bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Drug Delivery Systems of Curcumin for Cancer Chemoprevention
Authors: Bansal Shyam S. , Goel Mehak , Aqil Farrukh , Vadhanam Manicka V. , Gupta Ramesh C.
Published: May 2011

Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium. Cancer Prev Res; 4(8); 1158–71. ©2011 AACR.
Role of E-cadherin in Antimigratory and Antiinvasive Efficacy of Silibinin in Prostate Cancer Cells
Authors: Deep Gagan , Gangar Subhash Chander , Agarwal Chapla , Agarwal Rajesh
Published: May 2011

The epithelial-to-mesenchymal transition (EMT) in prostate cancer (PCA) cells is considered prerequisite for acquiring migratory/invasive phenotype, and subsequent metastasis. We hypothesized that promoting the E-cadherin expression in PCA cells by using nontoxic phytochemicals, like silibinin, would prevent EMT and consequently invasiveness. Our results showed that silibinin treatment (5–90 μmol/L) significantly inhibits migratory and invasive potential of advance human PCA PC3, PC3MM2, and C4–2B cells in in vitro assays. Importantly, the antimigratory/antiinvasive efficacy of silibinin was not due to its cytotoxicity toward PCA cells. Molecular analyses showed that silibinin increases E-cadherin level that was localized mainly at cellular membrane as evidenced by subcellular fractional and confocal analyses in PC3 cells, which might be responsible for morphologically observed shift toward epithelial character. Silibinin also decreased the levels of Slug, Snail, phospho-Akt(ser473), nuclear β-catenin, phospho-Src(tyr419) and Hakai; together they play an important role in regulating E-cadherin expression/function and EMT. Similar silibinin effects on E-cadherin, β-catenin, phospho-Src(tyr419), and Hakai levels were also observed in PC3MM2 and C4–2B PCA cells. Selective Src inhibition by dasatinib also showed increased E-cadherin expression in PC3 cells suggesting a possible involvement of Src inhibition in silibinin-caused increase in E-cadherin level. Additional studies in PC3 cells with stable knock-down of E-cadherin expression revealed that antimigratory/antiinvasive efficacy of silibinin is in-part dependent on E-cadherin expression. Together, our results showing antimigratory/antiinvasive effects of silibinin and associated mechanisms suggest that silibinin should be tested further in clinically relevant animal models toward exploiting its potential benefits against metastatic PCA. Cancer Prev Res; 4(8); 1222–32. ©2011 AACR.
Emotion Dysregulation as a Core Feature of Borderline Personality Disorder: Comparison of the Discriminatory Ability of Two Self-Rating Measures
Authors: Kröger Christoph , Vonau Melanie , Kliem Sören , Kosfelder Joachim
Published: May 2011

Background/Aims: There is growing evidence that emotion dysregulation (ED) is a core feature of borderline personality disorder (BPD). The present study examines whether a self-rating measure, the ED Scale, lets us distinguish between individuals with BPD and those diagnosed with other mental disorders in a way similar to that of a borderline-related screening measure, the German version of the McLean Screening Instrument for Borderline Personality Disorders (MSI-BPD). Method: Based on the signal detection theory, receiver operating characteristics as well as reliability and validity indicators are determined in a heterogeneous outpatient sample (n = 168). Results: The values of internal consistency and the validity indicators turned out to be in the expected range. The area under the curve (AUC) for the ED Scale was 0.86, and therefore emerged on a par with the AUC = 0.90 of the MSI-BPD. As required, analyses for both measures revealed equal and high values for sensitivity, as well as corresponding low negative predictive values. There was, however, a lower degree of specificity on the ED Scale as compared to the MSI-BPD. Conclusion: The results support the assumption that ED is a core feature of BPD, but should also be taken into account in the assessment and treatment of other mental disorders.
The Relationship between Insight and Uncertainty in Obsessive-Compulsive Disorder
Authors: Jaafari Nematollah , Aouizerate Bruno , Tignol Jean , El-Hage Wissam , Wassouf Issa , Guehl Dominique , Bioulac Bernard , Daniel Marie-Laure , Lacoste Jerome , Gil Roger , Burbaud Pierre , Rotge Jean-Yves ,   for the Insight Study Group
Published: May 2011

Background: The aim of this study was to investigate the relationship between the levels of insight and checking-related uncertainty in patients with obsessive-compulsive disorder (OCD). Sampling and Methods: Twenty OCD patients with checking compulsions and without current comorbidity were recruited. We used an experimental paradigm that gave subjects the opportunity to check during a decision-making task, thereby allowing for the calculation of a response time index (RTI) as the ‘uncertainty cost’ during decision-making. The level of insight was assessed with the Brown Assessment of Beliefs Scale (BABS). Results: Regression analyses indicated a significant positive correlation between RTI and BABS scores (r = 0.49). Conclusions: The level of insight is related to cognitive characteristics underlying OCD symptoms, in particular, checking-related uncertainty in checking OCD patients. Study Limitations: The absence of a comparison group and the low number of included patients are the main limitations of the present study.
Why Does Enamel in Klk4-Null Mice Break above the Dentino-Enamel Junction?
Authors: Simmer James P. , Hu Yuanyuan , Richardson Amelia S. , Bartlett John D. , Hu Jan C.-C.
Published: May 2011

