bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omega-3 Fatty Acids Prevent Pressure Overload–Induced Cardiac Fibrosis Through Activation of Cyclic GMP/Protein Kinase G Signaling in Cardiac Fibroblasts
Authors: Chen Jinghai , Shearer Gregory C. , Chen Quanhai , Healy Chastity L. , Beyer April J. , Nareddy Vijaya B. , Gerdes A. Martin , Harris William S. , O'Connell Timothy D. , Wang Dajun 
Published: February 2011

Background—
Omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) from fish oil ameliorate cardiovascular diseases. However, little is known about the effects of ω-3 polyunsaturated fatty acids on cardiac fibrosis, a major cause of diastolic dysfunction and heart failure. The present study assessed the effects of ω-3 polyunsaturated fatty acids on cardiac fibrosis.

Methods and Results—
We assessed left ventricular fibrosis and pathology in mice subjected to transverse aortic constriction after the consumption of a fish oil or a control diet. In control mice, 4 weeks of transverse aortic constriction induced significant cardiac dysfunction, cardiac fibrosis, and cardiac fibroblast activation (proliferation and transformation into myofibroblasts). Dietary supplementation with fish oil prevented transverse aortic constriction–induced cardiac dysfunction and cardiac fibrosis and blocked cardiac fibroblast activation. In heart tissue, transverse aortic constriction increased active transforming growth factor-β1 levels and phosphorylation of Smad2. In isolated adult mouse cardiac fibroblasts, transforming growth factor-β1 induced cardiac fibroblast transformation, proliferation, and collagen synthesis. Eicosapentaenoic acid and docosahexaenoic acid increased cyclic GMP levels and blocked cardiac fibroblast transformation, proliferation, and collagen synthesis. Eicosapentaenoic acid and docosahexaenoic acid blocked phospho-Smad2/3 nuclear translocation. DT3, a protein kinase G inhibitor, blocked the antifibrotic effects of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid and docosahexaenoic acid increased phosphorylated endothelial nitric oxide synthase and endothelial nitric oxide synthase protein levels and nitric oxide production.

Conclusion—
Omega-3 fatty acids prevent cardiac fibrosis and cardiac dysfunction by blocking transforming growth factor-β1–induced phospho-Smad2/3 nuclear translocation through activation of the cyclic GMP/protein kinase G pathway in cardiac fibroblasts.
Assessment of Air Quality During Mastoidectomy
Authors: Norris Byron K. , Goodier Aimee P. , Eby Thomas L. 
Published: January 2011

ObjectivesThe Occupational Health and Safety Administration (OSHA) outlines specific requirements governing the use of respiratory protection for workers dealing with dust or other aerosolized compounds. Health care workers may be exposed to bone dust produced during otologic procedures, creating an occupational hazard. The purpose of this research was to quantify the total suspended particulate matter (TSPM) and respirable particulate matter (PM5) created during cortical mastoidectomy and investigate whether the concentration of aerosolized dust during mastoidectomy would require the use of a particulate respirator.Study DesignCadaveric study to assess air quality during cortical mastoidectomy.SettingTemporal bone laboratory.MethodsA simple mastoidectomy was performed on 3 cadaveric temporal bones. Suspended particulate concentration was measured using gravimetric filter methodology for TSPM and PM5. Concentration of particulate exposure was compared between mannequins positioned near the surgical field with a standard surgical mask, surgical respirator, or controls.ResultsThe average total particulate matter concentration during cortical mastoidectomy was 1.89 mg/m3. The average quantity of respirable particles was below detection levels. The calculated particulate exposure concentrations for TSPM and PM5 did not exceed OSHA’s requirement for respirator use. The particulate respirator prevented exposure to bone particulates compared with controls (P =. 028).ConclusionThe concentration of bone dust produced during cortical mastoidectomy is below regulatory guidelines for use of particulate respirators. However, experimental studies show the use of a surgical respirator may decrease particulate exposure.
Salvianolic acid B and Tanshinone IIA attenuate myocardial ischemia injury in mice by NO production through multiple pathways
Authors: Pan Chunshui , Lou Lixia , Huo Yingqing , Singh Gurbakhshish , Chen Meng , Zhang Dongmei , Wu Aiming , Zhao Mingjing , Wang Shuoren , Li Jian 
Published: February 2011

