bluuebunny/crossref_metadata_2025 huggingface dataset:
Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1
Authors: Wei Dan , Tao Rongya , Zhang Yao , White Morris F. , Dong X. Charlie
Published: November 2010

Protein deacetylase Sirt1 has been implicated in the regulation of hepatic gluconeogenesis; however, the mechanisms are not fully understood. To further elucidate how Sirt1 regulates gluconeogenesis, we took a loss-of-function approach by deleting the coding DNA sequence for the catalytic domain of the Sirt1 gene in the liver of a wild-type mouse (LKOSirt1) or a genetic diabetic mouse in which hepatic insulin receptor substrates 1 and 2 are deleted (DKOIrs1/2). Whereas LKOSirt1 mice exhibited normal levels of fasting and fed blood glucose, inactivation of Sirt1 in DKOIrs1/2 mice (TKOIrs1/2:Sirt1) reduced blood glucose levels and moderately improved systemic glucose tolerance. Pyruvate tolerance was also significantly improved in TKOIrs1/2:Sirt1 mice, suggesting that Sirt1 promotes hepatic gluconeogenesis in this diabetic mouse model. To understand why inactivation of hepatic Sirt1 does not alter blood glucose levels in the wild-type background, we searched for a potential cause and found that expression of small heterodimer partner (SHP, encoded by the Nr0b2 gene), an orphan nuclear receptor, which has been shown to suppress the activity of forkhead transcription factor FoxO1, was decreased in the liver of LKOSirt1 mice. Furthermore, our luciferase reporter assays and chromatin immunoprecipitation analysis revealed that the Nr0b2 gene is a target of FoxO1, which is also regulated by Sirt1. After the gene is upregulated, Nr0b2 can feed back and repress FoxO1- and Sirt1-activated G6pc and Pdk4 gene expression. Thus, our results suggest that Sirt1 can both positively and negatively regulate hepatic gluconeogenesis through FoxO1 and Nr0b2 and keep this physiological process in control.
Overexpression of MAC30 in the Cytoplasm of Oral Squamous Cell Carcinoma Predicts Nodal Metastasis and Poor Differentiation
Authors: Yan Bao-Yong , Wang Da-Wei , Zhu Zhen-Long , Yang Yan-Hong , Wang Ming-Wei , Cui Dong-Sheng , Zhang Hong , Sun Xiao-Feng
Published: November 2010

Background: Expression of the meningioma-associated protein (MAC30) was increased in several types of tumors, including esophageal, gastric and colon tumors, compared to normal tissue. MAC30 expression levels gradually increased from normal colorectal mucosa to primary colorectal cancer and colorectal cancer spreading to the lymph nodes. MAC30 expression was related to survival in patients with colorectal cancer. However, there is no study on MAC30 in oral squamous cell carcinoma (OSCC). Methods: Therefore, MAC30 expression in OSCC was investigated and possible associations of MAC30 expression with clinicopathological variables in OSCC have been analyzed. MAC30 expression was immunohistochemically examined in 20 normal oral mucosa and 43 OSCC specimens. Results: Expression levels of MAC30 in the cytoplasm markedly increased from normal oral epithelial cells to primary OSCC. Strong cytoplasmic staining was significantly higher in primary OSCC compared to normal oral mucosa samples (51 vs. 20%, p = 0.019). Furthermore, MAC30 expression levels in primary tumors of patients with lymph node metastasis exceeded levels in those without metastasis (65 vs. 35%, p = 0.048), and MAC30 expression in poorly differentiated tumors was higher than in well-differentiated ones (90 vs. 39%, p = 0.005). Conclusion: Overexpression of MAC30 in the cytoplasm of OSCC may predict nodal metastasis and poor differentiation.
Guanidino Compounds as Cause of Cardiovascular Damage in Chronic Kidney Disease: An in vitro Evaluation
Authors: Schepers Eva , Glorieux Griet , Dou Laetitia , Cerini Claire , Gayrard Nathalie , Louvet Loïc , Maugard Charlotte , Preus Pierre , Rodriguez-Ortiz Maria , Argiles Angel , Brunet Philippe , Cohen Gerald , Jankowski Joachim , Jankowski Vera , Massy Ziad , Rodriguez Mariano , Vanholder Raymond ,   for the European Uremic Toxin Work Group (EUTox)
Published: November 2010

Chronic kidney disease is considered a major cause of cardiovascular risk and non-traditional risk factors remain largely unknown. The in vitro toxicity of 10 guanidino compounds (GCs) was evaluated via a standardized approach on different cell systems of relevance in cardiovascular disease. The parameters evaluated were production of reactive oxygen species, expression of surface molecules, cell proliferation, cytotoxicity and calcification. Several GCs had a stimulatory effect on monocytes and granulocytes (SDMA, creatine and guanidinobutyric acid (GBA)). Some GCs (guandine (G), guanidinosuccinic acid (GSA) and SDMA) inhibited endothelial cell proliferation or reduced calcification in osteoblast-like human VSMC (ADMA, GSA and SDMA). Stimulation of osteoclastogenesis could be demonstrated for ADMA, G, guanidinoacetic acid and GBA in a RAW264.7 cell line. No compounds were cytotoxic to AoSMC or endothelial cells, nor influenced their viability. GCs, especially SDMA, likely contribute to cardiovascular complications in uremia, mainly those related to microinflammation and leukocyte activation.
A Pilot Study Comparing Jejunal Pouch and Jejunal Interposition Reconstruction after Proximal Gastrectomy
Authors: Takagawa Ryo , Kunisaki Chikara , Kimura Jun , Makino Hirochika , Kosaka Takashi , Ono Hidetaka A. , Akiyama Hirotoshi , Endo Itaru
Published: November 2010

