bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs
Authors: Fernandes Tiago , Baraúna Valério G. , Negrão Carlos E. , Phillips M. Ian , Oliveira Edilamar M.
Published: June 2015

Left ventricular (LV) hypertrophy is an important physiological compensatory mechanism in response to chronic increase in hemodynamic overload. There are two different forms of LV hypertrophy, one physiological and another pathological. Aerobic exercise induces beneficial physiological LV remodeling. The molecular/cellular mechanisms for this effect are not totally known, and here we review various mechanisms including the role of microRNA (miRNA). Studies in the heart, have identified antihypertrophic miRNA-1, -133, -26, -9, -98, -29, -378, and -145 and prohypertrophic miRNA-143, -103, -130a, -146a, -21, -210, -221, -222, -27a/b, -199a/b, -208, -195, -499, -34a/b/c, -497, -23a, and -15a/b. Four miRNAs are recognized as cardiac-specific: miRNA-1, -133a/b, -208a/b, and -499 and called myomiRs. In our studies we have shown that miRNAs respond to swimming aerobic exercise by 1) decreasing cardiac fibrosis through miRNA-29 increasing and inhibiting collagen, 2) increasing angiogenesis through miRNA-126 by inhibiting negative regulators of the VEGF pathway, and 3) modulating the renin-angiotensin system through the miRNAs-27a/b and -143. Exercise training also increases cardiomyocyte growth and survival by swimming-regulated miRNA-1, -21, -27a/b, -29a/c, -30e, -99b, -100, -124, -126, -133a/b, -143, -144, -145, -208a, and -222 and running-regulated miRNA-1, -26, -27a, -133, -143, -150, and -222, which influence genes associated with the heart remodeling and angiogenesis. We conclude that there is a potential role of these miRNAs in promoting cardioprotective effects on physiological growth.
Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness
Authors: Song Weifeng , Yu Zhihong , Doran Stephen F. , Ambalavanan Namasivayam , Steele Chad , Garantziotis Stavros , Matalon Sadis
Published: June 2015

Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2(187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2exposure. Cl2exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2in vulnerable populations and the development of appropriate treatments.
Visualization of Fra-1/AP-1 activation during LPS-induced inflammatory lung injury using fluorescence optical imaging
Authors: Rajasekaran Subbiah , Tamatam Chandramohan R. , Potteti Haranatha R. , Raman Venu , Lee Jae-Woo , Matthay Michael A. , Mehta Dolly , Reddy Narsa M. , Reddy Sekhar P.
Published: June 2015

Inappropriate lung inflammatory response following oxidant and toxicant exposure can lead to abnormal repair and disease pathogenesis, including fibrosis. Thus early detection of molecular and cellular processes and mediators promoting lung inflammation is necessary to develop better strategies for therapeutic intervention and disease management. Previously, we have shown that transcription factor Fra-1/AP-1 plays key roles in lung inflammatory response, as Fra-1-null mice are less susceptible than wild-type mice to LPS-induced lung injury and mortality. Herein, we developed a transgenic reporter mouse model expressing tdTomato under the control of FRA-1 (human) promoter (referred to as FRA-1TdTgmice) to monitor its activation during inflammatory lung injury using fluorescence protein-based optical imaging and molecular analysis in vivo and ex vivo. A higher red fluorescent signal was observed in the lungs of LPS-treated FRA-1TdTgmice compared with vehicle controls, and Western blot and qRT-PCR analyses revealed a significant correlation with the FRA-1- tdTomato reporter expression. Immunocolocalization demonstrated expression of FRA-1- tdTomato largely in lung alveolar macrophages and to some extent in epithelial cells. Moreover, we validated these results with a second reporter mouse model that expressed green fluorescent protein upon activation of endogenous Fra-1 promoter. Additionally, we demonstrated increased expression of FRA-1 in alveolar macrophages in human lung instilled with Escherichia coli ex vivo. Collectively, our data obtained from two independent reporter mouse models and from human samples underscore the significance of Fra-1 activation in alveolar macrophages during inflammatory lung injury and may aid in developing strategies to target this transcription factor in lung injury and repair.
Absence of the inflammasome adaptor ASC reduces hypoxia-induced pulmonary hypertension in mice
Authors: Cero Fadila Telarevic , Hillestad Vigdis , Sjaastad Ivar , Yndestad Arne , Aukrust Pål , Ranheim Trine , Lunde Ida Gjervold , Olsen Maria Belland , Lien Egil , Zhang Lili , Haugstad Solveig Bjærum , Løberg Else Marit , Christensen Geir , Larsen Karl-Otto , Skjønsberg Ole Henning
Published: June 2015

