bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia
Authors: Visser Jantien , Ulander Veli-Matti , Helmerhorst Frans , Lampinen Katja , Morin-Papunen Laure , Bloemenkamp Kitty , Kaaja Risto 
Published: November 2010

SummaryRecurrent miscarriage affects 1–2% of women. In more than half of all recurrent miscarriage the cause still remains uncertain. Thrombophilia has been identified in about 50% of women with recurrent miscarriage and thromboprophylaxis has been suggested as an option of treatment. A randomised double-blind (for aspirin) multicentre trial was performed among 207 women with three or more consecutive first trimester (<13 weeks) miscarriages, two or more second trimester (13–24 weeks) miscarriages or one third trimester fetal loss combined with one first trimester miscarriage. Women were analysed for thrombophilia. After complete work-up, women were randomly allocated before seven weeks’ gestation to either enoxaparin 40 mg and placebo (n=68), enoxaparin 40 mg and aspirin 100 mg (n=63) or aspirin 100 mg (n=76). The primary outcome was live-birth rate. Secondary outcomes were pregnancy complications, neonatal outcome and adverse effects. The 0.92–1.48] was found for enoxaparin and placebo and 65% [RR 1.08, 95% CI 0.83–1.39] for enoxaparin and aspirin when compared to aspirin alone (61%, reference group). In the whole study group the live birth rate was 65% (95% CI 58.66–71.74) for women with three or more miscarriages (n=204). No difference in pregnancy complications, neonatal outcome or adverse effects was observed. No significant difference in live birth rate was found with enoxaparin treatment versus aspirin or a combination of both versus aspirin in women with recurrent miscarriage.
Expression and localisation of vascular ribonucleases in endothelial cells
Authors: Dadkhahi Sara , Gansler Julia , Saffarzadeh Mona , Shibamiyama Aya , Kral Nicolé , Baal Nelli , Koyama Takatoshi , Deindl Elisabeth , Fischer Silvia , Nishio Miwako , Preissner Klaus 
Published: November 2010

SummaryThe functions of extracellular RNA in the vascular system as new procoagulatory and permeability-increasing factor in vivoand in vitrowere shown to be counteracted by pancreatic type RNase1. Based on the identification of RNase1 in plasma and serum, it is proposed that the enzyme is expressed by vascular cells to contribute in the regulation of extracellular RNA. It is demonstrated that RNase1 and RNase5 (also termed angiogenin) were differentially expressed in various types of endothelial cells, whereby human umbilical vein endothelial cells (HUVEC) expressed and released the highest concentration of active RNase1. Expression and release of RNase5 were similar in all types of endothelial cells tested. Both RNases were constitutively produced and secreted, whereby a portion of RNase1, but not RNase5, was stored in Weibel-Palade bodies, co-localising with von Willlebrand factor and P-selectin. Accordingly, immediate release of RNase1 from these granules was demonstrated in vitroand in vivousing Weibel-Palade body exocytosis-inducing agents. Additionally, extracellular RNA or poly:IC (but not DNA) induced this short-term release of RNase1. Our results indicate that vascular RNase1 and RNase5 are mainly produced by vascular endothelial cells and can serve, depending on the vascular bed, different functions in vascular homeostasis and endothelial cell responses.
Identification of VKORC1 interaction partners by split-ubiquitin system and coimmunoprecipitation
Authors: Schaafhausen Anne , Rost Simone , Oldenburg Johannes , Müller Clemens 
Published: November 2010

