bluuebunny/crossref_metadata_2025 huggingface dataset:
Arachidonic Acid–Induced Dilation in Human Coronary Arterioles: Convergence of Signaling Mechanisms on Endothelial TRPV4‐Mediated Ca
2+
Entry
Authors: Zheng Xiaodong , Zinkevich Natalya S. , Gebremedhin Debebe , Gauthier Kathryn M. , Nishijima Yoshinori , Fang Juan , Wilcox David A. , Campbell William B. , Gutterman David D. , Zhang David X.
Published: May 2013

Background

Arachidonic acid (
AA
) and/or its enzymatic metabolites are important lipid mediators contributing to endothelium‐derived hyperpolarizing factor (
EDHF
)–mediated dilation in multiple vascular beds, including human coronary arterioles (
HCA
s). However, the mechanisms of action of these lipid mediators in endothelial cells (
EC
s) remain incompletely defined. In this study, we investigated the role of the transient receptor potential vanilloid 4 (
TRPV
4) channel in
AA
‐induced endothelial Ca
2+
response and dilation of
HCA
s.

Methods and Results

AA
induced concentration‐dependent dilation in isolated
HCA
s. The dilation was largely abolished by the
TRPV
4 antagonist
RN
‐1734 and by inhibition of endothelial Ca
2+
‐activated K
+
channels. In native and
TRPV
4‐overexpressing human coronary artery
EC
s (
HCAEC
s),
AA
increased intracellular Ca
2+
concentration ([Ca
2+
]
i
), which was mediated by
TRPV
4‐dependent Ca
2+
entry. The
AA
‐induced [Ca
2+
]
i
increase was inhibited by cytochrome P450 (
CYP
) inhibitors. Surprisingly, the
CYP
metabolites of
AA
, epoxyeicosatrienoic acids (
EET
s), were much less potent activators of
TRPV
4, and
CYP
inhibitors did not affect
EET
production in
HCAEC
s. Apart from its effect on [Ca
2+
]
i
,
AA
induced endothelial hyperpolarization, and this effect was required for Ca
2+
entry through
TRPV
4.
AA
‐induced and
TRPV
4‐mediated Ca
2+
entry was also inhibited by the protein kinase A inhibitor
PKI
.
TRPV
4 exhibited a basal level of phosphorylation, which was inhibited by
PKI
. Patch‐clamp studies indicated that
AA
activated
TRPV
4 single‐channel currents in cell‐attached and inside‐out patches of
HCAEC
s.

Conclusions

AA
dilates
HCA
s through a novel mechanism involving endothelial
TRPV
4 channel‐dependent Ca
2+
entry that requires endothelial hyperpolarization,
PKA
‐mediated basal phosphorylation of
TRPV
4, and direct activation of
TRPV
4 channels by
AA
.
Trends in Intracranial Stenting Among Medicare Beneficiaries in the United States, 2006–2010
Authors: Gupta Aakriti , Desai Mayur M. , Kim Nancy , Bulsara Ketan R. , Wang Yun , Krumholz Harlan M.
Published: May 2013

Background

It is uncertain how intracranial stenting (
ICS
) has been adopted nationally during a period characterized by a restrictive payment policy by the Centers for Medicare & Medicaid Services, humanitarian device exemption approval by the Food and Drug Administration, and insufficient evidence of effectiveness. We sought to determine the trends in rates of
ICS
use and associated outcomes in the United States.

Methods and Results

From 65 211 328 Medicare Fee‐for‐Service beneficiaries hospitalized between 2006 and 2010 in acute care hospitals in the United States, we included patients with
ICD
‐9‐
CM
procedure codes for intracranial angioplasty and stenting, excluding those with a principal discharge diagnosis code of cerebral aneurysm or subarachnoid hemorrhage. We report operative rates per 1 000 000 person‐years and outcomes including 30‐day and 1‐year mortality rates. There were 838
ICS
procedures performed among Fee‐for‐Service beneficiaries. The overall hospitalization rate for
ICS
increased significantly from ≈1 per 1 000 000 person‐years (n=35 procedures) in 2006 to 9 per 1 000 000 person‐years (n=258 procedures) in 2010 (
P
=0.0090 for trend). Procedure rates were higher in men than in women, and were highest among patients aged 75 to 84 years and lowest among those ≥85 years. The 30‐day mortality rate increased from 2.9% (95%
CI
, 0.1 to 15.3) to 12.9% (95%
CI
, 9.0 to 17.6),
P
=0.1294 for trend, and the 1‐year mortality rate increased from 14.7% (95%
CI
, 5.0 to 31.1) to 19.5% (95%
CI
, 14.9 to 24.9),
P
=0.0101; however, the annual changes were not significant after adjustment.

Conclusions

ICS
utilization in the United States has modestly increased during a period of inadequate supportive evidence. Humanitarian device exemption and a restrictive payment policy appear to have caused slow adoption of the technology.
The Value of Carotid Artery Plaque and Intima‐Media Thickness for Incident Cardiovascular Disease: The Multi‐Ethnic Study of Atherosclerosis
Authors: Polak Joseph F. , Szklo Moyses , Kronmal Richard A. , Burke Gregory L. , Shea Steven , Zavodni Anna E. H. , O'Leary Daniel H.
Published: May 2013

Background

Carotid artery plaques are associated with coronary artery atherosclerotic lesions. We evaluated various ultrasound definitions of carotid artery plaque as predictors of future cardiovascular disease (
CVD
) and coronary heart disease (
CHD
) events.

