bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of Bevacizumab in Patients with Metastatic Breast Cancer
Authors: Hamilton Erika P. , Blackwell Kimberly L.
Published: July 2011

Five randomized phase III trials – AVF2119g, E2100, AVADO, RIBBON-1, and RIBBON-2 – have reported data on the efficacy and safety of bevacizumab, combined with a variety of chemotherapy agents and in various settings, in patients with metastatic breast cancer (MBC). The E2100 trial demonstrated a significant improvement in progression-free survival according to the independent review facility, from 5.8 to 11.3 months when bevacizumab was combined with paclitaxel (p < 0.0001) as first-line therapy in patients with HER2-nonamplified MBC; subsequent trials of bevacizumab as first-line (AVADO, RIBBON-1) and second-line (RIBBON-2) therapy for patients with HER2-nonamplified MBC have also met their primary end point of prolonging progression-free survival (PFS). Accumulating safety data for bevacizumab in MBC show that it is generally well tolerated and associated with predictable adverse events, including hypertension and proteinuria. The majority of adverse events are mild and manageable, but bevacizumab is also associated with some severe toxicities. The management of bevacizumab-related adverse events in MBC has improved with increased experience. This review summarizes bevacizumab efficacy in MBC and focuses on bevacizumab-related toxicities as reported in 5 phase III clinical trials. Current adverse event management strategies, based on guidelines and experience from these trials, are outlined.
Mobilization of Bone Marrow Cells by CSF3 Protects Mice from Bleomycin-Induced Lung Injury
Authors: Zhang Fen , Zhang Lu , Jiang Han-shui , Chen Xue-yuan , Zhang Yuan , Li Hui-ping , Zhang Rong-xuan , Zheng Hui , Chu Jian-xin , Chen Xue-jin
Published: July 2011

Background: Bone marrow-derived cells may play a role in tissue injury and repair. Growth factors facilitate the mobilization of bone marrow-derived cells to the site of injury. Objectives: The aim of this study was to determine the effect of the mobilization of autologous bone marrow-derived cells by granulocyte colony-stimulating factor (CSF3) on bleomycin-induced lung injury in mice. Methods: The bone marrow from male green fluorescent protein transgenic (C57Bl/6J) mice was transplanted into irradiated female C57Bl/6J mice. Bleomycin lung injury was induced in these bone marrow-reconstituted mice and unreconstituted C57Bl/6J mice, and some mice were treated with recombinant CSF3. Lung histology, survival, cytokine expression and matrix metalloproteinase (MMP) expression were evaluated to determine the effect of CSF3 after bleomycin-induced lung injury. Results: Histology and flow cytometry analysis showed successful mobilization of bone marrow-derived cells by CSF3 treatment in the recipient lungs. Importantly, CSF3 attenuated bleomycin-induced lung injury and improved survival. Furthermore, CSF3 administration regulated transforming growth factor-β, interferon-γ, MMP9 and tissue inhibitors of MMP1 expression during bleomycin injury. Conclusions: These data demonstrated that the mobilization of bone marrow-derived cells by CSF3 has a protective effect against bleomycin-induced lung injury and fibrosis.
Socioeconomic Status and Health-Related Quality of Life of Patients with Chronic Obstructive Pulmonary Disease
Authors: Miravitlles Marc , Naberan Karlos , Cantoni Jordi , Azpeitia Angel
Published: July 2011

Background: Socioeconomic status (SES) is an important determinant of health and premature death. However, the impact of poor SES on the health status of patients with chronic obstructive pulmonary disease (COPD) has not been well determined. Objective: It was our aim to assess the impact of SES on the quality of life in COPD patients. Methods: This was a cross-sectional, observational, multicenter study. A total of 4,574 patients completed the EuroQol 5-dimension questionnaire (EQ-5D) and the Airways Questionnaire 20 (AQ20). SES was based on the subject’s occupation and educational level. Occupational categories were based on the major group classification of the International Standard Classification of Occupations. Results: The mean age of the population was 67.1 years and the mean forced expiratory volume was 43.4%. There was a gradient of impairment in health-related quality of life (HRQoL) according to the educational level, with significantly worse scores for the EQ-5D and the AQ20 for medium and low educational levels compared with high education (p < 0.001). Similarly, HRQoL was also significantly impaired in more unskilled workers, with a gradient of the AQ20 from 8.6 units (SD 4.8) in class I to 10.1 units (4.6) in class V (p < 0.001) and from 0.75 units in class I to 0.63 units in class V for the EQ-5D index, as well as from 62.9 units in class I to 55.6 units in class V for the EQ-5D visual analogue scale (p < 0.001 for all comparisons). These differences remained significant after controlling for covariates. Conclusions: Patients with a lower educational level and belonging to the unskilled professional groups had a poorer HRQoL. This is evident even in a country where access to health care services is universal and free.
Tandem Repeats in a New Toxin Gene from Bacillus thuringiensis and in Other cry11-Like Genes
Authors: Melnikov Olga , Baranes Nadine , Einav Monica , Ben-Dov Eitan , Manasherob Robert , Itsko Mark , Zaritsky Arieh
Published: July 2011