Background/Aims: The incidence of proximal gastric cancer is increasing, so proximal gastrectomies are often performed to preserve gastric function, but the optimal reconstruction method after surgery remains controversial. We therefore conducted a prospective pilot study comparing reconstructions using jejunal pouch interposition or jejunal interposition. Methods: Thirty-eight patients with early proximal gastric cancer were included in this study. Equal numbers of patients were randomly assigned for reconstruction using jejunal interposition (the IP group) or jejunal pouch interposition (the PO group). Postoperative morbidity and patient symptoms were compared between the 2 groups. Results: Postoperative morbidity was significantly more frequent in the IP than the PO group (p = 0.036). Moreover, the incidence of gastrointestinal complaints was more frequent in the IP group until 6 months after surgery. By contrast, the caloric intake was more favorable in the PO group until 1 year post-surgery. Conclusion: Short-term and mid-term outcomes were more favorable following jejunal pouch interposition compared with jejunal interposition after proximal gastrectomy.
Auditory Brainstem Response Changes during Exposure to GSM-900 Radiation: An Experimental Study
Authors: Kaprana Antigoni E. , Chimona Theognosia S. , Papadakis Chariton E. , Velegrakis Stylianos G. , Vardiambasis Ioannis O. , Adamidis Georgios , Velegrakis George A.
Published: November 2010

The objective of the present study was to investigate the possible electrophysiological time-related changes in auditory pathway during mobile phone electromagnetic field exposure. Thirty healthy rabbits were enrolled in an experimental study of exposure to GSM-900 radiation for 60 min and auditory brainstem responses (ABRs) were recorded at regular time-intervals during exposure. The study subjects were radiated via an adjustable power and frequency radio transmitter for GSM-900 mobile phone emission simulation, designed and manufactured according to the needs of the experiment. The mean absolute latency of waves III–V showed a statistically significant delay (p < 0.05) after 60, 45 and 15 min of exposure to electromagnetic radiation of 900 MHz, respectively. Interwave latency I–III was found to be prolonged after 60 min of radiation exposure in correspondence to wave III absolute latency delay. Interwave latencies I–V and III–V were found with a statistically significant delay (p < 0.05) after 30 min of radiation. No statistically significant delay was found for the same ABR parameters in recordings from the ear contralateral to the radiation source at 60 min radiation exposure compared with baseline ABR. The ABR measurements returned to baseline recordings 24 h after the exposure to electromagnetic radiation of 900 MHz. The prolongation of interval latencies I–V and III–V indicates that exposure to electromagnetic fields emitted by mobile phone can affect the normal electrophysiological activity of the auditory system, and these findings fit the pattern of general responses to a stressor.
Toll-Like Receptor 3 Polymorphism rs3775291 Is Not Associated with Choroidal Neovascularization or Polypoidal Choroidal Vasculopathy in Chinese Subjects
Authors: Sng Chelvin C.A. , Cackett Peter D. , Yeo Ian Y. , Thalamuthu Anbupalam , Venkatraman Anandalakshmi , Venkataraman Divya , Koh Adrian H. , Tai E-Shyong , Wong Tien Y. , Aung Tin , Vithana Eranga N.
Published: November 2010

Background/Aims: Age-related macular degeneration (AMD) is a leading cause of visual impairment. A single-nucleotide polymorphism (SNP; rs3775291) in the Toll-like receptor 3 (TLR3) gene has recently been implicated in the pathogenesis of AMD in Caucasian populations. The aim of this study was to examine this association in Chinese persons with choroidal neovascularization (CNV) secondary to AMD and polypoidal choroidal vasculopathy (PCV). Methods: This was an observational cross-sectional study in Singapore. Study subjects were of Chinese ethnicity and included patients with exudative maculopathy and normal control subjects. The diagnoses of CNV and PCV were made based on fundus examination, fluorescein angiography and indocyanine green angiography findings. Genomic DNA was extracted, and genotypes were determined by bidirectional DNA sequencing. We compared the allele and genotype frequencies between subjects with CNV and PCV with controls using the software PLINK. Results: A total of 246 subjects with exudative maculopathy (consisting of 126 with CNV and 120 with PCV) and 274 normal control subjects were recruited. The distribution of rs3775291 SNP genotypes for CNV and PCV was not significantly different from that for normal controls. Conclusion: This study indicates that the TLR3 rs3775291 gene polymorphism is not associated with CNV and PCV in Singaporean Chinese patients.
Bisphosphonates in Calcific Aortic Stenosis: Association with Slower Progression in Mild Disease – A Pilot Retrospective Study
Authors: Sterbakova Gabriela , Vyskocil Vaclav , Linhartova Katerina
Published: November 2010