Methods and Results

We studied the risk factors and ultrasound measurements of the carotid arteries at baseline of 6562 members (mean age 61.1 years; 52.6% women) of the Multi‐Ethnic Study of Atherosclerosis (
MESA
). ICA lesions were defined subjectively as >0% or ≥25% diameter narrowing, as continuous intima‐media thickness (
IMT
) measurements (maximum
IMT
or the mean of the maximum
IMT
of 6 images) and using a 1.5‐mm
IMT
cut point. Multivariable
C
ox proportional hazards models were used to estimate hazard ratios for incident
CVD
,
CHD
, and stroke.
H
arrell's
C
‐statistics, Net Reclassification Improvement, and Integrated Discrimination Improvement were used to evaluate the incremental predictive value of plaque metrics. At 7.8‐year mean follow‐up, all plaque metrics significantly predicted
CVD
events (n=515) when added to
F
ramingham risk factors. All except 1 metric improved the prediction of
CHD
(by
C
‐statistic,
Net Reclassification Improvement
, and Integrated Discrimination Improvement. Mean of the maximum
IMT
had the highest
NRI
(7.0%;
P
=0.0003) with risk ratio of 1.43/mm; 95% CI 1.26–1.63) followed by maximum
IMT
with an
NRI
of 6.8% and risk ratio of 1.27 (95% CI 1.18–1.38).

Conclusion

Ultrasound‐derived plaque metrics independently predict cardiovascular events in our cohort and improve risk prediction for
CHD
events when added to
F
ramingham risk factors.
A Novel Stress Echocardiography Pattern for Myocardial Bridge With Invasive Structural and Hemodynamic Correlation
Authors: Lin Shin , Tremmel Jennifer A. , Yamada Ryotaro , Rogers Ian S. , Yong Celina Mei , Turcott Robert , McConnell Michael V. , Dash Rajesh , Schnittger Ingela
Published: May 2013

Background

Patients with a myocardial bridge (
MB
) and no significant obstructive coronary artery disease (
CAD
) may experience angina presumably from ischemia, but noninvasive assessment has been limited and the underlying mechanism poorly understood. This study seeks to correlate a novel exercise echocardiography (
EE
) finding for
MB
s with invasive structural and hemodynamic measurements.

Methods and Results

Eighteen patients with angina and an
EE
pattern of focal end‐systolic to early‐diastolic buckling in the septum with apical sparing were prospectively enrolled for invasive assessment. This included coronary angiography, left anterior descending artery (
LAD
) intravascular ultrasound (
IVUS
), and intracoronary pressure and
D
oppler measurements at rest and during dobutamine stress. All patients were found to have an
LAD MB
on
IVUS
. The ratios of diastolic intracoronary pressure divided by aortic pressure at rest (Pd/Pa) and during dobutamine stress (diastolic fractional flow reserve [
dFFR
]) and peak
D
oppler flow velocity recordings at rest and with stress were successfully performed in 14 patients. All had abnormal
dFFR
(≤0.75) at stress within the bridge, distally or in both positions, and on average showed a more than doubling in peak
D
oppler flow velocity inside the
MB
at stress. Seventy‐five percent of patients had normalization of
dFFR
distal to the
MB
, with partial pressure recovery and a decrease in peak
D
oppler flow velocity.

Conclusions

A distinctive septal wall motion abnormality with apical sparing on
EE
is associated with a documented
MB
by
IVUS
and a decreased
dFFR
. We posit that the septal wall motion abnormality on
EE
is due to dynamic ischemia local to the compressed segment of the
LAD
from the increase in velocity and decrease in perfusion pressure, consistent with the
V
enturi effect.
T‐Helper Type 1 Bias in Healthy People Is Associated With Cytomegalovirus Serology and Atherosclerosis: The Multi‐Ethnic Study of Atherosclerosis
Authors: Tracy Russell P. , Doyle Margaret F. , Olson Nels C. , Huber Sally A. , Jenny Nancy S. , Sallam Reem , Psaty Bruce M. , Kronmal Richard A.
Published: May 2013

Background

Although T‐helper type 1 (Th1) cells are considered important in atherosclerosis, the relationships between Th1 and Th2 cells and atherosclerosis have not been examined in population‐based studies.

Methods and Results

We measured Th cells as a percentage of lymphocytes by flow cytometry using
CD
4 staining (%
CD
4) in 917 participants of the Multi‐Ethnic Study of Atherosclerosis. We also measured interferon gamma–positive and interleukin‐4‐positive
CD
4
+
cells, representing Th1 and Th2 subpopulations (%Th1 and %Th2), respectively. We found that %
CD
4 was 1.5% lower per 10 years of age (
P
<0.0001). Whites had higher %
CD
4 and lower %Th1 and %Th2 values than other race/ethnic groups. Body mass index (
BMI
) and blood pressure were associated with %
CD
4, but no traditional cardiovascular disease (
CVD
) risk factors were associated with %Th1 or %Th2. In multivariable models, the major independent variable associated with %Th1 was cytomegalovirus (
CMV
) antibody titer, with minor contributions from age, sex, seasonality, and interleukin‐6. In models with coronary artery calcification level as the outcome, significant independent variables included age, sex, smoking status, and %Th1 (β=0.25;
P
≤0.01). Both %Th1 and %Th2 were associated with common carotid intimal media thickness (β=0.02 and −0.02, respectively; both
P
<0.05), as were age, sex, race/ethnicity, blood pressure, and
BMI
.

