bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Lipidomic Analysis of Stable and Unstable Coronary Artery Disease
Authors: Meikle Peter J. , Wong Gerard , Tsorotes Despina , Barlow Christopher K. , Weir Jacquelyn M. , Christopher Michael J. , MacIntosh Gemma L. , Goudey Benjamin , Stern Linda , Kowalczyk Adam , Haviv Izhak , White Anthony J. , Dart Anthony M. , Duffy Stephen J. , Jennings Garry L. , Kingwell Bronwyn A. 
Published: September 2011

Objective—
Traditional risk factors for coronary artery disease (CAD) fail to adequately distinguish patients who have atherosclerotic plaques susceptible to instability from those who have more benign forms. Using plasma lipid profiling, this study aimed to provide insight into disease pathogenesis and evaluate the potential of lipid profiles to assess risk of future plaque instability.

Methods and Results—
Plasma lipid profiles containing 305 lipids were measured on 220 individuals (matched healthy controls, n=80; stable angina, n=60; unstable coronary syndrome, n=80) using electrospray-ionisation tandem mass spectrometry. ReliefF feature selection coupled with an L2-regularized logistic regression based classifier was used to create multivariate classification models which were verified via 3-fold cross-validation (1000 repeats). Models incorporating both lipids and traditional risk factors provided improved classification of unstable CAD from stable CAD (C-statistic=0.875, 95% CI 0.874–0.877) compared with models containing only traditional risk factors (C-statistic=0.796, 95% CI 0.795–0.798). Many of the lipids identified as discriminatory for unstable CAD displayed an association with disease acuity (severity), suggesting that they are antecedents to the onset of acute coronary syndrome.

Conclusion—
Plasma lipid profiling may contribute to a new approach to risk stratification for unstable CAD.
Role for Circulating Osteogenic Precursor Cells in Aortic Valvular Disease
Authors: Egan Kevin P. , Kim Jung-Hoon , Mohler Emile R. , Pignolo Robert J. 
Published: September 2011

Objective—
Approximately 13% of aortic valves removed from patients with end-stage aortic valve disease contain heterotopic ossification (HO). Recently, we identified a novel population of circulating osteogenic precursor (COP) cells that are derived from bone marrow and have the capability to form bone. These cells are identified by coexpression of the osteogenic marker type 1 collagen or osteoclacin and the hematopoietic marker CD45. We tested the hypothesis that these cells may contribute to heart valve stenosis.

Methods and Results—

Quantification of CD45
+
osteoclacin
+
COP cells by flow cytometry showed that they represent up to 1.1% of mononuclear cells. Clonally derived COP cells produce bone morphogenetic proteins 2 and 4 by immunohistochemical analysis. We reviewed 105 cases of end-stage aortic valvular disease and confirmed HO in 13 archived specimens. Using immunohistochemistry, we identified COP cells by coexpression of CD45 and type 1 collagen. There was a statistically significant association between the presence of COP cells and early HO lesions. COP cells were negligible in regions of unaffected valve leaflets (no HO) from the same individuals.

Conclusion—
This study provides the first evidence that osteogenic cells in the blood home to sites of vascular injury and are associated with HO formation in heart valves.
Nucleotide-Binding Oligomerization Domain Protein 2 Deficiency Enhances Neointimal Formation in Response to Vascular Injury
Authors: Kwon Min-Young , Liu Xiaoli , Lee Seon-Jin , Kang Young-Ho , Choi Augustine M.K. , Lee Ki-Up , Perrella Mark A. , Chung Su Wol 
Published: September 2011

Objective—
Nucleotide-binding oligomerization domain protein 2 (NOD2) stimulates diverse inflammatory responses resulting in differential cellular phenotypes. To identify the role of NOD2 in vascular arterial obstructive diseases, we investigated the expression and pathophysiological role of NOD2 in a vascular injury model of neointimal hyperplasia.

