bluuebunny/crossref_metadata_2025 huggingface dataset:
Relapse or Worsening of Nephrotic Syndrome in Idiopathic Membranous Nephropathy Can Occur even though the Glomerular Immune Deposits Have Been Eradicated
Authors: Barnes Chadwick E. , Wilmer William A. , Hernandez, Jr. Raul A. , Valentine Christopher , Hiremath Leena S. , Nadasdy Tibor , Satoskar Anjali A. , Shim Rose L. , Rovin Brad H. , Hebert Lee A.
Published: July 2011

Background: Relapse or worsening of nephrotic syndrome (NS) in idiopathic membranous nephropathy (IMN) is generally assumed to be due to recurrent disease. Here we document that often that may not be the case. Subjects and Methods: This is a prospective study of 7 consecutive IMN patients whose renal status improved, then worsened after completing a course of immunosuppressive therapy. Each underwent detailed testing and repeat kidney biopsy. Results: In 4 patients (group A), the biopsy showed recurrent IMN (fresh subepithelial deposits). Immunosuppressive therapy was begun. In the other 3 patients (group B), the biopsy showed that the deposits had been eradicated. However, the glomerular basement membrane (GBM) was thickened and vacuolated. Immunosuppressive therapy was withheld. Groups A and B were comparable except that group B had very high intakes of salt and protein, based on 24-hour urine testing. Reducing their high salt intake sharply lowered proteinuria to the subnephrotic range and serum creatinine stabilized. Conclusion: This work is the first to demonstrate that relapse/worsening of NS can occur in IMN even though the GBM deposits have been eradicated. High salt and protein intake in combination with thickened and vacuolated GBM appears to be the mechanism.
Involvement of Neuronal Nitric Oxide Synthase in Ongoing Fetal Brain Injury following Near-Term Rabbit Hypoxia-Ischemia
Authors: Rao Suma , Lin Zhenlang , Drobyshevsky Alexander , Chen Lina , Ji Xinhai , Ji Haitao , Yang Yirong , Yu Lei , Derrick Matthew , Silverman Richard B. , Tan Sidhartha
Published: July 2011

Neuronal nitric oxide synthase (nNOS) and nitric oxide (NO) are implicated in neuronal injury following acute hypoxia-ischemia (HI). Our hypothesis was that NO from nNOS is responsible for ongoing mitochondrial dysfunction in near-term fetal HI. Recently, we synthesized new selective nNOS inhibitors that prevent the cerebral palsy phenotype in our animal model. We tested the efficacy of a selective nNOS inhibitor (JI-8) in fetal brains after in utero HI in our rabbit model. Brain slices at 29 days gestation were obtained after in utero HI, and immediately cultured in medium containing JI-8 or saline for 3–6 days. Mitochondrial membrane integrity and function were determined by flow cytometry using rhodamine 123 and JC-1, and cell death by using propidium iodide. JI-8 decreased NO production in brain slices and also showed significant preservation of mitochondrial function at both 3 and 6 days (p < 0.05) when compared with saline and inducible NOS inhibitor 1400W. There was no difference in cell death. In conclusion, nNOS is involved in ongoing mitochondrial dysfunction after in utero HI. The subacute brain slice model could be a tool for studying the mechanisms involved in ongoing neuronal injury, and for rapidly assessing potential neuroprotectants.
Evaluation of Performance of Measurement of Faecal α1-Antitrypsin Clearance and Technetium-99m Human Serum Albumin Scintigraphy in Protein-Losing Enteropathy
Authors: Chau T.N. , Mok M.Y. , Chan E.Y.T. , Luk W.H. , Lai K.B. , Li F.T.W. , Leung V.K.S. , Wong R.
Published: July 2011

Background and Aim: Our study aimed to compare the performance of faecal α1-antitrypsin clearance (AATC) and radiolabelled human serum albumin (HSA) scintigraphy in protein-losing enteropathy (PLE). Methods: Patients studied by both AATC and technetium-99m (99mTc)-labelled HSA scintigraphy were recruited and categorized into PLE and non-PLE groups based on clinical and laboratory findings. The performance of AATC and 99mTc-labelled HSA scintigraphy was evaluated using clinical diagnosis of PLE as a gold standard. Results: 29 patients were recruited and 13 patients were considered to have definite PLE (PLE group). In the PLE group, all patients had a positive HSA scinigraphy and 10 (77%) had demonstrable positive tracing in the early phase. Conversely, only 6 of them (46%) had elevated AATC level (>13 m/day). Results of 99mTc-labelled HSA scan (but not AATC) showed significant agreement with the clinical diagnosis (ĸ 0.35, p = 0.013). 99mTc-labelled HSA scintigraphy carried higher sensitivity (100 vs. 46%) and negative predictive value (100 vs. 63%) compared to AATC in diagnosing PLE. The correlation between the results of these two investigations was only modest (ĸ 0.27, p = 0.04). The area under the receiver operating characteristic curve of AATC level showed no optimal diagnostic cut-off for PLE. Conclusion:99mTc-labelled HSA scintigraphy was superior to AATC in diagnosing PLE.
Healing Effects of Rebamipide and Omeprazole in Helicobacter pylori-Positive Gastric Ulcer Patients after Eradication Therapy: A Randomized Double-Blind, Multinational, Multi-Institutional Comparative Study
Authors: Song Kyung Ho , Lee Yong Chan , Fan Dai-Ming , Ge Zhi-Zheng , Ji Feng , Chen Min-Hu , Jung Hyun Chae , Bo Jiang , Lee Sang Woo , Kim Jin-Ho
Published: July 2011

