bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomised assessment of the pharmacokinetic, pharmacodynamic and safety interaction between apixaban and enoxaparin in healthy subjects
Authors: Wang Jessie , Song Yan , Pursley Janice , Wastall Philip , Wright Robert , LaCreta Frank , Frost Charles , Barrett Yu 
Published: March 2012

SummaryFollowing major orthopaedic surgery, guidelines usually recommend continued thromboprophylaxis after hospitalisation. The availability of an effective oral anticoagulant with an acceptable safety profile that does not require routine clinical monitoring may lead clinicians to switch patients from subcutaneous to an oral therapy either during hospitalisation or at discharge. The purpose of this study was to assess the effect of enoxaparin on the pharmacokinetics, pharmacodynamics and safety of apixaban, an oral, direct inhibitor of coagulation factor Xa. In this four-period, crossover study, 20 healthy subjects were randomised to receive single doses of apixaban 5 mg orally; enoxaparin 40 mg subcutaneously; apixaban 5 mg and enoxaparin 40 mg concomitantly; and apixaban 5 mg followed 6 hours (h) after by enoxaparin 40 mg. Pharmacokinetics of apixaban were not affected by enoxaparin. Average peak pharmacodynamic effect, measured by anti-Xa activity, was 1.36 U/ml after administration of apixaban and was 0.42 U/ml after enoxaparin. Following co-administration of apixaban and enoxaparin, peak anti-Xa activity was 42% higher than for apixaban alone. Following administration of enoxaparin 6 h after apixaban, peak anti-Xa activity was 15% higher than for apixaban alone. In conclusion, enoxaparin had no effect on the pharmacokinetics of apixaban. The increase in anti-Xa activity after co-administration was modest and appeared to be additive. Peak anti-Xa activity increases are mitigated by separating administration of subcutaneous anticoagulation and apixaban when switching between therapies; the potential for pharmacodynamic interaction may be further mitigated by transitioning at the next scheduled dose (12 h).
Variability of fibrinogen measurements in post-myocardial infarction patients
Authors: Baumert Jens , Karakas Mahir , Greven Sonja , Rückerl Regina , Peters Annette , Koenig Wolfgang 
Published: March 2012

SummaryElevated fibrinogen levels are strongly and consistently associated with incident coronary heart disease (CHD). A possible causal contribution of fibrinogen in the pathway leading to atherothrombotic cardiovascular disease complications has been suggested. However, for implementation in clinical practice, data on validity and reliability, which are still scarce, are needed that are still scarce, especially in subjects with a history of CHD. For the present study, levels of plasma fibrinogen were measured in 200 post-myocardial infarction (post-MI) patients aged 39–76 years, with approximately six blood samples collected at monthly intervals between May 2003 and March 2004, giving a total of 1,144 samples. Inter-individual variability (between-subject variance component, VCb and coefficient of variation, CVb), intra-individual and analytical variability (VCw+a and CVw+a), intraclass correlation coefficient (ICC) and the number of measurements required for an ICC of 0.75 were estimated to assess the reliability of serial fibrinogen measurements. Mean fibrinogen concentration of all subjects over all samples was 3.34 g/l (standard deviation 0.67). Between-subject variation for fibrinogen was VCb = 0.34 (CVb,=17.5%) whereas within-subject and analytical variation was estimated as VCw+a = 0.14 (CVw+a=11.0%). The variation was mainly explained by between-subject variability, shown by the proportion of total variance of 71.3%. Two different measurements were required to reach sufficient reliability, if subjects with extreme values were not excluded. The present study indicates a fairly good reproducibility of serial individual fibrinogen measurements in post-MI subjects.
Two missense mutations identified in venous thrombosis patients impair the inhibitory function of the protein Z dependent protease inhibitor
Authors: Birch Nigel P. , Browett Peter J. , Coughlin Paul B. , Horvath Anita J. , Van de Water Neil S. , Ockelford Paul A. , Harper Paul L. , Young Laura K. 
Published: March 2012