Objectives: An association between aortic valve calcification and osteoporosis has been observed. The aim of this study was to assess the association between bisphosphonate treatment for osteoporosis and the progression of calcific aortic stenosis (AS). Methods: A retrospective study of patients with AS (mean gradient ≧10 mm Hg), preserved renal function and two echocardiographies >8 months apart was performed. The patients were divided into those treated with bisphosphonates for osteoporosis and those not treated and then subdivided into mild (mean gradient <30 mm Hg) and moderate-to-severe AS groups. We compared the annualized gradient change between the groups and identified predictors of AS progression. Results: We analyzed the outcomes of 103 patients (51% females, age 68 ± 10 years, follow-up 29 ± 13 months), of whom 57 had mild and 46 moderate-to-severe AS. Bisphosphonates were taken by 28 patients, of whom 22 had mild and 6 moderate-to-severe AS. In the patients with mild AS, the annualized mean gradient change was lower in the bisphosphonate-treated than in the untreated patients (0.1 ± 3.3 vs. 2.8 ± 3.3 mm Hg/year; p = 0.002) and was negatively associated with bisphosphonate treatment (β coefficient –2.36%, 95% confidence interval –4.47 to –0.26; p = 0.028) independent of age, gender and baseline gradient. Conclusion: Bisphosphonate treatment was independently associated with slower progression of mild AS in patients with preserved renal function.
Polymorphism Ala54Thr of Fatty Acid-Binding Protein 2: Allelic Frequencies and Influence on Cardiovascular Risk Factors in a Multicenter Study of Castilla y Leon
Authors: de Luis D.A. , Ballesteros M. , Ruiz E. , Cordero M. , Muñoz C. , Penacho M.A. , Iglesias P. , Lopez Guzman A. , Maldonado A. , San Martin L. , Puigdevall V. , Romero E. , Gonzalez Sagrado M. , Izaola O. , Conde R.
Published: November 2010

Background: A transition of guanin to alanin at codon 54 of the fatty acid-binding protein 2 gene (FABP2) results in an amino acid substitution (Ala54 to Thr54). This polymorphism was associated with some cardiovascular risk factors. Objective: The aim of our study was to investigate the influence of the Thr54 polymorphism in the FABP2 gene on obesity anthropometric parameters and cardiovascular risk factors in the fasted state in obese subjects and the allelic distribution of this polymorphism in a geographic area of Spain. Design: A population of 264 obese subjects was analyzed in a cross-sectional study from all health centers of Castilla y Leon (Spain). A nutritional and biochemical evaluation was performed. The statistical analysis was performed for the combined Ala54/Thr54 and Thr54/Thr54 genotype as a dominant model. Results: The mean age was 41.1 ± 13.1 years and the mean BMI 36.5 ± 5.9, with 94 males (35.6%) and 170 females (74.4%). One hundred and fifty-three subjects (58%) had the genotype Ala54/Ala54 (wild-type group) and 111 (42%) participants had the genotype Ala54/Thr54 (n = 92, 34.8%) or Thr54/Thr54 (n = 19, 7.2%) (mutant-type group). The health area of Valladolid had a lower frequency of wild-type genotype and Ala54 allelic frequency than all the other health areas of Castilla y Leon. C-reactive protein was higher in the mutant-type than the wild-type group (3.4 ± 5.6 vs. 7.9 ± 10.4 mg/dl; p < 0.05). Conclusion: The finding of this study is the association of the Thr54/Ala54 and Thr54/Thr54 FABP2 phenotypes with higher levels of C-reactive protein without relation to insulin resistance. Frequencies of this polymorphism are different among health areas of Castilla y Leon.
Initial Visual Acuity Is an Important Prognostic Factor in Patients with Branch Retinal Vein Occlusion
Authors: Rehak Jiri , Dusek Ladislav , Chrapek Oldrich , Fric Evzen , Rehak Matus
Published: November 2010

Purpose: To evaluate the role of initial visual acuity (VA) as a potential prognostic factor for final VA in patients with branch retinal vein occlusion (BRVO). Methods: A retrospective data analysis involving 163 patients with macular edema secondary to BRVO treated according to the recommendations of the Branch Vein Occlusion Study Group was performed using univariate and multivariate logistic regression models, and receiver-operating characteristics analysis. The analyses take factors into account that can potentially influence final visual result: sex, age, type of occlusion (major temporal or macular), grid photocoagulation and ischemia. Results: The final VA ≤0.1 was statistically significantly related to initial VA ≤0.16 and age >70 years. Sex, type of occlusion, grid photocoagulation and ischemia did not significantly influence the prediction of final VA based on age and initial VA. Conclusions: The analysis shows that initial VA and age >70 years significantly influence the prognosis for final visual results in patients with BRVO.
Short Adult Stature and Overweight Are Associated with Poor Intellectual Performance in Subjects Born Preterm
Authors: Lundgren E. Maria , Tuvemo Torsten , Gustafsson Jan
Published: November 2010

Background/Aims: To study the association between preterm birth and adult intellectual performance, with special emphasis on the influence of postnatal growth. Methods: A population-based cohort study was performed on 272,046 males, born between 1973 and 1978, of whom 248,447 were conscripted for military service between 1991 and 1997. Birth characteristics were obtained from the Swedish Medical Birth Register and information on intellectual performance, final height and BMI were taken from the Swedish Conscript Register. Multiple logistic regression analysis was performed. Results: At conscription, males born preterm had lower results at tests of intellectual performance compared to those born at term. Short adult stature among these males enhanced the risk of low intellectual performance, as compared to those with normal adult stature. Moreover, a high adult BMI in the males born preterm was associated with an increased risk of subnormal performance as compared to those with normal BMI. Conclusions: Subjects born preterm had poorer intellectual performance than those born at term. Short adult stature or a high BMI was associated with an even higher risk for poor intellectual performance in the subjects born preterm. This indicates the occurrence of common mechanisms underlying growth and cognitive development.
Translesional Pressure Gradients to Predict Blood Pressure Response After Renal Artery Stenting in Patients With Renovascular Hypertension
Authors: Mangiacapra Fabio , Trana Catalina , Sarno Giovanna , Davidavicius Giedrius , Protasiewicz Marcin , Muller Olivier , Ntalianis Argyrios , Misonis Nerijus , Van Vlem Bruno , Heyndrickx Guy R. , De Bruyne Bernard
Published: November 2010

Background—

In previous studies on the effect of renal stenting on arterial hypertension, patients were selected mainly on the basis of angiographic parameters of the renal artery stenosis. The aim of the present study was to evaluate whether translesional pressure gradients could identify the patients with renal artery stenosis who might benefit from stenting.