Background and Aims: A recent placebo-controlled trial showed that rebamipide, which is a mucosal-protective antiulcer agent, promoted gastric ulcer healing without affecting the Helicobacter pylori status. We conducted a randomized, double-blind trial to compare the healing effects of rebamipide and the proton-pump inhibitor omeprazole in H. pylori-positive gastric ulcers after H. pylori eradication therapy. Methods: After completion of 1 week of eradication therapy, 132 patients with H. pylori-positive gastric ulcer were enrolled in 5 Chinese and 4 Korean institutions. Patients were randomly assigned to take either 20 mg of omeprazole (n = 63) or 300 mg of rebamipide (n = 65) daily for 7 weeks. Healing was defined as complete recovery and S1 and S2 stage ulcer according to the Sakita-Miwa classification. Results: Healing rates at 12 weeks were 81.5% (53/65) and 82.5% (52/63) in the rebamipide and omeprazole groups, respectively. There was no significant difference in treatment efficacy, as evidenced by gastric ulcer healing rates (absolute difference –1.0%; 95% confidence interval –10.7 to 8.7; p = 0.88). The H. pylori eradication rate and ulcer healing rate did not differ between the groups, the latter regardless of eradication outcome. Conclusions: Rebamipide is as effective as omeprazole in treating of H. pylori-positive gastric ulcer after eradication therapy.
Interleukin-33 Induces Expression of Adhesion Molecules and Inflammatory Activation in Human Endothelial Cells and in Human Atherosclerotic Plaques
Authors: Demyanets Svitlana , Konya Viktoria , Kastl Stefan P. , Kaun Christoph , Rauscher Sabine , Niessner Alexander , Pentz Richard , Pfaffenberger Stefan , Rychli Kathrin , Lemberger Christof E. , de Martin Rainer , Heinemann Akos , Huk Ihor , Gröger Marion , Maurer Gerald , Huber Kurt , Wojta Johann
Published: July 2011

Objective—

Interleukin (IL)-33 is the most recently described member of the IL-1 family of cytokines and it is a ligand of the ST2 receptor. While the effects of IL-33 on the immune system have been extensively studied, the properties of this cytokine in the cardiovascular system are much less investigated.

Methods/Results—

We show here that IL-33 promoted the adhesion of human leukocytes to monolayers of human endothelial cells and robustly increased vascular cell adhesion molecule-1, intercellular adhesion molecule-1, endothelial selectin, and monocyte chemoattractant protein-1 protein production and mRNA expression in human coronary artery and human umbilical vein endothelial cells in vitro as well as in human explanted atherosclerotic plaques ex vivo. ST2-fusion protein, but not IL-1 receptor antagonist, abolished these effects. IL-33 induced translocation of nuclear factor-κB p50 and p65 subunits to the nucleus in human coronary artery endothelial cells and human umbilical vein endothelial cells and overexpression of dominant negative form of IκB kinase 2 or IκBα in human umbilical vein endothelial cells abolished IL-33-induced adhesion molecules and monocyte chemoattractant protein-1 mRNA expression. We detected IL-33 and ST2 on both protein and mRNA level in human carotid atherosclerotic plaques.

Conclusion—

We hypothesize that IL-33 may contribute to early events in endothelial activation characteristic for the development of atherosclerotic lesions in the vessel wall, by promoting adhesion molecules and proinflammatory cytokine expression in the endothelium.
Left Atrial Size Is a Potent Predictor of Mortality in Mitral Regurgitation Due to Flail Leaflets
Authors: Rusinaru Dan , Tribouilloy Christophe , Grigioni Francesco , Avierinos Jean François , Suri Rakesh M. , Barbieri Andrea , Szymanski Catherine , Ferlito Marinella , Michelena Hector , Tafanelli Laurence , Bursi Francesca , Mezghani Sonia , Branzi Angelo , Habib Gilbert , Modena Maria G. , Enriquez-Sarano Maurice
Published: July 2011

Background—

Left atrium (LA) enlargement is common in organic mitral regurgitation (MR) and is an emerging prognostic indicator. However, outcome implications of LA enlargement have not been analyzed in the context of routine clinical practice and in a multicenter study.

Methods and Results—

The Mitral Regurgitation International DAtabase (MIDA) registry enrolls patients with organic MR due to flail leaflets, diagnosed in routine clinical practice, in 5 US and European centers. We investigated the relation between LA diameter and mortality under medical treatment and after mitral surgery in 788 patients in sinus rhythm (64±12 years; median LA, 48 [43 to 52] mm). LA diameter was independently associated with survival after diagnosis (hazard ratio, 1.08 [1.04 to 1.12] per 1 mm increment). Compared with patients with LA <55 mm, those with LA ≥55 mm had lower 8-year overall survival (
P
<0.001). LA ≥55 mm independently predicted overall mortality (hazard ratio, 3.67 [1.95 to 6.88]) and cardiac mortality (hazard ratio, 3.74 [1.72 to 8.13]) under medical treatment. The association of LA ≥55 mm and mortality was consistent in subgroups. Similar excess mortality associated with LA ≥55 mm was observed in asymptomatic and symptomatic patients (
P
for interaction, 0.77). In patients who underwent mitral surgery, LA ≥55 mm had no impact on postoperative outcome (
P
>0.20). Mitral surgery was associated with greater survival benefit in patients with LA ≥55 mm compared with LA <55 mm (
P
for interaction, 0.008).