SummarySince the discovery of vitamin K epoxide reductase complex subunit 1 (VKORC1), the key enzyme for the regeneration of vitamin KH2, numerous studies have addressed the role of VKORC1 in the posttranslational modification of vitamin K-dependent proteins. VKORC1 is also the target protein of anticoagulant drugs of the coumarin type (e.g. warfarin). Genetic variants in VKORC1 have recently been shown to significantly affect the coumarin dose and international normalised ratio level. In the present study, we have used the split-ubiquitin yeast two-hybrid system to identify potential interaction partners of VKORC1. With this system we could identify 90 candidates. Out of these, we focused on VKORC1 itself, its paralog VKORC1L1, emopamil binding protein (EBP) and stress-associated endoplasmic reticulum protein 1 (SERP1). By coimmunprecipitation and colocalisation experiments, we were able to demonstrate evidence for the interaction of these proteins. Mutations in the EBP gene cause X-linked dominant chondrodysplasia punctata (CDPX2) which can be considered as a phenocopy of warfarin embryo-pathy. The interaction could be a link between these phenotypes. SERP1 represents an oxidative stress-associated endoplasmatic reticulum protein with chaperon-like functions. Antioxidant capacities have been described for vitamin K hydroquinone, the substrate of VKORC1. Both VKORC1 and SERP1, might have a synergistic function in eliminating reactive oxygen species generated during the VKOR redox process. Further studies are needed to investigate the role of these proteins in the vitamin K pathway.
Characterisation of two novel large F8 deletions in patients with severe haemophilia A and factor VIII inhibitors
Authors: Marschalek Rolf , Oldenburg Johannes , Oyen Florian , Schneppenheim Reinhard , Roth Lukas 
Published: November 2010

SummaryLarge deletions are found in approximately 5% of patients with severe haemophilia A, but only a few deletion breakpoints have been char-acterised precisely so far. In this study we characterised the deletion breakpoints of two patients with severe haemophilia A, large deletions and factor VIII (FVIII) inhibitors, and subsequently established deletion-specific assays for the identification of carriers. Patient 1 had a deletion of 37,410 bp comprising exon 1 and the F8promoter region, and a 5 bp homology (GGGCC) is present at the chromosomal fusion site. In patient 2, a deletion of 22,230 bp including parts of intron 25, exon 26 and 3‘-UTR was identified. No homologous repetitive elements were found at the breakpoints. However, both breakpoints were located within long terminal repeats of endogenous retroviruses and the DNA motif TTTAAA – known to be able to bend DNA molecules – was identified at the centromeric breakpoint. By deletion-specific PCR experiments we were able to identify a heterozygous state in mother 2 (carrier) while mother 1 presented only with wild-type alleles (non-carrier). Both deletions are most likely created by DNA double strand breaks and subsequent DNA repair by the non-homologous end joining DNA repair pathway (NHEJ). The exact identification of the deletion breakpoints provides a reliable diagnostic tool for carrier identification in affected families by means of a deletion-specific PCR.
Magnetic Resonance–Guided Cardiac Interventions Using Magnetic Resonance–Compatible Devices
Authors: Tzifa Aphrodite , Krombach Gabriele A. , Krämer Nils , Krüger Sascha , Schütte Adrian , von Walter Matthias , Schaeffter Tobias , Qureshi Shakeel , Krasemann Thomas , Rosenthal Eric , Schwartz Claudia A. , Varma Gopal , Buhl Alexandra , Kohlmeier Antonia , Bücker Arno , Günther Rolf W. , Razavi Reza 
Published: November 2010

Background—
Percutaneous cardiac interventions are currently performed under x-ray guidance. Magnetic resonance imaging (MRI) has been used to guide intravascular interventions in the past, but mainly in animals. Translation of MR-guided interventions into humans has been limited by the lack of MR-compatible and safe equipment, such as MR guide wires with mechanical characteristics similar to standard guide wires. The aim of the present study was to evaluate the safety and efficacy of a newly developed MR-safe and compatible passive guide wire in aiding MR-guided cardiac interventions in a swine model and describe the 2 first-in-man solely MR-guided interventions.

Methods and Results—
In the preclinical trial, the new MR-compatible wire aided the performance of 20 interventions in 5 swine. These consisted of balloon dilation of nondiseased pulmonary and aortic valves, aortic arch, and branch pulmonary arteries. After ethics and regulatory authority approval, the 2 first-in-man MR-guided interventions were performed in a child and an adult, both with elements of valvar pulmonary stenosis. Catheter manipulations were monitored with real-time MRI sequence with interactive modification of imaging plane and slice position. Temporal resolution was 11 to 12 frames/s. Catheterization procedure times were 110 and 80 minutes, respectively. Both patients had successful relief of the valvar stenosis and no procedural complications.