Methods and Results—

A total of 53 consecutive hypertensive patients with unilateral RAS scheduled for renal artery intervention were recruited. Transstenotic pressure gradients were measured at baseline and during maximal hyperemia, before renal artery stenting. Twenty-four-hour ambulatory blood pressure measurements were performed in all patients before and 3 months after the intervention. Average reductions in systolic blood pressure and diastolic blood pressure at follow-up were −20±30 mm Hg and −2±12 mm Hg, respectively. At multivariate analysis, dopamine-induced mean gradient was the only independent predictor of the variations of both systolic blood pressure (regression coefficient=−4.03, standard error=1.11;
P
<0.001) and diastolic blood pressure (regression coefficient=−3.11, standard error=1.20;
P
=0.009). Patients who showed a decline in systolic blood pressure from the baseline value >20 mm Hg were considered as “responders.” The optimal cutoff for identification of “responders” was a dopamine-induced mean gradient ≥20 mm Hg (area under the curve, 0.77; 95% confidence interval, 0.64 to 0.90;
P
=0.001).

Conclusions—

A dopamine-induced mean pressure gradient of ≥20 mm Hg is highly predictive of arterial hypertension improvement after renal stenting, and therefore this measurement is useful for appropriate selection of patients with arterial hypertension.
Variation in Recovery
Authors: Lichtman Judith H. , Lorenze Nancy P. , D'Onofrio Gail , Spertus John A. , Lindau Stacy T. , Morgan Thomas M. , Herrin Jeph , Bueno Héctor , Mattera Jennifer A. , Ridker Paul M. , Krumholz Harlan M.
Published: November 2010

Background—

Among individuals with ischemic heart disease, young women with an acute myocardial infarction (AMI) represent an extreme phenotype associated with an excess mortality risk. Although women younger than 55 years of age account for less than 5% of hospitalized AMI events, almost 16 000 deaths are reported annually in this group, making heart disease a leading killer of young women. Despite a higher risk of mortality compared with similarly aged men, young women have been the subject of few studies.

Methods and Results—

Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) is a large, observational study of the presentation, treatment, and outcomes of young women and men with AMI. VIRGO will enroll 2000 women, 18 to 55 years of age, with AMI and a comparison cohort of 1000 men with AMI from more than 100 participating hospitals. The aims of the study are to determine sex differences in the distribution and prognostic importance of biological, demographic, clinical, and psychosocial risk factors; to determine whether there are sex differences in the quality of care received by young AMI patients; and to determine how these factors contribute to sex differences in outcomes (including mortality, hospitalization, and health status). Blood serum and DNA for consenting participants will be stored for future studies.

Conclusions—

VIRGO will seek to identify novel and prognostic factors that contribute to outcomes in this young AMI population. Results from the study will be used to develop clinically useful risk-stratification models for young AMI patients, explain sex differences in outcomes, and identify targets for intervention.
Prevalence and Clinical Significance of Papillary Muscle Infarction Detected by Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Tanimoto Takashi , Imanishi Toshio , Kitabata Hironori , Nakamura Nobuo , Kimura Keizo , Yamano Takashi , Ishibashi Kohei , Komukai Kenichi , Ino Yasushi , Takarada Shigeho , Kubo Takashi , Hirata Kumiko , Mizukoshi Masato , Tanaka Atsushi , Akasaka Takashi
Published: November 2010

Background—

The frequency of papillary muscle infarction (PapMI) without rupture has not been fully investigated in vivo. Furthermore, the relationship between papillary muscle dysfunction and mitral regurgitation (MR) has been controversial in patients with ST-segment elevation myocardial infarction. Therefore, the aim of this study was to assess the frequency and clinical characteristics of PapMI without rupture using late gadolinium-enhanced magnetic resonance imaging (MRI) in patients with ST-segment elevation myocardial infarction.

Methods and Results—

One hundred eighteen ST-segment elevation myocardial infarction patients with primary percutaneous coronary intervention underwent cardiac MRI twice 9±4 days and 8±1 months (n=104) after myocardial infarction. MR was categorized by echocardiography. Of these patients, 40% were found to have late gadolinium enhancement of papillary muscle, in which the posterior papillary muscle was involved more frequently than the anterior papillary muscle (77% versus 26%;
P
<0.001). PapMI was encountered more frequently in patients with left circumflex and right coronary artery lesions compared with left anterior descending artery lesion (78%, 48%, and 13%;
P
<0.001). By multiple logistic regression analysis, only coaptation height was identified as an independent predictor of the presence of MR. The second cardiac magnetic resonance imaging showed that the infarct size had a positive correlation with left ventricular end-diastolic volume (
r
=0.41,
P
<0.001) and that PapMI was not associated with left ventricular remodeling (
P
=0.31). Deterioration of MR was not observed in patients with PapMI.

