bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prasugrel inhibits platelet-leukocyte interaction and reduces inflammatory markers in a model of endotoxic shock in the mouse
Authors: Totani Licia , Dell’Elba Giuseppe , Martelli Nicola , Di Santo Angelomaria , Piccoli Antonio , Amore Concetta , Evangelista Virgilio 
Published: March 2012

SummaryPrasugrel, through its active metabolite, reduces atherothrombosis and its clinical manifestations by inhibiting platelet activation and aggregation. Platelets also contribute to inflammation through interaction with different classes of leukocytes. We investigated whether the inhibitory effect of prasugrel on platelets also counteract inflammatory responses. The effect of prasugrel active metabolite, R-138727, was investigated on platelet P-selectin expression, platelet adhesion to polymorphonuclear leukocytes (PMN) and monocytes (MN) and Mac-1 expression in PMN and MN, in vitro, in human cells. The ex vivo effect of prasugrel administration on P-selectin, thromboxane (TXB)2 formation, platelet-PMN conjugates and Mac-1 expression in PMN triggered by PAR-4 agonist peptide was examined in whole blood from healthy mice as well as from mice in which an acute inflammatory reaction was induced by treatment with endotoxin. The effect of prasugrel on inflammatory markers in endotoxin-treated animals was also tested in vivo. R-138727 inhibited agonist-stimulated expression of platelet P-selectin, platelet-PMN and platelet-MN adhesion and platelet-dependent Mac-1 expression in leukocytes. Addition of aspirin did not modify the inhibitory effect elicited by R-138727. Treatment of mice with prasugrel resulted in a profound inhibition of platelet P-selectin expression, TXB2 production, platelet-PMN adhesion and Mac-1 expression in PMN induced by ex vivo stimulation with PAR-4 agonist peptide of whole blood from healthy or endotoxin-treated mice. Measurement of markers revealed that prasugrel reduced TXB2 and tumour necrosis factor-α synthesis and increased nitric oxide metabolites in endotoxin-treated mice in vivo. In conclusion, prasugrel reduces platelet interactions with PMN and MN. Through these effects prasugrel may curb platelet-mediated inflammatory responses.
Short- Versus Long-Term Duration of Dual-Antiplatelet Therapy After Coronary Stenting
Authors: Valgimigli Marco , Campo Gianluca , Monti Monia , Vranckx Pascal , Percoco Gianfranco , Tumscitz Carlo , Castriota Fausto , Colombo Federico , Tebaldi Matteo , Fucà Giuseppe , Kubbajeh Moh'd , Cangiano Elisa , Minarelli Monica , Scalone Antonella , Cavazza Caterina , Frangione Alice , Borghesi Marco , Marchesini Jlenia , Parrinello Giovanni , Ferrari Roberto 
Published: March 2012

Background—
The optimal duration of dual-antiplatelet therapy and the risk-benefit ratio for long-term dual-antiplatelet therapy after coronary stenting remain poorly defined. We evaluated the impact of up to 6 versus 24 months of dual-antiplatelet therapy in a broad all-comers patient population receiving a balanced proportion of Food and Drug Administration–approved drug-eluting or bare-metal stents.

Methods and Results—

We randomly assigned 2013 patients to receive bare-metal, zotarolimus-eluting, paclitaxel-eluting, or everolimus-eluting stent implantation. At 30 days, patients in each stent group were randomly allocated to receive up to 6 or 24 months of clopidogrel therapy in addition to aspirin. The primary end point was a composite of death of any cause, myocardial infarction, or cerebrovascular accident. The cumulative risk of the primary outcome at 2 years was 10.1% with 24-month dual-antiplatelet therapy compared with 10.0% with 6-month dual-antiplatelet therapy (hazard ratio, 0.98; 95% confidence interval, 0.74–1.29;
P
=0.91). The individual risks of death, myocardial infarction, cerebrovascular accident, or stent thrombosis did not differ between the study groups; however, there was a consistently greater risk of hemorrhage in the 24-month clopidogrel group according to all prespecified bleeding definitions, including the recently proposed Bleeding Academic Research Consortium classification.