Conclusions—
The described preclinical study and case reports are encouraging that with the availability of the new MR-compatible and safe guide wire, certain percutaneous cardiac interventions will become feasible to perform solely under MR guidance in the future. A clinical trial is underway in our institution.
Identifying Important Risk Factors for Survival in Patient With Systolic Heart Failure Using Random Survival Forests
Authors: Hsich Eileen , Gorodeski Eiran Z. , Blackstone Eugene H. , Ishwaran Hemant , Lauer Michael S. 
Published: November 2010

Background—
Heart failure survival models typically are constructed using Cox proportional hazards regression. Regression modeling suffers from a number of limitations, including bias introduced by commonly used variable selection methods. We illustrate the value of an intuitive, robust approach to variable selection, random survival forests (RSF), in a large clinical cohort. RSF are a potentially powerful extensions of classification and regression trees, with lower variance and bias.

Methods and Results—
We studied 2231 adult patients with systolic heart failure who underwent cardiopulmonary stress testing. During a mean follow-up of 5 years, 742 patients died. Thirty-nine demographic, cardiac and noncardiac comorbidity, and stress testing variables were analyzed as potential predictors of all-cause mortality. An RSF of 2000 trees was constructed, with each tree constructed on a bootstrap sample from the original cohort. The most predictive variables were defined as those near the tree trunks (averaged over the forest). The RSF identified peak oxygen consumption, serum urea nitrogen, and treadmill exercise time as the 3 most important predictors of survival. The RSF predicted survival similarly to a conventional Cox proportional hazards model (out-of-bag C-index of 0.705 for RSF versus 0.698 for Cox proportional hazards model).

Conclusions—
An RSF model in a cohort of patients with heart failure performed as well as a traditional Cox proportional hazard model and may serve as a more intuitive approach for clinicians to identify important risk factors for all-cause mortality.
Long-Term Cardiovascular and Noncardiovascular Mortality of 1023 Patients With Confirmed Acute Pulmonary Embolism
Authors: Ng Austin Chin Chwan , Chung Tommy , Sze Chiang Yong Andy , Siu Ping Wong Helen , Chow Vincent , Celermajer David Stephen , Kritharides Leonard 
Published: November 2010

Background—
There are currently no guidelines advising long-term surveillance of patients following an acute pulmonary embolism (PE), because long-term outcome studies are rare. We investigated the long-term cardiovascular and all-cause mortality of a large patient cohort with confirmed PE in relation to baseline cardiovascular disease (CVD).

Methods and Results—
Clinical details of all patients presenting with acute PE to a tertiary hospital were retrieved from medical records, and their survival tracked from a statewide death registry. There were 1023 (45% males) patients admitted with confirmed PE from 2000 to 2007. During a mean follow-up of 3.8±2.6 years, 363 patients died (35.5%), of whom only 31 (3.0%) died in-hospital during the index PE admission. The 3-month, 6-month, 1-year, 3-year, and 5-year cumulative mortality rates were 8.3%, 11.1%, 16.3%, 26.7%, and 31.6% respectively. Annual mortality did not improve over the 7-year period. The postdischarge mortality of 8.5%/patient-year was 2.5-fold that of an age- and sex-matched general population, being 12.6-fold in the youngest quintile (<55 years) and 1.9-fold in the oldest quintile (≥83 years). Patients with known CVD at baseline had 2.2-fold greater all-cause mortality than those without CVD, and this effect, although at a lower level of risk, remained significant after multivariate analysis. Of the 332 deaths occurring postdischarge, 40% were attributed to cardiovascular causes.

Conclusions—
In a contemporary adult population, PE is associated with a substantially increased long-term mortality, of which nearly half is cardiovascular. Our study highlights the urgent need to develop long-term surveillance strategies in this population.
Assessment of Left Ventricular Function in Older Medicare Beneficiaries With Newly Diagnosed Heart Failure
Authors: Curtis Lesley H. , Greiner Melissa A. , Shea Alisa M. , Whellan David J. , Hammill Bradley G. , Schulman Kevin A. , Douglas Pamela S. 
Published: November 2010

Background—
Assessment of left ventricular function is a recommended performance measure for the care of patients with newly diagnosed heart failure. Little is known about the extent to which left ventricular function is assessed in real-world settings.