SummaryProtein Z-dependent protease inhibitor (ZPI) is a plasma inhibitor of factor (F)Xa and FXIa. In an earlier study, five mutations were identified within the ZPI gene of venous thrombosis patients and healthy controls. Two of these were nonsense mutations and three were missense mutations in important regions of the protein. Here we report that two of these latter three mutations, F145L and Q384R, impair the inhibitory function of ZPI in vitro. Recombinant wild-type and mutant proteins were prepared; stability in response to thermal challenge was similar. Inhibition of FXa in the presence of the cofactor protein Z was reduced 68-fold by the Q384R mutant; inhibition of FXIa by the F145L mutant was reduced two- to three-fold compared to the wild-type ZPI. An analysis of all five ZPI mutations was undertaken in a cohort of venous thrombosis patients (n=550) compared to healthy controls (n=600). Overall, there was a modest increase in incidence of these mutations in the thrombosis group (odds ratio 2.0, 1.05–3.7, p=0.044). However, in contrast to W324X (nonsense mutation), the Q384R missense mutation and R88X nonsense mutation were evenly distributed in patients and controls; F145L was rare. The final mutation (S143Y) was also rare and did not significantly alter ZPI function in laboratory studies. The F145L and particularly the Q384R mutation impaired the function of the coagulation inhibitor ZPI; however, there was no convincing association between these mutations and venous thrombosis risk. The functional role for ZPI in vivo has yet to be clarified.
Genome-Wide Screen for Metabolic Syndrome Susceptibility Loci Reveals Strong Lipid Gene Contribution But No Evidence for Common Genetic Basis for Clustering of Metabolic Syndrome Traits
Authors: Kristiansson Kati , Perola Markus , Tikkanen Emmi , Kettunen Johannes , Surakka Ida , Havulinna Aki S. , Stančáková Alena , Barnes Chris , Widen Elisabeth , Kajantie Eero , Eriksson Johan G. , Viikari Jorma , Kähönen Mika , Lehtimäki Terho , Raitakari Olli T. , Hartikainen Anna-Liisa , Ruokonen Aimo , Pouta Anneli , Jula Antti , Kangas Antti J. , Soininen Pasi , Ala-Korpela Mika , Männistö Satu , Jousilahti Pekka , Bonnycastle Lori L. , Järvelin Marjo-Riitta , Kuusisto Johanna , Collins Francis S. , Laakso Markku , Hurles Matthew E. , Palotie Aarno , Peltonen Leena , Ripatti Samuli , Salomaa Veikko 
Published: March 2012

Background—
Genome-wide association (GWA) studies have identified several susceptibility loci for metabolic syndrome (MetS) component traits, but have had variable success in identifying susceptibility loci to the syndrome as an entity. We conducted a GWA study on MetS and its component traits in 4 Finnish cohorts consisting of 2637 MetS cases and 7927 controls, both free of diabetes, and followed the top loci in an independent sample with transcriptome and nuclear magnetic resonance-based metabonomics data. Furthermore, we tested for loci associated with multiple MetS component traits using factor analysis, and built a genetic risk score for MetS.

Methods and Results—

A previously known lipid locus,
APOA1/C3/A4/A5
gene cluster region (SNP
rs964184
), was associated with MetS in all 4 study samples (
P
=7.23×10
−9
in meta-analysis). The association was further supported by serum metabolite analysis, where
rs964184
was associated with various very low density lipoprotein, triglyceride, and high-density lipoprotein metabolites (
P
=0.024–1.88×10
−5
). Twenty-two previously identified susceptibility loci for individual MetS component traits were replicated in our GWA and factor analysis. Most of these were associated with lipid phenotypes, and none with 2 or more uncorrelated MetS components. A genetic risk score, calculated as the number of risk alleles in loci associated with individual MetS traits, was strongly associated with MetS status.

Conclusions—
Our findings suggest that genes from lipid metabolism pathways have the key role in the genetic background of MetS. We found little evidence for pleiotropy linking dyslipidemia and obesity to the other MetS component traits, such as hypertension and glucose intolerance.
Comparison of the Framingham and Reynolds Risk Scores for Global Cardiovascular Risk Prediction in the Multiethnic Women's Health Initiative
Authors: Cook Nancy R. , Paynter Nina P. , Eaton Charles B. , Manson JoAnn E. , Martin Lisa W. , Robinson Jennifer G. , Rossouw Jacques E. , Wassertheil-Smoller Sylvia , Ridker Paul M 
Published: March 2012

Background—
Framingham-based and Reynolds Risk scores for cardiovascular disease (CVD) prediction have not been directly compared in an independent validation cohort.