Pulmonary hypertension is a serious condition that can lead to premature death. The mechanisms involved are incompletely understood although a role for the immune system has been suggested. Inflammasomes are part of the innate immune system and consist of the effector caspase-1 and a receptor, where nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) is the best characterized and interacts with the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC). To investigate whether ASC and NLRP3 inflammasome components are involved in hypoxia-induced pulmonary hypertension, we utilized mice deficient in ASC and NLRP3. Active caspase-1, IL-18, and IL-1β, which are regulated by inflammasomes, were measured in lung homogenates in wild-type (WT), ASC−/−, and NLRP3−/− mice, and phenotypical changes related to pulmonary hypertension and right ventricular remodeling were characterized after hypoxic exposure. Right ventricular systolic pressure (RVSP) of ASC−/− mice was significantly lower than in WT exposed to hypoxia (40.8 ± 1.5 mmHg vs. 55.8 ± 2.4 mmHg, P < 0.001), indicating a substantially reduced pulmonary hypertension in mice lacking ASC. Magnetic resonance imaging further supported these findings by demonstrating reduced right ventricular remodeling. RVSP of NLRP3−/− mice exposed to hypoxia was not significantly altered compared with WT hypoxia. Whereas hypoxia increased protein levels of caspase-1, IL-18, and IL-1β in WT and NLRP3−/− mice, this response was absent in ASC−/− mice. Moreover, ASC−/− mice displayed reduced muscularization and collagen deposition around arteries. In conclusion, hypoxia-induced elevated right ventricular pressure and remodeling were attenuated in mice lacking the inflammasome adaptor protein ASC, suggesting that inflammasomes play an important role in the pathogenesis of pulmonary hypertension.
Neutrophil Extracellular Traps Accumulate in Peripheral Blood Vessels and Compromise Organ Function in Tumor-Bearing Animals
Authors: Cedervall Jessica , Zhang Yanyu , Huang Hua , Zhang Lei , Femel Julia , Dimberg Anna , Olsson Anna-Karin
Published: June 2015

Cancer produces a variety of collateral effects in patients beyond the malignancy itself, including threats to distal organ functions. However, the basis for such effects, associated with either primary or metastatic tumors, are generally poorly understood. In this study, we show how heart and kidney vascular function is impaired by neutrophils that accumulate in those tissues as a result of tumor formation in two different transgenic mouse models of cancer (RIP1-Tag2 model of insulinoma and MMTV-PyMT model of breast cancer). Neutrophil depletion by systemic administration of an anti-Gr1 antibody improved vascular perfusion and prevented vascular leakage in kidney vessels. We also observed the accumulation of platelet–neutrophil complexes, a signature of neutrophil extracellular traps (NET), in the kidneys of tumor-bearing mice that were completely absent from healthy nontumor-bearing littermates. NET accumulation in the vasculature was associated with upregulation of the proinflammatory adhesion molecules ICAM-1, VCAM-1, and E-selectin, as well as the proinflammatory cytokines IL1β, IL6, and the chemokine CXCL1. Administering DNase I to dissolve NETs, which have a high DNA content, restored perfusion in the kidney and heart to levels seen in nontumor-bearing mice, and also prevented vessel leakage in the blood vasculature of these organs. Taken together, our findings strongly suggest that NETs mediate the negative collateral effects of tumors on distal organs, acting to impair vascular function, and to heighten inflammation at these sites. Cancer Res; 75(13); 2653–62. ©2015 AACR.
EGF Receptor Promotes Prostate Cancer Bone Metastasis by Downregulating miR-1 and Activating TWIST1
Authors: Chang Yung-Sheng , Chen Wei-Yu , Yin Juan Juan , Sheppard-Tillman Heather , Huang Jiaoti , Liu Yen-Nien
Published: June 2015

Dysregulation of the EGFR signaling axis enhances bone metastases in many solid cancers. However, the relevant downstream effector signals in this axis are unclear. miR-1 was recently shown to function as a tumor suppressor in prostate cancer cells, where its expression correlated with reduced metastatic potential. In this study, we demonstrated a role for EGFR translocation in regulating transcription of miR-1-1, which directly targets expression of TWIST1. Consistent with these findings, we observed decreased miR-1 levels that correlated with enhanced expression of activated EGFR and TWIST1 in a cohort of human prostate cancer specimens and additional datasets. Our findings support a model in which nuclear EGFR acts as a transcriptional repressor to constrain the tumor-suppressive role of miR-1 and sustain oncogenic activation of TWIST1, thereby leading to accelerated bone metastasis. Cancer Res; 75(15); 3077–86. ©2015 AACR.
EGFR Mutation Status and First-Line Treatment in Patients with Stage III/IV Non–Small Cell Lung Cancer in Germany: An Observational Study
Authors: Schuette Wolfgang , Schirmacher Peter , Eberhardt Wilfried Ernst Erich , Fischer Juergen R. , von der Schulenburg J.-Matthias Graf , Mezger Joerg , Schumann Christian , Serke Monika , Zaun Silke , Dietel Manfred , Thomas Michael
Published: June 2015

Introduction: EGFR mutations confer sensitivity to EGFR tyrosine kinase inhibitors (TKI) in advanced non–small cell lung cancer (NSCLC). We investigated the clinicopathologic characteristics associated with EGFR mutations and their impact on real-world treatment decisions and outcomes in Caucasian patients with advanced NSCLC.

Methods: REASON (NCT00997230) was a noninterventional multicenter study in patients (≥18 years) with stage IIIb/IV NSCLC, who were candidates for EGFR mutation testing and first-line systemic treatment, but not eligible for surgery or radiotherapy. Patients were followed up according to normal clinical practice and assessed for primary (correlation of mutation status with baseline characteristics) and secondary endpoints (first-line treatment decision).

