bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Background Predicts Poor Prognosis in Frontotemporal Lobar Degeneration
Authors: Borroni B. , Grassi M. , Archetti S. , Papetti A. , Del Bo R. , Bonvicini C. , Comi G.P. , Gennarelli M. , Bellelli G. , Di Luca M. , Padovani A.
Published: February 2011

Background: Ruling out predictors of survival in frontotemporal lobar degeneration (FTLD) is a clinical challenge for defining disease outcomes and monitoring therapeutic interventions. Little is known about determinants of survival in FTLD. Objective: The aim of the present study was to identify whether genetic determinants are key, not only as risk factors but as predictors of survival in FTLD. Methods: Ninety-seven FTLD patients were considered in the present study. A clinical evaluation and a standardized assessment were carried out. Each patient underwent blood sampling for genetic testing, and mutations within the progranulin (PGRN) gene, microtubule-associated protein tau (MAPT) haplotype, apolipoprotein E (APOE) genotype and 4 vascular endothelial growth factor (VEGF) polymorphisms were evaluated. Discrete-time survival models were applied. Results: Monogenic FTLD due to PGRN mutations [odds ratio (OR) = 3.62, 95% confidence interval (CI) = 1.12–11.7; p = 0.032], and MAPT *H2 haplotype (OR = 3.23, 95% CI = 1.08–9.69; p = 0.036) were associated with an increased hazard risk of poor outcome. Conversely, APOE genotype, and VEGF polymorphisms were not associated with survival risk in the FTLD sample. Conclusions: Genetic background is not only crucial in disease pathogenesis, but it also modulates disease course. Genetic factors influencing prognosis should be taken into account to include homogeneous groups in future clinical trials and to monitor efficacy of future interventions.
Further Evidence on Mitochondrial Targeting of β-Amyloid and Specificity of β-Amyloid-Induced Mitotoxicity in Neurons
Authors: Tillement Laurent , Lecanu Laurent , Papadopoulos Vassilios
Published: February 2011

Background/Aims: Impaired mitochondrial function has been described in Alzheimer’s disease. We previously reported that, in neuronal cells, β-amyloid 1–42 (Aβ1–42) is targeted to mitochondria. We have also reported that, when incubated with isolated rat brain mitochondria, Aβ1–42 inhibits complex IV, uncouples the mitochondrial respiratory chain, and promotes opening of the membrane permeability transition pore. Here, we further analyzed the targeting and mitotoxicity of Aβ1–42. Methods and Results: Immunoelectron microscopy revealed that the mitochondrial targeting of Aβ1–42 was concentration- and time-dependent. Incubation of human neuroblastoma cells with Aβ1–42 increased the release of adenylate kinase, a mitochondrial enzyme released after membrane permeability transition pore opening. However, it failed to trigger DNA fragmentation and apoptosis, suggesting that the ability of this peptide to uncouple the respiratory chain underlies its mitotoxicity and cytotoxicity. Aβ1–42 targeting to mitochondria was blocked by caprospinol, a steroid derivative shown to protect neuronal cells against Aβ1–42-induced neurotoxicity. Further experiments revealed that the mitotoxic effect of Aβ1–42 is specific to its primary amino acid sequence and suggested that it may be also related to its tertiary structure. Importantly, the mitotoxic effect of Aβ1–42 was not restricted to brain cells, indicating that it is not cell- or tissue-specific. Conclusion: Taken together, these results suggest that extracellular Aβ1–42 targets neuronal mitochondria to exert its toxic effects.
Validation of the Measurement of Haemodialysis Access Flow Using a Haemoglobin Dilution Test
Authors: Jiang Simon Hee-Tang , Clayton Philip Andrew , Maguire Anne , Talaulikar Girish Sricant
Published: February 2011

Monitoring of blood flows in arteriovenous fistulae and arteriovenous grafts is recommended to predict access thrombosis. The ultrasound dilution technique (UDT) is the gold standard. We compare a recently described haemoglobin dilution technique (HDT) with the UDT in measurement of vascular access flow. Access blood flow was measured in 67 stable dialysis patients using HDT by bedside Hemocue (Hemocue AB, Ängelholm, Sweden) and laboratory measurement. Access blood flow was then measured by UDT in the same dialysis session. Median flow rate by UDT was 950 ml/min (IQR 490–1,440 ml/min), by Hemocue HDT 935 ml/min (IQR 475–1,395 ml/min, p = 0.534), and by laboratory haemoglobin HDT 920 ml/min (IQR 463–1,378 ml/min). Bland-Altman plots demonstrated poor agreement between UDT and HDT (limits of agreement for Hemocue HDT –22.7 to 20.1%, for laboratory HDT –21.2 to 20.4%). HDT can be used to measure vascular access flow but requires validation against clinical outcomes before being recommended as an alternative to UDT.
Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Complications and Mortality in Patients Undergoing Non-Cardiac Major Surgery
Authors: Shavit Linda , Dolgoker Irena , Ivgi Heftziba , Assous Marc , Slotki Itzchak
Published: February 2011