A new gene, cry11Bb2 from a field isolate of Bacillus thuringiensis, was cloned for expression in Escherichia coli. The encoded protein, with a deduced molecular mass of 89.5 kDa, exhibits 97 and 79% identities with the overlap regions of Cry11Bb1 from B. thuringiensis ssp. medellin and Cry11Ba1 from ssp. jegathesan, respectively. It is however longer than Cry11Bb1 by 42 amino acids in its carboxy-terminus, of which 32 comprise 2 tandem repeats additional to the 5 existing in the latter polypeptide. Possible roles for this recurrent motif among Cry toxins and their accessory proteins, and for their encoding genes are proposed.
Gulf Survey of Atrial Fibrillation Events (Gulf SAFE)
Authors: Zubaid Mohammad , Rashed Wafa A. , Alsheikh-Ali Alawi A. , AlMahmeed Wael , Shehab Abdullah , Sulaiman Kadhim , Al-Zakwani Ibrahim , AlQudaimi Ahmed , Asaad Nidal , Amin Haitham
Published: July 2011

Background—

Atrial fibrillation (AF) is the most common serious cardiac arrhythmia, and its prevalence is expected to increase. There is lack of data about patient characteristics, practice patterns, and outcomes of AF in the Arab Middle East.

Methods and Results—

The Gulf Survey of Atrial Fibrillation Events (Gulf SAFE) is a prospective, observational registry of patients with AF with a 12-month follow-up. The registry was emergency room based. Between October 2009 and June 2010, 2043 consecutive patients with AF were enrolled from 23 hospitals in 6 Middle Eastern Gulf countries. Data were collected on a standardized case report form and entered online. Data collected included patient demographics, medical history, type of AF, treatment, and outcome of emergency room visit. If patients were admitted, details of their treatment, investigations, and outcomes during hospital stay were collected. Completion of 12-month follow-up is expected by July 2011. The mean age was 57 years, and 52% were men. The most common concomitant condition was hypertension, present in 1072 (52%) patients. At enrollment, 28% of patients had a history of coronary artery disease, 30% had diabetes, and 16% had rheumatic valve disease. History of stroke and transient ischemic attacks were reported in 9% and 4% of patients, respectively. The most common type of AF, first attack AF, occurred in 37%, whereas 19% of patients had lone AF.

Conclusions—

Gulf SAFE will provide valuable insights into AF management and outcomes in the Gulf region of the Middle East.
Flow-Dependent Regulation of Krüppel-Like Factor 2 Is Mediated by MicroRNA-92a
Authors: Wu Wei , Xiao Han , Laguna-Fernandez Andrés , Villarreal Guadalupe , Wang Kuei-Chun , Geary Greg G. , Zhang Yuzhi , Wang Wei-Chi , Huang Hsien-Da , Zhou Jing , Li Yi-Shuan , Chien Shu , Garcia-Cardena Guillermo , Shyy John Y.-J.
Published: July 2011

Background—

Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow–regulated KLF2.

Methods and Results—

Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA.
In silico
analysis predicted that miR-92a could bind to the 3′ untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow.

Conclusions—

Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis.
Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism
Authors: Lin Xiaobo , Racette Susan B. , Lefevre Michael , Ma Lina , Spearie Catherine Anderson , Steger-May Karen , Ostlund Richard E.
Published: July 2011

Background—

Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that the combination of ezetimibe and phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism.

Methods and Results—

Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple-crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo+phytosterol placebo, (2) 10 mg/d ezetimibe+phytosterol placebo, and (3) 10 mg/d ezetimibe+2.5 g phytosterols for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and low-density lipoprotein cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/d; 95% confidence interval [CI], 368 to 828) relative to control (2161 mg/d; 95% CI, 1112 to 3209) and ezetimibe alone (1054 mg/d; 95% CI, 546 to 1561; both
P
<0.0001). Fecal cholesterol excretion was significantly greater (
P
<0.0001) with combined treatment (962 mg/d; 95% CI, 757 to 1168) relative to control (505 mg/d; 95% CI, 386 to 625) and ezetimibe alone (794 mg/d; 95% CI, 615 to 973). Plasma low-density lipoprotein cholesterol values during treatment with control, ezetimibe alone, and ezetimibe+phytosterols averaged 129 mg/dL (95% CI, 116 to 142), 108 mg/dL (95% CI, 97 to 119), and 101 mg/dL (95% CI, 90 to 112; (
P
<0.0001 relative to control).

Conclusion—

The addition of phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma low-density lipoprotein cholesterol. The large cumulative action of combined dietary and pharmacological treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00863265.
Delayed Coverage in Malapposed and Side-Branch Struts With Respect to Well-Apposed Struts in Drug-Eluting Stents
Authors: Gutiérrez-Chico Juan Luis , Regar Evelyn , Nüesch Eveline , Okamura Takayuki , Wykrzykowska Joanna , di Mario Carlo , Windecker Stephan , van Es Gerrit-Anne , Gobbens Pierre , Jüni Peter , Serruys Patrick W.
Published: July 2011

Background—

Pathology studies on fatal cases of very late stent thrombosis have described incomplete neointimal coverage as common substrate, in some cases appearing at side-branch struts. Intravascular ultrasound studies have described the association between incomplete stent apposition (ISA) and stent thrombosis, but the mechanism explaining this association remains unclear. Whether the neointimal coverage of nonapposed side-branch and ISA struts is delayed with respect to well-apposed struts is unknown.

