bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation Transcription Factor-4 Induced by Fibroblast Growth Factor-2 Regulates Vascular Endothelial Growth Factor-A Transcription in Vascular Smooth Muscle Cells and Mediates Intimal Thickening in Rat Arteries Following Balloon Injury
Authors: Malabanan Kristine P. , Kanellakis Peter , Bobik Alexander , Khachigian Levon M.
Published: July 2008

Activation transcription factor (ATF)-4 is a member of the ATF/CREB family of basic leucine zipper transcription factors that regulates cellular responses to a variety of stresses. The role of ATF-4 in smooth muscle cells of the vessel wall is completely unknown. Here, we show that ATF-4 expression is induced in smooth muscle cells in response to injury, both in vitro using a model of mechanical injury and in the media of balloon-injured rat carotid arteries. We demonstrate that ATF-4 is activated by fibroblast growth factor (FGF)-2, an injury-induced mitogen, through the phosphatidylinositol 3-kinase pathway. Injury also activates vascular endothelial growth factor (VEGF)-A, whose expression is stimulated by ATF-4 overexpression and exposure to FGF-2. FGF-2 induces ATF-4 binding to a recognition element located in the VEGF-A gene at +1767 bp and luciferase reporter gene expression dependent on this site. Moreover, ATF-4 knockdown with small interfering RNA or ATF-4 deficiency ameliorates FGF-2–inducible VEGF-A expression. Intraluminal delivery of ATF-4 small interfering RNA in rat carotid arteries blocks balloon injury–inducible ATF-4 and VEGF-A expression after 4 hours and intimal thickening after 14 days. These findings reveal, for the first time, the induction of ATF-4 by both vascular injury and FGF-2. ATF-4 serves as a conduit for the inducible expression of 1 growth factor by another during the process of intimal thickening.
Homotypic and Endothelial Cell Adhesions via N-Cadherin Determine Polarity and Regulate Migration of Vascular Smooth Muscle Cells
Authors: Sabatini Peter J.B. , Zhang Ming , Silverman-Gavrila Rosalind , Bendeck Michelle P. , Langille B. Lowell
Published: July 2008

Migration of smooth muscle cells from the arterial media to the intima is central to several vascular pathologies including restenosis. This study demonstrates that, like directional migration of other cells, smooth muscle migration is accompanied by a dramatic, polarized reorganization of the cell cytoskeleton that is accompanied by activation of the Rho GTPase Cdc42 and inactivation of glycogen synthase kinase-3β. We also show, for the first time, that signals generated at the posterior–lateral aspects of wound edge cells by the cell–cell adhesion molecule N-cadherin are required for polarization and rapid migration of vascular smooth muscle. Importantly, when a cohort of migrating smooth muscle cells encounter CHO cells or the A10 smooth muscle cell line, neither of which expresses N-cadherin, polarity is only slightly suppressed. However, when smooth muscle cells encounter stably transfected, N-cadherin–expressing A10 cells or (N-cadherin–expressing) vascular endothelium, they rapidly lose their polarized phenotype. The latter finding indicates that endothelial signaling to innermost smooth muscle cells via N-cadherin may be critical to normal vessel wall stability. We infer that asymmetrical distribution of N-cadherin is necessary for the establishment of cell polarity during migration and that N-cadherin ligation is highly effective in abrogating polarized migration. Finally, we showed that endothelial cell polarity does not depend on N-cadherin; therefore, this molecule may be an attractive target for therapies to prevent restenosis without suppressing endothelial repair and risking late thrombosis.
Cardiovascular and Hematopoietic Defects Associated With Notch1 Activation in Embryonic Tie2-Expressing Populations
Authors: Venkatesh Deepak A. , Park Kyung-Sook , Harrington Anne , Miceli-Libby Laura , Yoon Jeong K. , Liaw Lucy
Published: July 2008

Notch signaling is critical for the development and maintenance of the cardiovasculature, with loss-of-function studies defining roles of Notch1 in the endothelial/hematopoietic lineages. No in vivo studies have addressed complementary gain-of-function strategies within these tissues to define consequences of Notch activation. We developed a transgenic model of Cre recombinase–mediated activation of a constitutively active mouse Notch1 allele (N1ICD
+
) and studied transgene activation in Tie2-expressing lineages. The in vivo phenotype was compared to effects of Notch1 activation on endothelial tubulogenesis, paracrine regulation of smooth muscle cell proliferation, and hematopoiesis. N1ICD
+
embryos showed midgestation lethality with defects in angiogenic remodeling of embryonic and yolk sac vasculature, cardiac development, smooth muscle cell investment of vessels, and hematopoietic differentiation. Angiogenic defects corresponded with impaired endothelial tubulogenesis in vitro following Notch1 activation and paracrine inhibition of smooth muscle cells when grown with Notch1-activated endothelial cells. Flow cytometric analysis of hematopoietic and endothelial precursor populations demonstrated a significant loss of CD71
+
/Ter119
+
populations with an active N1ICD
+
allele and a corresponding increase in c-Kit
+
/CD71 and Flk1
+
populations, suggesting a developmental block during the transition between c-Kit– and Ter119-expressing erythroblasts. Cardiovascular lineages are sensitive to an imbalance in Notch signaling, with aberrant activation reflecting a vascular phenotype comparable to a loss-of-function Notch1 mutation.
Impact of Anatomic Features in the Endovascular Embolization of 181 Anterior Communicating Artery Aneurysms
Authors: Gonzalez Nestor , Sedrak Mark , Martin Neil , Vinuela Fernando
Published: July 2008

Background and Purpose—

We analyzed the impact of detailed anatomic characteristics on the results of endovascular coil embolization for anterior communicating artery (AcoA) aneurysms and developed a predictive model estimating the probability of successful endovascular treatment.