Introduction: We tested the hypothesis that urinary and serum neutrophil gelatinase-associated lipocalins (NGAL) early after non-cardiac major surgery predict postoperative acute kidney injury (AKI), complications and mortality. Methods: We studied 74 patients undergoing orthopedic, vascular and abdominal surgery lasting ≧2 h. NGAL was measured in preoperative, as well as 2- and 6-hour postoperative samples. The primary outcome was AKI. Secondary outcome was postoperative infection and death. Results: 10 patients (13.5%) developed AKI, 19 (26%) reached secondary outcomes, of whom 5 (7%) died. Serum NGAL was significantly higher in patients with diabetes and chronic kidney disease (CKD). No significant correlation was detected between serum or urine NGAL and subsequent development of AKI. Urine NGAL at 6 h and serum NGAL at 2 and 6 h were strongly correlated with postoperative infection and death (p = 0.004, p = 0.013 and p = 0.001, respectively). Conclusions: Our data suggest that in the general surgical population, NGAL could serve as a potent early biomarker for postoperative infection, and that the presence of CKD and diabetes mellitus is associated with higher levels of NGAL and may influence its predictive value.
Differential Notch Signaling in the Epicardium Is Required for Cardiac Inflow Development and Coronary Vessel Morphogenesis
Authors: del Monte Gonzalo , Casanova Jesús C. , Guadix Juan Antonio , MacGrogan Donal , Burch John B.E. , Pérez-Pomares José María , de la Pompa José Luis
Published: February 2011

Rationale:

The proepicardium is a transient structure comprising epicardial progenitor cells located at the posterior limit of the embryonic cardiac inflow. A network of signals regulates proepicardial cell fate and defines myocardial and nonmyocardial domains at the venous pole of the heart. During cardiac development, epicardial-derived cells also contribute to coronary vessel morphogenesis.

Objective:

To study Notch function during proepicardium development and coronary vessel formation in the mouse.

Methods and Results:

Using in situ hybridization, RT-PCR, and immunohistochemistry, we find that Notch pathway elements are differentially activated throughout the proepicardial–epicardial–coronary transition. Analysis of
RBPJk
-targeted embryos indicates that Notch ablation causes ectopic procardiogenic signaling in the proepicardium that in turn promotes myocardial differentiation in adjacent mesodermal progenitors, resulting in a premature muscularization of the sinus venosus horns. Epicardium-specific
Notch1
ablation using a
Wt1-Cre
driver line disrupts coronary artery differentiation, reduces myocardium wall thickness and myocyte proliferation, and reduces
Raldh2
expression. Ectopic Notch1 activation disrupts epicardium development and causes thinning of ventricular walls.

Conclusions:

Epicardial Notch modulates cell differentiation in the proepicardium and adjacent pericardial mesoderm. Notch1 is later required for arterial endothelium commitment and differentiation and for vessel wall maturation during coronary vessel development and myocardium growth.
Mitochondrial Oxidative Stress Mediates Angiotensin II–Induced Cardiac Hypertrophy and Gαq Overexpression–Induced Heart Failure
Authors: Dai Dao-Fu , Johnson Simon C. , Villarin Jason J. , Chin Michael T. , Nieves-Cintrón Madeline , Chen Tony , Marcinek David J. , Dorn Gerald W. , Kang Y. James , Prolla Tomas A. , Santana Luis F. , Rabinovitch Peter S.
Published: February 2011

Rationale:

Mitochondrial dysfunction has been implicated in several cardiovascular diseases; however, the roles of mitochondrial oxidative stress and DNA damage in hypertensive cardiomyopathy are not well understood.

Objective:

We evaluated the contribution of mitochondrial reactive oxygen species (ROS) to cardiac hypertrophy and failure by using genetic mouse models overexpressing catalase targeted to mitochondria and to peroxisomes.

Methods and Results:

Angiotensin II increases mitochondrial ROS in cardiomyocytes, concomitant with increased mitochondrial protein carbonyls, mitochondrial DNA deletions, increased autophagy and signaling for mitochondrial biogenesis in hearts of angiotensin II–treated mice. The causal role of mitochondrial ROS in angiotensin II–induced cardiomyopathy is shown by the observation that mice that overexpress catalase targeted to mitochondria, but not mice that overexpress wild-type peroxisomal catalase, are resistant to cardiac hypertrophy, fibrosis and mitochondrial damage induced by angiotensin II, as well as heart failure induced by overexpression of Gαq. Furthermore, primary damage to mitochondrial DNA, induced by zidovudine administration or homozygous mutation of mitochondrial polymerase γ, is also shown to contribute directly to the development of cardiac hypertrophy, fibrosis and failure.

Conclusions:

These data indicate the critical role of mitochondrial ROS in cardiac hypertrophy and failure and support the potential use of mitochondrial-targeted antioxidants for prevention and treatment of hypertensive cardiomyopathy.
Ablation of the Leptin Receptor in the Hypothalamic Arcuate Nucleus Abrogates Leptin-Induced Sympathetic Activation
Authors: Harlan Shannon M. , Morgan Donald A. , Agassandian Khristofor , Guo Deng-Fu , Cassell Martin D. , Sigmund Curt D. , Mark Allyn L. , Rahmouni Kamal
Published: February 2011

Rationale:

The hypothalamic arcuate nucleus (ARC) is considered a major site for leptin signaling that regulates several physiological processes.

Objective:

To test the hypothesis that leptin receptor in the ARC is required to mediate leptin-induced sympathetic activation.