Conclusions—
A regimen of 24 months of clopidogrel therapy in patients who had received a balanced mixture of drug-eluting or bare-metal stents was not significantly more effective than a 6-month clopidogrel regimen in reducing the composite of death due to any cause, myocardial infarction, or cerebrovascular accident.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00611286.
25-Hydroxyvitamin D Levels and the Risk of Stroke
Authors: Sun Qi , Pan An , Hu Frank B. , Manson JoAnn E. , Rexrode Kathryn M. 
Published: March 2012

Background and Purpose—
Despite evidence suggesting that vitamin D deficiency may lead to elevated cardiovascular disease risk, results regarding the association of 25-hydroxyvitamin D (25[OH]D) levels with stroke risk are inconclusive. We aimed to examine this association in a prospective study in women and to summarize all existing data in a meta-analysis.

Methods—
We measured 25(OH)D levels among 464 women who developed ischemic stroke and an equal number of control subjects who were free of stroke through 2006 in the Nurses' Health Study (NHS). We searched MEDLINE and EMBASE for articles published through March 2011 that prospectively evaluated 25(OH)D levels in relation to stroke.

Results—

After multivariable adjustment for lifestyle and dietary covariates, lower 25(OH)D levels were associated with an elevated risk of ischemic stroke in the NHS: the OR (95% CI) comparing women in the lowest versus highest tertiles was 1.49 (1.01–2.18;
P
trend
=0.04). We found 6 other prospective studies that examined 25(OH)D in relation to stroke outcomes. After pooling our results with these prospective studies that included 1214 stroke cases in total, low 25(OH)D levels were associated with increased risk of developing stroke outcomes in comparison to high levels: the pooled relative risk (95% CI) was 1.52 (1.20–1.85;
I

2

=0.0%,
P
heterogeneity
=0.63). In 2 studies that explicitly examined ischemic stroke, this association was 1.59 (1.07–2.12;
I

2

=0.0%,
P
heterogeneity
=0.80).

Conclusions—
These data provide evidence that low vitamin D levels are modestly associated with risk of stroke. Maintaining adequate vitamin D status may lower the risk of stroke in women.
Association of Statins and Statin Discontinuation With Poor Outcome and Survival After Intracerebral Hemorrhage
Authors: Dowlatshahi Dar , Demchuk Andrew M. , Fang Jiming , Kapral Moira K. , Sharma Mukul , Smith Eric E. 
Published: March 2012

Background and Purpose—
Studies suggest a protective role for statins after intracerebral hemorrhage, but many failed to assess statin discontinuation, did not include postdischarge outcomes, or did not account for withdrawal of care. We studied the relationship between preintracerebral hemorrhage statin use and in-hospital statin discontinuation on stroke severity and 30-day mortality.

Methods—
We analyzed data from the Registry of the Canadian Stroke Network and determined the adjusted ORs for statin use and outcomes, controlling for stroke severity and other covariates.

Results—

We analyzed 2466 consecutive patients with intracerebral hemorrhage from 2003 to 2008: median age was 71 years, 53.6% were male, and 30-day mortality rate was 36.5%. Overall, 537 (21.7%) were taking statins before presentation. Compared with nonusers, statin users were less likely to have severe strokes on presentation (54.7% versus 63.3%) but had similar rates of poor outcome (70% versus 67%) and 30-day mortality (36% versus 37%). Statins were discontinued on admission in 158 of 537 (29.4%); these patients were more likely to have severe stroke (65% versus 27%,
P
<0.01), poor outcome (90% versus 62%,
P
<0.01), and to have died by 30 days (71% versus 21%,
P
<0.01). After adjusting for stroke severity, statin discontinuation was still associated with poor outcome (adjusted OR, 2.4; 95% CI, 1.13–4.56) and higher mortality (adjusted OR, 2.0; 95% CI, 1.30–3.04). However, these associations were attenuated and no longer significant after excluding patients treated palliatively.