Results: Baseline data were obtained for 4,200 patients; 4,196 fulfilled the inclusion criteria; EGFR mutations were detected in 431 patients; no EGFR mutations were detected in 3,590 patients; mutation status was not evaluable in 175 patients. In multivariate analysis, the odds of EGFR mutations were significantly higher (P < 0.0001) in females versus males (odds ratio: 1.85; 95% confidence interval, 1.48–2.32), never-smokers versus smokers (3.64; 2.91–4.56), and patients with adenocarcinoma versus other histologic subtypes (2.94; 2.17–4.08). The most commonly prescribed first-line systemic treatments were: EGFR-TKIs in EGFR mutation–positive NSCLC (56.6%) and combination chemotherapy in EGFR mutation–negative NSCLC (78.5%).

Conclusions: This represents the largest dataset for EGFR mutations in Caucasian patients and shows EGFR mutations to be most prevalent in females with adenocarcinoma who had never smoked.

Impact: These findings add to our understanding of the prognostic and predictive factors of NSCLC, supporting future improved treatment selection. Cancer Epidemiol Biomarkers Prev; 24(8); 1254–61. ©2015 AACR.
Gallbladder Cancer Incidence and Mortality, United States 1999–2011
Authors: Henley S. Jane , Weir Hannah K. , Jim Melissa A. , Watson Meg , Richardson Lisa C.
Published: June 2015

Background: Gallbladder cancer is a rare cancer with unusual distribution, and few population-based estimates for the United States have been published.

Methods: Using population-based cancer incidence and mortality data, we examined U.S. gallbladder cancer incidence and death rates for 2007–2011 and trends for 1999–2011.

Results: During 2007 to 2011, approximately 3,700 persons were diagnosed with primary gallbladder cancer (rate = 1.13 cases per 100,000) and 2,000 died from the disease (rate = 0.62 deaths per 100,000) each year in the United States. Two thirds of gallbladder cancer cases and deaths occurred among women. Gallbladder cancer incidence and death rates were three times higher among American Indian and Alaska Native persons than non-Hispanic white persons. By state, gallbladder cancer incidence and death rates ranged by about 2-fold. During 1999 to 2011, gallbladder cancer incidence rates decreased among women but remained level among men; death rates declined among women but stabilized among men after declining from 1999 to 2006. Gallbladder cancer incidence rates increased in some subgroups, notably among black persons, those aged <45 years, and for endocrine tumors.

Conclusions: Data from U.S. population-based cancer registries confirm that gallbladder cancer incidence and death rates are higher among women than men, highest among American Indian and Alaska Native persons, and differ by region. While overall incidence and death rates decreased during 1999 to 2011, incidence rates increased among some small subgroups.

Impact: Surveillance of gallbladder cancer incidence and mortality, particularly to monitor increases in subgroups, may provide clues to etiology and stimulate further research. Cancer Epidemiol Biomarkers Prev; 24(9); 1319–26. ©2015 AACR.
Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3–FOXO1-Positive Alveolar Rhabdomyosarcoma
Authors: Kephart Julie J.G. , Tiller Rosanne G.J. , Crose Lisa E.S. , Slemmons Katherine K. , Chen Po-Han , Hinson Ashley R. , Bentley Rex C. , Chi Jen-Tsan Ashley , Linardic Corinne M.
Published: June 2015

Purpose: Rhabdomyosarcoma (RMS) is a soft tissue sarcoma associated with the skeletal muscle lineage. Of the two predominant subtypes, known as embryonal (eRMS) and alveolar (aRMS), aRMS has the poorer prognosis, with a five-year survival rate of <50%. The majority of aRMS tumors express the fusion protein PAX3–FOXO1. As PAX3–FOXO1 has proven chemically intractable, this study aims to identify targetable proteins that are downstream from or cooperate with PAX3–FOXO1 to support tumorigenesis.

Experimental Design: Microarray analysis of the transcriptomes of human skeletal muscle myoblasts expressing PAX3–FOXO1 revealed alteration of several Wnt pathway gene members, including secreted frizzled related protein 3 (SFRP3), a secreted Wnt pathway inhibitor. Loss-of-function using shRNAs against SFRP3 was used to interrogate the role of SFRP3 in human aRMS cell lines in vitro and conditional murine xenograft systems in vivo. The combination of SFRP3 genetic suppression and the chemotherapeutic agent vincristine was also examined.

Results: In vitro, suppression of SFRP3 inhibited aRMS cell growth, reduced proliferation accompanied by a G1 arrest and induction of p21, and induced apoptosis. In vivo, doxycycline-inducible suppression of SFRP3 reduced aRMS tumor growth and weight by more than three-fold, in addition to increasing myogenic differentiation and β-catenin signaling. The combination of SFRP3 suppression and vincristine was more effective at reducing aRMS cell growth in vitro than either treatment alone, and ablated tumorigenesis in vivo.

Conclusions: SFRP3 is necessary for the growth of human aRMS cells both in vitro and in vivo and is a promising new target for investigation in aRMS. Clin Cancer Res; 21(21); 4868–80. ©2015 AACR.
Autocrine Activation of CHRM3 Promotes Prostate Cancer Growth and Castration Resistance via CaM/CaMKK–Mediated Phosphorylation of Akt
Authors: Wang Naitao , Yao Ming , Xu Jin , Quan Yizhou , Zhang Kaiqing , Yang Ru , Gao Wei-Qiang
Published: June 2015

Purpose: Although a previous study reported nerve ending–derived acetylcholine promoted prostate cancer invasion and metastasis by regulating the microenvironment of cancer cells, the present study aims to determine whether there is autocrine cholinergic signaling in prostate epithelial cells that promotes prostate cancer growth and castration resistance.

