bluuebunny/crossref_metadata_2025 huggingface dataset:
Airways in smooth muscle α-actin null mice experience a compensatory mechanism that modulates their contractile response
Authors: Shardonofsky Felix R. , Moore Joan , Schwartz Robert J. , Boriek Aladin M.
Published: December 2011

We hypothesized that ablation of smooth muscle α-actin (SM α-A), a contractile-cytoskeletal protein expressed in airway smooth muscle (ASM) cells, abolishes ASM shortening capacity and decreases lung stiffness. In both SM α-A knockout and wild-type (WT) mice, airway resistance (Raw) determined by the forced oscillation technique rose in response to intravenous methacholine (Mch). However, the slope of Raw (cmH2O·ml−1·s) vs. log2Mch dose (μg·kg−1·min−1) was lower ( P = 0.007) in mutant (0.54 ± 0.14) than in WT mice (1.23 ± 0.19). RT-PCR analysis performed on lung tissues confirmed that mutant mice lacked SM α-A mRNA and showed that these mice had robust expressions of both SM γ-A mRNA and skeletal muscle (SKM) α-A mRNA, which were not expressed in WT mice, and an enhanced SM22 mRNA expression relative to that in WT mice. Compared with corresponding spontaneously breathing mice, mechanical ventilation-induced lung mechanical strain increased the expression of SM α-A mRNA in WT lungs; in mutant mice, it augmented the expressions of SM γ-A mRNA and SM22 mRNA and did not alter that of SKM α-A mRNA. In mutant mice, the expression of SM γ-A mRNA in the lung during spontaneous breathing and its enhanced expression following mechanical ventilation are consistent with the likely possibility that in the absence of SM α-A, SM γ-A underwent polymerization and interacted with smooth muscle myosin to produce ASM shortening during cholinergic stimulation. Thus our data are consistent with ASM in mutant mice experiencing compensatory mechanisms that modulated its contractile muscle capacity.
A Generalization of a Class of Matrices: Analytic Inverse and Determinant
Authors: Valvi F. N.
Published: December 2011

The aim of this paper is to present the structure of a class of
matrices that enables explicit inverse to be obtained. Starting from an
already known class of matrices, we construct a Hadamard product that
derives the class under consideration. The latter are defined by
parameters, analytic expressions of which provide the elements of the
lower Hessenberg form inverse. Recursion formulae of these expressions
reduce the arithmetic operations in evaluating the inverse to .
Proteomics Analyses of the Opportunistic Pathogen Burkholderia vietnamiensis Using Protein Fractionations and Mass Spectrometry
Authors: Wickramasekara Samanthi , Neilson Julie , Patel Naren , Breci Linda , Hilderbrand Amy , Maier Raina M. , Wysocki Vicki
Published: December 2011

The main objectives of this work were to obtain a more extensive coverage of the Burkholderia vietnamiensis proteome than previously reported and to identify virulence factors using tandem mass spectrometry. The proteome of B. vietnamiensis was precipitated into four fractions to as extracellular, intracellular, cell surface and cell wall proteins. Two different approaches were used to analyze the proteins. The first was a gel‐based method where 1D SDS‐PAGE was used for separation of the proteins prior to reverse phase liquid chromatography tandem mass spectrometry (LC‐MS/MS). The second method used MudPIT analysis (Multi dimensional Protein Identification Technique), where proteins are digested and separated using cation exchange and reversed phase separations before the MS/MS analysis (LC/LC‐MS/MS). Overall, gel‐based LC‐MS/MS analysis resulted in more protein identifications than the MudPIT analysis. Combination of the results lead to identification of more than 1200 proteins, approximately 16% of the proteins coded from the annotated genome of Burkholderia species. Several virulence factors were detected including flagellin, porin, peroxiredoxin and zinc proteases.
Tripled Fixed Points of Multivalued Nonlinear Contraction Mappings in Partially Ordered Metric Spaces
Authors: Abbas Mujahid , Aydi Hassen , Karapınar Erdal
Published: December 2011

Berinde and Borcut (2011), introduced the concept of tripled fixed point for single mappings in partially ordered metric spaces. Samet and Vetro (2011) established some coupled fixed point theorems for multivalued nonlinear contraction mappings in partially ordered metric spaces. In this paper, we obtain existence of tripled fixed point of multivalued nonlinear contraction mappings in the framework of partially ordered metric spaces. Also, we give an example.
Age-Related Health Hazards in Old Patients with First-Time Referral to a Rheumatologist: A Descriptive Study
Authors: van Lankveld W. , Fransen M. , van den Hoogen F. , den Broeder Alfons
Published: December 2011

Objective. To study the prevalence of generic age-related health hazards in elderly patient referred to a rheumatologist. Methods. Patients aged 75 or older referred to a specialized gerontorheumatological outpatient service over a period of 2 years were studied prospectively to determine the prevalence of comorbidities, a history of falls, inactivity, cognitive dysfunction, loneliness, and depression in this patient group. Results. A group of 154 patients were included in the study. Comorbidities were observed in 88% of the patients. At least one fall was reported in the last year by 44% of the patients; 44% of the patients reported low levels of health-enhancing physical activity. Depressed mood and loneliness were elevated in 30% and 31% of the patients, respectively. Mild or moderate cognitive impairment was observed in 13% of the patients. Conclusion. Patients in this study were characterized by poor physical ability, high levels of pain, and high prevalence of age-related health hazards.
Electrodynamical Coupling of Earth's Atmosphere and Ionosphere: An Overview
Authors: Singh A. K. , Siingh Devendraa , Singh R. P. , Mishra Sandhya
Published: December 2011