Methods and Results—

We selected a case-cohort sample of the multiethnic Women's Health Initiative Observational Cohort, comprising 1722 cases of major CVD (752 myocardial infarctions, 754 ischemic strokes, and 216 other CVD deaths) and a random subcohort of 1994 women without prior CVD. We estimated risk using the Adult Treatment Panel III (ATP-III) score, the Reynolds Risk Score, and the Framingham CVD model, reweighting to reflect cohort frequencies. Predicted 10-year risk varied widely between models, with ≥10% risk in 6%, 10%, and 41% of women with the ATP-III, Reynolds, and Framingham CVD models, respectively. Calibration was adequate for the Reynolds model, but the ATP-III and Framingham CVD models overestimated risk for coronary heart disease and major CVD, respectively. After recalibration, the Reynolds model demonstrated improved discrimination over the ATP-III model through a higher c statistic (0.765 versus 0.757;
P
=0.03), positive net reclassification improvement (NRI; 4.9%;
P
=0.02), and positive integrated discrimination improvement (4.1%;
P
<0.0001) overall, excluding diabetics (NRI=4.2%;
P
=0.01), and in white (NRI=4.3%;
P
=0.04) and black (NRI=11.4%;
P
=0.13) women. The Reynolds (NRI=12.9%;
P
<0.0001) and ATP-III (NRI=5.9%;
P
=0.0001) models demonstrated better discrimination than the Framingham CVD model.

Conclusions—
The Reynolds Risk Score was better calibrated than the Framingham-based models in this large external validation cohort. The Reynolds score also showed improved discrimination overall and in black and white women. Large differences in risk estimates exist between models, with clinical implications for statin therapy.
Mechanism of Ischemic Infarct in Spontaneous Cervical Artery Dissection
Authors: Morel Audrey , Naggara Olivier , Touzé Emmanuel , Raymond Jean , Mas Jean-Louis , Meder Jean-Francois , Oppenheim Catherine 
Published: March 2012

Background and Purpose—
It is unclear whether strokes in patients with spontaneous cervical artery dissection (CAD) are due to secondary thromboembolism or to a reduction in cerebral blood flow from the primary cervical lesion. The aim of this study was to identify the most likely mechanism of stroke using cervical and cerebral imaging parameters in patients with CAD.

Methods—
The study was approved by the local Ethics Committee. Informed consent was waived. We retrospectively evaluated the cerebrovascular ultrasound, cervical MR angiography, and stroke brain MRI in consecutive patients with CAD. An embolic mechanism was considered in the case of direct visualization of an intracranial embolism as a susceptibility vessel sign on T2* or in the case of pial artery territory infarction on diffusion-weighted imaging. A hemodynamic mechanism was considered in the case of watershed infarction and in the case of an association of watershed infarction and pial artery territory infarction when ≥2 of the following were present: severe stenotic or occlusive CAD, reduced intracranial velocity on cerebrovascular ultrasound or signal on MR angiography, or hyperintense vessel sign on fluid-attenuated inversion recovery. The remaining patients were considered to have a mixed mechanism.

Results—
Of 172 consecutive patients with CAD, 100 (58%) had acute stroke on diffusion-weighted imaging. Stroke was attributed to a thromboembolic mechanism in 85 of 100 patients, a hemodynamic mechanism in 12 of 100 patients, and a mixed mechanism in 3 of 100 patients.

Conclusions—
Stroke in patients with CAD is most frequently associated with both direct and indirect signs of artery-to-artery embolization on imaging, a finding that should help design future therapeutic trials.
Dissociative Effects of Methylphenidate in Nonhuman Primates: Trade-offs between Cognitive and Behavioral Performance
Authors: Rajala Abigail Z. , Henriques Jeffrey B. , Populin Luis C. 
Published: March 2012