Experimental design: In this study, IHC was performed to detect protein expression in mouse prostate tissue sections and human prostate cancer tissue sections. Subcutaneously and orthotopically xenografted tumor models were established to evaluate the functions of autocrine cholinergic signaling in regulating prostate cancer growth and castration resistance. Western blotting analysis was performed to assess the autocrine cholinergic signaling–induced signaling pathway.

Results: We found the expression of choline acetyltransferase (ChAT), the secretion of acetylcholine and the expression of CHRM3 in prostate epithelial cells, supporting the presence of autocrine cholinergic signaling in the prostate epithelium. In addition, we found that CHRM3 was upregulated in clinical prostate cancer tissues compared with adjacent non-cancer tissues. Overexpression of CHRM3 or activation of CHRM3 by carbachol promoted cell proliferation, migration, and castration resistance. On the contrary, blockading CHRM3 by shRNA or treatment with darifenacin inhibited prostate cancer growth and castration resistance both in vitro and in vivo. Furthermore, we found that autocrine cholinergic signaling caused calmodulin/calmodulin–dependent protein kinase kinase (CaM/CaMKK)–mediated phosphorylation of Akt.

Conclusions: These findings suggest that blockade of CHRM3 may represent a novel adjuvant therapy for castration-resistant prostate cancer. Clin Cancer Res; 21(20); 4676–85. ©2015 AACR.
Exome Sequencing Reveals AMER1 as a Frequently Mutated Gene in Colorectal Cancer
Authors: Sanz-Pamplona Rebeca , Lopez-Doriga Adriana , Paré-Brunet Laia , Lázaro Kira , Bellido Fernando , Alonso M. Henar , Aussó Susanna , Guinó Elisabet , Beltrán Sergi , Castro-Giner Francesc , Gut Marta , Sanjuan Xavier , Closa Adria , Cordero David , Morón-Duran Francisco D. , Soriano Antonio , Salazar Ramón , Valle Laura , Moreno Victor
Published: June 2015

Purpose: Somatic mutations occur at early stages of adenoma and accumulate throughout colorectal cancer progression. The aim of this study was to characterize the mutational landscape of stage II tumors and to search for novel recurrent mutations likely implicated in colorectal cancer tumorigenesis.

Experimental Design: The exomic DNA of 42 stage II, microsatellite-stable colon tumors and their paired mucosae were sequenced. Other molecular data available in the discovery dataset [gene expression, methylation, and copy number variations (CNV)] were used to further characterize these tumors. Additional datasets comprising 553 colorectal cancer samples were used to validate the discovered mutations.

Results: As a result, 4,886 somatic single-nucleotide variants (SNV) were found. Almost all SNVs were private changes, with few mutations shared by more than one tumor, thus revealing tumor-specific mutational landscapes. Nevertheless, these diverse mutations converged into common cellular pathways, such as cell cycle or apoptosis. Among this mutational heterogeneity, variants resulting in early stop codons in the AMER1 (also known as FAM123B or WTX) gene emerged as recurrent mutations in colorectal cancer. Losses of AMER1 by other mechanisms apart from mutations such as methylation and copy number aberrations were also found. Tumors lacking this tumor suppressor gene exhibited a mesenchymal phenotype characterized by inhibition of the canonical Wnt pathway.

Conclusions: In silico and experimental validation in independent datasets confirmed the existence of functional mutations in AMER1 in approximately 10% of analyzed colorectal cancer tumors. Moreover, these tumors exhibited a characteristic phenotype. Clin Cancer Res; 21(20); 4709–18. ©2015 AACR.
A Novel Pharmacologic Activity of Ketorolac for Therapeutic Benefit in Ovarian Cancer Patients
Authors: Guo Yuna , Kenney S. Ray , Cook Linda , Adams Sarah F. , Rutledge Teresa , Romero Elsa , Oprea Tudor I. , Sklar Larry A. , Bedrick Edward , Wiggins Charles L. , Kang Huining , Lomo Lesley , Muller Carolyn Y. , Wandinger-Ness Angela , Hudson Laurie G.
Published: June 2015

Purpose: We previously identified the R-enantiomer of ketorolac as an inhibitor of the Rho-family GTPases Rac1 and Cdc42. Rac1 and Cdc42 regulate cancer-relevant functions, including cytoskeleton remodeling necessary for tumor cell adhesion and migration. This study investigated whether administration of racemic (R,S) ketorolac after ovarian cancer surgery leads to peritoneal distribution of R-ketorolac, target GTPase inhibition in cells retrieved from the peritoneal cavity, and measureable impact on patient outcomes.

Experimental Design: Eligible patients had suspected advanced-stage ovarian, fallopian tube or primary peritoneal cancer. Secondary eligibility was met when ovarian cancer was confirmed and optimally debulked, an intraperitoneal port was placed, and there were no contraindications for ketorolac administration. R- and S-ketorolac were measured in serum and peritoneal fluid, and GTPase activity was measured in peritoneal cells. A retrospective study correlated perioperative ketorolac and ovarian cancer–specific survival in ovarian cancer cases.