Conclusions—

PapMI is more frequent than previously thought yet appears to have significant clinical latency. The size of the myocardial infarction, but not the presence of PapMI, seems to affect left ventricular remodeling, and PapMI is not obligatorily associated with MR.
Adverse Bioenergetic Consequences of Na
+
-Ca
2+
Exchanger–Mediated Ca
2+
Influx in Cardiac Myocytes
Authors: Kohlhaas Michael , Maack Christoph
Published: November 2010

Background—

In heart failure, the Na
+
-Ca
2+
exchanger (NCX) is upregulated and mediates Ca
2+
influx (instead of efflux) during the cardiac action potential. Although this partly compensates for impaired sarcoplasmic reticulum Ca
2+
release and supports inotropy, the energetic consequences have never been considered. Because NCX-mediated Ca
2+
influx is rather slow and mitochondrial Ca
2+
uptake (which stimulates NADH production by the Krebs cycle) is thought to be facilitated by high Ca
2+
gradients in a “mitochondrial Ca
2+
microdomain,” we speculated that NCX-mediated Ca
2+
influx negatively affects the bioenergetic feedback response.

Methods and Results—

With the use of a patch-clamp–based approach in guinea-pig myocytes, cytosolic and mitochondrial Ca
2+
([Ca
2+
]
c
and [Ca
2+
]
m
, respectively) was determined within the same cell after varying Ca
2+
influx via L-type Ca
2+
channels (
I
Ca,L
) or the NCX. The efficiency of mitochondrial Ca
2+
uptake, indexed by the slope of plotting [Ca
2+
]
m
against [Ca
2+
]
c
during each Ca
2+
transient, was maximal during
I
Ca,L
-triggered sarcoplasmic reticulum Ca
2+
release. Depletion of sarcoplasmic reticulum Ca
2+
load and increased contribution of the NCX to cytosolic Ca
2+
influx independently reduced the efficiency of mitochondrial Ca
2+
uptake. The upstroke velocity of cytosolic Ca
2+
transients closely correlated with the efficiency of mitochondrial Ca
2+
uptake. Despite comparable [Ca
2+
]
c
, sarcoplasmic reticulum Ca
2+
release, but not NCX-mediated Ca
2+
influx, led to stimulation of Ca
2+
-sensitive dehydrogenases of the Krebs cycle.

Conclusions—

Increased contribution of the NCX to cytosolic Ca
2+
transients, which occurs in cardiac myocytes from failing hearts, impairs mitochondrial Ca
2+
uptake and the bioenergetic feedback response. This mechanism could contribute to energy starvation of failing hearts.
Primary Results From the SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) Trial
Authors: Ellenbogen Kenneth A. , Gold Michael R. , Meyer Timothy E. , Fernndez Lozano Ignacio , Mittal Suneet , Waggoner Alan D. , Lemke Bernd , Singh Jagmeet P. , Spinale Francis G. , Van Eyk Jennifer E. , Whitehill Jeffrey , Weiner Stanislav , Bedi Maninder , Rapkin Joshua , Stein Kenneth M.
Published: November 2010

Background

One variable that may influence cardiac resynchronization therapy response is the programmed atrioventricular (AV) delay. The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) Trial prospectively randomized patients to a fixed empirical AV delay (120 milliseconds), echocardiographically optimized AV delay, or AV delay optimized with SmartDelay, an electrogram-based algorithm.

Methods and Results

A total of 1014 patients (68% men; mean age, 66±11 years; mean left ventricular ejection fraction, 25±7%) who met enrollment criteria received a cardiac resynchronization therapy defibrillator, and 980 patients were randomized in a 1:1:1 ratio. All patients were programmed (DDD-60 or DDDR-60) and evaluated after implantation and 3 and 6 months later. The primary end point was left ventricular end-systolic volume. Secondary end points included New York Heart Association class, quality-of-life score, 6-minute walk distance, left ventricular end-diastolic volume, and left ventricular ejection fraction. The medians (quartiles 1 and 3) for change in left ventricular end-systolic volume at 6 months for the SmartDelay, echocardiography, and fixed arms were −21 mL (−45 and 6 mL), −19 mL (−45 and 6 mL), and −15 mL (−41 and 6 mL), respectively. No difference in improvement in left ventricular end-systolic volume at 6 months was observed between the SmartDelay and echocardiography arms (
P
=0.52) or the SmartDelay and fixed arms (
P
=0.66). Secondary end points, including structural (left ventricular end-diastolic volume and left ventricular ejection fraction) and functional (6-minute walk, quality of life, and New York Heart Association classification) measures, were not significantly different between arms.