AbstractLow doses of methylphenidate reduce hyperactivity and improve attention in individuals with attention deficit hyperactivity disorder (ADHD) as well as in healthy humans and animals. Despite its extensive use, relatively little is known about its mechanisms of action. This study investigated the effects of methylphenidate on working memory performance, impulsivity, response accuracy and precision, and the ability to stay on task in rhesus monkeys using an oculomotor delayed response task. Methylphenidate affected task performance in an inverted-U manner in all three subjects tested. The improvements resulted from a reduction in premature responses and, importantly, not from improvement in the memory of target location. The length of time subjects participated in each session was also affected dose dependently. However, the dose at which the length of participation was maximally increased significantly impaired performance on the working memory task. This dissociation of effects has implications for the treatment of ADHD, for the nonprescription use of methylphenidate for cognitive enhancement, and for furthering the basic understanding of the neural substrate underlying these processes.
Hurricane Clusters in the Vicinity of Florida
Authors: Jagger Thomas H. , Elsner James B. 
Published: March 2012

AbstractModels that predict annual U.S. hurricane activity assume a Poisson distribution for the counts. Here the authors show that this assumption applied to Florida hurricanes leads to a forecast that underpredicts both the number of years without hurricanes and the number of years with three or more hurricanes. The underdispersion in forecast counts arises from a tendency for hurricanes to arrive in groups along this part of the coastline. The authors then develop an extension to their earlier statistical model that assumes that the rate of hurricane clusters follows a Poisson distribution with cluster size capped at two hurricanes. Hindcasts from the cluster model better fit the distribution of Florida hurricanes conditional on the climate covariates including the North Atlantic Oscillation and Southern Oscillation index. Results are similar to models that parameterize the extra-Poisson variation in the observed counts, including the negative binomial and the Poisson inverse Gaussian models. The authors argue, however, that the cluster model is physically consistent with the way Florida hurricanes tend to arrive in groups.
Effects of Three-Dimensional Photon Transport on the Radiative Forcing of Realistic Contrails
Authors: Forster Linda , Emde Claudia , Mayer Bernhard , Unterstrasser Simon 
Published: March 2012

Abstract
Estimates of the global radiative forcing (RF) of line-shaped contrails and contrail cirrus exhibit a high level of uncertainty. In most cases, 1D radiative models have been used to determine the RF on a global scale. In this paper the effect of neglecting the 3D radiative effects of realistic contrails is quantified. Calculating the 3D effects of an idealized elliptical contrail as in the work of Gounou and Hogan with the 3D radiative transfer model MYSTIC (for “Monte Carlo code for the physically correct tracing of photons in cloudy atmospheres”) produced comparable results: as in Gounou and Hogan’s work the 3D effect (i.e., the difference in RF between a 3D calculation and a 1D approximation) on contrail RF was on the order of 10% in the longwave and shortwave. The net 3D effect, however, can be much larger, since the shortwave and longwave RF largely cancel during the day. For the investigation of the 3D effects of more realistic contrails, the microphysical input was provided by simulations of a 2D contrail-to-cirrus large-eddy simulation (LES) model. To capture some of the real variability in contrail properties, this paper examines two contrail evolutions from 20 min up to 6 h in an environment with either high or no vertical wind shear. This study reveals that the 3D effects show a high variability under realistic conditions since they depend strongly on the optical properties and the evolutionary state of the contrails. The differences are especially large for low elevations of the sun and contrails spreading in a sheared environment. Thus, a parameterization of the 3D effects in climate models would need to consider both geometry and microphysics of the contrail.
Projected Twenty-First-Century Changes in Temperature, Precipitation, and Snow Cover over North America in CCSM4
Authors: Peacock Synte 
Published: March 2012

Abstract
Results from a suite of ensembles of twenty-first-century climate projections made using the Community Climate System Model, version 4 (CCSM4) are analyzed to document model bias and to explore possible future changes in air temperature, precipitation, and snow cover over North America. Large biases still exist in all analyzed fields in this version of the model, and the necessary assumption in future climate projections is therefore that the bias persists into the future, such that the differences in a field between two time periods are meaningful indications of potential changes. Projected temperature increases show strong regional patterns with spatial similarities for all the emissions scenarios considered, although there are considerable differences in the magnitude of the projected change. Projections indicate an increase in total precipitation over much of North America for all emissions scenarios, with the exception of the Southwest United States. All of North America except parts of northern Canada shows a projected decrease in snow cover over the twenty-first century.
Role of the Boundary Layer Moisture Asymmetry in Causing the Eastward Propagation of the Madden–Julian Oscillation*
Authors: Hsu Pang-chi , Li Tim 
Published: March 2012