Methods and Results:

First, we used the ROSA Cre-reporter mice to establish the feasibility of driving Cre expression in the ARC in a controlled manner with bilateral microinjection of adenovirus-expressing Cre-recombinase (Ad-Cre). Ad-Cre microinjection into the ARC of ObR
flox/flox
mice robustly reduced ObR expression and leptin-induced Stat3 activation in the ARC but not in the adjacent nuclei, confirming the efficacy and selectivity of the ARC deletion of ObR. Critically, deletion of ObR in the ARC attenuated brown adipose tissue and renal sympathetic nerve responses to leptin. We also examined whether ObR in the ARC is required for the preserved leptin-induced increase in renal sympathetic activity in dietary obesity. We found that deletion of ARC ObR abrogated leptin-induced increases in renal sympathetic discharge and resolved arterial pressure elevation in diet-induced obese ObR
flox/flox
mice.

Conclusions:

These data demonstrate a critical role for ObR in the ARC in mediating the sympathetic nerve responses to leptin and in the adverse sympathoexcitatory effects of leptin in obesity.
Dynamic Calcium Movement Inside Cardiac Sarcoplasmic Reticulum During Release
Authors: Picht Eckard , Zima Aleksey V. , Shannon Thomas R. , Duncan Alexis M. , Blatter Lothar A. , Bers Donald M.
Published: February 2011

Rationale:

Intra–sarcoplasmic reticulum (SR) free [Ca] ([Ca]
SR
) provides the driving force for SR Ca release and is a key regulator of SR Ca release channel gating during normal SR Ca release or arrhythmogenic spontaneous Ca release events. However, little is known about [Ca]
SR
spatiotemporal dynamics.

Objective:

To directly measure local [Ca]
SR
with subsarcomeric spatiotemporal resolution during both normal global SR Ca release and spontaneous Ca sparks and to evaluate the quantitative implications of spatial [Ca]
SR
gradients.

Methods and Results:

Intact and permeabilized rabbit ventricular myocytes were subjected to direct simultaneous measurement of cytosolic [Ca] and [Ca]
SR
and FRAP (fluorescence recovery after photobleach). We found no detectable [Ca]
SR
gradients between SR release sites (junctional SR) and Ca uptake sites (free SR) during normal global Ca release, clear spatiotemporal [Ca]
SR
gradients during isolated Ca blinks, faster intra-SR diffusion in the longitudinal versus transverse direction, 3- to 4-fold slower diffusion of fluorophores in the SR than in cytosol, and that intra-SR Ca diffusion varies locally, dependent on local SR connectivity. A computational model clarified why spatiotemporal gradients are more detectable in isolated local releases versus global releases and provides a quantitative framework for understanding intra-SR Ca diffusion.

Conclusions:

Intra-SR Ca diffusion is rapid, limiting spatial [Ca]
SR
gradients during excitation–contraction coupling. Spatiotemporal [Ca]
SR
gradients are apparent during Ca sparks, and these observations constrain models of dynamic Ca movement inside the SR. This has important implications for myocyte SR Ca handling, synchrony, and potentially arrhythmogenic spontaneous contraction.
Emergency Department Crowding and Time to Care in Patients With Acute Stroke
Authors: Chatterjee Pia , Cucchiara Brett L. , Lazarciuc Nicole , Shofer Frances S. , Pines Jesse M.
Published: February 2011

Background and Purpose—

Emergency department (ED) crowding occurs when demands for ED care exceed the supply of available resources. Prior studies have shown that ED crowding is associated with a delay in provision of critical ED services, but the impact of ED crowding on acute stroke care has not been extensively studied.

Methods—

We conducted a retrospective study of patients who presented to the ED with acute stroke symptoms (ischemic stroke, transient ischemic attack, intracerebral hemorrhage) at 2 hospitals. All patients with active stroke symptoms who presented within 3 hours were included and a random sample of patients with symptoms >3 hours was used for comparison. The association between ED crowding measures (waiting room number, ED occupancy, number of admitted patients, and total patient hours) and time to head CT order, completion, and interpretation, and time to administration of thrombolysis was determined.

Results—

Of 253 patients presenting with acute stroke symptoms ≤3 hours from symptom onset, 52 (21%) received thrombolysis. A random comparison group of 253 patients with symptoms >3 hours was identified. There was no significant association between ED crowding and delays in CT timing or thrombolysis in patients with symptoms ≤3 hours. Several measures of ED crowding were associated with prolonged times to CT order and completion in patients with symptoms >3 hours.

Conclusions—

ED crowding was not associated with care delays in thrombolysis-eligible patients with stroke. However, those with symptoms >3 hours do experience CT delays at higher levels of ED crowding.
Restenosis Is More Frequent After Carotid Stenting Than After Endarterectomy
Authors: Arquizan Caroline , Trinquart Ludovic , Touboul Pierre-Jean , Long Anne , Feasson Séverine , Terriat Béatrice , Gobin-Metteil Marie-Pierre , Guidolin Brigitte , Cohen Serge , Mas Jean-Louis
Published: February 2011

Background and Purpose—

Carotid angioplasty and stenting (CAS) may be more often associated with residual or recurrent stenosis than carotid endarterectomy (CEA). We compared the rates of restenosis in patients treated with CAS or CEA in the EVA-3S trial.

Methods—

Five hundred seven patients (242 treated by CAS and 265 by CEA) had carotid ultrasound follow-up (mean carotid ultrasound follow-up, 2.1 years) according to a predefined protocol. Carotid restenosis of 50% to 69% was diagnosed on planimetry, whereas carotid restenosis of ≥70% or occlusion was diagnosed using either planimetry or velocity criteria.