Electrical processes occurring in the atmosphere couple the atmosphere and ionosphere, because both DC and AC effects operate at the speed of light. The electrostatic and electromagnetic field changes in global electric circuit arise from thunderstorm, lightning discharges, and optical emissions in the mesosphere. The precipitation of magnetospheric electrons affects higher latitudes. The radioactive elements emitted during the earthquakes affect electron density and conductivity in the lower atmosphere. In the present paper, we have briefly reviewed our present understanding of how these events play a key role in energy transfer from the lower atmosphere to the ionosphere, which ultimately results in the Earth's atmosphere-ionosphere coupling.
Chromatin Evolution and Molecular Drive in Speciation
Authors: Sawamura Kyoichi
Published: December 2011

Are there biological generalities that underlie hybrid sterility or inviability? Recently, around a dozen “speciation genes” have been identified mainly inDrosophila, and the biological functions of these genes are revealing molecular generalities. Major cases of hybrid sterility and inviability seem to result from chromatin evolution and molecular drive in speciation. Repetitive satellite DNAs within heterochromatin, especially at centromeres, evolve rapidly through molecular drive mechanisms (both meiotic and centromeric). Chromatin-binding proteins, therefore, must also evolve rapidly to maintain binding capability. As a result, chromatin binding proteins may not be able to interact with chromosomes from another species in a hybrid, causing hybrid sterility and inviability.
Comparison of CD63 Upregulation Induced by NSAIDs on Basophils and Monocytes in Patients with NSAID Hypersensitivity
Authors: Abuaf N. , Rostane H. , Barbara J. , Toly-Ndour C. , Gaouar H. , Mathelier-Fusade P. , Leynadier F. , Francès C. , Girot R.
Published: December 2011

Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial. Objectives. In patients with a history of nonallergic NSAID hypersensitivity, stratified according to the severity of the symptoms, to assess with NSAIDs the predictive value of basophil (BAT) and monocyte (MAT) activation tests. Patients/Methods. Sixty patients who had NSAIDs-induced or exacerbated urticaria/angiooedema and 20 controls was included. After incubation with NSAIDs or acetaminophen, leukocytes were analysed for CD63 upregulation. Results. With aspirin, the sensitivity (37%) and specificity (90%) of BAT agree with already published results. In contrast, when patients had had cutaneous and visceral reactions, the frequency of positive BAT 14/22 (64%, P<0.001) or MAT 10/22 (46%, P<0.01) were increased. Conclusions. Positive tests were more frequent among patients having a severe hypersensitivity contrasting with the other patients who had results similar to controls.
Classifying Human Brain Tumors by Lipid Imaging with Mass Spectrometry
Authors: Eberlin Livia S. , Norton Isaiah , Dill Allison L. , Golby Alexandra J. , Ligon Keith L. , Santagata Sandro , Cooks R. Graham , Agar Nathalie Y.R.
Published: December 2011

Brain tissue biopsies are required to histologically diagnose brain tumors, but current approaches are limited by tissue characterization at the time of surgery. Emerging technologies such as mass spectrometry imaging can enable a rapid direct analysis of cancerous tissue based on molecular composition. Here, we illustrate how gliomas can be rapidly classified by desorption electrospray ionization-mass spectrometry (DESI-MS) imaging, multivariate statistical analysis, and machine learning. DESI-MS imaging was carried out on 36 human glioma samples, including oligodendroglioma, astrocytoma, and oligoastrocytoma, all of different histologic grades and varied tumor cell concentration. Gray and white matter from glial tumors were readily discriminated and detailed diagnostic information could be provided. Classifiers for subtype, grade, and concentration features generated with lipidomic data showed high recognition capability with more than 97% cross-validation. Specimen classification in an independent validation set agreed with expert histopathology diagnosis for 79% of tested features. Together, our findings offer proof of concept that intraoperative examination and classification of brain tissue by mass spectrometry can provide surgeons, pathologists, and oncologists with critical and previously unavailable information to rapidly guide surgical resections that can improve management of patients with malignant brain tumors. Cancer Res; 72(3); 645–54. ©2011 AACR.
Chromogranin A Regulates Tumor Self-Seeding and Dissemination
Authors: Dondossola Eleonora , Crippa Luca , Colombo Barbara , Ferrero Elisabetta , Corti Angelo
Published: December 2011

Cancer progression involves the seeding of malignant cells in circulation and the colonization of distant organs. However, circulating neoplastic cells can also reinfiltrate the tumor of origin. This process, called “tumor-self seeding,” can select more aggressive cells that may contribute to cancer progression. Here, using mouse mammary adenocarcinoma models, we observed that both tumor self-seeding and organ colonization were inhibited by chromogranin A (CgA), a protein present in variable amounts in the blood of cancer patients. Mechanism studies showed that CgA inhibited the shedding of cancer cells in circulation from primary tumors, as well as the reinfiltration of tumors and the colonization of lungs by circulating tumor cells. CgA reduced gap formation induced by tumor cell–derived factors in endothelial cells, decreased vascular leakage in tumors, and inhibited the transendothelial migration of cancer cells. Together, our findings point to a role for circulating CgA in the regulation of tumor cell trafficking from tumor-to-blood and from blood-to-tumor/normal tissues. Inhibition of the multidirectional trafficking of cancer cells in normal and neoplastic tissues may represent a novel strategy to reduce cancer progression. Cancer Res; 72(2); 449–59. ©2011 AACR.
Extreme All-Cause Mortality in JUPITER Requires Reexamination of Vital Records
Authors: Serebruany Victor L.
Published: December 2011