Conclusions—

In MR caused by flail leaflets, LA diameter ≥55 mm is associated with increased mortality under medical treatment, independent of the presence of symptoms or left ventricular dysfunction.
Integration of 3D Imaging Data in the Assessment of Aortic Stenosis
Authors: O'Brien Bridget , Schoenhagen Paul , Kapadia Samir R. , Svensson Lars G. , Rodriguez Leonardo , Griffin Brian P. , Tuzcu E. Murat , Desai Milind Y.
Published: July 2011

Background—

In patients with aortic stenosis (AS), precise assessment of severity is critical for treatment decisions. Estimation of aortic valve area (AVA) with transthoracic echocardiographic (TTE)-continuity equation (CE) assumes a circular left ventricular outflow tract (LVOT). We evaluated incremental utility of 3D multidetector computed tomography (MDCT) over TTE assessment of AS severity.

Methods and Results—

We included 51 patients (age, 81±8 years; 61% men; mean gradient, 42±12 mm Hg) with calcific AS who underwent evaluation for treatment options. TTE parameters included systolic LVOT diameter (D) and continuous and pulsed wave (CW and PW) velocity-time integrals (VTI) through the LVOT and mean transaortic gradient. MDCT parameters included systolic LVOT area, ratio of maximal to minimal LVOT diameter (eccentricity index), and aortic planimetry (AVA
p
). TTE-CE AVA [(D
2
×0.786×VTIpw)/VTIcw] and dimensionless index (DI) [VTIpw/VTIcw] were calculated. Corrected AVA was calculated by substituting MDCT LVOT area into CE. The majority (96%) of patients had eccentric LVOT. LVOT area, measured on MDCT, was higher than on TTE (3.84±0.8 cm
2
versus 3.03±0.5 cm
2
,
P
<0.01). TTE-AVA was smaller than AVA
p
and corrected AVA (0.67±0.1cm
2
, 0.82±0.3 cm
2
, and 0.86±0.3 cm
2
,
P
<0.01). Using TTE measurements alone, 73% of patients had congruence for severe AS (DI ≤0.25 and CE AVA <0.8 cm
2
), which increased to 92% using corrected CE.

Conclusions—

In patients with suspected severe AS, incorporation of MDCT-LVOT area into CE improves congruence for AS severity.
Biased Ligands for Better Cardiovascular Drugs
Authors: DeWire Scott M. , Violin Jonathan D.
Published: July 2011

Drug discovery efforts targeting G-protein-coupled receptors (GPCR) have been immensely successful in creating new cardiovascular medicines. Currently marketed GPCR drugs are broadly classified as either agonists that activate receptors or antagonists that prevent receptor activation by endogenous stimuli. However, GPCR couple to a multitude of intracellular signaling pathways beyond classical G-protein signals, and these signals can be independently activated by biased ligands to vastly expand the potential for new drugs at these classic targets. By selectively engaging only a subset of a receptor's potential intracellular partners, biased ligands may deliver more precise therapeutic benefit with fewer side effects than current GPCR-targeted drugs. In this review, we discuss the history of biased ligand research, the current understanding of how biased ligands exert their unique pharmacology, and how research into GPCR signaling has uncovered previously unappreciated capabilities of receptor pharmacology. We focus on several receptors to illustrate the approaches taken and discoveries made, and how these are steadily illuminating the intricacies of GPCR pharmacology. Discoveries of biased ligands targeting the angiotensin II type 1 receptor and of separable pharmacology suggesting the potential value of biased ligands targeting the β-adrenergic receptors and nicotinic acid receptor GPR109a highlight the powerful clinical promise of this new category of potential therapeutics.
Intramyocardial, Autologous CD34+ Cell Therapy for Refractory Angina
Authors: Losordo Douglas W. , Henry Timothy D. , Davidson Charles , Sup Lee Joon , Costa Marco A. , Bass Theodore , Mendelsohn Farrell , Fortuin F. David , Pepine Carl J. , Traverse Jay H. , Amrani David , Ewenstein Bruce M. , Riedel Norbert , Story Kenneth , Barker Kerry , Povsic Thomas J. , Harrington Robert A. , Schatz Richard A. ,   the ACT34-CMI Investigators
Published: July 2011

Rationale:

A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function.

Objective:

Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options.

Methods and Results:

In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×10
5
or 5×10
5
cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2,
P
=0.020) and 12 months (6.3±1.2 versus 11.0±1.2,
P
=0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds,
P
=0.014; 12 months: 140±171 versus 58±146 seconds,
P
=0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients.

Conclusions:

Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (10
5
cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.
Differential Roles of GSK-3β During Myocardial Ischemia and Ischemia/Reperfusion
Authors: Zhai Peiyong , Sciarretta Sebastiano , Galeotti Jonathan , Volpe Massimo , Sadoshima Junichi
Published: July 2011

Rationale:

Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart during ischemia/reperfusion (I/R), yet the underlying mechanisms of cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be elucidated.

Objective:

We studied the molecular mechanism mediating the effect of GSK-3β activation/inhibition upon myocardial injury during prolonged ischemia and I/R.