Results—

The rate of carotid restenosis of ≥50% or occlusion was significantly higher after CAS (12.5%) than after CEA (5.0%; time ratio, 0.16; 95% CI, 0.03–0.76;
P
=0.02). The rates of severe restenosis of ≥70% or occlusion were low and did not differ significantly between the 2 groups (3-year rates are 3.3% in the CAS group and 2.8% in the CEA group). Age at baseline was the only vascular risk factor significantly associated with carotid restenosis. Our study could not detect any effect of carotid restenosis on ipsilateral stroke.

Conclusions—

The short-term rate of carotid restenosis of ≥50% or occlusion is ≈2.5-times more common after CAS than after CEA, a difference accounted for by an excess risk in moderate restenosis. More data with longer follow-up are needed to assess the rates of late severe restenosis and to determine the relation between restenosis and recurrent stroke over time.
Carotid Plaque Area and Intima-Media Thickness in Prediction of First-Ever Ischemic Stroke
Authors: Mathiesen Ellisiv B. , Johnsen Stein Harald , Wilsgaard Tom , Bønaa Kaare H. , Løchen Maja-Lisa , Njølstad Inger
Published: February 2011

Background and Purpose—

Carotid plaque and intima-media thickness (IMT) are recognized as risk factors for ischemic stroke, but their predictive value has been debated and varies between studies. The purpose of this longitudinal population-based study was to assess the risk of ischemic stroke associated with plaque area and IMT in the carotid artery.

Methods—

IMT and total plaque area in the right carotid artery were measured with ultrasound in 3240 men and 3344 women aged 25 to 84 years who participated in a population health study in 1994 to 1995. First-ever ischemic strokes were identified through linkage to hospital and national diagnosis registries, with follow-up until December 31, 2005.

Results—

Incident ischemic strokes occurred in 7.3% (n=235) of men and 4.8% (n=162) of women. The hazard ratio for 1 SD increase in square-root-transformed plaque area was 1.23 (95% CI, 1.09–1.38;
P
=0.0009) in men and 1.19 (95% CI, 1.01–1.41;
P
=0.04) in women when adjusted for other cardiovascular risk factors. The multivariable-adjusted hazard ratio in the highest quartile of plaque area versus no plaque was 1.73 (95% CI, 1.19–2.52;
P
=0.004) in men and 1.62 (95% CI, 1.04–2.53;
P
=0.03) in women. The multivariable-adjusted hazard ratio for 1 SD increase in IMT was 1.08 (95% CI, 0.95–1.22;
P
=0.2) in men and 1.24 (95% CI, 1.05–1.48;
P
=0.01) in women. There were no differences in stroke risk across quartiles of IMT in multivariable analysis.

Conclusions—

In the present study, total plaque area appears to be a stronger predictor than IMT for first-ever ischemic stroke.
Cognitive Context Determines Dorsal Premotor Cortical Activity During Hand Movement in Patients After Stroke
Authors: Dennis Andrea , Bosnell Rose , Dawes Helen , Howells Ken , Cockburn Janet , Kischka Udo , Matthews Paul , Johansen-Berg Heidi
Published: February 2011

Background and Purpose—

Stroke patients often have difficulties in simultaneously performing a motor and cognitive task. Functional imaging studies have shown that movement of an affected hand after stroke is associated with increased activity in multiple cortical areas, particularly in the contralesional hemisphere. We hypothesized patients for whom executing simple movements demands greater selective attention will show greater brain activity during movement.

Methods—

Eight chronic stroke patients performed a behavioral interference test using a visuo-motor tracking with and without a simultaneous cognitive task. The magnitude of behavioral task decrement under cognitive motor interference (CMI) conditions was calculated for each subject. Functional MRI was used to assess brain activity in the same patients during performance of a visuo-motor tracking task alone; correlations between CMI score and movement-related brain activation were then explored.

Results—

Movement-related activation in the dorsal precentral gyrus of the contralesional hemisphere correlated strongly and positively with CMI score (
r
2
at peak voxel=0.92;
P
<0.05). Similar but weaker relationships were observed in the ventral precentral and middle frontal gyrus. There was no independent relationship between hand motor impairment and CMI.

Conclusions—

Results suggest that variations in the degree to which a cognitive task interferes with performance of a concurrent motor task explains a substantial proportion of the variations in movement-related brain activity in patients after stroke. The results emphasize the importance of considering cognitive context when interpreting brain activity patterns and provide a rationale for further evaluation of integrated cognitive and movement interventions for rehabilitation in stroke.
Altered Expression of PIWI RNA in the Rat Brain After Transient Focal Ischemia
Authors: Dharap Ashutosh , Nakka Venkata Prasuja , Vemuganti Raghu
Published: February 2011

Background and Purpose—

The PIWI-interacting RNA (piRNA) is the most predominant RNA species in eukaryotes. The piRNA are a class of noncoding RNAs that bind and degrade the RNA formed by the transposons to control the transposon-induced gene mutations. The role of piRNA after focal ischemia is not yet evaluated.

Methods—

We profiled 39 727 piRNAs in the cerebral cortex of adult rats subjected to transient focal ischemia using microarrays. The RT targets of stroke-responsive piRNAs were identified with bioinformatics. To understand how piRNAs are controlled, we analyzed the transcription factor binding sites in the putative promoters of 10 representative stroke-responsive piRNAs.

Results—

In the ipsilateral cortex of ischemic rats, 105 piRNAs showed altered expression (54 up- and 51 downregulated; >2.5-fold) compared with shams. Twenty-five of those showed a >5-fold change. A bioinformatics search showed that the transposon targets of the highly stroke-responsive piRNAs are distributed among the 20 autosomal chromosomes and there is a redundancy in the targets between the piRNAs. Furthermore, the transposon targets were observed to be highly repetitious for each piRNA across the chromosome length. Of the 159 transcription factors observed to have binding sites in the piRNA gene promoters, 59% belonged to 20 major families indicating that transcription factors control stroke-responsive piRNAs in a redundant manner.