Objective: To compare all-cause mortality in JUPITER with other statin trials at 21 months of follow-up. Background: Outcome advantages including all-cause mortality reduction yielded from the JUPITER trial support aggressive use of rosuvastatin and, perhaps by extension, other statins for primary prevention. Despite enrolling apparently healthy subjects and early trial termination at 21 months of mean follow-up, JUPITER revealed very high all-cause mortality in both the placebo (2.8%) and rosuvastatin (2.2%) arms. Methods: Comparison of all-cause mortality prorated for 21 months in 10 primary prevention studies and 1 acute coronary syndromes statin trial. Findings: The all-cause mortality in JUPITER was more than twice that of the average of primary prevention studies, matching well only with specific trials designed in diabetics (ASPEN or CARDS), early hypertension studies (ALLHAT-LLT) or a trial in patients with acute coronary syndromes (PROVE IT). Since the ‘play of chance’ is unlikely to explain these discrepancies due to excellent baseline match, excess death rates and all-cause mortality rates in both JUPITER arms must be questioned. It may be important that the study sponsor self-monitored sites. Conclusions: Excess all-cause mortality rates in the apparently relatively healthy JUPITER population are alarming and require independent verification. If, indeed, the surprising outcomes in JUPITER are successfully challenged, and considering established harm of statins with regard to rhabdomyolysis as well as, potentially, diabetes, millions of patients may find better and safer options for primary prevention of vascular events.
Gamma-Hydroxybutyrate Detoxification by Titration and Tapering
Authors: de Jong Cor A.J. , Kamal Rama , Dijkstra Boukje A.G. , de Haan Hein A.
Published: December 2011

Objective: To determine the effectiveness and safety of a new detoxification procedure in γ-hydroxybutyrate (GHB)-dependent patients. GHB is an endogenous inhibitory neurotransmitter and anesthetic agent that is being abused as a club drug. In many GHB-dependent patients a severe withdrawal syndrome develops that does not respond to treatment with high dosages of benzodiazepines and often requires an admission to an intensive care unit. Methods: Based on the knowledge of detoxification procedures in opioid and benzodiazepine dependence, we developed a titration and tapering procedure. A consecutive series of 23 GHB-dependent inpatients were transferred from illegal GHB (mostly self-produced) in various concentrations to pharmaceutical GHB. They were given initial doses that resulted in a balance between sedation and withdrawal symptoms. After this titration period, patients were placed on a 1-week taper. Results: We have found that after titration the patients experienced a low level of withdrawal symptoms. During tapering these symptoms decreased significantly and no patient developed a delirium or a psychosis. None of the patients had to be transferred to a medium or intensive care unit. Conclusions: This detoxification procedure proved to be safe and convenient in patients with moderate to severe GHB dependence.
Relative Etiological Role of Prior Hepatitis B Virus Infection and Nonalcoholic Fatty Liver Disease in the Development of Non-B Non-C Hepatocellular Carcinoma in a Hepatitis B-Endemic Area
Authors: Cho Eun Ju , Kwack Min Sun , Jang Eun Sun , You Su Jong , Lee Jeong-Hoon , Kim Yoon Jun , Yoon Jung-Hwan , Lee Hyo-Suk
Published: December 2011

Background and Aims: We investigated the relative etiological role of prior hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) in the development of non-B non-C, non-alcohol or specific cause-related hepatocellular carcinoma (NBNC-NA-NS HCC) in an HBV-endemic area of Korea. Methods: A total of 329 patients with NBNC-NA-NS HCC were enrolled in this study. Prior HBV infection was defined as the presence of isolated IgG hepatitis B core antibody (anti-HBc), and NAFLD was diagnosed by the findings from the imaging in the absence of a history of excessive alcohol consumption. Results: Prior HBV infection was the most common cause of underlying liver disease (76.6%). Only 8.2% of the patients had NAFLD as the only risk factor and the same proportion of patients had evidence of both prior HBV infection and NAFLD. Patients without definitive causes accounted for 7.0% of the cases. During the past 10 years, the relative proportion of isolated IgG anti-HBc-positive HCC decreased significantly from 86.6% in 2001–2005 to 67.4% in 2006–2010 (p < 0.0001) and that of NAFLD-related HCC increased from 3.8% to 12.2% in the same period, respectively (p = 0.008). The mean age of NAFLD-related HCC patients (67.3 years) was significantly older than that of HCC patients related to prior HBV infection (61.2 years, p < 0.001). Conclusions: NAFLD-related HCC increased significantly while HCC related to prior HBV infection decreased during the past 10 years in an HBV-endemic area of Korea; however, the relative etiological role of prior HBV infection was still greater than that of NAFLD in the development of NBNC-NA-NS HCC.
Clinical Characteristics of Non-B Non-C Hepatocellular Carcinoma: A Single-Center Retrospective Study
Authors: Kim Soo Ki , Marusawa Hiroyuki , Eso Yuji , Nishikawa Hiroki , Ueda Yoshihide , Kita Ryuichi , Kimura Toru , Chiba Tsutomu , Osaki Yukio , Kudo Masatoshi
Published: December 2011