Methods—

One hundred eighty-one AcoA aneurysms were treated with endovascular coil embolization between August 1991 and November 2005. Morphological characteristics that were analyzed included direction of the dome, location of the neck, association with hypoplasia or aplasia of AcoA complex vessels, sac, and neck size. Immediate clinical and anatomic results, long-term morbidity/mortality, recanalization rate, and delayed aneurysm thrombosis were analyzed. ORs were calculated for each anatomic and clinical result and logistic regression was used in formulating a predictive model.

Results—

There were 115 females and 66 males. Age range was 9 to 86 years (mean 57). Factors significantly associated with complete embolization included small aneurysms (<10 mm), small neck (<4 mm), and anterior dome orientation. Factors significantly associated with aneurysm recanalization after long-term follow-up included aneurysm domes >10 mm, neck location on the AcoA, posterior dome orientation, and incomplete original embolization. Globally, the majority of patients remained neurologically intact or unchanged after the procedure (92.8%). Mortality was significantly influenced by the preoperative condition of the patient. The predictive model successfully represented the likely outcomes based on morphological features.

Conclusions—

AcoA aneurysm coil embolization can be safely performed with acceptable rates of morbidity. Dome and neck orientation, sack and neck size, sac-to-neck ratio, and associated anomalies should be considered to accurately assess the probability of successful treatment for AcoA aneurysms.
Effectiveness of PSD95 Inhibitors in Permanent and Transient Focal Ischemia in the Rat
Authors: Sun Hong-Shuo , Doucette Tracy A. , Liu Yitao , Fang Yuan , Teves Lucy , Aarts Michelle , Ryan Catherine L. , Bernard Paul B. , Lau Anthony , Forder Joan P. , Salter Michael W. , Wang Yu Tian , Tasker R. Andrew , Tymianski Michael
Published: July 2008

Background and Purpose—

Postsynaptic density-95 inhibitors reduce ischemic brain damage without inhibiting excitatory neurotransmission, circumventing the negative consequences of glutamatergic inhibition. However, their efficacy in permanent ischemia and in providing permanent neuroprotection and neurobehavioral improvement in a practical therapeutic window is unproven. These were tested here under conditions that included fever, which is a common occurrence in clinical stroke.

Methods—

Six studies were performed in unfasted Sprague-Dawley rats. Two involved permanent pial vessel occlusion in male and female rats. Two involved permanent middle cerebral artery occlusion, which induced severe hyperthermia, and 2 involved transient middle cerebral artery occlusion. Animals were treated with a single intravenous injection of postsynaptic density-95 inhibitors (Tat-NR2B9c
[SDV]
or Tat-NR2B9c
[TDV]
) 1 hour or 3 hours after stroke. Infarct volumes and neurobehavior were assessed in a blinded manner at 24 hours (pial vessel occlusion and permanent middle cerebral artery occlusion) or at 62 days (transient middle cerebral artery occlusion).

Results—

Postsynaptic density-95 inhibitors dramatically reduced infarct size in male and female animals exposed to pial vessel occlusion (>50%), in hyperthermic animals with fever exceeding 39°C exposed to permanent middle cerebral artery occlusion (approximately 50%), and at 62 days poststroke in animals exposed to transient middle cerebral artery occlusion (approximately 80%). Effectiveness of postsynaptic density-95 inhibitors was achieved without the drugs affecting body temperature. In transient middle cerebral artery occlusion, a single dose of postsynaptic density-95 inhibitor given 3 hours after stroke onset permanently maintained reduced infarct size and improved neurobehavior.

Conclusions—

Postsynaptic density-95 inhibitors administrated 3 hours after stroke onset reduced infarct volumes and improved long-term neurobehavioral functions in a wide therapeutic window. This raises the possibility that they may have future clinical usefulness.
Choline and Creatine Are Not Reliable Denominators for Calculating Metabolite Ratios in Acute Ischemic Stroke
Authors: Muñoz Maniega Susana , Cvoro Vera , Armitage Paul A. , Marshall Ian , Bastin Mark E. , Wardlaw Joanna M.
Published: July 2008

Background and Purpose—

Choline and creatine are commonly used as denominators for other metabolites in ischemic stroke spectroscopy, assuming that they do not change. We investigated their concentration variation over time after stroke.

Methods—

Choline and creatine concentrations were measured by proton MR spectroscopic imaging in 51 patients at 5 times up to 3 months after stroke.

Results—

Choline and creatine levels changed significantly in the ischemic region. Choline was significantly reduced during the first 2 weeks after stroke onset (
P
=0.034). Creatine was significantly reduced during the whole period of the study (
P
=0.011).

Conclusion—

Choline and creatine concentrations are not reliable denominators for metabolite ratios in acute stroke because their levels vary significantly in ischemic brain regions.
Escalating Levels of Access to In-Hospital Care and Stroke Mortality
Authors: Saposnik Gustavo , Fang Jiming , O'Donnell Martin , Hachinski Vladimir , Kapral Moira K. , Hill Michael D.
Published: July 2008

Background and Purpose—

Organized stroke care is an integrated approach to managing stroke to improve stroke outcomes by ensuring that optimal treatment is offered. However, limited information is available comparing different levels of organized care. Our aim was to determine whether escalating levels of organized care can improve stroke outcomes.