Background: The enamel layerof kallikrein 4 (Klk4)-null mice has a normal thickness and a decussating pattern of enamel rods, but it contains residual enamel proteins, is less highly mineralized, and fractures in its deepest part just above the dentino-enamel junction (DEJ). The plane of fracture is puzzling because the deepest enamel is deposited earliest and, through the action of the secretory stage enamel protease (Mmp20), is the most mature part of the enamel layer at the time of the onset of Klk4 expression. Objectives: To characterize the planes of fracture in Mmp20- and Klk4-null mice and to localize Klk4 expression in developing teeth. Methods:Klk4- and Mmp20-null mice were sacrificed at 7 weeks and their mandibular incisors were characterized by scanning electron microscopy. Klk4+/lacZ mice were mated with Klk4+/lacZ mice. Offspring were genotyped by polymerase chain reaction. Klk4+/+, Klk4+/lacZ, and Klk4lacZ/lacZ (null) littermates on postnatal days 5, 8, 11, and 14 were processed for β-galactosidase histochemistry. Results: The enamel layer fractures at the DEJ in Mmp20-null mice, and fractures occur in enamel above the DEJ in Klk4-null mice. Klk4 is not expressed by secretory-stage ameloblasts, murine odontoblasts beneath the secretory stage, or maturation-stage ameloblasts. Klk4 is specifically expressed by transition and maturation-stage ameloblasts. Conclusions: The breakage of enamel near the DEJ in Klk4-null mice is not due to a failure of odontoblasts to express Klk4, but it relates to a progressive hypomineralization of enamel with depth.
Regulation of Bmp4 Expression in Odontogenic Mesenchyme: From Simple to Complex
Authors: Kong Hui , Wang Ying , Patel Manshi , Mues Gabriele , D’Souza Rena N.
Published: May 2011

For many years the molecular mechanisms governing bone morphogenetic protein 4 (Bmp4) expression in tooth bud mesenchyme could be explained by an uncomplicated model involving the interaction of the homeobox gene Msx1 and the paired domain gene Pax9 and a limited proximal promoter segment of Bmp4. New insights have led to major revisions, but we are still far from understanding the role of Msx1 and Pax9 in the complex processes that result in the expression of Bmp4 in the mesenchymal layer of the developing tooth bud. The objective of these studies was to gain further insight into the molecular relationship between Pax9, Msx1, and Bmp4 in dental mesenchyme and explore its association with nonsyndromic tooth agenesis in humans.
Testing the Terrain Hypothesis: Canada Geese See Their World Laterally and Obliquely
Authors: Fernández-Juricic Esteban , Moore Bret A. , Doppler Megan , Freeman Joseph , Blackwell Bradley F. , Lima Steven L. , DeVault Travis L.
Published: May 2011

The distribution of ganglion cells in the retina determines the specific regions of the visual field with high visual acuity, and thus reflects the perception of a species’ visual environment. The terrain hypothesis proposes that animals living in open areas should have a horizontal visual streak across the retina with high ganglion cell density to increase visual acuity along the horizon. We tested this hypothesis in Canada geese (Branta canadensis) by assessing retinal topography, visual field configuration, and scanning behavior. We found that geese have an oblique rather than a horizontal visual streak across the retina: from a dorsal-nasal to a ventral-temporal position. Geese showed narrow blind areas, which increased the range of their lateral vision, and a relatively large degree of eye movement. Canada geese have relatively wide binocular fields and can see their bill tips. Goose head movement rates were low compared to species with a single fovea, and head movement rates increased in visually obstructed habitats. Canada geese have high acuity across their retina, which would allow them to simultaneously scan the ground and the sky when the head is up and parallel to the ground, as well as align the visual streak with the horizon when the head is tilted downwards. Their visual streak, along with their large eye size, may reduce the need for large amplitude head movements during vigilance bouts in visually unobstructed habitats. Overall, the visual system of geese combines features related to the detection of predators/conspecifics in open areas (visual streak, large lateral field, reduced head movements) as well as visual specializations that would allow for monitoring both the ground and sky (oblique streak) and for extracting and handling of food items (wide binocular fields, visualization of the bill tip).
Characteristic Neurobiological Patterns Differentiate Paternal Responsiveness in Two Peromyscus Species
Authors: Lambert Kelly G. , Franssen Catherine L. , Bardi Massimo , Hampton Joseph E. , Hainley Leslie , Karsner Stephanie , Tu Eddie B. , Hyer Molly M. , Crockett Ashly , Baranova Anya , Ferguson Tajh , Ferguson Tenaj , Kinsley Craig H.
Published: May 2011