Conclusions

Neither SmartDelay nor echocardiography was superior to a fixed AV delay of 120 milliseconds. The routine use of AV optimization techniques assessed in this trial is not warranted. However, these data do not exclude possible utility in selected patients who do not respond to cardiac resynchronization therapy.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
Unique identifier: NCT00677014.
Predictive Role of the Nighttime Blood Pressure
Authors: Hansen Tine W. , Li Yan , Boggia José , Thijs Lutgarde , Richart Tom , Staessen Jan A.
Published: November 2010

Numerous studies addressed the predictive value of the nighttime blood pressure (BP) as captured by ambulatory monitoring. However, arbitrary cutoff limits in dichotomized analyses of continuous variables, data dredging across selected subgroups, extrapolation of cross-sectional studies to prospective outcomes, and lack of comprehensive adjustments for confounders make interpretation of the literature difficult. We reviewed prospective studies with total mortality or a composite cardiovascular end point as an outcome in relation to the level and the circadian profile of systolic BP. We analyzed studies in hypertensive patients (n=23 856) separately from those in individuals randomly recruited from populations (n=9641). We pooled summary statistics and individual subject data, respectively. In both patients and populations, in analyses in which nighttime BP was additionally adjusted for daytime BP and vice versa, nighttime BP was a stronger predictor than daytime BP. With adjustment for the 24-hour BP, both the night-to-day BP ratio and dipping status remained significant predictors of outcome but added little prognostic value over and beyond the 24-hour BP level. In the absence of conclusive evidence proving that nondipping is a reversible risk factor, the option whether or not to restore the diurnal blood pressure profile to a normal pattern should be left to the clinical judgment of doctors and should be individualized for each patient. Current guidelines on the interpretation of ambulatory BP recording need to be updated.
MMP-2 Mediates Angiotensin II–Induced Hypertension Under the Transcriptional Control of MMP-7 and TACE
Authors: Odenbach Jeffrey , Wang Xiang , Cooper Stephan , Chow Fung Lan , Oka Tatsujiro , Lopaschuk Gary , Kassiri Zamaneh , Fernandez-Patron Carlos
Published: November 2010

Development of cardiovascular disease induced by excessive Gq protein–coupled receptor agonist stimulation depends on signaling networks involving multiple matrix metalloproteinases (MMPs) and metalloproteinase disintegrins (ADAMs). Here, we hypothesized that MMP-2, being a major gelatinase in cardiac and vascular tissue, was likely to play a key role in cardiovascular homeostasis. We targeted MMP-2 using complementary and overlapping approaches involving pharmacological inhibition and RNA interference in mice treated with angiotensin II (1.4 mg/kg per day) for 12 days. We studied the development of hypertension (by tail cuff plethysmography), cardiac hypertrophy (by M-mode echocardiography, cardiomyocyte cross-sectional area, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis of hypertrophy marker genes), and fibrosis (by picrosirius red collagen staining and qRT-PCR analysis of fibrosis marker genes) in mice receiving angiotensin II. We found that angiotensin II infusion upregulated MMP-2 concurrent with the development of hypertension, hypertrophy, and fibrosis. This upregulation of MMP-2 depended on MMP-7 and TACE (tumor necrosis factor-α convertase, ADAM-17). RNA interference targeting MMP-7 and TACE attenuated the angiotensin II–induced upregulation of MMP-2 and prevented the development of hypertension, as well as development of cardiac hypertrophy and fibrosis. In contrast, pharmacological inhibition and RNA interference of MMP-2 attenuated angiotensin II–induced hypertension, without influencing development of cardiac hypertrophy or fibrosis. Downstream of MMP-7 and TACE, MMP-2 mediated angiotensin II–induced hypertension, but did not mediate cardiac hypertrophy or fibrosis. This suggests a functional specialization of MMP-2 in agonist–induced cardiovascular disease development that has potential implications for the design of metalloproteinase-based therapeutic strategies.
Association Between Placental Morphology and Childhood Systolic Blood Pressure
Authors: Wen Xiaozhong , Triche Elizabeth W. , Hogan Joseph W. , Shenassa Edmond D. , Buka Stephen L.
Published: November 2010

We tested hypotheses that disproportionately large placental size and vascular lesions were associated with high systolic blood pressure (SBP); and these associations might be more evident with age. The sample included 13 273 of 40 666 full-term singletons in the Collaborative Perinatal Project. Placentas were examined by pathologists blinded of pregnancy courses and outcomes. The 4-month and 7-year SBPs were measured with palpation and auscultation methods, respectively. We found that placental weight (adjusted mean difference corresponding to an increase by 1 SD 0.50 [95% CI, 0.33 to 0.68]) and placenta–fetus weight ratio (0.37 [95% CI, 0.19 to 0.54]) was positively associated with 7-year SBP but not associated with 4-month SBP. Placental largest and smallest diameters and area were negatively associated with 4-month SBP but positively with 7-year SBP. Placental thickness was negatively associated with 4-month SBP only. Placental volume was negatively associated with 4-month SBP (−0.60 [95% CI, − 0.85 to −0.35]) but positively associated with 7-year SBP (0.48 [95% CI, 0.30 to 0.67]). Thrombi in cord vessels (adjusted mean difference versus absence 2.73 [95% CI, − 0.03 to 5.50]) and decidual vessels (2.58 [95% CI, 0.24 to 4.91]), villous microinfarcts (1.63 [95% CI, 0.71 to 2.55]), necrosis at the decidual margin (1.57 [95% CI, 0.54 to 2.59]), and basalis (3.44 [95% CI, 1.55 to 5.32]) were associated with higher 4-month SBP only. We conclude that placental inefficiency, reflected by disproportionately large weight and size, predicts long-term blood pressure, whereas vascular resistance and lesions may only influence short-term blood pressure.
Risk Aversion and Support for Merit Pay: Theory and Evidence from Minnesota's Q Comp Program
Authors: Nadler Carl , Wiswall Matthew
Published: November 2010