Conclusions

Th1 bias is associated with subclinical atherosclerosis in a multiethnic population. The main Th1 correlate was
CMV
infectious burden. These findings are consistent with a role of Th1 cells in atherosclerosis and suggest the importance of prospective studies of T‐helper cell biasing in
CVD
.
Effects of Recombinant Human Erythropoietin on Resistance Artery Endothelial Function in Stage 4 Chronic Kidney Disease
Authors: Briet Marie , Barhoumi Tlili , Mian Muhammad Oneeb Rehman , Sierra Cristina , Boutouyrie Pierre , Davidman Michael , Bercovitch David , Nessim Sharon J. , Frisch Gershon , Paradis Pierre , Lipman Mark L. , Schiffrin Ernesto L.
Published: May 2013

Background

Recent studies have raised concern about the safety of erythropoiesis‐stimulating agents because of evidence of increased risk of hypertension and cardiovascular morbidity and mortality in chronic kidney disease (
CKD
) patients. In the present study, we investigated the effects of recombinant human erythropoietin (
EPO
) on endothelial function of gluteal subcutaneous resistance arteries isolated from 17 stage 4 patients (estimated glomerular filtration rate 21.9±7.4 mL/min per 1.73 m
2
) aged 63±13 years.

Methods and Results

Arteries were mounted on a pressurized myograph.
EPO
impaired endothelium‐dependent relaxation in a concentration‐dependent manner. The maximal response to acetylcholine with
EPO
at 1, 10, and 20 IU/mL was reduced by 12%, 34%, and 43%, respectively, compared with the absence of
EPO
(
P
<0.001).
EPO
‐induced endothelial dysfunction was significantly associated with carotid stiffness and history of cardiovascular events.
EPO
had no effect on norepinephrine‐induced vasoconstriction or sodium nitroprusside–induced relaxation.
ABT
‐627, an endothelin type A receptor antagonist, and tempol, a superoxide dismutase mimetic, partially reversed the altered endothelial function in the presence of
EPO
(
P
<0.01). Increased expression of endothelin‐1 was found in the vessel wall after incubation with
EPO
.

Conclusions

EPO
alters endothelial function of resistance arteries in
CKD
patients via a mechanism involving in part oxidative stress and signaling through an endothelin type A receptor.
EPO
‐induced endothelial dysfunction could contribute to deleterious effects of
EPO
described in large interventional trials.
Deficiency of TDAG51 Protects Against Atherosclerosis by Modulating Apoptosis, Cholesterol Efflux, and Peroxiredoxin‐1 Expression
Authors: Hossain Gazi S. , Lynn Edward G. , Maclean Kenneth N. , Zhou Ji , Dickhout Jeffrey G. , Lhoták Šárka , Trigatti Bernardo , Capone John , Rho Jaerang , Tang Damu , McCulloch Christopher A. , Al‐Bondokji Imtisal , Malloy Mary J. , Pullinger Clive R. , Kane John P. , Li Yonghong , Shiffman Dov , Austin Richard C.
Published: May 2013

Background

Apoptosis caused by endoplasmic reticulum (
ER
) stress contributes to atherothrombosis, the underlying cause of cardiovascular disease (
CVD
).
T
‐cell death‐associated gene 51 (

TDAG51

), a member of the pleckstrin homology‐like domain gene family, is induced by
ER
stress, causes apoptosis when overexpressed, and is present in lesion‐resident macrophages and endothelial cells.

Methods and Results

To study the role of
TDAG51
in atherosclerosis, male mice deficient in

TDAG51

and
apolipoprotein E
(
TDAG51

−/−

/
ApoE

−/−

) were generated and showed reduced atherosclerotic lesion growth (56±5% reduction at 40 weeks, relative to
ApoE

−/−

controls,
P
<0.005) and necrosis (41±4% versus 63±8% lesion area in
TDAG51

−/−

/ApoE

−/−

and
ApoE

−/−

, respectively;
P
<0.05) without changes in plasma levels of lipids, glucose, and inflammatory cytokines.

TDAG51

deficiency caused several phenotypic changes in macrophages and endothelial cells that increase cytoprotection against oxidative and
ER
stress, enhance
PPAR
γ‐dependent reverse cholesterol transport, and upregulate peroxiredoxin‐1 (Prdx‐1), an antioxidant enzyme with antiatherogenic properties (1.8±0.1‐fold increase in Prdx‐1 protein expression, relative to control macrophages;
P
<0.005). Two independent case–control studies found that a genetic variant in the human

TDAG51

gene region (rs2367446) is associated with
CVD
(
OR
, 1.15; 95%
CI
, 1.07 to 1.24;
P
=0.0003).

Conclusions

These findings provide evidence that
TDAG51
affects specific cellular pathways known to reduce atherogenesis, suggesting that modulation of
TDAG51
expression or its activity may have therapeutic benefit for the treatment of
CVD
.
Increased Expression of HCN Channels in the Ventricular Myocardium Contributes to Enhanced Arrhythmicity in Mouse Failing Hearts
Authors: Kuwabara Yoshihiro , Kuwahara Koichiro , Takano Makoto , Kinoshita Hideyuki , Arai Yuji , Yasuno Shinji , Nakagawa Yasuaki , Igata Sachiyo , Usami Satoru , Minami Takeya , Yamada Yuko , Nakao Kazuhiro , Yamada Chinatsu , Shibata Junko , Nishikimi Toshio , Ueshima Kenji , Nakao Kazuwa
Published: May 2013

Background

The efficacy of pharmacological interventions to prevent sudden arrhythmic death in patients with chronic heart failure remains limited. Evidence now suggests increased ventricular expression of hyperpolarization‐activated cation (
HCN
) channels in hypertrophied and failing hearts contributes to their arrythmicity. Still, the role of induced
HCN
channel expression in the enhanced arrhythmicity associated with heart failure and the capacity of
HCN
channel blockade to prevent lethal arrhythmias remains undetermined.