Methods—

Cohort study including patients with acute ischemic stroke between July 2003 and March 2005 in the Registry of the Canadian Stroke Network (RCSN). The RCSN is the largest clinical database of patients with acute stroke patients seen at selected acute care hospitals in Canada. As stroke unit admission does not automatically imply receipt of comprehensive care, we created the organized care index to represent different levels of access to organized care ranging from 0 to 3 as determined by the presence of occupational therapy/physiotherapy, stroke team assessment, and admission to a stroke unit. The primary end point was early stroke mortality. Secondary end points include 30-day and 1-year mortality.

Results—

Overall, 3631 ischemic stroke patients were admitted to 11 hospitals. Seven day stroke mortality was 6.9% (249/3631), 30-day stroke mortality was 12.6% (457/3631), and 1-year stroke mortality was 23.6% (856/3631). Risk-adjusted 7-day mortality was 2.0%, 3.2%, 7.8%, and 22.5% for organized care index of 3, 2, 1, and 0. Higher level of care was associated with lower adjusted mortality (for organized care index 3, OR 0.03, 95% CI 0.02 to 0.07 for 7-day mortality; OR 0.09, 95% CI 0.05 to 0.17 for 30-day mortality; and OR 0.40, 95% CI 0.25 to 0.64 for 1-year mortality).

Conclusions—

Higher level of access to care was associated with lower stroke mortality rates. Establishing a well-organized and multidisciplinary system of stroke care will help improve the quality of service delivered and reduce the burden of stroke.
Cellular NAD Replenishment Confers Marked Neuroprotection Against Ischemic Cell Death
Authors: Wang Suping , Xing Zili , Vosler Peter S. , Yin Hannah , Li Wenjin , Zhang Feng , Signore Armando P. , Stetler R. Anne , Gao Yanqin , Chen Jun
Published: July 2008

Background and Purpose—

NAD
+
is an essential cofactor for cellular energy production and participates in various signaling pathways that have an impact on cell survival. After cerebral ischemia, oxidative DNA lesions accumulate in neurons because of increased attacks by ROS and diminished DNA repair activity, leading to PARP-1 activation, NAD
+
depletion, and cell death. The objective of this study was to determine the neuroprotective effects of NAD
+
repletion against ischemic injury and the underlying mechanism.

Methods—

In vitro ischemic injury was induced in rat primary neuronal cultures by oxygen-glucose deprivation (OGD) for 1 to 2 hours. NAD
+
was replenished by adding NAD
+
directly to the culture medium before or after OGD. Cell viability, oxidative DNA damage, and DNA base-excision repair (BER) activity were measured quantitatively up to 72 hours after OGD with or without NAD
+
repletion. Knockdown of BER enzymes was achieved in cultures using AAV-mediated transfection of shRNA.

Results—

Direct NAD
+
repletion in neurons either before or after OGD markedly reduced cell death and OGD-induced accumulation of DNA damage (AP sites, single and double strand breaks) in a concentration- and time-dependent manner. NAD
+
repletion restored nDNA repair activity by inhibiting serine-specific phosphorylation of the essential BER enzymes AP endonuclease and DNA polymerase-β. Knocking down AP endonuclease expression significantly reduced the prosurvival effect of NAD
+
repletion.

Conclusion—

Cellular NAD
+
replenishment is a novel and potent approach to reduce ischemic injury in neuronal cultures. Restoration of DNA repair activity via the BER pathway is a key signaling event mediating the neuroprotective effect of NAD
+
replenishment.
Factors That Influence the Stroke Care Team’s Effectiveness in Reducing the Length of Hospital Stay
Authors: Schouten Loes M.T. , Hulscher Marlies E.J.L. , Akkermans Reinier , van Everdingen Jannes J.E. , Grol Richard P.T.M. , Huijsman Robbert
Published: July 2008

Background and Purpose—

The purpose of this study was to explore the effects of a quality improvement program for improving stroke care and the determinants of success at the team and hospital levels.

Method—

For 16 months, 23 multidisciplinary stroke service teams participated in a quality improvement collaborative designed to set up stroke services and reduce the length of hospital stay (LOHS). We monitored the LOHS and the discharge delay during the project and measured indicators of well organized stroke services at baseline and after the intervention. A multiple and multilevel regression model was used to relate the outcome variables to the team and hospital characteristics. National LOHS figures served as reference data.

Results—

Data regarding 4549 stroke patients were included in the analyses. The LOHS decreased significantly from 18.3 to 13.3 days. The mean LOHS varied substantially (9.2 to 20.9 days) after the intervention. Teams with higher team functioning scores showed lower LOHS scores and higher scores for the indicators of well organized stroke services. Team characteristics explain almost 40% of the variance in LOHS and 53% in the indicators of well organized stroke care.

Conclusion—

Participation in a national quality improvement collaborative effected a significant decrease of the LOHS and a significant increase in the presence of key features of stroke services. Variation in ability to reduce the LOHS and increase key features of stroke services were related to team functioning. The data suggest that the composite of team functioning is pivotal in quality-of-care improvement and may need specific attention in any quality improvement program.
Extent of Hypoattenuation on CT Angiography Source Images Predicts Functional Outcome in Patients With Basilar Artery Occlusion
Authors: Puetz Volker , Sylaja P.N. , Coutts Shelagh B. , Hill Michael D. , Dzialowski Imanuel , Mueller Pia , Becker Ulf , Urban Gabriele , O'Reilly Christine , Barber Philip A. , Sharma Pranshu , Goyal Mayank , Gahn Georg , von Kummer Ruediger , Demchuk Andrew M.
Published: July 2008

Background and Purpose—

Quantification of early ischemic changes (EIC) may predict functional outcome in patients with basilar artery occlusion (BAO). We tested the validity of a novel CT score, the posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS).