Methods and Results—

Optical coherence tomography studies from 178 stents implanted in 99 patients from 2 randomized trials were analyzed at 9 to 13 months of follow-up. The sample included 38 sirolimus-eluting, 33 biolimus-eluting, 57 everolimus-eluting, and 50 zotarolimus-eluting stents. Optical coherence tomography coverage of nonapposed side-branch and ISA struts was compared with well-apposed struts of the same stent by statistical pooled analysis with a random-effects model. A total of 34 120 struts were analyzed. The risk ratio of delayed coverage was 9.00 (95% confidence interval, 6.58 to 12.32) for nonapposed side-branch versus well-apposed struts, 9.10 (95% confidence interval, 7.34 to 11.28) for ISA versus well-apposed struts, and 1.73 (95% confidence interval, 1.34 to 2.23) for ISA versus nonapposed side-branch struts. Heterogeneity of the effect was observed in the comparison of ISA versus well-apposed struts (H=1.27; I
2
=38.40) but not in the other comparisons.

Conclusions—

Coverage of ISA and nonapposed side-branch struts is delayed with respect to well-apposed struts in drug-eluting stents, as assessed by optical coherence tomography.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00389220, NCT00617084.
Prognostic Value of Admission Glycosylated Hemoglobin and Glucose in Nondiabetic Patients With ST-Segment–Elevation Myocardial Infarction Treated With Percutaneous Coronary Intervention
Authors: Timmer Jorik R. , Hoekstra Miriam , Nijsten Maarten W.N. , van der Horst Iwan C.C. , Ottervanger Jan Paul , Slingerland Robbert J. , Dambrink Jan-Henk E. , Bilo Henk J.G. , Zijlstra Felix , van 't Hof Arnoud W.J.
Published: July 2011

Background—

In nondiabetic patients with ST-segment–elevation myocardial infarction, acute hyperglycemia is associated with adverse outcome. Whether this association is due merely to hyperglycemia as an acute stress response or whether longer-term glycometabolic derangements are also involved is uncertain. It was our aim to determine the association between both acute and chronic hyperglycemia (hemoglobin A
1c
[HbA
1c
]) and outcome in nondiabetic patients with ST-segment–elevation myocardial infarction.

Methods and Results—

This observational study included consecutive patients (n=4176) without known diabetes mellitus admitted with ST-segment–elevation myocardial infarction. All patients were treated with primary percutaneous intervention. Both glucose and HbA
1c
were measured on admission. Main outcome measure was total long-term mortality; secondary outcome measures were 1-year mortality and enzymatic infarct size. One-year mortality was 4.7%, and mortality after total follow-up (3.3±1.5 years) was 10%. Both elevated HbA
1c
levels (
P
<0.001) and elevated admission glucose (
P
<0.001) were associated with 1-year and long-term mortality. After exclusion of early mortality (within 30 days), HbA
1c
remained associated with long-term mortality (
P
<0.001), whereas glucose lost significance (
P
=0.09). Elevated glucose, but not elevated HbA
1c
, was associated with larger infarct size. After multivariate analysis, HbA
1c
(hazard ratio, 1.2 per interquartile range;
P
<0.01), but not glucose, was independently associated with long-term mortality.

Conclusions—

In nondiabetic patients with ST-segment–elevation myocardial infarction, both elevated admission glucose and HbA
1c
levels were associated with adverse outcome. Both of these parameters reflect different patient populations, and their association with outcome is probably due to different mechanisms. Measurement of both parameters enables identification of these high-risk groups for aggressive secondary risk prevention.
Effect of Torcetrapib on Glucose, Insulin, and Hemoglobin A
1c
in Subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) Trial
Authors: Barter Philip J. , Rye Kerry-Anne , Tardif Jean-Claude , Waters David D. , Boekholdt S. Matthijs , Breazna Andrei , Kastelein John J.P.
Published: July 2011

Background—

High-density lipoproteins have antidiabetic properties in vitro. Furthermore, elevated high-density lipoprotein levels accompanying a genetic deficiency of cholesteryl ester transfer protein are associated with decreased levels of plasma glucose. We now investigate effects on glucose homeostasis of inhibiting cholesteryl ester transfer protein with torcetrapib.