Results: Elevated expression and activity of Rac1 and Cdc42 was detected in ovarian cancer patient tissues, confirming target relevance. Ketorolac in peritoneal fluids was enriched in the R-enantiomer and peritoneal cell GTPase activity was inhibited after ketorolac administration when R-ketorolac was at peak levels. After adjusting for age, AJCC stage, completion of chemotherapy, and neoadjuvant therapy, women given perioperative ketorolac had a lower hazard of death (HR, 0.30; 95% confidence interval, 0.11–0.88).

Conclusions: Ketorolac has a novel pharmacologic activity conferred by the R-enantiomer and R-ketorolac achieves sufficient levels in the peritoneal cavity to inhibit Rac1 and Cdc42, potentially contributing to the observed survival benefit in women who received ketorolac. Clin Cancer Res; 21(22); 5064–72. ©2015 AACR.
Left Ventricular Early Inflow–Outflow Index: A Novel Echocardiographic Indicator of Mitral Regurgitation Severity
Authors: Lee Ming‐Ming , Salahuddin Ayesha , Garcia Mario J. , Spevack Daniel M.
Published: June 2015

Background

No gold standard currently exists for quantification of mitral regurgitation (
MR
) severity. Classification by echocardiography is based on integrative criteria using color and spectral Doppler and anatomic measurements. We hypothesized that a simple Doppler left ventricular early inflow–outflow index (
LVEIO
), based on flow velocity into the left ventricle (
LV
) in diastole and ejected from the
LV
in systole, would add incrementally to current diagnostic criteria.
LVEIO
was calculated by dividing the mitral E‐wave velocity by the
LV
outflow velocity time integral.

Methods and Results

Transthoracic echocardiography reports from Montefiore Medical Center and its referring clinics from July 1, 2011, to December 31, 2011 (n=11 235) were reviewed. The
MR
severity reported by a cardiologist certified by the National Board of Echocardiography was used as a reference standard. Studies reporting moderate or severe
MR
(n=550) were reanalyzed to measure effective regurgitant orifice area by the proximal isovelocity surface area method, vena contracta width,
MR
jet area, and left‐sided chamber volumes.
LVEIO
was 9.3±3.9, 7.0±3.2, and 4.2±1.7 among those with severe, moderate, and insignificant
MR
, respectively (
ANOVA
P
<0.001). By receiver operating characteristic analysis, area under the curve for
LVEIO
was 0.92 for severe
MR
. Those with
LVEIO
≥8 were likely to have severe
MR
(likelihood ratio 26.5), whereas those with
LVEIO
≤4 were unlikely to have severe
MR
(likelihood ratio 0.11).
LVEIO
performed better in those with normal
LV ejection fraction
(≥50%) compared with those with reduced
LV ejection fraction
(<50%) (area under the curve 0.92 versus 0.80,
P
<0.001). By multivariate logistic regression analysis,
LVEIO
was independently associated with severe
MR
when compared with
vena contracta
width,
MR
jet area, and
effective regurgitant orifice area measured
by
the proximal isovelocity surface area method
.

Conclusion

LVEIO
is a simple‐to‐use echocardiographic parameter that accurately identifies severe
MR
, particularly in patients with normal
LV ejection fraction
.
National Quality Assessment Evaluating Spironolactone Use During Hospitalization for Acute Myocardial Infarction (AMI) in China: China Patient‐centered Evaluation Assessment of Cardiac Events (PEACE)‐Retrospective AMI Study, 2001, 2006, and 2011
Authors: Guan Wenchi , Murugiah Karthik , Downing Nicholas , Li Jing , Wang Qing , Ross Joseph S. , Desai Nihar R. , Masoudi Frederick A. , Spertus John A. , Li Xi , Krumholz Harlan M. , Jiang Lixin ,   the China PEACE Collaborative Group
Published: June 2015

Background

Spironolactone, the only aldosterone antagonist available in China, improves outcomes in acute myocardial infarction (
AMI
) among patients with systolic dysfunction and either diabetes or heart failure (
HF
). However, national practice patterns in the use of spironolactone in China are unknown.

Methods and Results

From a nationally representative sample of
AMI
patients from in 2001, 2006, and 2011, we identified 6906 patients with either diabetes or
HF
and classified them into 1 of 4 groups according to their eligibility for spironolactone—“ideal”(left ventricular ejection fraction [
LVEF
] ≤40% and without contraindications), “contraindicated,” “not indicated” (neither ideal nor contraindicated), and “unknown indications” (
LVEF
unmeasured)—to determine how frequently patient eligibility for this drug is assessed in the hospital, how it is used in several groups, and to identify factors associated with the use in these groups. From 2001 to 2011, the proportion of patients whose eligibility for spironolactone was not assessed decreased (66.9% in 2001 to 32.8% in 2011). Spironolactone use significantly increased among ideal patients over this period (28.6% to 72.4%;
P
<0.001 for trend), but also in contraindicated patients (11.4% to 27.5%;
P
=0.002 for trend) and in other patients groups (not indicated: 27.5% to 38.3%; unknown indications: 21.3% to 35.1%; both
P
<0.01 for trend). In all 4 groups, patients presenting with
HF
on admission were more likely to receive spironolactone.