Objective: Salvia miltiorrhiza (Danshen) has been widely used for the treatment of cardiac and cerebrovascular disease throughout history. The objective of this study is to further elucidate the mechanisms underlying Danshen’s cardiac protective effects to support its clinical evidence. Methods and Results: Salvianolic acid B (Sal B) and Tanshinone IIA (Tan IIA) are two of the major components in Danshen. We observed that Sal B and Tan IIA have cardioprotective effects in an in vivo myocardial infarction model of C57 mice, have vasodilator action in a ex vivo micro-artery system through the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway and are involved in the regulation of the L-arginine/eNOS/NO pathways in human umbilical vein endothelial cells (HUVECs). Both Sal B and Tan IIA inhibited cardiac hypertrophy and infarction sizes and improved cardiac function at 4 weeks after induction of infarction. Furthermore, an eNOS inhibitor (L-NAME) obliterated the observed effects. Sal B and Tan IIA mediated vasodilatation in mice coronaries ex vivo, the effect of which was decreased with either L-NAME or PI3K inhibitor (LY294002). In addition, Sal B and Tan IIA-induced vasodilatation was observed ex vivo in the microvessels of eNOS-/- mice. Sal B and Tan IIA also stimulated eNOS phosphorylation in a concentration- and time-dependent manner in the HUVEC culture, which was diminished by LY294002. In addition, Sal B and Tan IIA were found to stimulate the phosphorylation of AMPK (Thr172) and Akt (Ser473), while compound C significantly decreased the phosphorylation of Akt (Ser473) mediated by both. Finally, Sal B and Tan IIA were found to increase NO production, induce [3H]-L-arginine uptake and increase the CAT-1 and CAT-2B mRNA levels in HUVEC culture. Conclusions: These findings suggest that both Sal B and Tan IIA have cardioprotective function in certain levels through multiple targets related with NO production, such as eNOS phosphorylation, L-arginine uptake and CAT expression, which may have major clinical implications.
Neutrophil survival and c-kit+-progenitor proliferation in Staphylococcus aureus–infected skin wounds promote resolution
Authors: Kim Min-Ho , Granick Jennifer L. , Kwok Cindy , Walker Naomi J. , Borjesson Dori L. , Curry Fitz-Roy E. , Miller Lloyd S. , Simon Scott I. 
Published: January 2011

AbstractPolymorphonuclear neutrophils (PMNs) are critical for the formation, maintenance, and resolution of bacterial abscesses. However, the mechanisms that regulate PMN survival and proliferation during the evolution of an abscess are not well defined. Using a mouse model of Staphylococcus aureus abscess formation within a cutaneous wound, combined with real-time imaging of genetically tagged PMNs, we observed that a high bacterial burden elicited a sustained mobilization of PMNs from the bone marrow to the infected wound, where their lifespan was markedly extended. A continuous rise in wound PMN number, which was not accounted for by trafficking from the bone marrow or by prolonged survival, was correlated with the homing of c-kit+-progenitor cells from the blood to the wound, where they proliferated and formed mature PMNs. Furthermore, by blocking their recruitment with an antibody to c-kit, which severely limited the proliferation of mature PMNs in the wound and shortened mouse survival, we confirmed that progenitor cells are not only important contributors to PMN expansion in the wound, but are also functionally important for immune protection. We conclude that the abscess environment provides a niche capable of regulating PMN survival and local proliferation of bone marrow–derived c-kit+-progenitor cells.
Phase III Trial of Vandetanib Compared With Erlotinib in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer
Authors: Natale Ronald B. , Thongprasert Sumitra , Greco F. Anthony , Thomas Michael , Tsai Chun-Ming , Sunpaweravong Patrapim , Ferry David , Mulatero Clive , Whorf Robert , Thompson Joyce , Barlesi Fabrice , Langmuir Peter , Gogov Sven , Rowbottom Jacqui A. , Goss Glenwood D. 
Published: February 2011