Methods and Results:

Beta isoform–specific inhibition of GSK-3 by dominant negative GSK-3β in transgenic mice (Tg-DnGSK-3β) or in heterozygous GSK-3β knock-out mice (GSK-3β+/−) significantly increased, whereas activation of GSK-3β in constitutively active GSK-3β knock-in mice (βKI) significantly decreased, myocardial ischemic injury after prolonged ischemia. In contrast, inhibition of GSK-3β in Tg-DnGSK-3β or GSK-3β+/− significantly reduced, while activation of GSK-3β in βKI significantly enhanced, myocardial I/R injury. Inhibition of GSK-3β stimulated mTOR signaling and inhibited autophagy through a rapamycin-sensitive (mTOR dependent) mechanism. Rapamycin enhanced autophagy and, at the same time, abolished the effects of GSK-3β inhibition on both prolonged ischemic injury and I/R injury. Importantly, the influence of rapamycin over the effects of GSK-3β inhibition on myocardial injury was reversed by inhibition of autophagy.

Conclusions:

Our results suggest that beta isoform–specific inhibition of GSK-3 exacerbates ischemic injury but protects against I/R injury by modulating mTOR and autophagy.
Small-Molecule Inhibitors of the Wnt Pathway Potently Promote Cardiomyocytes From Human Embryonic Stem Cell–Derived Mesoderm
Authors: Willems Erik , Spiering Sean , Davidovics Herman , Lanier Marion , Xia Zebin , Dawson Marcia , Cashman John , Mercola Mark
Published: July 2011

Rationale:

Human embryonic stem cells can form cardiomyocytes when cultured under differentiation conditions. Although the initiating step of mesoderm formation is well characterized, the subsequent steps that promote for cardiac lineages are poorly understood and limit the yield of cardiomyocytes.

Objective:

Our aim was to develop a human embryonic stem cell–based high-content screening assay to discover small molecules that drive cardiogenic differentiation after mesoderm is established to improve our understanding of the biology involved. Screening of libraries of small-molecule pathway modulators was predicted to provide insight into the cellular proteins and signaling pathways that control stem cell cardiogenesis.

Methods and Results:

Approximately 550 known pathway modulators were screened in a high-content screening assay, with hits being called out by the appearance of a red fluorescent protein driven by the promoter of the cardiac-specific MYH6 gene. One potent small molecule was identified that inhibits transduction of the canonical Wnt response within the cell, which demonstrated that Wnt inhibition alone was sufficient to generate cardiomyocytes from human embryonic stem cell–derived mesoderm cells. Transcriptional profiling of inhibitor-treated compared with vehicle-treated samples further indicated that inhibition of Wnt does not induce other mesoderm lineages. Notably, several other Wnt inhibitors were very efficient in inducing cardiogenesis, including a molecule that prevents Wnts from being secreted by the cell, which confirmed that Wnt inhibition was the relevant biological activity.

Conclusions:

Pharmacological inhibition of Wnt signaling is sufficient to drive human mesoderm cells to form cardiomyocytes; this could yield novel tools for the benefit of pharmaceutical and clinical applications.
Collateral Flow Averts Hemorrhagic Transformation After Endovascular Therapy for Acute Ischemic Stroke
Authors: Bang Oh Young , Saver Jeffrey L. , Kim Suk Jae , Kim Gyeong-Moon , Chung Chin-Sang , Ovbiagele Bruce , Lee Kwang Ho , Liebeskind David S. ,   for the UCLA-Samsung Stroke Collaborators
Published: July 2011

Background and Purpose—

Collaterals sustain the ischemic penumbra to limit growth of the infarct core before revascularization, yet the impact of baseline collateral flow on hemorrhagic transformation (HT) after endovascular therapy remains unknown.

Methods—

A collaborative study from 2 stroke centers in distinct geographic regions included 222 consecutive patients who received endovascular therapy for acute cerebral ischemia. The influence of collaterals on HT was analyzed in distinct case scenarios relative to baseline collateral grade at angiography (0 to 1 versus 2 to 4) and recanalization (Thrombolysis in Myocardial Ischemia scale, 0 to 1 versus 2 to 3): good collaterals and successful recanalization (n=98), poor collaterals with successful recanalization (n=43), good collaterals and no recanalization(n=46), and poor collaterals and no recanalization (n=35).

Results—

HT after endovascular therapy occurred in 103 (46.4%) patients; 42 (18.9%) were symptomatic. HT was more frequently observed in patients with poor collaterals and recanalization than in other groups (
P
=0.048). When revascularization was achieved, patients with poorer collaterals were more likely to have symptomatic worsening with HT (
r
=−0.181,
P
=0.032). Multiple logistic regression analysis identified aggressive treatment (OR, 2.558 for Merci clot retrieval; 95% CI, 1.153 to 5.678; OR, 3.618 for combined fibrinolytics and mechanical therapy; 95% CI, 1.551 to 8.437; and OR, 2.085 for intravenous thrombolysis before endovascular therapy; 95% CI, 1.096 to 3.969), poor collaterals and recanalization (OR, 2.666; 95% CI, 1.163 to 6.113), and serum glucose levels (OR, 1.007; 95% CI, 1.000 to 1.014) as independent predictors of HT.

Conclusions—

Angiographic grade of collateral flow strongly influences the rate of HT after therapeutic recanalization for acute ischemic stroke. Collateral status readily available from baseline angiography may therefore refine therapeutic decision-making in acute cerebral ischemia.
Factors Associated With Impaired Kidney Function and Its Impact on Long-Term Outcome in Young Ischemic Stroke
Authors: Putaala Jukka , Haapaniemi Elena , Gordin Daniel , Liebkind Ron , Groop Per-Henrik , Kaste Markku , Tatlisumak Turgut
Published: July 2011

Background and Purpose—

After ischemic stroke, kidney dysfunction is linked to poor outcomes in the elderly, but regarding young patients, data are lacking.