Methods and Results—
We analyzed a 5% national sample of data from the Centers for Medicare and Medicaid Services from 1991 through 2008. Patients were 65 years or older, with incident heart failure in 1995, 1999, 2003, or 2007. We searched for evidence of tests of left ventricular function from 30 days before through 60 days after an incident heart failure diagnosis. We used logistic regression to identify patient characteristics associated with assessment of left ventricular function. There were 45 005 patients with incident heart failure in 1995, 38 425 in 1999, 39 529 in 2003, and 32 629 in 2007. Assessment of left ventricular function increased from 46% to 60%, with rest echocardiography being the predominant mode. Patients diagnosed with heart failure during a hospitalization had the highest assessment rates (58% in 1995, 64% in 1999, 69% in 2003, and 73% in 2007). After adjustment for other patient characteristics, odds of assessment were 4 times higher among patients diagnosed in inpatient settings.

Conclusions—
Nearly 40% of Medicare beneficiaries do not undergo assessment of left ventricular function when newly diagnosed with heart failure. Quality-improvement strategies are needed to optimize the care of these patients, especially in outpatient settings.
The Forms of International Institutional Law: An Historical Analysis of the scheduling Decisions of Narcotic Drugs and Psychotropic substances taken by the United Nations' Commission on Narcotics Drugs
Authors: Corte Cristián Gimenez 
Published: November 2010

AbstractThe objective of this study is to analyze the legal form of the drug scheduling decisions made by the United Nations' Commission on Narcotic Drugs (CND) to place a given narcotic drug or psychotropic substance under international control in accordance with the drug control treaties. In particular, this study will focus upon the historical evolution of the legal form of the decisions of the CND from the inception of the 1961 Single Convention until the latest decision on this matter in 2007. This study will also seek to show how and to explain why the form of the decisions 'evolved' from a very informal and vague way to a strict and concrete legal form. By doing so, this study will interpret these decisions, systematizing them within the general framework of UN law. This exercise will lead, ultimately, to the determination of the meaning of the decisions.
Amsterdam Center for International Law Introduction to the symposium on Responsibility of International Organizations and of (Member) states: Attributed or Direct Responsibility or Both?
Authors: Kuijper Pieter Jan 
Published: November 2010

AbstractThis is the introduction to three articles that resulted from the Symposium on Responsibility of International Organizations and of (Member) States organized by the Amsterdam Center for International Law (ACIL) under direction of Professors André Nollkaemper and Pieter Jan Kuijper in April 2009. The Symposium concentrated on those articles of the ILC draft articles on the Responsibility of International Organizations which are concerned with the responsibility of States for the unlawful acts of International Organizations as well as with the responsibility of International Organizations for unlawful acts of States, and in particular Member States. This introductory article seeks to place the articles relating to these issues in the context of the draft articles as a whole and of their predecessors, the draft articles on State Responsibility. Moreover, since the articles in question are based on the notion of a directly incurred responsibility on the part of the international organization or State concerned, rather than the classical conception of responsibility through attribution, they are also analyzed in the light of these two conceptions of responsibility. The issue of shared responsibility deserves special attention in this respect.
Classification of Weather Patterns and Associated Trajectories of High-Ozone Episodes in the Houston–Galveston–Brazoria Area during the 2005/06 TexAQS-II
Authors: Ngan Fong , Byun Daewon 
Published: November 2010