Methods and Results

We examined the effects of ivabradine, a specific
HCN
channel blocker, on survival and arrhythmicity in transgenic mice (dn
NRSF
‐Tg) expressing a cardiac‐specific dominant‐negative form of neuron‐restrictive silencer factor, a useful mouse model of dilated cardiomyopathy leading to sudden death. Ivabradine (7 mg/kg per day orally) significantly reduced ventricular tachyarrhythmias and improved survival among dn
NRSF
‐Tg mice while having no significant effect on heart rate or cardiac structure or function. Ivabradine most likely prevented the increase in automaticity otherwise seen in dn
NRSF
‐Tg ventricular myocytes. Moreover, cardiac‐specific overexpression of
HCN
2 in mice (
HCN
2‐Tg) made hearts highly susceptible to arrhythmias induced by chronic β‐adrenergic stimulation. Indeed, ventricular myocytes isolated from
HCN
2‐Tg mice were highly susceptible to β‐adrenergic stimulation‐induced abnormal automaticity, which was inhibited by ivabradine.

Conclusions

HCN
channel blockade by ivabradine reduces lethal arrhythmias associated with dilated cardiomyopathy in mice. Conversely, cardiac‐specific overexpression of
HCN
2 channels increases arrhythmogenicity of β‐adrenergic stimulation. Our findings demonstrate the contribution of
HCN
channels to the increased arrhythmicity seen in failing hearts and suggest
HCN
channel blockade is a potentially useful approach to preventing sudden death in patients with heart failure.
Reduced Neointima Formation After Arterial Injury in CD4−/− Mice Is Mediated by CD8
+
CD28
hi
T Cells
Authors: Dimayuga Paul C. , Chyu Kuang‐Yuh , Lio Wai Man , Zhao Xiaoning , Yano Juliana , Zhou Jianchang , Honjo Tomoyuki , Shah Prediman K. , Cercek Bojan
Published: May 2013

Background

CD
8
+
T
‐cell activation, characterized by increased
CD
28 expression, reduces neointima formation after arterial injury in mice. The
CD
8
+
CD
28
hi
phenotype is associated with increased effector function. In this study, we used a mouse model that has
CD
8
+
but no
CD
4
+
T
cells (
CD
4−/−) to assess the role of
CD
8
+
T
cells and test the function of
CD
8
+
CD
28
hi
T
cells in modulating neointima formation after arterial injury.

Methods and Results

Neointima formation after pericarotid arterial cuff injury was significantly less in
CD
4−/− mice compared with wild‐type (
WT
) mice. Negligible baseline lytic activity by splenic
CD
8
+
T
cells from uninjured
WT
mice against target syngeneic smooth muscle cells was significantly increased 7 days after injury. Interestingly,
CD
8
+
T
cells from uninjured
CD
4−/− mice had significant lytic activity at baseline that remained elevated 7 days after injury.
CD
8
+
T
‐cell lytic activity was significantly reduced by depletion of
CD
28
hi
cells.
CD
8
+
CD
28
hi
T
cells adoptively transferred into recipient Rag‐1−/− mice significantly reduced neointima formation compared with
CD
8
+
CD
28
+
T
‐cell recipient mice.

Conclusions

CD
8
+
T
cells reduced neointima formation after arterial injury, attributed in part to increased function of the
CD
8
+
CD
28
hi
phenotype.
Glucose Regulation of Load‐Induced mTOR Signaling and ER Stress in Mammalian Heart
Authors: Sen Shiraj , Kundu Bijoy K. , Wu Henry Cheng‐Ju , Hashmi S. Shahrukh , Guthrie Patrick , Locke Landon W. , Roy R. Jack , Matherne G. Paul , Berr Stuart S. , Terwelp Matthew , Scott Brian , Carranza Sylvia , Frazier O. Howard , Glover David K. , Dillmann Wolfgang H. , Gambello Michael J. , Entman Mark L. , Taegtmeyer Heinrich
Published: May 2013

Background

Changes in energy substrate metabolism are first responders to hemodynamic stress in the heart. We have previously shown that hexose‐6‐phosphate levels regulate mammalian target of rapamycin (
mTOR
) activation in response to insulin. We now tested the hypothesis that inotropic stimulation and increased afterload also regulate
mTOR
activation via glucose 6‐phosphate (G6P) accumulation.

Methods and Results

We subjected the working rat heart
ex vivo
to a high workload in the presence of different energy‐providing substrates including glucose, glucose analogues, and noncarbohydrate substrates. We observed an association between G6P accumulation,
mTOR
activation, endoplasmic reticulum (
ER
) stress, and impaired contractile function, all of which were prevented by pretreating animals with rapamycin (
mTOR
inhibition) or metformin (
AMPK
activation). The histone deacetylase inhibitor 4‐phenylbutyrate, which relieves ER stress, also improved contractile function. In contrast, adding the glucose analogue 2‐deoxy‐
d
‐glucose, which is phosphorylated but not further metabolized, to the perfusate resulted in
mTOR
activation and contractile dysfunction. Next we tested our hypothesis in vivo by transverse aortic constriction in mice. Using a micro‐
PET
system, we observed enhanced glucose tracer analog uptake and contractile dysfunction preceding dilatation of the left ventricle. In contrast, in hearts overexpressing SERCA2a,
ER
stress was reduced and contractile function was preserved with hypertrophy. Finally, we examined failing human hearts and found that mechanical unloading decreased G6P levels and
ER
stress markers.