Purpose Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This phase III study assessed the efficacy of vandetanib versus erlotinib in unselected patients with advanced non–small-cell lung cancer (NSCLC) after treatment failure with one to two prior cytotoxic chemotherapy regimens. Patients and Methods One thousand two hundred forty patients were randomly assigned to receive vandetanib 300 mg/d (n = 623) or erlotinib 150 mg/d (n = 617). The primary objective was to show superiority in progression-free survival (PFS) for vandetanib versus erlotinib. If the difference did not reach statistical significance for superiority, a noninferiority analysis was conducted. Results There was no significant improvement in PFS for patients treated with vandetanib versus erlotinib (hazard ratio [HR], 0.98; 95.22% CI, 0.87 to 1.10; P = .721); median PFS was 2.6 months for vandetanib and 2.0 months for erlotinib. There was also no significant difference for the secondary end points of overall survival (HR, 1.01; P = .830), objective response rate (both 12%), and time to deterioration of symptoms for pain (HR, 0.92; P = .289), dyspnea (HR, 1.07; P = .407), and cough (HR, 0.94; P = .455). Both agents showed equivalent PFS and overall survival in a preplanned noninferiority analysis. Adverse events (AEs; any grade) more frequent with vandetanib than erlotinib included diarrhea (50% v 38%, respectively) and hypertension (16% v 2%, respectively); rash was more frequent with erlotinib than vandetanib (38% v 28%, respectively). The overall incidence of grade ≥ 3 AEs was also higher with vandetanib than erlotinib (50% v 40%, respectively). Conclusion In patients with previously treated advanced NSCLC, vandetanib showed antitumor activity but did not demonstrate an efficacy advantage compared with erlotinib. There was a higher incidence of some AEs with vandetanib.
A New Goodness-of-Fit Test for Event Forecasting and Its Application to Credit Defaults
Authors: Blöchlinger Andreas , Leippold Markus 
Published: January 2011

We develop a new goodness-of-fit test for validating the performance of probability forecasts. Our test statistic is particularly powerful under sparseness and dependence in the observed data. To build our test statistic, we start from a formal definition of calibrated forecasts, which we operationalize by introducing two components. The first component tests the level of the estimated probabilities; the second validates the shape, measuring the differentiation between high and low probability events. After constructing test statistics for both level and shape, we provide a global goodness-of-fit statistic, which is asymptotically χ2distributed. In a simulation exercise, we find that our approach is correctly sized and more powerful than alternative statistics. In particular, our shape statistic is significantly more powerful than the Kolmogorov–Smirnov test. Under independence, our global test has significantly greater power than the popular Hosmer–Lemeshow's χ2test. Moreover, even under dependence, our global test remains correctly sized and consistent. As a timely and important empirical application of our method, we study the validation of a forecasting model for credit default events.This paper was accepted by Wei Xiong, finance.
A Model of Probabilistic Choice Satisfying First-Order Stochastic Dominance
Authors: Blavatskyy Pavlo R. 
Published: January 2011

This paper presents a new model of probabilistic binary choice under risk. In this model, a decision maker always satisfies first-order stochastic dominance. If neither lottery stochastically dominates the other alternative, a decision maker chooses in a probabilistic manner. The proposed model is derived from four standard axioms (completeness, weak stochastic transitivity, continuity, and common consequence independence) and two relatively new axioms. The proposed model provides a better fit to experimental data than do existing models. The baseline model can be extended to other domains such as modeling variable consumer demand. This paper was accepted by Peter Wakker, decision analysis.
Reference-Point Formation and Updating
Authors: Baucells Manel , Weber Martin , Welfens Frank 
Published: January 2011