Methods—

We investigated estimated glomerular filtration rate (eGFR) on admission according to the Modification of Diet in Renal Disease equation in 958 consecutive patients aged 15 to 49 years with their first-ever ischemic stroke. Logistic regression adjusted for demographics and stroke risk factors served to identify factors related to low (<60) and high (>120 mL/min/1.73 m
2
) eGFR. In the long-term follow-up (mean, 8.9±3.8 years) study, Cox proportional hazards analysis described the association between eGFR and the following end points: nonfatal/fatal ischemic stroke; composite vascular event of any stroke, myocardial infarction, revascularization/other arterial occlusive event, or vascular death; and death of any cause.

Results—

Estimated GFR was normal in 809 (84.4%), low in 43 (4.5%), and high in 106 (11.1%) patients. Type 1 diabetes (OR, 18.84; 95% CI, 8.65 to 41.03), hypertension (4.29; 1.94 to 9.48), and cardiovascular disease (2.66; 1.19 to 5.96) were independently associated with low eGFR. Type 2 diabetes (3.82; 1.93 to 7.55), lower age (0.95 per year; 0.93 to 0.98), and male gender (1.74; 1.08 to 2.82) were associated with high eGFR. Both low (hazard ratio, 5.73; 95% CI, 3.54 to 9.25) and high eGFR (1.78; 1.01 to 3.14) were associated with long-term mortality when adjusted for age, gender, risk factors, stroke severity, and subtype. No independent association appeared between eGFR and vascular events.

Conclusions—

Despite their different associated risk factors in our young patient cohort, both low and high eGFR predicted long-term mortality after ischemic stroke.
Restoring Neuronal Function After Stroke by Cell Replacement
Authors: Dihné Marcel , Hartung Hans-Peter , Seitz Rüdiger J.
Published: July 2011

Background and Purpose—

A major challenge to effective treatment after stroke is the restoration of neuronal function. In recent years, cell-based therapies for stroke have been explored in experimental animal models, and the results have suggested behavioral improvements. However, the anatomic targets of a cell-based stroke therapy and the relationship of cell grafts to post stroke reorganization are poorly understood, which results in difficulties defining strategies for neuronal substitution. Given that stroke causes a variety of secondary changes at locations beyond the infarct lesion, overcoming these difficulties is even more important.

Summary of Review

We describe which brain structures and cell types are candidates for substitution and how new neuronal functionality could be implemented in a damaged brain by capitalizing on current concepts of post stroke plasticity.
Matrix Metalloproteinase-9 in an Exploratory Trial of Intravenous Minocycline for Acute Ischemic Stroke
Authors: Switzer Jeffrey A. , Hess David C. , Ergul Adviye , Waller Jennifer L. , Machado Livia S. , Portik-Dobos Vera , Pettigrew L. Creed , Clark Wayne M. , Fagan Susan C.
Published: July 2011

Background and Purpose—

Plasma matrix metalloproteinase-9 levels predict posttissue plasminogen activator (tPA) hemorrhage.

Methods—

The authors investigated the effect of minocycline on plasma matrix metalloproteinase-9 in acute ischemic stroke in the Minocycline to Improve Neurological Outcome in Stroke (MINOS) trial and a comparison group.

Results—

Matrix metalloproteinase-9 level decreased at 72 hours compared with baseline in MINOS (tPA,
P
=0.0022; non-tPA,
P
=0.0066) and was lower than in the non-MINOS comparison group at 24 hours (tPA,
P
<0.0001; non-tPA,
P
=0.0019).

Conclusions—

Lower plasma matrix metalloproteinase-9 was seen among tPA-treated subjects in the MINOS trial. Combining minocycline with tPA may prevent the adverse consequences of thrombolytic therapy through suppression of matrix metalloproteinase-9 activity.
Iodinated Contrast Media and Cerebral Hemorrhage After Intravenous Thrombolysis
Authors: MacDougall Niall J.J. , McVerry Ferghal , Baird Sally , Baird Tracey , Teasdale Evelyn , Muir Keith W.
Published: July 2011

Background and Purpose—

Iodinated contrast is increasingly used in CT perfusion or angiographic examinations in acute stroke. Increased risk of intracranial hemorrhage (ICH) complicating microcatheter contrast injections has recently been reported in the second Interventional Management of Stroke (IMS 2) trial with contrast toxicity potentially contributory.

Methods—

We reviewed clinical and radiological data on all patients treated with intravenous alteplase at a single center between May 2003 and November 2008.

Results—

Of 312 patients treated with intravenous alteplase, 69 (22.1%) received intravenous iodinated contrast in volumes between 50 and 150 mL. Incidence of symptomatic ICH defined as per European Cooperative Acute Stroke Study 2 was 16 of 312 (5.1%; 95% CI, 2.7% to 7.6%); among patients not given contrast, it was 12 of 243 (4.9%; 2.2% to 7.7%) compared with 4 of 69 (5.8%; 0.3% to 11.3%) in those given contrast. Incidence of symptomatic ICH defined as per Safe Implementation of Thrombolysis in Stroke-MOnitoring Study (SITS-MOST) criteria was 12 of 312 (3.9%; 1.7% to 6%), 9 of 243 (3.7%; 1.3% to 6%) among those not given contrast, and 3 of 69 (4.4%; 95% CI, −0.5% to 9.2%) among those given contrast. Patients with symptomatic ICH were older, had higher pretreatment National Institutes of Health Stroke Scale, and blood glucose than those without symptomatic ICH. In logistic regression analysis, pretreatment blood glucose was the only significant predictor of symptomatic ICH by either definition (OR, 1.23; 95% CI, 1.03 to 1.48 per mmol/L increment;
P
=0.024). Contrast administration or dose was not associated with symptomatic ICH.