Conclusions

We propose that glucose metabolic changes precede and regulate functional (and possibly also structural) remodeling of the heart. We implicate a critical role for G6P in load‐induced
mTOR
activation and
ER
stress.
Cardiovascular Risk Score, Cognitive Decline, and Dementia in Older Mexican Americans: The Role of Sex and Education
Authors: Hazzouri Adina Zeki Al , Haan Mary N. , Neuhaus John M. , Pletcher Mark , Peralta Carmen A. , López Lenny , Pérez Stable Eliseo J.
Published: May 2013

Background

The purpose of this study was to examine the associations of cardiovascular disease (
CVD
) risk with cognitive decline and incidence of dementia and cognitive impairment but not dementia (
CIND
) and the role of education as a modifier of these effects.

Methods and Results

One thousand one hundred sixteen Mexican American elderly were followed annually in the Sacramento Area Latino Study on Aging. Our sex‐specific 10‐year
CVD
risk score included baseline age, systolic blood pressure, total cholesterol, high‐density lipoprotein, smoking, body mass index, and diabetes. From adjusted linear mixed models, errors on the Modified Mini–Mental State Exam (3
MSE
) were annually 0.41% lower for women at the 25th percentile of
CVD
risk, 0.11% higher at the 50th percentile, and 0.83% higher at the 75th percentile (
P
value of
CVD
risk×time <0.01). In men, 3
MSE
errors were annually 1.76% lower at the 25th percentile of
CVD
risk, 0.96% lower at the 50th percentile, and 0.12% higher at the 75th percentile (
P
value of
CVD
risk×time <0.01). From adjusted linear mixed models, the annual decrease in the Spanish and English Verbal Learning Test score was 0.09 points for women at the 25th percentile of
CVD
risk, 0.10 points at the 50th percentile, and 0.12 points at the 75th percentile (
P
value of
CVD
risk×time=0.02). From adjusted Cox models in women, compared with having <6 years of education, having 12+ years of education was associated with a 76% lower hazard of dementia/
CIND
(95%
CI
, 0.08 to 0.71) at the 25th percentile of
CVD
risk and with a 45% lower hazard (95%
CI
, 0.28 to 1.07) at the 75th percentile (
P
value of
CVD
risk×education=0.05).

Conclusions

CVD
risk score may provide a useful tool for identifying individuals at risk for cognitive decline and dementia.
Traditional Risk Factors Are Not Major Contributors to the Variance in Carotid Intima-Media Thickness
Authors: Rundek Tatjana , Blanton Susan H. , Bartels Susanne , Dong Chuanhui , Raval Ami , Demmer Ryan T. , Cabral Digna , Elkind Mitchell S.V. , Sacco Ralph L. , Desvarieux Moise
Published: May 2013

Background and Purpose—

Carotid intima-media thickness (cIMT) was a widely accepted ultrasound marker of subclinical atherosclerosis in the past. Although traditional risk factors may explain ≈50% of the variance in plaque burden, they may not explain such a high proportion of the variance in IMT, especially when measured in plaque-freel ocations. We aimed this study to identify individuals with cIMT unexplained by traditional risk factors for future environmental and genetic research.

Methods—

As part of the Northern Manhattan Study, 1790 stroke-free individuals (mean age, 69±9 years; 60% women; 61% Hispanic; 19% black; 18% white) were assessed for cIMT using B-mode carotid ultrasound. Multiple linear regression models were evaluated: (1) incorporating prespecified traditional risk factors; and (2) including less traditional factors, such as inflammation biomarkers, adiponectin, homocysteine, and kidney function. Standardized cIMT residual scores were constructed to select individuals with unexplained cIMT.

Results—

Mean total cIMT was 0.92±0.09 mm. The traditional model explained 11% of the variance in cIMT. Age (7%), male sex (3%), glucose (<1%), pack-years of smoking (<1%), and low-density lipoprotein cholesterol (<1%) were significant contributing factors. The model, including inflammatory biomarkers, explained 16% of the variance in cIMT. Adiponectin was the only additional significant contributor to the variance in cIMT. We identified 358 individuals (20%) with cIMT unexplained by the investigated risk factors.

Conclusions—

Vascular risk factors explain only a small proportion of variance in cIMT. Identification of novel genetic and environmental factors underlying unexplained subclinical atherosclerosis is of utmost importance for future effective prevention of vascular disease.
Clot Burden Score on Admission T2*-MRI Predicts Recanalization in Acute Stroke
Authors: Legrand Laurence , Naggara Olivier , Turc Guillaume , Mellerio Charles , Roca Pauline , Calvet David , Labeyrie Marc-Antoine , Baron Jean-Claude , Mas Jean-Louis , Meder Jean-François , Touzé Emmanuel , Oppenheim Catherine
Published: May 2013

Background and Purpose—

To propose a T2*-MR adaptation of the computed tomography angiography-clot burden score (CBS), and assess its value as predictor of 24-hour recanalization and clinical outcome in anterior circulation stroke treated by intravenous thrombolysis ≤4.5 hours from onset.

Methods—

Two independent observers retrospectively analyzed pretreatment T2* images for evaluation of clot burden, using a 10-point scale T2*-CBS. Three points are subtracted for susceptibility vessel sign in the supraclinoid internal carotid artery, 2 points each for susceptibility vessel sign in the proximal and distal part of middle cerebral artery, and 1 point each for susceptibility vessel sign in middle cerebral artery branches (with a maximum of 2 points) and for susceptibility vessel sign in anterior cerebral artery. Associations with 24-hour recanalization and favorable outcome (3-month modified Rankin Scale score, ≤2) were assessed in multivariate analyses.

Results—

We analyzed 184 consecutive patients (mean age, 67 years) with median (interquartile range) admission National Institutes of Health Stroke Scale score and onset-to-treatment time of 15 (9–19) and 151 (120–185) minutes, respectively. The intraclass correlation for T2*-CBS between observers was 0.97 (95% confidence interval, 0.97–0.98). In multivariate analyses, T2*-CBS >6 was significantly associated with 24-hour recanalization (adjusted odds ratio, 5.1 [1.9–13.5];
P
=0.001) or with favorable outcome (adjusted odds ratio, 4.2 [1.7–10.8];
P
=0.003).