Methods and Results—

A post hoc analysis of the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial was conducted to investigate effects of the cholesteryl ester transfer protein inhibitor torcetrapib on glycemic control in the 6661 diabetic patients in the trial. At baseline, there were no differences between the 2 treatment arms with respect to plasma glucose, insulin, hemoglobin A
1c
, or the homeostasis model assessment of insulin resistance. After 3 months, the diabetic subjects taking the combination of torcetrapib plus atorvastatin had plasma glucose levels 0.34 mmol/L lower (
P
<0.0001) and insulin levels 11.7 μU/mL lower (
P
<0.0001) than in those receiving atorvastatin alone. Homeostasis model assessment of insulin resistance values decreased from 49.1 to 47.3 (
P
<0.0001) in the torcetrapib/atorvastatin arm compared with an increase in homeostasis model assessment of insulin resistance in the atorvastatin arm. At the 6-month time point, the mean hemoglobin A
1c
level in the atorvastatin arm was 7.29% compared with 7.06% in the torcetrapib/atorvastatin arm (
P
<0.0001). These effects of torcetrapib remained apparent for up to 12 months. Torcetrapib also lowered both glucose and insulin levels in the participants without diabetes mellitus, although the effects were not as great as in those with diabetes mellitus.

Conclusions—

Treatment with torcetrapib improves glycemic control in atorvastatin-treated patients with type 2 diabetes mellitus. It remains to be determined whether this effect is the consequence of raising high-density lipoprotein.at

Clinical Trial Registration—

http:www.clinicaltrials.gov
. Unique identifier: NCT00134264.
Polymer-Free Sirolimus- and Probucol-Eluting Versus New Generation Zotarolimus-Eluting Stents in Coronary Artery Disease
Authors: Massberg Steffen , Byrne Robert A. , Kastrati Adnan , Schulz Stefanie , Pache Jürgen , Hausleiter Jörg , Ibrahim Tareq , Fusaro Massimiliano , Ott Ilka , Schömig Albert , Laugwitz Karl-Ludwig , Mehilli Julinda
Published: July 2011

Background—

Durable polymer coatings have been implicated in mid- and long-term adverse events after drug-eluting stent implantation. A polymer-free dual-drug sirolimus- and probucol-eluting stent and a new generation permanent polymer zotarolimus-eluting stent are recently developed technologies demonstrating encouraging results.

Methods and Results—

In a clinical trial with minimal exclusion criteria, we randomly assigned 3002 patients to treatment with sirolimus- and probucol-eluting stents versus zotarolimus-eluting stents. The trial was designed to demonstrate noninferiority of the sirolimus- and probucol-eluting stents. The primary end point was the combined incidence of cardiac death, target-vessel–related myocardial infarction, or target-lesion revascularization at 1-year follow-up. Follow-up angiography was scheduled at 6 to 8 months.

The sirolimus- and probucol-eluting stent was noninferior to the zotarolimus-eluting stent in terms of occurrence of the primary end point (13.1% versus 13.5%, respectively,
P
noninferiority
=0.006; hazard ratio=0.97, 95% confidence interval, 0.78 to 1.19;
P
superiority
=0.74). The incidence of definite/probable stent thrombosis was low in both groups (1.1% versus 1.2%, respectively; hazard ratio=0.91 [95% confidence interval, 0.45 to 1.84],
P
=0.80). With regard to angiographic efficacy, there were no differences between the sirolimus- and probucol-eluting stent and the zotarolimus-eluting stent in terms of either in-segment binary angiographic restenosis (13.3% versus 13.4% respectively;
P
=0.95) or in-stent late luminal loss (0.31±0.58 mm versus 0.29±0.56 mm, respectively;
P
=0.46).

Conclusion—

In this large-scale study powered for clinical end points, a polymer-free sirolimus- and probucol-eluting stent was noninferior to a new generation durable polymer-based zotarolimus-eluting stent out to 12 months.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier NCT 00598533.
Early Treatment With Lisinopril and Spironolactone Preserves Cardiac and Skeletal Muscle in Duchenne Muscular Dystrophy Mice
Authors: Rafael-Fortney Jill A. , Chimanji Neeraj S. , Schill Kevin E. , Martin Christopher D. , Murray Jason D. , Ganguly Ranjit , Stangland Jenna E. , Tran Tam , Xu Ying , Canan Benjamin D. , Mays Tessily A. , Delfín Dawn A. , Janssen Paul M.L. , Raman Subha V.
Published: July 2011

Background—

Nearly universal cardiomyopathy in Duchenne muscular dystrophy (DMD) contributes to heart failure and death. Because DMD patients show myocardial fibrosis well before functional impairment, we postulated that earlier treatment using drugs with antifibrotic effect may be beneficial.

Methods and Results—

Three groups of 10
utrn
+/−
;
mdx
, or “het” mice, deficient for dystrophin and haploinsufficient for utrophin with skeletal myopathy and cardiomyopathy that closely mimics clinical DMD were studied. One het group received spironolactone and lisinopril starting at 8 weeks of life (het-treated-8); a second received the same starting at 4 weeks of life (het-treated-4), and the third het group was untreated. At 20 weeks, all mice had normal ejection fractions though circumferential strain rate was abnormal (−0.21±0.08) in untreated hets. This improved to −0.40±0.07 in het-treated-8 mice (
P
=0.003) and further improved to −0.56±0.10 in het-treated-4 mice (
P
=0.014 for het-treated-4 versus het-treated-8). Treated mice showed less cardiomyocyte damage, with a 44% reduction in intracardiomyocyte serum immunoglobulin G localization in het-treated-8 mice (
P
<0.0001) and a further 53% reduction in het-treated-4 mice (
P
=0.0003 versus het-treated-8); matrix metalloproteinases were similarly reduced. Cardiac, limb, and diaphragm function by ex vivo muscle testing remained at 80% of normal with early treatment compared to a decline to 40% of normal skeletal muscle function without treatment.