Conclusions—

Intravenous iodinated contrast in doses typically required for CT angiography and perfusion imaging was not associated with symptomatic intracranial hemorrhage in patients treated with alteplase.
Flow Diversion for Intracranial Aneurysms
Authors: D'Urso Pietro I. , Lanzino Giuseppe , Cloft Harry J. , Kallmes David F.
Published: July 2011

The introduction of flow diverters for treatment of intracranial aneurysms represents a major paradigm shift in the treatment of these lesions. The theoretical hallmark of flow diverters is the treatment of the diseased segment harboring the aneurysm instead of treating the aneurysm itself. Flow diverters are designed to induce disruption of flow near the aneurysm neck while preserving flow into parent vessel and adjacent branches. After flow diversion, intra-aneurysmal thrombosis occurs, followed by shrinkage of the aneurysmal sac as the thrombus organizes and retracts. Preliminary clinical series document effective treatment of wide-neck and/or large and giant aneurysms with acceptable complication rates. However, several questions remain unanswered related to the incidence and mechanisms of aneurysm rupture after treatment with flow diverters, fate of small perforating vessels, and long-term patency rates.
An Optimal Feedback Control Framework for Grasping Objects with Position Uncertainty
Authors: Christopoulos Vassilios N. , Schrater Paul R.
Published: July 2011

As we move, the relative location between our hands and objects changes in uncertain ways due to noisy motor commands and imprecise and ambiguous sensory information. The impressive capabilities humans display for interacting and manipulating objects with position uncertainty suggest that our brain maintains representations of location uncertainty and builds compensation for uncertainty into its motor control strategies. Our previous work demonstrated that specific control strategies are used to compensate for location uncertainty. However, it is an open question whether compensation for position uncertainty in grasping is consistent with the stochastic optimal feedback control, mainly due to the difficulty of modeling natural tasks within this framework. In this study, we develop a stochastic optimal feedback control model to evaluate the optimality of human grasping strategies. We investigate the properties of the model through a series of simulation experiments and show that it explains key aspects of previously observed compensation strategies. It also provides a basis for individual differences in terms of differential control costs—the controller compensates only to the extent that performance benefits in terms of making stable grasps outweigh the additional control costs of compensation. These results suggest that stochastic optimal feedback control can be used to understand uncertainty compensation in complex natural tasks like grasping.
A Systematic Method for Configuring VLSI Networks of Spiking Neurons
Authors: Neftci Emre , Chicca Elisabetta , Indiveri Giacomo , Douglas Rodney
Published: July 2011

An increasing number of research groups are developing custom hybrid analog/digital very large scale integration (VLSI) chips and systems that implement hundreds to thousands of spiking neurons with biophysically realistic dynamics, with the intention of emulating brainlike real-world behavior in hardware and robotic systems rather than simply simulating their performance on general-purpose digital computers. Although the electronic engineering aspects of these emulation systems is proceeding well, progress toward the actual emulation of brainlike tasks is restricted by the lack of suitable high-level configuration methods of the kind that have already been developed over many decades for simulations on general-purpose computers. The key difficulty is that the dynamics of the CMOS electronic analogs are determined by transistor biases that do not map simply to the parameter types and values used in typical abstract mathematical models of neurons and their networks. Here we provide a general method for resolving this difficulty. We describe a parameter mapping technique that permits an automatic configuration of VLSI neural networks so that their electronic emulation conforms to a higher-level neuronal simulation. We show that the neurons configured by our method exhibit spike timing statistics and temporal dynamics that are the same as those observed in the software simulated neurons and, in particular, that the key parameters of recurrent VLSI neural networks (e.g., implementing soft winner-take-all) can be precisely tuned. The proposed method permits a seamless integration between software simulations with hardware emulations and intertranslatability between the parameters of abstract neuronal models and their emulation counterparts. Most important, our method offers a route toward a high-level task configuration language for neuromorphic VLSI systems.
The Impact of Climate Change on Air Quality–Related Meteorological Conditions in California. Part II: Present versus Future Time Simulation Analysis
Authors: Zhao Zhan , Chen Shu-Hua , Kleeman Michael J. , Mahmud Abdullah
Published: July 2011