Rodent paternal models provide unique opportunities to investigate the emergence of affiliative social behavior in mammals. Using biparental and uniparental Peromyscus species (californicus and maniculatus, respectively) we assessed paternal responsiveness by exposing males to biological offspring, unrelated conspecific pups, or familiar brothers following a 24-hour separation. The putative paternal circuit we investigated included brain areas involved in fear/anxiety [cingulate cortex (Cg), medial amygdala (MeA), paraventricular nucleus of the hypothalamus (PVN), and lateral septum (LS)], parental motivation [medial preoptic area (MPOA)], learning/behavioral plasticity (hippocampus), olfaction [pyriform cortex (PC)], and social rewards (nucleus accumbens). Paternal experience in californicus males reduced fos immunoreactivity (ir) in several fear/anxiety areas; additionally, all californicus groups exhibited decreased fos-ir in the PC. Enhanced arginine vasopressin (AVP) and oxytocin (OT)-ir cell bodies and fibers, as well as increased neuronal restructuring in the hippocampus, were also observed in californicus mice. Multidimensional scaling analyses revealed distinct brain activation profiles differentiating californicus biological fathers, pup-exposed virgins, and pup-naïve virgins. Specifically, associations among MPOA fos, CA1 fos, dentate gyrus GFAP, CA2 nestin-, and PVN OT-ir characterized biological fathers; LS fos-, Cg fos-, and AVP-ir characterized pup-exposed virgins, and PC-, PVN-, and MeA fos-ir characterized pup-naïve virgins. Thus, whereas fear/anxiety areas characterized pup-naïve males, neurobiological factors involved in more diverse functions such as learning, motivation, and nurturing responses characterized fatherhood in biparental californicus mice. Less distinct paternal-dependent activation patterns were observed in uniparental maniculatus mice. These data suggest that dual neurobiological circuits, leading to the inhibition of social-dependent anxiety as well as the activation of affiliative responses, characterize the transition from nonpaternal to paternal status in californicus mice.
Neuroanatomical Projections of the Species-Specific Tyrosine Hydroxylase-Immunoreactive Cells of the Male Prairie Vole Bed Nucleus of the Stria Terminalis and Medial Amygdala
Authors: Northcutt Katharine V. , Lonstein Joseph S.
Published: May 2011

The principal nucleus of the bed nucleus of the stria terminalis (BSTpr) and posterodorsal part of the medial amygdalar nucleus (MEApd) are densely interconnected sites transmitting olfactory information to brain areas mediating sociosexual behaviors. In male prairie voles (Microtus ochrogaster), the BSTpr and MEApd contain hundreds of cells densely immunoreactive for tyrosine hydroxylase (TH). Such tremendous numbers of TH-immunoreactive (TH-ir) cells do not exist in other rodents examined, and studies from our laboratory suggest these cells may be part of a unique chemical network necessary for monogamous behaviors in prairie voles. To obtain information about how these TH-ir cells communicate with other sites involved in social behaviors, we first used biotinylated dextran amine (BDA) to determine sites that receive BSTpr efferents and also contain TH-ir fibers. Only in the medial preoptic area (MPO) and MEApd did we find considerable comingling of BDA-containing and TH-ir fibers. To examine if these sites receive input specifically from BSTpr TH-ir cells, the retrograde tracer Fluorogold was infused into the MPO or MEApd. Almost 80% of TH-ir projections to the MPO originated from the BSTpr or MEApd, involving about 40% of all TH-ir cells in these sites. In contrast, the MEApd received almost no input from TH-ir cells in the BSTpr, and received it primarily from the ventral tegmental area. Retrograde tracing from the BSTpr itself revealed substantial input from MEApd TH-ir cells. Thus, the male prairie vole brain contains a species-specific TH-ir network involving the BSTpr, MEApd, and MPO. By connecting brain sites involved in olfaction, sociality and motivation, this network may be essential for monogamous behaviors in this species.
Sterol Regulatory Element–Binding Protein-1 Determines Plasma Remnant Lipoproteins and Accelerates Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice
Authors: Karasawa Tadayoshi , Takahashi Akimitsu , Saito Ryo , Sekiya Motohiro , Igarashi Masaki , Iwasaki Hitoshi , Miyahara Shoko , Koyasu Saori , Nakagawa Yoshimi , Ishii Kiyoaki , Matsuzaka Takashi , Kobayashi Kazuto , Yahagi Naoya , Takekoshi Kazuhiro , Sone Hirohito , Yatoh Shigeru , Suzuki Hiroaki , Yamada Nobuhiro , Shimano Hitoshi
Published: May 2011

Objective—

Sterol regulatory element–binding protein-1 (SREBP-1) is nutritionally regulated and is known to be a key transcription factor regulating lipogenic enzymes. The goal of this study was to evaluate the roles of SREBP-1 in dyslipidemia and atherosclerosis.

Methods and Results—

Transgenic mice that overexpress SREBP-1c in the liver and SREBP-1-deficient mice were crossed with low-density lipoprotein receptor (LDLR)–deficient mice, and the plasma lipids and atherosclerosis were analyzed. Hepatic SREBP-1c overexpression in LDLR-deficient mice caused postprandial hypertriglyceridemia, increased very-low-density lipoprotein (VLDL) cholesterol, and decreased high-density lipoprotein cholesterol in plasma, which resulted in accelerated aortic atheroma formation. Conversely, absence of SREBP-1 suppressed Western diet–induced hyperlipidemia in LDLR-deficient mice and ameliorated atherosclerosis. In contrast, bone marrow-specific SREBP-1 deficiency did not alter the development of atherosclerosis. The size of nascent VLDL particles secreted from the liver was increased in SREBP-1c transgenic mice and reduced in SREBP-1-deficient mice, accompanied by upregulation and downregulation of phospholipid transfer protein expression, respectively.