Abstract
The moisture budget associated with the eastward-propagating Madden–Julian oscillation (MJO) was diagnosed using 1979–2001 40-yr ECMWF Re-Analysis (ERA-40) data. A marked zonal asymmetry of the moisture relative to the MJO convection appears in the planetary boundary layer (PBL, below 700 hPa), creating a potentially more unstable stratification to the east of the MJO convection and favoring the eastward propagation of MJO. The PBL-integrated moisture budget diagnosis indicates that the vertical advection of moisture dominates the low-level moistening ahead of the convection. A further diagnosis indicates that the leading term in the vertical moisture advection is the advection of the background moisture by the MJO ascending flow associated with PBL convergence. The cause of the zonally asymmetric PBL convergence is further examined. It is found that heating-induced free-atmospheric wave dynamics account for 75%–90% of the total PBL convergence, while the warm SST anomaly induced by air–sea interaction contributes 10%–25% of the total PBL convergence.
The horizontal moisture advection also plays a role in contributing to the PBL moistening ahead of the MJO convection. The leading term in the moisture advection is the advection across the background moisture gradient by the MJO flow. In the western Indian Ocean, Maritime Continent, and western Pacific, the meridional moisture advection by the MJO northerly flow dominates, while in the eastern Indian Ocean the zonal moisture advection is greater. The contribution of the moisture advection by synoptic eddies is in general small; it has a negative effect over the tropical Indian Ocean and western Pacific and becomes positive in the Maritime Continent region.
The Diurnal Cycle of the Boundary Layer, Convection, Clouds, and Surface Radiation in a Coastal Monsoon Environment (Darwin, Australia)
Authors: May Peter T. , Long Charles N. , Protat Alain 
Published: March 2012

Abstract
The diurnal variation of convection and associated cloud and radiative properties remains a significant issue in global NWP and climate models. This study analyzes observed diurnal variability of convection in a coastal monsoonal environment examining the interaction of convective rain clouds, their associated cloud properties, and the impact on the surface radiation and corresponding boundary layer structure during periods where convection is suppressed or active on the large scale. The analysis uses data from the Tropical Warm Pool International Cloud Experiment (TWP-ICE) as well as routine measurements from the Australian Bureau of Meteorology and the U.S. Department of Energy Atmospheric Radiation Measurement (ARM) program. Both active monsoonal and large-scale suppressed (buildup and break) conditions are examined and demonstrate that the diurnal variation of rainfall is much larger during the break periods and the spatial distribution of rainfall is very different between the monsoon and break regimes. During the active monsoon the total net radiative input to the surface is decreased by more than 3 times the amount than during the break regime—this total radiative cloud forcing is found to be dominated by the shortwave (SW) cloud effects because of the much larger optical thicknesses and persistence of long-lasting anvils and cirrus cloud decks associated with the monsoon regime. These differences in monsoon versus break surface radiative energy contribute to low-level air temperature differences in the boundary layer over the land surfaces.
An Artificial Neural Network Approach to Multispectral Rainfall Estimation over Africa
Authors: Chadwick Robin , Grimes David 
Published: March 2012

Abstract
Multispectral Spinning Enhanced Visible and IR Interferometer (SEVIRI) data, calibrated with daily rain gauge estimates, were used to produce daily high-resolution rainfall estimates over Africa. An artificial neural network (ANN) approach was used, producing an output of satellite pixel–scale daily rainfall totals. This product, known as the Rainfall Intensity Artificial Neural Network African Algorithm (RIANNAA), was calibrated and validated using gauge data from the highland Oromiya region of Ethiopia. Validation was performed at a variety of spatial and temporal scales, and results were also compared against Tropical Applications of Meteorology Using Satellite Data (TAMSAT) single-channel IR-based rainfall estimates. Several versions of RIANNAA, with different combinations of SEVIRI channels as inputs, were developed. RIANNAA was an improvement over TAMSAT at all validation scales, for all versions of RIANNAA. However, the addition of multispectral data to RIANNAA only provided a statistically significant improvement over the single-channel RIANNAA at the highest spatial and temporal-resolution validation scale. It appears that multispectral data add more value to rainfall estimates at high-resolution scales than at averaged time scales, where the cloud microphysical information that they provide may be less important for determining rainfall totals than larger-scale processes such as total moisture advection aloft.