Background/Aims: To clarify risk factors and clinical features of both hepatitis B surface antigen and anti-HCV negative hepatocellular carcinoma (NBNC-HCC). Methods: HCC patients (n = 1,109) diagnosed at a single center were categorized based on the presence of serum hepatitis B surface antigen and HCVAb. Clinical characteristics of 127 NBNC-HCC patients were evaluated. Results: NBNC-HCC patients were stratified as those with alcoholic liver disease (ALD-HCC, n = 42) and alcohol-unrelated liver disease (non-ALD-HCC, n = 85). Compared with the ALD-HCC group, the non-ALD-HCC group had a higher prevalence of diabetes (p = 0.015), larger tumor size (p = 0.007), and higher tumor marker levels (p = 0.014). Liver function results were significantly worse in ALD-HCC than in non-ALD-HCC. Although the ALD-HCC group had a higher tendency toward recurrence than the non-ALD-HCC group, survival rates were similar between groups (p = 0.352). Conclusion: Alcohol consumption was the most common etiologic factor for NBNC-HCC, and diabetes may be related to the development of HCC in non-ALD-HCC patients. Non-ALD-HCC tended to be diagnosed at a more advanced stage, whereas liver function was worse, and tumor recurrence rate was higher in ALD-HCC patients. Further examination of the risk factors and establishment of a precise surveillance system are necessary for early diagnosis and the development of curative therapies for NBNC-HCC.
Effects of Monounsaturated Fatty Acids on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis
Authors: Schwingshackl L. , Strasser B. , Hoffmann G.
Published: December 2011

The appropriate pattern of macronutrient distribution for dietary protocols aimed at treating or preventing obesity and its associated cardiovascular diseases is still a controversial topic of discussion. Recommendations considering a specific percentage or range for monounsaturated fatty acids (MUFA) are rare. It was the aim of this study to analyze long-term, randomized, controlled dietary intervention trials and to investigate the effects of MUFA on the biomarkers of obesity and cardiovascular risk factors. Dietary regimens with a high amount of MUFA (>12%) were compared to those with ≤12%. The biomarkers taken into account were weight, waist circumference, fat mass, total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, systolic and diastolic blood pressure, as well as C-reactive protein. A total of 12 studies met the inclusion criteria. Data analysis was performed using the Review Manager 5.0.25 software. Significant differences between high- and low-MUFA protocols could be observed with respect to fat mass [–1.94 kg (confidence interval –3.72, –0.17), p = 0.03], systolic blood pressure [–2.26 mm Hg (confidence interval –4.28, –0.25), p = 0.03] and diastolic blood pressure [–1.15 mm Hg (confidence interval –1.96, –0.34), p = 0.005] favoring the dietary protocols with >12% MUFA. Therefore, MUFA might represent a useful tool in the design of dietary regimens for obesity and cardiovascular disease.
Effects of an Intervention and Maintenance Weight Loss Diet with and without Exercise on Anthropometric Indices in Overweight and Obese Healthy Women
Authors: Andreou Eleni , Philippou Christiana , Papandreou Dimitrios
Published: December 2011

Background and Aims: There is growing evidence that excess body weight and body fat levels may lead to various diseases. A low-calorie diet has been found to reduce body weight and fat; however, 95% of patients regain the weight within a short period of time. The aim of this study was to investigate the effects of a reduced-calorie diet with and without exercise on body composition profile as well as to evaluate maintenance of weight loss 18 weeks after the intervention had concluded. Methods: Two hundred and six overweight and/or obese women were randomized by a computer to either diet only (DO) or diet and exercise (DE) for an 18-week intervention period and 18 weeks of maintenance. Statistical significance was set at p < 0.05. Results: Body mass index (BMI) was reduced by 5.1 in the DE group compared to 3.2 in the DO group 18 weeks after the intervention period had ended; waist circumference (WC) was 14.2 cm lower in the exercise group and 8 cm lower in the diet alone group, and body fat was reduced by 15.5% in the DE group, while no changes were observed in the DO group. Conclusion: A combination of a reduced-calorie diet with exercise may successfully reduce weight, BMI, WC and body fat levels.
Excess of Rare Variants in Non–Genome-Wide Association Study Candidate Genes in Patients With Hypertriglyceridemia
Authors: Johansen Christopher T. , Wang Jian , McIntyre Adam D. , Martins Rebecca A. , Ban Matthew R. , Lanktree Matthew B. , Huff Murray W. , Péterfy Miklós , Mehrabian Margarete , Lusis Aldons J. , Kathiresan Sekar , Anand Sonia S. , Yusuf Salim , Lee Ann-Hwee , Glimcher Laurie H. , Cao Henian , Hegele Robert A.
Published: December 2011

Background—

Rare variant accumulation studies can implicate genes in disease susceptibility when a significant burden is observed in patients versus control subjects. Such analyses might be particularly useful for candidate genes that are selected based on experiments other than genome-wide association studies (GWAS). We sought to determine whether rare variants in non-GWAS candidate genes identified from mouse models and human mendelian syndromes of hypertriglyceridemia (HTG) accumulate in patients with polygenic adult-onset HTG.

Methods and Results—

We resequenced protein coding regions of 3 genes with established roles (
APOC2, GPIHBP1
,
LMF1
) and 2 genes recently implicated (
CREB3L3
and
ZHX3
) in TG metabolism. We identified 41 distinct heterozygous rare variants, including 29 singleton variants, in the combined sample; in total, we observed 47 rare variants in 413 HTG patients versus 16 in 324 control subjects (odds ratio=2.3;
P
=0.0050). Post hoc assessment of genetic burden in individual genes using 3 different tests suggested that the genetic burden was most prominent in the established genes
LMF1
and
APOC2
, and also in the recently identified
CREB3L3
gene.