Conclusion—

Hepatic SREBP-1c determines plasma triglycerides and remnant cholesterol and contributes to atherosclerosis in hyperlipidemic states. Hepatic SREBP-1c also regulates the size of nascent VLDL particles.
Insulin-Like Growth Factor-1 Receptor Identifies a Pool of Human Cardiac Stem Cells With Superior Therapeutic Potential for Myocardial Regeneration
Authors: D'Amario Domenico , Cabral-Da-Silva Mauricio C. , Zheng Hanqiao , Fiorini Claudia , Goichberg Polina , Steadman Elisabeth , Ferreira-Martins João , Sanada Fumihiro , Piccoli Marco , Cappetta Donato , D'Alessandro David A. , Michler Robert E. , Hosoda Toru , Anastasia Luigi , Rota Marcello , Leri Annarosa , Anversa Piero , Kajstura Jan
Published: May 2011

RETRACTION

This article has been retracted:

Circ Res
. 2018;123:e00. DOI: 10.1161/RES.0000000000000250.
Antiangiogenic Activity of rPAI-1
23
Promotes Vasa Vasorum Regression in Hypercholesterolemic Mice Through a Plasmin-Dependent Mechanism
Authors: Mollmark Jessica , Ravi Saranya , Sun Baiming , Shipman Samantha , Buitendijk Maarten , Simons Michael , Mulligan-Kehoe Mary Jo
Published: May 2011

Rationale:

The antiangiogenic activity of rPAI-1
23
, a truncated plasminogen activator inhibitor-1 (PAI-1) protein, induces vasa vasorum collapse and significantly reduces plaque area and plaque cholesterol in hypercholesterolemic low-density lipoprotein receptor–deficient/apolipoprotein B48–deficient mice.

Objective:

The objective of this study was to examine rPAI-1
23
–stimulated mechanisms that cause vasa vasorum collapse.

Methods and Results:

The rPAI-1
23
protein opposed PAI-1 antiproteolytic function by stimulating a 1.6-fold increase in plasmin activity compared with the saline-treated counterpart. The increased proteolytic activity corresponded to increased activity of matrix metalloproteinase-3 and degradation of fibrin(ogen), nidogen, and perlecan in the adventitia of descending aortas. PAI-1 activity was reduced by 48% in response to rPAI-1
23
; however, PAI-1 protein expression levels were similar in the rPAI-1
23
– and saline-treated hypercholesterolemic mice. Coimmunoprecipitation assays demonstrated a novel PAI-1–plasminogen complex in protein from the descending aorta of rPAI-1
23
– and saline-treated mice, but complexed PAI-1 was 1.6-fold greater in rPAI-1
23
–treated mice. Biochemical analyses demonstrated that rPAI-1
23
and PAI-1 binding interactions with plasminogen increased plasmin activity and reduced PAI-1 antiproteolytic activity.

Conclusions:

We conclude that rPAI-1
23
causes regression or collapse of adventitial vasa vasorum in hypercholesterolemic mice by stimulating an increase in plasmin activity. The rPAI-1
23
–enhanced plasmin activity was achieved through a novel mechanism by which rPAI-1
23
and PAI-1 bound plasminogen in a cooperative manner to increase plasmin activity and reduce PAI-1 activity.
Ischemic Stroke During Sleep
Authors: Kim Beom Joon , Lee Seung-Hoon , Shin Chae-Won , Ryu Wi-Sun , Kim Chi Kyung , Yoon Byung-Woo
Published: May 2011

Background and Purpose—

Approximately one fourth of stroke occur during sleep. Despite the clinical and radiological similarities between wake-up stroke (WUS) and non-WUS, the functional outcomes of WUS are largely unknown.

Methods—

This retrospective analysis reviewed 2289 consecutive patients with acute ischemic stroke who were admitted between November 2002 and December 2009. We used 3 end-point analytic techniques to evaluate the association between WUS and functional outcomes: dichotomized analysis for “functional dependency” (a discharge modified Rankin Scale [mRS] score ≥2 regardless of initial stroke severity), severity-adjusted responder analysis for “unfavorable outcome” (a discharge mRS ≥1 for an admission National Institutes of Health Stroke Scale score 0 to 7; mRS ≥2 for National Institutes of Health Stroke Scale 8 to 14; or mRS ≥3 for National Institutes of Health Stroke Scale ≥15), and shift analysis for changes in overall distributions of discharge mRS scores.

Results—

The initial National Institutes of Health Stroke Scale score of patients with WUS was significantly higher than that of their non-WUS counterparts (median [interquartile range]; 4 [2 to 7] versus 3 [1 to 6];
P
<0.01). The dichotomized analysis strategy failed to detect a significant association between WUS and functional dependency at discharge (adjusted OR, 0.99; 95% CI, 0.76 to 1.28). However, the responder analysis showed that patients with WUS were more likely to have “unfavorable outcomes” (adjusted OR, 1.33; 95% CI, 1.02 to 1.72), and the shift analysis also detected significant effect of WUS on the mRS score distributions toward increased dependency (adjusted OR, 1.22; 95% CI, 1.01 to 1.48).

Conclusions—

From our study, we documented that WUS was associated with worse short-term outcomes after ischemic stroke. Careful selection of appropriate analytic techniques may help to detect modest associations in observational studies.
Associations of Edge-Detected and Manual-Traced Common Carotid Intima-Media Thickness Measurements With Framingham Risk Factors
Authors: Polak Joseph F. , Pencina Michael J. , Herrington David , O'Leary Daniel H.
Published: May 2011

Background and Purpose—

Carotid intima-media thickness (IMT) is a marker of cardiovascular disease derived from ultrasound images of the carotid artery. In most outcome studies, human readers identify and trace the key IMT interfaces. We evaluate an alternate approach using automated edge detection.

Methods—

We studied a subset of 5640 participants with an average age 61.7 years (48% men) of the Multi-Ethnic Study of Atherosclerosis composed of whites, Chinese, Hispanic, and blacks that are part of the Multi-Ethnic Study of Atherosclerosis IMT progression study. Manual tracing IMT (mt-IMT) and edge-detected IMT (ed-IMT) measurements of the far wall of the common carotid artery served as outcome variables for multivariable linear regression models using Framingham cardiovascular risk factors and ethnicity as independent predictors.