Methods—

Pc-ASPECTS allots the posterior circulation 10 points. Two points each are subtracted for EIC in midbrain or pons and 1 point each for EIC in left or right thalamus, cerebellum or PCA-territory, respectively. We studied 2 different populations: (1) patients with suspected vertebrobasilar ischemia and (2) patients with BAO. We applied pc-ASPECTS to noncontrast CT (NCCT), CT angiography source images (CTASI), and follow-up image by 3-reader consensus. We calculated sensitivity for ischemic changes and analyzed the predictivity of pc-ASPECTS for independent (modified Rankin Scale [mRS] score ≤2) and favorable (mRS score ≤3) outcome.

Results—

Of 130 patients with suspected vertebrobasilar ischemia, 72% (94) had posterior circulation stroke, 8% (10) transient ischemic attack, and 20% (26) nonischemic etiology. Sensitivity for ischemic changes was improved with CTASI compared to NCCT (65% [95% CI, 57% to 73%] versus 46% [95% CI, 37% to 55%], respectively). Pc-ASPECTS score on CTASI but not NCCT predicted functional independence (OR 1.58;
P
=0.005 versus 1.22;
P
=0.42, respectively). Of 46 patients with BAO, 52% (12/23) with CTASI pc-ASPECTS score ≥8 but only 4% (1/23) with a score <8 had favorable functional outcome (RR 12.1; 95% CI, 1.7 to 84.9). This difference was consistent in 21 patients with angiographic recanalization (RR 7.7; 95% CI, 1.1 to 52.1).

Conclusion—

The CTASI pc-ASPECTS score may identify BAO patients unlikely to have a favorable outcome despite recanalization.
Risk of Stroke and Myocardial Infarction After Reduction or Cessation of Cigarette Smoking
Authors: Song Yun-Mi , Cho Hong-Jun
Published: July 2008

Background and Purpose—

The effect of smoking reduction on cardiovascular disease outcomes has not been studied in Asian populations.

Methods—

A total of 475 734 Korean men aged 30 to 58 years, stratified into 9 groups based on smoking status at 2 different time points (1990 and 1992), were followed from 1992 to 2001 for the occurrence of stroke or myocardial infarction (MI) events.

Results—

Compared with nonreducing heavy smokers (≥20 cigarettes/d), those who quit smoking showed significantly lower risks of ischemic stroke, subarachnoid hemorrhage, and MI with hazard ratios (95% confidence intervals [CI]) of 0.66 (0.55 to 0.79), 0.58 (0.38 to 0.90), and 0.43 (0.34 to 0.53), respectively. For hemorrhagic stroke, quitters showed lower risk compared with heavy smokers, but the difference was not statistically significant (hazard ratio 0.82, 95% CI: 0.64 to 1.06). Compared with nonreducing heavy smokers, the risks of all stroke combined and MI among reducers tended to decrease, although the reductions were not statistically significant. The risks of subarachnoid hemorrhage and MI in those who reduced from moderate to light smoking tended to be lower than in nonreducing moderate (10 to 19 cigarettes/d) smokers. The association between the reduction of smoking level and the risk of stroke and MI did not change significantly when the analysis was limited to those whose smoking status in 1992 was maintained up to 1994.

Conclusions—

Smoking cessation was associated with a decrease in the risks of ischemic stroke, subarachnoid hemorrhage, and MI. More studies are needed to verify the likely health benefits of reducing smoking.
High Prevalence of Supine Sleep in Ischemic Stroke Patients
Authors: Brown Devin L. , Lisabeth Lynda D. , Zupancic Michael J. , Concannon Maryann , Martin Cory , Chervin Ronald D.
Published: July 2008

Background and Purpose—

Sleep apnea is very common after stroke and is associated with poor outcome. Supine sleep is known to exacerbate apneas in the general sleep apnea population. We therefore investigated the pattern of sleep positions in the acute stroke period.

Methods—

Inpatients with acute ischemic stroke underwent full polysomnography that included continuous monitoring of sleep positions. Sleep apnea severity was measured using the apnea-hypopnea index (AHI). Stroke severity was measured by the NIH Stroke Scale (NIHSS) at the time of study enrollment by certified study personnel. Percent total sleep time spent in the supine position was calculated and compared by stroke severity based on a median split of NIHSS using a Wilcoxon rank-sum test.

Results—

Of the 30 patients, the median age was 67. The median AHI was 23 (IQR: 6, 47). Twenty-two patients (73%) had sleep apnea with an AHI ≥5. The vast majority of sleep time among the stroke cases was spent supine, with a median percent sleep time spent supine of 100 (IQR: 62, 100). The majority (63%) of subjects spent no time asleep in any of the nonsupine positions (prone, left, right). Median percent sleep time supine was 100 (IQR: 100, 100) in those with a higher NIHSS and 63 (IQR: 51, 100) in those with a lower NIHSS (
P
<0.01).