Conclusions

Although the appropriate use of spironolactone and assessment of eligibility increased in China over the past decade, there remains marked opportunities for improvement.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
Unique identifier:
NCT
01624883.
Age and sex variation in serum albumin concentration: an observational study
Authors: Weaving Gary , Batstone Gifford F , Jones Richard G
Published: June 2015

Background

In the UK, a common reference interval for serum albumin is widely used irrespective of age or sex. Implicit in this is that laboratories produce analytically similar results. This paper challenges the validity of this approach.

Methods

A three-week collection of results sent to all primary care centres in England has been analysed by age, sex and laboratory. In all, 1,079,193 serum albumin reports were included in this analysis.

Results

The mean population serum albumin concentration increases to peak at around age 20 years and then decreases with increasing age. Values in females decrease more rapidly but become close to male values at 60 years. The variation between laboratories was large and potentially clinically significant.

Conclusions

Reference intervals for serum albumin should be stratified by age and sex. Until there is greater methodological standardization, laboratories should determine their own reference intervals and not accept a single consensus reference interval.
‘The Beast of Blenheim’, risk and the rise of the security sanction
Authors: Pratt John , Anderson Jordan
Published: June 2015

This paper discusses and explains a new penal phenomenon in the main Anglophone societies – the rise of the security sanction. Rather than reacting to crime, its purpose is to protect public safety by reducing the risk of future crime. It can be applied to both the most serious offenders and those who have not committed any crime. It can involve extended/prolonged terms of imprisonment and it can involve extensive restrictions on movement in public space. Its emergence can be explained by the post-1980s political, economic and social restructuring of these societies and the attendant uncaging of risk.
Menstrual cycle characteristics in women with persistent schizophrenia
Authors: Gleeson Pia C , Worsley Roisin , Gavrilidis Emorfia , Nathoo Shainal , Ng Elisabeth , Lee Stuart , Kulkarni Jayashri
Published: June 2015

Objective:

Oestradiol has been implicated in the pathogenesis of schizophrenia. Women with schizophrenia often suffer with menstrual dysfunction, usually associated with low oestradiol levels, but whether menstrual dysfunction has an effect on their psychiatric symptoms is not well researched. The aim of this study is to document the menstrual characteristics of women with chronic schizophrenia with focus upon menstrual regularity, menstrual cycle length and menstrual symptoms. To determine which patient characteristics are associated with irregular menses and whether irregular menses are associated with the severity of psychotic symptoms, menstrual symptoms or depressive symptoms.

Method:

Cross-sectional analyses using baseline data of women enrolled in a clinical trial. Inclusion criteria include Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective or schizophreniform disorder; aged between 18 and 51 years; residual symptoms of psychosis despite treatment with a stable dose of antipsychotic medication for at least 4 weeks. Menstrual cycle characteristics including regularity, cycle length and menstrual associated symptoms were documented. Symptoms of schizophrenia were measured using Positive and Negative Syndrome Scale, cognition was measured using Repeatable Battery for the Assessment of Neuropsychological Status and depression was assessed using the Montgomery–Asberg Depression Rating Scale. Blood samples were collected at baseline for hormone assays.

Results:

Of the 139 women, 77 (55.4%) had regular menses, 57 (41%) had irregular menses and 5 (3.6%) women had missing data on their menstrual cycle. Use of atypical antipsychotics associated with hyperprolactinaemia was positively associated with irregular menses (odds ratio = 4.4, 95% confidence interval = [1.8, 10.9], p = 0.001), while age more than 30 years was negatively associated (odds ratio = 0.3, 95% confidence interval = [0.1, 0.6], p = 0.004). Women with irregular cycles had significantly lower oestradiol levels than women with regular cycles (213.2 ± 25.0 vs 299.0 ± 27.3, p = 0.03), but there was no difference in Positive and Negative Syndrome Scale, Montgomery–Asberg Depression Rating Scale or Repeatable Battery for the Assessment of Neuropsychological Status between those with regular and irregular cycles. The most common menstrual associated symptoms were decrease in mood with the menstrual cycle (64.8%), bloating (64.8%), cramps (59.7%), back pain (37.6%) and worsening of psychosis symptoms (32.4%).

Conclusion:

Regular menses are associated with higher oestradiol levels and higher rates of cyclical mood symptoms but are not associated with Positive and Negative Syndrome Scale scores. Understanding the effect the menstrual cycle can have on psychiatric illness, such as premenstrual exacerbations, is important for the holistic care of women with schizophrenia.
Corporate Social Performance and Financial Performance: Sample-Selection Issues
Authors: Shahzad Ali M. , Sharfman Mark P.
Published: June 2015