Conclusions—

These findings offer clinically available medications with proven antifibrotic effect as a new therapeutic strategy in DMD. Early initiation greatly attenuated myocardial disease and, for the first time with these drugs, improved skeletal myopathy. Thus, early initiation of such agents warrants further clinical evaluation to maintain ambulatory, respiratory, and cardiac function for patients with DMD and related myopathies.
Role of Adenosine 5′-Triphosphate in Regulating Renal Microvascular Function and in Hypertension
Authors: Guan Zhengrong , Inscho Edward W.
Published: July 2011

ATP is an essential energy substrate for cellular metabolism, but it can also influence many biological processes when released into the extracellular milieu. Research has established that extracellular ATP acts as an autocrine/paracrine factor that regulates many physiological functions. Alternatively, excessive extracellular ATP levels contribute to pathophysiological processes, such as inflammation, cell proliferation and apoptosis, and atherosclerosis. Renal P2 receptors are widely distributed throughout glomeruli, vasculature, and tubular segments and participate in controlling renal vascular resistance, mediating renal autoregulation, and regulating tubular transport function. This review will focus on the role of ATP-P2 receptor signaling in regulating renal microvascular function and autoregulation, recent advances on the role of ATP-P2 signaling in hypertension-associated renal vascular injury, and emerging new directions.
Association Between Plasma Vitamin C Concentrations and Blood Pressure in the European Prospective Investigation Into Cancer-Norfolk Population-Based Study
Authors: Myint Phyo K. , Luben Robert N. , Wareham Nicholas J. , Khaw Kay-Tee
Published: July 2011

The effect of fruit and vegetable consumption and blood pressure is unclear. A population-based cross-sectional study was conducted in 20 926 men and women aged 40 to 79 years participating in the European Prospective Investigation Into Cancer-Norfolk who completed a health questionnaire and attended a clinic from 1993 to 1997. The relationship between plasma vitamin C concentrations, as an indicator of fruit and vegetable intake, and systolic BP was examined. The magnitude of their association was assessed using dichotomized values of high (≥140 mm Hg) and low (<140 mm Hg) systolic blood pressure. A total of 20 926 participants (46% men; mean [SD] 58.5 years [9.2 years]) were included after excluding participants with any missing data for variables of interest. People with high vitamin C concentrations had lower clinic blood pressure. The likelihood of having high blood pressure was 22% lower (odds ratio: 0.78 [95% CI: 0.71 to 0.86]) for those who were in the top quartiles of plasma vitamin C levels compared with the bottom quartiles after adjusting for age, sex, body mass index, cholesterol, prevalent medical conditions, smoking, physical activity, alcohol consumption, social class, education, use of vitamin C–containing supplement, and antihypertensive medication. Sex-specific analysis, as well as repeated analysis after exclusion of people who used vitamin C–containing supplements or who were taking antihypertensive medication, did not alter the results. There appears to be a strong association between vitamin C concentrations, an indicator of fruit and vegetable consumption, and a lower level of blood pressure. This may provide further evidence for health benefits of dietary patterns with higher fruit and vegetable consumption.
Interleukin 10 Deficiency Exacerbates Toll-Like Receptor 3–Induced Preeclampsia-Like Symptoms in Mice
Authors: Chatterjee Piyali , Chiasson Valorie L. , Kopriva Shelley E. , Young Kristina J. , Chatterjee Victor , Jones Kathleen A. , Mitchell Brett M.
Published: July 2011

Preeclampsia may result from overactivation of the maternal immune system and is characterized by endothelial dysfunction and excessive inflammation. Given the importance of maternal immune system regulation and anti-inflammatory cytokines in normotensive pregnancies, we hypothesized that maternal immune system activation via Toll-like receptor 3 during pregnancy would cause preeclampsia-like symptoms in mice, which would be made worse by deficiency of the anti-inflammatory cytokine interleukin 10. The Toll-like receptor 3 agonist polyinosine-polycytidylic acid (poly I:C) caused hypertension, endothelial dysfunction, and proteinuria in mice only when pregnant. In the absence of poly I:C, pregnant interleukin 10 knockout mice exhibited a significant increase in systolic blood pressure, endothelial dysfunction, and serum proinflammatory cytokines, as well as aortic and placental platelet-endothelial cell adhesion molecule expression compared with pregnant wild-type mice. Deficiency of interleukin 10 further augmented these measures in poly I:C–treated pregnant mice. In addition, sera from poly I:C-treated pregnant wild-type mice significantly decreased relaxation responses and increased platelet-endothelial cell adhesion molecule expression in isolated aortas from nonpregnant wild-type mice, and these effects were augmented by sera from poly I:C-treated interleukin 10 knockout mice. Coincubation with recombinant interleukin 10 normalized relaxation responses and platelet-endothelial cell adhesion molecule expression in all of the groups. Collectively, Toll-like receptor 3 activation during pregnancy causes preeclampsia-like symptoms, which are exacerbated by the absence of interleukin 10. Exogenous interleukin 10 treatment had beneficial effects on endothelial function and may be beneficial in women with preeclampsia.
Implications of New Hypertension Guidelines in the United States
Authors: Bertoia Monica L. , Waring Molly E. , Gupta Priya S. , Roberts Mary B. , Eaton Charles B.
Published: July 2011