Conclusions—

Given the high prevalence of supine sleep identified, research into positional therapy for stroke patients with sleep apnea seems warranted.
Relative Effects of Statin Therapy on Stroke and Cardiovascular Events in Men and Women
Authors: Goldstein Larry B. , Amarenco Pierre , LaMonte Marian , Gilbert Steven , Messig Michael , Callahan Alfred , Hennerici Michael , Sillesen Henrik , Welch K. Michael A.
Published: July 2008

Background and Purpose—

In SPARCL, treatment with atorvastatin 80 mg daily reduced stroke risk in patients with recent stroke or TIA and no known coronary heart disease by 16% versus placebo over 4.9 years of follow-up. The purpose of this secondary analysis was to determine whether men and women similarly benefited from randomization to statin treatment.

Methods—

The effect of sex on treatment-related reductions in stroke and other cardiovascular outcomes were analyzed with Cox regression modeling testing for sex by treatment interactions.

Results—

Women (n=1908) constituted 40% of the SPARCL study population. At baseline, men (n=2823) were younger (62.0±0.21versus 63.9±0.27 years), had lower systolic BPs (138.1±0.35 versus 139.5±0.47 mm Hg), higher diastolic BPs (82.2±0.20 versus 81.0±0.25 mm Hg), more frequently had a history of smoking (73% versus 38%), and had lower total cholesterol (207.0±0.54 versus 218.9±0.67 mg/dL) and LDL-C levels (132±0.45 versus 134±0.57 mg/dL) than women. Use of antithrombotics and antihypertensives were similar. After prespecified adjustment for region, entry event, time since event, and age, there were no sex by treatment interactions for the combined risk of nonfatal and fatal stroke (treatment Hazard Ratio, HR=0.84, 95% CI 0.68, 1.02 in men versus HR=0.84, 95% CI 0.63, 1.11 in women; treatment×sex interaction
P
=0.99), major cardiac events (HR=0.61, 95% CI 0.42, 0.87 in men versus HR=0.76, 95% CI 0.48, 1.21 in women;
P
=0.45), major cardiovascular events (HR=0.78, 95% CI 0.65, 0.93 in men versus HR=0.84, 95% CI 0.65, 1.07 in women;
P
=0.63), revascularization procedures (HR=0.50, 95% CI 0.37, 0.67 in men versus HR=0.76, 95% CI 0.46, 1.24 in women;
P
=0.17), or any CHD event (HR=0.54, 95% CI 0.41, 0.72 in men versus 0.67 95% CI 0.46, 0.98 in women;
P
=0.40).

Conclusion—

Stroke and other cardiovascular events are similarly reduced with atorvastatin 80 mg/d in men and women with recent stroke or TIA.
Alcohol Consumption and Mortality From Stroke and Coronary Heart Disease Among Japanese Men and Women
Authors: Ikehara Satoyo , Iso Hiroyasu , Toyoshima Hideaki , Date Chigusa , Yamamoto Akio , Kikuchi Shogo , Kondo Takaaki , Watanabe Yoshiyuki , Koizumi Akio , Wada Yasuhiko , Inaba Yutaka , Tamakoshi Akiko ,   Japan Collaborative Cohort Study Group
Published: July 2008

Background and Purpose—

Previous studies have demonstrated the association between alcohol consumption and cardiovascular mortality. However, the sex-specific association between alcohol consumption and mortality from stroke and coronary heart disease remains unclear.

Methods—

Between 1988 and 1990, 34 776 men and 48 906 women aged 40 to 79 years completed a self-administered questionnaire including information about alcohol consumption. They were followed-up for a median duration of 14.2 years.

Results—

Of the 83 682 respondents, 1628 died from stroke and 736 died from coronary heart disease. For men, heavy drinking (≥46.0 g ethanol/day) was associated with increased mortality from total, hemorrhagic, and ischemic strokes, whereas light-to-moderate drinking was associated with reduced mortality from total cardiovascular disease, compared with not drinking. The respective multivariable hazard ratios (95% CI) were 1.48 (1.22 to 1.80) for total stoke, 1.67 (1.17 to 2.38) for hemorrhagic stroke, 1.35 (1.04 to 1.75) for ischemic stroke, and 0.88 (0.78 to 1.00) for total cardiovascular disease. Women who were heavy drinkers (≥46.0 g ethanol/day) showed increased mortality from coronary heart disease, and there was reduced mortality from total cardiovascular disease for drinkers of 0.1 to 22.9 g ethanol per day compared with mortality for nondrinkers. The respective multivariable hazard ratios (95% CI) for the 2 categories of drinkers were 4.10 (1.63 to 10.3) and 0.75 (0.62 to 0.91).

Conclusions—

Heavy alcohol consumption is associated with increased mortality from total stroke, particularly hemorrhagic stroke, and total cardiovascular disease for men, and from coronary heart disease for women, whereas light-to-moderate drinking may be associated with reduced mortality from cardiovascular disease for both sexes.
A Spatial Analysis of Radar Reflectivity Regions within Hurricane Charley (2004)
Authors: Matyas Corene J.
Published: July 2008