Results—

Measurements of mt-IMT were obtainable in 99.9% (5633/5640) and measurements of ed-IMT were obtainable in 98.9% (5579/5640) of individuals. Average ed-IMT was 0.19 mm larger than mt-IMT. Inter-reader systematic differences (bias) in IMT measurements were apparent for mt-IMT but not ed-IMT. Based on complete data for 5538 individuals, associations of IMT with risk factors were stronger (
P
<0.0001) for mt-IMT (model
r
2
, 19.5%) than for ed-IMT (model
r
2
, 18.5%).

Conclusions—

We conclude that this edge-detection process generates IMT values equivalent to manually traced ones because it preserves key associations with cardiovascular risk factors. It also decreases inter-reader bias, potentially making it applicable for use in cardiovascular risk assessment.
Three-Month and Long-Term Outcomes and Their Predictors in Acute Basilar Artery Occlusion Treated With Intra-Arterial Thrombolysis
Authors: Jung Simon , Mono Marie-Luise , Fischer Urs , Galimanis Aekaterini , Findling Oliver , De Marchis Gian Marco , Weck Anja , Nedeltchev Krassen , Colucci Giuseppe , Mordasini Pasquale , Brekenfeld Caspar , El-Koussy Marwan , Gralla Jan , Schroth Gerhard , Mattle Heinrich P. , Arnold Marcel
Published: May 2011

Background and Purpose—

Intra-arterial thrombolysis can be used for treatment of basilar artery occlusion. Predictors of outcome before initiation of treatment are of special interest.

Methods—

From 1992 to 2010, we treated 106 consecutive patients with basilar artery occlusion with intra-arterial thrombolysis. Baseline characteristics, treatment, clinical course, and 3-month and long-term outcomes (≥12 months) were assessed. Outcome parameters were vessel recanalization after treatment, complications, modified Rankin scale (mRS) score, and mortality after 3 months and in the long-term.

Results—

At 3 months, clinical outcome was good (mRS score, 0–2) in 33.0% of the patients and moderate (mRS score, 3) in 11.3%. Mortality was 40.6%. Partial or complete recanalization was achieved in 69.8% of the patients, and symptomatic intracranial hemorrhage occurred in 1 patient (0.9%). Between 3-month and long-term follow-up, 22 survivors (40.8%) showed clinical improvement of at least 1 point on the mRS score, 29 (53.7%) were functionally unchanged, and 3 (5.7%) showed functional worsening (
P
<0.0001). Multivariate analysis identified diabetes as a predictor of poor vessel recanalization (
P
=0.028). Low baseline National Institutes of Health Stroke Scale score was identified as a predictor of good or moderate clinical outcome (
P
<0.0001) and survival (
P
=0.001) at 3 months, and younger age was identified as an additional predictor of survival (
P
=0.012). For prediction of long-term clinical outcome, age was also an independent predictor (
P
=0.018).

Conclusions—

In our series, intra-arterial thrombolysis as treatment of basilar artery occlusion was safe. National Institutes of Health Stroke Scale score at admission and age were identified as predictors of outcome, and these predictors should be considered for treatment allocation in future randomized trials.
Resistin, but Not Adiponectin and Leptin, Is Associated With the Risk of Ischemic Stroke Among Postmenopausal Women
Authors: Rajpathak Swapnil N. , Kaplan Robert C. , Wassertheil-Smoller Sylvia , Cushman Mary , Rohan Thomas E. , McGinn Aileen P. , Wang Tao , Strickler Howard D. , Scherer Philipp E. , Mackey Rachel , Curb David , Ho Gloria Y.F.
Published: May 2011

Background and Purpose—

Adipose tissue is considered an endocrine organ that secretes adipokines, which possibly mediate the effects of obesity on the risk of cardiovascular disease. However, there are yet limited prospective data on the association between circulating adipokine levels and the risk of ischemic stroke. We aimed to examine the associations of 3 adipokines (adiponectin, leptin, and resistin) with the risk of ischemic stroke.

Methods—

We conducted a prospective nested case–control study (972 stroke cases and 972 matched control subjects) within the Women's Health Initiative Observational Study cohort. The control subjects were matched to cases on age, race/ethnicity, date of study enrollment, and follow-up time.

Results—

Adipokine levels were associated with established stroke risk factors such as obesity and systolic blood pressure. Adjusted for body mass index, the ORs for incident ischemic stroke comparing the highest (Quartile 4) with the lowest quartile (Quartile 1) were 0.81 (95% CI, 0.61 to 1.08;
P
trend=0.068) for adiponectin, 1.15 (95% CI, 0.83 to 1.59;
P
trend
=
0.523) for leptin, and 1.57 (95% CI, 1.18 to 2.08;
P
trend=0.002) for resistin. The association for resistin remained significant even after accounting for established stroke risk factors (OR, 1.39; 95% CI, 1.01 to 1.90;
P
trend=0.036). Further adjustment for markers for inflammation, angiogenesis, and endothelial function also did not affect our results.