Conclusions—

These extensive resequencing studies show a significant accumulation of rare genetic variants in non-GWAS candidate genes among patients with polygenic HTG, and indicate the importance of testing specific hypotheses in large-scale resequencing studies.
Association Between Diffuse Myocardial Fibrosis by Cardiac Magnetic Resonance Contrast-Enhanced T
1
Mapping and Subclinical Myocardial Dysfunction in Diabetic Patients
Authors: Ng Arnold C.T. , Auger Dominique , Delgado Victoria , van Elderen Saskia G.C. , Bertini Matteo , Siebelink Hans-Marc , van der Geest Rob J. , Bonetti Cosimo , van der Velde Enno T. , de Roos Albert , Smit Johannes W.A. , Leung Dominic Y. , Bax Jeroen J. , Lamb Hildo J.
Published: December 2011

Background—

Diabetic patients have increased interstitial myocardial fibrosis on histological examination. Magnetic resonance imaging (MRI) T
1
mapping is a previously validated imaging technique that can quantify the burden of global and regional interstitial fibrosis. However, the association between MRI T
1
mapping and subtle left ventricular (LV) dysfunction in diabetic patients is unknown.

Methods and Results—

Fifty diabetic patients with normal LV ejection fraction (EF) and no underlying coronary artery disease or regional macroscopic scar on MRI delayed enhancement were prospectively recruited. Diabetic patients were compared with 19 healthy controls who were frequency matched in age, sex and body mass index. There were no significant differences in mean LV end-diastolic volume index, end-systolic volume index and LVEF between diabetic patients and healthy controls. Diabetic patients had significantly shorter global contrast-enhanced myocardial T
1
time (425±72 ms vs. 504±34 ms,
P
<0.001). There was no correlation between global contrast-enhanced myocardial T
1
time and LVEF (
r
=0.14,
P
=0.32) in the diabetic patients. However, there was good correlation between global contrast-enhanced myocardial T
1
time and global longitudinal strain (
r
=−0.73,
P
<0.001). Global contrast-enhanced myocardial T
1
time was the strongest independent determinant of global longitudinal strain on multivariate analysis (standardized β=−0.626,
P
<0.001). Similarly, there was good correlation between global contrast-enhanced myocardial T
1
time and septal E′ (
r
=0.54,
P
<0.001). Global contrast-enhanced myocardial T
1
time was also the strongest independent determinant of septal E′ (standardized β=0.432,
P
<0.001).

Conclusions—

A shorter global contrast-enhanced myocardial T
1
time was associated with more impaired longitudinal myocardial systolic and diastolic function in diabetic patients.
Molecular Imaging of Mesenchymal Stem Cell
Authors: Wang Jingxiong , Najjar Amer , Zhang Sui , Rabinovich Brian , Willerson James T. , Gelovani Juri G. , Yeh Edward T.H.
Published: December 2011

Background—

Mesenchymal stem cells (MSCs) can differentiate into endothelial cells in vivo. However, it is unknown if the differentiated MSCs persist in vivo and if this potential persistence contributes to functional improvement after experimental myocardial infarction.

Methods and Results—

We generated a lentivector encoding 2 distinct reporter genes, one driven by a constitutive murine stem cell virus promoter and the other driven by an endothelial-specific Tie-2 promoter. The endothelial specificity of the lentivector was validated by its expression in endothelial cells but not in human MSCs (hMSCs). The lentivirus-transduced hMSCs were injected into peri-infarct areas of the hearts of severe combined immune-deficient mice. Persistence of injected cells was tracked by bioluminescence imaging (BLI) and verified by immunohistochemical staining. The BLI signal from the endothelial-specific reporter revealed that hMSCs differentiated into endothelial cells 48 hours after injection. However, both the constitutive and endothelial-specific BLI signals disappeared by day 50. Nonetheless, the improvement in left ventricle ejection fraction with hMSC therapy persisted for up to 6 months. Immunohistochemical staining showed that hMSC-derived endothelial cells integrated into endogenous CD31
+
vessels. Furthermore, hMSC-transplanted hearts had more CD31
+
vessels and a lesser degree of cardiac fibrosis compared with the controls at 6 months.

Conclusions—

hMSCs differentiated into endothelial cells and integrated into blood vessels after experimental myocardial infarction. The differentiated hMSCs only lasted for up to 50 days in vivo, but improvement in cardiac function persisted for up to 6 months. Increased angiogenesis and decreased fibrosis were associated with cardiac functional improvement after hMSC transplantation.
Impact of Prosthesis-Patient Mismatch on the Regression of Secondary Mitral Regurgitation After Isolated Aortic Valve Replacement With a Bioprosthetic Valve in Patients With Severe Aortic Stenosis
Authors: Angeloni Emiliano , Melina Giovanni , Pibarot Philippe , Benedetto Umberto , Refice Simone , Ciavarella Giuseppino M. , Roscitano Antonino , Sinatra Riccardo , Pepper John R.
Published: December 2011

Background—

Secondary mitral regurgitation (SMR) is generally reduced after isolated aortic valve replacement (AVR), but there is important interindividual variability in the magnitude of this reduction. Prosthesis-patient mismatch (PPM) may hinder normalization of left ventricular geometry and pressure overload following AVR, therefore we aimed to investigate the relationship between PPM and regression of SMR following AVR for aortic valve stenosis.