Conclusions—

The present study is the first to show that many piRNAs are expressed in adult rodent brain and several of them respond to focal ischemia.
An Analysis of Inflation Times During Balloon-Assisted Aneurysm Coil Embolization and Ischemic Complications
Authors: Spiotta Alejandro M. , Bhalla Tarun , Hussain Muhammad S. , Sivapatham Thinesh , Batra Ayush , Hui Ferdinand , Rasmussen Peter A. , Moskowitz Shaye I.
Published: February 2011

Background and Purpose—

The introduction of balloon remodeling has revolutionized the approach to coiling of wide-neck aneurysms. We studied the effects of balloon inflation during coil embolization on ischemic complications.

Methods—

A retrospective review was undertaken of the most recent 147 patients undergoing balloon remodeling for unruptured intracranial aneurysm coil embolization at a single institution (81 balloon, 66 unassisted). All underwent postprocedural MRI.

Results—

Among patients in the “balloon” group, the mean total inflation time was 18 minutes (range, 1–43), a mean number of inflations of 4 (range, 1–9), a mean maximum single inflation time of 7 minutes (range, 1–19), a mean reperfusion time of 2.2 minutes between inflations, and an average procedure time of 2 hours and 10 minutes. Asymptomatic diffusion-weighted imaging abnormalities were detected on postprocedural MRI in 21.5% of patients and symptomatic lesions were identified in 3.8%. Both silent and symptomatic ischemic rates were similar in the internal control group. Patients with ischemic findings were older and more likely have diabetes; no differences were found with respect to total balloon inflation time, number of inflations, maximum inflation time, or reperfusion times.

Conclusions—

We found no significant relationship between balloon inflation practices and ischemic events. Older and diabetic patients were more likely to have ischemic events develop.
Visual Perfusion–Diffusion Mismatch Is Equivalent to Quantitative Mismatch
Authors: Luby Marie , Ku Katherine D. , Latour Lawrence L. , Merino José G. , Hsia Amie W. , Lynch John K. , Warach Steven
Published: February 2011

Background and Purpose—

The concept of stroke MRI mismatch based on qualitative evaluation of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) has been applied in clinical practice for several years. The benefit of MRI in providing pathological evidence of ischemia before thrombolytic treatment has been demonstrated. The purpose of this study is to determine the reliability of the qualitative method and compare it with quantitative mismatch measurement in thrombolytic-treated patients.

Methods—

Patients (n=70) were selected from the Lesion Evolution of Stroke and Ischemic On Neuroimaging (LESION) database if they: (1) were treated with intravenous recombinant tissue plasminogen activator; (2) had a pretreatment MRI with evaluable DWI and PWI; and (3) had acute ischemic lesion volume >10 mL on DWI as determined by core imaging laboratory measurements. Quantitative mismatch was defined as a difference of >50 mL between abnormal mean transit time and DWI volumes. Sample characteristics and postdischarge modified Rankin Scale for the positive mismatch patients were compared between the subgroups identified by qualitative versus quantitative methods.

Results—

Patient characteristics and thrombolytic outcomes (sex, age, National Institutes of Health Stroke Scale, mismatch volume, and modified Rankin Scale) did not differ for mismatch patients identified by qualitative versus quantitative methods. Qualitative mismatch selection among neurologists had a high sensitivity (0.82), specificity (0.80), accuracy (0.81), and positive predictive value (0.88) compared with quantitative measurements.

Conclusions—

We observed that qualitative evaluation of mismatch identified the same thrombolytic-treated patients compared with retrospective quantitative mismatch measurements.
Traditional Risk Factors for Incident Cardiovascular Events Have Limited Importance in Later Life Compared With the Health in Men Study Cardiovascular Risk Score
Authors: Beer Christopher , Alfonso Helman , Flicker Leon , Norman Paul E. , Hankey Graeme J. , Almeida Osvaldo P.
Published: February 2011

Background and Purpose—

This study aimed to determine, among older men, the risk and independent significant baseline prognostic factors for first-ever stroke and MI.

Methods—

We performed a prospective cohort study of 4382 community-dwelling older men (mean age, 75.4±4.2 years) with no history of stroke or MI. Baseline data comprised questionnaire responses, clinical measurements, and comorbidity.

Results—

After a median of 6 years (interquartile range, 5.2–7.2) of follow-up, the overall rate of stroke/MI was 2.61 (95% CI, 2.42–2.81) per 100 person-years. Among major traditional risk prediction variables, only age and smoking were significantly associated with stroke/MI. In our final multivariate model, the independent significant predictors of stroke/MI were age (HR for age older than 85, 3.18; 95% CI, 2.05–4.93), diastolic blood pressure <70 mm Hg (Hazard ratio [HR], 1.45; 95% CI, 1.18–1.78), high-sensitivity C-reactive protein >3 mg/L (HR, 1.29; 95% CI, 1.05–1.59), homocysteine >15 umol/L (HR, 1.35; 95% CI, 1.09–1.67), waist-to-hip ratio >1 (HR, 1.47; 95% CI, 1.20–1.18), and fair or poor self-reported health (HR, 1.52; 95% CI, 1.19–1.94). A new risk model incorporating these variables performed well compared with the Framingham risk equation (Harrell C of 0.660 versus C of 0.620; integrated discrimination improvement of 1.85%; z=4.95;
P
<0.001; net reclassification index of 0.08; z=2.0;
P
=0.023). The model was used to develop an 8- point clinical risk score comprising the independent predictors of stroke/MI among this population.