Abstract
The 850-hPa synoptic flow patterns over eastern Texas and adjacent states during the 2005/06 Second Texas Air Quality Studies (TexAQS-II) period were classified into six groups using a two-stage clustering method. This study identifies synoptic weather patterns that are conducive to creating high-ozone events and reveals potential emission source regions leading to ozone exceedances through backward trajectory analysis. Clusters with dominant southerly synoptic flows and higher average wind speeds (C1 and C2 clusters) were related to low mean daytime ozone levels. Easterly (C3) and northerly (C5) clusters showed a higher probability to exceed the 8-h ozone standard than the other clusters. The dry and sunny postfrontal days with weak northerly or easterly weather patterns were often associated with ozone exceedances in the Houston–Galveston–Brazoria (HGB) area during September 2006. The majority of backward trajectories on ozone episode days were from the east, which brought polluted air from the Houston Ship Channel resulting in high ozone in the southwestern part of the metropolitan area. The shifting trajectories of the C3 and C5 weather patterns were associated with surface wind turning from weak northerly to southeasterly/southerly because of the development of bay/sea breeze. Pollutants were shifting inside the metropolitan area and high ozone built up in the afternoon or early evening. A small portion of trajectories of C3 and C5 that caused high ozone passed over a short distance from the south of Houston, picking up emissions from the industries along the coast.
Estimation of the Upper-Layer Rotation and Maximum Wind Speed of Tropical Cyclones via Satellite Imagery
Authors: Chao Chun-Chieh , Liu Gin-Rong , Liu Chung-Chih 
Published: November 2010

Abstract
The movement of convective rainbands embedded in a tropical cyclone (TC) is usually derived from satellite images via the atmospheric motion vector (AMV) method or through the calculation of a radar’s echo track. In estimating the rotation speed of a TC rainband, however, the land-based radar can only detect approaching tropical cyclones within the vicinity. The AMV method is unable to fully account for the TC eyewall movement, thus making it difficult to estimate the TC intensity. The widely used method in estimating the TC maximum wind speed is the Dvorak technique in which the cloud pattern is extracted from only one image. In this study, the rainband rotation speeds are computed via satellite imagery and further applied in estimating the TC maximum wind speed. In contrast to previous research, this study adopts an innovative method by using two subsequent geostationary satellite images. The TC spin rates observed by weather satellites could often be seen to be positively related to the TC intensity. Analyses of the relationship between the typhoon wind intensity and estimated rotation speed at the 130–260-km ring via infrared channels are conducted for major typhoon cases that occurred during 2000–05 in the northwestern Pacific Ocean. Results show that the correlation between the wind intensity and estimated rotation speeds is strong for most of the cases. The highest R2 value from the individual cases could reach 0.93, and on an annual basis it could attain a value of 0.67. The mean R2 value for the 2000–05 dataset was roughly 0.53. The correlation between the wind intensity and estimated rotation speeds is further improved by factoring in the previous 6-h average rotation speeds. A regression equation is derived from the chosen typhoon cases between 2000 and 2005, which is utilized in verifying the major typhoon occurrences during 2006–08. The mean absolute error (MAE) of the hourly and 6-h average intensity estimates during 2000–08 was 20 and 18.7 kt, respectively (1 kt ≃ 0.5 m s−1). The best verification result occurred during 2008, for which the R2 value and MAE could reach 0.7 and 15.6, respectively. These research results demonstrate the suitability of using geostationary satellite image data in estimating the maximum wind speed. Nevertheless, the drawback of this study is that sometimes the rotation speeds will become slower when tropical cyclones mature because of the strong outflow of the secondary circulation. It is assumed that the relationship between the estimated rotation speeds and wind intensity can be further improved if the outflow speed of the tropical cyclones is also considered.
The Resonant Interaction of a Tropical Cyclone and a Tropopause Front in a Barotropic Model. Part II: Frontal Waves
Authors: Scheck Leonhard , Jones Sarah C. , Juckes Martin 
Published: November 2010

Abstract
The influence of frontal waves on the interaction of a tropical cyclone and a tropopause front is investigated in an idealized framework. In a nondivergent barotropic model the front is represented by a vorticity step with a superimposed sinusoidal perturbation. This gives rise to a jet that meanders to the north and south and can be viewed as a sequence of upper-level troughs and ridges. The model evolution depends sensitively on the position of the cyclone relative to the troughs and ridges. Here a bifurcation point is identified that is located on the trough axis at a distance where the zonal speed of the background flow equals the phase speed of the wave. Arbitrarily small displacements from this position determine whether a cyclone is advected toward the front or repelled. Only a limited range of wavelengths can lead to track bifurcations. The largest effects are obtained for resonant frontal waves propagating with a phase speed matching the initial zonal translation speed of the cyclone. Weak and large-scale vortices can be disrupted when approaching the bifurcation point, where they are exposed to continuously strong shear deformation.