Methods and Results—

We first analyzed for neointimal hyperplasia following femoral artery injury in NOD2
+/+
and NOD2
−/−
mice. NOD2
−/−
mice showed a 2.86-fold increase in neointimal formation that was mainly composed of smooth muscle (SM) α-actin positive cells. NOD2 was expressed in vascular smooth muscle cells (VSMCs) and NOD2
−/−
VSMCs showed increased cell proliferation in response to mitogenic stimuli, platelet-derived growth factor-BB (PDGF-BB), or fetal bovine serum, compared with NOD2
+/+
VSMCs. Furthermore, NOD2 deficiency markedly promoted VSMCs migration in response to PDGF-BB, and this increased cell migration was attenuated by a phosphatidylinositol 3-kinase inhibitor. However, protein kinase C and c-Jun N-terminal kinase inhibitors exerted negligible effects. Moreover, muramyl dipeptide–stimulated NOD2 prevented PDGF-BB-induced VSMCs migration.

Conclusion—
Functional NOD2 was found to be expressed in VSMCs, and NOD2 deficiency promoted VSMCs proliferation, migration, and neointimal formation after vascular injury. These results provide evidence for the involvement of NOD2 in vascular homeostasis and tissue injury, serving as a potential molecular target in the modulation of arteriosclerotic vascular disease.
Prognostic Importance of Early Worsening Renal Function After Initiation of Angiotensin-Converting Enzyme Inhibitor Therapy in Patients With Cardiac Dysfunction
Authors: Testani Jeffrey M. , Kimmel Stephen E. , Dries Daniel L. , Coca Steven G. 
Published: September 2011

Background—
Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin-converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we investigated the relative early WRF-associated mortality rates in subjects randomized to ACE-I or placebo.

Methods and Results—

Subjects in the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337) were studied. The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary end point. In the overall population, early WRF was associated with increased mortality (adjusted hazard ratio [HR], 1.2; 95% CI, 1.0–1.4;
P
=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR, 1.4; 95% CI, 1.1–1.8;
P
=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR, 1.0; 95% CI, 0.8–1.3;
P
=1.0;
P
=0.09 for the interaction). In patients who continued to receive study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR, 0.66; 95% CI, 0.5–0.9;
P
=0.018).

Conclusions—
These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event that is not associated with a loss of benefit from continued ACE-I therapy.
Outcomes in Mild or Rapidly Improving Stroke Not Treated With Intravenous Recombinant Tissue-Type Plasminogen Activator
Authors: Smith Eric E. , Fonarow Gregg C. , Reeves Mathew J. , Cox Margueritte , Olson DaiWai M. , Hernandez Adrian F. , Schwamm Lee H. 
Published: September 2011

Background and Purpose—
Mild or rapidly improving stroke is a frequently cited reason for not giving intravenous recombinant tissue-type plasminogen activator (rtPA), but some of these patients may have poor outcomes. We used data from a large nationwide study (Get With The Guidelines–Stroke) to determine risk factors for poor outcomes after mild or improving stroke at hospital discharge.

Methods—
Between 2003 and 2009, there were 29 200 ischemic stroke patients (from 1092 hospitals) arriving within 2 hours after symptom onset with mild or rapidly improving stroke symptoms as the only contraindication to rtPA. Logistic regression was used to determine the independent predictors of discharge to home.

Results—

Among 93 517 patients arriving within 2 hours, 31.2% (29 200) did not receive rtPA solely because of mild/improving stroke. Among the 29 200 mild/improving cases, 28.3% were not discharged to home, and 28.5% were unable to ambulate without assistance at hospital discharge. The likelihood of home discharge was strongly related to initial National Institutes of Health Stroke Scale score (
P
<0.001). In multivariable-adjusted analysis, patients not discharged to home were more likely to be older, female, and black; have a higher National Institutes of Health Stroke Scale score and vascular risk factors; and were less likely to be taking lipid-lowering medication before admission.

Conclusions—
In this large, nationwide study, a sizeable minority of patients who did not receive intravenous rtPA solely because of mild/improving stroke had poor short-term outcomes, raising the possibility that stroke-related disability is relatively common, even in “mild” stroke. A controlled trial of reperfusion therapy in this population may be warranted.
Impact of Extracranial–Intracranial Bypass on Cerebrovascular Reactivity and Clinical Outcome in Patients With Symptomatic Moyamoya Vasculopathy
Authors: Han Jay S. , Abou-Hamden Amal , Mandell Daniel M. , Poublanc Julien , Crawley Adrian P. , Fisher Joseph A. , Mikulis David J. , Tymianski Michael 
Published: September 2011

Background and Purpose—
The purpose of this study was to evaluate in symptomatic moyamoya patients the effect of surgical revascularization on impaired cerebrovascular reactivity (CVR) and its relationship to clinical outcome.