Conclusions—

T2*-CBS, a new reproducible semiquantitative score adapted from the computed tomography angiography-CBS, is associated with 24-hour recanalization and 3-month outcome after intravenous thrombolysis. This score needs external validation and could be useful to identify poor responders to intravenous thrombolysis.
Systemic Inflammatory Response Syndrome in Tissue-Type Plasminogen Activator–Treated Patients is Associated With Worse Short-term Functional Outcome
Authors: Boehme Amelia K. , Kapoor Niren , Albright Karen C. , Lyerly Michael J. , Rawal Pawan V. , Bavarsad Shahripour Reza , Alvi Muhammad , Houston J. Thomas , Sisson April , Beasley T. Mark , Alexandrov Anne W. , Alexandrov Andrei V. , Miller David W.
Published: May 2013

Background and Purpose—

Systemic inflammatory response syndrome (SIRS) is a generalized inflammatory state. The primary goal of the study was to determine whether differences exist in outcomes in SIRS and non-SIRS intravenous tissue-type plasminogen activator–treated patients.

Methods—

Consecutive patients were retrospectively reviewed for the evidence of SIRS during their admission. SIRS was defined as the presence of ≥2 of the following: body temperature <36°C or >38°C, heart rate >90, respiratory rate >20, and white blood cells <4000/mm or >12 000 mm, or >10% bands. Patients diagnosed with infection (via positive culture) were excluded.

Results—

Of the 241 patients, 44 had evidence of SIRS (18%). Adjusting for pre–tissue-type plasminogen activator National Institutes of Health Stroke Scale, age, and race, SIRS remained a predictor of poor functional outcome at discharge (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.16–5.73;
P
=0.0197).

Conclusions—

In our sample of tissue-type plasminogen activator–treated (tPA) patients, ~1 in 5 patients developed SIRS. Furthermore, we found the presence of SIRS to be associated with poor short-term functional outcomes and prolonged length of stay.
Onset Headache Predicts Good Outcome in Patients With First-Ever Ischemic Stroke
Authors: Chen Ping-Kun , Chiu Pai-Yi , Tsai I-Ju , Tseng Hung-Pin , Chen Jiunn-Rong , Yeh Shoou-Jeng , Yeh Shin-Joe , Sheu Jau-Jiuan , Chung Chih-Ping , Wu Ming-Hisu , Hu Chaur-Jong , Chang Chun-Yuan , Wei Cheng-Yu , Yip Ping-Keung , Sung Sheng-Feng , Wang Shuu-Jiun , Hsu Chung Y.
Published: May 2013

Background and Purpose—

The study aimed to assess whether onset headache is an ominous sign in patients with first-ever ischemic stroke.

Methods—

A large population of ischemic stroke patients was obtained from the Taiwan Stroke Registry. Stroke subtypes were classified by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. On the basis of the International Classification of Headache Disorders, second version, onset headache was defined as a new headache that developed at the onset of ischemic stroke. Clinical features and impact on stroke outcomes, including in-hospital stroke in evolution, changes in National Institutes of Health Stroke Scale on discharge, and Barthel index and modified Rankin scale ≤6 months after stroke were compared between those with and without onset headache.

Results—

Among 11 523 patients with first-ever ischemic stroke, 848 had onset headache (7.4%). Patients with specific cause, large-artery atherosclerosis, or cardioembolism were more likely to have onset headache. Patients with onset headache were younger, predominantly female, and more likely to have posterior circulation ischemic lesions. Compared with patients without onset headache, those with onset headache had a lower frequency of stroke in evolution (4.5% versus 6.7%; adjusted relative risk, 0.64; 95% confidence interval, 0.52–0.79), greater improvement in National Institutes of Health Stroke Scale score on discharge (0.08 versus −0.20;
P
=0.02), higher mean Barthel index scores (86.5±20.0 versus 83.9±23.3; adjusted difference, 1.43; 95% confidence interval, 0.28–2.89), and a lower frequency of modified Rankin scale higher than 2 (27.6% versus 31.5%; adjusted relative risk, 0.85; 95% confidence interval, 0.72–0.95) at 1-month follow-up. There was also a trend for better functional outcome in 3- and 6-month follow-ups.

Conclusions—

By adopting standard classification criteria, this large-scale study demonstrated that onset headache was associated with modest but significantly better outcomes after ischemic stroke.
Adjusted Poverty Measures and the Distribution of Title I Aid: Does Title I Really Make the Rich States Richer?
Authors: Baker Bruce D. , Taylor Lori , Levin Jesse , Chambers Jay , Blankenship Charles
Published: May 2013

Federal and state governments in the United States make extensive use of student poverty rates in compensatory aid programs like Title I. Unfortunately, the measures of student poverty that drive funding allocations under such programs are biased because they fail to reflect geographic differences in the cost of living. In this study, we construct alternative poverty income thresholds based on regional differences in the wage level for low-skilled workers. We then examine the distribution of Title I revenues after adjusting poverty rates for geographic differences in the cost of living and adjusting Title I revenues for geographic differences in the purchasing power of school districts. Our findings turn conventional wisdom on its head. We find that when we fully adjust for regional differences, Title I funding patterns disproportionately favor rural school districts in low cost-of-living states. We conclude with policy recommendations for revising Title I funding formulas.
Value Added and Its Uses: Where You Stand Depends on Where You Sit
Authors: Corcoran Sean , Goldhaber Dan
Published: May 2013