The American Heart Association Task Force released a scientific statement in 2007 for the treatment of hypertension in the prevention of coronary artery disease (CAD). These guidelines recommend more aggressive control of blood pressure (BP) among those at high risk for CAD: individuals with diabetes mellitus, chronic kidney disease, cardiovascular disease, congestive heart failure, or a 10-year Framingham risk score ≥10%. These individuals are advised to maintain a BP <130/80 mm Hg. We estimated the burden of uncontrolled BP among those at an increased risk of CAD using the updated task force guidelines. We used a cross-sectional analysis of National Health and Nutrition Examination Survey 2005–2008 participants. Participants were 24 989 adults aged 18 to 85 years. Using the old definition of hypertension (>140/90 mm Hg), 98 million (21%) Americans have hypertension. Using the updated guidelines, an additional 52 million (11%) American adults now have elevated BP requiring treatment, for a total of 150 million adults (32%). Adults with diabetes mellitus have the greatest population burden of uncontrolled BP (50.6 million), followed by adults with chronic kidney disease (43.7 million) and cardiovascular disease (43.3 million). Although individuals at a higher risk for CAD are more likely to be aware of their hypertension and to be taking antihypertension medication, they are less likely to have their BP under control. Additional efforts are needed in the treatment of elevated BP, especially among individuals with an increased risk of CAD.
A Comparison of Statistical and Dynamical Downscaling of Winter Precipitation over Complex Terrain
Authors: Gutmann Ethan D. , Rasmussen Roy M. , Liu Changhai , Ikeda Kyoko , Gochis David J. , Clark Martyn P. , Dudhia Jimy , Thompson Gregory
Published: July 2011

Statistical downscaling is widely used to improve spatial and/or temporal distributions of meteorological variables from regional and global climate models. This downscaling is important because climate models are spatially coarse (50–200 km) and often misrepresent extremes in important meteorological variables, such as temperature and precipitation. However, these downscaling methods rely on current estimates of the spatial distributions of these variables and largely assume that the small-scale spatial distribution will not change significantly in a modified climate. In this study the authors compare data typically used to derive spatial distributions of precipitation [Parameter-Elevation Regressions on Independent Slopes Model (PRISM)] to a high-resolution (2 km) weather model [Weather Research and Forecasting model (WRF)] under the current climate in the mountains of Colorado. It is shown that there are regions of significant difference in November–May precipitation totals (>300 mm) between the two, and possible causes for these differences are discussed. A simple statistical downscaling is then presented that is based on the 2-km WRF data applied to a series of regional climate models [North American Regional Climate Change Assessment Program (NARCCAP)], and the downscaled precipitation data are validated with observations at 65 snow telemetry (SNOTEL) sites throughout Colorado for the winter seasons from 1988 to 2000. The authors also compare statistically downscaled precipitation from a 36-km model under an imposed warming scenario with dynamically downscaled data from a 2-km model using the same forcing data. Although the statistical downscaling improved the domain-average precipitation relative to the original 36-km model, the changes in the spatial pattern of precipitation did not match the changes in the dynamically downscaled 2-km model. This study illustrates some of the uncertainties in applying statistical downscaling to future climate.
Precise Calculations of the Existence of Multiple AMOC Equilibria in Coupled Climate Models. Part II: Transient Behavior
Authors: Sijp Willem P. , England Matthew H.
Published: July 2011

In Part I of this paper an evolution equation for the Atlantic salinity and the reverse cell strength in the North Atlantic Deep Water (NADW) OFF state was formulated. Here, an analytical solution to this equation is used to test its validity in the context of transient solutions. In this study several transient scenarios in the general circulation model are examined to determine the accuracy of the predictions made with the material in Part I. The authors also determine how well the basic premises of Part I hold throughout these transient behaviors. The unstable equilibria that mark the upper boundary of the OFF state attraction basin are elucidated by the time-dependent behavior shown here. Transient equilibration from one stable NADW OFF state to another in response to changes in the anomalous salt flux H is accurately described by the evolution equation. The theory also explains the distribution of decay times for the NADW OFF state around the maximum critical Atlantic surface flux. Exceedingly long collapse times in excess of 50 000 years are found for surface flux values slightly in excess of the critical value.
Numerical Study on the Formation of Typhoon Ketsana (2003). Part I: Roles of the Mesoscale Convective Systems
Authors: Lu Xinyan , Cheung Kevin K. W. , Duan Yihong
Published: July 2011

The effects of multiple mesoscale convective systems (MCSs) on the formation of Typhoon Ketsana (2003) are analyzed in this study. Numerical simulations using the Weather Research and Forecasting (WRF) model with assimilation of Quick Scatterometer (QuikSCAT) and Special Sensor Microwave Imager (SSM/I) oceanic winds and total precipitable water are performed. The WRF model simulates well the large-scale features, the convective episodes associated with the MCSs and their periods of development, and the formation time and location of Ketsana. With the successive occurrence of MCSs, midlevel average relative vorticity is strengthened through generation of mesoscale convective vortices (MCVs) mainly via the vertical stretching mechanism. Scale separation shows that the activity of the vortical hot tower (VHT)-type meso-γ-scale vortices correlated well with the development of the MCSs. These VHTs have large values of positive relative vorticity induced by intense low-level convergence, and thus play an important role in the low-level vortex enhancement with aggregation of VHTs as one of the possible mechanisms.