Methods—
Brain revascularization was performed using a direct superficial temporal artery to middle cerebral artery bypass or indirect encephalo-dural–arterial synangiosis. CVR was measured pre- and 3 months postoperatively using blood oxygen level-dependent MRI during iso-oxic hypercapnic changes in end-tidal carbon dioxide. Outcomes were assessed by MRI, clinical examination, and modified Rankin Scale scores.

Results—

Fifty-five hemispheres were revascularized in 39 patients (superficial temporal artery to middle cerebral artery in 47, encephalo-dural–arterial synangiosis in 8). Surgery reversed CVR impairment in 52 hemispheres (94.5%) and in 36 of 39 patients (92.3%; Fisher exact test,
P
<0.001), and this was predictive of a patent extracranial–intracranial bypass. New, clinically silent perioperative hemorrhages, cortical foci of ischemia, or new white matter T2 hyperintensities were detected after 11 surgeries (20%), but no new lesions arose after 3 postoperative months. One patient had a clinical perioperative stroke (1.8%). In clinical follow-up, 37 of 39 patients (95%) had stable or improved modified Rankin Scale scores and 2 patients (5.1%) worsened. No patients with patent bypasses or CVR improvements exhibited new clinical symptoms, but failure of CVR improvement corresponded to a poorer long-term outcome (Fisher exact test,
P
<0.001).

Conclusions—
Cerebral revascularization surgery is a safe and effective treatment for reversing preoperative CVR defects and may prevent recurrence of preoperative symptoms. Moreover, CVR measurements may be useful in long-term follow-up and for predicting bypass patency.
Longitudinal Magnetic Resonance Imaging of Sildenafil Treatment of Embolic Stroke in Aged Rats
Authors: Ding Guangliang , Jiang Quan , Li Lian , Zhang Li , Zhang Zhenggang , Lu Mei , Li Qingjiang , Gu Steven , Ewing James , Chopp Michael 
Published: September 2011

Background and Purpose—
Sildenafil provides restorative therapeutic benefits in the treatment of experimental stroke. The majority of experimental studies on treatment of stroke have been performed in young animals; however, stroke is primarily a disease of the aged. Thus, using MRI, we evaluated the effects of sildenafil treatment of embolic stroke in aged animals.

Methods—
Aged male Wistar rats (18 months) were subjected to embolic stroke and treated daily with saline (n=10) or with sildenafil (n=10) initiated at 24 hours and subsequently for 7 days after onset of ischemia. MRI measurements were performed at 24 hours and weekly to 6 weeks after embolization.

Results—
MRI and histological measurements demonstrated that sildenafil treatment of aged rats significantly enhanced angiogenesis and axonal remodeling after stroke compared to saline-treated aged rats. Local cerebral blood flow in the angiogenic area was elevated and expansion of the ipsilateral ventricle and, consequently, brain atrophy was significantly reduced in the sildenafil-treated rats.

Conclusions—
Treatment of embolic stroke in aged rats with sildenafil significantly augments angiogenesis and axonal remodeling, which increased local blood flow and reduced expansion of the ipsilateral ventricle 6 weeks after stroke compared to control aged rats. MRI can be used to investigate brain repair after stroke in aged rats.
Therapeutic Modulation of Cerebral Microhemorrhage in a Mouse Model of Cerebral Amyloid Angiopathy
Authors: Fisher Mark , Vasilevko Vitaly , Passos Giselle F. , Ventura Christopher , Quiring Daniel , Cribbs David H. 
Published: September 2011

Background and Purpose—
The aging brain demonstrates frequent MRI and pathological evidence of cerebral microbleeds, which are often associated with cerebral amyloid angiopathy. To develop new therapeutic strategies for this disorder, we studied cerebral microhemorrhage in a well-characterized mouse model of cerebral amyloid angiopathy.