In this study, the Weather Research and Forecasting (WRF) model was applied to dynamically downscale the Parallel Climate Model (PCM) projection for the climate change impact on regional meteorological conditions in California. Comparisons were made for meteorological fields that strongly influence regional air quality between the current (2000–06) and future (2047–53) downscaling results to infer potential air pollution changes in California. Changes in both the meteorological fields and the implied future air quality vary by region and season. Analyses showed that the normalized number of stagnation days (NNSD) integrating all stagnation events, during which most of the air pollution episodes occur, in California's San Joaquin Valley (SJV) will increase and the intensity of stagnation will be stronger in the future for the two main air pollution seasons (i.e., summer and winter). Increases in surface wind and planetary boundary layer height (PBLH) were observed for the coastal part of Los Angeles County (LAC) during summer, suggesting stronger ventilation in this region. Contrary situations were seen in other parts of the South Coast Air Basin (SoCAB) and SJV. Although a surface wind change was not evident in SJV during winter, there was a significant PBLH decrease. Climatechangeinduced variations in surface wind and PBLH were only statistically significant in coastal SoCAB and the southern portion of SJV relative to the corresponding interannual variability; changes in temperature are significant throughout the regions studied. The sea breeze along the coast of California plays an important role in the state's climate and air quality, especially during summertime owing to the stronger intensity compared to wintertime. Analysis of the land–sea temperature contrast and the southwesterly wind along the California coastline indicated that the summertime sea breeze will be stronger in the Central Valley (CV) but weaker for the SoCAB region in the future.
Meteorological Events Affecting Cold-Air Pools in a Small Basin
Authors: Dorninger Manfred , Whiteman C. David , Bica Benedikt , Eisenbach Stefan , Pospichal Bernhard , Steinacker Reinhold
Published: July 2011

Meteorological events affecting the evolution of temperature inversions or cold-air pools in the 1-km-diameter, high-altitude (~1300 m MSL) Grünloch basin in the eastern Alps are investigated using data from lines of temperature dataloggers running up the basin sidewalls, nearby weather stations, and weather charts. Nighttime cold-air-pool events observed from October 2001 to June 2002 are categorized into undisturbed inversion evolution, late buildups, early breakups, mixing events, layered erosion at the inversion top, temperature disturbances occurring in the lower or upper elevations of the pool, and inversion buildup caused by the temporary clearing of clouds. In addition, persistent multiday cold-air pools are sometimes seen. Analyses show that strong winds and cloud cover are the governing meteorological parameters that cause the inversion behavior to deviate from its undisturbed state, but wind direction can also play an important role in the life cycle of the cold-air pools, because it governs the interaction with steep or gentle slopes of the underlying topography. Undisturbed cold-air pools are unusual in the Grünloch basin. A schematic diagram illustrates the different types of cold-air-pool events.
Lagrangian Coherent Structure Analysis of Terminal Winds Detected by Lidar. Part II: Structure Evolution and Comparison with Flight Data
Authors: Tang Wenbo , Chan Pak Wai , Haller George
Published: July 2011

Using observational data from coherent Doppler light detection and ranging (lidar) systems situated at the Hong Kong International Airport (HKIA), the authors extract Lagrangian coherent structures (LCS) intersecting the flight path of landing aircraft. They study the time evolution of LCS and compare them with onboard wind shear and altitude data collected during airplane approaches. Their results show good correlation between LCS extracted from the lidar data and updrafts and downdrafts experienced by landing aircraft. Overall, LCS analysis shows promise as a robust real-time tool to detect unsteady flow structures that impact airplane traffic.
Sensitivity of the Overturning Circulation in the Southern Ocean to Decadal Changes in Wind Forcing
Authors: Meredith Michael P. , Naveira Garabato Alberto C. , Hogg Andrew McC. , Farneti Riccardo
Published: July 2011

The sensitivity of the overturning circulation in the Southern Ocean to the recent decadal strengthening of the overlying winds is being discussed intensely, with some works attributing an inferred saturation of the Southern Ocean CO2 sink to an intensification of the overturning circulation, while others have argued that this circulation is insensitive to changes in winds. Fundamental to reconciling these diverse views is to understand properly the role of eddies in counteracting the directly wind-forced changes in overturning. Here, the authors use novel theoretical considerations and fine-resolution ocean models to develop a new scaling for the sensitivity of eddy-induced mixing to changes in winds, and they demonstrate that changes in Southern Ocean overturning in response to recent and future changes in wind stress forcing are likely to be substantial, even in the presence of a decadally varying eddy field. This result has significant implications for the ocean’s role in the carbon cycle, and hence global climate.
Sensitivity in the Overland Reintensification of Tropical Cyclone Erin (2007) to Near-Surface Soil Moisture Characteristics
Authors: Evans Clark , Schumacher Russ S. , Galarneau Thomas J.
Published: July 2011

This study investigates the impact of abnormally moist soil conditions across the southern Great Plains upon the overland reintensification of North Atlantic Tropical Cyclone Erin (2007). This is tested by analyzing the contributions of three soil moisture–related signals—a seasonal signal, an along-track rainfall signal, and an early postlandfall rainfall signal—to the intensity of the vortex. In so doing, a suite of nine convection-permitting numerical simulations using the Advanced Research Weather Research and Forecasting model (WRF-ARW) is used. Of the signals tested, soil moisture contributions from the anomalously wet months preceding Erin are found to have the greatest positive impact upon the intensity of the vortex, though this impact is on the order of that from climatological soil moisture conditions. The greatest impact of the early rainfall signal contributions is found when it is added to the seasonal signal. Along-track rainfall during the simulation period has a minimal impact.