Conclusions—

Circulating levels of resistin, but not those of adiponectin or leptin, are associated with an increased risk of incident ischemic stroke in postmenopausal women, independent of obesity and other cardiovascular disease risk factors.
Dose Effect of Intraventricular Fibrinolysis in Ventricular Hemorrhage
Authors: Staykov Dimitre , Wagner Ingrid , Volbers Bastian , Huttner Hagen B. , Doerfler Arnd , Schwab Stefan , Bardutzky Juergen
Published: May 2011

Background and Purpose—

The aim of the current study was to investigate the dose-dependent efficacy of intraventricular fibrinolysis (IVF) in patients with severe intraventricular hemorrhage (IVH).

Methods—

Patients with intracerebral hemorrhage, severe IVH, and obstructive hydrocephalus with the need for external ventricular drainage were treated with IVF through external ventricular drainage. The time course of IVH resolution and the safety profile were compared between patients treated with high-dose IVF (4 mg alteplase every 12 hours, maximum 20 mg; n=32) and low-dose IVF (1 mg alteplase every 8 hours, maximum 12 mg; n=22). CT scans on Days 1 to 4, 7±1 and 10±1 after admission, were analyzed volumetrically. Outcome was assessed after 3 months.

Results—

The overall effect of IVF dosage was not significantly different between the 2 groups (F=1.3,
P
=0.25). The course of IVH volume in the third and fourth ventricles was similar with high- and low-dose IVF. High-dose IVF resulted in lower total IVH volumes on Days 7 (4.4±4.2 mL versus 8.8±8.1 mL;
P
=0.01) and 10 (1.4±2.8 mL versus 4.9±65.8 mL;
P
=0.005). Total clot half-life was 78±43 hours in the low-dose and 56±25 hours in the high-dose group (
P
=0.02). One asymptomatic ventricular bleeding, 2 cases of ventriculitis, and 1 death due to pulmonary embolism occurred in the high-dose group. There was no difference in outcome at 3 months.

Conclusions—

Low-dose IVF (3 mg alteplase/day) has a similar effect on IVH clearance from the third and fourth ventricles and a similar safety profile when compared with high-dose IVF (8 mg alteplase/day).
Hospitalization for Infection and Risk of Acute Ischemic Stroke
Authors: Elkind Mitchell S.V. , Carty Cara L. , O'Meara Ellen S. , Lumley Thomas , Lefkowitz David , Kronmal Richard A. , Longstreth W.T.
Published: May 2011

Background and Purpose—

Little is known about the acute precipitants of ischemic stroke, although evidence suggests infections contribute to risk. We hypothesized that acute hospitalization for infection is associated with the short-term risk of stroke.

Methods—

The case-crossover design was used to compare hospitalization for infection during case periods (90, 30, or 14 days before an incident ischemic stroke) and control periods (equivalent time periods exactly 1 or 2 years before stroke) in the Cardiovascular Health Study, a population-based cohort of 5888 elderly participants from 4 US sites. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by conditional logistic regression. Confirmatory analyses assessed hazard ratios of stroke from Cox regression models, with hospitalization for infection as a time-varying exposure.

Results—

During a median follow-up of 12.2 years, 669 incident ischemic strokes were observed in participants without a baseline history of stroke. Hospitalization for infection was more likely during case than control time periods; for 90 days before stroke, OR=3.4 (95% CI, 1.8 to 6.5). The point estimates of risks were higher when we examined shorter intervals: for 30 days, OR=7.3 (95% CI, 1.9 to 40.9), and for 14 days, OR=8.0 (95% CI, 1.7 to 77.3). In survival analyses, risk of stroke was associated with hospitalization for infection in the preceding 90 days, adjusted hazard ratio=2.4 (95% CI, 1.6 to 3.4).

Conclusions—

Hospitalization for infection is associated with a short-term increased risk of stroke, with higher risks observed for shorter intervals preceding stroke.
CT Cerebral Blood Flow Maps Optimally Correlate With Admission Diffusion-Weighted Imaging in Acute Stroke but Thresholds Vary by Postprocessing Platform
Authors: Kamalian Shahmir , Kamalian Shervin , Maas Matthew B. , Goldmacher Greg V. , Payabvash Seyedmehdi , Akbar Adnan , Schaefer Pamela W. , Furie Karen L. , Gonzalez R. Gilberto , Lev Michael H.
Published: May 2011

Background and Purpose—

Admission infarct core lesion size is an important determinant of management and outcome in acute (<9 hours) stroke. Our purposes were to: (1) determine the optimal CT perfusion parameter to define infarct core using various postprocessing platforms; and (2) establish the degree of variability in threshold values between these different platforms.

Methods—

We evaluated 48 consecutive cases with vessel occlusion and admission CT perfusion and diffusion-weighted imaging within 3 hours of each other. CT perfusion was acquired with a “second-generation” 66-second biphasic cine protocol and postprocessed using “standard” (from 2 vendors, “A-std” and “B-std”) and “delay-corrected” (from 1 vendor, “A-dc”) commercial software. Receiver operating characteristic curve analysis was performed comparing each CT perfusion parameter—both absolute and normalized to the contralateral uninvolved hemisphere—between infarcted and noninfarcted regions as defined by coregistered diffusion-weighted imaging.

Results—

Cerebral blood flow had the highest accuracy (receiver operating characteristic area under the curve) for all 3 platforms (
P
<0.01). The maximal areas under the curve for each parameter were: absolute cerebral blood flow 0.88, cerebral blood volume 0.81, and mean transit time 0.82 and relative Cerebral blood flow 0.88, cerebral blood volume 0.83, and mean transit time 0.82. Optimal receiver operating characteristic operating point thresholds varied significantly between different platforms (Friedman test,
P
<0.01).