Regions of 35-dBZ radar reflectivity returns are examined within a landfalling hurricane to determine whether these regions are composed of stratiform, convective, or transition-type precipitation. After calculating spatial attributes of the reflectivity regions such as elongation and edge roughness within a GIS, discriminant analysis is performed to determine whether the 35-dBZ regions are more similar to 40-dBZ regions of convective precipitation or to 30-dBZ regions of stratiform precipitation. Results show that within the outer region rainbands of Hurricane Charley (2004) a sharp horizontal reflectivity gradient exists, indicating that 35-dBZ regions are similar in shape to adjacent convective regions of 40-dBZ reflectivity values. Within the interior region, the 35-dBZ regions are identified as transition regions similar to those found within mesoscale convective complexes rather than being strictly stratiform or convective in nature. The rain rates produced by the reflectivity regions are examined using rain gauge and radar estimates. In 32% of cases, the 35-dBZ regions produced rain rates in excess of 10 mm h−1, exceeding both the radar-estimated rain rates and the 8.4 mm h−1 rain rate ascribed to 35-dBZ regions by the tropical Z–R relationship. Thus, 35-dBZ regions surrounding the convective cores of additional landfalling TCs should be examined to determine whether they also represent transition-type rainfall regions capable of producing convective rainfall rates exceeding 10 mm h−1.
Sigma-Point Kalman Filter Data Assimilation Methods for Strongly Nonlinear Systems
Authors: Ambadan Jaison Thomas , Tang Youmin
Published: July 2008

Performance of an advanced, derivativeless, sigma-point Kalman filter (SPKF) data assimilation scheme in a strongly nonlinear dynamical model is investigated. The SPKF data assimilation scheme is compared against standard Kalman filters such as the extended Kalman filter (EKF) and ensemble Kalman filter (EnKF) schemes. Three particular cases—namely, the state, parameter, and joint estimation of states and parameters from a set of discontinuous noisy observations—are studied. The problems associated with the use of tangent linear model (TLM) or Jacobian when using standard Kalman filters are eliminated when using SPKF data assimilation algorithms. Further, the constraints and issues of SPKF data assimilation in real ocean or atmospheric models are emphasized. A reduced sigma-point subspace model is proposed and investigated for higher-dimensional systems.

A low-dimensional Lorenz 1963 model and a higher-dimensional Lorenz 1995 model are used as the test beds for data assimilation experiments. The results of SPKF data assimilation schemes are compared with those of standard EKF and EnKF, in which a highly nonlinear chaotic case is studied. It is shown that the SPKF is capable of estimating the model state and parameters with better accuracy than EKF and EnKF. Numerical experiments showed that in all cases the SPKF can give consistent results with better assimilation skills than EnKF and EKF and can overcome the drawbacks associated with the use of EKF and EnKF.
The Kelvin versus the Raoult Term in the Köhler Equation
Authors: Wex Heike , Stratmann Frank , Topping David , McFiggans Gordon
Published: July 2008

A comprehensive sensitivity study was carried out examining the sensitivity of hygroscopic growth and activation as modeled with the Köhler equation. Different parameters in the Köhler equation were varied within the range of their currently known uncertainties. The parameters examined include not only those describing the nature of the soluble substances in a particle/droplet and the surface tension σ of the droplet solution, but also the recently proposed representation of parameters coupling the Raoult and Kelvin terms (i.e., partitioning of solute between the surface and bulk phases, although the recently proposed adsorption to wettable but insoluble material was not considered). The examined variations cause significant changes in both hygroscopic growth and activation. Whereas the hygroscopic growth regime below 95% RH is insensitive toward the surface tension σ, σ has a large influence on the activation, increasing with decreasing particle size. This implies that a cloud condensation nuclei (CCN) closure, connecting particle hygroscopic growth to activation, has to account for an influence of the examined substance on σ of the particle, especially for smaller particles in the size range from 50 to 100 nm. A simple estimate showed that a lowering of σ by only 10% can cause a change in the activated fraction (i.e., in the cloud droplet number concentration) of at least 10%–20%. Where organic molecules are present in sufficient concentration to reduce σ, surface tension may be an important factor in determining the activation of aerosol particles to cloud droplets.
The Role of Radiation in Influencing Tropical Cloud Distributions in a Radiative–Convective Equilibrium Cloud-Resolving Model
Authors: Pakula Lyle , Stephens Graeme L.
Published: July 2008

Observations by Johnson et al. depict regions of active tropical convection as possessing increased relative humidity through a deep layer and reduced low-level static stability when compared to nonconvecting regions. Shallow cumulus clouds, congestus clouds, and deep convection all coexist within these convecting regions. This investigation explores the effect that radiation might have on the tropical cloud distributions by using large-domain (20 000 km) radiative–convective equilibrium cloud-resolving model (RCE-CRM) experiments that reproduce similar moisture, stability, and cloud structures to those observed.

Radiation is found to significantly increase the amount of shallow and intermediate-level clouds (tops between 1.5 and 5 km) by increasing low-level stability and thus promoting additional low-level cloud detrainment. The mechanism by which radiation stabilizes the low levels is found to differ between convectively suppressed and active regions. In convectively suppressed regions, strong relative humidity gradients within the trade inversion layer produce a low-level cooling maximum that further stabilizes the stable layer, much as proposed by Mapes and Zuidema. In convectively active regions, sufficiently moist columns with no relative humidity gradients are also found to produce a low-level cooling maximum that stabilizes the lower levels. This cooling maximum is due to the complicated effects of the water vapor continuum and is sensitive to the absolute moisture path. Because of the dependence on absolute moisture, the radiative enhancement of shallow and intermediate-level clouds in convectively active regions is potentially sensitive to SSTs.
How Generic Are Dipolar Jet EOFs?
Authors: Monahan Adam H. , Fyfe John C.
Published: July 2008