The vast majority of extant empirical research examining the relationship between corporate social performance (CSP) and financial performance (FP) selects samples of only those firms which are observed engaging in CSP. In this study, the authors assert that firms’ efforts to pursue CSP and subsequently their appearance in social-choice investment advisory (SIA) firms’ ranking databases are non-random. Studying the CSP–FP link using selected samples of only those firms whose social performance is ranked by SIA firms introduces a sample-selection bias which limits generalization of results to a population of all firms, and at worst provides alternate explanations for observed relationships. The authors test these assertions on a large sample of public corporations in the United States over 6 years and find a sample-selection bias. Upon correction of this bias, this study confirms the positive impact of CSP on FP.
The emerging sociology of international criminal courts: Between global restructurings and scientific innovations
Authors: Christensen Mikkel Jarle
Published: June 2015

Since the emergence of the idea of international criminal courts as a form of international governance between and after the two world wars, scholarly interest in the role and functionality of these institutions has been dominated by the academic disciplines of law and political science. Recently, this literature has been challenged and supplemented by an emerging sociology of international criminal courts. In contrast to previous scholarship, this sociology has taken the social dynamics that drive the development of these institutions as its object. More than simply responding to the international transformations that led to the resurgence of international criminal courts in the 1990s, the emerging sociology of these institutions was predicated on an epistemological break with previous forms of social science that created scientific innovations in the form of original research tools. Crucially, these innovations also made new types of international research objects visible to sociological scholarship.
My American Dream
Authors: Knight Michelle G. , Roegman Rachel , Edstrom Lisa
Published: June 2015

This article presents findings of a qualitative, interpretive case study of the experiences of 1.5- and 2nd-generation West African immigrants who self-identify as pursuing the American Dream, defined by them as academic attainment and career success. Employing structuration theory, the authors examine the interplay between structures and agency in participants’ educational and professional decision making. Participants’ perspectives on the American Dream are filled with references to dominant narratives of hard work, economic success, and the power of formal education. At the same time, findings illuminate a conceptual shift in understanding the nature of hard work and personal freedom experienced in pursuit of the American Dream as participants recognized that as African immigrants, they had to work harder to achieve the Dream while highlighting the role and influence of family expectations and schooling structures. Their expanded notions of the Dream include understandings of individual agency, social supports and constraints, and cultural forces.
Effect of stamp-forming parameters and bend radius on the mechanical performance of curved beam carbon fiber/polyphenylene sulfide specimens
Authors: Jamin Thibault , Dubé Martine , Laberge Lebel Louis
Published: June 2015

The stamp-forming process is used to manufacture S-shape parts made of carbon fiber/polyphenylene sulfide thermoplastic composites. The processing parameters and part layup, thickness, and bend radius are varied in order to investigate their effects on the parts’ quality and mechanical performance. The interlaminar tensile strength of the formed parts is measured using the results of curved beam four-point bending tests and recommended analytical equations. A nonlinear finite element model of the tested coupons is developed, taking into account the contact between the loading bars and the coupon as well as the plies’ interface properties. The results of the model are used to verify the precision of the analytical equations for various bend radii and part layup and thickness. Conclusions as to the optimum set of processing parameters that should be used for the stamp forming of carbon fiber/polyphenylene sulfide are drawn.
Microplane triad model for simple and accurate prediction of orthotropic elastic constants of woven fabric composites
Authors: Kirane Kedar , Salviato Marco , Bažant Zdeněk P
Published: June 2015

An accurate prediction of the orthotropic elastic constants of woven composites from the constituent properties can be achieved if the representative unit cell is subdivided into a large number of finite elements. But this would be prohibitive for microplane analysis of structures consisting of many representative unit cells when material damage alters the elastic constants in each time step in every element. This study shows that predictions almost as accurate and sufficient for practical purposes can be achieved in a much simpler and more efficient manner by adapting to woven composites the well-established microplane model, in a partly similar way as recently shown for braided composites. The undulating fill and warp yarns are subdivided into segments of different inclinations and, in the center of each segment, one microplane is placed normal to the yarn. As a new idea, a microplane triad is formed by adding two orthogonal microplanes parallel to the yarn, one of which is normal to the plane of the laminate. The benefit of the microplane approach is that it is easily extendable to damage and fracture. The model is shown to give realistic predictions of the full range of the orthotropic elastic constants for plain, twill, and satin weaves and is extendable to hybrid weaves and braids.
Walking with the ghosts of the past: Unearthing the value of residents’ urban nostalgias
Authors: Adams David , Larkham Peter
Published: June 2015

Nostalgia has historically been negatively characterised by desire to reconnect with an idealised past lost to the ‘destructive’ forces of modernity, but studies across the social sciences have recently sought to re-appraise the creative and embodied significance of individuals’ recollections. This paper contributes to this developing debate by empirically exploring the value of individual remembering in relation to the urban material landscape. First, drawing on recently collected go-along data from long-term residents of two UK cities, Birmingham and Coventry, it is argued that nostalgia could be considered a more progressive force in urban life, especially amongst residents in cities that have undergone and are undergoing physical change as a consequence of ‘official’ attempts to reconstruct, regenerate and/or repackage particular urban spaces; developing a richer understanding of the interplay between official and unofficial nostalgias can better inform planning decisions that are more likely to be socially acceptable and supported by local communities. Second, though there are clear advantages of developing a fuller theoretical and methodological consideration of urban nostalgia, this paper then uses go-along data to demonstrate that much remains to be learnt from exploring how the material urban environment can encourage and/or limit individual efforts to keep potentially distressing aspects of their past concealed.
Local embedding of international discourse: Chile and the international and transnational anti-corruption campaign
Authors: Gephart Malte
Published: June 2015