Reference-dependent preferences have been well accepted in decision sciences, experimental economics, behavioral finance, and marketing. However, we still know very little about how decision makers form and update their reference points given a sequence of information. Our paper provides some novel experiments in a financial context to advance the understanding of reference-point formation over time. Our subjects' reference price is best described as a combination of the first and the last price of the time series, with intermediate prices receiving smaller and nondecaying weights. Hence, reference prices are not recursive. We provide a parsimonious formula to predict the reference points, which we test out-of-sample. The fit of the model is reasonably good. This paper was accepted by George Wu, decision analysis.
Search Engine Advertising: Channel Substitution When Pricing Ads to Context
Authors: Goldfarb Avi , Tucker Catherine 
Published: January 2011

We explore substitution patterns across advertising platforms. Using data on the advertising prices paid by lawyers for 139 Google search terms in 195 locations, we exploit a natural experiment in “ambulance-chaser” regulations across states. When lawyers cannot contact clients by mail, advertising prices per click for search engine advertisements are 5%–7% higher. Therefore, online advertising substitutes for offline advertising. This substitution toward online advertising is strongest in markets with fewer customers, suggesting that the relationship between the online and offline media is mediated by the marketers' need to target their communications. This paper was accepted by Pradeep Chintagunta, marketing.
Evaluating Heuristics Used When Designing Product Costing Systems
Authors: Balakrishnan Ramji , Hansen Stephen , Labro Eva 
Published: January 2011

The academic and practitioner literature justifies firms' use of product costs in product pricing and capacity planning decisions as heuristics to address an otherwise intractable problem. However, product costs are the output of a cost reporting system, which itself is the outcome of heuristic design choices. In particular, because of informational limitations, when designing cost systems firms use simple rules of thumb to group resources into cost pools and to select drivers used to allocate the pooled costs to products. Using simulations, we examine how popular choices in costing system design influence the error in reported costs. Taking information needs into account, we offer alternative ways to translate the vague guidance in the literature to implementable methods. Specifically, we compare size-based rules for forming cost pools with more informationally demanding correlation-based rules and develop a blended method that performs well in terms of accuracy. In addition, our analysis suggests that significant gains can be made from using a composite driver rather than selecting a driver based on the consumption pattern for the largest resource only, especially when combined with correlation-based rules to group resources. We vary properties of the underlying cost structure (such as the skewness in resource costs, the traceability of resources to products, the sharing of resources across products, and the variance in resource consumption patterns) to address the generalizability of our findings and to show when different heuristics might be preferred. This paper was accepted by Stefan Reichelstein, accounting.
Short- and long-term mortality following primary total hip replacement for osteoarthritis
Authors: Pedersen A. B. , Baron J. A. , Overgaard S. , Johnsen S. P. 
Published: February 2011

We evaluated the short-term of 0 to 90 days and the longer term, up to 12.7 years, mortality for patients undergoing primary total hip replacement (THR) in Denmark in comparison to the general population. Through the Danish Hip Arthroplasty Registry we identified all primary THRs undertaken for osteoarthritis between 1 January 1995 and 31 December 2006. Each patient (n = 44 558) was matched at the time of surgery with three people from the general population (n = 133 674). We estimated mortality rates and mortality rate ratios with 95% confidence intervals for THR patients compared with the general population. There was a one-month period of increased mortality immediately after surgery among THR patients, but overall short-term mortality (0 to 90 days) was significantly lower (mortality rate ratio 0.8; 95% confidence interval 0.7 to 0.9). However, THR surgery was associated with increased short-term mortality in subjects under 60 years old, and among THR patients without comorbidity. Long-term mortality was lower among THR patients than in controls (mortality rate ratio 0.7; 95% confidence interval 0.7 to 0.7). Overall, THR was associated with lower short- and long-term mortality among patients with osteoarthritis. Younger patients and patients without comorbidity before surgery may also experience increased mortality after THR surgery, although the absolute risk of death is small.
Gitelman’s syndrome
Authors: Quinlan C. S. , Walsh J. C. , Moran A.-M. , Moran C. , O’Rourke S. K. 
Published: February 2011