Methods and Results—

A total of 419 patients with AS who underwent isolated AVR at 2 institutions and presenting moderate SMR (mitral regurgitant volume 30 to 45 mL/beat) not considered for surgical correction were included in this study. Clinical and echocardiographic follow-up were completed at a median follow-up time of 37 months. PPM was defined as an indexed effective orifice area ≤0.85 cm
2
/m
2
and was found in 170/419 patients (40.6%). There were no significant differences in baseline and operative characteristics between patients with or without PPM. Patients with PPM had less regression of SMR following AVR compared with those with no PPM (change in mitral regurgitant volume:−11±4 versus −17±5 mL, respectively;
P
<0.0001). Variables significantly associated with postoperative change in mitral regurgitant volume on univariable analysis were entered in a multivariable linear regression model, which showed indexed effective orifice area (
P
<0.0001) and left atrial diameter (
P
=0.006) to be independently associated with mitral regurgitant volume improvement. Patients with PPM also had less postoperative improvement in 6-minute walking test distance (80±78 versus 42±41 m,
P
<0.0001).

Conclusions—

PPM is associated with lesser regression of SMR following AVR. This unfavorable effect was associated with worse functional capacity. These findings emphasize the importance of operative strategies aiming to prevent PPM in patients with aortic valve stenosis and concomitant SMR.
Etsrp/Etv2 Is Directly Regulated by
Foxc1a/b
in the Zebrafish Angioblast
Authors: Veldman Matthew B. , Lin Shuo
Published: December 2011

Rationale:

Endothelial cells are developmentally derived from angioblasts specified in the mesodermal germ cell layer. The transcription factor
etsrp/etv2
is at the top of the known genetic hierarchy for angioblast development. The transcriptional events that induce
etsrp
expression and angioblast specification are not well understood.

Objective:

We generated
etsrp:gfp
transgenic zebrafish and used them to identify regulatory regions and transcription factors critical for
etsrp
expression and angioblast specification from mesoderm.

Methods and Results:

To investigate the mechanisms that initiate angioblast cell transcription during embryogenesis, we have performed promoter analysis of the
etsrp
locus in zebrafish. We describe three enhancer elements sufficient for endothelial gene expression when place in front of a heterologous promoter. The deletion of all 3 regulatory regions led to a near complete loss of endothelial expression from the
etsrp
promoter. One of the enhancers, located 2.3 kb upstream of
etsrp
contains a consensus FOX binding site that binds Foxc1a and Foxc1b in vitro by EMSA and in vivo using ChIP. Combined knockdown of
foxc1a/b
, using morpholinos, led to a significant decrease in
etsrp
expression at early developmental stages as measured by quantitative reverse transcriptase–polymerase chain reaction and in situ hybridization. Decreased expression of primitive erythrocyte genes
scl
and
gata1
was also observed, whereas pronephric gene
pax2a
was relatively normal in expression level and pattern.

Conclusions:

These findings identify mesodermal
foxc1a/b
as a direct upstream regulator of
etsrp
in angioblasts. This establishes a new molecular link in the process of mesoderm specification into angioblast.
Aortic Event Rate in the Marfan Population
Authors: Jondeau Guillaume , Detaint Delphine , Tubach Florence , Arnoult Florence , Milleron Olivier , Raoux Francois , Delorme Gabriel , Mimoun Lea , Krapf Laura , Hamroun Dalil , Beroud Christophe , Roy Carine , Vahanian Alec , Boileau Catherine
Published: December 2011

Background—

Optimal management, including timing of surgery, remains debated in Marfan syndrome because of a lack of data on aortic risk associated with this disease.

Methods and Results—

We used our database to evaluate aortic risk associated with standardized care. Patients who fulfilled the international criteria, had not had previous aortic surgery or dissection, and came to our center at least twice were included. Aortic measurements were made with echocardiography (every 2 years); patients were given systematic β-blockade and advice about sports activities. Prophylactic aortic surgery was proposed when the maximal aortic diameter reached 50 mm. Seven hundred thirty-two patients with Marfan syndrome were followed up for a mean of 6.6 years. Five deaths and 2 dissections of the ascending aorta occurred during follow-up. Event rate (death/aortic dissection) was 0.17%/y. Risk rose with increasing aortic diameter measured within 2 years of the event: from 0.09%/y per year (95% confidence interval, 0.00–0.20) when the aortic diameter was <40 mm to 0.3% (95% confidence interval, 0.00–0.71) with diameters of 45 to 49 mm and 1.33% (95% confidence interval, 0.00–3.93) with diameters of 50 to 54 mm. The risk increased 4 times at diameters ≥50 mm. The annual risk dropped below 0.05% when the aortic diameter was <50 mm after exclusion of a neonatal patient, a woman who became pregnant against our recommendation, and a 72-year-old woman with previous myocardial infarction.

Conclusions—

Risk of sudden death or aortic dissection remains low in patients with Marfan syndrome and aortic diameter between 45 and 49 mm. Aortic diameter of 50 mm appears to be a reasonable threshold for prophylactic surgery.
Intravenous Thrombolysis for Stroke Increases Over Time at Primary Stroke Centers
Authors: Prabhakaran Shyam , McNulty Maggie , O'Neill Kathleen , Ouyang Bichun
Published: December 2011

Background and Purpose—

We evaluated the impact that duration as a primary stroke center (PSC) had on tissue-type plasminogen activator (tPA) utilization for acute ischemic stroke.