Dipolar structures arise as empirical orthogonal functions (EOFs) of extratropical tropospheric zonal-mean zonal wind in observations, in idealized dynamical models, and in complex general circulation models. This study characterizes the conditions under which dipoles emerge as EOFs of a jet of fixed shape f (x), which takes a unique localized extremum and is smooth but is otherwise arbitrary, characterized by fluctuations in strength, position, and width of arbitrary distribution. It is shown that the factors that influence the extent to which a dipolelike structure will arise as an EOF are (i) the skewness of position fluctuations, (ii) the dependence of position fluctuations on strength and width fluctuations, and (iii) the relative strength of the position and width fluctuations. In particular, the leading EOF will be a dipole if jet position fluctuations are not strongly skewed, not strongly dependent on strength and width fluctuations, and sufficiently large relative to strength and width fluctuations. Because these conditions are generally satisfied to a good approximation by observed and simulated tropospheric eddy-driven jets, this analysis provides a simple explanation of the ubiquity of dipolar jet EOFs.
The Impact of Stratospheric Ozone Recovery on Tropopause Height Trends
Authors: Son Seok-Woo , Polvani Lorenzo M. , Waugh Darryn W. , Birner Thomas , Akiyoshi Hideharu , Garcia Rolando R. , Gettelman Andrew , Plummer David A. , Rozanov Eugene
Published: July 2008

The evolution of the tropopause in the past, present, and future climate is examined by analyzing a set of long-term integrations with stratosphere-resolving chemistry climate models (CCMs). These CCMs have high vertical resolution near the tropopause, a model top located in the mesosphere or above, and, most important, fully interactive stratospheric chemistry. Using such CCM integrations, it is found that the tropopause pressure (height) will continue to decrease (increase) in the future, but with a trend weaker than that in the recent past. The reduction in the future tropopause trend is shown to be directly associated with stratospheric ozone recovery. A significant ozone recovery occurs in the Southern Hemisphere lower stratosphere of the CCMs, and this leads to a relative warming there that reduces the tropopause trend in the twenty-first century.

The future tropopause trends predicted by the CCMs are considerably smaller than those predicted by the Intergovernmental Panel on Climate Change Fourth Assessment Report (AR4) models, especially in the southern high latitudes. This difference persists even when the CCMs are compared with the subset of the AR4 model integrations for which stratospheric ozone recovery was prescribed. These results suggest that a realistic representation of the stratospheric processes might be important for a reliable estimate of tropopause trends. The implications of these finding for the Southern Hemisphere climate change are also discussed.
Contrasting Eastern-Pacific and Central-Pacific Types of ENSO
Authors: Kao Hsun-Ying , Yu Jin-Yi
Published: July 2008

Surface observations and subsurface ocean assimilation datasets are examined to contrast two distinct types of El Niño–Southern Oscillation (ENSO) in the tropical Pacific: an eastern-Pacific (EP) type and a central-Pacific (CP) type. An analysis method combining empirical orthogonal function (EOF) analysis and linear regression is used to separate these two types. Correlation and composite analyses based on the principal components of the EOF were performed to examine the structure, evolution, and teleconnection of these two ENSO types. The EP type of ENSO is found to have its SST anomaly center located in the eastern equatorial Pacific attached to the coast of South America. This type of ENSO is associated with basinwide thermocline and surface wind variations and shows a strong teleconnection with the tropical Indian Ocean. In contrast, the CP type of ENSO has most of its surface wind, SST, and subsurface anomalies confined in the central Pacific and tends to onset, develop, and decay in situ. This type of ENSO appears less related to the thermocline variations and may be influenced more by atmospheric forcing. It has a stronger teleconnection with the southern Indian Ocean. Phase-reversal signatures can be identified in the anomaly evolutions of the EP-ENSO but not for the CP-ENSO. This implies that the CP-ENSO may occur more as events or epochs than as a cycle. The EP-ENSO has experienced a stronger interdecadal change with the dominant period of its SST anomalies shifted from 2 to 4 yr near 1976/77, while the dominant period for the CP-ENSO stayed near the 2-yr band. The different onset times of these two types of ENSO imply that the difference between the EP and CP types of ENSO could be caused by the timing of the mechanisms that trigger the ENSO events.
Three-Dimensional Structure of Tropical Cells in the Central Equatorial Pacific Ocean*
Authors: Perez Renellys C. , Kessler William S.
Published: July 2008

The shallow tropical cells (TCs) in the central equatorial Pacific Ocean are characterized by strong equatorial upwelling, near-surface wind-driven poleward flow, downwelling near the cold tongue boundaries, and equatorward flow below the surface mixed layer. Meridional and vertical velocity fluctuations associated with tropical instability waves (TIWs) in the central equatorial Pacific are much larger than those associated with the TCs and can modify the background circulation. OGCM experiments are used to simulate the spinup of the cells along 140°W in response to perturbed trade winds during various phases of the annual cycle. Equatorially modified versions of geostrophy and Ekman theory, and zonal filtering, are used to isolate the large-zonal-scale wind-driven response. Weakening of the trade winds in any season rapidly weakens the TCs, decreases the zonal current shear, and reduces the amplitude and propagation speed of the TIWs. In boreal fall and winter, when the background TCs and TIWs are seasonally strong, the ocean response is equatorially asymmetric (stronger flows north of the equator) and there is evidence of rectification by the modified TIWs onto the TCs. The linear equatorially modified Ekman solutions largely explain the meridional structure and temporal evolution of the anomalous ageostrophic response in the TCs. In fall and winter, however, deviations from the modified Ekman solutions were attributed to interactions with the background TCs and TIWs. An observing system able to quantify the relative contributions of these two processes to the seasonally varying equatorial asymmetry of background circulation would require fine meridional and temporal sampling.
Estimating the Evaporative Cooling Bias of an Airborne Reverse Flow Thermometer
Authors: Wang Yonggang , Geerts Bart
Published: July 2008