Conclusions—
We found no association between preadmission statin use and outcomes in intracerebral hemorrhage. Statin discontinuation may worsen outcomes or may simply be a marker of worse underlying prognosis.
Clinical Prediction Rule to Estimate the Absolute 3-Year Risk of Major Cardiovascular Events After Carotid Endarterectomy
Authors: van Lammeren Guus W. , Catanzariti Louise M. , Peelen Linda M. , de Vries Jean-Paul P.M. , de Kleijn Dominique P.V. , Moll Frans L. , Pasterkamp Gerard , Bots Michiel L. 
Published: March 2012

Background and Purpose—
Prognosis after carotid endarterectomy is mainly determined by the occurrence of major adverse cardiovascular events (MACEs). Optimal medical treatment to reduce risk is the mainstay of MACE prevention. The level of risk of MACE may determine the initiation and aggressiveness of medical treatment, yet a prediction rule to assess that absolute MACE risk after carotid endarterectomy is currently unavailable.

Methods—
The prediction model was developed in a consecutive cohort of 1138 patients who underwent carotid endarterectomy between 2002 and 2009. Primary end point was MACE and encompassed myocardial infarction, stroke, and cardiovascular death. Fourteen potential clinical predictors were entered into a Cox proportional hazard model. After backward stepwise regression, internal validation was conducted with bootstrapping techniques to correct for overfitting. To provide an easily applicable clinical tool, a score chart was constructed, dividing patients into 4 risk groups. Model performance was assessed in terms of discrimination, calibration, and risk stratification.

Results—

During a mean follow-up of 2.28 (±0.95) years, 148 events occurred, corresponding to a cumulative incidence of 13%. Clinical predictors in the final model were age, history of coronary or peripheral artery disease, smoking, systolic blood pressure, use of antihypertensive drugs, clinical presentation, presence of contralateral carotid stenosis, and serum creatinine levels. Discrimination of the final model, in terms of a C statistic, was 0.69 (0.64–0.73) and calibration showed a good overall fit (Gronnesby and Borgan,
P
=0.39). The observed incidence of MACE in the 4 risk groups was 6%, 9%, 19%, and 35%, respectively, indicating good overall risk stratification.

Conclusions—
The clinical prediction model for MACE in the first 3 years after carotid endarterectomy may be used to identify high-risk patients to help optimize medical treatment and risk factor management as part of secondary prevention to increase life expectancy free from MACE. Despite our success in stratifying risk among these patients, even the lowest stratum remains at high risk and all of these patients should receive maximal secondary preventive measures.
Study of Horizontally Oriented Ice Crystals with CALIPSO Observations and Comparison with Monte Carlo Radiative Transfer Simulations
Authors: Zhou Chen , Yang Ping , Dessler Andrew E. , Hu Yongxiang , Baum Bryan A. 
Published: March 2012

AbstractData from the Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) indicate that horizontally oriented ice crystals (HOIC) occur frequently in both ice and mixed-phase clouds. When compared with the case for clouds consisting of randomly oriented ice crystals (ROIC), lidar measurements from clouds with HOIC, such as horizontally oriented hexagonal plates or columns, have stronger backscatter signals and smaller depolarization ratio values. In this study, a 3D Monte Carlo model is developed for simulating the CALIOP signals from clouds consisting of a mixture of quasi HOIC and ROIC. With CALIOP’s initial orientation with a pointing angle of 0.3° off nadir, the integrated attenuated backscatter is linearly related to the percentage of HOIC but is negatively related to the depolarization ratio. At a later time in the CALIOP mission, the pointing angle of the incident beam was changed to 3° off nadir to minimize the signal from HOIC. In this configuration, both the backscatter and the depolarization ratio are similar for clouds containing HOIC and ROIC. Horizontally oriented columns with two opposing prism facets perpendicular to the lidar beam and horizontally oriented plates show similar backscattering features, but the effect of columns is negligible in comparison with that of plates because the plates have relatively much larger surfaces facing the incident lidar beam. From the comparison between the CALIOP simulations and observations, it is estimated that the percentage of quasi-horizontally oriented plates ranges from 0% to 6% in optically thick mixed-phase clouds, from 0% to 3% in warm ice clouds (>−35°C), and from 0% to 0.5% in cold ice clouds.
A New Drag Relation for Aerodynamically Rough Flow over the Ocean
Authors: Andreas Edgar L , Mahrt Larry , Vickers Dean 
Published: March 2012