Methods—

A retrospective analysis of the Illinois Hospital Association CompData was performed identifying those patients with primary discharge diagnosis of acute ischemic stroke based on
International Classification of Diseases
version 9 codes. We assessed utilization of tPA by
International Classification of Diseases
version 9 procedure code (99.10). We categorized patients as cared for at non-PSC, PSC >1 year before, ≤1 year before, ≤1 year after, and >1 year after certification. We used generalized estimating equations to calculate adjusted odds ratios for tPA utilization by PSC category.

Results—

Among 119 539 acute ischemic stroke patients (mean age, 72 years; 55.2% women), tPA use was 1.9% but increased by PSC category (
P
<0.001): (1) non-PSC 0.9%; (2) >1 year before PSC certification 1.4%; (3) ≤1 year before certification 3.2%; (4) ≤1 year after certification 4.3%; and (5) >1 year after certification 6.5%. Adjusting for age, insurance status, admission source, year of study, region of Illinois, and hospital bed size, the odds of tPA utilization increased with advancing stage of PSC certification (highest category: adjusted odds ratio, 2.37; 95% confidence interval, 1.52–3.71).

Conclusions—

Although increasing over time, stroke thrombolysis is strongly impacted by the PSC certification process. Rather than waning or stagnating, tPA utilization increases at PSC from the earliest phases of preparation through certification and subsequent maintenance.
A 3DVAR-Based Dynamical Initialization Scheme for Tropical Cyclone Predictions*
Authors: Zhang Shengjun , Li Tim , Ge Xuyang , Peng Melinda , Pan Ning
Published: December 2011

A combined tropical cyclone dynamic initialization–three-dimensional variational data assimilation scheme (TCDI–3DVAR) is proposed. The specific procedure for the new initialization scheme is described as follows. First, a first-guess vortex field derived from a global analysis will be spun up in a full-physics mesoscale regional model in a quiescent environment. During the spinup period, the weak vortex is forced toward the observed central minimum sea level pressure (MSLP). The so-generated balanced TC vortex with realistic MSLP and a warm core is then merged into the environmental field and used in the subsequent 3DVAR data assimilation. The observation system simulation experiments (OSSEs) demonstrate that this new TC initialization scheme leads to much improved initial MSLP, warm core, and asymmetric temperature patterns compared to those from the conventional 3DVAR scheme. Forecasts of TC intensity with the new initialization scheme are made, and the results show that the new scheme is able to predict the “observed” TC intensity change, compared to runs with the conventional 3DVAR scheme or the TCDI-only scheme. Sensitivity experiments further show that the intensity forecasts with knowledge of the initial MSLP and wind fields appear more skillful than do the cases where the initial MSLP, temperature, and humidity fields are known. The numerical experiments above demonstrate the potential usefulness of the proposed new initialization scheme in operational applications. A preliminary test of this scheme with a navy operational model shows encouraging results.
Citizens into wolves? Carl Schmitt’s fictive account of security
Authors: Moore Thomas
Published: December 2011

This article assesses the extent to which security regimes are the products of authorization in the thought of Thomas Hobbes and Carl Schmitt. The Hobbesian security regime offers a contingent construction of security in terms of processes of authorization and brings into view questions about the epistemic construction of security within security discourse today. The Schmittian concept of security involves the naturalization of security through the state, meaning that security is understood as condition rather than regime. Rather than look to Carl Schmitt’s concept of security as the paradigm of international security today, there are clear benefits in returning to the contractual account of security evident in the Hobbesian emphasis on authorization. Security is not the primary value of political community, but the means by which political communities realize their internal goods. Schmitt’s security regime is fictive, driven by colourful metaphor and political theology. By returning to classic questions of authorization—how a security regime authorizes itself—International Relations theory can examine the legitimation of security beyond an exclusively state-centric model.
Cambodia: Moving away from democracy?
Authors: Un Kheang
Published: December 2011

This article examines the quality of democracy in Cambodia, arguing that Cambodian democracy since its inception in 1993 has evolved from unstructured competitive authoritarianism toward an authoritarianism characterized by the presence of a stable hegemonic party system wherein the minimum criteria for democracy have been severely curtailed. Although the quality of democracy has declined, the regime’s legitimacy has risen, due mainly to sustained economic growth and political stability, and increased patronage-based development. Economic performance-based legitimacy has become path-dependent; without growth the ruling party’s legitimacy might be called into question. Given the current political, social, economic and international contexts that favor economic growth with political stability, Cambodia will sustain a dominant party authoritarian regime with limited quality of democracy.
Cochlear Implantation in Children with Anomalous Cochleovestibular Anatomy
Authors: Pakdaman Michael N. , Herrmann Barbara S. , Curtin Hugh D. , Van Beek‐King Jessica , Lee Daniel J.
Published: December 2011

Objective

To determine the influence of inner ear dysplasia on both surgical and audiologic outcomes following pediatric cochlear implant (CI) surgery.

Data Sources

MEDLINE (1982‐2009) and data from Massachusetts Eye and Ear Infirmary.

Review Methods

A systematic review of the literature was performed. Variables assessed included age at implantation, duration of CI use, radiologic and operative findings, and speech perception outcome data.

Results

The initial search yielded 1326 articles. Including data from our own study, twenty‐two fulfilled criteria for inclusion, representing 311 patients. Data for bilateral implants were recorded only for the first implant. Data on simultaneous bilateral implants were not recorded. The most common anomaly seen was large vestibular aqueduct (89/311 or 29%). When comparing patients with mild‐moderate or severe dysplasia, rates of cerebrospinal fluid gusher were 31% versus 35% (odds ratio [OR] = 0.50), anomalous facial nerve anatomy was seen in 11% versus 51% (OR = 0.15), and postoperative speech perception abilities were found in 84% versus 54% (OR = 1.93), respectively. A large heterogeneity was found among studies regarding all outcome measures.