Airborne reverse flow immersion thermometers were designed to prevent sensor wetting in cloud. Yet there is strong evidence that some wetting does occur and therefore also sensor evaporative cooling as the aircraft exits a cloud. Numerous penetrations of cumulus clouds in a broad range of environmental and cloud conditions are used to estimate the resulting negative temperature bias. This cloud exit “cold spike” can be found in all cumulus clouds, even at subfreezing temperatures, both in continental and maritime cumuli. The magnitude of the spike correlates most strongly with the dryness of the ambient air. A temperature correction based on this relationship is proposed. More important than the cloud exit cold spike, from a cumulus dynamics perspective, is the negative bias within cloud. Such bias is expected, due to evaporative cooling as well. Evaporation from the wetted sensor in cloud is surmised because air decelerates into the thermometer housing, and thus is heated and becomes subsaturated. Thus an in-cloud temperature correction is proposed, based on the composite cloud exit evaporative cooling behavior. This correction leads to higher and more realistic estimates of cumulus buoyancy and lower estimates of entrainment.
A Modified Kain–Fritsch Scheme and Its Application for the Simulation of an Extreme Precipitation Event in Vietnam
Authors: Truong Nguyen Minh , Tien Tran Tan , Pielke Roger A. , Castro Christopher L. , Leoncini Giovanni
Published: July 2008

From 24 to 26 November 2004, an extreme heavy rainfall event occurred in the mountainous provinces of central Vietnam, resulting in severe flooding along local rivers. The Regional Atmospheric Modeling System, version 4.4, is used to simulate this event. In the present study, the convective parameterization scheme includes the original Kain–Fritsch scheme and a modified one in which a new diagnostic equation to compute updraft velocity, closure assumption, and trigger function are developed. These modifications take the vertical gradient of the Exner function perturbation into account, with an on–off coefficient to account for the role of the advective terms. According to the event simulations, the simulated precipitation shows that the modified scheme with the new trigger function gives much better results than the original one. Moreover, the interaction between convection and the larger-scale environment is much stronger near the midtroposphere where the return flow associated with lower-level winter monsoon originates. As a result, the modified scheme produces larger and deeper stratiform clouds and leads to a significant amount of resolvable precipitation. On the contrary, the resolvable precipitation is small when the original scheme is used. The improvement in the simulated precipitation is caused by a more explicit physical mechanism of the new trigger function and suggests that the trigger function needs to be developed along with other components of the scheme, such as closure assumption and cloud model, as a whole. The formalistic inclusion of the advective terms in the new equation gives almost no additional improvement of the simulated precipitation.
Life of a Six-Hour Hurricane
Authors: Shelton Kay L. , Molinari John
Published: July 2008

Hurricane Claudette developed from a weak vortex in 6 h as deep convection shifted from downshear into the vortex center, despite ambient vertical wind shear exceeding 10 m s−1. Six hours later it weakened to a tropical storm, and 12 h after the hurricane stage a circulation center could not be found at 850 hPa by aircraft reconnaissance. At hurricane strength the vortex contained classic structure seen in intensifying hurricanes, with the exception of 7°–12°C dewpoint depressions in the lower troposphere upshear of the center. These extended from the 100-km radius to immediately adjacent to the eyewall, where equivalent potential temperature gradients reached 6 K km−1. The dry air was not present prior to intensification, suggesting that it was associated with vertical shear–induced subsidence upshear of the developing storm. It is argued that weakening of the vortex was driven by cooling associated with the mixing of dry air into the core, and subsequent evaporation and cold downdrafts. Evidence suggests that this mixing might have been enhanced by eyewall instabilities after the period of rapid deepening. The existence of a fragile, small, but genuinely hurricane-strength vortex at the surface for 6 h presents difficult problems for forecasters. Such a “temporary hurricane” in strongly sheared flow might require a different warning protocol than longer-lasting hurricane vortices in weaker shear.
Three-Dimensional Idealized Simulations of Barrier Jets along the Southeast Coast of Alaska
Authors: Olson Joseph B. , Colle Brian A.
Published: July 2008

Three-dimensional idealized simulations using the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) down to 6-km grid spacing were performed in order to understand how different ambient conditions (wind speed and direction, stability, and inland cold pool) and terrain characteristics impact barrier jets along the southeastern Alaskan coast. The broad inland terrain of western North America is important in Alaskan jet development, since it rotates the impinging flow cyclonically (more coast parallel) well upstream of the coast, thus favoring more low-level flow blocking while also adding momentum and width to the barrier jet. Near the steep coastal terrain, the largest wind speed enhancement factor (1.9–2.0) in the terrain-parallel direction relative to the ambient onshore-directed wind speed occurs at relatively low Froude numbers (Fr ∼ 0.3–0.4). These low Froude numbers are associated with (10–15 m s−1) ambient wind speeds and wind directions orientated 30°–45° from terrain-parallel. For simulations with an inland cold pool and nearly coast-parallel flow, strong gap outflows develop through the coastal mountain gaps, shifting the largest wind speed enhancement to Fr < 0.2. The widest barrier jets occur with ambient winds oriented nearly terrain-parallel with strong static stability. The gap outflows shift the position of the jet maximum farther offshore from the coast and increase the jet width. The height of the jet maxima is typically located at the top of the shallow gap outflow (∼500 m MSL), but without strong gap outflows, the jet heights are located at the top of the boundary layer, which is higher (lower) for large (small) frictionally induced vertical wind shear and weak (strong) static stability.