Four sensitivity experiments are performed to analyze the possible different roles of the MCSs during the formation of Ketsana by modifying the vertical relative humidity profile in each MCS and consequently the strength of convection within. The results show that the development of an MCS depends substantially on that of the prior ones through remoistening of the midtroposphere, and thus leading to different scenarios of system intensification during the tropical cyclone (TC) formation. The earlier MCSs are responsible for the first stage vortex enhancement, and depending on the location can affect quite largely the simulated formation location. The extreme convection within the last MCS before formation largely determines the formation time.
Tropopause Structure and the Role of Eddies
Authors: Haqq-Misra Jacob , Lee Sukyoung , Frierson Dargan M. W.
Published: July 2011

This paper presents a series of dynamical states using an idealized three-dimensional general circulation model with gray radiation and latent heat release. Beginning with the case of radiative–convective equilibrium, an eddy-free two-dimensional state with zonally symmetric flow is developed, followed by a three-dimensional state that includes baroclinic eddy fluxes. In both dry and moist cases, it is found that the deepening of the tropical tropospheric layer and the shape of the extratropical tropopause can be understood through eddy-driven processes such as the stratospheric Brewer–Dobson circulation. These results suggest that eddies alone can generate a realistic tropopause profile in the absence of moist convection and that stratospheric circulation is an important contributor to tropopause structure.
Climate Feedbacks and Their Implications for Poleward Energy Flux Changes in a Warming Climate
Authors: Zelinka Mark D. , Hartmann Dennis L.
Published: July 2011

Feedbacks determine the efficiency with which the climate system comes back into equilibrium in response to a radiative perturbation. Although feedbacks are integrated quantities, the processes from which they arise have rich spatial structures that alter the distribution of top of atmosphere (TOA) net radiation. Here, the authors investigate the implications of the structure of climate feedbacks for the change in poleward energy transport as the planet warms over the twenty-first century in a suite of GCMs. Using radiative kernels that describe the TOA radiative response to small perturbations in temperature, water vapor, and surface albedo, the change in poleward energy flux is partitioned into the individual feedbacks that cause it.

This study finds that latitudinal gradients in the sum of climate feedbacks reinforce the preexisting latitudinal gradient in TOA net radiation, requiring that the climate system transport more energy to the poles on a warming planet. This is primarily due to structure of the water vapor and cloud feedbacks, which are strongly positive at low latitudes and decrease dramatically with increasing latitude. Using the change in surface fluxes, the authors partition the anomalous poleward energy flux between the atmosphere and ocean and find that reduced heat flux from the high-latitude ocean further amplifies the equator-to-pole gradient in atmospheric energy loss. This implied reduction in oceanic poleward energy flux requires the atmosphere to increase its share of the total poleward energy transport. As is the case for climate sensitivity, the largest source of intermodel spread in the change in poleward energy transport can be attributed to the shortwave cloud feedback.
Implementation and Evaluation of Dynamic Subfilter-Scale Stress Models for Large-Eddy Simulation Using WRF*
Authors: Kirkil Gokhan , Mirocha Jeff , Bou-Zeid Elie , Chow Fotini Katopodes , Kosović Branko
Published: July 2011

The performance of a range of simple to moderately-complex subfilter-scale (SFS) stress models implemented in the Weather Research and Forecasting (WRF) model is evaluated in large-eddy simulations of neutral atmospheric boundary layer flow over both a flat terrain and a two-dimensional symmetrical transverse ridge. Two recently developed dynamic SFS stress models, the Lagrangian-averaged scale-dependent (LASD) dynamic model and the dynamic reconstruction model (DRM), are compared with the WRF model’s existing constant-coefficient linear eddy-viscosity and (as of version 3.2) nonlinear SFS stress models to evaluate the benefits of more sophisticated and accurate, but also more computationally expensive approaches.