Variations in soil moisture content result in impacts upon the boundary layer thermodynamic environment via boundary layer mixing. Greater soil moisture content results in weaker mixing, a shallower boundary layer, and greater moisture and instability. Differences in the intensity of convection that develops and its accompanying latent heat release aloft result in greater warm-core development and surface vortex intensification within the simulations featuring greater soil moisture content. Implications of these findings to the tropical cyclone development process are discussed. Given that the reintensification is shown to occur in, apart from land, an otherwise favorable environment for tropical cyclone development and results in a vortex with a structure similar to developing tropical cyclones, these findings provide new insight into the conditions under which tropical cyclones develop.
Retrieval of Ice Cloud Optical Thickness and Effective Particle Size Using a Fast Infrared Radiative Transfer Model
Authors: Wang Chenxi , Yang Ping , Baum Bryan A. , Platnick Steven , Heidinger Andrew K. , Hu Yongxiang , Holz Robert E.
Published: July 2011

A computationally efficient radiative transfer model (RTM) is developed for the inference of ice cloud optical thickness and effective particle size from satellite-based infrared (IR) measurements and is aimed at potential use in operational cloud-property retrievals from multispectral satellite imagery. The RTM employs precomputed lookup tables to simulate the top-of-the-atmosphere (TOA) radiances (or brightness temperatures) at 8.5-, 11-, and 12-μm bands. For the clear-sky atmosphere, the optical thickness of each atmospheric layer resulting from gaseous absorption is derived from the correlated-k-distribution method. The cloud reflectance, transmittance, emissivity, and effective temperature are precomputed using the Discrete Ordinate Radiative Transfer model (DISORT). For an atmosphere containing a semitransparent ice cloud layer with a visible optical thickness τ smaller than 5, the TOA brightness temperature differences (BTDs) between the fast model and the more rigorous DISORT results are less than 0.1 K, whereas the BTDs are less than 0.01 K if τ is larger than 10. With the proposed RTM, the cloud optical and microphysical properties are retrieved from collocated observations from the Moderate Resolution Imaging Spectroradiometer (MODIS) and Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) in conjunction with the Modern Era Retrospective-Analysis for Research and Applications (MERRA) data. Comparisons between the retrieved ice cloud properties (optical thickness and effective particle size) based on the present IR fast model and those from the Aqua/MODIS operational collection-5 cloud products indicate that the IR retrievals are smaller. A comparison between the IR-retrieved ice water path (IWP) and CALIOP-retrieved IWP shows robust agreement over most of the IWP range.
Improved Analyses and Forecasts of Hurricane Ernesto’s Genesis Using Radio Occultation Data in an Ensemble Filter Assimilation System
Authors: Liu Hui , Anderson Jeffrey , Kuo Ying-Hwa
Published: July 2011

Radio occultation (RO) refractivity observations provide information about tropospheric water vapor and temperature in all weather conditions. The impact of using RO refractivity observations on analyses and forecasts of Hurricane Ernesto’s genesis (2006) using an ensemble Kaman filter data assimilation system is investigated. Assimilating RO refractivity profiles in the vicinity of the storm locally moistens the analysis of the lower troposphere and also adjusts the wind analysis in both the lower and upper troposphere through forecast multivariate correlations of RO refractivity and wind. The model forecasts propagate and enhance the added water vapor and the wind adjustments leading to more accurate analyses of the later stages of the genesis of the storm. The root-mean-square errors of water vapor and wind forecasts compared to dropsonde and radiosonde observations are reduced consistently. As a result, assimilating RO refractivity data in addition to traditional observations leads to a stronger initial vortex of the storm and improved forecasts of the storm’s intensification. The benefits of the RO data are much reduced when the RO data in the lower troposphere (below 6 km) are ignored.
In and Out of a Daydream
Authors: Birnbaum Gurit E. , Mikulincer Mario , Gillath Omri
Published: July 2011

In this study, the authors examined the contribution of attachment orientations to the content of daily sexual fantasies. The two partners of 48 couples independently reported on their attachment orientations and provided daily reports on relationship interactions and sexual fantasies for a period of 21 days. Results showed that attachment anxiety was associated with wishes for intimacy and representations of others as more affectionate in sexual fantasies. Conversely, avoidant attachment was associated with avoidance-related wishes and representations of the self and others as more aggressive and alienated. Negative couple interactions increased habitual attachment-related wishes and self-representations. Specifically, during days characterized by negative couple interactions (relationship-damaging behaviors), attachment anxiety was associated with portrayal of the self as more helpless and avoidant attachment was associated with the expression of more avoidant wishes and portrayal of the self as less helpless. The discussion focuses on the manifestations of attachment-related interpersonal goals in sexual fantasies.
How Does Supervisory Family Support Influence Employees’ Attitudes and Behaviors? A Social Exchange Perspective
Authors: Bagger Jessica , Li Andrew
Published: July 2011

In this two-study article, the authors investigate the mechanism through which supervisory family support is linked to outcome variables and examine the moderating effect of family-friendly benefits on this relationship. Drawing on social exchange theory, they propose and find that the quality of leader–member exchange, a form of social exchange relationships, mediated the relationship between supervisory family support and work-related outcomes in Study 1 ( N = 82). Furthermore, in Study 2 ( N = 225), the model linking supervisory family support to outcome variables through social exchange relationships was moderated by the level of family-friendly benefits offered by the organization. Implications for research and practice are discussed.
Neoliberal restructuring, limited autonomy, and relational distance in Manitoba’s nonprofit field
Authors: Woolford Andrew , Curran Amelia
Published: July 2011

This article draws on the work of Pierre Bourdieu to describe the nonprofit field. We highlight the ways in which the neoliberal restructuring of the nonprofit field has introduced new market conditions and valuational standards that have compelled social service providers within this field to adapt to or resist its structural transformation. Our study is focused on social service providing nonprofit agencies in Winnipeg, Manitoba, where the limited autonomy of the nonprofit field has facilitated neoliberal domination in the form of new technologies of management and accountability that threaten to create relational distance between social service providers and service users.