Abstract
From almost 7000 near-surface eddy-covariance flux measurements over the sea, the authors deduce a new air–sea drag relation for aerodynamically rough flow:Here u* is the measured friction velocity, and UN10 is the neutral-stability wind speed at a reference height of 10 m. This relation is fitted to UN10 values between 9 and 24 m s−1. A drag relation formulated as u* versus UN10 has several advantages over one formulated in terms of . First, the multiplicative coefficient on UN10 has smaller experimental uncertainty than do determinations of CDN10. Second, scatterplots of u* versus UN10 are not ill posed when UN10 is small, as plots of CDN10 are; u*–UN10 plots presented here suggest aerodynamically smooth scaling for small UN10. Third, this relation depends only weakly on Monin–Obukhov similarity theory and, consequently, reduces the confounding effects of artificial correlation. Finally, with its negative intercept, the linear relation produces a CDN10 function that naturally rolls off at high wind speed and asymptotically approaches a constant value of 3.40 × 10−3. Hurricane modelers and the air–sea interaction community have been trying to rationalize such behavior in the drag coefficient for at least 15 years. This paper suggests that this rolloff in CDN10 results simply from known processes that influence wind–wave coupling.
Discrepancies between parent- and adolescent-perceived problem severity and influences on help seeking from mental health services
Authors: Wahlin Tim , Deane Frank 
Published: March 2012

Objectives: Attitudinal and practical barriers prevent many young people who are experiencing mental health problems from seeking professional help. The influence of others can help young people to overcome barriers to help seeking. Understanding the relative influence of parents and others on the help-seeking decision and the extent of parent–child agreement on the severity of the young person’s problems, may be helpful in facilitating intake processes in child and adolescent mental health services (CAMHS). Methods: One hundred and nineteen parent–child (14–18-years-old) dyads attending an initial appointment at a Sydney and regional CAMHS completed the parent and youth Strength and Difficulties Questionnaires (SDQs) prior to their assessment interview. Parents and children also answered three equivalent questions on sources of influence in their decision to access services. Results: Ninety-four per cent of young people reported that others had influenced their decision to access help, with parents being the strongest influence. Higher levels of parental influence in the help-seeking process were related to greater disagreement between parent and child on the severity of the problems. Parent and child ratings of influence were related to the severity of externalizing problems. Conclusion: The findings are consistent with models that highlight help seeking as a social process involving high degrees of influence particularly from parents. Referral sources and clinicians need to be aware of the effects of discrepant views between parent and child regarding the presenting problem. To facilitate joint therapy it may be helpful for clinicians to address the level of influence involved in having the young person attend their first appointment with parents and children.
WikiLeaks: the illusion of transparency
Authors: Roberts Alasdair 
Published: March 2012

It has been said that the 2010 WikiLeaks disclosures mark ‘the end of secrecy in the old fashioned, cold-war-era sense’. This is not true. Advocates of WikiLeaks have overstated the scale and significance of the leaks. They also overlook many ways in which the simple logic of radical transparency – leak, publish, and wait for the inevitable outrage – can be defeated in practice. WikiLeaks only created the illusion of a new era in transparency. In fact the 2010 leaks revealed the obstacles to achievement of increased transparency, even in the digital age. Points for practitioners Some commentators have regarded the WikiLeaks disclosures of 2010 as evidence of a broader breakdown in the conventional mechanisms for controlling government-held information. This new world has been described as one of ‘radical transparency’. But claims about the breakdown of old-style secrecy are overwrought. This article says that the significance of the WikiLeaks disclosures has been exaggerated, and provides reasons why it will be harder to achieve radical transparency, especially in the security sector of government.
Open government: connecting vision and voice
Authors: Meijer Albert J. , Curtin Deirdre , Hillebrandt Maarten 
Published: March 2012