The international and transnational anti-corruption campaign (ITACC) has successfully called global attention to the ‘abuse of delegated power for private gain’. However, several anti-corruption scholars have argued that the currently dominant ITACC is flawed because it ignores the fact that local understandings of corruption vary around the world. Others who have analysed the ITACC have claimed it is capable of effectively covering up these differences, in turn creating misunderstandings about the aims in the fight against corruption. While both arguments have been developed quite separately, this article combines and thereby advances both. It applies constructionist interviews and argumentative discourse analysis (ADA) to explore the local anti-corruption discourse in Chile – a country that is considered a success case in Latin America. The exploration shows that Chile’s anti-corruption activities are highly political and they are deeply related to narratives of the country’s transition to democracy. By relating these narratives back to the ITACC, the article reveals a complex interplay between local (competing) corruption narratives and the ITACC.
Unobserved Heterogeneity in Hospitality and Tourism Research
Authors: Assaf A. George , Oh Haemoon , Tsionas Mike G.
Published: June 2015

Despite the growing complexity of structural equation model (SEM) applications in tourism, it is surprising that most applications have estimated these models without accounting for unobserved heterogeneity. In this article, we aim to discuss the concept of unobserved heterogeneity in more detail, highlighting its serious threats to the validity and reliability of SEMs. We describe a Bayesian finite mixture modeling framework for estimating SEMs while accounting for unobserved heterogeneity. We provide a comprehensive description of this model, and provide guidance on its estimation using the WinBUGS software. We illustrate the importance of unobserved heterogeneity and the finite mixture modeling framework using a didactic application on brand equity where heterogeneity is likely to play an important role because of the differences in how consumers perceive the different dimensions of brand equity. We compare between various models and illustrate the differences between the standard and heterogeneous SEM and discuss the implications for research and practice.
Fuzzy logic model for prediction of fusion characteristics in rigid polyvinyl chloride nanocomposite
Authors: Tavana R , Moghri M , Esmaili M
Published: June 2015

Fusion is a key parameter in achieving polyvinyl chloride (PVC) nanocomposites with desired properties. In the present research, a fuzzy logic (FL)-based model is developed to predict fusion time (FT) for the contents of nanoclay, processing aid, and calcium stearate in PVC processing. In order to have precise rules for the FL model, data mining algorithm RepTree is employed to detect dominating patterns among experimental data. The model parameters are then well adjusted using genetic algorithm. The modeling results show a correlation of 0.86 between predicted and observed values for FT. So, it proved reliability of the idea of employing the decision tree resulted from a data mining algorithm as the base knowledge of FL models. Also, applying genetic algorithm optimization, the correlation coefficient increased from a value of less than 0.83 to 0.86. The calculated correlation coefficient for the test data was 0.88, which denotes good model universalizing ability.
Predictive pitch control of an electro-hydraulic digital pitch system for wind turbines based on the extreme learning machine
Authors: Yin Xiu-xing , Lin Yong-gang , Li Wei
Published: June 2015

An electro-hydraulic digital pitch system is proposed in this paper to regulate output power and drive-train torque for wind turbines. This pitch system is driven by an electro-hydraulic digital servo system and can be digitally controlled to regulate the blade pitch angle with relatively high control accuracy and fast response. A closed control loop of this pitch system is presented and an extreme learning machine is online trained to represent the nonlinear wind turbine characteristics in this control loop. Furthermore, a predictive pitch controller is designed to improve the final pitch control performances by using the established extreme learning machine. Comparative experimental results are presented to illustrate the achievable significant performance improvements on output power and drive-train torque regulations by using the proposed pitch system and predictive pitch controller.
Accounting Conservatism and Firm Growth Financed by External Debt
Authors: Kang Tony , Lobo Gerald J. , Wolfe Michael C.
Published: June 2015

Previous research shows that accounting conservatism facilitates debt contracting. Extending this line of literature, we examine whether the role of accounting conservatism in accessing external debt to attain firm growth varies with its maturity. We find evidence of a positive relationship between conservatism and debt maturity. We also observe a positive relationship between conservative accounting and future growth funded by all classes of debt, but this relation is due to long-term rather than short-term debt, which is less prone to agency risk. Furthermore, the associations between conservatism and debt maturity and conservatism and growth financed by long-term debt are mostly observed for firms with fewer anti-takeover provisions in place. These findings suggest that the demand for accounting conservatism is not uniform across different debt maturity horizons.
Problems of Implementing Audit Committee and Supervisory Board Simultaneously in China
Authors: Lee Pao-Chen
Published: June 2015

Imposing the mechanism of a single audit committee (AC) on the dual supervisory mechanism of a Board of Directors alongside a supervisory board (SB) has raised questions regarding the problems in implementing effective monitoring functions. A comparison of these different governance mechanisms is documented in this article by interviewing two governors of all listed companies in the Shanghai Stock Exchange (SSE) and of 79 investment corporations in Hangzhou. Both comparisons of regulation and the issues raised in the interview point out the problems in implementing effective supervision through these distinct governance mechanisms. The evidence presented provides useful guidelines of how key characteristics of effectiveness and co-ordination can be improved to make supervisory functions in China more effective.