Methods—
Tg2576 mice were studied at ages ranging from 2 to 21 months. Spontaneous and induced microscopic bleeding was analyzed with and without a passive anti-amyloid immunization regimen and dietary supplementation of ischemic stroke prevention medication dipyridamole.

Results—
Areas of microhemorrhage were easily demonstrated and were significantly more prominent in the oldest mice and in animals treated with anti-amyloid immunotherapy. Dipyridamole supplementation in the diet generated plasma levels >790 ng/mL within the range seen clinically. Dipyridamole treatment did not worsen frequency and size of cerebral microscopic bleeding.

Conclusions—
The Tg2576 mouse is a useful model to study progression and modification of spontaneous and immunotherapy-induced cerebral microhemorrhage. Absence of microhemorrhage worsening with dipyridamole treatment suggests a potential therapeutic role of this agent when ischemic and microhemorrhagic lesions coexist.
Trust but Verify: Building Cultures of Support for the Responsibility to Protect Norm
Authors: Zuber Robert , Laso Ana Carolina Barry 
Published: September 2011

AbstractWhether we wish to acknowledge it or not, trust issues permeate all security policy deliberations, including recent discussions at United Nations headquarters focused on building acceptance of the Responsibility to Protect (RtoP) norm and laying out plans for the full implementation of all three of its programmatic 'pillars.' This paper assesses resources for and commitments to trust building in three core areas – trust in the viability of the norm itself, trust in the persons most closely associated with the norm, and trust in the institutions (UN and Regional Bodies) projected to 'house' the norm and oversee all phases of its implementation. As this implementation process moves from consideration of state-focused, 'first pillar' preventive and early warning capacities to 'third pillar,' last-resort, direct responses to threats of atrocity crimes, the need for durable and dependable bonds of trust between RtoP advocates, diplomats and policymakers becomes more acute.
Some Concerns About 'The Responsibility Not to Veto'
Authors: Levine Daniel H. 
Published: September 2011

AbstractAriela Blätter and Paul D. Williams propose that the international community could more effectively end serious abuses such as genocide and crimes against humanity if the permanent five members of the UN Security Council adopted a 'responsibility not to veto;' that is, an informal agreement not to use their veto power when action to respond to genocide or mass atrocities is proposed and has the support of a simple majority on the Council. While there is much to recommend the proposal, it may not in fact promote the protection of civilians as it is intended to do. The historical record shows a number of instances where inappropriate military action was counterproductive to civilian protection, and it is not clear how easy it would have been for a military intervention to help rather than harm civilians in some cases in which intervention was not forthcoming. Ultimately, the RN2V proposal would be stronger if it were part of a package of more fundamental institutional changes, including improving the UN's ability to respond to budding crises non-violently.
Simulations of Historical and Future Trends in Snowfall and Groundwater Recharge for Basins Draining to Long Island Sound
Authors: Bjerklie David M. , Trombley Thomas J. , Viger Roland J. 
Published: September 2011

AbstractA regional watershed model was developed for watersheds contributing to Long Island Sound, including the Connecticut River basin. The study region covers approximately 40 900 km2, extending from a moderate coastal climate zone in the south to a mountainous northern New England climate zone dominated by snowmelt in the north. The input data indicate that precipitation and temperature have been increasing for the last 46 years (1961–2006) across the region. Minimum temperature has increased more than maximum temperature over the same period (1961–2006). The model simulation indicates that there was an upward trend in groundwater recharge across most of the modeled region. However, trends in increasing precipitation and groundwater recharge are not significant at the 0.05 level if the drought of 1961–67 is removed from the time series. The trend in simulated snowfall is not significant across much of the region, although there is a significant downward trend in southeast Connecticut and in central Massachusetts. To simulate future trends, two input datasets, one assuming high carbon emissions and one assuming low carbon emissions, were developed from GCM forecasts. Under both of the carbon emission scenarios, simulations indicate that historical trends will continue, with increases in groundwater recharge over much of the region and substantial snowfall decreases across Massachusetts, Connecticut, southern Vermont, and southern New Hampshire. The increases in groundwater recharge and decreases in snowfall are most pronounced for the high emission scenario.
Estimation of Daily Mean Photosynthetically Active Radiation under All-Sky Conditions Based on Relative Sunshine Data
Authors: Qin Jun , Yang Kun , Liang Shunlin , Tang Wenjun 
Published: September 2011