The term open government is often used to describe initiatives of putting government information on the Internet. This conceptualization is too restricted since open government is not only about openness in informational terms ( vision) but also about openness in interactive terms ( voice). On the basis of an analysis of 103 articles, this article provides insight into the concepts of openness, transparency and participation, their interactions, and the manner in which they have been discussed in the literature. This analysis shows the differences and similarities between economic, political science and legal perspectives on open government and argues that a multidisciplinary approach needs to be taken. The authors conclude that open government is much too important to leave it to the ‘techies’: scientists and practitioners with backgrounds in law, economics, political science and public administration should also get involved to build sound connections between vision and voice that facilitate active citizenship. Points for practitioners This article provides guidelines for the realization of open government: (1) design open government for synergistic or complementary relationships between transparency and participation, (2) design open government for a diverse population, (3) design open government for direct and indirect effects, (4) design open government acknowledging a variety in desirables and (5) design for continuous learning about effects and side-effects. The authors emphasize that a diversified approach to the design of open government will be more fruitful in the long run than merely understanding it in terms of making information publicly available.
Linking transparency, knowledge and citizen trust in government: an experiment
Authors: Grimmelikhuijsen Stephan 
Published: March 2012

Declining citizen trust in government is an important driver for NPM-style reforms. Increasing people’s knowledge by providing factual knowledge about government performance outcomes is seen as an important way of increasing citizen trust in government. Does this promise hold or is knowledge about performance outcomes not that important? Two rivalling hypotheses are being investigated. One proposition postulates a link between knowledge and trust, whereas the alternative hypothesis borrows from social-psychological research arguing that subconscious and affective cues are more important. In order to investigate this question, this article presents the results of an experiment ( N = 658) investigating the effect of performance outcome transparency on citizen trust in a specific government organization. Four groups visited different websites with varying degrees of transparency and performance outcome. The results demonstrate that the link between transparency and trust in a government organization is determined by a mix of knowledge and feelings. Further, the overall effect of transparency is limited. Pre-existing and fundamental ideas about what government does and whether it is benign or not are far more determining than a single experience with a government organization. This article concludes that knowledge about performance outcomes is only part of the link between transparency and trust, and that more realistic views about transparency’s effects should be developed. Points for practitioners Transparency is generally hailed by many as the key to trust in government. This study shows that the magnitude of transparency on citizens’ trust in government is often exaggerated as most people have pre-existing, fundamental beliefs about government which are only marginally influenced by transparency. However, transparency can contribute to maintaining existing trust levels through a mix of people’s cognition and feeling about government. Transparency is necessary, yet professionals in public management and administration should develop realistic expectations about what transparency can really achieve for trust in government.
Why is transparency about public expenditure so elusive?
Authors: Heald David 
Published: March 2012

Fiscal transparency is fundamentally important but difficult to achieve. The conceptualization of transparency has to be more sophisticated than current rhetoric implies. Analytical tools relating to the generic concept of transparency can be applied to public expenditure. Achieving transparency about public expenditure presents challenges that require explicit strategies in the context of what can be very different sets of local conditions. This article identifies the specific meaning of transparency about public expenditure, defined in terms of the four directions of transparency: inwards, outwards, upwards and downwards. It identifies barriers to the effective transparency of public expenditure, characterizing these as intrinsic or constructed. Tackling these barriers, especially those constructed by policy actors, constitutes a route towards more effective transparency, not only about public expenditure itself but about surrogates for it. It is not just quantity that matters: different varieties of transparency will have differential effects on the achievement of public policy objectives. How transparency mechanisms are structured will therefore shape their impact on public policy – on efficiency, on equity and on democratic accountability. Points for practitioners Public expenditure transparency is fundamentally important, but elusive. The difficulty stems from technical complexities and from the political process. Governments that genuinely wish to improve public expenditure transparency must address intrinsic barriers (such as low public understanding of budgeting numbers and their relationship to national accounts) and desist from building constructed barriers (such as misleading spinned numbers and substituting surrogates for direct public expenditure). It is not just the quantity of transparency that matters: different varieties of transparency will have differential effects on the achievement of public policy objectives. How transparency mechanisms are structured will shape their impact on public policy – on efficiency, on equity and on democratic accountability.