Simulation results using the different SFS stress models are compared among each other, as well as against the Monin–Obukhov similarity theory. For the flat terrain case, vertical profiles of mean wind speed from the newly implemented dynamic models show the best agreement with the similarity solution, improving even upon the nonlinear model, which likewise yields a significant improvement compared to the Smagorinsky model. The more sophisticated SFS stress models more successfully predict the expected production and inertial range scaling of power spectra, especially near the surface, with the dynamic models achieving the best scaling overall. For the transverse ridge case, the nonlinear model predicts the greatest amount of reverse flow in the lee of the ridge, and also demonstrates the greatest ability to duplicate qualitative features of the highest-resolution simulations at coarser resolutions. The dynamic models’ flow distributions in the lee of the ridge did not differ significantly from the constant-coefficient Smagorinsky model.
Heavy Precipitation at the Alpine South Side and Saharan Dust over Central Europe: A Predictability Study Using TIGGE
Authors: Wiegand Lars , Twitchett Arwen , Schwierz Cornelia , Knippertz Peter
Published: July 2011

Around 26 May 2008 a pronounced potential vorticity (PV) streamer penetrated from the North Atlantic into the western Mediterranean Sea followed by widespread dust mobilization over the Maghreb region of northwest Africa and a subsequent northward transport into central Europe. At the same time, strong southerly flow over the Mediterranean Sea caused heavy precipitation and flooding at the windward side of the European Alps. Using continuous and feature-based error measures, as well as ensemble correlation techniques, this study investigates the forecast quality and predictability of synoptic and mesoscale aspects of this high-impact event in operational ensemble predictions from nine meteorological centers participating in The Observing System Research and Predictability Experiment (THORPEX) Interactive Grand Global Ensemble (TIGGE) project. TIGGE is a recently established program providing ensemble forecasts in a standardized format, which allows for an exciting new multimodel approach to investigating the predictability of, for example, high-impact weather and its dynamics. The main conclusions from this study are that 1) the quality of the PV streamer forecasts degrades with lead time showing a general tendency toward too weak Rossby wave; 2) when focusing on the region around the streamer, most models show root-mean-square errors of the same magnitude or larger than the ensemble spread (underdispersive behavior); 3) errors are reduced by about 50% if the comparison is made to each center’s own analysis instead of the ECMWF analysis; 4) peak wind speeds over the Sahara tend to be underpredicted, with differences in model formulation dominating over differences in the representation of the PV streamer; and 5) ensemble-mean multimodel forecasts of 4-day accumulated precipitation appear accurate enough for a successful severe-weather warning.
Understanding Non-Tenure Track Faculty
Authors: Kezar Adrianna , Sam Cecile
Published: July 2011

This article examines the underlying assumptions brought to bear on studies of non–tenure track faculty. The authors examine the deficit views that characterize non–tenure track as other than professional. Furthermore, they explore and challenge theories brought to bear to currently understand this population and suggest other theories that may better explain research outcomes. Finally, they note the importance of grounded theories that develop out of non–tenure track faculties’ own experience rather than derive from deductive assumptions from temporary employees in business.
Closing the Classroom Door and the Achievement Gap
Authors: Heineke Amy J. , Cameron Quanna
Published: July 2011

This qualitative study explored Teach for America (TFA) alumni teachers’ discourse on Arizona language policy, conducted with eight teachers in the Phoenix metropolitan area who received their professional teacher preparation from TFA, a national organization that uses alternative paths to certification to place teachers in low-income schools. During the 2009-2010 school year, we investigated how TFA alumni teachers described the state-mandated English-only language policy, which requires all labeled English language learners (ELLs) to enroll in English language development (ELD) classrooms for 4 hr of daily skill-based English instruction. In addition to their open evaluation and critique of the language policy, teachers’ discourse revealed language policy appropriation, as the teachers tweaked and stretched the language policy directives to match their ideology, pedagogy, and classroom context. Findings from our discourse analysis of the interview data demonstrate that the teachers’ discourse reflected their TFA preparation regarding recognizing the flaws in the educational system and taking action to make change within the four walls of their urban classrooms. The research holds implications for language education reform through recognizing the active role of the teacher in language policy formation and implementation.
School Choice and Market Imperfections
Authors: Thieme Claudio , Treviño Ernesto
Published: July 2011

The purpose of this study is to inform public policies aimed at improving parental school-choice processes. The study estimates both the utility obtained by parents from different school attributes and the effective utility obtained with the actual school choice made by parents. The difference between both types of utilities provides a panorama on how market imperfections affect the general equilibrium of the education market. The results show that parents have different preference functions depending on their socioeconomic level. Nevertheless, regardless of the socioeconomic level, in all preference functions teacher performance remains highly significant. The findings suggest that even if parents would want the schools that serve their children to fulfill a series of academic criteria, they cannot use academic attributes when choosing a school for their children. This seems to be the result of either lack of information or because there is no quality alternative available to them.
Gender Earnings and Poverty Reduction: Post-Communist Uzbekistan
Authors: Bhat Bilal Ahmad
Published: July 2011

Women get less of the material resources, social status, power and opportunities for self-actualization than men do who share their social location – be it a location based on class, race, occupation, ethnicity, religion, education, nationality, or any intersection of these factors. The process of feminization of poverty in Central Asia and Uzbekistan is intimately connected to the cultural and institutional limitations that put a ceiling on women’s involvement in economic activity. This article attempts to study and explore gender in the context of poverty reduction in Uzbekistan, the most populated state of Central Asia, to understand the ways and manner in which poverty and other forms of deprivation demand women’s participation in variety of contexts. The study is primarily an empirical one and is based on an extensive sociological investigation in the field.