AbstractPhotosynthetically active radiation (PAR) is absorbed by plants to carry out photosynthesis. Its estimation is important for many applications such as ecological modeling. In this study, a broadband transmittance scheme for solar radiation at the PAR band is developed to estimate clear-sky PAR values. The influence of clouds is subsequently taken into account through sunshine-duration data. This scheme is examined without local calibration against the observed PAR values under both clear- and cloudy-sky conditions at seven widely distributed Surface Radiation Budget Network (SURFRAD) stations. The results indicate that the scheme can estimate the daily mean PAR at these seven stations under all-sky conditions with root-mean-square error and mean bias error values ranging from 6.03 to 6.83 W m−2 and from −2.86 to 1.03 W m−2, respectively. Further analyses indicate that the scheme can estimate PAR values well with globally available aerosol and ozone datasets. This suggests that the scheme can be applied to regions for which observed aerosol and ozone data are not available.
Probability Density Functions of Liquid Water Path and Total Water Content of Marine Boundary Layer Clouds: Implications for Cloud Parameterization
Authors: Kawai Hideaki , Teixeira João 
Published: September 2011

Abstract
Mathematical forms of probability density functions (PDFs) of liquid water path (LWP) and total water content for marine boundary layer clouds are investigated using the homogeneity, skewness, and kurtosis of PDFs of LWP obtained from observations described in a companion paper. First, observed LWP PDF data are divided into four categories depending on the stability between 775 and 1000 hPa in order to investigate the characteristics of the PDFs of LWP depending on stability of the atmospheric boundary layer (ABL). The relationships between cloud amount and higher moments of LWP PDFs for different ABLs show different features. When the stability becomes larger, the LWP PDFs have larger homogeneity, smaller skewness, and smaller kurtosis for similar cloud amounts.
To extract useful information about the PDFs of total water content for strongly and moderately stable ABLs, the relationship between LWP PDFs and PDFs of total water content is determined by introducing a set of simple assumptions for the vertical structure of total water content in well-mixed boundary layers. By comparing the observed relationships between cloud amount and higher moments of LWP PDFs, with similar relationships deduced theoretically from various forms of PDFs of total water content, it is found that, in general, the triangular and Gaussian PDFs are a realistic approximation for PDFs of total water content in marine boundary layer clouds for strongly and moderately stable ABLs. Results concerning the correction ratio for the autoconversion rate of cloud water content to precipitation and the reduction factor for shortwave reflectance, as functions of cloud amount, are also discussed.
Estimation of Rain Intensity Spectra over the Continental United States Using Ground Radar–Gauge Measurements
Authors: Lin Xin , Hou Arthur Y. 
Published: September 2011

Abstract
A high-resolution surface rainfall product is used to estimate rain characteristics over the continental United States as a function of rain intensity. By defining data at 4-km horizontal resolutions and 1-h temporal resolutions as an individual precipitating or nonprecipitating sample, statistics of rain occurrence and rain volume including their geographical and seasonal variations are documented. Quantitative estimations are also conducted to evaluate the impact of missing light rain events due to satellite sensors’ detection capabilities.
It is found that statistics of rain characteristics have large seasonal and geographical variations across the continental United States. Although heavy rain events (&gt;10 mm h−1) only occupy 2.6% of total rain occurrence, they may contribute to 27% of total rain volume. Light rain events (&lt;1.0 mm h−1), occurring much more frequently (65%) than heavy rain events, can also make important contributions (15%) to the total rain volume.
For minimum detectable rain rates setting at 0.5 and 0.2 mm h−1, which are close to sensitivities of the current and future spaceborne precipitation radars, there are about 43% and 11% of total rain occurrence below these thresholds, and they respectively represent 7% and 0.8% of total rain volume. For passive microwave sensors with their rain pixel sizes ranging from 14 to 16 km and the minimum detectable rain rates around 1 mm h−1, the missed light rain events may account for 70% of rain occurrence and 16% of rain volume.
Statistics of rain characteristics are also examined on domains with different temporal and spatial resolutions. Current issues in estimates of rain characteristics from satellite measurements and model outputs are discussed.