Recent research attributes the lack of merit pay in teaching to the resistance of teachers. This article examines whether the structure of merit pay affects the types of teachers who support it. We develop a model of the relative utility teachers receive from merit pay versus the current fixed schedule of raises. We show that if teachers are risk averse, teachers with higher base salaries would be more likely to support a merit pay program that allows them to keep their current base salary and risk only future salary increases. We test the predictions of the model using data from a new merit pay program, the Minnesota Q Comp program, which requires the approval of the teachers in each school district. Consistent with the model's predictions, we find that districts with higher base salaries and a higher proportion of teachers with master's degrees are more likely to approve merit pay.
Long-Run Trends in School Productivity: Evidence from Australia
Authors: Leigh Andrew , Ryan Chris
Published: November 2010

Outside the United States, very little is known about long-run trends in school productivity. We present new evidence using two data series from Australia, where comparable tests are available back to the 1960s. For young teenagers (aged 13–14), we find a small but statistically significant fall in numeracy over the period 1964–2003 and in both literacy and numeracy over the period 1975–98. The decline is in the order of one-tenth to one-fifth of a standard deviation. Adjusting this decline for changes in student demographics does not affect this conclusion; if anything, the decline appears to be more acute. The available evidence also suggests that any changes in student attitudes, school violence, and television viewing are unlikely to have had a major impact on test scores. Real per child school expenditure increased substantially over this period, implying a fall in school productivity. Although we cannot account for all the phenomena that might have affected school productivity, we identify a number of plausible explanations.
The Helsinki Testbed: A Mesoscale Measurement, Research, and Service Platform
Authors: Koskinen Jarkko T. , Poutiainen Jani , Schultz David M. , Joffre Sylvain , Koistinen Jarmo , Saltikoff Elena , Gregow Erik , Turtiainen Heikki , Dabberdt Walter F. , Damski Juhani , Eresmaa Noora , Göke Sabine , Hyvärinen Otto , Järvi Leena , Karppinen Ari , Kotro Janne , Kuitunen Timo , Kukkonen Jaakko , Kulmala Markku , Moisseev Dmitri , Nurmi Pertti , Pohjola Heikki , Pylkkö Pirkko , Vesala Timo , Viisanen Yrjö
Published: November 2010

The Finnish Meteorological Institute and Vaisala have established a mesoscale weather observational network in southern Finland. The Helsinki Testbed is an open research and quasi-operational program designed to provide new information on observing systems and strategies, mesoscale weather phenomena, urban and regional modeling, and end-user applications in a high-latitude (~60°N) coastal environment. The Helsinki Testbed and related programs feature several components: observing system design and implementation, small-scale data assimilation, nowcasting and short-range numerical weather prediction, public service, and commercial development of applications. Specifically, the observing instrumentation focuses on meteorological observations of meso-gamma-scale phenomena that are often too small to be detected adequately by traditional observing networks. In particular, more than 40 telecommunication masts (40 that are 120 m high and one that is 300 m high) are instrumented at multiple heights. Other instrumentation includes one operational radio sounding (and occasional supplemental ones), ceilometers, aerosol-particle and trace-gas instrumentation on an urban flux-measurement tower, a wind profiler, and four Doppler weather radars, three of which have dual-polarimetric capability. The Helsinki Testbed supports the development and testing of new observational instruments, systems, and methods during coordinated field experiments, such as the NASA Global Precipitation Measurement (GPM). Currently, the Helsinki Testbed Web site typically receives more than 450,000 weekly visits, and more than 600 users have registered to use historical data records. This article discusses the three different phases of development and associated activities of the Helsinki Testbed from network development and observational campaigns, development of the local analysis and prediction system, and testing of applications for commercial services. Finally, the Helsinki Testbed is evaluated based on previously published criteria, indicating both successes and shortcomings of this approach.
The History (and Future) of Tornado Warning Dissemination in the United States
Authors: Coleman Timothy A. , Knupp Kevin R. , Spann James , Elliott J. B. , Peters Brian E.
Published: November 2010

Since the successful tornado forecast at Tinker AFB in 1948 paved the way for the issuance of tornado warnings, the science of tornado detection and forecasting has advanced greatly. However, tornado warnings must be disseminated to the public to be of any use. The Texas tornado warning conferences in 1953 began to develop the framework for a modern tornado warning system and included radar detection of tornadoes, a spotter network, and improved communications between the U.S. Weather Bureau, spotters, and public officials, allowing more timely warnings and dissemination of those warnings to the public.

Commercial radio and television are a main source of warnings for many, and the delivery methods on TV have changed much since 1960. NOAA Weather Radio (NWR) was launched after the 1974 Super Outbreak of tornadoes, with the most important feature being the tone alert that allowed receivers to alert people even when the radio broadcast was turned off. Today, NWR reaches most of the U.S. population, and Specific Area Message Encoding technology has improved its warning precision. Outdoor warning sirens, originally designed for use in enemy attack, were made available for use during tornado warnings around 1970.