Conclusions—

Traditional vascular risk factors did not optimally predict stroke/MI among this cohort of community-dwelling older men. We have constructed a new risk score that requires validation in other data sets.
Bone Marrow Stromal Cells Promote Skilled Motor Recovery and Enhance Contralesional Axonal Connections After Ischemic Stroke in Adult Mice
Authors: Liu Zhongwu , Li Yi , Zhang Rui Lan , Cui Yisheng , Chopp Michael
Published: February 2011

Background and Purpose—

We tested the effect of bone marrow stromal cells (BMSCs) on neuronal remodeling of the corticospinal tract originating from the contralesional cortex in mice subjected to unilateral pyramidotomy (PT) followed by middle cerebral artery occlusion (MCAO).

Methods—

Adult mice with transgenic yellow fluorescent protein labeling in the corticospinal tract were subjected to right hemispheric PT and right permanent or sham MCAO. One day later, the mice were treated intravenously with BMSCs or phosphate-buffered saline. A Foot-Fault test and a single pellet-reaching test were performed before surgery, 3 days after MCAO, and weekly thereafter. Pseudorabies virus-614-monomeric red fluorescent protein was injected into the left forelimb flexor muscles 28 days after surgery (4 days before euthanasia). The brain and cervical cord were processed for fluorescent microscopy to detect red fluorescent protein and yellow fluorescent protein labeling, respectively.

Results—

Significant functional improvements were evident in PT-MCAO mice treated with BMSCs (n=9) compared with phosphate-buffered saline-treated mice (n=9,
P
<0.05), but not in mice with PT-sham MCAO treated with either phosphate-buffered saline (n=9) or BMSCs (n=10). Furthermore, in PT-MCAO mice, both corticospinal tract axonal density in the denervated side of the cervical gray matter and red fluorescent protein-labeled pyramidal neurons in the left intact cortex were significantly increased compared with PT-sham MCAO mice (
P
<0.05). BMSCs significantly enhanced both corticospinal tract density and red fluorescent protein labeling in PT-MCAO mice (
P
<0.05) only. The behavioral outcome was highly correlated with corticospinal tract density and red fluorescent protein labeling.

Conclusions—

BMSCs amplify stroke-induced contralesional neuronal remodeling, which contributes to motor recovery after stroke.
Perceiving Opponent Hues in Color Induction Displays
Authors: Mingolla Ennio , Livitz Gennady , Eskew, Jr. Rhea , Yazdanbakhsh Arash
Published: February 2011

According to Hering's color theory, certain hues (red vs green and blue vs yellow) are mutually exclusive as components of a single color; consequently a color cannot be perceived as reddish-green or bluish-yellow. The goal of our study is to test this key postulate of the opponent color theory. Using the method of adjustment, our observers determine the boundaries of chromatic zones in a red–green continuum. We demonstrate on two distinct stimulus sets, one formed using a chromatic grid and neon spreading and the other based on solid colored regions, that the chromatic contrast of a purple surround over a red figure results in perception of 'forbidden' reddish-green colors. The observed phenomenon can be understood as resulting from the construction of a virtual filter, a process that bypasses photoreceptor summation and permits forbidden color combinations. Showing that opponent hue combinations, previously reported only under artificial image stabilization, can be present in normal viewing conditions offers new approaches for the experimental study of the dimensionality and structure of perceptual color space.
The Effect of Set Size on the Dynamics of Binocular Rivalry
Authors: Paffen Chris , Hooge Ignace
Published: February 2011

During binocular rivalry, the percept alternates between dissimilar images presented dichoptically. A central question in studies on binocular rivalry is whether its dynamics are affected by attention. Here we approach this question by studying how set size affects the number of alternations reported from a rivalry-inducing display. The results show that the number of alternations reported increased only slightly with increasing set size. In follow-up experiments we show that neither (1) limitations in response speed nor (2) grouping cues are responsible for this result, and that (3) increasing set size decreases the number of alternations reported per rivalry-inducing element. Our results show that the spatial distribution of attention affects the number of alternations reported in a rivalry-inducing display.
Perceptual Upright: The Relative Effectiveness of Dynamic and Static Images Under Different Gravity States
Authors: Jenkin Michael , Zacher James , Dyde Richard , Harris Laurence , Jenkin Heather
Published: February 2011

The perceived direction of up depends on both gravity and visual cues to orientation. Static visual cues to orientation have been shown to be less effective in influencing the perception of upright (PU) under microgravity conditions than they are on earth (Dyde et al., 2009). Here we introduce dynamic orientation cues into the visual background to ascertain whether they might increase the effectiveness of visual cues in defining the PU under different gravity conditions. Brief periods of microgravity and hypergravity were created using parabolic flight. Observers viewed a polarized, natural scene presented at various orientations on a laptop viewed through a hood which occluded all other visual cues. The visual background was either an animated video clip in which actors moved along the visual ground plane or an individual static frame taken from the same clip. We measured the perceptual upright using the oriented character recognition test (OCHART). Dynamic visual cues significantly enhance the effectiveness of vision in determining the perceptual upright under normal gravity conditions. Strong trends were found for dynamic visual cues to produce an increase in the visual effect under both microgravity and hypergravity conditions.
Lagrangian Eddy Scales in the Northern Atlantic Ocean
Authors: Lumpkin Rick , Treguier Anne-Marie , Speer Kevin
Published: February 2011