Conclusions—

Admission absolute and normalized “second-generation” cine acquired CT cerebral blood flow lesion volumes correlate more closely with diffusion-weighted imaging-defined infarct core than do those of CT cerebral blood volume or mean transit time. Although limited availability of diffusion-weighted imaging for some patients creates impetus to develop alternative methods of estimating core, the marked variability in quantification among different postprocessing software limits generalizability of parameter map thresholds between platforms.
The Albumin in Acute Stroke Part 1 Trial
Authors: Hill Michael D. , Martin Renee H. , Palesch Yuko Y. , Tamariz Diego , Waldman Bonnie D. , Ryckborst Karla J. , Moy Claudia S. , Barsan William G. , Ginsberg Myron D.
Published: May 2011

Background and Purpose—

The Albumin in Acute Stroke (ALIAS) Part 2 Trial is directly testing whether 2 g/kg of 25% human albumin (ALB) administered intravenously within 5 hours of ischemic stroke onset results in improved clinical outcome. Recruitment into Part 1 of the ALIAS Trial was halted for safety reasons. ALIAS Part 2 is a new, reformulated trial with more-stringent exclusion criteria. Our aim was to explore the efficacy of ALB in the ALIAS Part 1 data and to assess the statistical assumptions underlying the ALIAS Part 2 Trial.

Methods—

ALIAS is a multicenter, blinded, randomized controlled trial. Data on 434 subjects, comprising the ALIAS Part 1 subjects, were analyzed. We examined both the thrombolysis and nonthrombolysis cohorts combined and separately in a “target population” by excluding subjects who would not have been eligible for the ALIAS Part 2 Trial; the latter comprised patients >83 years of age, those with elevated baseline troponin values, and those with in-hospital stroke. We examined the differences in the primary composite outcome, defined as a modified Rankin Scale score of 0 to 1 and/or a National Institutes of Health Stroke Scale score of 0 to 1 at 90 days after randomization.

Results—

In the combined thrombolysis plus nonthrombolysis cohorts of the target population, 44.7% of subjects in the ALB group had a favorable outcome compared with 36.0% in the saline group (absolute effect size=8.7%; 95% CI, −2.2% to 19.5%). Among thrombolyzed subjects of the target population, 46.7% had a favorable outcome in the ALB group compared with 36.6% in the saline group (absolute effect size=10.1%; 95% CI, −2.0% to 20.0%).

Conclusions—

Preliminary results from the ALIAS Part 1 suggest a trend toward a favorable primary outcome in subjects treated with ALB and support the validity of the statistical assumptions that underlie the ALIAS Part 2 Trial. The ALIAS Part 2 Trial will confirm or refute these results.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov/ALIAS
. Unique identifier: NCT00235495.
Analyzing the Sensitivity of WRF’s Single-Layer Urban Canopy Model to Parameter Uncertainty Using Advanced Monte Carlo Simulation
Authors: Wang Zhi-Hua , Bou-Zeid Elie , Au Siu Kui , Smith James A.
Published: May 2011

Single-layer physically based urban canopy models (UCM) have gained popularity for modeling urban–atmosphere interactions, especially the energy transport component. For a UCM to capture the physics of conductive, radiative, and turbulent advective transport of energy, it is important to provide it with an accurate parameter space, including both mesoscale meteorological forcing and microscale surface inputs. While field measurement of all input parameters to a UCM is rarely possible, understanding the model sensitivity to individual parameters is essential to determine the relative importance of parameter uncertainty for model performance. In this paper, an advanced Monte Carlo approach—namely, subset simulation—is used to quantify the impact of the uncertainty of surface input parameters on the output of an offline modified version of the Weather Research and Forecasting (WRF)-UCM. On the basis of the conditional sampling technique, the importance of surface parameters is determined in terms of their impact on critical model responses. It is found that model outputs (both critical energy fluxes and surface temperatures) are highly sensitive to uncertainties in urban geometry, whereas variations in emissivities and building interior temperatures are relatively insignificant. In addition, the sensitivity of the model to input surface parameters is also shown to be very weakly dependent on meteorological parameters. The statistical quantification of the model’s sensitivity to input parameters has practical implications, such as surface parameter calibrations in UCM and guidance for urban heat island mitigation strategies.
A Transilient Matrix for Moist Convection
Authors: Romps David M. , Kuang Zhiming
Published: May 2011

A method is introduced for diagnosing a transilient matrix for moist convection. This transilient matrix quantifies the nonlocal transport of air by convective eddies: for every height z, it gives the distribution of starting heights z′ for the eddies that arrive at z. In a cloud-resolving simulation of deep convection, the transilient matrix shows that two-thirds of the subcloud air convecting into the free troposphere originates from within 100 m of the surface. This finding clarifies which initial height to use when calculating convective available potential energy from soundings of the tropical troposphere.
The Summer North Atlantic Oscillation Influence on the Eastern Mediterranean
Authors: Chronis Themis , Raitsos Dionysios E. , Kassis Dimitris , Sarantopoulos Athanassios
Published: May 2011