“Storm based” warnings, adopted by the National Weather Service in 2007, replaced countybased warnings and greatly reduce the warning area. As communications advances continue, tornado warnings will eventually be delivered to precise locations, using GPS and other location technology, through cellular telephones, outdoor sirens, e-mails, and digital television, in addition to NWR.
Statistical Reliability of Neighboring Range Bin Estimates of Coherent Fractional Contributions to Radar Backscattered Power
Authors: Jameson A. R.
Published: November 2010

It was recently demonstrated that magnitudes of the power-normalized cross-correlation functions of complex amplitudes in neighboring range bins are identical to the fractional contributions made by radar coherent backscatter in the direction of propagation to the total backscattered power in rain and snow. Here, a theoretical framework is presented for calculating the noise associated with estimates of these normalized cross correlations. This noise is identical to the statistical uncertainties in . Radar signals consist of two components: the usual incoherent backscatter often modeled by a Gaussian process and a coherent component modeled for the purposes of these calculations by a phasor C of fixed magnitude that rotates at a constant angular velocity ωC. Using the representation of the cross-correlation function as the average over the real part of the phasor dot products, it is found that the noise in this function comes from the dot products of C with the incoherent-scatter phasors in each range bin as well as the dot product between the two incoherent phasors. Furthermore, as long as ωC ≠ 0 and the number of statistically independent realizations (samples) k is sufficiently large, the noise is represented well by a normal distribution with mean 0 and with a variance that goes as 1/(2k). It is then shown that as the magnitude of C increases it acts to suppress the variance of . A formula is derived that gives the standard deviation of as a function of the number of statistically independent samples in the observation and the observed value of . Two examples, one in rain and the other in snow, are also presented.
Characterizing the Variability and Extremes of the Stratospheric Polar Vortices Using 2D Moment Analysis
Authors: Mitchell Daniel M. , Charlton-Perez Andrew J. , Gray Lesley J.
Published: November 2010

The mean state, variability, and extreme variability of the stratospheric polar vortices, with an emphasis on the Northern Hemisphere (NH) vortex, are examined using two-dimensional moment analysis and extreme value theory (EVT). The use of moments as an analysis tool gives rise to information about the vortex area, centroid latitude, aspect ratio, and kurtosis. The application of EVT to these moment-derived quantities allows the extreme variability of the vortex to be assessed. The data used for this study are 40-yr ECMWF Re-Analysis (ERA-40) potential vorticity fields on interpolated isentropic surfaces that range from 450 to 1450 K.

Analyses show that the most extreme vortex variability occurs most commonly in late January and early February, consistent with when most planetary wave driving from the troposphere is observed. Composites around sudden stratospheric warming (SSW) events reveal that the moment diagnostics evolve in statistically different ways between vortex splitting events and vortex displacement events, in contrast to the traditional diagnostics. Histograms of the vortex diagnostics on the 850-K (~10 hPa) surface over the 1958–2001 period are fitted with parametric distributions and show that SSW events constitute the majority of data in the tails of the distributions. The distribution of each diagnostic is computed on various surfaces throughout the depth of the stratosphere; it shows that in general the vortex becomes more circular with higher filamentation at the upper levels. The Northern and Southern Hemisphere (SH) vortices are also compared through the analysis of their respective vortex diagnostics, confirming that the SH vortex is less variable and lacks extreme events compared to the NH vortex. Finally, extreme value theory is used to statistically model the vortex diagnostics and make inferences about the underlying dynamics of the polar vortices.
Short-Wave Signatures of Stratospheric Mountain Wave Breaking
Authors: Woods Bryan K. , Smith Ronald B.
Published: November 2010

Recent stratospheric mountain wave measurements over the Sierra Nevada indicate that downgoing secondary waves may be common or even ubiquitous in large wave events. Because of their short wavelengths, they may dominate the vertical velocity field near the tropopause, and they give a remote indicator of wave breaking farther aloft. Using a 2D numerical model, the authors have simulated the secondary wave generation process with qualitative agreement in the wave location, phase speed, wavelength (i.e., 10–20 km), and amplitude. A key to the analysis was the use of Morlet wavelet cross spectra on both the observational and simulated fields.

Several characteristics of the simulated secondary waves were unexpected. First, the secondary waves are generated with good efficiency, approaching 20% of the primary upgoing wave momentum flux. Second, whereas most of the secondary waves are downward, the shorter components reflect upward from the tropopause, giving a kind of lee wave trapping in the lower stratosphere. Long waves are also observed propagating upward and downward away from the wave breaking region. Third, the phase speed of the secondary waves is nearly zero so the Eliassen–Palm relationship between momentum and energy flux is satisfied. While the 2D results are robust to grid size and subgrid parameterization, an extension of the modeling to three dimensions is disappointing. The secondary waves’ amplitudes in the 3D runs are much smaller than observed.
Climate Variability and the Shape of Daily Precipitation: A Case Study of ENSO and the American West
Authors: Feldl Nicole , Roe Gerard H.
Published: November 2010

Characterizing the relationship between large-scale atmospheric circulation patterns and the shape of the daily precipitation distribution is fundamental to understanding how dynamical changes are manifest in the hydrological cycle, and it is also relevant to issues such as natural hazard mitigation and reservoir management. This relationship is pursued using ENSO variability and the American West as a case study. When considering the full range of wintertime precipitation and consistent with conventional wisdom, mean precipitation intensity is enhanced during El Niño relative to La Niña in the Southwest and vice versa in the Northwest. This change in mean is attributed to a shift in the distribution of daily precipitation toward more intense daily rainfall rates. In addition, fundamental changes in the shape of the precipitation distributions are observed, independent of shifts in the mean. Surprisingly, for intense precipitation, La Niña winters actually demonstrate a significant increase in intensity (but not frequency) across the Southwest. A main lesson from this analysis is that, in response to ENSO variability, changes in extreme events can be significantly different from changes in the mean. In some instances, even the sign of the change is reversed. This result suggests that patterns of large-scale variability have an effect on the precipitation distribution that is nuanced, and they cannot be regarded as simply causing a shift in climatic zones. It also raises interesting questions concerning how best to establish confidence in climate predictions.