In this policy brief we argue that there is little debate about the statistical properties of value-added model (VAM) estimates of teacher performance, yet, despite this, there is little consensus about what the evidence about VAMs implies for their practical utility as part of high-stakes performance evaluation systems. A review of the evidence base that underlies the debate over VAM measures, followed by our subjective opinions about the value of using VAMs, illustrates how different policy conclusions can easily arise even given a high-level general agreement about an existing body of evidence. We conclude the brief by offering a few thoughts about the limits of our knowledge and what that means for those who do wish to integrate VAMs into their own teacher-evaluation strategy.
The Strategic Data Project's Strategic Performance Indicators
Authors: Page Lindsay C. , Fullerton Jon , Bacher-Hicks Andrew , Owens Antoniya , Cohodes Sarah R. , West Martin R. , Glover Sarah
Published: May 2013

Strategic Performance Indicators (SPIs) are summary measures derived from parallel, descriptive analyses conducted across educational agencies. The SPIs are designed to inform agency management and efforts to improve student outcomes. We developed the SPIs to reveal patterns common across partner agencies, to highlight exceptions to those patterns, and to provide tools for educational agencies to understand their own successes and challenges. We present two examples of SPI briefs and highlight specific steps partner agencies have taken in response to such analyses. Our goal is that, with data, the SPIs will catalyze educational agencies to engage in deep investigation. If educational systems must rely on academic researchers to make progress on core management challenges, progress will be slow. The ability to use and analyze administrative data must be integrated into the everyday management of educational systems, much as it has been in many other sectors of the modern economy.
The Wasatī and Salafī Approaches to the Religious Law of Muslim Minorities
Authors: Shavit Uriya
Published: May 2013

The article explores the evolution of competing approaches to the religious law of Muslim minorities (fiqh al-aqalliyyāt al-muslima): the wasatī and the salafī. Both approaches are grounded in a similar triumphalist and revivalist contextualization of Muslim presence in the West. The wasatī approach, led by al-Azhar graduates and Islamist activists, presents two objectives: making the lives of Muslim minorities easier in order to preserve their Islamic identity, and endorsing efforts to Islamize the West. To promote these objectives wasatīs emphasize a systematic search in all four religiolegal schools and beyond them and the liberal application of maslaha (public or individual interest). Some of the results achieved by this methodology demonstrate the potential of maslaha to revise any religious law relating to mu'āmalāt (social transactions). The stricter salafī approach associated with conservative elements in Saudi Arabia's religious establishment emphasizes the concept of al-walā' wa'l-barā' (loyalty and disavowal). Its juristic interpretations are based on opposition to perceived innovations, imitation of infidels and cooperation with them. I examine the two approaches through a systematic analysis of three issues that are central to the religious law of Muslim minorities: non-Muslim holidays, mortgages and service in non-Muslim militaries.
Sub-components of the Rule of Law: Reassessing the Relevance of Diminished Subtypes
Authors: Møller Jørgen , Skaaning Svend-Erik
Published: May 2013

Abstract

The rule of law research agenda is in many ways still in its infancy. This is reflected, inter alia, in the fact that no attempt has been made to investigate the empirical relationship between sub-components of the rule law. In this article, we set out to make such an appraisal. We take our cue from a recent attempt to get at this relationship with a typology of ‘defective’ subtypes of the rule of law. Insofar as the underlying radial logic characterizes the relationship between constituent units of the rule of law, it would mean that countries tend to be situated in a range of so-called diminished subtypes, i.e., combinations defined by the presence of all attributes save one. The upshot of this is that we cannot simply aggregate the sub-component scores into composite indices. However, our analyses show that the scores on different rule of law attributes are highly correlated and that – if less fine-grained distinctions are used – cases tend to be characterized by either the presence of all attributes, by moderate scores on all attributes, or by severe shortcomings in every regard. These findings can be taken to support, first, that the value of constructing diminished subtypes of the rule of law is limited, and, second, that the creation of composite measures by aggregating across the rule of law subcomponents is not hampered by multidimensionality. At the end of the article, we use the extant literature on democratization and state formation to identify some potential reasons for the high co-variation between rule of law attributes.
Global Exposure and Openness: Comparative Analysis of Japan, South Korea and Taiwan
Authors: Tsai Ming-Chang , Iwai Noriko
Published: May 2013

Abstract

This empirical study investigates the phenomenon of global mobility and networking at a quotidian level. A typology of global experience is constructed to characterize the qualitative distinctions among individuals’ involvement in global flows. Derived from our understanding of individual border-crossing mobility and transnational relationships, we propose a system of four contrasts: the “global exposed,” “global surfer,” “networked,” and the “local.” Using East Asian Social Survey data, our empirical study compares three Asian countries. It is found that Japan produces more global surfers while Taiwan and South Korea produce more of the global exposed. Locals, however, still account for a large share of the population in all three countries. This study further investigates global exposure as a class-stratified phenomenon by modeling it on various socio-economic variables as well as on speaking English as a form of cultural capital. A multinomial logistic regression analysis shows that the “global exposed” group represents a very select population with rich resources and capital. Despite this notable difference – or perhaps because of it – they, as well as the globally networked, are found to be more likely to accept the increase in foreign workers, imports, and foreign cultural artifacts than are locals and global surfers.
Comparing “Cosmopolitanism”: Taste, Nation and Global Culture in Finland and the UK
Authors: Wright David , Purhonen Semi , Heikkilä Riie
Published: May 2013