This study highlights an important and previously overlooked summer North Atlantic Oscillation (NAO) influence over the eastern Mediterranean. The featured analysis is based on a synergistic use of reanalysis data, satellite retrievals, and coastal and buoy meteorological observations. The physical mechanisms at play reveal a strong summer NAO involvement on the pressure fields over northern Europe and the Anatolian plateau. Especially during August, the summer NAO modulates the Anatolian low, together with the air temperature, meridional atmospheric circulation, and cloudiness over the eastern Mediterranean. Including the dominant action centers over Greenland and the Arctic, the identified modulations rank among the strongest summer NAO-related signals over the entire Northern Hemisphere.
Persistent Atmospheric and Oceanic Anomalies in the North Atlantic from Summer 2009 to Summer 2010
Authors: Hu Zeng-Zhen , Kumar Arun , Huang Bohua , Xue Yan , Wang Wanqiu , Jha Bhaskar
Published: May 2011

In this work, the authors analyze the air–sea interaction processes associated with the persistent atmospheric and oceanic anomalies in the North Atlantic Ocean during summer 2009–summer 2010 with a record-breaking positive sea surface temperature anomaly (SSTA) in the hurricane Main Development Region (MDR) in the spring and summer of 2010. Contributions to the anomalies from the El Niño–Southern Oscillation (ENSO), the North Atlantic Oscillation (NAO), and a long-term trend are identified. The warming in the tropical North Atlantic during summer 2009–summer 2010 represented a typical response to ENSO, preconditioned and amplified by the influence of a strong and persistent negative phase of the NAO. The long-term trends enhanced the warming in the high and low latitudes and weakened the cooling in the midlatitudes. The persistent negative phase of the NAO was associated with active thermodynamic air–sea interaction in the North Atlantic basin. Surface wind anomalies associated with the NAO altered the ocean surface heat flux and changed the SSTA, which was likely further enhanced by the positive wind speed–evaporation–SST feedback. The total heat flux was dominated by the latent and sensible heat fluxes, while the shortwave radiation contributed to the tropical SSTA to a lesser degree. Sensitivity experiments with an atmospheric general circulation model forced by observed SST in the Atlantic Ocean alone suggested that the Atlantic SSTA, which was partly forced by the NAO, had some positive contribution to the persistence of the negative phase of the NAO. Therefore, the persistent NAO condition is partly an outcome of the global climate anomalies and the ocean–atmosphere feedback within the Atlantic basin. The combination of the ENSO, NAO, and long-term trend resulted in the record-breaking positive SSTA in the MDR in the boreal spring and summer of 2010. On the basis of the statistical relationship, the SSTA pattern in the North Atlantic was reasonably well predicted by using the preceding ENSO and NAO as predictors.
A Consistent Hybrid Variational-Smoothing Data Assimilation Method: Application to a Simple Shallow-Water Model of the Turbulent Midlatitude Ocean
Authors: Krysta Monika , Blayo Eric , Cosme Emmanuel , Verron Jacques
Published: May 2011

In the standard four-dimensional variational data assimilation (4D-Var) algorithm the background error covariance matrix remains static over time. It may therefore be unable to correctly take into account the information accumulated by a system into which data are gradually being assimilated.

A possible method for remedying this flaw is presented and tested in this paper. A hybrid variational-smoothing algorithm is based on a reduced-rank incremental 4D-Var. Its consistent coupling to a singular evolutive extended Kalman (SEEK) smoother ensures the evolution of the matrix. In the analysis step, a low-dimensional error covariance matrix is updated so as to take into account the increased confidence level in the state vector it describes, once the observations have been introduced into the system. In the forecast step, the basis spanning the corresponding control subspace is propagated via the tangent linear model.

The hybrid method is implemented and tested in twin experiments employing a shallow-water model. The background error covariance matrix is initialized using an EOF decomposition of a sample of model states. The quality of the analyses and the information content in the bases spanning control subspaces are also assessed. Several numerical experiments are conducted that differ with regard to the initialization of the matrix. The feasibility of the method is illustrated. Since improvement due to the hybrid method is not universal, configurations that benefit from employing it instead of the standard 4D-Var are described and an explanation of the possible reasons for this is proposed.
Evaluations of Upper-Level Turbulence Diagnostics Performance Using the Graphical Turbulence Guidance (GTG) System and Pilot Reports (PIREPs) over East Asia
Authors: Kim Jung-Hoon , Chun Hye-Yeong , Sharman Robert D. , Keller Teddie L.
Published: May 2011

The forecast skill of upper-level turbulence diagnostics is evaluated using available turbulence observations [viz., pilot reports (PIREPs)] over East Asia. The six years (2003–08) of PIREPs used in this study include null, light, and moderate-or-greater intensity categories. The turbulence diagnostics used are a subset of indices in the Graphical Turbulence Guidance (GTG) system. To investigate the optimal performance of the component GTG diagnostics and GTG combinations over East Asia, various statistical evaluations and sensitivity tests are performed. To examine the dependency of the GTG system on the operational numerical weather prediction (NWP) model, the GTG system is applied to both the Regional Data Assimilation and Prediction System (RDAPS) analysis data and Global Forecasting System (GFS) analysis and forecast data with 30-km and 0.3125° (T382) horizontal grid spacings. The dependency of the temporal variation in the PIREP and GFS data and the forecast lead time of the GFS-based GTG combination are also investigated. It is found that the forecasting performance of the GTG system varies with year and season according to the annual and seasonal variations in the large-scale atmospheric conditions over the East Asia region. The wintertime GTG skill is the highest, because most GTG component diagnostics are related to jet streams and upper-level fronts. The GTG skill improves as the number of PIREP samples and the vertical resolution of the underlying NWP analysis data increase, and the GTG performance decreases as the forecast lead time increases from 0 to 12 h.