungwook
Published: July 2012

An experimental investigation was performed to investigate the effect of a split-injection strategy on the combustion and exhaust emission characteristics as well as on the particle number distribution for a single-cylinder compression ignition engine with gasoline–dimethyl ether dual fuelling. The gasoline–dimethyl ether dual-fuel injection system utilized port injection for gasoline and direct injection for dimethyl ether. In the present system, premixed fuel (i.e. gasoline) was injected into the premixing chamber at an injection pressure of 3 MPa using gasoline direct injection to mix the air–gasoline mixture sufficiently. However, dimethyl ether fuel was injected at an injection pressure of 50 MPa directly into a combustion chamber in order to control the combustion phase, resulting in a change in the direct-injection timing from −20° to +2° crank angle. The experimental results show that the gasoline–dimethyl ether dual-fuel engine exhibited benefits in the indicated mean effective pressure for early-injection cases (i.e. near −10° crank angle after top dead centre). However, the indicated mean effective pressure of the gasoline–dimethyl ether dual-fuel engine deteriorated for delayed-injection cases owing to incomplete combustion. In addition, a significant reduction in the nitrogen oxide emissions was observed using gasoline–dimethyl ether dual fuel compared with those obtained using conventional dimethyl ether combustion. In particular, soot emissions are almost at zero level for all the cases. On the other hand, hydrocarbon and carbon dioxide emissions increase with an increasing portion of premixed injection fuel (i.e. gasoline) in conventional injection timing, which is near top dead centre.