Eddy time and length scales are calculated from surface drifter and subsurface float observations in the northern Atlantic Ocean. Outside the energetic Gulf Stream, subsurface timescales are relatively constant at depths from 700 m to 2000 m. Length scale and the characteristic eddy speed decrease with increasing depth below 700 m, but length scale stays relatively constant in the upper several hundred meters of the Gulf Stream. It is suggested that this behavior is due to the Lagrangian sampling of the mesoscale field, in limits set by the Eulerian eddy scales and the eddy kinetic energy. In high-energy regions of the surface and near-surface North Atlantic, the eddy field is in the “frozen field” Lagrangian sampling regime for which the Lagrangian and Eulerian length scales are proportional. However, throughout much of the deep ocean interior, the eddy field may be in the “fixed float” regime for which the Lagrangian and Eulerian timescales are nearly equal. This does not necessarily imply that the deep interior is nearly linear, as fixed-float sampling is possible in a flow field of O(1) nonlinearity.
A Climatological Interpretation of the Circulation in the Western South Pacific*
Authors: Qu Tangdong , Lindstrom Eric J.
Published: February 2011

Time-averaged circulation is examined using historical hydrographic data near the Australia and Papua New Guinea coast in the Pacific. By averaging the data along isopycnal surfaces in a 0.5° × 0.5° grid, the authors are able to show many detailed phenomena associated with the narrow western boundary currents, including the vertical structure of the bifurcation latitude of the South Equatorial Current (SEC) and the connection between the Solomon and Coral Seas. The bifurcation latitude of the SEC is found to move southward from about 15°S near the surface to south of 22°S in the intermediate layers. The origin of the Great Barrier Reef Undercurrent (GBRUC) is identified to be at about 22°S. Farther to the north, the GBRUC intensifies underlying the surface East Australian Current, and merges with the North Queensland Current (NQC) at about 15°S. The NQC turns eastward to flow along the Papua New Guinea coast and feeds into the New Guinea Coastal Undercurrent (NGCUC) through the Louisiade Archipelago. Further analysis shows that there is a strong water property connection between the Coral and Solomon Seas, confirming the earlier speculation on the water mass origins of the NGCUC.
On Determining the Onset and Strength of Breaking for Deep Water Waves. Part II: Influence of Wind Forcing and Surface Shear
Authors: Banner Michael L. , Song Jin-Bao
Published: February 2011

Part I of this study describes the authors' findings on a robust threshold variable that determines the onset of breaking for unforced, irrotational deep water waves and proposes a means of predicting the strength of breaking if the breaking threshold is exceeded. Those results were based on a numerical study of the unforced evolution of fully nonlinear, two-dimensional inviscid wave trains and highlight the fundamental role played by the nonlinear wave group dynamics. In Part II the scope of these calculations is extended to investigate the additional influence of wind forcing and background shear on the evolution to breaking.

Using the methodology described in Part I, the present study focuses on the influence of wind forcing and vertical shear on long-term evolution toward breaking or recurrence of the maximum of the local energy density within a wave group. It investigates the behavior of a dimensionless local growth rate parameter that reflects the mean energy flux to the energy maximum in the wave group and provides a clearer physical interpretation of the evolution toward recurrence or breaking. Typically, the addition of the wind forcing and surface layer shear results in only small departures from the irrotational, unforced cases reported in Part I. This indicates that nonlinear hydrodynamic energy fluxes within wave groups still dominate the evolution to recurrence or breaking even in the presence of these other mechanisms. Further, the calculations confirm that the breaking threshold for this growth rate found for unforced irrotational wave groups in Part I is also applicable for cases with wind forcing and shear typical of open ocean conditions. Overall, this approach provides an earlier and more decisive indicator for the onset of breaking than previously proposed breaking thresholds and suggests a foundation for predicting the strength of breaking events.
North Atlantic Modeling of Low-Frequency Variability in Mode Water Formation
Authors: Paiva Afonso M. , Chassignet Eric P.
Published: February 2011

The generation of interannual and near-decadal variability in the formation of mode waters in the western North Atlantic is investigated in the realistic framework of an isopycnic coordinate ocean model forced with atmospheric data from 1946 to 1988. At Bermuda, the model reproduces quite well the observed potential vorticity and isopycnal depth anomalies associated with the subtropical mode water (STMW). Heat storage and preconditioning of the convective activity are found to be the important factors for the generation of STMW variability, with persistence of cold (warm) conditions, associated with anomalous heat loss (gain) over the western subtropics, being more significant for the generation of the simulated variability than are strong anomalous events in isolated years.