Conclusion

Although we found that severe inner ear dysplasia was associated with increased surgical difficulty and lower speech perception, the lack of uniformity in published clinical data limited the strength of these results. Standardization of surgical and radiologic reporting as well as more consistent speech perception testing is needed to better determine the association between anomalous cochleovestibular anatomy and clinical outcomes.
Early Intervention
Authors: Mudd Pamela A. , Perkins Jonathan N. , Harwood Jeri E. F. , Valdez Sondra , Allen Gregory C.
Published: December 2011

Objective

To determine benefits of early intervention in neonates with symptomatic micrognathia who underwent bilateral mandibular distraction osteogenesis within the first 90 days of life as relates to growth, need for supportive care, and further invasive procedures.

Study Design

Case series with chart review.

Setting

Tertiary care, academic children’s hospital.

Subjects and Methods

Review of neonates with symptomatic micrognathia who underwent bilateral mandibular distraction osteogenesis in the past 5 years. Inclusion criteria included mandibular distraction osteogenesis performed within the first 90 days of life. Outcome measures included hospital course, growth curves, supportive home care needs, and airway at cleft repair.

Results

Twenty‐four patients met inclusion criteria. The mean age at distraction was 30 days, and the average discharge was postoperative day 14. One patient required home oxygen, 50% were able to feed exclusively by oral diet, and no patients required tracheotomy. In addition, airway results were substantial, with 90% of patients showing objective improvement in airway grade from time of mandibular distraction to time of cleft repair.

Conclusion

We present our initial outcomes on mandibular distraction osteogenesis in neonates with symptomatic micrognathia. Early intervention allows discharge to home with minimal supportive care needs by avoiding tracheostomy and facilitating transition to oral feeds. The airway improvement is significant and is sustained and allows for easier intubation at time of cleft repair.
Data Derivatives
Authors: Amoore Louise
Published: December 2011

In a quiet London office, a software designer muses on the algorithms that will make possible the risk flags to be visualized on the screens of border guards from Heathrow to St Pancras International. There is, he says, ‘real time decision making’ – to detain, to deport, to secondarily question or search – but there is also the ‘offline team who run the analytics and work out the best set of rules’. Writing the code that will decide the association rules between items of data, prosaic and mundane – flight route, payment type, passport – the analysts derive a novel preemptive security measure. This paper proposes the analytic of the data derivative – a visualized risk flag or score drawn from an amalgam of disaggregated fragments of data, inferred from across the gaps between data and projected onto an array of uncertain futures. In contrast to disciplinary and enclosed techniques of collecting data to govern population, the data derivative functions via ‘differential curves of normality’, imagining a range of potential futures through the association rule, thus ‘opening up to let things happen’ ( Foucault 2007 ). In some senses akin to the risk orientation of the financial derivative, itself indifferent to actual underlying people, places or events by virtue of modulated norms, the contemporary security derivative is not centred on who we are, nor even on what our data say about us, but on what can be imagined and inferred about who we might be – on our very proclivities and potentialities.
Early mobilization out of bed after ischaemic stroke reduces severe complications but not cerebral blood flow: a randomized controlled pilot trial
Authors: Diserens Karin , Moreira Tiago , Hirt Lorenz , Faouzi Mohamed , Grujic Jelena , Bieler Gilles , Vuadens Philippe , Michel Patrik
Published: December 2011

Objective: To evaluate whether early mobilization after acute ischaemic stroke is better than delayed mobilization with regard to medical complications and if it is safe in relation to neurological function and cerebral blood flow.

Design: Randomized controlled pilot trial of early versus delayed mobilization out of bed with incidence of severe complications as the primary outcome.

Setting: Acute stroke unit in the neurology department of a University Hospital.

Participants: Fifty patients after ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score >6 were recruited.

Intervention: All patients were treated with physiotherapy immediately after their admission. In the early protocol patients were mobilized out of bed after 52 hours, in the delayed protocol after seven days.

Results: Eight out of 50 randomized patients were excluded from the per-protocol analysis because of early transfer to other hospitals. There were 2 (8%) severe complications in the 25 early mobilization patients and 8 (47%) in the 17 delayed mobilization patients ( P < 0.006). There were no differences in the total number of complications or in clinical outcome. In the 26 patients (62%) who underwent serial transcranial Doppler ultrasonography, no blood flow differences were found.

Conclusion: We found an apparent reduction in severe complications and no increase in total complications with an early mobilization protocol after acute ischaemic stroke. No influence on neurological three-month outcomes or on cerebral blood flow was seen. These results justify larger trials comparing mobilization protocols with possibly even faster mobilization out of bed than explored here.
The Mekong Delta
Authors: Dapice David , Xuan Vo Tong
Published: December 2011

The Mekong Delta is the agricultural heart of Vietnam and home to nearly 20 million people. Its contributions to the entire country and global food consumers are enormous. The Delta’s delicate ecosystem, however, is distressed by several domestic and regional forces, including rural development, resource mismanagement, upstream damming, climate change, and failure to implement policies to link several systems. The authors examine trends and forces affecting the Delta and offer plausible adjustments to enhance the watershed’s well-being. Solutions will come from scale economies; higher value crops and branding; improvements to marketing channels, technologies to improve data collection and analysis, crop yields, and communication; foreign and domestic investment; and integrative policies to sustain Vietnam’s southern Delta and the entire Mekong Basin.