Abstract

This paper adds a comparative perspective to the study of taste, cosmopolitanism and social organisation. Drawing on material provided by two similar projects in the UK and Finland it explores the relationships between national and cosmopolitan taste cultures. Whilst there have been some recent attempts to study taste in a comparative perspective, the weight of sociological inquiry into taste is focussed on specific national spaces, including the France of Bourdieu’s (1984) seminal contribution. This tendency persists even as the production and circulation of culture is increasingly accepted as global. Global culture is assumed to be the driver of cosmopolitan ways of being, but is also interpreted as a threat to distinct national cultures. Studies of taste provide an empirical setting where the lived experience of global culture and the ambiguities of cosmopolitanism can be observed. Based on interviews and focus group discussions from the UK and Finland, the paper broadly concurs with those critics who see cosmopolitanism in the context of the maintenance of privileged political or symbolic positions of classes/status groups.
Interdecadal Connection between Arctic Temperature and Summer Precipitation over the Yangtze River Valley in the CMIP5 Historical Simulations
Authors: Li Yuefeng , Leung L. Ruby , Xiao Ziniu , Wei Min , Li Qingquan
Published: May 2013

This study assesses the ability of the Coupled Model Intercomparison Project phase 5 (CMIP5) simulations in capturing the interdecadal precipitation enhancement over the Yangtze River valley (YRV) and investigates the contributions of Arctic temperature and mid- to high-latitude warming to the interdecadal variability of the East Asian summer monsoon rainfall. Six CMIP5 historical simulations including models from the Canadian Centre for Climate Modeling and Analysis (CCCma), the Beijing Climate Center, the Max Planck Institute for Meteorology, the Meteorological Research Institute, the Met Office Hadley Centre, and NCAR are used. The NCEP–NCAR reanalysis and observed precipitation are also used for comparison. Among the six CMIP5 simulations, only CCCma can approximately simulate the enhancement of interdecadal summer precipitation over the YRV in 1990–2005 relative to 1960–75; the various relationships between the summer precipitation and surface temperature (Ts), 850-hPa winds, and 500-hPa height field (H500); and the relationships between Ts and H500 determined using regression, correlation, and singular value decomposition (SVD) analyses. It is found that CCCma can reasonably simulate the interdecadal surface warming over the boreal mid- to high latitudes in winter, spring, and summer. The summer Baikal blocking anomaly is postulated to be the bridge that links the winter and spring surface warming over the mid- to high latitude and Arctic with the enhancement of summer precipitation over the YRV. Models that missed some or all of these relationships found in CCCma and the reanalysis failed to simulate the interdecadal enhancement of precipitation over the YRV. This points to the importance of Arctic and mid- to high-latitude processes on the interdecadal variability of the East Asian summer monsoon and the challenge for global climate models to correctly simulate the linkages.
Diagnostic Computation of Moisture Budgets in the ERA-Interim Reanalysis with Reference to Analysis of CMIP-Archived Atmospheric Model Data*
Authors: Seager Richard , Henderson Naomi
Published: May 2013

The diagnostic evaluation of moisture budgets in archived atmosphere model data is examined. Sources of error in diagnostic computation can arise from the use of numerical methods different from those used in the atmosphere model, the time and vertical resolution of the archived data, and data availability. These sources of error are assessed using the climatological moisture balance in the European Centre for Medium-Range Weather Forecasts Interim Re-Analysis (ERA-Interim) that archives vertically integrated moisture fluxes and convergence. The largest single source of error arises from the diagnostic evaluation of divergence. The chosen second-order accurate centered finite difference scheme applied to the actual vertically integrated moisture fluxes leads to significant differences from the ERA-Interim reported moisture convergence. Using daily data, instead of 6-hourly data, leads to an underestimation of the patterns of moisture divergence and convergence by midlatitude transient eddies. A larger and more widespread error occurs when the vertical resolution of the model data is reduced to the 8 levels that is quite common for daily data archived for the Coupled Model Intercomparison Project (CMIP). Dividing moisture divergence into components due to the divergent flow and advection requires bringing the divergence operator inside the vertical integral, which introduces a surface term for which a means of accurate evaluation is developed. The analysis of errors is extended to the case of the spring 1993 Mississippi valley floods, the causes of which are discussed. For future archiving of data (e.g., by CMIP), it is recommended that monthly means of time-step-resolution flow–humidity covariances be archived at high vertical resolution.
Examining Rapid Onset Drought Development Using the Thermal Infrared–Based Evaporative Stress Index
Authors: Otkin Jason A. , Anderson Martha C. , Hain Christopher , Mladenova Iliana E. , Basara Jeffrey B. , Svoboda Mark
Published: May 2013

Reliable indicators of rapid drought onset can help to improve the effectiveness of drought early warning systems. In this study, the evaporative stress index (ESI), which uses remotely sensed thermal infrared imagery to estimate evapotranspiration (ET), is compared to drought classifications in the U.S. Drought Monitor (USDM) and standard precipitation-based drought indicators for several cases of rapid drought development that have occurred across the United States in recent years. Analysis of meteorological time series from the North American Regional Reanalysis indicates that these events are typically characterized by warm air temperature and low cloud cover anomalies, often with high winds and dewpoint depressions that serve to hasten evaporative depletion of soil moisture reserves. Standardized change anomalies depicting the rate at which various multiweek ESI composites changed over different time intervals are computed to more easily identify areas experiencing rapid changes in ET. Overall, the results demonstrate that ESI change anomalies can provide early warning of incipient drought impacts on agricultural systems, as indicated in crop condition reports collected by the National Agricultural Statistics Service. In each case examined, large negative change anomalies indicative of rapidly drying conditions were either coincident with the introduction of drought in the USDM or lead the USDM drought depiction by several weeks, depending on which ESI composite and time-differencing interval was used. Incorporation of the ESI as a data layer used in the construction of the USDM may improve timely depictions of moisture conditions and vegetation stress associated with flash drought events.