We describe a case of bilateral weakness of the lower limbs, sensory disturbance and intermittent urinary incontinence, secondary to untreated Gitelman’s syndrome, in a 42-year-old female who was referred with presumed cauda equina syndrome. On examination, the power of both legs was uniformly reduced, and the perianal and lower-limb sensation was altered. However, MRI of the lumbar spine was normal. Measurements of serum and urinary potassium were low and blood gas analysis revealed metabolic alkalosis. Her symptoms resolved following potassium replacement. We emphasise the importance of measurement of the plasma and urinary levels of electrolytes in the investigation of patients with paralysis of the lower limbs and suggest that they, together with blood gas analysis, allow the exclusion of unusual causes of muscle weakness resulting from metabolic disorders such as metabolic alkalosis.
Prevalence of Major Depressive Episode among Patients with Pre-Dialysis Chronic Kidney Disease
Authors: Sumanathissa Manannalage , De Silva Varuni A. , Hanwella Raveen 
Published: February 2011

Objective: To ascertain the prevalence of depression among pre-dialysis chronic kidney disease (CKD) patients. Methods: A cross-sectional study was carried out using the Structured Clinical Interview for DSM IV (SCID) to detect major depressive episode. Study was carried out in a nephrology outpatient clinic in Sri Lanka. Every fifth patient with CKD diagnosed according to the K/DQOI of the National Kidney Foundation of USA criteria stages 2–5 not undergoing dialysis was recruited. Primary outcome was major depressive episode diagnosed using the Structured Clinical Interview for DSM disorders (SCID). Results: Sample consisted of 140 patients. Eighty-nine (63.6%) were male. The mean age was 57.9 years ( SD = 10.4). Only 41 (29.3%) were in paid employment. Percentage of patients in CKD stages 2, 3, 4, and 5 were 2.9%, 19.6%, 51.4%, and 25%, respectively. Only three patients had diabetes. One hundred and five were on treatment for hypertension. Prevalence of a major depressive episode was 27.9%. Among males, prevalence was 27% (95% CI 17.6–36.3) and among females, 29.4% (95% CI 16.5–42.4). Age, gender, income, employment status, and education were not associated with depression. The only significant variable associated with depression was patient's understanding of prognosis. Conclusions: Prevalence of major depressive episode among pre-dialysis CKD patients was 27.9%. Rate of depression diagnosed using a structured clinical interview was lower than that reported when screening instruments were used. The only significant variable associated with depression was patient's understanding of prognosis. Future studies should aim to identify risk factors for depression among patients with kidney disease.
A Randomized Controlled Trial to Assess Effectiveness of a Spiritually-Based Intervention to Help Chronically Ill Adults
Authors: McCauley Jeanne , Haaz Steffany , Tarpley Margaret J. , Koenig Harold G. , Bartlett Susan J. 
Published: February 2011

Objective: Creative, cost-effective ways are needed to help older adults deal effectively with chronic diseases. Spiritual beliefs and practices are often used to deal with health problems. We evaluated whether a minimal intervention, consisting of a video and workbook encouraging use of patient spiritual coping, would be inoffensive and improve perceived health status. Methods: A randomized clinical trial of 100 older, chronically ill adults were assigned to a Spiritual (SPIRIT) or Educational (EDUC—standard cardiac risk reduction) intervention. Individuals in each group were shown a 28–minute video and given a workbook to complete over 4 weeks. Selected psychosocial and health outcome measures were administered at baseline and 6 weeks later. Results: Participants were mostly female (62%), with a mean age of 65.8 α 9.6 years and had an average of three chronic illnesses. More than 90% were Christian. At baseline, frequent daily spiritual experiences (DSE) were associated with being African American ( p < .05) and increased pain ( p < .01) and co-morbidities ( p < .01). Energy increased significantly ( p < .05) in the SPIRIT group and decreased in the EDUC group. Improvements in pain, mood, health perceptions, illness intrusiveness, and self-efficacy were not statistically significant. Conclusions: A minimal intervention encouraging spiritual coping was inoffensive to patients, associated with increased energy, and required no additional clinician time.