In the Labrador Sea, the model captures the phase and order of magnitude of the observed near-decadal variability in the convective activity, if not its maximum amplitude. The simulated potential vorticity anomalies are, as observed, out-of-phase with those in the western subtropics and correlate well with the North Atlantic Oscillation (NAO) at near-decadal timescales, with the oceanic response lagging the NAO by ∼2–3 years. These results support the idea that the variability in water mass formation in the western North Atlantic can be attributed, to a large extent, to changes in the pattern of the large-scale atmospheric circulation, which generate sensible and latent heat flux variability by modifying the strength and position of the westerly winds and the advection of heat and moisture over the ocean. To the authors' knowledge, this is the first time that the interannual and near-decadal subsurface variability associated with STMW and Labrador Sea Water, and its relationship to the NAO, has been simulated in an ocean general circulation model.
Long-Term Observations of Tropical Instability Waves
Authors: Contreras Robert F.
Published: February 2011

Reynolds sea surface temperature (SST) data showing tropical instability waves (TIWs) in the tropical Pacific are analyzed along with current measurements from the Tropical Atmosphere–Ocean (TAO) buoy array and wind speeds from the European Remote Sensing Satellite (ERS) -1 and -2 scatterometers. TIWs are visible as undulations in the SST cold fronts that delineate the northern and southern boundaries of the cold tongue in the equatorial Pacific. The SST pattern results from advection of the SST front by instabilities in the near-surface equatorial currents. Although the waves are seen on both sides of the Pacific cold tongue and north of the equator in the Atlantic, they are most intense, and thereby most observable, in the north equatorial Pacific. The combination of data used in this analysis provides information about these waves, the factors controlling them, and their coupling to the atmosphere on annual and interannual timescales. On annual timescales, the TIWs generally establish a strong signal in July east of about 140°W with a westward phase speed of about 0.5 m s−1. By August, the waves usually occupy the longitudes between 160° and 100°W and continue to propagate west at roughly the same speed. With the onset of the warm season in the equatorial cold tongue (spring), the signal typically weakens and the propagation speeds show large variations. On interannual timescales, activity is strongest during the cold phase of the ENSO cycle (La Niña) when the cold tongue is most pronounced; the waves are weak or nonexistent during the warm phase of ENSO (El Niño) when the SST front is weak. The TIW signature in SST is noticeable throughout all seasons of the year provided that the gradient in SST at 140°W is greater than about 0.25°C (100 km)−1. In addition, analysis of the currents underlines the importance of the background currents to the zonal propagation speeds.
Dynamically Forced Increase of Tropical Upwelling in the Lower Stratosphere
Authors: Garny Hella , Dameris Martin , Randel William , Bodeker Greg E. , Deckert Rudolf
Published: February 2011

Drivers of upwelling in the tropical lower stratosphere are investigated using the E39C-A chemistry–climate model. The climatological annual cycle in upwelling and its wave forcing are compared to the interim ECMWF Re-Analysis (ERA-Interim). The strength in tropical upwelling and its annual cycle can be largely explained by local resolved wave forcing. The climatological mean forcing is due to both stationary planetary-scale waves that originate in the tropics and extratropical transient synoptic-scale waves that are refracted equatorward.

Increases in atmospheric greenhouse gas (GHG) concentrations to 2050 force a year-round positive trend in tropical upwelling, which maximizes in the lowermost stratosphere. Tropical ascent is balanced by downwelling between 20° and 40°. Strengthening of tropical upwelling can be explained by stronger local forcing by resolved wave flux convergence, which is driven in turn by processes initiated by increases in tropical sea surface temperatures (SSTs). Higher tropical SSTs cause a strengthening of the subtropical jets and modification of deep convection affecting latent heat release. While the former can modify wave propagation and dissipation, the latter affects tropical wave generation. The dominant mechanism leading to enhanced vertical wave propagation into the lower stratosphere is an upward shift of the easterly shear zone due to the strengthening and upward shift of the subtropical jets.
A Simple, Coherent Framework for Partitioning Uncertainty in Climate Predictions
Authors: Yip Stan , Ferro Christopher A. T. , Stephenson David B. , Hawkins Ed
Published: February 2011

A simple and coherent framework for partitioning uncertainty in multimodel climate ensembles is presented. The analysis of variance (ANOVA) is used to decompose a measure of total variation additively into scenario uncertainty, model uncertainty, and internal variability. This approach requires fewer assumptions than existing methods and can be easily used to quantify uncertainty related to model–scenario interaction—the contribution to model uncertainty arising from the variation across scenarios of model deviations from the ensemble mean. Uncertainty in global mean surface air temperature is quantified as a function of lead time for a subset of the Coupled Model Intercomparison Project phase 3 ensemble and results largely agree with those published by other authors: scenario uncertainty dominates beyond 2050 and internal variability remains approximately constant over the twenty-first century. Both elements of model uncertainty, due to scenario-independent and scenario-dependent deviations from the ensemble mean, are found to increase with time. Estimates of model deviations that arise as by-products of the framework reveal significant differences between models that could lead to a deeper understanding of the sources of uncertainty in multimodel ensembles. For example, three models show a diverging pattern over the twenty-first century, while another model exhibits an unusually large variation among its scenario-dependent deviations.
Observed Influences of Autumn–Early Winter Eurasian Snow Cover Anomalies on the Hemispheric PNA-like Variability in Winter
Authors: Wu Qigang , Hu Haibo , Zhang Lujun
Published: February 2011

The impact of the Eurasian snow cover extent on the Northern Hemisphere (NH) circulation is investigated by applying a lagged maximum covariance analysis (MCA) to monthly satellite-derived snow cover and NCEP reanalysis data. Wintertime atmospheric signals significantly correlated with persistently autumn–early winter snow cover anomalies are found in the leading two MCA modes. The first MCA mode indicates the effect of Eurasian snow cover anomalies on the Arctic Oscillation/North Atlantic Oscillation (AO/NAO). The second MCA mode corresponds with the forcing of Eurasian snow cover anomalies on the hemispheric Pacific–North America (PNA)-like atmospheric variations. This snow–atmosphere relationship may present a significant potential for wintertime predictability.